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Alternative Designs for the Human Artificial Heart: Patients in Heart Failure – Outcomes of Transplant (donor)/Implantation (artificial) and Monitoring Technologies for the Transplant/Implant Patient in the Community


Alternative Designs for the Human Artificial Heart: Patients in Heart Failure –  Outcomes of Transplant (donor)/Implantation (artificial) and Monitoring Technologies for the Transplant/Implant Patient in the Community

Authors and Curators: Larry H Bernstein, MD, FCAP and Justin D Pearlman, MD, PhD, FACC

and

Article Curator and Reporter: Aviva Lev-Ari, PhD, RN

When the heart fails to function adequately, whether from large or multiple myocardial infarctions (tissue death/scarring) or from permanent inflammatory, toxic, microvascular or infectious muscle injury, it has two modes of failure: forward failure = inadequate pumping of blood to tissues, and backward failure = inadequate withdrawal of blood from the lungs, resulting in pulmonary congestion and elevated back-pressures which cause fluid to seep into air spaces (pulmonary edema) interfering with oxygen uptake. When the heart cannot be repaired, replacement is considered. Additional pumps may be placed in parallel and/or in series with the heart to assist circulation of blood. A heart from another patient (usually a patient deemed brain dead from trauma) or from a baboon may be transplanted to replace the ailing heart, or may be placed in tandem with the ailing heart, or the heart and lungs may be replaced together (heart-lung transplant). Additional options include the intra-aortic balloon pump, the Impella catheter pump, other ventricular assist devices. There is far greater demand for heart transplants than there are available suitable organs, so work continues on alternatives. Additional reasons to seek alternatives include the complications of transplantation. Transplantation requires shutting down the body defenses against foreign materials, called immune suppression, but the immune defense system protects against cancer and infection, so a one in five of the transplant patients succomb to cancer or infection, while others die of rejection due to insufficient suppression of the autoimmune system. Artificial materials exist that do not trigger autoimmune defenses, thereby avoiding that major issue, but energizing the pump, providing sufficient circulatory support and avoiding damage to the blood have been major hurdles.

This article has the following FIVE Parts:

Part I.  Alternative Models of Artificial Hearts, US and Europe

By Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

Part  II.  Comparison of the Cardiac Operations involved in an Organ Transplant of a Donor’s Heart vs Implantation of an Artificial Heart

By Justin D Pearlman, MD, PhD, FACC 

Part III. Comparative Analysis of Transplant Clinical Outcomes based on Data in:

Heart Transplant (HT) Indication for Heart Failure (HF): Procedure Outcomes and Research on HF, HT @ Two Nation’s Leading HF & HT Centers

By Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN 

Part IV.  Imaging Technologies in use for Clinical Monitoring of Patients with Heart Transplant: Donor Human Heart and Artificial Heart

By Justin D Pearlman, MD, PhD, FACC 

Part V. The Failure of a Heart Transplant – Pathology and Autopsy Findings

by Larry H Bernstein, MD, FCAP

Conclusions

by Larry H Bernstein, MD, FCAP

 

Part I

Alternative Models of Artificial Hearts, US and Europe

By Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

 

Latest Innovations in Alternative Models of Artificial Hearts, US and Europe

by Aviva Lev-Ari, PhD, RN

UPDATED on 12/29/2013

Total Artificial Heart Manufacturer SynCardia Secures $14M in Growth Financing

December 17, 2013

Total Artificial Heart Manufacturer SynCardia Secures $14M in Growth Financing

$10M Financed by SWK of Dallas with $4M from Athyrium Opportunities Fund

A $14 million infusion of funding will allow SynCardia Systems, Inc. to respond to the rapid growth in the number of Total Artificial Heart implants and SynCardia Certified Centers that has occurred since 2010. As of Dec. 16, 2013, there were 155 implants of the SynCardia Total Artificial Heart, making 2013 another record-breaking year.

TUCSON, Ariz., Dec. 17, 2013 /PRNewswire/ — Privately held SynCardia Systems, Inc. announced today that it had raised $14 million to fund the rapid growth of the only approved medical device that eliminates the symptoms and source of end-stage heart failure, the SynCardia temporary Total Artificial Heart. The SynCardia Total Artificial Heart is the world’s first and only FDA, Health Canada and CE (Europe) approved Total Artificial Heart.

“SWK is very pleased to provide SynCardia this new capital in order to help further the growth of the company’s Total Artificial Heart,” Brett Pope, CEO of SWK Holdings Corporation, says of its $10-million financing. “We are very gratified to help expand the availability of this lifesaving device.”

“In 2013 we are setting another record for SynCardia Heart implants, nearly double what was then our 2011 record-breaking year of 81 implants,” says Michael Garippa, President and CEO of SynCardia. “As of Dec. 16, 155 SynCardia Total Artificial Hearts have been implanted this year.”

The financing positively affects the development of the new, smaller 50cc version of the approved 70cc SynCardia Total Artificial Heart, the availability of the Freedom portable driver and the use of SynCardia technology for destination therapy.

“We are pleased to support SynCardia’s continued clinical and commercial successes,” says Laurent Hermouet, a partner at Athyrium. “This latest financing will help reinforce SynCardia’s supply chain and manufacturing capabilities ahead of new product launches and increased production levels.”

The $4 million provided by Athyrium Capital Management in last week’s funding supplemented $15 million in long-term growth capital it provided to SynCardia in March 2013.

Wedbush PacGrow Life Sciences acted as exclusive placement agent for the offering.

The new financing allows SynCardia to accelerate the development and launch of its 50cc Total Artificial Heart* through an FDA-approved clinical study. Together, the 50cc and 70cc sizes of the Total Artificial Heart will fit almost all women and men, as well as many pediatric patients. With this expanded product line, SynCardia anticipates the tripling of the market size and sales potential for the SynCardia Total Artificial Heart.

The funds also will help the company meet the increasing demand for the Freedom portable drivers. In a letter dated Oct. 21, 2013, the FDA determined that the Freedom PMA supplement is approvable with the submission of additional information. The 13.5-pound wearable Freedom driver, which powers the SynCardia Heart while giving patients nearly unrestricted mobility, is already approved by Health Canada and has a CE Mark for Europe.

SynCardia is an innovative, 85-employee company focused on advanced medical technology targeting the NYHA Class IV heart failure market. There are 93 SynCardia Certified Centers worldwide where the SynCardia Heart is immediately available with an additional 35 hospitals undergoing the company’s four-phase certification program. As of Dec. 16, 2013, there have been 1,262 total implants of the SynCardia Total Artificial Heart worldwide.

SWK Holdings Corporation is a specialized finance company with a focus on the global healthcare sector. SWK partners with ethical product marketers and royalty holders to provide flexible financing solutions at an attractive cost of capital to create long-term value for both SWK’s business partners and its investors. SWK believes its financing structures achieve an optimal partnership for companies, institutions and inventors seeking capital for expansion or capital and estate planning by allowing its partners to monetize future cash flow with minimal dilution to their equity stakes. Additional information on the life science finance market is available on the company’s website at http://www.swkhold.com.

Athyrium Capital Management, LLC is an asset management company formed in 2008 to focus on investment opportunities in the global healthcare sector. Athyrium invests across all healthcare verticals including biopharma, medical devices and products and healthcare services, and partners with management teams to implement creative financing solutions to companies’ capital needs. The Athyrium team has substantial investment experience in the healthcare sector across a wide range of asset classes, including public equity, private equity, fixed income, royalties and other structured securities. Athyrium has over $600 million under management as of Sept. 30, 2013. The firm’s investors include public and corporate pension funds, charitable endowments, insurance companies, funds-of-funds, family offices and university endowments. For more information, please visit http://www.athyrium.com.

*The 50cc Total Artificial Heart is designed for use as a bridge to transplant in patients of smaller stature, including women and adolescents. It has been designated as a Humanitarian Use Device (HUD) by the FDA for destination therapy in adults and as a bridge to transplant in pediatric patients. Prior to clinical study, an Investigational Device Exemption (IDE) application that includes each indication must be approved by the FDA.
** CAUTION – The Freedom portable driver is an investigational device, limited by United States law to investigational use.
About the SynCardia temporary Total Artificial Heart
For additional information, please visit: http://www.syncardia.com
Like SynCardia on Facebook
Follow SynCardia on Twitter – @SynCardia
Connect with SynCardia on LinkedIn

SOURCE

SynCardia Systems, Inc.

Read more: Total Artificial Heart Manufacturer SynCardia Secures $14M in Growth Financing – FierceMedicalDevices http://www.fiercemedicaldevices.com/press-releases/total-artificial-heart-manufacturer-syncardia-secures-14m-growth-financing#ixzz2otlLCH8I
Subscribe at FierceMedicalDevices

UPDATED on 12/23/2013

First Carmat artificial heart implanted in human in France

http://medcitynews.com/2013/12/first-artificial-heart-implanted-human/

UPDATED on 3/27/2014

Carmat Investigates Death of First Artificial Heart Recipient

Posted in Cardiovascular by Stephen Levy on March 18, 2014

French artificial heart maker Carmat says it will not perform another human implant until it has determined the cause of death of the first patient fitted with the device.

That first patient, a 76-year-old man suffering from terminal heat failure, died March 2. He received the implanted artificial heart 75 days before, on December 18. The Georges Pompidou European Hospital in Paris, where the implantation was performed, announced the death.

 

Carmat
Artificial heart internals (Courtesy Carmat)

Alain Carpentier, MD, the inventor of the heart, told the Journal du Dimanche on March 16 that the heart had stopped after a short circuit, although the exact reasons behind the death were still unknown.

“We are trying to understand where this electronic problem came from and why,” Carpentier told the French weekly. “Our engineers are working night and day to understand, and they will find (the reason).”

Velizy Villacoublay, France–based Carmat said in a news release on March 17 that it is continuing to analyze the data from the first implanted prosthesis. The company further stated that it will continue the clinical trial once it has obtained the results of the data from the first implantation.

Reuters reports that Philippe Pouletty, director general of Truffle Capital, one of Carmat’s main shareholders, told i>Tele television, “Patients are still being chosen, but of course we will wait to hear a little more on the causes of the death of the first patient before transplanting another artificial heart.”

The company explained that its detailed analysis of the data is still being carried out. More than 4000 pieces of data are recorded every second, it said. These include inputs from the artificial heart itself, its control console, and their respective power supplies.

Also of great interest are the very complex interactions between the weakened heart of the patient and the prosthesis. At the current time, Carmat says, there is no single explanation, only hypotheses that will be substantiated or not in the coming weeks by in-house and external experts. The results of the analyses of the first implantation, and the subsequent implantations, will be reviewed by the Data and Safety Monitoring Board (DSMB).

From the company’s point of view, the first implantation was a success. The patient survived for 74 days within the framework of a trial where the benchmark for success was 30 days. Carmat says that the approved medical centers are continuing to assess next patients for the ongoing clinical trial.

Pouletty said that the data analysis would be complete within “a few weeks.” The company has previously stated that if it passed this first safety test, it intends to fit the device into about 20 more patients with less severe heart failure later this year. It hopes to apply for CE Marking to market its device in Europe by 2015.

Stephen Levy is a contributor to Qmed and MPMN.

SOURCE

http://www.qmed.com/news/carmat-investigates-death-first-artificial-heart-recipient?cid=nl.qmed02

 

UPDATED on 3/6/2014

Artificial heart patient in France dies – Frenchman died 75 days after surgery

Thomson Reuters Posted: Mar 04, 2014 5:11 PM ET Last Updated: Mar 04, 2014 5:12 PM ET

The first patient fitted with an artificial heart made by the French company Carmat has died, the hospital that had performed the transplant in December has announced.

Carmat artificial heartCarmat’s bioprosthetic device is designed to replace the real heart for as much as five years, mimicking nature’s work using biological materials and sensors. (Benoit Tessier/Reuters)

The 76-year-old man died on Sunday, 75 days after the operation, the Georges Pompidou European Hospital in Paris said in a statement, adding that the cause of his death could not be known for sure at this stage.

When he was fitted with the device, the man was suffering from terminal heart failure, when the sick heart can no longer pump enough blood to sustain the body, and was said to have only a few weeks, or even days, to live.

Carmat’s bioprosthetic device is designed to replace the real heart for as much as five years, mimicking nature’s work using biological materials and sensors. It aims to help the thousands of patients who die each year while awaiting a donor, and reducing the side-effects associated with transplants.

“Carmat wishes to pay tribute to the courage and the pioneering role of this patient and his family, as well as the medical team’s dedication,” a company spokeswoman said.

She stressed that it was premature to draw any conclusions on Carmat’s artificial heart at this stage.

Three more patients in France with terminal heart failure are due to be fitted with the device. The clinical trial will be considered a success if the patients survive with the implant for at least a month.

If it passes the test, Carmat has said it would fit the device into about 20 patients with less severe heart failure.

Extending life

“The doctors directly involved in the post-surgical care wish to highlight the value of the lessons learned from this first clinical trial, with regard to the selection of the patient, his surveillance, the prevention and treatment of difficulties encountered,” the hospital said in its statement.

An in-depth analysis of the medical and technical data gathered since the patient’s operation will be needed to establish the cause of his death, the hospital added.

Carmat estimates around 100,000 patients in the United States and Europe could benefit from its artificial heart, a market worth more than $12 billion.

Among Carmat’s competitors for artificial heart implants are privately-held SynCardia Systems and Abiomed, both of the United States.

SynCardia’s artificial heart is the only one approved both in the United States and the European Union and has been implanted in more than 1,200 patients to keep them waiting for a heart from a matching donor. The longest a patient has lived with the device is just under four years prior to a transplant.

Carmat’s heart is designed to serve not as a bridge to transplant but as a permanent implant, extending life for terminally ill patients who cannot hope for a real organ, generally because they are too old and donors too scarce.

Carmat’s shares, which have risen nearly five-fold since floating on the Paris stock market in 2010, closed at 95 euros before Monday’s news, giving the company a market capitalization of around 407 million euros

SOURCE

 

December 20, 2013 12:11 pm by 

healthy heartPARIS (Reuters) – France’s Carmat said on Friday it had carried out the first human implantation of its artificial heart.The operation, performed on Wednesday at the Georges Pompidou European Hospital in Paris, went smoothly, Carmat said in a statement, adding that the patient was being monitored in the intensive care unit but was awake and talking.(Reporting by Natalie Huet; editing by Mark John)

Read more: http://medcitynews.com/2013/12/first-artificial-heart-implanted-human/#ixzz2oLlFRyDG

An artificial heart from a French company is to be tested in patients in four countries.

ArtificialHeart

By ANNE EISENBERG
Published: July 13, 2013 – The New York Times, Novelties

SCIENTISTS have long searched for a durable artificial heart that can work as efficiently as the one supplied by nature.

Carmat

Cow tissue will be used on surfaces of membranes — represented by elliptical shapes in this rendering — that touch the blood.

Now Carmat, a company based in Paris, has designed an artificial heart fashioned in part from cow tissue. The device, soon to be tested in patients with heart failure, is regulated by sensors, software and microelectronics.  Its power will come from two external, wearable lithium-ion batteries.

Fifteen years in development, the heart has been approved for clinical trials at cardiac surgery centers in Belgium, Poland, Saudi Arabia and Slovenia, where staff members are receiving training and patients are being screened, said Dr. Piet Jansen, medical director at Carmat.

In France, where the device is not yet cleared for human implantation, regulators have requested more animal tests, Dr. Jansen said; those tests are continuing.

Artificial hearts aren’t new, of course, but the Carmat heart is unusual in its design, said Dr. Joseph Rogers, an associate professor at Duke University and medical director of its cardiac transplant and mechanical circulatory support program. Surfaces in the new heart that touch human blood are made from cow tissue instead of artificial materials like plastic that can cause problems like clotting.

“The way they’ve incorporated biological surfaces for any place that contacts blood is a really nice advantage,” Dr. Rogers said. “If they have this design right, this could be a game changer.” He added that it could lessen the need for anticoagulation medicines. (Dr. Rogers has no financial connections to Carmat.)

This is the first artificial heart to use cow-derived materials — specifically, tissue from the pericardial sac that surrounds the heart. Biological tissue has been used in earlier mechanical blood pumps only in valves, Dr. Rogers said.

Thousands of people in the United States need a replacement heart, said Dr. Lynne Warner Stevenson, a professor at Harvard Medical School and director of the cardiomyopathy and heart-failure program at Brigham and Women’s Hospital in Boston. “It’s estimated that if we had enough donor hearts to go around, 100,000 to 150,000 people in the United States with heart failure would benefit,” she said. “Transplants work best, but we have only 2,000 or so adult hearts” that are available each year, she said. “It’s a huge problem.”

There are long-established options for patients while they await transplants, Dr. Stevenson said, including installing an artificial heart made by SynCardia until a donor heart is available.

When the natural heart is partly damaged or diseased, patients might keep it and have a mechanical aid implanted to bolster blood flow. Such pumps — especially those that aid the left side of the heart (LVAD)— are in wide use both as a bridge to a transplant and for lifetime therapy.

A totally artificial heart for extended use would be of great value, but it’s far too early to know if the Carmat heart, as yet untried in humans, will be that device. “The whole history of mechanical devices is that people thought they had devices where blood wouldn’t clot. But they didn’t,” Dr. Stevenson said.

Dr. Jansen said that the cost of the Carmat heart would be about $200,000 and that he did not expect it to be brought to market in Europe before the end of 2014. Once the company gains momentum with its European clinical studies, he said, it plans to start working through the regulatory process in the United States.

The Carmat heart has two chambers, each divided by a membrane. That membrane has cow tissue on one side — the side that is in contact with blood — and polyurethane on the other side, which touches the miniaturized pumping system of motors and hydraulic fluids that changes the membrane’s shape. (The motion of the membrane pushes the blood out to the body.) The embedded electronics and software adjust the rate of blood flow. Patients can wear the batteries under the arm in a holster, or in a belt, among other options.

Cow tissue is also used for the heart’s artificial valves, which were created by Dr. Alain Carpentier, a cardiac surgeon and a pioneer of heart valve repair who is also a co-founder of Carmat and its scientific director. Such valves have been used in heart-valve replacement surgery for decades. The cow tissue is chemically treated so that it is sterile and biologically inert.

The heart’s design and development relied heavily on aerospace testing strategies by EADS, the European Aeronautic Defense and Space Company, one of Carmat’s backers, Dr. Jansen said. Even so, duplicating the durability of a human heart will not be easy, said Dr. Robert Kormos, director of the artificial heart program at the University of Pittsburgh Medical Center and co-director of its heart transplant program.

“We can test these pumps on the bench in the laboratory, and in animals, but there is no true long-term data until you implant them in people for trials,” he said.

DR. JANSEN said that one design requirement for the heart was that it last five years. The company has been doing bench tests to see whether the new heart will stand up to that level of wear and tear. “Whether it lasts five years in the patient we will have to prove clinically,” he said.

Dr. Stevenson of Harvard is optimistic about the new device.

“Innovation is what we need,” she said. “This new device is exciting. I applaud the pioneers who developed it, and the patients and families who will go down this path for the first time.”

A version of this article appeared in print on July 14, 2013, on page BU3 of the New York edition with the headline: The Artificial Heart Is Getting a Bovine Boost.

SOURCE
An American designed Artificial Heart by ABIOMED, the Symphony model, assists in remodeling of heart tissue cells by design, as described in

Mechanical Circulatory Assist Devices as a Bridge to Heart Transplantation or as “Destination Therapy“: Options for Patients in Advanced Heart Failure

By Larry H Bernstein, MD, FCAP

A total artificial heart (TAH) is a device that replaces the two ventricles of the heart. Those who benefit from a TAH usually have end-stage heart failure. Since the condition is so severe that the heart can’t pump enough blood to meet the body’s needs, all treatments, except heart transplant, have failed.

The TAH is attached the atria, and mechanical valves are between the TAH and the atria functioning like the heart’s valves, controlling the flow of blood in pulmonary and systemic circulation.

Currently, the two types of TAHs are the CardioWest and the AbioCor. The main difference between these TAHs is that the CardioWest is connected to an outside power source.  The CardioWest has tubes that, through holes in the abdomen, run from inside the chest to an outside power source.

CardioWest Total Artificial Heart

Figure A shows a CardioWest TAH. Tubes exit the body and connect to a machine that powers the TAH and controls how it works.

Cardiowest_TAHt_Photo

The AbioCor TAH is completely contained inside the chest. A battery powers this TAH, and the battery is charged through the skin with a special magnetic charger. Energy from the external charger reaches the internal battery through an energy transfer device called transcutaneous energy transmission, or TET. An implanted TET device is connected to the implanted battery. An external TET coil is connected to the external charger. Also, an implanted controller monitors and controls the pumping speed of the heart.

AbioCor Total Artificial Heart

Figure B shows an AbioCor TAH and the internal devices that control how it works.

Abiomed_AB5000

A TAH usually extends life for months beyond what is expected with end-stage heart failure. It can keep one alive while waiting for a donor heart.  It is a challenge for surgeons to implant, and it can cause complications.  TAHs are devices used only in a small number of people.

There is a Difference Between Artificial Heart & Ventricular Assist Device

(see Michael Paul Maupin, eHow Contributor)

http://www.ehow.com/facts_6713118_difference-_amp_-ventricular-assist-devices.html#ixzz2a5BH465n

A ventricular assist device (VAD) utilizes the patient’s own heart, and it operates as a bridge device until a donor heart is procured for transplant. A TAH replaces a patient’s explanted heart.  The VAD is grafted onto a patient’s left ventricle, boosting the impaired ventricular function.  A VAD is either continuous or pulsatile in function. In a continuous VAD, blood is circulated through the heart like water through a hose.  A pulsatile VAD more mimics the expulsion of blood in rhythmic patterns.

http://www.ehow.com/facts_6713118_difference-_amp_-ventricular-assist-devices.html#ixzz2a5Bcbszh

On the other hand, an artificial heart completely replaces the human heart. The device functions in every way a healthy human heart would in the absence of cardiac disease.  The TAH creates the same pattern of squeeze-and-release seen in a real heart.

http://www.ehow.com/facts_6713118_difference-_amp_-ventricular-assist-devices.html#ixzz2a5Bn6xaR

As of 2010, the longest any human being has lived with an artificial heart is 21 months. In comparison, documentation exists in which a VAD recipient was still enjoying a vigorous quality of life after seven years.

Read more: http://www.ehow.com/facts_6713118_difference-_amp_-ventricular-assist-devices.html#ixzz2a5C1cPFV

The SynCardia temporary Total Artificial Heart

(An artificial heart displayed at the London Science Museum)

200px-Artificial-heart-london

http://www.wikipedia.com/Artificial Heart

An artificial heart is a device is typically used to bridge the time to heart transplantation, or to permanently replace the heart in case heart transplantation is impossible. The first artificial heart to be successfully implanted in a human was the Jarvik-7, designed and implemented by Robert Jarvik in 1982, but the first two patients to receive these hearts survived 112 (4 m) and 620 (21 m) days beyond their surgeries, respectively.[1]

Jarvik-7

It has already been stated that a TAH is distinct from a VAD, both used to support a failing heart. It is also distinct from a cardiopulmonary bypass machine, which is an external device used to provide the functions of both the heart and lungs, and it is used for only a few hours during cardiac bypass surgery.

Origin and Development of the Heart-Lung Bypass

A synthetic replacement for the severely failing heart would be expected to lower the need for heart transplants, because the demand for organs always greatly exceeds supply.  However, the first devices had problems with reactivity to synthetic materials and power supplies. For example, the Jarvik models were not created of a material that the human body would accept. This problem was improved when Dayton, Ohio’s Ival O. Salyer, along with various colleagues, developed a polymer material that the human body would not necessarily reject.

Prior to Jarvik-7, 41-year-old Henry Opitek made medical history in 1952 at Harper Hospital, Wayne State University in Detroit, Michigan when Dr. Forest Dewey Dodrill used the Dodrill-GMR heart machine to bypass Henry Opitek’s left ventricle for 50 minutes while he repaired the mitral valve. [2][3]  In this case In Dr. Dodrill’s post-operative report, he notes, “To our knowledge, this is the first instance of survival of a patient when a mechanical heart mechanism was used to take over the complete body function of maintaining the blood supply of the body while the heart was open and operated on.”[4]  A heart-lung machine was used in 1953 during a successful open heart surgery by Dr. John Heysham Gibbon, the inventor, who  performed the operation with the heart-lung substitute (distinct from an artificial heart substitute).

Designs of total artificial hearts

A precursor to the modern artificial heart pump was built by doctors William Sewell and William Glenn of the Yale School of Medicine in 1949 using an assortment of parts, and successfully bypassed the heart of a dog for more than an hour.[5]

The first patent for an artificial heart was held by Paul Winchell invented and Dr. Henry Heimlich (of the Heimlich Maneuver), which preceded the Jarvik heart.  On December 12, 1957, Dr. Willem Johan Kolff, the world’s most prolific inventor of artificial organs, implanted an artificial heart into a dog at Cleveland Clinic before he relocated to Salt Lake City, Utah, where there was established an Institute for artificial organs.  There, more than 200 physicians, engineers, students and faculty at the University of Utah Division of Artificial Organs developed, tested and improved Dr. Kolff’s artificial heart. To help manage his many endeavors, Dr. Kolff assigned project managers. Each project was named after its manager. Graduate student Robert Jarvik was the project manager for the artificial heart, which was subsequently renamed the Jarvik 7.

In 1958, Domingo Liotta initiated the studies of TAH replacement at Lyon, France, and in 1959–60 at the National University of Córdoba, Argentina. He presented his work at the meeting of the American Society for Artificial Internal Organs held in Atlantic City in March 1961. At that meeting, Dr. Liotta described the implantation of three types of orthotopic (inside the pericardial sac) TAHs in dogs, each of which used a different source of external energy: an implantable electric motor, an implantable rotating pump with an external electric motor, and a pneumatic pump.[6][7]

In 1964, the National Institutes of Health started the Artificial Heart Program, with the goal of putting a man-made organ into a human by the end of the decade.[8]  The first success followed in February 1966, when Dr. Adrian Kantrowitz performed the world’s first permanent implantation of a partial mechanical heart (left ventricular assist device) at Maimonides Medical Center, Brooklyn, NY.[9]  He relocated to Detroit’s Sinai and Wayne Stae University.

In 1981, Dr. William DeVries submitted a request to the FDA to implant the Jarvik 7 into a human being. On December 2, 1982, Dr. Kolff implanted the Jarvik 7 artificial heart into Barney Clark, who was suffering from severe congestive heart failure. With Clark tethered to an external 400 lb pneumatic compressor, he suffered prolonged periods of confusion, a number of instances of bleeding, and asked several times to be allowed to die.[10]

Total Artificial Heart (TAH)

On April 4, 1969, Domingo Liotta and Denton A. Cooley replaced a dying man’s heart with a mechanical heart inside the chest at The Texas Heart Institute in Houston as a bridge for a transplant. The patient woke up and recovered well. After 64 hours, the pneumatic-powered artificial heart was removed and replaced by a donor heart. However thirty-two hours after transplantation, the patient died of what was later proved to be an acute pulmonary infection, extended to both lungs, caused by fungi, most likely caused by an immunosuppressive drug complication.[11]

The original prototype of Liotta-Cooley artificial heart used in this historic operation is prominently displayed in the Smithsonian Institution’s National Museum of American History “Treasures of American History” exhibit in Washington, D.C..[12]

Permanent Pneumatic Total Artificial Heart (TAH)

The eighty-fifth clinical use of an artificial heart designed for permanent implantation rather than a bridge to transplant occurred in 1982 at the University of Utah. Artificial kidney pioneer Dr. Willem Johan Kolff started the Utah artificial organs program in 1967.[13] There, physician-engineer Dr. Clifford Kwan-Gett invented two components of an integrated pneumatic artificial heart system: a ventricle with hemispherical diaphragms that did not crush red blood cells (a problem with previous artificial hearts) and an external heart driver that inherently regulated blood flow without needing complex control systems.[14]   Dr. Robert Jarvik combined several modifications of the original: an ovoid shape to fit inside the human chest, a more blood-compatible polyurethane developed by biomedical engineer Dr. Donald Lyman, and a fabrication method by Kwan-Gett that made the inside of the ventricles smooth and seamless to reduce dangerous stroke-causing blood clots.[16]

Today, the modern version of the Jarvik 7 is known as the SynCardia temporary CardioWest Total Artificial Heart. It has been implanted in more than 800 people as a bridge to transplantation.

Artificial Heart   Cardiowest TAH-t (improvement of Jarvik-7)

In the mid-1980s, artificial hearts were powered by dishwasher-sized pneumatic power sources whose lineage went back to Alpha-Laval milking machines and required two catheters to cross the abdominal wall to carry the pneumatic pulses to the implanted heart. The National Heart, Lung, and Blood Institute opened a competition for implantable electrically powered artificial hearts funding  Cleveland Clinic in Cleveland, Ohio; the College of Medicine of Pennsylvania State University (Penn State Hershey Medical Center) in Hershey, Pennsylvania; and AbioMed, Inc. of Danvers, Massachusetts.

Abiomed_AB5000

Polymeric trileaflet valves ensure unidirectional blood flow with a low pressure gradient and good longevity. State-of-the-art transcutaneous energy transfer eliminates the need for electric wires crossing the chest wall.

AbioCor

The first AbioCor to be surgically implanted in a patient was on July 3, 2001.[17] The AbioCor is made of titanium and plastic with a weight of two pounds, and its internal battery can be recharged with a transduction device that sends power through the skin.[17] The internal battery lasts for a half hour, and a wearable external battery pack lasts for four hours.[18] The FDA announced on September 5, 2006, that the AbioCor, intended for critically ill patients who can not receive a heart transplant[19]  could be implanted after the device had been tested on 15 patients.[19]  But limitations of the current AbioCor are that its size makes it suitable for only about 50% of the male population, and its useful life is only 1–2 years.[20]  AbioMed designed a smaller, more stable heart, the AbioCor II, by combining its valved ventricles with the control technology and roller screw developed at Penn State. This pump, which should be implantable in most men and 50% of women with a life span of up to five years,[20] had animal trials in 2005, and the company hoped to get FDA approval for human use in 2008.[21]

Intrathoracic Pump (LVAD)

On July 19, 1963, E. Stanley Crawford and Domingo Liotta implanted the first clinical Left Ventricular Assist Device (LVAD) at The Methodist Hospital in Houston, Texas, in a patient who had a cardiac arrest after surgery. The patient survived for four days under mechanical support but did not recover from the complications of the cardiac arrest.

On April 21, 1966, Michael DeBakey and Liotta implanted the first clinical LVAD in a paracorporeal position (where the external pump rests at the side of the patient) at The Methodist Hospital in Houston, in a patient experiencing cardiogenic shock after heart surgery. The patient developed neurological and pulmonary complications and died after few days of mechanical support. In October 1966, DeBakey and Liotta implanted the paracorporeal Liotta-DeBakey LVAD in a new patient who recovered well and was discharged from the hospital after 10 days, marking the first successful use of an LVAD for postcardiotomy shock.

Recent developments

In June 1996, a 46-year-old Taiwanese American Mr. Yao ST received the world’s first total artificial heart implantation done by Dr. Jeng Wei at Cheng-Hsin General Hospital[26] in the Republic of China (Taiwan). This technologically advanced pneumatic Phoenix-7 Total Artificial Heart was manufactured by a Taiwanese dentist Kelvin K. Cheng, a Chinese physican T. M. Kao and colleagues at the Taiwan TAH Research Center in Tainan, Republic of China (Taiwan). With this experimental artificial heart, the patient’s BP was maintained at 90-100/40-55 mmHg and cardiac output at 4.2-5.8 L/min. After 15 days of bridging, Mr. Yao received combined heart and kidney transplantation. As of March 2013, he is still very well and is currently living in San Francisco, USA. Mr. Yao ST is the world first successful combined heart and kidney transplantation patient after bridging with total artificial heart.[27]

In August 2006, an artificial heart was implanted into a 15-year-old girl at the Stollery Children’s Hospital in Edmonton, Alberta. It was intended to act as a temporary fixture until a donor heart could be found. Instead, the artificial heart (called a Berlin Heart) allowed for natural processes to occur and her heart healed on its own. After 146 days, the Berlin Heart was removed, and the girl’s heart was able to function properly on its own.[22]

On December 16, 2011 the Berlin Heart, a ventricular assist intended for children age 16 and under, gained U.S. FDA approval. The device has since been successfully implanted in several children including a 4-year-old Honduran girl at Children’s Hospital Boston.[23]

In 2012, a study published in the New England Journal of Medicine compared the Berlin Heart to extracorporeal membrane oxygenation (ECMO) and concluded that “a ventricular assist device available in several sizes for use in children as a bridge to heart transplantation [such as the Berlin Heart] was associated with a significantly higher rate of survival as compared with ECMO.”[24] The study’s primary author, Dr. Charles D. Fraser, Jr., surgeon in chief at Texas Children’s Hospital, explained: “With the Berlin Heart, we have a more effective therapy to offer patients earlier in the management of their heart failure. ..This is a giant step forward.” [25]

Total artificial heart (TAH) invention abroad

On October 27, 2008, French professor and leading heart transplant specialist Alain F. Carpentier announced that a fully implantable artificial heart will be ready for clinical trial by 2011 and for alternative transplant in 2013. It was developed and will be manufactured by him, biomedical firm CARMAT SA, and venture capital firm Truffle Capital. The prototype uses embedded electronic sensors and is made from chemically treated animal tissues, called “biomaterials”, or a “pseudo-skin” of biosynthetic, microporous materials.[28] According to an interview of the professor Alain Carpentier in Paris (2011), a number of leading cardiac clinics already conducted successful partial replacement of the organic components of the artificial heart, for example, replacing valves, large vessels, atria, ventricles. In addition to cardio-surgery, there is the medico-psychological aspect of an artificial heart. A quarter of patients in the postoperative period after prosthetic valvular surgery developed specific psychopathological symptoms, which later received the name Skumin syndrome in 1978. It is possible that a similar problem will be discovered when conducting large-scale operations to implant an artificial heart.[29]

Another U.S. team with a prototype called 2005 MagScrew Total Artificial Heart, including Japan and South Korea researchers are racing to produce similar projects.[30][31][32]

In August 2010, 50-year-old Angelo Tigano of Fairfield, New South Wales, Australia, had his failing heart removed in a five-hour operation and it was replaced with the SynCardia temporary Total Artificial Heart by surgeon Dr Phillip Spratt, head of the heart transplant unit at St Vincent’s Hospital, Sydney.[33]

On 12 March 2011, an experimental artificial heart was implanted in 55-year-old Craig Lewis at The Texas Heart Institute in Houston by Drs. O. H. Frazier and William Cohn. The device is a combination of two modified HeartMate II pumps that is currently undergoing bovine trials.[34]

On 9 June 2011, 40 year old Matthew Green was implanted with the SynCardia temporary Total Artificial Heart in a seven hour operation at Papworth Hospital. He was the first Briton to leave hospital supported by an artificial Heart on 2 August 2011.[35]

A centrifugal pump[36][37] or an axial-flow pump[38][39] can be used as an artificial heart, resulting in the patient being alive without a pulse.

Imachi et al. described a centrifugal artificial heart which alternately pumps the pulmonary circulation and the systemic circulation, causing a pulse.[40]

Heart Assist Devices

Patients who have some remaining heart function but who can no longer live normally may be candidates for ventricular assist devices (VAD), which do not replace the human heart but complement it by taking up much of the function.

The first Left Ventricular Assist Device (LVAD) system was created by Domingo Liotta at Baylor College of Medicine in Houston in 1962.[41]

Another VAD, the Kantrowitz CardioVad, designed by Adrian Kantrowitz boosts the native heart by taking up over 50% of its function.[42] Additionally, the VAD can help patients on the wait list for a heart transplant. In a young person, this device could delay the need for a transplant by 10–15 years, or even allow the heart to recover, in which case the VAD can be removed.[42] The artificial heart is powered by a battery that needs to be changed several times while still working.

The first heart assist device was approved by the FDA in 1994, and two more received approval in 1998.[43] While the original assist devices emulated the pulsating heart, newer versions, such as the Heartmate II,[44] developed by The Texas Heart Institute of Houston, provide continuous flow. These pumps (which may be centrifugal or axial flow) are smaller and potentially more durable and last longer than the current generation of total heart replacement pumps. A major advantage of a VAD is that the patient keeps the natural heart, which may provide enough support to keep the patient alive until a solution to the problem is implemented.

Impella 2.5 cardiac assist device in LV

Suffering from end-stage heart failure, former Vice President Dick Cheney underwent a procedure in July 2010 to have a VAD implanted at INOVA Fairfax Hospital, in Fairfax Virginia. In 2012, he received a heart transplant at age 71 after 20 months on a waiting list.

REFERENCES

1^ American Heart Association. The Mechanical Heart celebrates 50 lifesaving years. 22 10 2002. 9 Feb 2008 <http://www.americanheart.org/presenter.jhtml;jsessionid=EFNP3NSFUBXLICQFCXQCDSQ?identifier=3005888>

2^ Stephenson, Larry W, et al. “The Michigan Heart: The World’s First Successful Open Heart Operation?” Journal of Cardiac Surgery 17.3 (2002): 238–246.

3^ Lavietes, Stuart. William Glenn, 88, Surgeon Who Invented Heart Procedure, The New York Times, March 17, 2003. Accessed May 21, 2009.

4^ Artificial Heart in the chest: Preliminary report. Trans. Amer. Soc. Inter. Organs, 1961, 7:318

5^ Ablation experimentale et replacement du coeur par un coer artificial intra-thoracique. Lyon Cirurgical, 1961, 57:704

6^ Sandeep Jauhar, M.D., Ph.D.: The Artificial Heart. New England Journal of Medicine (2004): 542–544.

7^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676518/, NCBI In Memoriam Dr. Adrian Kantrowitz

8^ Barron H. Lerner, MD, PhD (December 1, 2007). “The 25th Anniversary of Barney Clark’s Artificial Heart”. Celebrity Health. HealthDiaries.com. Retrieved 15 November 2010.

9^ Orthotopic cardiac prosthesis for two-staged cardiac replacement. Am J Cardio 1969; 24:723–730.

10^ “Treasures of American History”, National Museum of American History

11^ Spare Parts: Organ Replacement in American Society. Renee C. Fox and Judith P. Swazey. New York: Oxford University Press; 1992, pp. 102–104

12^ Kwan-Gett CS, Van Kampen KR, Kawai J, Eastwood N, Kolff WJ. “Results of total artificial heart implantation in calves.” Journal of Thoracic and Cardiovascular Surgery. 1971 Dec; 62(6):880–889.

13^ “Winchell’s Heart”. Time. March 12, 1973. Retrieved April 25, 2010.

14^ Kolff

15^ a b “Patient gets first totally implanted artificial heart”. CNN.com. 2001-07-03. Archived from the original on 7 June 2008. Retrieved 2008-07-13.

16^ “AbioCor FAQs”. AbioMed. Archived from the original on 3 July 2008. Retrieved 2008-07-13.

17^ a b “FDA Approves First Totally Implanted Permanent Artificial Heart for Humanitarian Uses”. FDA.gov. 2006-09-05. Retrieved 2008-07-13.

18^ a b “Will We Merge With Machines?”. popsci.com. 2005-08-01. Archived from the original on 19 July 2008. Retrieved 2008-07-13.

19^ “14th Artificial Heart Patient Dies: A Newsmaker Interview With Robert Kung, PhD”. medscape.com. 2004-11-11. Retrieved 2008-07-13.

20^ Capital Health: One year later: Berlin Heart bridges patient back to health (August 28, 2007), Capital Health, Edmonton (archived from [1] the original) on 2007-10-01).

21^ approved Berlin Heart helps patients waiting for a transplant (December 30, 2011), Children’s Hospital Boston.

22^ http://www.nejm.org/doi/pdf/10.1056/NEJMoa1014164

23^ http://www.texaschildrens.org/About-Us/News/Berlin-Heart-NEJM-2012/

24^ Cheng-Hsin General Hospital

25^ J. Wei, K. K. Cheng, D. Y. Tung, C. Y. Chang, W. M. Wan, Y. C. Chuang: Successful Use of Phoenix-7 Total Artificial Heart. Transplantation Proceedings, 1998, 30:3403-4

26^ The Carmat Heart,- The technology behind the prosthesis

27^ “About artificial heart”. Heart For Your Soul. Retrieved 2011-02-19.

28^ Total artificial heart to be ready by 2011: research team, news.yahoo.com

29^ Scientists develop artificial heart that beats like the real thing, timesonline.co.uk

30-^ Total artificial heart to be ready by 2011: research team, afp.google.com

31^ Sydney man receives Total Artificial Heart, dailyTelegraph.com.au

32^ Berger, Eric. “New artificial heart ‘a leap forward'”. Houston Chronicle. Retrieved 23 March 2011.

33^ “Plastic heart gives dad Matthew Green new lease of life”. BBC News. August 2, 2011.

34^ Black, Rosemary (January 5, 2011). “Former vice president Dick Cheney now has no pulse”. Daily News (New York).

35^ http://www.scribd.com/doc/21241693/Pulseless-Pumps-Artificial-Hearts

36^ The pulseless life

37^ Dan Baum: No Pulse: How Doctors Reinvented The Human Heart. 2012-02-29.

38^ ‘#A new pulsatile total artificial heart using a single centrifugal pump., K. Imachi, T. Chinzei, Y. Abe, K. Mabuchi, K. Imanishi, T. Yonezawa, A. Kouno, T. Ono, K. Atsumi, T. Isoyama, et al.. Institute of Medical Electronics, Faculty of Medicine, University of Tokyo, Japan.

39^ Prolonged Assisted circulation after cardiac or aortic surgery. Prolonged partial left ventricular bypass by means of intracorporeal circulation. This paper was finalist in The Young Investigators Award Contest of the American College of Cardiology. Denver, May 1962 Am. J. Cardiol. 1963, 12:399–404

40^ a b Mitka, Mike. “Midwest Trials of Heart-Assist Device.” Journal of the American Medical Association 286.21 (2001): 2661.

41^ FDA APPROVES TWO PORTABLE HEART-ASSIST DEVICES at FDA.gov

42^ An Artificial Heart That Doesn’t Beat at TechnologyReview.com

How does an artificial heart work?

The development and operation of these life-saving devices requires understanding and application of a combination of biology, materials science and physics.
Institute of Physics website  http://www.physics.org/article-questions.asp?id=74

The artficial heart

Image: Syncardia Systems

The right atrium collects blood and the right ventricle then pumps it to the lungs where it is oxygenated. The blood is then picked up by the left atrium and distributed around the body and brain by the left ventricle. Each side of the heart has a pair of valves – one pair per lung – controlling the flow of blood.

Artificial hearts can now completely, if temporarily, replace the ventricles and valves with a device made of plastic or other man-made materials, which does the job of pumping blood around.

The type of artificial heart made by Syncardia Systems, works by using a pump carried externally in a backpack – previously, patients would have to be connected to a large, immobile pump and would not have the freedom to move around.

Cardiowest_TAHt_Photo

The NHS Choices website explains that tubes connecting the heart to the pump “send pulses of air into two expandable, balloon-like sacs in the artificial ventricles, forcing out blood in much the same way that a beating heart would”.

Other models such as that produced by AbioMed use an internal pump and battery, which can be charged via transcutaneous energy transmission – a method of transferring power under the skin without having to penetrate it, thereby decreasing the chance of infection.

Energy transmission

In the artificial hearts produced by AbioMed, an electronics package is implanted in the abdomen of the recipient of the transplant to monitor and control the pumping of the heart.

Power is supplied from an external source to components under the skin, without penetrating it, using inductive electromagnetic coupling – the same principle as used by transformers to transfer electricity between different circuits, as in the national grid.

At their simplest, systems of transcutaneous energy transmission will use an external power supply connected to an external coil of wire, generating a magnetic field in it. This, in turn, produces an induced voltage in a second coil implanted under the skin, and a rectifier is used to change this alternating current into direct current that can be used to power the electronics of the heart and its controller.

Though simple in theory, in practice there are complications that arise from the need to keep the two coils aligned correctly as the patient moves, in delivering the correct level of power so that there is no excess dissipated as heat to potentially damage surrounding tissue in the patient’s body, and in making the components small enough to be carried around without too much discomfort.

Monitoring blood flow

A replacement heart needs to be able to monitor the flow of blood to regulate its pumping and ensure that the correct amount of blood is delivered around the body.

Quicker pumping is required when the transplant recipient is more active, whereas the opposite is true while he or she is resting.

Blood-flow monitors make use of ultrasound – they bounce high-frequency sound waves off blood cells coming out of the heart, the volume and speed can be measured using similar basic principles to those behind radar.

Ultrasound is used because it can monitor the flow of blood without having to be in contact with it.

Appropriate materials

Artificial hearts need to be made of light but durable materials – the Syncardia version is plastic whereas that made by AbioMed is a combination of titanium and a specially developed polyurethane, called ‘Angioflex’.

Although the Abiomed heart is designed to have as few moving parts as possible, those that it does have are made from Angioflex and are tested to ensure that they are safe for contact with blood and capable of withstanding beating 100 000 times a day for years on end.

Materials scientists can develop substances with specific properties by manipulating the constituent elements and the way in which they are processed. Materials are characterised using various techniques from condensed-matter physics including electron microscopy, x-ray diffraction and neutron diffraction.

Because they were still quite large, the first devices produced were limited to around half the male population – those with the largest chest cavities. A newer, smaller, model is intended to extend their availability to smaller people.

An artificial heart being produced by the French medical company Carmat and expected to be available by 2013 will use chemically treated animal tissue to help avoid rejection by the host’s immune system. Aerospace engineers from Airbus were also involved in its development.

Artificial hearts combine, and improve upon, many existing physics ideas to produce a piece of technology that saves lives – although they are currently only approved as a stopgap until a donor heart can be found.

Expressions of Experience: Heart Assist Devices

Video interview with O. H. “Bud” Frazier, MD; Chief, Center for Cardiac Support; Director, Cardiovascular Surgery Research; and Co-Director, Cullen Cardiovascular Research Laboratories, at Texas Heart Institute.

 O. H. “Bud” Frazier, MD, on his inspiration for developing treatments for heart failure at the Texas Heart Institute.

The Texas Heart Institute is a world leader in the development, testing and application of heart assist devices. Our goal for the surgical research conducted here is to develop and determine the best assist device to use for each individual patient. Devices may be referred to as mechanical assist devices, ventricular assist devices (VAD), left ventricular assist devices (LVAD), total artificial hearts (TAH), or simply heart pumps.

January 23, 2013

Keeping hearts pumping   Dr. Bud Frazier and Dr. Billy Cohn with heart pump BiVacor. [Photo credit Mayra Beltran, Houston Chronicle]

Doctors push the limits of heart-pump technology in an effort to save lives. Dr. Bud Frazier often tells a story about when he was a medical student in the 1960s . . . Frazier had this thought: If I can keep a man alive with my hand, why can’t we make a pump that we can pull off of the shelf to do the same thing? Dr. Billy Cohn, another physician who works at the cutting edge of heart pump technology, likes to use the history of human flight as an analogy for the evolution in his field. Experimenters in both domains had to give up the idea of bio-mimicry to advance the technology. “It is similar to when man first tried to build a flying machine with flapping wings that mimic the birds. It is obvious now that fixed wings were the way to go,” he says. “We think it is the same with the nonpulsatile pump, which, because it has only one moving part, is much more durable.” – Houston Chronicle [Photo credit Mayra Beltran]

January 13, 2013

BiVACOR artificial heart device

Australian engineer Daniel Timm’s revolutionary device to be developed at THI. “I think we’re beyond the Kitty Hawk stage with this,” – Drs. Bud Frazier and Billy Cohn. Read Eric Berger’s Houston Chronicle article.

November 20, 2012

FDA Approves HeartWare LVAD for HF

The FDA gave the green light for the HeartWare Ventricular Assist System as a bridge to heart transplantation in patients with heart failure. “The miniaturized device with an integrated inflow cannula is placed within the pericardial sac . . . simplifying the surgical insertion,” said O.H. “Bud” Frazier, MD, of Texas Heart Institute. Read the full story from medpagetoday.com.

Drs. Bud Frazier & Billy Cohn TEDMED 2012

Is this the future of artificial hearts?

At TEDMED 2012, Bud Frazier and Billy Cohn of the Texas Heart Institute preview a continuous-flow heart pump with minimal parts that works via a screw pump. Watch the VIDEO.

Cameron Engineers, THI researchers collaborate on heart pump

Engineers and scientists at Cameron Manufacturing & Engineering have worked with THI researchers in developing a new heart pump. On March 1, 2012, Cameron donated $500,000 to Texas Heart Institute at St. Luke’s Episcopal Hospital to develop a prototype heart pump which could save countless lives.

Can Tiny Heart Pump Limit Heart Muscle Damage after STEMI?

Interventional cardiologists affiliated with THI at St. Luke’s recently implanted the first two patients in the nation with a tiny heart pump in a feasibility trial to determine the pump’s potential to limit damage to heart muscle following a STEMI (ST-elevation myocardial infarction). Read the full news release to learn about the FDA-approved trial and the first enrolled patients. (November 2011)

Miniature Heart Pump: Smaller May Be Better!

Dr. William “Billy” Cohn discusses recent advances in left ventricular assist devices (LVADs) and other mechanical circulatory blood pumps as they get smaller and more adaptable to individual patients. View the video of his presentation at the Pumps & Pipes Conference (15 minutes, December 2010).

Video: Artificial hearts giving hope, saving lives. (August 19, 2011)

imeplla-LD-video

Companion 2 and Freedom Drivers

C2 Driver Supports Total Artificial Heart Patients in the Hospital Until They Are Stable and Eligible for the Freedom® Portable Driver

The Companion 2 Driver, which can be docked in the Hospital Cart or Caddy, powers the SynCardia Total Artificial Heart from implant until the patient’s condition stabilizes. Once stable, patients who are eligible can be switched to the smaller, wearable Freedom® portable driver. The Companion 2 Driver, which can be docked in the Hospital Cart or Caddy, powers the SynCardia Total Artificial Heart from implant until the patient’s condition stabilizes. Once stable, patients who are eligible can be switched to the smaller, wearable Freedom® portable driver.

The Companion 2 (C2) Driver System, which powers the SynCardia temporary Total Artificial Heart in the hospital, was selected as the Silver Winner in the Critical-Care and Emergency Medicine Products category of the Medical Design Excellence Awards (MDEA) held on June 19 in Philadelphia.

“It is a tremendous honor to have one of our products selected as a winner for the second consecutive year,” said Michael Garippa, SynCardia Chairman/CEO/President. “Our Freedom® portable driver, the world’s first wearable power supply for the Total Artificial Heart, was selected as the Bronze Winner in the same category last year. These drivers support Total Artificial Heart patients from implant with the C2 through discharge with the Freedom.”

Once stable, patients who are eligible can be switched to the 13.5-pound Freedom portable driver. Patients who meet discharge criteria can then leave the hospital and wait for a matching donor heart at home and in their communities.

The Medical Design Excellence Awards are the industry’s premier design awards competition and is the only awards program exclusively recognizing contributions and advances in the design of medical products. Entries were evaluated on the basis of their design and engineering features, including innovative use of materials, user-related functions that improve healthcare delivery and change traditional medical attitudes or practices, features that provide enhanced benefits to the patient, and the ability to overcome design and engineering challenges to meet clinical objectives.

About the SynCardia temporary Total Artificial Heart

The SynCardia Total Artificial Heart is currently approved as a bridge to transplant for people suffering from end-stage heart failure affecting both sides of the heart (biventricular failure). There have been more than 1,200 implants of the Total Artificial Heart, accounting for more than 315 patient years of life on the device. It is the only device that eliminates the symptoms and source of end-stage biventricular failure. The TAH provides immediate, safe blood flow of up to 9.5 liters per minute through each ventricle. This high volume of blood flow helps speed the recovery of vital organs, helping make the patient a better transplant candidate.

Artificial Heart Devices used at Barnes-Jewish Hospital Washington University, St. Louis

The cardiac surgeons at the Barnes-Jewish & Washington University Heart & Vascular Center are one of the leading heart surgery teams in the nation. Our permanent and temporary artificial heart devices can dramatically improve symptoms of late-stage heart failure, and sometimes even provide long-term treatment.

Mechanical Circulatory Support

The field of mechanical circulatory support in the management of patients with heart failure has seen significant advances over the past few years.  The heart failure program at Washington University and Barnes-Jewish Hospital utilizes the latest technology for both temporary and long-term mechanical support of the heart failure patient.

Temporary Support

Patients that experience severe symptoms of heart failure that cannot be stabilized with medical therapy may require a temporary support device. These implantable devices are usually placed in a cardiac catheterization lab by interventional cardiologists and/or cardiac surgeons. Temporary support devices typically serve to stabilize the patient until long-term mechanical support can be introduced. These devices include:

  • intra-aortic balloon pump
  • Impella 2.5, 4.0 and 5.0
  • TandemHeart
  • Thoratec CentriMag

Long-Term Mechanical Support

Patients may require long-term circulatory support either as a bridge to a heart transplant (bridge-to-transplant, or BTT) or as long-term treatment of heart failure in non-transplant candidates (destination therapy, or DT).  The mechanical assist device program at Barnes-Jewish & Washington University Heart & Vascular Center is one of the largest programs in the country. The program has a multidisciplinary group of dedicated specialists to ensure excellent outcomes in this patient population. Currently available devices include both left ventricular assist devices (LVAD) and the total artificial heart:

  • HeartMate II
  • HeartWare HVAD
  • Syncardia Total Artificial Heart 

The cardiac surgeons at the Barnes-Jewish & Washington University Heart & Vascular Center are one of only 13 surgical teams in the country to implant the CardioWest™ temporary Total Artificial Heart (TAH-t) as a bridge-to-transplantation in specific heart transplant candidates.

The CardioWest™ TAH-t is an improved version of the Jarvik-7 Artificial Heart, which was first implanted in 1982. This unique technology allows us to treat patients who would not survive without full circulatory support.  The CardioWest™ TAH-t completely replaces the patient’s diseased heart with a goal of restoring normal blood pressure, increasing cardiac output and giving organs such as the kidney and liver a chance to recover. As a result, patients become better candidates for transplantation.  The program is currently involved in testing the Freedom portable driver which will allow patients to leave the hospital following implantation of the TAH.

cardiowest_tah

An American designed Artificial Heart by ABIOMED, the Symphony model, assists in remodeling of heart tissue cells by design, as described in

Impella_Thumb_small  5.0 for heart failure

Heart Remodeling by Design – Implantable Synchronized Cardiac Assist Device:Abiomed’s Symphony

Table IABT vs Impella

SOURCE

Heart Remodeling by Design – Implantable Synchronized Cardiac Assist Device:Abiomed’s Symphony

Part  II  

Comparison of the Cardiac Operations involved in an Organ Transplant of a Donor’s Heart vs Implantation of an Artificial Heart

By Justin D Pearlman, MD, PhD, FACC 

A heart donor is a patient deemed brain dead who had forethought (a designation on the driver’s license) or a designated decision-maker (Healthcare Proxy) elected to make the heart available to help save another person’s life. Every tissue in the body has proteins that render a unique signature or “smell” and every patient has a limited set of markers it will accept without a fight (the histocompatibility complex, and in particular, the human leukocyte antigen).  The immune system is a major part of the body’s defenses against infection and abnormal tissues (cancer) which consists of cells trained to attack foreign protein chemistry and/or mark it for destruction with anti-bodies.

I. Heart Transplant of a Human Donor

The steps for heart transplant include:

(1) demonstration of need,

(2) identification of suitable donors,

(3) surviving while waiting for a suitable donor,

(4) surviving the removal of the damaged heart or heart and lungs to make room for the replacement (accomplished with a bypass pump),

(5) survival of the donor heart (or heart and lungs) pending preparation of the patient for receipt of the transplant,

(6) inserting the donor heart (or heart and lungs),

(7) taking the patient off the bypass pump and directing circulation through the transplant,

(8) recovery and healing,

(9) establishing and maintaining sufficient immune suppression to avoid rejection of the transplant,

(10) monitoring for functional losses or rejection.

(11) monitoring for cancer or infection,

(12) resuming enjoyment of life. Each year in the United states 800 patients die waiting for a transplant, while 2300 receive transplants.

The first heart transplant is credited to Vladimer Demikhov when he transplanted dog hearts in 1946; Dr. Shumway reported successful transplantation of the heart in 1966, and Dr. Christiaan Barnard performed the operation successfully on humans in 1967 (that patient lived 18 days). Replacing the heart with a donor heart is called orthotopic (true location) heart transplantation.  Durability of a transplant improved markedly with the approval of the immune suppression medication ciclosporineNOVA has created a shockwave video demonstrating the heart transplant operation: view video.

The actual transplantation requires only five or six lines of sutures (stitches):

  • inferior and superior vena cava (venous input to the right ventricle),
  • the main (or left and right) pulmonary arteries (delivery of blood from right ventricle to the lungs),
  • the upper half of the original left atrium to route the 3-5 pulmonary veins to the left ventricle (return of blood from the lungs), and the
  • aorta (to route blood from the left ventricle to the brain and body).

The donor heart harvesting typically includes a segment of the superior and inferior vena cava which feed

  • the right atrium,
  • the four pulmonary veins which feed the left atrium, and
  • a portion of the pulmonary artery, and
  • the aorta.

The heart is chilled to minimized its metabolic demands while it is disconnected and transferred.

The recipient heart explantation (removal of the bad heart) after the patient is supported by a bypass pump involves:

  • cannulation (tubing placement) into the aorta,
  • the superior vena cava and
  • the inferior vena cava, then
  • explantation leaving the posterior aspect of the left atrium and the posterolateral aspect of the right atrium in the recipient patient.

The left and right pulmonary veins of the donor are divided and the veins are threaded into the retained portion of the recipient left atrium. The inferor vena cava, superior vena cava, pulmonary artery, and aorta are respectively anastomosed (sewed onto the truncated portion of the corresponding native vessels end-to-end). Clots and air are flushed out and the patient is taken off bypass pump.

II. Artificial Heart:  Implant of an Assist Device

Implantation of ventricular assist device or an artificial heart is easier than a heart transplant, but it has been challenging to match nature’s ability to place the pump and keep it powered and regulated. Also durability is a major issue. The most common ventricular assist device, the intra-aortic balloon pump, is a temporizing tool to sustain a patient for just a few days while alternatives are evaluated and pursued.The steps for implanting a ventricular assist pump can be as simple as:

(1) cleaning and applying antiseptics to the skin,

(2) placing a needle in the femoral artery at the groin area,

(3) threading a wire into the artery,

(4) threading a series of hollow tubes over the wire (dilators) and leaving the largest in place (introducer),

(5) threading a catheter-pump  through the introducer and up the aorta to the desired location,

(6) synchronizing the pump the the cardiac cycle by electrocardiogram.

If the device is an intra-aortic balloon pump (IABP) then the device is advanced to the aortic arch so that an inflatable balloon expands and contracts within the aorta from the aortic arch down to just above the renal arteries. The IABP is designed to deflate when the heart contracts (systole), to make space for blood ejecting from the failing heart (afterload reduction), then inflate when the heart relaxes (diastole), effectively converting a blood pressure of 120/80 to 80/120. The coronary arteries are stressed during systole and receive their blood supply during diastole, so the diastolic augmentation (inflation of the balloon during heart relaxation) markedly improves blood delivery to the coronary arteries, which is very helpful when the coronary arteries are diseased and not well suited for immediate repair. The actions of the balloon damage blood cells and can rupture the aorta. The blood cell damage activates clotting, so full anticoagulation is required.
If the device is an Impella catheter pump, then the distal end (farthest into the patient) crosses the aortic valve into the left ventricle to draw blood from there and deliver it beyond the heart in the descending aorta.
 The ins and outs of the IABP. Shows diastole and systole. The IABP rapidly shuttles helium gas in and out of the balloon, which is located in the descending aorta. The balloon is inflated at the onsetImpellaIABP  www.fda.gov/MedicalDevices/Safety                           Impella  www.abiomed.com

Devices draw their input from

  • arterial blood (aorta or femoral artery)
  • venous blood (vena cava), or
  • a puncture wound created in the apex of the left ventricle of the heart

The next example of a ventricular assist device to consider during open heart surgery, is the bypass pump that is used during most cardiovascular surgeries, and in particular during heart or heart-lung transplant. The bypass pump relies on a tube (cannula) placed in a large source of deoxygenated blood

  • the right atrium,
  • the inferior vena cava or
  • the femoral vein

to draw its input blood from there (diverting it from the heart), and a second cannula placed in a large artery (the aorta or the femoral artery) for output. The blood passes out of the patient (extra-corporeal) to a very large mechanical pump, that typically consists of compressible tubing and rollers to minimize trauma to the blood, passing the red cells of the blood by membranes that enable uptake of oxygen. Despite the attempts not to damage the blood, blood does get damaged, so full anti-coagulation is required. The anti-coagulation consists of intravenous heparin to bind the coagulation factors. When the patient comes off the pump, the heparinization of the blood is counteracted by intravenous protamine sulfate. Also the blood is cooled because low temperatures slow down metabolism and make the cells of the body less needy during the sub-optimal circulation support. Cooled blood has increased viscosity, offset by dilution of the blood with saline (Normal Saline, isotonic solution,  w/v of NaCl, about 300 mOsm/L or 9.0 g per liter). As the pump takes over circulation, the blood supply to the heart is clamped off (cross-clamp), at which point the surgeon can work to repair the heart (valve repair, valve replacement, aorta graft, coronary grafts) or replace the heart or heart and lungs.

Artificial hearts are extensions of the concepts above, and differ primarily in

  • how the pump in energized and
  • how the pump is regulated.

An artificial heart is designed for long term use so it must be more gentle on the blood. In Part I: Alternative Models of Artificial Hearts, US and Europe, in this article, we reported on the Latest Innovations in Alternative Models of Artificial Hearts, the Carmat Heart, it is unusual in its design, said Dr. Joseph Rogers, an associate professor at Duke University and medical director of its cardiac transplant and mechanical circulatory support program. Surfaces in the new heart that touch human blood are made from cow tissue instead of artificial materials like plastic that can cause problems like clotting, it will decrease the anticoagulation dependence by design.

Artificial hearts  must accommodate changes in demands of the body, not just in the chilled low metabolic state imposed by cardiovascular surgeons. The demands of the heart are measured by oxygen consumption in units of metabolic equivalents (METS) where 1 MET represents basal metabolism (awake at rest). MET values of activities range from 0.9 (sleeping) to 23 or more (running at 14 miles/hour = 22.5 km/hour). Thus, the artificial heart should be capable of increasing its output 2300% without damage the blood cells or running out of power. The goal of long term use generally is met by linking to an external power supply that is considered portable (on wheels), or in some cases, wearable

In contrast to Transplant of a human donor’s heart, described above, we present below the procedure for implantation of:

  • Left Ventricular Assist Device (LVAD)
  • Right Ventricular Assist Device (RVAD)
  • Bi-Ventricular Assist Device (BiVAD)
  • Total artificial heart
Heartmate II (Thoratec, Pleasanton, CA). HeartHeartmate II (Thoratec, Pleasanton, CA).  http://thenatureofhiking.com/heartless-man.html#.UiPybNKsh8E
A left ventricular assist device has two aims:
(1) reduce the work on an ailing heart and
(2) boost the forward circulation to the brain and other vital organs.
Those goals require access to the aorta and/or the left ventricle. Most LVAD devices use the apex of the left ventricle (LV) to draw blood into the pump and they deliver the blood to the aorta (for example, Heartmate II (Thoratec, Pleasanton, CA). Thus an LVAD has the following components:
(A) Input conduit,
(B) Pump,
(C) Control lines and power drive lines (may be bundled or separate),
(D) Outflow conduit and
(E) Controller and power source (may be bundled or separate, generally external).
The connections require opening the chest to gain access to the LV apex for (A) and the aorta for (E). A cannula (hollow tube conduit) is inserted through incisions in each, and secured to those two targets. The other ends of those tubes can exit the chest wall through holes created for the purpose, but a short path to the outside invites infection. Therefore longer tunnels may be created to provide a longer passage beneath the skin for body defenses against infection, or a tunnel may be created alongside the esophagus down alongside the stomach so the pump can sit in the abdomen.  Power and control for the pump (C) may require a tunnel to the surface to reach (E) (length provides greater opportunity for the skin to defend against infection), or energy transfer may be accomplished by magnetic induction (a loop of wire below the skin paired with a loop outside the patient, well aligned) and control can also be wireless.

Complications related to Open Heart Surgery

Early complications include
  • perioperative hemorrhage,
  • air embolism, and
  • ventricular failure.
Late complications include
  • infection,
  • thromboembolism, and
  • device failure.  If the power drive is connected to a power line, the patient is tethered. Alternatively, the power may be provided by a battery pack that the patient may wear or wheel alongside.

Open Heart Surgery and Reoperative Sternotomy

The e-Reader is recommended to review the Authors’ article on this topic:

Pearlman, JD and A. Lev-Ari 7/23/2013 Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions

https://pharmaceuticalintelligence.com/2013/07/23/cardiovascular-complications-of-multiple-etiologies-repeat-sternotomy-post-cabg-or-avr-post-pci-pad-endoscopy-andor-resultant-of-systemic-sepsis/

Similar to the intra-aortic balloon pump, the role of the LVAD does not require access to the left ventricle. Both goals (afterload reduction and improved forward circulation) can be accomplished in the aorta: the afterload on the left ventricle can be reduced by removing volume from the aorta during contraction of the ailing heart (systole), thereby facilitating its forward emptying. Next, both
  • perfusion of the heart and
  • promotion of circulation
can be boosted by delivering volume to the aorta during relaxation of the ailing heart (diastole).
Alternatively, there is experimentation with a continuous pump rather than mimicking the pulsation of the native heart.
A Right ventricular assist device (RVAD) draws blood from either the right atrium or the right ventricle and delivers it to the pulmonary artery. Otherwise, it has the same components and the analogous surgical requirements.
A Biventricular assist device (BiVAD) is used when neither ventricle can perform adequately. It consists of the two devices, LVAD plus RVAD, with opportunity to share components (may share the controller system, the power drive system, and even share a single pump with two circulation channels can serve as RVAD plus LVAD).

III. Implant of a Total Artificial Heart

  • A total artificial heart is similar to a BiVAD except for the option that it can replace most of the native heart instead of connecting in tandem to it
  • If a total artificial heart is placed in tandem, the procedure is basically the same as for an RVAD plus and LVAD.
  • If the total artificial heart replaces the native heart, the surgery is very similar to the heart transplant procedure explained above, plus handling for
– pump placement,
– power drive, and
– controller as for LVAD.
As a heart replacement,
  • the native right atrium connects to the right intake of the total artificial heart,
  • the main pulmonary artery connects to the right output,
  • the native left atrium connects to the left input, and
  • the aorta connects to the left output.
The so-called “heartless man”  walked more than 400 miles (six miles every day) after a SynCardia Total Artificial Heart was placed, powered by a Freedom(R) portable backpack device.

REFERENCES

  1. Shumway NE, Lower RR, Stofer RC. Transplantation of the heart. Adv Surg 1966;2:265-84.
  2. Gilles Dreyfus G, Jebara V, Mihaileanu S, Carpentier AF.  Total orthotopic heart transplantation: An alternative to the standard technique. The Annals of Thoracic Surgery Volume 52, Issue 5 , Pages 1181-1184, November 1991
  3. Angermann CE, Spes CH, Tammew A, et al. Anatomic characteristics and valvular function of the transplanted heart:
    transthoracic versus transoesophageal echocardiographic findings. J Heart Transplant 1990;9:331-8.
  4. Griepp RB, Ergin MA. The history of experimental heart transplantation. J Heart Transplant. 1984;3:145.
  5. Copeland JG, Emery RW, Levinson MM, et al. Selection of patients for cardiac transplantation. Circulation. Jan 1987;75(1):2-9. [Medline].
  6. Ramakrishna H, Jaroszewski DE, Arabia FA. Adult cardiac transplantation: A review of perioperative management Part – I. Ann Card Anaesth. Jan-Jun 2009;12(1):71-8. [Medline]
  7. Hill JD. Bridging to cardiac transplantation. Ann Thorac Surg. Jan 1989;47(1):167-71. [Medline].
  8. Portner PM, Oyer PE, Pennington DG, et al. Implantable electrical left ventricular assist system: bridge to transplantation and the future. Ann Thorac Surg. Jan 1989;47(1):142-50. [Medline].
  9. Holman WL, Kormos RL, Naftel DC, Miller MA, Pagani FD, Blume E, et al. Predictors of death and transplant in patients with a mechanical circulatory support device: a multi-institutional study. J Heart Lung Transplant. Jan 2009;28(1):44-50. [Medline].
  10. Overcast TD, Evans RW, Bowen LE, et al. Problems in the identification of potential organ donors. Misconceptions and fallacies associated with donor cards. JAMA. Mar 23-30 1984;251(12):1559-62.[Medline].
  11. Reichart B, Brandl U. 40 years of heart transplantation and the DFG-Transregio Research Group Xenotransplantation. Xenotransplantation. Sep 2008;15(5):293-294. [Medline].
  12. Moriguchi J, Davis S, Jocson R, Esmailian F, Ardehali A, Laks H, et al. Successful use of a pneumatic biventricular assist device as a bridge to transplantation in cardiogenic shock. J Heart Lung Transplant. Oct 2011;30(10):1143-7. [Medline].
  13. Kilic A, Conte JV, Shah AS, Yuh DD. Orthotopic Heart Transplantation in Patients With Metabolic Risk Factors. Ann Thorac Surg. Feb 2 2012;[Medline].
  14. Arnaoutakis GJ, George TJ, Allen JG, Russell SD, Shah AS, Conte JV, et al. Institutional volume and the effect of recipient risk on short-term mortality after orthotopic heart transplant. J Thorac Cardiovasc Surg. Jan 2012;143(1):157-67, 167.e1. [Medline].
  15. Lee I, Localio R, Brensinger CM, Blumberg EA, Lautenbach E, Gasink L, et al. Decreased post-transplant survival among heart transplant recipients with pre-transplant hepatitis C virus positivity. J Heart Lung Transplant. Nov 2011;30(11):1266-74. [Medline].
  16. Caves PK, Stinson EB, Billingham M, Shumway NE. Percutaneous transvenous endomyocardial biopsy in human heart recipients. Experience with a new technique. Ann Thorac Surg. Oct 1973;16(4):325-36.[Medline].
  17. Hunt J, Lerman M, Magee MJ, et al. Improvement of renal dysfunction by conversion from calcineurin inhibitors to sirolimus after heart transplantation. J Heart Lung Transplant. Nov 2005;24(11):1863-7.[Medline].
  18. Pedotti P, Mattucci DA, Gabbrielli F, Venettoni S, Costa AN, Taioli E. Analysis of the complex effect of donor’s age on survival of subjects who underwent heart transplantation. Transplantation. Oct 27 2005;80(8):1026-32. [Medline].
  19. Griffith BP, Hardesty RL, Deeb GM, et al. Cardiac transplantation with cyclosporin A and prednisone. Ann Surg. Sep 1982;196(3):324-9. [Medline].
  20. Ye F, Ying-Bin X, Yu-Guo W, Hetzer R. Tacrolimus versus cyclosporine microemulsion for heart transplant recipients: a meta-analysis. J Heart Lung Transplant. Jan 2009;28(1):58-66. [Medline].
  21. Khan MS, Mery CM, Zafar F, Adachi I, Heinle JS, Cabrera AG, et al. Is mechanically bridging patients with a failing cardiac graft to retransplantation an effective therapy? Analysis of the United Network of Organ Sharing database. J Heart Lung Transplant. Aug 17 2012;[Medline].
  22. Hofflin JM, Potasman I, Baldwin JC, et al. Infectious complications in heart transplant recipients receiving cyclosporine and corticosteroids. Ann Intern Med. Feb 1987;106(2):209-16. [Medline].
  23. Tambur AR, Pamboukian SV, Costanzo MR, et al. The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome. Transplantation. Oct 27 2005;80(8):1019-25.[Medline].
  24. Kfoury AG, Renlund DG, Snow GL, Stehlik J, Folsom JW, Fisher PW, et al. A clinical correlation study of severity of antibody-mediated rejection and cardiovascular mortality in heart transplantation. J Heart Lung Transplant. Jan 2009;28(1):51-7. [Medline].
  25. Sweeney MS, Macris MP, Frazier OH, et al. The treatment of advanced cardiac allograft rejection. Ann Thorac Surg. Oct 1988;46(4):378-81. [Medline].
  26. Ford MA, Almond CS, Gauvreau K, Piercey G, Blume ED, Smoot LB, et al. Association of graft ischemic time with survival after heart transplant among children in the United States. J Heart Lung Transplant. Nov 2011;30(11):1244-9. [Medline].

Part III

Comparative Analysis of Transplant Clinical Outcomes based on Data in: Heart Transplant (HT) Indication for Heart Failure (HF): Procedure Outcomes and Research on HF, HT @ Two Nation’s Leading HF & HT Centers

By Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN 

 

Procedures Outcomes of Heart Transplant (HT) Indication for Heart Failure (HF)Center for Heart Failure @Cleveland Clinic, and Transplant Center @Mayo Clinic

Center for Heart Failure @Cleveland Clinic: Institution Profile

The treatment of heart failure requires a specialized multidisciplinary approach to manage the overall patient care plan.   The Kaufman Center for Heart Failure Team brings together clinicians that specialize in cardiomyopathies and ischemic heart failure for patients with:

  • All types of heart failure
  • Dilated Cardiomyopathy
  • Restrictive Cardiomyopathy
  • Arrhythmogenic Right Ventricular Dysplasia (ARVD)

Heart Failure – National Hospital Quality Measures
Cleveland Clinic, 2011 (N = 1,163) 96.9%
UHC Top Decile, 2011 99.2%
SOURCE
University Health System Consortium (UHC) Comparative Database, January through November 2011 discharges.

The Centers for Medicare and Medicaid Services (CMS) calculates two heart failure outcome measures:

  • all-cause mortality and
  • all-cause readmission rates,

each based on Medicare claims and enrollment information.

Heart Failure All-Cause 30-Day Mortality (N = 762)  July 2008 – June 2011
Cleveland Clinic 9.2%
National Average 11.6%
Heart Failure All-Cause 30-Day Readmission (N = 1,)  July 2008 – June 2011
Cleveland Clinic 27.3%
National Average 24.7%
SOURCE:
hospitalcompare.hhs.gov

The results for risk-adjusted all-cause mortality is 2% lower than the National Average and 30-day risk-adjuted readmission rates for 2008-2011 are 2% higher than the National Average.  There is no definitive information provided to explain the higher readmission rate.  One might consider that they take most difficult referrals.  The heart failure risk-adjusted readmission rate is higher than the national average; and both differences are statistically significant. To further reduce this rate, a multidisciplinary team was tasked with improving transitions from hospital to home or post-acute care facility. Specific initiatives have been implemented in each of these focus areas: communication, education and follow-up.  There is no data for comparing 1-month, 1-year, and 3-year survivals.
http://my.clevelandclinic.org/Documents/outcomes/2011/outcomes

Additional Cleveland Clinic Data is provided related to Pre- and Post-operative conditions

Preoperative patient characteristics

Prob

Diabetes mellitus 499 (21.5%) 61 (26.4%)

0.084

Congestive heart failure 758 (32.6%) 89 (38.5%)

0.069

III-IV 1830 (78.8%) 184 (84.0%)

Previous operation No injury (2324) Injury (231) P

CABG 1375 (59.2%) 162 (70.1%)

0.001

Current operation No injury (2324) Injury (231) P

CABG 897 (38.6%) 104 (45.0%)

0.056

Aortic valve surgery 1020 (43.9%) 118 (51.1%)

0.036

Tricuspid valve surgery 414 (17.8%) 52 (22.5%)

0.078

Aortic surgery 232 (10.0%) 37 (16.0%)

0.004

Postoperative results

No injury (2324) —  Injury (231) – P

PRCs 4.5  7.2 6.5  8.9

0.046

ICU stay (h) 102.3  228.6 146.3 +/- 346.9

<.001

Reoperation for bleeding 127 (5.5%) 21 (9.1%)

0.024

Sepsis 86 (3.7%) 16 (6.9%)

0.017

Stroke 56 (2.4%) 11 (4.8%)

0.033

Prolonged ventilation 505 (21.7%) 97 (42.0%)

<.001

Pneumonia 123 (5.3%) 25 (10.8%)

<.001

ARDS 32 (1.4%) 8 (3.5%)

0.015

Postoperative renal failure 237 (10.2%) 51 (22.1%)

<.001

Multisystem failure 45 (1.9%) 13 (5.6%)

<.001

Hospital death 151 (6.5%) 43 (18.6%)

<.001

Cleveland Clinic
LVAD mortality 2007-2011   5%
VAD mortality   2011
Obs 10%  Exp   17.5%  N 56
HF- NHQM
2010    1194    93.9%
2011    1163    96.9%
UHC Top decile, 2011   99.2%

Transplant Center @ Mayo Clinic: Alternative Solutions to Treatment of Heart Failure.  Mayo Clinic performs has pre-eminent adult and pediatric transplant programs.

Success Measures   2009-2011

1 mo

1 year

3 year

Heart Transplant Patient Survival — Adult
Mayo – Phoenix, AZ (n=40)

97.50%

94.63%

82.22%

Mayo – Jacksonville, FL (n=61)

95.08%

91.50%

81.82%

Saint Marys Hospital – Rochester, MN (n=48)

95.83%

95.83%

82.61%

National Average

95.89%

90.21%

81.79%

Heart Transplant – Children
Saint Marys Hospital – Rochester, MN (n=5)

100%

100%

60%

Adult Heart Organ (Graft)
Mayo – Phoenix, AZ (n=41)

97.56%

94.77%

82.22%

Mayo – Jacksonville, FL (n=61)

95.08%

91.50%

80.00%

Mayo -Rochester, MN (n=49)

93.88%

93.88%

82.61%

National Average

95.71%

89.91%

80.92%

Standards for Comparison:  SRTR function, data acquisition, analysis, and reporting.

Curator: Larry H Bernstein, MD and Curator: Aviva Lev-Ari, PhD, RN
Source: Program Specific Reprting, by S Everson [SRTR]

http://srtr.transplant.hrsa.gov/

The Scientific Registry of Transplant Recipients

supports the ongoing evaluation of solid organ transplantation in the United States. SRTR designs and carries out data analyses and maintains two websites to disseminate organ transplant information.

This site is srtr.transplant.hrsa.gov. Here you will find the OPTN/SRTR Annual Data Report, which publishes organ transplant statistics and is produced each year by SRTR staff and staff of the national Organ Procurement and Transplantation Network (OPTN).

At www.srtr.org, you will find older (pre-2010) annual data reports, current and past reports on organ procurement organizations and transplant programs, and information for researchers (including additional data tables and information about SRTR data and statistical methods).

Both sites aim to inform transplant programs, organ procurement organizations, policy makers, transplant professionals, transplant recipients, organ donors and donor families, and the general public about the current state of solid organ transplantation in the US.

SRTR also helps facilitate transplant research by providing access to data for qualified researchers interested in studying various aspects of solid organ transplantation.

The SRTR supports ongoing evaluation of the scientific and clinical status of solid organ transplantation and it provides data on all solid organ transplants and donations in the United States with oversight and funding from the Health Resources and Services Administration (HRSA), a division of the US Department of Health and Human Services, and is admionitered by the Chronic Disease Research Group of the Minneapolis Medical Research Foundation.
How SRTR differs from the Organ Procurement and Transplantation Network (OPTN).
Program-Specific Reports and their intended audience.
  1. Timeline and cohort selection.
  2. Patients who are lost to follow-up: censoring and extra ascertainment.
  3. Expected survival and risk-adjustment.
  4. Comparison points: norms versus targets.
Interpretation of survival statistics: what is important to whom? 
SRTR Products and Responsibilities: Inferential Analyses to Support Policymaking and Patient Care
*Analytic support for policy committees (OPTN, Advisory Committee on Organ Transplantation [ACOT]).
*OPTN/SRTR Annual Report.
Publications
*Report to Congress.
Journal articles and scientific presentations.
Public release data files for researchers.
*Program-specific analyses (Program-Specific Reports, Organ Procurement Organization [OPO] reports, etc).
Inferential requests.
Primary data from OPTN, supplemented with other sources.
*legislatively mandated
^Primary data source is the transplant center, submitting data through the OPTN system. Includes WL and organ allocation, tiedi, match runs.
  1. Range of other data here are incorporated either on a person-level matching basis or on an aggregate basis for comparison.
  2. Primary data source is the transplant center, submitting data through the OPTN system. Includes WL and organ allocation, tiedi, match runs.
  3. Range of other data here are incorporated either on a person-level matching basis or on an aggregate basis for comparison.
  4. Primary data source is the transplant center, submitting data through the OPTN system. Includes WL and organ allocation, tiedi, match runs.
  5. Range of other data here are incorporated either on a person-level matching basis or on an aggregate basis for comparison.
  6. National Death Index is not be used for analyses, but is used to evaluate completeness of extra ascertainment.
Each month, the SRTR receives an updated version of all data submitted by transplant centers, organ procurement organizations, and histocompatibility laboratories, along with data produced by the OPTN itself regarding organ offers, match runs, and the like.  Data linkages are used to add patient-level data, and additional ascertainment of mortality events is provided via linkage to the Social Security Death Master File.   Analysis files optimized for research are created and merged with analysis variables from the National Center for Health Statistics and the annual survey of the American Hospital Association to produce a set of Standard Analysis Files.  These are the data files used for SRTR analyses.
Regularly scheduled analyses are produced, including those available to the public such as the center-specific reports of transplant programs and OPOs, reports to the OPTN Membership and Professional Standards Committee, and the standardized insurance request for information data reports.  Program-Specific Reporting (http://www.srtr.org) uses different formats for different audiences. Feedback from centers enables data fixes and data quality improvements to occur over time.
Additional research is presented in the form of journal articles, the SRTR Report on the State of Transplantation published each year in the American Journal of Transplantation, conference proceedings, reports to OPTN and ACOT committees, an Annual Report published on the web and on CD, and a Biennial Report to Congress.  The same Standard Analysis Files that are used by SRTR are available to all researchers and can be obtained via submission of an analysis plan and completion of a Data Use Agreement.
Using SRTR-calculated center-specific statistics provides several advantages – for each audience of the CSR — over having each center self-report these characteristics:
  • Uniform methodology: The SRTR provides a uniform methodology of calculation. These methods are standard and accepted within the statistical and medical communities, however they are not the only ones available.
  • Audited data collection: All data on which these statistics are based are audited by the OPTN. The United Network for Organ Sharing (UNOS), the contractor for the OPTN, works to ensure the accuracy and reliability of these data.
  • Extra ascertainment of mortality: The SRTR helps find information about patients who become lost-to-follow-up that may be unavailable to transplanting centers, or very difficult to find.
  • Risk adjustment: Comparison of outcomes should be based on risk-adjusted models that account for the types of patients treated. Without national data, it is impossible for centers to calculate risk-adjusted comparison points.

Program-Specific Reporting –  different formats for different audiences: What we choose to focus on 

 

 Percent survival at one year, three years.

  1. What choices do our patients have?
  2. How well are we doing?

*Report Contents – Focus on patient outcomes

 Report Tables [10-11]– 
  1. Graft and patient survival rates compared with expected values
  2. Updated every 6 months (January, July).
  3. Patient and graft survival tables report 1-month, 1-year, and 3-year outcomes for 2.5-year cohorts of recipients.

Calculating Survival

 

Transplant Month Follow-up Group A: Transplant > 1 Y Group B:Transplant 6-12 Mo All
Months 0-6 Transplants
Deaths
100
10
100
14
200
24
Survival 90% 86% 88%
Months 7-12 At-Risk
Deaths
Survival
90
18
80%
Not yet observed,
Use 80%
.88*.80 = 70.4%or  (72 + 68.8)/2 = 70.4
1 Year Survival .90 * .80 = 72% .86*.80 = 68.8%

Incomplete Data and Loss to Follow-Up

  • Censoring (Kaplan Meier/Cox) works only if “lost” patients have similar failure rates as followed patients (unbiased).
  • Censoring can produce unstable estimates for small samples
  • NDI study indicates that the SRTR identifies > 99% of deaths
  • Observed rates are compared with rates that would be expected based on characteristics of recipients and donors at each center.
  • Allows fair comparison among centers that treat different types of patients
  • Is the difference we see between the observed survival of 87.78% and the expected rate of 89.41% large enough to be meaningful? The answer may depend perspective.

The percent surviving at one year is only 2% lower than expected, an apparently small difference. However, the same difference appears more consequential when comparing the percent died that implied by subtracting survival percents from 100: the percent of patients who had died by the end of the first year was a full 15% higher than expected. Finally, in our example center that performed 90 transplants during a 2.5-year period, the count of deaths observed during follow-up was 30% higher, accounting for 2.5 deaths more than we would expect during time these patients were followed.

The difference between each of these is stark. The first change from a 2% difference to a 15% difference reflects the change in denominator: a small percentage point difference is a much smaller fraction of survival (usually a large number at one year) than of mortality (usually a small number). Several years after transplant, when survival rates may be close to 50%, the contrast would not be as evident.

The difference between the percent died and death count is more subtle: the expected number of deaths is calculated according to the time that patients are followed after transplant, so a patient whose follow-up ends immediately after transplant – for any reason, including death — is smaller than the expected number of deaths for a patient who died after ten months. Therefore, this last statistic accounts for the difference between a patient who survives only briefly during follow-up, and one who survives nearly the entire period, despite the fact that they have both died in the end-of-period accounting of “percent died”.

Survival time -expected deaths

Risk Adjustment

What rate would be expected for patients at this center if their outcomes were comparable to national outcomes for similar patients?
“Similar” defined by characteristics that affect the rate, such as:

  • Demographics
  • Etiology
  • Severity of illness

Differences between observed and expected outcomes are not due to these adjustment factors.

*notion of a “similar” patient: have in-common characteristics that may influence the outcome –
include basic demographic factors such as age, etiology of disease, and the patient’s severity of illness.

journal.pmed.0020133.g001  Global Mortality and Burden of Disease Attributable to Cardiovascular Diseases and Their Major Risk Factors for People 30 y of Age and Older

278px-Preventable_causes_of_death
Causes_of_death_by_age_group

Adjusted odds ratios comparing the results of CABG and PCI-stenting in the various prespecified subsets.

50-Graph-4-33_2012  Hospitalization Rates for Heart Failure, Ages 45–64 and 65 and Older, U.S., 1971–2010

48-Graph-4-30_2012  Age-Adjusted Prevalence of Cardiovascular Disease Risk Factors in Adults, U.S., 1961–2011

Risk-Adjustment Models

Each risk-adjustment model is published one month in advance of the PSRs (Figure 5). These tables serve not only as a list of all characteristics incorporated, but also tell the reader:

  1. The beta, or calculated coefficient, tells what was the effect of that characteristic on expected risk of dying or failed transplant?
  2. The standard error and p-value tell how much random variance there was around this estimate, and how sure we are that there is a real effect of this characteristic.
  3. Models are repeated for a series of three different cohorts of transplants, allowing a comparison of how stable the coefficients are across time.
  4. The index of concordance, for each model, tells the percent of variation in the order of events (deaths or graft failures) that is accurately predicted by the model. A index of 100% would suggest that the model perfectly predicts the order of events; 50% would suggest that the order is random with regard to predictors.

*Odds Ratio >1 = Failure/Death More Likely = Lower Expected;
Odds Ratio <1 = Failure/Death Less Likely = Higher Expected

Adjusting for Age

Nationally: Average survival, 85%.

  • 50% of patients are young with 95% survival.
  • 50% of patients are old with 75% survival.

Center A treats only older patients, 80% survival:
Center survival of 80% worse than national average of 85%.
100% are older patients with expected 75% survival.
Center A patients have better expected survival compared with similar patients nationwide
Center X Treats More Older Recipients than the National Average

more older recipients

Adjustment: Account for Case Mix

The older recipient age at Center X (along with other factors) gives Center X an expected 13.1% deaths, compared with the national average of 9.5%.
Use ratio of observed/expected deaths.

Adjustment: Random Variation

Obs/Exp Deaths: Center X = 1.1 (0.88-1.37); National Ave = 1.0
The confidence interval for Center X, reflecting random variation in this measure over time, overlaps the national average.
Do not flag Center X.

Concepts: Actionable, Important, and Significant

The first principle in these criteria is that all comparisons should be based on observed and expected events during the time a patient is actually followed either by the center or, in the case of patient survival, by extra ascertainment; no imputed survival should be used. They should also account for the difference in outcomes between a patient who dies in the 1st week after transplant versus 51st week.
The following criteria, applied by the MPSC, are based on comparison of counts of observed and expected deaths (graft failures) as presented in “Deaths during follow-up period”. To be identified for further review by the MPSC, differences between observed and expected must meet all of the following criteria:
Actionable: the magnitude of the problem, in terms of potential lives saved, should be sufficient to take action
  1. MPSC Criteria: Observed (O) – Expected (E) greater than 3, O – E > 3
  2. Interpretation: 3 excess deaths per 2-year transplant cohort
Important: a clinically significant pattern, suggesting that it may be changeable, indicated by a high fraction of excess deaths
  1. MPSC Criteria: Standardized Mortality Ratio (SMR) > 1.5; O / E > 1.5
  2. Interpretation: 50% more deaths than expected
Significant: it should be unlikely that the difference occurred by random chance alone
  1. MPSC Criteria: one-sided p-value less than .05
  2. Interpretation: there is less than a 5 percent chance that a poor outcome occurred by simple random variation

Important: More than 3 excess deaths

more than 3 excess deaths

Actionable: More than 50% excess deaths

more than s 50% excess deaths

excess deaths unlikely due to hance

MPSC Flagging Boundaries

1-s2.0-S0194599809003301-gr1    action statement may be classified as an option, recommendation, or strong recommendation

Part IV

Imaging Technologies in use for Clinical Monitoring of Patients with Heart Transplant: Donor Human Heart and Artificial Heart

By Justin D Pearlman, MD, PhD, FACC

Imaging of the heart monitors success and viability of the transplanted heart in terms of

what fraction of the contents of each ventricle moves out of the heart (ejection fraction),

  • what volumes the heart sees
  1. end-diastolic volume, or EDV, and
  2. end-diastolic diameter, or
  3. LVIDd,
  4. end systolic volume or ESV),
  5. how well the walls move (wall motion) and
  6. wall thickening analysis,
  • tissue character
  1. visual evidence for changes in the heart muscle,
  2. perfusion (delivery of nutrient blood supply to the heart muscle), and
  3. various means to detect coronary artery disease (obstructions to blood delivery to the heart muscle).

Clinical tools for imaging the heart include:

  1. The major tool – ultrasound (echocardiography),
  2. cardiac magnetic resonance (CMR),
  3. computed xray tomography (CT),
  4. catheterization with xray imaging (coronary angiography and ventriculography),
  5. metabolic marker distribution by positron emission tomography (PET), and
  6. radioactive marker distribution (nuclear imaging, SPECT).

Ultrasound applies alternating current to a piezoelectric crystal (lead zirconate) to produce compressions and expansions of material as a wave pattern that relies on tissue elastic properties to propagate into the tissue, reflecting back when the wave encounters a change of properties (acoustic impedance mismatch). Display of signal versus time on an oscilloscope (like an ECG monitor) constitutes “A-mode”(amplitude) display, whereby the distance between peaks corresponds to distances along the path that can report thickness of the left ventricle, and diameter of the left ventricular cavity. Time translates to distance because the speed of sound through tissue is fairely constant, ~1540 meters/second. Collapsing the peaks to bright dots represents the same data in “B-mode” (brightness) which reduces the data to a line of variable intensity with bright dots marking changes in tissue (e.g., muscle versus blood). Attaching a position sensor to the handle of the sound source (the transducer) enabled plotting the B-mode signal on a 2D screen to indicate the position of the sound beam. Gynecologists showed that a steady sweep of the transducer (C-mode, composite) then generated 2D images that delineated the shape of a fetal head, and as quality improved, the gender prior to birth. The invention of phased-array crystal sets (multiple sources electrically activated sequentially with specific timing) enabled generation of a composite beam that is electronically swept in an arc with no mechanically moving parts. That is now the main method of ultrasound imaging, called phased-array sector scanning. More advanced phased arrays sweep in a 2D pattern to generate 3D imaging (4D or dynamic 3D, when you include repeating over time).

The e-Reader is encourage to review Cardiovascular Imaging Chapters in each of the three volumes.

For new technological developments in achieving Optimal PCI Outcomes and for Visual Tools for Characterization of endovascular tissue affecting Coronary Circulation, review the following article:

Coronary Circulation Combined Assessment: Optical Coherence Tomography (OCT), Near-Infrared Spectroscopy (NIRS) and Intravascular Ultrasound (IVUS) – Detection of Lipid-Rich Plaque and Prevention of ACS

Part V

The Failure of a Heart Transplant – Pathology and Autopsy Findings

by Larry H Bernstein, MD, FCAP 

Section A.  SRTR Graft and Patient Survival Data

Table 1.  Transplant Survivals, 2011, and related conditions

Activities    2011 Numbers
Deceased donor transplants (n=number) 2,322
Adult graft survival (based on 4595  transplants) 89.91 (%)
Adult patient survival (based on 4449 transplants) 90.21 (%)
Pediatric graft survival (based on 886  transplants) 90.74 (%)
Pediatric patient survival (based on 829  transplants) 91.31 (%)
Primary Disease (%) of Waitlist
Cardiomyopathy 49.4
Coronary Artery Disease 34.7
Retransplant/Graft Failure   4.4
Valvular Heart Disease   1.7
Congenital Heart Disease   8.4

Table 2.  Recipient Condition at Transplant (%)

Not Hospitalized 54.0
Hospitalized 14.6
ICU 31.0
No Support Mechanism 25.2
Devices 42.4
Other Support Mechanism 32.2

Table 3.  Donor Characteristics

Cause of Death (%)
Stroke 20.9
MVA 23.4
Other 55.7
Age (years)
18-34 48.8
35-49 24.5
12-17 9.4
Cold ischemic time 1.5-4.5 h 85.3

Table 4.  Graft and Patient Survival

Survival by… time since transplant
1 mo 1 yr 3 yrs
Adult (Age 18+)
Graft survival (%)   95.7   89.9   80.9
# failures

197

442

847

Patient survival (%)   95.9   90.2   81.8
# deaths

183

415

783

Pediatric (Age < 18)
Graft Survival (%)   96.3   90.7   82.0
Graft Failures

  33

  80

151

Patient Survival (%)

  96.4

  91.3

 82.93

Deaths

  30

  70 134

* 07/01/2006 and 12/31/2008 for the 3 Year Model

Table 4.    Risk Model Documentation – Adult, Three−Year Graft Survival

Characteristic Level Estimate Std. Err. P−Value
Bilirubin at Transplant mg/dL 0.0364 0.008 <0.0001
Dialysis at Transplant Yes 0.8026 0.169 <0.0001
Donor Age 0−17 −0.5789 0.140 <0.0001
18−34 −0.3098 0.074 <0.0001
Ischemic Time hrs 0.1298 0.033 <0.0001
Previous Transplant Yes 0.4251 0.157 0.0069
Recipient DX Cardiomyopathy −0.1933 0.078 0.0130
Recipient Age 18-34 0.2806 0.110 0.0107
65+ 0.2694 0.101 0.0074
Recipient Race Black 0.4104 0.086 <0.0001
Recipient SCrea >1 & <=1.5 mg/dL 0.0115 0.086 0.8933
>1.5 mg/dL 0.4316 0.095 <0.0001
Recipient on VAD Yes 0.2777 0.086 0.0013
Recipient on Vent Yes 0.7014 0.169 <0.0001

* SRTR Program−Specific Report   July 12, 2012

Table 5.  Risk Model Documentation  Adult, Three−Year Patient Survival

Characteristic Level Estimate Std. Err. P−Value
Donor Age 0−17 −0.4758 0.1452 0.0010
18−34 −0.3066 0.0764 0.0001
Ischemic Time hrs 0.1400 0.0344 <0.0001
Most Recent CPRA/PRA% 0.0039 0.0019 0.0359
Recipient Age 18−34 0.3041 0.1157 0.0086
65+ 0.3089 0.1013 0.0023
Recipient DX Cardiomyopathy −0.2151 0.0809 0.0078
Congen Heart Dis 0.5504 0.2085 0.0083
Recipient Race Black 0.4942 0.0895 <0.0001
Recipient SCrea >1 and <=1.5 0.0245 0.0887 0.7827
>1.5 mg/dL 0.5053 0.0991 <0.0001
Recipient on VAD Yes 0.2559 0.0816 0.0017
Recipient on Vent Yes 0.7340 0.1852 0.0001

Note the following: 

1. The most common transplant recipients in adults are cardiomyopathy and CAD, and congenital heart disease in children.
2.  recipient on VAD or on vantilator is significant
3.  ischemic time for donor heart is usually 1.5-4.5 hours, but longer time has an effect on graft and patient survival
4. Recipient serum creatinine exceeding 1.5 mg/dl is unfavorable, but considering BMI and age related renal nephron loss, eGFR would be a better measure.5.  African-American has an effect, but it is not at all clear whether sickle cell trait or disease is a factor.
6. Half the recipients are not hospitalized, and they might coincide with no or other support.

Section B.  Special Concerns

Topic 1

Cellular repopulation of myocardial infarction in patients with sex-mismatched heart transplantation
Source: Georg-August-University G€ottingen.  c2004, Eur Soc Cardiol

Recent studies have suggested that human extracardiac progenitor cells are capable of differentiating into cardiomyocytes. In animal studies, myocardial infarction attracted bone marrow stem cells and enhanced their differentiation into cardiomyocytes.
Myocardial infarction enhances the invasion of extracardiac progenitor cells and their  regeneration of endothelial cells. However, a significant differentiation into cardiomyocytes as a physiological mechanism of postischaemic regeneration does not occur in transplanted patients.

Topic 2

Five-year follow-up of hepatitis C-naïve heart transplant recipients who received hepatitis C-positive donor hearts.
G S Gudmundsson, K Malinowska, J A Robinson, B A Pisani, J C Mendez, B K Foy, G M Mullen
Advanced Heart Failure/Heart Transplant Program, Loyola University, Maywood, Illinois, USA.
Transplantation Proceedings (impact factor: 1). 07/2003; 35(4):1536-8.
Source: PubMed

Due to the risk of transmission of hepatitis C virus, the use of hepatitis C seropositive donors in heart transplantation is controversial. The transmission rate of hepatitis C in this patient population is estimated to range from 67% to 80%. Long-term clinical outcomes of heart transplant recipients of hepatitis C-positive donor hearts are not well described. We report the 5-year long-term outcome of seven hepatitis C-naïve heart transplant recipients who received hepatitis C-positive donor hearts.

Seven hearts transplant recipients, six men and one woman were included in our study. After a mean follow-up of 63.3 +/- 20.4 months (range 28.2 to 85.9), four of seven (57.1%) patients are hepatitis C-negative, have normal liver function tests, and no clinical evidence of hepatitis. Three of seven (43%) have been diagnosed with hepatitis C by liver biopsy or the HCV-RNA reverse transcriptase polymerase chain reaction at a mean follow-up of 35.1 months (18.8 months posttransplantation). One had an accelerated course of hepatitis that was ultimately fatal, one was successfully treated with interferon, and the third died from other causes than liver injury. Overall, the 5-year survival was 71.4%.

Topic 3

Cryptococcus neoformans Infection in Organ Transplant Recipients: Variables Influencing Clinical Characteristics and Outcome
Shahid Husain, Marilyn M. Wagener, and Nina Singh
Veterans Affairs Medical Center and University of Pittsburgh
Thomas E. Starzl Transplantation Institute, Pittsburgh, Pennsylvania, USA
Emerging Infectious Diseases 376 Vol. 7, No. 3, May–June 2001

Unique clinical characteristics and other variables influencing the outcome of Cryptococcus neoformans infection in organ transplant recipients have not been well defined. From a review of published reports, we found that C. neoformans infection was documented in 2.8% of organ transplant recipients (overall death rate 42%). The type of primary immunosuppressive agent used in transplantation influenced the predominant clinical manifestation of cryptococcosis. Patients receiving tacrolimus were significantly less likely to have central nervous system involvement (78% versus 11%, p =0.001) and more likely to have skin, soft-tissue, and osteoarticular involvement (66% versus 21%, p = 0.006) than patients receiving nontacrolimus-based immunosuppression. Renal failure at admission was the only independently significant predictor of death in these patients (odds ratio 16.4, 95% CI 1.9–143, p = 0.004). Hypotheses based on these data may elucidate the pathogenesis and may ultimately guide the management of C. neoformans infection in organ transplant recipients.

Patients were 12 to 67 years of age (median 44 years); 78% were male. The mean incidence of C. neoformans infection was 2.8 per 100 transplants (0.3 to 5.3 per 100). The overall incidence was 2.4% in liver, 2.0% in lung, 3.0% in heart, and 2.8% in renal transplant recipients. Of 127 transplant recipients who could be evaluated, 100 (79%) had azathioprine as the primary immunosuppressive agent, 9 (7%) had tacrolimus, 11 (9%) had cyclosporine, and 7 (6%) had cyclosporine and azathioprine. Of these 127 patients, 78 were also receiving prednisone in various dosages. The incidence of cryptococcosis was 4.5 per 100 transplants in patients who received tacrolimus, 2.4 per 100 transplants in patients who received cyclosporine, and 3.4 per 100 transplants in patients who received azathioprine. These rates did not differ significantly. Rejection episodes preceding cryptococcal infection were documented in 17 (25%) of 67 patients; rejection had occurred a median of 7 months (from 5 days to 49 months) before onset of infection.

Cryptococcosis occurred a median of 1.6 years (from 2 days to 12 years) after transplantation. Overall, 14 (15%) of 94 cases occurred within 3 months, 10 (11%) of 94 in 3 to 6 months, 15 (16%) of 94 in 6 to 12 months, and 55 (59%) of 94 >12 months after transplantation.  The median time to onset after transplantation was 35 months for kidney, 25 months for heart, 8.8 months for liver, and 3 months for lung transplant recipients (p = 0.001). Overall, cryptococcosis developed in 100% of the lung, 75% of the liver, 33% of the heart, and 30% of the kidney transplant recipients within 12 months of transplantation (p = 0.002).

Topic 4

Diagnostic Accuracy of Mortality on a Population of Heart Transplant Patients
M AMUCHÁSTEGUI, AE CONTRERAS, O SALOMONE, A DILLER, et al.
Hospital Privado Centro Médico de Córdoba
REV ARGENT CARDIOL 2008;76:292-294.

Although morbidity and mortality rates in heart transplant have been extensively analyzed, most mortality studies and mortality registries in heart transplant patients are based on clinical data.
Between January 1990 and January 2005 all dead transplant patients were included. The final diagnosis of the cause of death was confirmed with necropsy or biopsy of a solid organ. The causes of death assessed were early graft failure, cellular rejection, graft vascular disease, neoplasms and others.
Seventy three patients underwent heart transplantation during the study period. Thirty one patients died. The cause of death was certified in 61% of cases by 12 necropsies and 7 solid organ biopsies.

  • Cellular rejection greater than grade III was the most frequent cause of death.
  • Histopathology studies differed from the clinically suspected cause of death in 12.9% of cases.

Clinical and pathological information derived from post mortem studies is an indicator of the reality of our practice and constitutes an underlying mainstay for understanding transplant patients and for their further management; in this sense, performing necropsies is of vital importance for these patients.

Topic 5

How do Heart Failure patients die?
S. Orn and K. Dickstein
Central Hospital in Rogaland, Stavanger, Norway
European Heart Journal Supplements (2002) 4 (Supplement D), D59-D65
http://eurheartjsupp.oxfordjournals.org/

Approximately 90% of heart failure patients die from cardiovascular causes. Fifty per cent die from progressive heart failure, and the remainder die suddenly from arrhythmias and ischaemic events. Autopsy reveals the presence of an acute ischaemic event inapproximately 50% of sudden deaths and in 35% of all deaths among patients with ischaemic heart failure.

An accurate description of the cause and mode of death is important if we are to elucidate the mechanisms that are operative in the heart failure population.

At present, the most accurate data on mode of death are obtained from large randomized heart failure trials. They indicate that current treatment strategies for heart failure prolong life expectancy, but have relatively little impact on the proportion of heart failure patients who die from cardiovascular causes. The ultimate goal of intervention is to shift the balance toward more deaths from non-cardiovascular causes. (Eur Heart J Supplements 2002; 4 (Suppl D): D59-D65)
The heterogeneity of the heart failure population is reflected in the different ways in which these patients die.

  • Some deteriorate progressively, whereas others
  • die after acute episodes of decompensation.
  • Others die suddenly and unexpectedly, and some (relatively few)
  • die from noncardiac causes.

Before the angiotensin-converting enzyme (ACE) inhibitor era, it was estimated that

  • 90% of the total deaths in heart failure patients were from cardiovascular causes,
  • 49% were related to worsening heart failure,
  • 22% to arrhythmias and
  • 11% to acute myocardial infarction[S].

It is conventional to categorise death according to mode and cause of death.

  • Cause of death addresses the mechanisms by which death occurs, such as arrhythmia, acute myocardial infarction or progressive heart failure (Table 1).
  • Mode of death is perhaps easier to categorise.
  • Mode and cause of death are not the same, although they are often used interchangeably.

Sudden death has various underlying causes, such as

  • arrhythmia,
  • acute myocardial infarction,
  • pulmonary embolism,
  • myocardial or aortic rupture, and
  • stroke.

Sudden cardiac death is defined as natural death due to cardiac causes, heralded by abrupt loss of consciousness within 1 h of the onset of acute symptoms[2].

In order to avoid confusion in terminology, some clinical trials subclassify death without using the term ’cause of death’ and end-point committees focus instead on mode and place of death (Table 1)[31]. However, although it is more difficult to classify cause of death than mode of death, it is nevertheless productive to examine the causes of death among heart failure patients. The cause of death reflects the underlying pathophysiology of the disease, and helps us to understand the mechanisms responsible for its progression. Unravelling the mechanisms that lead to death is clinically relevant and may reveal potential new treatment targets. Effective treatment may alter the cause of death, and should ideally shift the operative mechanism from cardiovascular to noncardiovascular. Most of our knowledge of the cause and mode of death in heart failure comes from the

  • large randomized mortality trials and from
  • official death registries.

However, both of these sources of information have their problems.

A simplified classification of heart failure deaths

  • Cardiovascular
  • Non-cardiovascular
  • Cardiac
  • Myocardial infarction
  • Progressive heart failure
  • Other cardiac
  • Sudden death
  • Non-cardiac
  • Stroke
  • Other
  • Procedure-related

Conclusions

by Larry H Bernstein, MD, FCAP 

Part I

Leading Causes of Death

Number of Deaths – Leading Causes

Heart disease

597,689

Cancer

574,743

Chronic Lung Disease

138,080

Stroke

129,476

Accidents

120,859

Alzheimer’s

83,494

Diabetes

69,071

Kidney disease

50,476

Influenza and Pneumonia

50,097

Suicide

38,364

*National Vital Statistics Report (NVSR) “Deaths: Final Data for 2010.”   MortalityData@cdc.gov.

WHO Leading Causes of Death

Low income countries

Deaths (mil)

% of deaths

Lower respiratory infections

1.05

11.3

Diarrheal diseases

0.76

8.2

HIV/AIDS

0.72

7.8

Ischemic heart disease

0.57

6.1

Malaria

0.48

5.2

High-income countries

Deaths (mil)

% of deaths

Ischemic heart disease

1.42

15.6

Cerebrovascular disease

0.79

8.7

Bronchioepithelial cancers

0.54

5.9

Alzheimer and dementias

0.37

4.1

Pneumonias

0.35

3.8

High-income countries

Deaths (mil)

% of deaths

Ischemic heart disease

5.27

13.7

Stroke

4.91

12.8

COPD

2.79

7.2

Lower respiratory infections

2.07

5.4

Diarrheal diseases

1.68

4.4

World

Deaths (mil)

% of deaths

Ischaemic heart disease

7.25

12.8

Stroke

6.15

10.8

Pneumonias

3.46

6.1

COPD

3.28

5.8

Diarrheal diseases

2.46

4.3

HIV/AIDS

1.78

3.1

Q: What is the number one cause of death throughout the world?
Cardiovascular diseases kill more people each year than any others. In 2008, 7.3 million people died of ischaemic heart disease, 6.2 million from stroke or another form of cerebrovascular disease.

Q: Isn’t smoking a top cause of death?
Tobacco use is a major cause of many of the world’s top killer diseases – including cardiovascular disease, chronic obstructive lung disease and lung cancer.

Deaths across the globe: an overview

Imagine a diverse international group of 1000 individuals representative of the women, men and children from all over the globe who died in 2008. Of those 1000 people,

  • 159 would have come from high-income countries,
  • 677 from middle-income countries and
  • 163 from low-income countries.

What would be the top 10 causes of their deaths?
Low income countries
http://who.int/entity/mediacentre/factsheets/fs310_graph3.gif
Middle income countries
http://who.int/entity/mediacentre/factsheets/fs310_graph3.gif
High income countries
http://who.int/entity/mediacentre/factsheets/fs310_graph3.gif

Note: In this fact sheet, we use low-, middle- and high-income categories as defined by the World Bank. Countries are grouped based on their 2009 gross national income. See World health statistics 2011 for more information.

SOURCE

World health statistics 2011

Part II

Advances in Imaging Technology

This document discusses the advances in cardiac surgery assisted by rapid advances in cardiac imaging technology over the last 15 years.  This portion concentrates on the treatments for advanced and disabling congestive heart failure as the age expectancy has increased to a range of early 8th and mid-9th decade, depending on patient related comorbidities, nutrition and activity status.  Many of the patients who require a heart transplant have coincident metabolic syndrome, advanced coronary artery circulation compromise, and/or atherosclerotic disease at the aortic arch.  The advances in cardiothoracic technique has enabled a parallel advance in ventricular assist devices and a total artificial heart, which has allowed the maintenance of patients on waitlists until a suitable donor can be found, which is usually under a 5 year period.  The ventricular assist device is selected for those patients who have sufficient reserve of left ventricular function. The cardiac and cardiosurgical advances have been advanced by the development of vastly improved imaging for both diagnosis and for enabling safety of procedures.

Cardiac magnetic resonance imaging is a noninvasive technique for assessing heart structure and function without the need for ionizing radiation. Its ability to precisely outline regions of myocardial ischemia and infarction gives it an important role in guiding interventional cardiologists in revascularization. Its ability to characterize and precisely quantify abnormal regurgitant flow volumes or abnormal shunts also makes it a valuable tool for many noncoronary interventions. The evidence is sufficient to show that cardiac magnetic resonance in guiding complex therapies in the catheter laboratory, as well as practical issues that need to be addressed to allow the application of this powerful tool to an increasing number of patients.  But this advantage extends as well to the transplantation arena.1 (Cardiac magnetic resonance imaging for the interventional cardiologist. GA Figtree, JLønborg, SM Grieve, MR Ward, RBhindi. University of Sydney, Sydney, Australia.  PubMed 02/2011; 4(2):137-48.  http://dx.doi.org/10.1016/j.jcin.2010.09.026.)

Further, A novel approach to three-dimensional (3D) visualization of high quality, respiratory compensated cardiac magnetic resonance (MR) data is presented with the purpose of assisting the cardiovascular surgeon and the invasive cardiologist in the pre-operative planning2. Developments included:

(1) optimization of 3D, MR scan protocols;
(2) dedicated segmentation software;
(3) optimization of model generation algorithms;
(4) interactive, virtual reality visualization.

The approach is based on a tool for interactive, real-time visualization of 3D cardiac MR datasets in the form of 3D heart models displayed on virtual reality equipment. This allows the cardiac surgeon and the cardiologist to examine the model as if they were actually holding it in their hands. To secure relevant examination of all details related to cardiac morphology, the model can be re-scaled and the viewpoint can be set to any point inside the heart. Finally, the original, raw MR images can be examined on line as textures in cut-planes through the heart models3. (A new virtual reality approach for planning of cardiac interventions. T S Sørensen, SV Therkildsen, P Makowski, JL Knudsen, EM Pedersen. University of Aarhus Abogade 34, 8200 N, Arhus, Denmark. PubMed 07/2001; 22(3):193-214.

In addition, TeraRecon, (www.terarecon.com), the largest dedicated provider of advanced visualization and decision support solutions for medical imaging, showcased iNtuitionREVIEW™, a powerful new multi-modality, multi-monitor review and collaboration tool at the 24th European Congress Of Radiology4, held at the Austria Center, Vienna, Austria, March 8th-11th 2013. iNtuitionREVIEW is part of the iNtuition™ solution suite for advanced image management and quantitative decision support.

iNtuition has always complemented PACS with advanced functionality to resolve specialized use cases and workflow challenges not adequately addressed by existing PACS solutions.  Features relevant to this discussion are:

  • Time-Volume Analysis – Enhanced support for Cardiac MRI image acquisitions
  • 3D/4D Visualization – Enhanced TAVI (transcatheter valve implantation) analysis
  • Lesion-Specific Analysis – Support for research into downstream impact of stenosis

Editorial5: Seeing the heart; the success story of cardiac imaging
European Heart Journal 2000; 21(16): 1281–1288
http://dx.doi.org/10.1053/euhj.2000.2299

In 1896 a large audience at the Wurzburg Physical Medical Society attended a lecture and a demonstration, published a paper in 1895 ‘Eine Neue Art von Strahlen’ in the Annals of the Society. He showed an image of the hand of the famous anatomist F. Von Kolliker (1817– 1905). He was awarded the first Nobel prize laureate in Physics in 1901.  FH Williams (1852–1936) began lecturing on the use of X-rays in visualization of the heart. In his paper ‘A method for more fully determining the outline of the heart by means of a fluoroscope together with otheruses of this instrument in medicine, he laid the basis for quantitative cardiac measurements from the chest X-ray.

To make angiocardiography of the heart possible, the feasibility of human cardiac catheterization had to be demonstrated. In 1929 W. Forssman (1904–1979) introduced ‘. . . a well oiled 65 cm long ureteral catheter’ into his antecubital vein to reach the right atrium. Soon thereafter he performed the first cardiac angiocardiogram on himself using 20 cc of 25% sodium iodide. Forssman shared the Nobel Prize for Medicine with A. Cournard and D. Richards in 1956.

The modern era of cardiac X-ray imaging began after the Second World War. G. Hounsfield of EMI Ltd tested their mathematical solutions and constructed the first clinical CT, which was installed in the Atkinson Morle Hospital in London in 1971 for brain scanning. This instrument revolutionized radiological imaging. Electronic and computer developments resulted in the image intensifier in 1952, which was a critical tool for analysing internal cardiac anatomy and the performing of selective coronary arteriography. Cormack and Hounsfield received the Nobel Prize for Physiology in 1979.  Subsequent major advances have been the dramatic increase in the speed of scanning and image reconstruction and improved image quality as a result of faster and more sophisticated computers. At the Mayo Clinic, dynamic volume scanning was achieved in 1975 with the dynamic spatial reconstructor which is based on multiple X-ray sources  and multiplex detectors for scanning the heart using the mathematical principles of CT.  Fast computed tomography, or electron beam tomography of the heart, was introduced by D. Boyd and co-workers in 1979 at Imatron. Contrary to the conventional CT scanner, this instrument has no moving parts and can acquire an image in as little as 50 ms, obviating the need for ECG-gating. By successively steering a small focal spot size electron beam at four tungsten target rings, producing a moving beam 180o about the patient, with a 180o ring of detectors, the heart is imaged virtually free of motion artifacts.

The existence of ultrasound was recognized by L. Spallanzani (1729–1799). He demonstrated that bats who are blind navigate by means of echo reflection using inaudible sound. In 1880, Jacques and Pierre Curie discovered the piezo-electric effect, a peculiar phenomenon observed in certain quartz crystals, which were the basis of early ultrasound systems and were later replaced by ferroelectric materials. The first suggestion that submerged objects could be located by echo-reflection probably came after theTitanic disaster in 1912. During World War I, P.Langevin (1872–1946) conceived the idea in 1917 of using a piezo-electric quartz crystal as both transmitter and receiver, and this ultimately led to the development of sonar which was completed with the invention of the cathode ray tube, extensively used in World War II for ship navigation and remote submarine detection.  In 1950, the German W. D. Keidel, also using an echo-transmission technique, performed the first cardiac examinations in an attempt to measure cardiac output.

In the late 1960s, the fibreoptic recorder, a spin-off from space technology, was introduced allowing the M-mode recording of all structures along the ultrasound beam: this constituted the definitive breakthrough in echocardiography. Today, M-mode echocardiography remains an important part of a complete cardiac ultrasound examination because of its high temporal resolution.  J Griffith and W Henry introduced the mechanical sector-scanner in 1974, in the same year that FL Thurstone and OT.von Ramm constructed their electronic phased-array scanner. Today, phased-array scanners are the most widely available tomographic imaging instruments with a tremendous impact on cardiac diagnosis. Recently, new computer technologies have enabled the development of volume-rendered data which display tissue information possible even in real-time.   The mono- and biplane electronic phased-array probes developed by J. Souquet in 1982 and his multiplane probe in 1985 represented the definitive clinical breakthrough of transoesophageal echocardiography.

The pulsed-wave Doppler technique allowed depth selection for blood flow velocity interrogation, but the major step forward for its clinical acceptance was its combination with imaging: the duplex scanner, reported by F. E. Barber et al. in 1974[35]. This development ultimately led to the integration of pulsed-wave Doppler with two-dimensional phased-array systems and allowed blood flow to be studied at selected regions within the image plane. The Bernouilli equation is now the cornerstone for Doppler assessment of cardiac haemodynamics and was published by the Dutch born D. Bernouilli (1700–1782) in his treatise ‘Hydrodynamica’ in 1738.  The rapid progress in interventional cardiology renewed the interest in imaging devices, allowing circumferential imaging of the arterial wall under the endothelial surface. Both mechanical single-element and multi-element electronic systems are now increasingly used.

De Hevesy introduced the red cell blood volume measurement and the1284 anniversary ‘dilution principle’ in humans using the first man-made radioisotope 32P produced by the cyclotron in Berkeley, a milestone invention by EO Lawrence in 1931 for which he received the Nobel Prize in 1939. With the cyclotron it was now possible to artificially produce radiopharmaceuticals and radionuclides, which became increasingly available for clinical research. Diagnostic nuclear imaging techniques can be divided into four general groups, depending on localization, dilution, flow or diffusion and biochemical and metabolic properties. Most of these basic principles were first demonstrated by de Hevesy using cyclotron-produced radioisotopes and techniques that he had described many years before—he should therefore be considered the ‘father of nuclear medicine’. It was the introduction of technetium-99m which spurred on the growth of nuclear medicine because of its ideal properties for gamma camera imaging, its short half life and the possibility of producing it in a hospital radiopharmacy. There are now radiopharmaceuticals labelled with 99mTc for almost every application in nuclear medicine. However, the clinical application of nuclear imaging required both counting and detection of radioisotope emissions. Modern counting equipment dates back to 1908 when H Geiger made his first electron counting tube, the precursor of the 1928 Geiger counter. The major breakthrough in radioisotope emission detection was the development of the scintillation scanner by B. Cassen in Los Angeles in 1949, an instrument rapidly followed by refinements. The scintillation camera was designed by Anger based on a concept proposed by DE Copeland and EW Benjamin and was followed by the electronic gamma camera in 1952, which is still the basis of the scintillation camera used today.

Single photon emission tomography (SPET) is based on the pioneering work of Kuhl and Edwards and the first clinical system became available in 1953. However, digital computer technology was necessary for emission tomography as we use it today and put the ‘C’ in SPECT. Tomographic capabilities have proved invaluable in the clinical use of nuclear imaging of the heart. Clinical application rapidly followed technical advances. Although Wren et al. laid the foundation of PET in 1951 it was Sweet and Brownell of Massachusetts General Hospital who conceived the idea of positron imaging which relies on the annihilation radiation emitted at 180o when positrons and electrons meet. PET has a clinical role in defining myocardial viability in patients with ischemic left  ventricular dysfunction who may benefit from revascularization rather than transplantation. It allows the sympathetic nervous system to be studied as regards the development of a number of cardiac disorders by receptor imaging. Although PET was developed before SPECT, it is less accessible because it requires direct access to a cyclotron to produce the short-lived positron emitting tracers and a radiopharmaceutical laboratory, which is not required for SPECT.

F Bloch et al. at Stanford and E Purcell et al. at Harvard in 1946 published a paper on the nuclear magnetic resonance (NMR) phenomenon in bulk matter for which they received the Nobel Prize in Physics in 1952. Initially, the major limitation to NMR spectroscopy in intact living systems was the small bore of the superconducting magnets. In the early 1980s, the Oxford Instrument Company started to produce superconducting magnets with increasing bores and extremely uniform and intense magnetic fields allowing the whole human body to be studied.  The major advantages of MRI are that contrary to ultrasound, the images are not degraded by overlying bony structures, that there is a high natural contrast between flowing blood and soft tissue, the wide field of view, and that cross-sections of the heart can be obtained in any arbitrary orientation. The ideal cardiovascular imaging technique would provide the cardiologist with integrated information on structure function, myocardial characteristics, perfusion and metabolism. Potentially, magnetic resonance imaging offers all this and will probably become the one-stop non-invasive diagnostic test of cardiology.

Real-time dynamic display of registered 4D cardiac MR and ultrasound images using a GQ Zhanga,

Huanga, R Eagleson,G. Guiraudona, and TM Peters

University of Western Ontario, London, ON, Canada

In minimally invasive image-guided surgical interventions, different imaging modalities, such as magnetic resonance imaging (MRI) or computed tomography (CT), and real-time three-dimensional (3D) ultrasound (US), can provide complementary, multi-spectral image information. Multimodality dynamic image registration is a well-established approach that permits real-time diagnostic information to be enhanced by placing lower-quality real-time images within a high quality anatomical context. For the guidance of cardiac procedures, it would be valuable to register dynamic MRI or CT with intraoperative US. However, in practice, either the high computational cost prohibits such real-time visualization of volumetric multimodal images in a real-world medical environment, or else the resulting image quality is not satisfactory for accurate guidance during the intervention. Modern graphics processing units (GPUs) provide the programmability, parallelism and increased computational precision to begin to address this problem.

The Use of Rapid Prototyping in Clinical Applications

G Biglino, S Schievano and AM Taylor
UCL Institute of Cardiovascular Sciences, London
http://www.intechopen.com

Rapid prototyping broadly indicates the fabrication of a three-dimensional (3D) model from a computer-aided design (CAD), traditionally built layer by layer according to the 3D input (Laoui & Shaik, 2003). Rapid prototyping has also been indicated as solid free-form, computer-automated or layer manufacturing (Rengier et al., 2008). The development of this technique in the clinical world has been rendered possible by the concomitant advances in all its three fundamental steps:

1. Medical imaging (data acquisition),
2. Image processing (image segmentation and reconstruction by means of appropriate software) and
3. Rapid prototyping itself (3D printing).

Particular advantages in this discussion are:

1. Customised implants: Instead of using a standard implant and adapting it to the implantation site during the surgical procedure, rapid prototyping enables the fabrication of patient-specific implants, ensuring better fitting and reduced operation time.

2.  Microelectromechanical systems (MEMS): These are micro-sized objects that are fabricated by the same technique as integrated circuits. MEMS can have different. applications, including diagnostics (used in catheters, ultrasound intravascular diagnostics, angioplasty, ECG), pumping systems, drug delivery systems, monitoring, artificial organs, minimally invasive surgery.

Example: Stages of rapid prototyping in a clinical setting. From left to right: data acquisition (in this case with magnetic resonance (MR) imaging), image processing, 3D volume reconstruction with appropriate software (in this case, Mimics®, Materialise, Leuven, Belgium) and final 3D model printed in a transparent resin.

Despite its clinical use to the present day is still somewhat limited, considering the potential and flexibility of this technique, it is likely that applications of rapid prototyping such as individual patient care and academic research will be increasingly utilised (Rengier et al., 2010).

Nuclear Cardiology — In the Era of the Interventional Cardiology

B Baskot, I Ivanov, D Kovacevic, S Obradovic, N Ratkovic and M Zivkovic
Chap 10, InTech.  http://dx.doi.org/10.5772/55484

The strength and breadth of nuclear cardiology lie in its great potential for future creative growth. This growth involves the development of new biologically derived radiopharmaceuticals, advanced imaging techologies, and a broad/based set of research and clinical applications involving diagnosis, functional categorization, prognosis, evaluation of therapeutic interventions, and the ability to deal with many of the major investigative issues in contemporary cardiology such as myocardial hibernation, stunning, and viability. The past decade has been characterized by major advances in nuclear cardiology that have greatly enhanced the clinical utility of the various radionuclide techniques used for the assessment of regional myocardial perfusion and regional and global left ventricular function under resting and stress conditions. Despite the emergence of alternative noninvasive techniques for the diagnosis of coronary aretry disease (CAD) and the assessment of prognosis of viability, such as ergo- stress tests, stress echocardiography, the use and application of nuclear cardiology techniques have continued to increase.

For many years, planar imaging and SPECT with 201Tl (201 Thalium) constituted the only scintigraphic techniques available for detecting CAD and assessing prognosis in patients undergoing stress perfusion imaging. The major limitation of 201Tl scintigraphy is the high false/positive rate observed in many laboratories, which is attributed predominantly to image attenuation artefact and variants of normal that are interpreted as defects consequent to a significant coronary artery stenoses.

In recent years, new 99mTc (technetium) labeled perfusion agents have been introduced into clinical practice to enhance the specificity of Single Photon Emission Cumputed Tomography (SPECT) and to provide additional information regarding and global left ventricular systolic function via ECG gating of images [3, 4, 8]. It was immediately apparent that the quality of images obtained with these 99mTc-labeled radionuclides was superior to that images obtained with 201Tl because of the more favorable psysical characteristic of 99mTc imaging with gamma camera. Perhaps most importantly, 99mTc imaging allows easy gated acquisition, permitting simultaneous evaluation of regional systolic thickening, global left ventricular function (LVEF), and myocardial perfusion. One the most significant avdances in myocardial perfusion imaging in the past decade is the development of quantitative SPECT perfusion imaging.

Indications for nuclear cardiology procedures

CAD is still the single greatest cause of death of men and women in the world, despite a declining total death rate. The reduction of the morbidity and mortality due to CAD is thus primary importance. The first step in evaluating patients for CAD involves the assessment of the presence of traditional risk factors. Symptoms suggestive of CAD, in addition to other risk factors, drive decisions for further testing.
In patients able to exercise, the diagnostic accuracy of stress myocardial perfusion imaging (MPI) is significantly higher than the ETT alone and provides greater risk stratification for predicting the future cardiac events.

Nuclear cardiology –practical applications

  • ETT exercise treadmill test
  • DIP-ECHO dipyridamole echocardiography
  • DOB-ECHO dobutamine echocardiography
  • DIP- MIBI dipyridamole myocardial perfusion imaging with Tc-99m MIBI
  • DOB-MIBI dobutamine myocardial perfusion imaging with Tc-99m MIBI

Evaluating and determination CULPRIT lesion, an indication for interventional cardiology


One of the most powerfull uses of MPI is the evaluation of the risk for future events in patients with suspected or known CAD. Over the years, MPI has evolved as an essential tool in the evaluation and assessment of patient prior to coronary revascularization. It has a dual role. Prior to coronary angiography, MPI is extremely useful in documenting ischemia and determining the functional impact of single or multiple lesions subsequently identified. Despite some limitations in the setting of multivessel disease, MPI remains the test of choice for identifying the lesion responsible for the ischemic symptoms.  The primary objective of those study is to determine and localize the culprit lesion. The authors introduce parameters SRS (summary reversible score) and ISRS (index of summary reversible score), under the angiographically detected coronary narrowing ≥75% for the least one coronary artery. Coronary angiography, considered the “gold standard” for the diagnosis of CAD, often does not provide information about the physiologic significance of atherosclerotic lesions, especially in borderline lesions. More importantly, it does not provide a clear marker of risk of adverse events, especially in patients with moderate disease severity.  The presence of normal scintigraphic MPI study at a high level of stress ( ≥ 85 % of maximum predicted heart rate) or proper pharmacologic stress carries a very benign prognosis, with mortality rate less than 0.5% per year. This finding has been reproduced in many studies. Iskander and Iskandiran, pooling the results of SPECT imaging from more than 12000 patients in 14 studies, demonstrated that the events rate (death/MI) for patients with normal MPI finding is 0.6%, whereas abnormal study carries 7.4% per year event rate, a 12-fold increase.

The size and severity of the perfusion abnormality provide powerful prognostic information and has been shown to directly relate to outcome. MPI perfusion imaging and determination of culprit lesion is more predicitble of cardiac events than coronary angiography. As MPI imaging may identify those patients at high risk for subsequent cardiac events, perfusion imaging may be used to help guide further testing and revascularization procedures. Myocardial perfusion imaging provides information on the extent and location  of myocardial ischemia. The assessment of jeopardized myocardium may be performed and provides a measure of the relative value of PTCA in terms of the amount of jeopardized myocardium. The location of the stenosis may dictate the area at risk: extent and severity of perfusion defects were significantly smaller in patients with proximal compared with distal coronary artery occlusions.

The aim of the study Baskot at al.(*)  was to determine and localize culprit lesion by MPI in cases of angiographically detected coronary narrowing ≥ 75% of at least one coronary artery. In the study four hundred and thirty-seven [437] patients were studied. Angiographically detected significant coronary narrowing (≥ 75% luminal stenosis) was found in all before PCI. All the patients were submitted to MPI 99mTc-MIBI, with pharmacologic dipyridamole stress protocol with concomitant low level bicycle exercise 50 W (DipyEX). We measured relative uptake 99mTc-MIBI for each myocardial segment using short-axis tomogram study. A 5-point scoring system was used to assess the difference between uptake degree in stress and rest studies for the same segment, and we created two indices: Sum reversible score (SRS), Index of sum reversibility score (ISRS). In the results a total 1311 vascular territories (7429 segments) were analyzed before elective percutaneous coronary intervention (ePCI). Overall sensitivity, specificity and accuracy using SRS were 89.7%, 86, 7%, and 88, 2%, with a positive predictive value of 92, 7%. Overall sensitivity, specificity and accuracy using ISRS were 92.8%, 89.1%, and 92.3%, and the positive predictive value was 93.7%.

Pathophysiology and investigation of coronary artery disease

Ever D Grech
University of Manitoba, Winnipeg
BMJ 2003;326:1027–30

In affluent societies, coronary artery disease causes severe disability and more death than any other disease, including cancer. It manifests as angina, silent ischemia, unstable angina, myocardial infarction, arrhythmias, heart failure, and sudden death.  Coronary artery disease is almost always due to atheromatous narrowing and subsequent occlusion of the vessel. A mature plaque is composed of two constituents, each associated with a particular cell population. The lipid core is mainly released from necrotic “foam cells”—monocyte derived macrophages, which migrate into the intima and ingest lipids. The connective tissue matrix is derived from smooth muscle cells, which migrate from the media into the intima, where they proliferate and change their phenotype to form a fibrous capsule around the lipid core.

Stress echocardiography

Stress induced impairment of myocardial contraction is a sensitive marker of ischemia and precedes electrocardiographic changes and angina. Cross sectional echocardiography can be used to evaluate regional and global left ventricular impairment during ischaemia, which can be induced by exercise or an intravenous infusion of drugs that increase myocardial contraction and heart rate (such as dobutamine) or dilate coronary arterioles (such as dipyridamole or adenosine).

Radionuclide myocardial perfusion imaging

Thallium-201 or technetium-99m (99mTc-sestamibi, 99mTc-tetrofosmin) is injected intravenously at peak stress, and its myocardial distribution relates to coronary flow. Images are acquired with a gamma camera. This test can distinguish between reversible and irreversible ischemia (the latter signifying infarcted tissue). Although it is expensive and requires specialised equipment, it is useful in patients whose exercise test is non-diagnostic or whose exercise ability is limited.

A multigated acquisition (MUGA) scan assesses left ventricular function and can reveal salvageable myocardium in patients with chronic coronary artery disease. It can be performed with either thallium scintigraphy at rest or metabolic imaging with fluorodeoxyglucose by means of either positron emission tomography (PET) or single photon emission computed tomography (SPECT).

Intravascular ultrasound (IVUS)

In contrast to angiography, which gives a two dimensional luminal silhouette with little information about the vessel wall, intravascular ultrasound provides a cross sectional, three dimensional image of the full circumference of the artery. It allows precise measurement of plaque length and thickness and minimum lumen diameter, and it may also characterise the plaque’s composition. It is often used to clarify ambiguous angiographic findings and to identify wall dissections or thrombus. It is most useful during percutaneous coronary intervention, when target lesions can be assessed before, during, and after the procedure and at follow up. The procedure can also show that stents which seem to be well deployed on angiography are, in fact, suboptimally expanded.

Interventional Cardiology for Structural Heart Disease

Georgios Parcharidis
Hellenic J Cardiol 2012; 53: 403-404

Many questions arise from this “explosion” of new technologies. Is all this enthusiasm justified and supported by robust scientific evidence? Which is the best way to implement these new treatment options? What is the role of “traditional” surgical treatment? How can we decide which patient should be treated percutaneously and which surgically? What level of training and experience should an interventional cardiologist (or a centre) have in order to perform structural and/or congenital heart disease interventions?

With regard to the scientific evidence, it should be noted that, currently, the number of randomized clinical trials and the duration of follow up is quite limited. Thus, great caution should be exercised in patient selection and planning for these complex procedures. In addition, careful data collection and, ideally, inclusion in a patient registry would increase surveillance and, therefore, patient safety.

Notably, for the majority of structural and congenital heart diseases, surgery is still considered the “gold standard”. It is now globally accepted that decision making for patients with cardiovascular disease should be done in the context of a “Heart Team”, with close collaboration between cardiologists, cardiothoracic surgeons, anesthesiologists, imaging specialists and, occasionally, other specialists. Some patients will benefit more from transcatheter interventions whereas others will do better with surgery. Based on specific criteria, the role of the Heart Team is to identify (and treat) those patients.

PET vs. SPECT: Will PET Dominate Over the Next Decade?

DAIC  July/August 2013  pp28-31.  www. DIcardiology.com

The future success of PET may be grounded in its inherently better image resolution. In cardiac scanning, it has generally been reported that PET offers a resolution of 5 to 7 mm, compared with a cardiac SPECT resolution of 12 to 15 mm. Better performance has allowed data to emerge suggesting that as many as one in 10 scans interpreted as normal on SPECT would have been abnormal if done on PET due to the presence of unseen microvascular, triple-vessel disease. PET’s superior diagnostic capability is achieved partly through advances in hardware, particularly quantification, which leverages numerical precision to identify global perfusion defects in the heart that otherwise might be hidden from qualitative SPECT scans.

A big difference between the two technologies is the half-life of the isotope that each radiopharmaceutical tracer uses. SPECT tracers have a relatively long half-life (technetium-99m has a half-life of six hours), whereas rubidium-82 is only 75 seconds. This short half-life is a limitation of the current front-line cardiac PET radiotracer, which does not leave much room for error when imaging and presents the inability to do exercise stress testing. New iterative reconstruction (IR) software such as UltaSPECT is improving SPECT image quality by boosting the signal-to-noise ratio. Just as in CT scans, IR can also help reduce dose by enhancing lower-quality scans.

Part III

Heart Failure Patients

Heart Failure Complicating Non–ST-Segment Elevation Acute Coronary Syndrome -Timing, Predictors, and Clinical Outcomes

MC Bahit, RD Lopes, RM Clare, LK Newby,KS Pieper, et al.
J Am Coll Cardiol HF 2013;1(3): 223–9This study sought to describe the occurrence and timing of heart failure (HF), associated clinical factors, and 30-day outcomes in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS). Using pooled patient-level data from 7 clinical trials from 1994 to 2008, we describe the occurrence and timing of HF,associated clinical factors, and 30-day outcomes in NSTE-ACS patients. HF at presentation was defined as Killip classes II to III; patients with Killip class IV or cardiogenic shock were excluded. New in-hospital cases of HF included new pulmonary edema. After adjusting for baseline variables, we created logistic regression models to identify clinical factors associated with HF at presentation and to determine the association between HF and 30-day mortality.Of 46,519 NSTE-ACS patients, 4,910 (10.6%) had HF at presentation. Of the 41,609 with no HF at presentation, 1,194 (2.9%) developed HF during hospitalization. A total of 40,415 (86.9%) had no HF at any time. Patients presenting with or developing HF during hospitalization were older, more often female, and had a higher risk of death at 30 days than patients without HF (adjusted odds ratio [OR]: 1.74; 95% confidence interval: 1.35 to 2.26). Older age, higher presenting heart rate, diabetes, prior myocardial infarction (MI), and enrolling MI were significantly associated with HF during hospitalization. In this large cohort of NSTE-ACS patients, presenting with or developing HF during hospitalization was associated with an increased risk of 30-day mortality.

Outcomes Following Heart Transplantation among Those Bridged with VAD

Jeffrey Shuhaiber MD
University of Cincinnati and Cincinnati Children’s Hospital
www.intechopen.com

Clinical assessment of outcome for post heart transplant recipients who were bridged with ventricular assist device is essential for service evaluation, device evaluation and audit. We will review the clinical outcomes measured so far in the field of heart transplant recipients who were bridged with VAD. In this chapter we will review the ongoing methods of assessment of outcomes for transplant recipients bridged by VAD and discuss the potential challenges facing the clinicians. We will finalize with brief conclusions and future directions.

Survival following heart transplantation: Does VAD Type matter?

There have been many clinical studies comparing outcomes following heart transplantation. Only one has been done in a multicenter fashion with clinically relevant as well as a robust risk-adjustment. In 2006 we asked the question- does survival differ between those who did and did not receive the left ventricular assist device (LVAD) following heart transplantation? And in summary we found that survival following heart transplantation for patients who received an LVAD prior to transplantation was comparable to those who did not receive an LVAD. The results of this study were published as lead research article in the British Medical Journal earlier this year (Shuhaiber).

We reviewed all patients above 18 years of age who received heart transplants registered in the United Network for Organ Sharing (UNOS) Registry from 1996 to 2004. The study included 2786 status 1/1A/1B heart transplant patients. We used the entry data for all patients who received LVAD pulsatile device. Our study design included a prospective cohort study in which post-transplant survival between patients who received an LVAD and those who did not receive an LVAD was compared.

1:1 propensity score matching analysis was also performed. Comparisons of survival distributions were made using the Kaplan-Meier method and the risk ratios were estimated using Cox proportional model. Our primary outcomes as well as risks and exposures included survival following heart transplantation in heart transplant recipients who did or did not receive ventricular assist device. The strength of the study was in adopting a robust statistical methodology that can adequately control for confounding variables. A stratified  propensity score analysis of data revealed that the risk of death following heart transplantation in an LVAD patient was not significantly different from those who did not have an LVAD within each stratum (see table for estimated hazard ratios and their 95% confidence intervals). A 1:1 propensity score matching analysis also revealed no significant difference in post heart transplant survival between the two groups (hazard ratio = 1.18, 95% CIs=0.75 to1.86). The propensity score matching was performed in order to control potential selection biases that can lead to a false association (or false lack of association) between LVAD and survival.

Part IV

Mechanical Heart Devices

The treatment of heart failure at end stage myocardial function has depended on having patients on waiting lists until the time that a donor heart becomes available.  Waiting times are within 1.5 to 4.5 years.  This required the development for mechanical support until a suitable donor is found.  The expectation for future devices will be that suitable mechanical heart assist devices for selected patients will possibly alleviate the need for a donor heart.

There are two main types of mechanical assist devices.  One type ios actually a total artificial heart, and the other is an assist that in complementary to the still functioning weak left ventricle.  The VAD was just discussed in the preceding discussion.  It has a pump that is attached to the atria and the pump controls the flow of blood through the pulmonary circulation.  This device is extremely important for patients who have sufficient LV function to not require a TAH.

The total artificial heart  (TAH) has been dominated by use of either of two models – the Syncardia temporary artificial heart, and the AbiCor.  The difference between them is that one has an externalization outside the thorax to an electrical source.  The Syncardia model is a modern day improvement of Jarvik-7.
The controlled flow is a miniature motor that has a rotor that moves the blood forward.  Of course, it presents a problem with respect to blood cell damage and anemia.  One of the innovations to the blood flow control has been that it flows without a heart beat.  The most significant innovation is the entry into the market of a new model, the Carmat, from France.  The Carmat would reduce the hemolysis that is associated with the flow of RBCs along a synthetic lining.  How?  It has the blood in contact with a cow skin lining.

Part V

Heart Transplant


The heart transplant is a technique that has been mastered at a number of excellent cardiothoracic surgical sites, and the facilities are being replaced by Hybrid Units that accommodate cardiology and surgical interventions. This brings to fruition the concept of a “Heart Team”.  The procedure has risks of complication, either in the patient condition, or in environmental, or other factors the surgeon has no control over.

These factors include, associated comorbidities, such as

  • diabetes mellitus
  • Late NYHF Stage 4
  • Late stage renal disease
  • mismatch of Graft vs Host
  • infection

Other related articles published on this Open Access Online Scientific Journal, include the following: 

Pearlman, JD and A. Lev-Ari, Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions

https://pharmaceuticalintelligence.com/2013/07/23/cardiovascular-complications-of-multiple-etiologies-repeat-sternotomy-post-cabg-or-avr-post-pci-pad-endoscopy-andor-resultant-of-systemic-sepsis/

Larry H Bernstein, Advanced Topics in Sepsis and the Cardiovascular System at its End Stage

https://pharmaceuticalintelligence.com/2013/08/18/advanced-topics-in-sepsis-and-the-cardiovascular-system-at-its-end-stage/

Pearlman, JD and A. Lev-Ari  Cardiac Resynchronization Therapy (CRT) to Arrhythmias: Pacemaker/Implantable Cardioverter Defibrillator (ICD) Insertion

https://pharmaceuticalintelligence.com/2013/07/22/cardiac-resynchronization-therapy-crt-to-arrhythmias-pacemakerimplantable-cardioverter-defibrillator-icd-insertion/

Lev-Ari, A.  3D Cardiovascular Theater – Hybrid Cath Lab/OR Suite, Hybrid Surgery, Complications Post PCI and Repeat Sternotomy

https://pharmaceuticalintelligence.com/2013/07/19/3d-cardiovascular-theater-hybrid-cath-labor-suite-hybrid-surgery-complications-post-pci-and-repeat-sternotomy/

Read Full Post »


Treatment Options for Left Ventricular Failure  –  Temporary Circulatory Support: Intra-aortic balloon pump (IABP)Impella Recover LD/LP 5.0 and 2.5, Pump Catheters (Non-surgical) vs Bridge Therapy: Percutaneous Left Ventricular Assist Devices (pLVADs) and LVADs (Surgical) 

Author: Larry H Bernstein, MD, FCAP
And
Curator: Justin D Pearlman, MD, PhD, FACC

 

UPDATED on 12/2/2013 – HeartMate II – LVAD

http://www.nytimes.com/2013/11/28/business/3-hospital-study-links-heart-device-to-blood-clots.html?pagewanted=1&_r=0&emc=eta1

Hospital Studies Link Heart Device to Clots

David Maxwell for The New York Times

Dr. Randall Starling, right, said that he could only speculate about the reason for the rapid rise in early blood clots.

By 
Published: November 27, 2013

Doctors at the Cleveland Clinic began to suspect in 2012 that something might be wrong with a high-tech implant used to treat patients with advanced heart failure like former Vice President Dick Cheney.

Thoratec Corportation

The HeartMate II is a left ventricular assist device, which contains a pump that continuously pushes blood through the heart.

The number of patients developing potentially fatal blood clots soon after getting the implant seemed to be rising. Then early this year, researchers completed a check of hospital records and their concern turned to alarm.

The data showed that the incidence of blood clots among patients who got the device, called the HeartMate II, after March 2011 was nearly four times that of patients who had gotten the same device in previous years. Patients who developed pump-related clots died or needed emergency steps like heart transplants or device replacements to save them.

“When we got the data, we said, ‘Wow,’ ” said Dr. Randall C. Starling, a cardiologist at Cleveland Clinic.

On Wednesday, The New England Journal of Medicineposted a study on its website detailing the findings from the Cleveland Clinic and two other hospitals about the device. The HeartMate II belongs to a category of products known as a left ventricular assist device and it contains a pump that continuously pushes blood through the heart.

The abrupt increase in pump-related blood clots reported in the study is likely to raise questions about whether its manufacturer, Thoratec Corporation, modified the device, either intentionally or accidentally. By March, the Cleveland Clinic had informed both Thoratec and the Food and Drug Administration about the problems seen there, Dr. Starling said.

Officials at Thoratec declined to be interviewed. But in a statement, the company, which is based in Pleasanton, Calif., said that the HeartMate II had been intensively studied and used in more 16,000 patients worldwide with excellent results. It added that the six-month survival rate of patients who received the device had remained consistently high.

“Individual center experience with thrombosis varies significantly, and Thoratec actively partners with clinicians at all centers to minimize this risk,” the company said in a statement.

Thoratec and other cardiologists also pointed to a federally funded registry that shows a smaller rise in the rate of blood clots, or thrombosis, among patients getting a HeartMate II than the one reported Wednesday by the three hospitals. In the registry, which is known as Intermacs, the rate of pump-related blood clot associated with the HeartMate II rose to about 5 percent in devices implanted after May 2011 compared with about 2 percent in previous years.

The data reported on Wednesday in The New England Journal of Medicine found rates of clot formation two months after a device’s implant had risen to 8.4 percent after March 2011 from 2.2 percent in earlier years. Researchers also suggested in the study that the Intermacs registry might not capture all cases of pump-related blood clots, such as when patients gets emergency heart transplants after a clot forms.

Not only did the rate of blood clots increase, but the clots also occurred much sooner than in the past, according to the study. After March 2011, the median time before a clot was 2.7 months, compared with 18.6 months in previous years. In addition to the Cleveland Clinic, the report on Wednesday included data from Duke University and Washington University in St. Louis.

All mechanical heart implants are prone to producing blood clots that can form on a device’s surface. And experts say that the rate of blood clot formation can be affected by a variety of factors like changes in the use of blood-thinning drugs or the health of a patient.

In a telephone interview, Dr. Starling described the Thoratec officials as cooperative, adding that they have been looking into the problem since March to understand its cause. He said that he could only speculate about the reason for the rapid rise in early blood clots but believed it was probably device-related.

“My belief is that it is something as subtle as a change in software that affects pump flow or heat dissipation near a bearing,” said Dr. Starling, who is a consultant to Thoratec.

Asked about his comments, Thoratec responded that it had yet to determine the reason for even the smaller rise in blood clots seen in the federally funded database. “We have performed extensive analysis on HeartMate II and have not identified any change that would cause the increase observed in the Intermacs registry,” the company said.

In a statement, the F.D.A. said that it was reviewing the findings of the study. “The agency shares the authors concerns about the possibility of increased pump thrombosis,” the F.D.A. said in a statement.

The fortunes of Thoratec, which has been a favorite of Wall Street investors, may depend on its ability to find an answer to the apparent jump in pump-related blood clots. Over the last two years, the company’s stock has climbed from about $30 a share to over $43 a share. In trading Wednesday, Thoratec stock closed at $42.12 a share, up 61 cents. (The New England Journal of Medicine article was released after the stock market closed.)

The HeartMate II has been a lifesaver for many patients like Mr. Cheney in the final stages of heart failure, who got his device in 2010, sustaining them until they get a heart transplant or permanently assisting their heart. Dr. Starling said that he planned to keep using the HeartMate II in appropriate patients at the Cleveland Clinic because those facing death from heart failure had few options.

But the company has also been pushing to expand the device’s use beyond patients who face imminent death from heart failure. For example, the F.D.A. approved a clinical trial for patients with significant, but less severe, heart failure to receive a HeartMate II to compare their outcomes with patients who take drugs for the same condition. Researchers at the University of Michigan Medical Center who are leading the trial said on Wednesday that, based on the lower rates of blood clots seen in the Intermacs registry, they are planning to move forward with the trial.

Dr. Starling and researchers at the Cleveland Clinic tried this spring to get The New England Journal of Medicine to publish a report about the findings at that hospital, but the publication declined, saying the data might simply represent the experience of one facility. As a result, Dr. Starling contacted Duke University and Washington University for their data. When analyzed, it mirrored events at the Cleveland Clinic, he said.

The problems seen with the HeartMate II at the three hospitals were continuing as recently as this summer, when researchers paused the collection of data to prepare Wednesday’s study. The study also noted that a preliminary analysis of data provided by a fourth hospital, the University of Pennsylvania, showed the same pattern of blood clot formation, but that the data had been submitted too late for full analysis.

 SOURCE

 

This article presents the following four Sections:

I.     Impella LD – ABIOMED, Inc.

II.   IABP VS. Percutaneous LVADS

III. Use of the Impella 2.5 Catheter in High-Risk Percutaneous Coronary Intervention

IV.  PROTECT II Study – Experts Discussion

This account is a vital piece of recognition of very rapid advances in cardiothoracic interventions to support cardiac function mechanically by pump in the situation of loss of contractile function and circulatory output sufficient to sustain life, as can occur with the development of cardiogenic shock.  This has been mentioned and its use has been documented in other portions of this series.   On the one hand, PCI has a long and steady history in the development of interventional cardiology. This necessitated the availability of thoracic-surgical operative support. The situation is changed, and is more properly, conditional.

I. Impella LD – ABIOMED, Inc.

This micro-axial blood pump can be inserted into the left ventricle via open chest procedures. The Impella LD device has a 9 Fr catheter-based platform and a 21 Fr micro-axial pump and is  inserted through the ascending aorta, across the aortic and mitral valves and into the left ventricle.  It requires minimal bedside support and a 9 Fr single-access point  requires no priming outside the body.

Impella.LD_

Impella Recover LD/LP 5.0

The Impella Recover miniaturized impeller pump located within a catheter. The Impella Recover LD/LP 5.0 Support System has been developed to address the need for ventricular support in patients who develop heart failure after heart surgery (called cardiogenic shock) and who have not responded to standard medical therapy. The system is designed to provide immediate support and restore hemodynamic stability for a period of up to 7 days. Used as a bridge to therapy, it allows time for developing a definitive treatment strategy.

The Pump

The Impella Recover LD 5.0 showing implantation via direct placement into the left ventricle.
 Insert B – location in LV
imeplla-LD-video
The Impella Recover system is a miniaturized impeller pump located within a catheter. The device can provide support for the left side of the heart using either the
  • Recover LD 5.0 (implanted via direct placement into the left ventricle) or the
  • Recover LP 5.0 LV (placed percutaneously through the groin and positioned in the left ventricle).
The microaxial pump of the Recover LP/LD 5.0 can pump up to 4.5 liters per minute at a speed of 33,000 rpm. The pump is located at the distal end of a 9 Fr catheter.

II.   IABP VS. Percutaneous LVADS

An intra-aortic balloon pump (IABP) remains the method of choice for mechanical assistance1 in patients experiencing LV failure because of its

  • proven hemodynamic capabilities,
  • prompt time to therapy, and
  • low complication rates.

Percutaneous left ventricular assist devices (pLVADs), such as described above, represent an emerging option for partial or total circulatory support2 and several studies have compared the and efficacy of these devices with intra-aortic balloon pump (IABP) (IABP.)

Despite some randomized controlled trials demonstrating better hemodynamic profiles for pLVADs compared with IABP, there is no difference in  30-day survival or trend toward a reduced 30-day mortality rate associated with pLVADs.  Patients treated with pLVADs tended to have a
  • higher incidence of leg ischemia and
  • device related bleeding.3
Further, no differences have been detected in the overall use of
  • positive inotropic drugs or
  • vasopressors in patients with pLVADs.4,5
However, pLVADs may increase their use for patients not responding to
  • PCI,
  • fluids,
  • inotropes, and
  • IABP
Therefore, the decision making process on how to treat requires an integrated stepwise approach. A pLVAD might be considered on the basis of
  • anticipated individual risk,
  • success rates, and for
  • postprocedural events.6

Potential Algorithm for Device Selection during High-Risk PCI

PADS_HRPCI cardiac assist device selection

Potential Algorithm for Device Selection during Cardiogenic Shock
device_selection_CS
Until an alternative modality, characterized by improved efficacy and safety features compared with IABP, is developed, IABP remains the cornerstone of temporary circulatory support.2

Device Comparison for Treatment of Cardiogenic Shocktraditional intra-aortic balloon therapy with Impella 2.5 percutaneous ventricular assist device

 
1. Percutaneous LVADs in AMI complicated by cardiogenic shock. H Thiele, et al. EHJ 2007;28:2057-2063
2. Cardiogenic shock current concepts and improving outcomes. H R Reynolds et al. Circulation 2008 ;117 :686-697
3. Percutaneous left ventricular assist devices vs. IABP counterpulsation for treatment of cardiogenic shock. J M Cheng, et al. EHJ doi:10.1093/eurheart/ehp292
4. A randomized clinical trial to evaluate the safety and efficacy of a pLVAD vs. IABP for treatment of cardiogenic shock caused by MI. M Seyfarth, et al. JACC 2008;52:1584-8
5. A randomized multicenter clinical study to evaluate the safety and efficacy of the tandem heart pLVAD vs. conventional therapy with IABP for treatment of cardiogenic shock.
6. Percutaneous LVADs in AMI complicated by cardiogenic shock. H Thiele, et al. EHJ 2007;28:2057-2063

III. Use of the Impella 2.5 Catheter in High-Risk Percutaneous Coronary Intervention

Brenda McCulloch, RN, MSN
Sutter Heart and Vascular Institute, Sutter Medical Center, Sacramento, California
Crit Care Nurse 2011; 31(1): e1-e16    http://dx.doi.org/10.4037/ccn2011293
Abstract
The Impella 2.5 is a percutaneously placed partial circulatory assist device that is increasingly being used in high-risk coronary interventional procedures to provide hemodynamic support. The Impella 2.5 is able to unload the left ventricle rapidly and effectively and increase cardiac output more than an intra-aortic balloon catheter can. Potential complications include bleeding, limb ischemia, hemolysis, and infection. One community hospital’s approach to establishing a multidisciplinary program for use of the Impella 2.5 is described.
Patients who undergo high-risk percutaneous coronary intervention (PCI), such as procedures on friable saphenous vein grafts or the left main coronary artery, may have an intra-aortic balloon catheter placed if they require hemodynamic support during the procedure. Currently, the intra-aortic balloon pump (IABP) is the most commonly used device for circulatory support. A newer option that is now available for select patients is the Impella 2.5, a short-term partial circulatory support device or percutaneous ventricular assist device (VAD).
In this article, I discuss the Impella 2.5, review indications and contraindications for its use, delineate potential complications of the Impella 2.5, and discuss implications for nursing care for patients receiving extended support from an Impella 2.5. Additionally, I share our experiences as we developed our Impella program at our community hospital. Routine management of patients after PCI is not addressed.

IABP Therapy: Background

  • decreases after-load,
  • decreases myocardial oxygen consumption,
  • increases coronary artery perfusion, and
  • modestly enhances cardiac output.1,2
The IABP cannot provide total circulatory support. Patients must have some level of left ventricular function for an IABP to be effective.
Optimal hemodynamic effect from the IABP is dependent  on:
  • the balloon’s position in the aorta,
  • the blood displacement volume,
  • the balloon diameter in relation to aortic diameter,
  • the timing of balloon inflation in diastole and deflation in systole, and
  • the patient’s own blood pressure and vascular resistance.3,4

Impella 2.5 Catheter – ABIOMED, Inc.

Effect
  • reduces myocardial oxygen consumption,
  • improves mean arterial pressure, and
  • reduces pulmonary capillary wedge pressure.2

The Impella 2.5 has been used for

  • hemodynamic support during high-risk PCI and for
  • hemodynamic support of patients with
  1. myocardial infarction complicated by cardiogenic shock or ventricular septal defect,
  2. cardiomyopathy with acute decompensation,
  3. postcardiotomy shock,
  4. off-pump coronary artery bypass grafting surgery, or
  5. heart transplant rejection and
  6. as a bridge to the next decision.9
The Impella provides a greater increase in cardiac output than the other IABP provides. In one trial5 in which an IABP was compared with an Impella in cardiogenic shock patients, after 30 minutes of therapy, the cardiac index (calculated as cardiac output in liters per minute divided by body surface area in square meters) increased by 0.5 in the patients with the Impella compared with 0.1 in the patients with an IABP.
Unlike the IABP, the Impella does not require timing, nor is a trigger from an electrocardiographic rhythm or arterial pressure needed (Table 1). The device received 510(k) clearance from the Food and Drug Administration in June 2008 for providing up to 6 hours of partial circulatory support. In Europe, the Impella 2.5 is approved for use up to 5 days. Reports of longer duration of therapy in both the United States and Europe have been published.8,9
Table IABT vs Impella

Clinical Research and Registry Findings

Abiomed has sponsored several trials, including PROTECT I, PROTECT II, RECOVER I, RECOVER II, and ISAR-SHOCK.
The PROTECT I study was done to assess the safety and efficacy of device placement in patients undergoing high-risk PCI.10

Twenty patients who had

  • poor ventricular function (ejection fraction =35%) and had
  • PCI on an unprotected left main coronary artery or the
  • last remaining patent coronary artery or graft.

The device was successfully placed in all patients, and the duration of support ranged from 0.4 to 2.5 hours. Following this trial, the Impella 2.5 device received its 510(k) approval from the Food and Drug Administration.

The ISAR-SHOCK trial was done to evaluate the safety and efficacy of the Impella 2.5 versus the IAPB in patients with cardiogenic shock due to acute myocardial infarction.5 Patients were randomized to support from an IABP (n=13) or an Impella (n=12).

The trial’s primary end point of hemodynamic improvement was defined as improved cardiac index at 30 minutes after implantation.

  1. Improvements in cardiac index were greater with the Impella (P=.02).
  2. The diastolic pressure increased more with Impella (P=.002).
  3. There was a nonsignificant difference in the MAP (P=.09), as was the use of inotropic agents and vasopressors similar in both groups of patients.

Device Design: Impella 2.5 Catheter

The Impella 2.5 catheter contains a nonpulsatile microaxial continuous flow blood pump that pulls blood from the left ventricle to the ascending aorta, creating increased forward flow and increased cardiac output. An axial pump is one that is made up of impellar blades, or rotors, that spin around a central shaft; the spinning of these blades is what moves blood through the device.13

The Impella 2.5 catheter has 2 lumens. A tubing system called the Quick Set-Up has been developed for use in the catheterization laboratory. It is a single tubing system that bifurcates and connects to each port of the catheter. This arrangement allows rapid initial setup of the console so that support can be initiated quickly. When the Quick Set-Up is used, the 10% to 20% dextrose solution used to purge the motor is not heparinized. One lumen carries fluid to the impellar blades and continuously purges the motor to prevent the formation of thrombus. The proximal port of this lumen is yellow. The second lumen ends near the motor above the level of the aortic valve and is used to monitor aortic pressure.
The components required to run the device are assembled on a rolling cart and include the power source, the Braun Vista infusion pump, and the Impella console. The Impella console powers the microaxial blood pump and monitors the functioning of the device, including the purge pressure and several other parameters. The console can run on a fully charged battery for up to 1 hour.

Placement of the Device

The Impella 2.5 catheter is placed percutaneously through the common femoral artery and advanced retrograde to the left ventricle over a guidewire. Fluoroscopic guidance in the catheterization laboratory or operating room is required. After the device is properly positioned, it is activated and blood is rapidly withdrawn by the microaxial blood pump from the inlet valve in the left ventricle and moved to the aorta via the outlet area, which sits above the aortic valve in the aorta.
If the patient tolerates the PCI procedure and hemodynamic instability does not develop, the Impella 2.5 may be removed at the end of the case, or it can be withdrawn, leaving the arterial sheath in place, which can be removed when the patient’s activated clotting time or partial thromboplastin time has returned to near normal levels. For patients who become hemodynamically unstable or who have complications during the PCI (eg, no reflow, hypotension, or lethal arrhythmias), the device can remain in place for continued partial circulatory support, and the patient is transported to the critical care setting.

Potential Complications of Impella Therapy

The most commonly reported complications of Impella 2.5 placement and support include

  • limb ischemia,
  • vascular injury, and
  • bleeding requiring blood transfusion.6,9
Hemolysis is an inherent risk of the axial construction, and results in transfusions.5,10
Hemolysis can be mechanically induced when red blood cells are damaged as they pass through the microaxial pump. Other potential complications include
  • aortic valve damage,
  • displacement of the distal tip of the device into the aorta,
  • infection, and
  • sepsis.
  • Device failure, although not often reported, can occur.
Patients on Impella 2.5 support who may require
  • interrogation of a permanent pacemaker or
  • implantable cardioverter defibrillator
present an interesting situation. In order for the interrogator to connect with the permanent pacemaker or implantable cardioverter defibrillator, the Impella console must be turned off for a few seconds while the signal is established. As soon as the signal has been established, Impella support is immediately restarted.

Impella 2.5 Console Management

The recommended maximum performance level for continuous use is P8. At P8, the flow rate is 1.9 to 2.6 L/min and the motor is turning at 50000 revolutions per minute. When activated, the console is silent. No sound other than alarms is audible during Impella support, unlike the sound heard with an IABP. Ten different performance levels ranging from P0 to P9 are available. As the performance level increases, the flow rate and number of revolutions per minute increase. At maximum performance (P9), the pump rotates at 50000 revolutions per minute and delivers a flow rate of 2.1 to 2.6 L/min. P9 can be activated only for 5-minute intervals when the Impella 2.5 is in use.

IV.  PROTECT II Study – Experts Discussion

the use of the Impella support device and the intraortic balloon pump for high-risk percutaneous coronary intervention
 
DR. SMALLING: Well, the idea about the PROTECT trial is that it would show that using the Impella device to support high-risk angioplasty was not inferior to utilizing the balloon pump for the same patient subset. Ejection fraction’s were in the 30%–35% range. Supposedly last remaining vessel or left main disease or left-main plus three-vessel disease and low EF; so I think that was the screening for entry into the trial.
major adverse cardiac event endpoints
  1. Acute myocardial infarction,
  2. mortality,
  3. bleeding,
mortality was the same. Their endpoints really didn’t show that much difference. In subgroup analysis, they felt that they Impella may have had a little advantage over balloon pump.
DR. KERN: So do you think this study would tip the interventionalist to move in one direction or the other for high-risk angioplasty?
DR. SMALLING: That’s an interesting concept, you know? One has to get to: What is really a high-risk angioplasty. I think you and I are both old enough to remember that back in the mid-’80s, we determined that high-risk angioplasty was a patient with an ejection fraction of 25% or less, with a jeopardy score over 6. The EFs were a little higher. And, I guess, based on our prior experience with other support devices — like, for instance, CPS and then, later on, the Tandem Heart — there really was not an advantage of so-called more vigorous support systems. And so, the balloon pump served as well.
DR. SMALLING:
Those of us that have looked carefully at what it can really do, I think it may get one liter a minute at most, maybe more.1-6 But I think, for all intents and purposes, it doesn’t support at a very vigorous level. So I think personally, if I had someone I was really worried about, I would opt for something more substantial like, for instance, a Tandem Heart device.
DR. KERN: I think this is a really good summary of the study and the. Are there any final thoughts for those of us who want to read the PROTECT II study when it comes out?
DR. SMALLING: We have to consider a $20,000, $25,000 device. Is that really necessary to do something that we could often do without any support at all, or perhaps with a less costly device like a balloon pump.
DR. KERN: We’re going to talk for a few minutes about the PROTECT II study results that were presented here in their form. And Ron, I know you’ve been involved with following the work of the PROTECT II investigators. Were you a trial site for this study?
DR. WAKSMAN: No, actually, we were not, but we have a lot of interest in high-risk PCI and using devices to make this safe — mainly safe — and also effective. We were not investigators, but we did try to look, based on the inclusion/exclusion criteria, on our own accord with the balloon pump. If you recall, this study actually was comparing balloon time to the Impella device for patients who are high-risk PCI.
The composite endpoint was very complicated. They added like probably nine variables there, which is unusual for a study design. … They basically estimated that the event rate on the balloon pump would be higher than what we thought it should be. So we looked at our own data, and we found out that the actual — if you go by the inclusion/exclusion criteria and their endpoints — the overall event rate in the balloon pump would be much lower than they predicted and built in their sample size.
DR. KERN: And, so, the presentation of the PROTECT II trial, was it presented as a positive study or a negative study.
DR. WAKSMAN: Overall the study did not meet the endpoint. So the bottom line, you can call it the neutral study, which is a nice way to say it.
if you go and do all those analyses, you may find some areas that you can tease a P value, but I don’t think that this has any scientific value, and people should be very careful. We’re not playing now with numbers or with statistics, this is about patient care. You’re doing a study — the study, I think, has some flaws in the design to begin with — and we actually pointed that out when we were asked to participate in the study. But if the study did not meet the endpoint, then I think all those subanalyses, subgroups, you extract from here, you add to there, and you get a P value, that means nothing. So we have to be careful when we interpret this, other than as a neutral study that you basically cannot adopt any of the … it did not meet the hypothesis, that’s the bottom line.

A first-in-man study of the Reitan catheter pump for circulatory support in patients undergoing high-risk percutaneous coronary intervention.

Smith EJ, Reitan O, Keeble T, Dixon K, Rothman MT.
Department of Cardiology, London Chest Hospital, United Kingdom.
Catheter Cardiovasc Interv. 2009 Jun 1;73(7):859-65.
http://dx.doi.org/10.1002/ccd.21865.

To investigate the safety of a novel percutaneous circulatory support device during high-risk percutaneous coronary intervention (PCI).

BACKGROUND:

The Reitan catheter pump (RCP) consists of a catheter-mounted pump-head with a foldable propeller and surrounding cage. Positioned in the descending aorta the pump creates a pressure gradient, reducing afterload and enhancing organ perfusion.

METHODS:

Ten consecutive patients requiring circulatory support underwent PCI; mean age 71 +/- 9; LVEF 34% +/- 11%; jeopardy score 8 +/- 2.3. The RCP was inserted via the femoral artery. Hemostasis was achieved using Perclose sutures. PCI was performed via the radial artery. Outcomes included in-hospital death, MI, stroke, and vascular injury. Hemoglobin (Hb), free plasma Hb (fHb), platelets, and creatinine (cre) were measured pre PCI and post RCP removal.

RESULTS:

The pump was inserted and operated successfully in 9/10 cases (median 79 min). Propeller rotation at 10,444 +/- 1,424 rpm maintained an aortic gradient of 9.8 +/- 2 mm Hg.  Although fHb increased,

  • there was no significant hemolysis (4.7 +/- 2.4 mg/dl pre vs. 11.9 +/- 10.5 post, P = 0.04, reference 20 mg/dl).
  • Platelets were unchanged (pre 257 +/- 74 x 10(9) vs. 245 +/- 63, P = NS).
  • Renal function improved (cre pre 110 +/- 27 micromol/l vs. 99 +/- 28, P = 0.004).

All PCI procedures were successful with no deaths or strokes, one MI, and no vascular complications following pump removal.

14F RCP first in man mechanical device post PCI LVEF 25% JS 10

CONCLUSIONS:

The RCP can be used safely in high-risk PCI patients.

(c) 2009 Wiley-Liss, Inc.  PMID: 19455649

Todd J. Brinton, MD and Peter J. Fitzgerald, MD, PhD, Chapter 14: VENTRICULAR ASSIST TECHNOLOGIES

http://www.sis.org/docs/2006Yearbook_Ch14.pdf

Other related articles published on this Open Access Online Scientific Journal include the following:

A coronary angiogram that shows the LMCA, LAD ...

A coronary angiogram that shows the LMCA, LAD and LCX. (Photo credit: Wikipedia)

English: Simulation of a wave pump human ventr...

English: Simulation of a wave pump human ventricular assist device (Photo credit: Wikipedia)

English: Figure A shows the structure and bloo...

English: Figure A shows the structure and blood flow in the interior of a normal heart. Figure B shows two common locations for a ventricular septal defect. The defect allows oxygen-rich blood from the left ventricle to mix with oxygen-poor blood in the right ventricle. (Photo credit: Wikipedia)

 

Read Full Post »


Mechanical Circulatory Assist Devices as a Bridge to Heart Transplantation or as “Destination Therapy“: Options for Patients in Advanced Heart Failure

Writer and Curator: Larry H. Bernstein, MD, FCAP

and

Curator: Aviva Lev-Ari, PhD, RN 

 

UPDATED on 10/22/2018

HeartMate 3 gets FDA approval for extended use

Revamped Abbott Labs device is seen as an option for cardiac patients who are unlikely to get transplants.

“When heart failure (HF) progresses to an advanced stage, difficult decisions must be made,” the AHA says on its website. “Do I want to receive aggressive treatment? Is quality of life more important than living as long as possible? How do I feel about resuscitation?”

LVADs can take over the pumping function of a failing heart, but they also present some of the most expensive implantable-device surgeries. An article in the peer-reviewed journal JACC: Heart Failure reported last year that the average total cost to implant an LVAD in Medicare beneficiaries was $175,000, more than double the cost of a heart transplant.

Amador said between 5,000 and 5,500 Americans will have LVAD implants this year. That compares with 2,200 adult heart transplants that happen annually in the U.S., according to the JACC article.

Starling RC.
Cleve Clin J Med. 2013 Jan; 80(1):33-40. http://dx.doi.org/10.3949/ccjm.80gr.12003

For patients with advanced heart failure, outcomes are good after heart transplantation, but not enough donor hearts are available. Fortunately, mechanical circulatory assist devices have become an excellent option and should be considered either as a bridge to transplantation or as “destination therapy.” Current mechanical circulatory assist devices improve quality of life in patients who are candidates.
For some patients, conventional treatments are inadequate to relieve the effects of heart failure. Under these circumstances, mechanical circulatory support is considered. There are now a variety of devices capable of pumping blood to restore circulation of vital organs, even temporarily replacing the function of the native heart.

The ABIOMED AB5000™ Circulatory Support System is a short-term mechanical system that can provide left, right, or biventricular support for patients whose hearts have failed but have the potential for recovery. The AB5000™ can be used to support the heart, giving it time to rest – and potentially recover native heart function. The device can also be used as a bridge to definitive therapy.

http://med.umich.edu/cardiac-surgery/images/content/Abiomed_AB5000.jpg

Abiomed_AB5000

CardioWest™ temporary Total Artificial Heart (TAH-t) http://www.syncardia.com/cardiowesttaht/index.php
This medical device is the modern version of the Jarvik 7 artificial heart first implanted into Barney Clark in 1982. The CardioWest™ temporary Total Artificial Heart is the only FDA approved temporary total artificial heart in the world.
The TAH-t is used as a bridge to heart transplant for eligible patients suffering from end-stage biventricular failure.
http://med.umich.edu/cardiac-surgery/images/content/Cardiowest_TAHt_Photo.jpg

Cardiowest_TAHt_Photo

Other related articles published on this Scientific Journal include the following:

Ventricular Assist Device (VAD): A Recommended Approach to the Treatment of Intractable Cardiogenic Shock (larryhbern)
https://pharmaceuticalintelligence.com/2013/06/18/a-recommended-approach-to-the-treatmnt-of-intractable-cardiogenic-shock/

Trans-apical Transcatheter Aortic Valve Replacement in a Patient with Severe and Complex Left Main Coronary Artery Disease (LMCAD) (larryhbern)
https://pharmaceuticalintelligence.com/2013/06/17/management-of-difficult-trans-apical-transcatheter-aortic-valve-replacement-in-a-patient-with-severe-and-complex-arterial-disease/
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https://pharmaceuticalintelligence.com/2013/06/03/clinical-indications-for-use-of-inhaled-nitric-oxide-ino-in-the-adult-patient-market-clinical-outcomes-after-use-therapy-demand-and-cost-of-care

Gene Therapy Into Healthy Heart Muscle: Reprogramming Scar Tissue In Damaged Hearts
(Aviva Lev-Ari)
https://pharmaceuticalintelligence.com/2013/01/09/gene-therapy-into-healthy-heart-muscle-reprogramming-scar-tissue-in-damaged-hearts/

Heart Renewal by pre-existing Cardiomyocytes: Source of New Heart Cell Growth Discovered
(Aviva Lev-Ari)
https://pharmaceuticalintelligence.com/2012/12/23/heart-renewal-by-pre-existing-cardiomyocytes-source-of-new-heart-cell-growth-discovered/

Heart Remodeling by Design – Implantable Synchronized Cardiac Assist Device: Abiomed’s Symphony (Aviva Lev-Ari)
https://pharmaceuticalintelligence.com/2012/07/23/heart-remodeling-by-design-implantable-synchronized-cardiac-assist-device-abiomeds-symphony/

Economic Toll of Heart Failure in the US: Forecasting the Impact of Heart Failure in the United States – A Policy Statement From the American Heart Association (Aviva Lev-Ari)
https://pharmaceuticalintelligence.com/2013/04/25/economic-toll-of-heart-failure-in-the-us-forecasting-the-impact-of-heart-failure-in-the-united-states-a-policy-statement-from-the-american-heart-association/

Stenosis, Ischemia and Heart Failure (Aviva Lev-Ari)
https://pharmaceuticalintelligence.com/2013/05/16/stenosis-ischemia-and-heart-failure/

Congestive Heart Failure & Personalized Medicine: Two-gene Test predicts response to Beta Blocker Bucindolol (Aviva Lev-Ari)
https://pharmaceuticalintelligence.com/2012/10/17/chronic-heart-failure-personalized-medicine-two-gene-test-predicts-response-to-beta-blocker-bucindolol/

Phrenic Nerve Stimulation in Patients with Cheyne-Stokes Respiration and Congestive Heart Failure (larryhbern)
https://pharmaceuticalintelligence.com/2013/06/20/phrenic-nerve-stimulation-in-patients-with-cheyne-stokes-respiration-and-congestive-heart-failure/

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Meta-analysis: Heart Failure Worsens Short-term Prognosis of NSTE-ACS Patients – TCTMD
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Implantable Synchronized Cardiac Assist Device Designed for Heart Remodeling: Abiomed’s Symphony

Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/07/11/implantable-synchronized-cardiac-assist-device-designed-for-heart-remodeling-abiomeds-symphony/

 

What is Acute Heart Failure?

What is Acute Heart Failure? (Photo credit: Novartis AG)

English: The CardioWest™ temporary Total Artif...

English: The CardioWest™ temporary Total Artificial Heart (Photo credit: Wikipedia)

English: Graph showing the correlation between...

English: Graph showing the correlation between BNP serum level and mortality. Source: Inder S. Anand, Lloyd D. Fisher, Yann-Tong Chiang, Roberto Latini, Serge Masson,Aldo P. Maggioni, Robert D. Glazer, Gianni Tognoni, Jay N. Cohn (24th Feb 2003). Changes in Brain Natriuretic Peptide and Norepinephrine Over Time and Mortality and Morbidity in the Valsartan Heart Failure Trial (Val-HeFT). Circulation 107: 1278-83. DOI: 10.1161/01.CIR.0000054164.99881.00 (Photo credit: Wikipedia)

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Ventricular Assist Device (VAD): A Recommended Approach to the Treatment of Intractable Cardiogenic Shock

Writer: Larry H Bernstein, MD, FCAP

 and

Curator: Aviva Lev-Ari, PhD, RN

A ventricular assist device (VAD) is an implantable mechanical pump that helps pump blood from the lower chambers of your heart (the ventricles) to the rest of your body. VADs are used in people who have weakened hearts or heart failure. Although VADs can be placed in the left, right or both ventricles of your heart, they are most frequently used in the left ventricle. When placed in the left ventricle they are called left ventricular assist devices (LVADs).

You may have a VAD implanted while you wait for a heart transplant or for your heart to become strong enough to effectively pump blood on its own. Your doctor may also recommend having a VAD implanted as a long-term treatment if you have heart failure and you’re not a good candidate for a heart transplant.

The procedure to implant a VAD requires open-heart surgery and has serious risks. However, a VAD can be lifesaving if you have severe heart failure.

http://www.mayoclinic.com/health/lvad/MY01077

This is an assessment of the development and progression of cardiogenic shock  and review of the use of ventricular assist devices in that setting.  It is another piece of the chapter on cardiothoracic surgical management at Columbia University Medical Center, New York, NY.

A stepwise progression in the treatment of cardiogenic shock.

Pollack AUriel NGeorge IKodali STakayama HNaka YJorde U.

Source

Department of Medicine, New York Presbyterian Hospital/Columbia University Medical Center, New York, New York, USA.

Abstract

Cardiogenic shock remains a deadly complication of acute myocardial infarction (MI). Early revascularization, inotropic support, and intraaortic balloon counterpulsation are the mainstays of treatment, but these are not always sufficient. New mechanical approaches, both percutaneous and surgical, are available in this high-risk population. We present a case of a young woman with a massive anterior wall MI and subsequent cardiogenic shock who was treated with advanced mechanical circulatory support. This case serves as an illustration of the stepwise escalation of mechanical support that can be applied in a patient with an acute MI complicated by refractory cardiogenic shock. We also review the literature with regard to the use of percutaneous left ventricular assist devices in the setting of cardiogenic shock.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID: 22608034

Care of the Critically Ill:  A Stepwise Progression in the Treatment of Cardiogenic Shock.

Pollack A, Uriel N, George I, Kodali S, Takayama H, Naka Y, Jorde U
J Heart & Lung 2012; 41:500-504.

Initial Presentation

 A 21-year-old woman with a history of migraine headaches was admitted to the hospital with nonradiating substernal chest pain onset that morning. When she presented to another hospital she had a normal electrocardiogram (EKG) and was discharged. When the patient’s chest discomfort became crushing  she presented again to the same hospital where her EKG revealed ST-segment elevations in an anterolateral distribution. Her peak (hs) troponin was 229 ng/mL and peak creatinine kinase was 6900 U/L.  This was an elevation of CK far out of proportion to the troponin increase (suggestive of decreased peripheral circulation with massive release of CK from muscle). There was no family history of early myocardial infarction (MI), sudden cardiac death, clotting disorders, or hypercholesterolemia. She had been taking amitriptyline for migraines and oral contraceptives for 3 years.  The patient developed significant hypotension, after she was given metoprolol and morphine, for which dobutamine and dopamine were administered. Medication was switched to norepinephrine because of excessive tachycardia. Cardiac catheterization was performed emergently approximately 12 hours after the onset of the patient’s chest pain.
Thrombectomy of an angiographically identified clot in the proximal portion of the left anterior descending artery was performed, followed by placement of a bare metal stent with no residual occlusion. An intraaortic balloon bump (IABP) was placed. The initial transthoracic echocardiogram revealed an ejection fraction of 25% and global hypokinesis with regional wall motion abnormalities, worst in the anterior, apical, and lateral walls. She was intubated and required significant hemodynamic support with norepinephrine. Her antiplatelet regimen consisted of oral aspirin, clopidogrel, and intravenous eptifibatide. The patient was transferred to the New York Presbyterian Hospital/Columbia University Medical Center approximately 12 hours after revascularization.

Transfer to  NY Presbyteran Columbia Hospital

On arrival, the patient was intubated and sedated. Her blood pressure was 80/51mmHg, pulse rate was 140 beats/min, and oral temperature was 101F. On examination, she was tachycardic with warm extremities. The jugular veins were not distended. Her lactate was 7.0 mmol/L. (If she was so severely hypotensive with lactic acidemia, possibly from impaired liver and/or muscle circulation with aerobic glycolysis, then why was the temperature 101 deg F?)  The patient was not tested for procalcitonin (Brahms, BioMerieux), but sepsis is now considered bacterial or abacterial.  Whether there was release of bacterial endotoxin secondary to poor decreased circulation in the superior mesenteric artery is not known, which complicates the situation more.  In a study of acute phase changes in liver proteins by Bernstein and associates [Transthyretin as a marker to predict outcome in critically ill patients. Devakonda A, George L, Raoof S, Esan A, Saleh A, Bernstein LH.   Clin Biochem 2008; 41(14-15):1126-1130. ICID: 939927], and another on  procalcitonin and sepsis [The role of procalcitonin in the diagnosis of sepsis and patient assignment to medical intensive care. Bernstein LH, Devakonda A, Engelman E, Pancer G,  Ferrar J, Rucinski J, Raoof S,  George L, Melniker L.  J Clin Ligand Assay] there was a notable case of negative bacterial culture in a patient with highly elevated procalcitonin, considered a reliable early indicator of sepsis.sepsis classification with PCT and MAP
Procalcitonin (PCT) is a sensitive and specific inflammation marker, which can be used to detect both inflammatory infections and noninflammatory complications in postsurgical monitoring of patients after cardiac surgery using extracorporeal circulation. The optimum cut-off value for PCT levels, as a predictor of postoperative complications, appears to be 1.2 ng/mL with a sensitivity of 80% and a specificity of 90%. PCT may be used to monitor response to therapy because blood concentrations increase in an inflammatory disease relapse. Importance of procalcitonin in post-cardiosurgical patients. Topolcan O, Bartunek L, Holubec Jr L,  Polivkova V, eta al. Journal of Clinical Ligand Assay 2008; 31(1-4): 57-60.]This might be expected to be associated with a CRP increase over 50-70 mg/ml.  In addition, the hemogram would have been of some interest, perhaps raising the question of whether the cardiovascular impairment triggered other events [Validation and Calibration of the Relationship between Granulocyte Maturation and the Septic State. Bernstein LH and Rucinski J.  Clin Chem Lab Med 2011; 49. Walter de Gruyter . http://dx.doi.org/10.1515cclm.2011.688Converting Hematology Based Data into an Inferential Interpretation. Bernstein LH, David G, Rucinski J and Coifman RR.  In Hematology – Science and Practice, 2012. Chapter 22, pp 541-552. InTech Open Access Publ. Croatia]. 
A chest radiograph showed pulmonary edema. Her EKG revealed sinus tachycardia at 121 beats/min with ST-segment elevation of 3 mm in leads V1 to V4 and poor R-wave progression throughout the precordial leads with pathologic Q waves in V1 to V6, I, and aVL. Eptifibatide (Integrilin, Merck & Co., Inc., Whitehouse Station, NJ) was stopped, and norepinephrine was continued at 20 mg/min. Dobutamine 2.5 mg/min and broad-spectrum antibiotics were administered. During the next 4 hours, the patient’s mean arterial pressure fluctuated between 60 and 70 mm Hg with a heart rate between 120 and 140 beats/min on 20 mg/min of norepinephrine, 2.5 mg/min of dobutamine, and the IABP. Rapid escalation of mechanical support with a left ventricular assist device (LVAD) was deemed necessary.  Right-sided heart catheterization after placement of an Impella 2.5 assist device (ABIOMED, Inc.) revealed a cardiac output of 3.3 L/min and a cardiac index (CI) of 2.1 L/min/m2, despite addition of 3 ug/min and 4 U/h of vassopressin.

Day 2

On the second day after transfer she was severely hyponatremic, but her plasma sodium stabilized at 131 to 138 mmol/L after discontinuing the vasopressin. She also developed significant bleeding at the site of the Impella and hemolysis requiring several blood transfusions. Her hemoglobin on transfer was 10.4 g/dL, which trended down to 7.8 g/dL after Impella placement. The patient’s lactate dehydrogenase was 1980 U/L (probably reflecting poor liver perfusion), and total bilirubin was 2.6 mg/dL on day 2 of her hospitalization compared with 1.1 mg/dL on transfer.

Day 3

After the Impella device was removed on day 3 because of persistent bleeding, the patient’s hemoglobin, bilirubin, and platelet count stabilized, but while the patient was able to maintain end-organ perfusion initially as manifested by a normal creatinine, as the day progressed, the patient’s systemic blood pressure trended downward and urine output decreased, and she could not tolerate discontinuation of the vasoactive agents being administered. Pulmonary hypertension developed with a rate-dependent cardiac output as manifested by persistent tachycardia, and had an ejection fraction of 20% with severe hypokinesis of all segments except the basal inferior and inferolateral walls. As a consequence of the enduring cardiogenic shock and the low likelihood for recovery of left ventricular function, it was evident the patient required long-term mechanical support. A continuous flow LVAD (HeartMate II; Thoratec Corporation) was implanted as a rescue therapy, and the patient was emergently listed for transplantation.

Recovery

A comprehensive heart failure regimen was introduced, and the patient was discharged with warfarin 25 days after her transfer. A comprehensive hypercoagulability workup performed while the patient was receiving anticoagulation with negative results. Aside from oral contraceptive use, no other obvious risk factor for an acute arterial thrombosis could be identified, which is not surprising given that up to 40% of all thrombotic events occur in patients without a recognizable risk factor. Early revascularization, inotropic support, and intraaortic balloon counterpulsation are the mainstays of treatment, but these are not always sufficient.  New mechanical approaches, both percutaneous and surgical, are available in this high-risk population. This case serves as an illustration of the stepwise escalation of mechanical support that can be applied in a patient with an acute MI complicated by refractory cardiogenic shock. We also review the literature with regard to the use of percutaneous left ventricular assist devices in the setting of cardiogenic shock.

Recommendation

The authors recommend the following protocol for patients with cardiogenic shock superimposed on acute MI.    Treatment of cardiogenic shock.  PCI, percutaneous coronary intervention; IABP, intraaortic balloon pump; VAD, ventricular assist device; VA-ECMO, venoarterial extracorporeal membrane oxygenation; OHT, orthotopic heart transplantation; pVAD, percutaneous ventricular assist device. It is important to note that it includes immediate revascularization in conjunction with IABP placement. In patients with refractory cardiogenic shock who are unable to be weaned from the IABP, mechanical circulatory support using a percutaneous or surgical device is the next essential measure to be taken. The type of mechanical support to be used depends on many factors, including the reversibility of the shock state, chances of ventricular recovery, and risk of bleeding. Mechanical circulatory support with left ventricular assists devices can improve cardiac performance and reduce myocardial ischemic injury. Principle mechanisms include unloading of the left ventricle, thereby decreasing myocardial oxygen demand and improvement of systemic hypotension, thus increasing coronary perfusion.
Although there were complications related to the use of the device, its deployment resulted in the improvement of the patient’s surgical candidacy by virtue of maintaining her end-organ function.  After the removal of the Impella device, we thought the left ventricle in this patient would not recover, and for this reason, we chose a definitive surgical procedure as opposed to alternative temporary support device.  Clinical studies focusing on the use of VA-ECMO in refractory cardiogenic shock after an acute MI are limited. Observational and retrospective series have thus far demonstrated a high mortality rate in these patients.  However, a recent retrospective study of 33 patients who received ECMO support for advanced refractory cardiogenic shock after an acute MI demonstrated a mortality rate of 46% and 52% at 30 days and 1 year, respectively. In addition to mny complications with VA-ECMO, the procedure also can lead to increased afterload from the retrograde flow of peripheral cannulation., which may to lead to increased left ventricular pressure and wall stress, thereby compromising myocardial recovery and worsening pulmonary edema, both of which were major concerns
in this patient.

Conclusions

This case demonstrates that a sequential approach using percutaneous mechanical support as a bridge to surgical mechanical support is feasible in this high-risk population (Figure ). Advantages of percutaneous mechanical support include its rapid and straightforward placement. Disadvantages include its limited cardiac output and bleeding. Future technology should focus on a device that is capable of providing significant cardiac output and that can be easily placed, like the Impella. Such a device could alter the natural history of intractable cardiogenic shock.

Other related articles published on this Open Access Online Scientific Journal include the following:

Implantable Synchronized Cardiac Assist Device Designed for Heart Remodeling: Abiomed’s Symphony

Aviva Lev-Ari, PhD, RN, 7/11/2012

https://pharmaceuticalintelligence.com/2012/07/11/implantable-synchronized-cardiac-assist-device-designed-for-heart-remodeling-abiomeds-symphony/

Biomaterials Technology: Models of Tissue Engineering for Reperfusion and Implantable Devices for Revascularization

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/5_04_2013/bernstein_lev-ari/Bioengineering_of_Vascular_and_Tissue_Models

Foreseen changes in Guideline of Treatment of Cardiogenic Shock with Intra-aortic Balloon counterPulsation (IABP)

Evidence for Overturning the Guidelines in Cardiogenic Shock

Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care

Aviva Lev-Ari, PhD, RN, 6/3/2013

English: Ventricular assist device

English: Ventricular assist device (Photo credit: Wikipedia)

English: Simulation of a wave pump human ventr...

English: Simulation of a wave pump human ventricular assist device (Photo credit: Wikipedia)

myocardial infarction - Myokardinfarkt - scheme

myocardial infarction – Myokardinfarkt – scheme (Photo credit: Wikipedia)

English: Graphic presentation of an LVAD, left...

English: Graphic presentation of an LVAD, left ventricular assist device. (Photo credit: Wikipedia)

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