Funding, Deals & Partnerships: BIOLOGICS & MEDICAL DEVICES; BioMed e-Series; Medicine and Life Sciences Scientific Journal – http://PharmaceuticalIntelligence.com
CentraCare First in World to Use 4D Hologram Technology to Successfully Complete Structural Heart Procedure
Reporter: Aviva Lev-Ari, PhD, RN
Published Jun 23, 2021 in Heart & Vascular, Media ReleasesAuthor: CentraCare
EchoPixel’s pre-planning and intra-operative technologies reduced complex heart procedure time while improving quality of outcomes
CentraCare, one of the largest health systems in Minnesota, has successfully completed the first structural heart procedure in the world using 4D hologram technology, which was developed by EchoPixel. Jacob Dutcher, MD, an interventional cardiologist and director of the structural heart program at CentraCare Heart & Vascular Center, conducted the WATCHMAN implant, which is a one-time, minimally invasive procedure for people with atrial fibrillation who need an alternative to blood thinners to protect them from a stroke. Approximately six million people in the U.S. suffer from atrial fibrillation and many of them are intolerant to blood thinners.
This new approach to the WATCHMAN procedure combines both EchoPixel’s pre-planning True3D software with its intra-operative Holographic Therapy Guidance (HTG) software platform. By leveraging mixed reality capabilities, EchoPixel brings precision to structural heart procedures by utilizing HTG, a transformative 4D technology that enables the entire heart team to interact with a patient’s specific organs and tissues as if they were actual, physical objects. These technologies reduce procedure time, improve accuracy of the procedure, reduce risk of complication and hasten recovery.
CentraCare Heart & Vascular Center is the first in the world to use EchoPixel’s technology both before and during a structural heart procedure. “EchoPixel pre-planning True3D software helped us reduce our procedure times by more than 27% and increase optimal procedure outcome by 20%. EchoPixel-HTG is taking us to the next level,” says Dr. Dutcher. “As one of the world’s largest WATCHMAN implanting sites, we are always looking for new ways to advance and improve patient care, and are proud to be the first center in the world to offer this novel imaging technology.”
“Dr. Dutcher has been very influential in the development and evolution of our HTG technology,” says Sergio Aguirre, CEO of EchoPixel. “Having him on board has helped us hone our device and approach as we draw on his vast experience with this procedure. We are looking forward to continuing to work with him and CentraCare to adapt our software to other structural heart procedures, providing an even greater benefit to patients.”
About CentraCare Heart & Vascular Center
CentraCare Heart & Vascular Center is one of the largest cardiovascular programs in Minnesota, offering the latest advancements in care, technology and treatment. In 2020 U.S. News & World Report rated the program as #41 in the nation for cardiology and heart surgery. It is part of CentraCare, a Minnesota health system that includes eight hospitals in St. Cloud, Long Prairie, Melrose, Monticello, Paynesville, Redwood Falls, Sauk Centre and Willmar. The health system also owns more than 30 clinics along with 18 senior housing facilities and long-term care facilities throughout the region. Learn more about CentraCare Heart & Vascular Center
About EchoPixel
Headquartered in Silicon Valley, EchoPixel is a venture capital-backed startup and a pioneer in creating the operating room of the future. The company’s technologies include the first pre-operative True3D planning platform and intra-operative Holographic Therapy Guidance (HTC) software, which allow physicians to interact with patient-specific organs and tissues as if they were actual, physical objects. EchoPixel’s True3D software platform has already become the standard of care at world-leading congenital heart defect and structural heart centers. Learn more at echopixeltech.com.
Changes in Levels of Sex Hormones and N-Terminal Pro–B-Type Natriuretic Peptide as Biomarker for Cardiovascular Diseases
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
Considerable differences exist in the prevalence and manifestation of atherosclerotic cardiovascular disease (CVD) and heart failure (HF) between men and women. Premenopausal women have a lower risk of CVD and HF compared with men; however, this risk increases after menopause. Sex hormones, particularly androgens, are associated with CVD risk factors and events and have been postulated to mediate the observed sex differences in CVD.
B-type natriuretic peptides (BNPs) are secreted from cardiomyocytes in response to myocardial wall stress. BNP plays an important role in cardiovascular remodelling and volume homeostasis. It exerts numerous cardioprotective effects by promoting vasodilation, natriuresis, and ventricular relaxation and by antagonizing fibrosis and the effects of the renin-angiotensin-aldosterone system. Although the physiological role of BNP is cardioprotective, pathologically elevated N-terminal pro–BNP (NT-proBNP) levels are used clinically to indicate left ventricular hypertrophy, dysfunction, and myocardial ischemia. Higher NT-proBNP levels among individuals free of clinical CVD are associated with an increased risk of incident CVD, HF, and cardiovascular mortality.
BNP and NT-proBNP levels are higher in women than men in the general population. Several studies have proposed the use of sex- and age-specific reference ranges for BNP and NT-proBNP levels, in which reference limits are higher for women and older individuals. The etiology behind this sex difference has not been fully elucidated, but prior studies have demonstrated an association between sex hormones and NT-proBNP levels. Recent studies measuring endogenous sex hormones have suggested that androgens may play a larger role in BNP regulation by inhibiting its production.
Data were collected from a large, multiethnic community-based cohort of individuals free of CVD and HF at baseline to analyze both the cross-sectional and longitudinal associations between sex hormones [total testosterone (T), bioavailable T, freeT, dehydroepiandrosterone (DHEA), SHBG, and estradiol] and NT-proBNP, separately for women and men. It was found that a more androgenic pattern of sex hormones was independently associated with lower NT-proBNP levels in cross-sectional analyses in men and postmenopausal women.
This association may help explain sex differences in the distribution of NT-proBNP and may contribute to the NP deficiency in men relative to women. In longitudinal analyses, a more androgenic pattern of sex hormones was associated with a greater increase in NT-proBNP levels in both sexes, with a more robust association among women. This relationship may reflect a mechanism for the increased risk of CVD and HF seen in women after menopause.
Additional research is needed to further explore whether longitudinal changes in NT-proBNP levels seen in our study are correlated with longitudinal changes in sex hormones. The impact of menopause on changes in NT-proBNP levels over time should also be explored. Furthermore, future studies should aim to determine whether sex hormones directly play a role in biological pathways of BNP synthesis and clearance in a causal fashion. Lastly, the dual role of NTproBNP as both
a cardioprotective hormone and
a biomarker of CVD and HF, as well as
the role of sex hormones in delineating these processes,
should be further explored. This would provide a step toward improved clinical CVD risk stratification and prognostication based on
Renowned Electrophysiologist Dr. Arthur Moss Died on February 14, 2018 at 86
Reporter: Aviva Lev-Ari, PhD, RN
— Stephen
Dr. Moss never lost the opportunity to get to know who an individual is by name, to complement one, to greet one, to teach one, to be available, and to show respect. His contributions to clinical medicine, patient care and physician education, along with pivotal research, is among the ver most notable of our era. I will miss him greatly and extend my most heartfelt gratitude to him and his family.
Stephen Winters, MD Morristown Medical Center
Comments Section
Renowned Cardiologist Arthur J. Moss, Pioneer of Research and Treatment in Sudden Death, Passes Away
Friday, February 16, 2018
Arthur J. Moss, M.D.
Cardiologist Arthur J. Moss, whose research saved hundreds of thousands of lives and improved the standard of care for legions of people with heart disease, died on February 14, 2018. He was 86.
During a career spanning six decades, Moss made some of the most significant and long-lasting discoveries in the prevention and treatment of sudden cardiac death. His astounding accomplishments in scientific research and clinical care stemmed especially from his special devotion to patients; he understood the importance of listening, building trust and working together to bring about change. He was also a skilled leader, able to foster meaningful collaborations that led to some of the most productive clinical trials in all of cardiology.
“Arthur was a man of absolute integrity, both of science and of character, and an amazing visionary who could see where the field of electrophysiology was headed long before others,” said Wojciech Zareba, M.D., Ph.D.,director of the Heart Research Follow-up Program at the University of Rochester Medical Center, who worked closely with Moss for the past 26 years. “He was eternally optimistic in all aspects of his life; he brought a positive attitude to everything he did and didn’t worry about the small stuff, which helped him accomplish great things.”
In 1958, as an intern at Massachusetts General Hospital, Moss planned to pursue a career in hematology. That summer he was called to serve in the United States Navy. When he arrived in Pensacola, Fla., his commanding officers thought he was a cardiologist, for reasons unbeknownst to him. They asked Moss to teach flight surgeons electrocardiography, a test known as an EKG that checks the electrical activity of the heart. Undaunted, he read multiple books on the topic and taught them. The intricacy of the heart’s electrical activity captured Moss’ interest and he never looked back.
Moss spent the first half of his career figuring out which patients were at high risk of sudden cardiac death and the second half finding the best ways to treat them. He became an eminent authority on common arrhythmias that afflict hundreds of thousands of adults with heart disease and often lead to sudden death, as well as rare heart rhythm disorders that are smaller in number but no less deadly.
An unexpected patient visit in 1970 started what Moss called the most rewarding part of his career: his life-long quest to help individuals with Long QT syndrome (LQTS). Doctors could not understand why this patient – a woman in her 30s – would suddenly fall unconscious when she got excited while bowling. An unusual EKG led Moss, then a young cardiologist at URMC, to diagnose LQTS. An uncommon genetic condition caused by a glitch in the heart’s electrical system, LQTS puts patients at high risk of arrhythmias, fainting spells and sudden death.
Moss devised the first effective surgical treatment for the disorder and had the foresight to create the International Long QT Syndrome Registry in 1979, one of the first rare disease registries in the world. The registry allowed Moss and colleagues to identify risk factors that enable early diagnosis; develop multiple treatment options that have achieved an 80 percent reduction in life-threatening events; and contribute to the discovery of multiple genes associated with the disorder. The National Institutes of Health has supported the registry since its creation, and in 2014 Moss received a NIH grant to fund the registry and associated research projects through 2019.
“Not only was Arthur extraordinary in understanding the immediate problem, but he was also visionary in that long before we knew how to analyze genes he started the registry and preserved blood samples that could be used in the future,” said Mark B. Taubman, M.D., CEO of URMC and dean of the School of Medicine and Dentistry. “The registry has become one of the most important repositories in the world, helping prevent thousands of untimely deaths from Long QT and enabling the in-depth investigation of how genetics influence a form of heart disease. The impact of his work is unparalleled.”
Beginning in the 1990s, Moss led the MADIT (Multicenter Automatic Defibrillator Implantation Trial) series of clinical trials, which showed that the implantable cardioverter defibrillator or ICD – a device that detects arrhythmias and shocks the heart back into a normal rhythm – significantly reduces the risk of sudden death in patients who’ve experienced a heart attack. In the early 2000s these findings changed medical guidelines worldwide and led to the use of life-saving ICD therapy in hundreds of thousands of patients.
Later, in 2009, Moss completed the MADIT-CRT trial, which found that cardiac resynchronization therapy plus defibrillator – CRT-D therapy – prevents the progression of heart failure in patients living with mild forms of the disease. The device, which improves the mechanical pumping action of the heartand corrects fatal rhythms, was originally approved to treat patients with severe heart failure. Moss’ work opened the door for multitudes more patients to benefit and live longer, better lives.
“Arthur’s research was so successful and powerful because the results of his studies were usually strikingly positive or negative. This came from his rare ability to ask a simple question, and use a simple clinical trial design,” said Bradford C. Berk, M.D., Ph.D., professor of Medicine and Cardiology at URMC. “He did this so well because he was a superb clinician who had a remarkable insight into the underlying pathologic mechanisms of heart disease.”
Colleagues also credit Moss’ research success to his unique ability to bring people together, trigger discussion, and make all involved – from the highest-ranking physician to the newest graduate student or fellow – feel welcome and valued.
“I first met Art in 1976 and was at least three academic ranks lower than anyone else at the meeting,” said Henry (Hank) Greenberg, M.D., special lecturer of Epidemiology and Medicine at the Columbia University Medical Center. “Art sensed this and stated that everyone at the table contributed. This carried forward for four decades and was a reason why his trials were always superbly done. His ego did not get in the way.”
Moss was founding director of URMCs Heart Research Follow-up Program, a worldwide hub of international studies on medical interventions for sudden death, cardiac arrhythmias, heart attack and heart failure. He published more than 750 scientific papers, including a 1962 article – his first of many in the New England Journal of Medicine – highlighting the first three published cases of cardiopulmonary resuscitation (CPR), which included external chest massage followed by external defibrillation.
Charles J. Lowenstein, M.D., chief of Cardiology at URMC, said, “Arthur’s contributions to cardiac electrophysiology were vast and he was extremely well respected as a clinician and researcher. He also trained hundreds of medical students, residents, and fellows, and inspired many of us to dedicate our lives to medicine. This is his greatest legacy.”
Moss attended Yale as an undergraduate then Harvard Medical School. He interned at Massachusetts General Hospital and finished his residency in Rochester, where he also did a fellowship in cardiology. Moss joined the faculty at URMC in 1966 and stayed for the rest of his career, ultimately becoming the Bradford C. Berk, M.D., Ph.D. Distinguished Professor in Cardiology. A valued member of the faculty, Moss received the Eastman Medal in 2012, the University of Rochester’s highest honor that recognizes individuals who, through their outstanding achievement and dedicated service, embody the high ideals for which the University stands.
On numerous other occasions, Moss was recognized locally, nationally and internationally for his tenacity and advancement of medical and cardiologic science. In 2008 he received the Glorney-Raisbeck Award in Cardiology, the highest honor of the New York Academy of Medicine. A year later he was awarded the prestigious Golden Lionel Awardat the Venice International Cardiac Arrhythmias Meeting. The Heart Rhythm Society, the major international electrophysiology society, bestowed its top honor, theDistinguished Scientist Award, to Moss in 2011 and its Pioneer in Cardiac Pacing and EP Award to Moss in 2017.
On November 11, 2017, just four months before his death, Moss was given the 2017 James B. Herrick Award at the American Heart Association’s Scientific Sessions. The award is given annually to a physician whose scientific achievements have contributed profoundly to the advancement and practice of clinical cardiology.
“Arthur’s passing is very sad news for the world of cardiology and clinical trials,” said David Cannom, director of Cardiology at Good Samaritan Hospital in Los Angeles. “There was no one quite like Arthur in terms of intelligence, judgement, leadership skills and thoughtful friendship. Plus good humor. An era is closing and he will be sorely missed.” Other colleagues from around the world described him as a “true giant” in the field, a “role model,” and a “pioneer.”
Moss’s daughter Deborah, herself a physician, was always inspired by her dad’s curiosity, creativity and perseverance. “He paid close attention to his patients, their stories and their situations, and generated research questions that would make a difference not just for one patient, but for many patients. He was bold, never afraid to try something new, and wouldn’t stop until he solved a problem. Looking back on the entirety of his career, it was really incredible.”
Moss is survived by his wife Joy F. Moss, three children – Katherine M. Lowengrub, M.D., instructor in Psychiatry at the Sackler School of Medicine in Tel Aviv, Israel; Deborah R. Moss, M.D., M.P.H., associate professor of Pediatrics at the University of Pittsburgh Medical Center; and David A. Moss, Ph.D., professor at Harvard Business School – and nine grandchildren and two great-grandchildren. A memorial service will take place at Temple B’rith Kodesh on Elmwood Ave at 11 a.m. on Sunday, February 18. In lieu of flowers, donations may be sent to:
His legacy is a career spanning more than 60 years that was marked by major contributions to cardiac electrophysiology, including the first surgical treatment for long QT syndrome and his leadership in the MADIT trials showing that an implantable cardioverter defibrillator could reduce the risk of sudden cardiac death.
Moss started his career in risk stratification studies and evaluating the potential of ventricular arrhythmias, according to longtime colleague Sanjeev Saksena, MD, past president of the North American Society of Pacing and Electrophysiology. Sakesna said that in 1983 Moss published “pivotal studies on risk stratification after myocardial infarction that led to his recognition as a leader in this field and was famously covered by TIME magazine for these contributions.”
Saksena also noted his early support of Michel Mirowski’s concept of an implanted standby defibrillator. This support, Saksena said “made him a lone voice arguing against the medical establishment more than 40 years ago for development of a therapy that is now a cornerstone of cardiovascular medicine.”
Douglas Zipes, MD, Past President, American College of Cardiology: “Wonderful man, scientist. He was the gold standard role model for the clinician investigator: he took care of patients and advanced the science of cardiology. A great loss, but his observations will live on.”
Robert Myerberg, MD, Professor of Medicine, University of Miami: “Art Moss had had an incredibly productive career. His dominant characteristic was a lack of fear of stepping into areas where there were gaps in our knowledge or untested hypotheses, and find a way to get us on to a path that would ultimately answer important and practical questions … His impact will continue to be felt long into the future. And on a personal level, his warmth and collegiality will be missed by his friends and colleagues.”
Bernard Gersh, MD, Professor of Medicine, Mayo Clinic: “Major contributions to our understanding of the long QT syndrome and the PI [principal investigator] of the major trials that established the clinical role of the ICD.”
Richard L. Page, MD, Chair, Department of Medicine, University of Wisconsin, School of Medicine & Public Health: “Arthur Moss was a consummate professional, gentleman, scholar, and physician. He was a role model for me and for a generation of cardiologists.”
Jagmeet P. Singh MD, Roman W. DeSanctis Endowed Chair in Cardiology, Massachusetts General Hospital Heart Center: “A huge loss for our community. He was my mentor.”
Question What is the association of inferior vena cava filter placement with 30-day mortality in patients with venous thromboembolic disease and a contraindication to anticoagulation?
Findings In this cohort study, using 2 different statistical methods with adjustment for immortal time bias, inferior vena cava filter placement in patients with venous thromboembolic disease and a contraindication to anticoagulation was associated with an increased risk of 30-day mortality.
Meaning Randomized clinical trials are needed to define the role of inferior vena cava filter placement in patients with venous thromboembolic disease and a contraindication to anticoagulation.
Abstract
Importance Despite the absence of data from randomized clinical trials, professional societies recommend inferior vena cava (IVC) filters for patients with venous thromboembolic disease (VTE) and a contraindication to anticoagulation therapy. Prior observational studies of IVC filters have suggested a mortality benefit associated with IVC filter insertion but have often failed to adjust for immortal time bias, which is the time before IVC filter insertion, during which death can only occur in the control group.
Objective To determine the association of IVC filter placement with 30-day mortality after adjustment for immortal time bias.
Design, Setting, and Participants This comparative effectiveness, retrospective cohort study used a population-based sample of hospitalized patients with VTE and a contraindication to anticoagulation using the State Inpatient Database and the State Emergency Department Database, part of the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, from hospitals in California (January 1, 2005, to December 31, 2011), Florida (January 1, 2005, to December 31, 2013), and New York (January 1, 2005, to December 31, 2012). Data analysis was conducted from September 15, 2015, to March 14, 2018.
Exposure Inferior vena cava filter placement.
Main Outcomes and Measures Multivariable Cox proportional hazard models were constructed with IVC filters as a time-dependent variable that adjusts for immortal time bias. The Cox model was further adjusted using the propensity score as an adjustment variable.
Results Of 126 030 patients with VTE, 61 281 (48.6%) were male and the mean (SD) age was 66.9 (16.6) years. In this cohort, 45 771 (36.3%) were treated with an IVC filter, whereas 80 259 (63.7%) did not receive a filter. In the Cox model with IVC filter status analyzed as a time-dependent variable to account for immortal time bias, IVC filter placement was associated with a significantly increased hazard ratio of 30-day mortality (1.18; 95% CI, 1.13-1.22; P < .001). When the propensity score was included in the Cox model, IVC filter placement remained associated with an increased hazard ratio of 30-day mortality (1.18; 95% CI, 1.13-1.22; P < .001).
Conclusions and Relevance After adjustment for immortal time bias, IVC filter placement was associated with increased 30-day mortality in patients with VTE and a contraindication to anticoagulation. Randomized clinical trials are needed to determine the efficacy of IVC filter placement in patients with VTE and a contraindication to anticoagulation.
EDITORIAL
Requiem for Liberalizing Indications for Vena Caval Filters?
Use of inferior vena caval (IVC) filters has proliferated.
In 1979, ≈2000 vena caval filters were inserted.
In 1999, the number of IVC filters inserted annually had increased ≈25-fold to 49 000.
Retrievable IVC filters were first approved in 2003 and gained popularity rapidly.
By 2006, retrievable IVC filters accounted for about half of all IVC filters that were inserted.
The largest proportional increase in IVC filter use was subsequently in patients at risk for pulmonary embolism (PE) but who had had neither PE nor deep vein thrombosis (DVT).1
The Controversy by Samuel Z. Goldhaber, MD
Appropriate use of IVC filters is a hot topic. On the one hand,
filters hold the promise of reducing PE rates by trapping moderate and large DVT that have detached from the deep veins of the legs and pelvis and that are hurtling toward the heart. On the other hand, we do not have clear-cut definitions of which patients with PE and DVT will benefit most from this technology.
an array of complications can ensue, including
caval perforation,2
caval thrombosis,
fracture,
fragment embolization,
intracardiac migration,3
cardiac perforation, and
cardiac tamponade.4
In a systematic review of retrievable IVC filters, only 34% were retrieved, and the majority remained in place permanently. Most of the complications from retrievable filters occurred with long-term use.5
Guidelines
However, it is premature to hammer nails into the coffin and to gather as a medical community for a requiem that celebrates no indication for liberalizing indications for placing an IVC filter. Instead, we need to shift the focus of the questions that we investigate and pour resources into further randomized and observational trials of IVC filter insertion in special highrisk populations.
There remain important groups of patients who may benefit from IVC filters with reduction in PE and PE-associated mortality (Table 2). In some cases, tantalizing data suggest that these populations warrant filters. In other cases, we lack data to guide us. Patients with massive PE—accompanied by cardiogenic shock requiring vasopressors to support blood pressure—are desperately ill. They are clinically unstable. An additional PE under these circumstances can be the fatal blow. Data from the National Inpatient Sample and the International Cooperative PE Registry suggest that filters in these patients may be lifesaving.
Patients with severe PE who undergo acute surgical pulmonary embolectomy are vulnerable to recurrent PE, especially during the early postoperative period where full anticoagulation cannot be immediately implemented. I have had personal experience managing this type of patient where the embolectomy is successful but the patient dies of recurrent PE.19
Table 1. Generally Accepted Consensus Recommendations for IVC Filter Insertion in Patients With VTE
Major bleeding on full-dose anticoagulation
Major contraindication to full-dose anticoagulation
New-onset acute PE (especially recurrent PE) despite well-documented fulldose anticoagulation for an existing VTE
Other related articles published in this Open Access Online Scientific Journal include the follwoing:
Xarelto (Rivaroxaban): Anticoagulant Therapy gains FDA New Indications and Risk Reduction for: (DVT) and (PE), while in use for Atrial fibrillation increase in Gastrointestinal (GI) Bleeding Reported
Venous Thromboembolism (VTE): Blood Clots in Leg and Lungs – No. 3 Cardiovascular Killer Globally – Is Leading Cause of Premature Death and Disability in Hospitals
The presence of any Valvular Heart Disease (VHD) did not influence the comparison of Dabigatran [Pradaxa, Boehringer Ingelheim] with Warfarin
Reporter: Aviva Lev-Ari, PhD, RN
UPDATED on 10/22/2018
Dabigatran (Pradaxa) was no better than aspirin for prevention of recurrent stroke among patients with an embolic stroke of undetermined source in the RE-SPECT ESUS trial reported at the World Stroke Congress.
Pradaxa® (dabigatran etexilate)
Clinical experience of Pradaxa® equates to over 9 million patient-years in all licensed indications worldwide. Pradaxa® has been in the market for more than ten years and is approved in over 100 countries.15
Currently approved indications for Pradaxa® are:16,17
Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke
Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery or total knee replacement surgery
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and the prevention of recurrent DVT and recurrent PE in adults
Dabigatran, a direct thrombin inhibitor (DTI), was the first widely approved drug in a new generation of direct oral anticoagulants, available to target a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.18,19,20
REFERENCES
16 Pradaxa® US Prescribing Information, 2018.
17 Pradaxa® European Summary of Product Characteristics, 2018.
18 Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95.
19 Di Nisio M. et al. Direct thrombin inhibitors. N Engl J Med.2005;353:1028–40.
20 Stangier J. et al. Pharmacokinetic Profile of the Oral Direct Thrombin Inhibitor Dabigatran Etexilate in Healthy Volunteers and Patients Undergoing Total Hip Replacement. J Clin Pharmacol. 2005;45:555–63
Event Rate and Outcome Risk, With vs Without Valvular Heart Disease
Outcome
Valvular heart disease, event rate/y, %
No valvular heart disease, event rate/y, %
HR (95% CI)*
P
Stroke, systemic embolic event
1.61
1.41
1.09 (0.88–1.33)
0.43
Major bleeding
4.36
2.84
1.32 (1.16–1.33)
<0.001
Intracranial hemorrhage
0.51
0.41
1.20 (0.83–1.74)
0.32
All-cause mortality
4.45
3.67
1.09 (0.96–1.23)
0.18
*Adjusted using propensity scores
ORIGINAL RESEARCH ARTICLE
Comparison of Dabigatran versus Warfarin in Patients with Atrial Fibrillation and Valvular Heart Disease: The RE-LY Trial
Michael D. Ezekowitz, Rangadham Nagarakanti, Herbert Noack, Martina Brueckmann, Claire Litherland, Mark Jacobs, Andreas Clemens,Paul A. Reilly, Stuart J. Connolly, Salim Yusuf and Lars Wallentin
stroke or systemic embolism (SEE) rates (HR 1.09; 95% CI 0.88-1.33).
For D110 patients, major bleed rates were lower than warfarin (HR 0.73; 95% CI 0.56-0.95 with and HR 0.84; 95% CI 0.71-0.99 without VHD) and
For D150 similar to warfarin in patients with (HR 0.82; 95% CI 0.64-1.06) or without VHD (HR 0.98; 95% CI 0.83-1.15).
For D150 patients stroke/SEE rates were lower versus warfarin with (HR 0.59; 95% CI 0.37-0.93) and without VHD (HR 0.67; 95% CI 0.52-0.86) and similar to warfarin for D110 irrespective of presence of VHD (HR 0.97 CI 0.65-1.45 and 0.85 CI 0.70-1.10).
For intracranial bleeds and death rates for D150 and D110 were lower vs warfarin independent of presence of VHD.
Conclusions—The presence of any VHD did not influence the comparison of dabigatran with warfarin.
Patient was diagnosed with heart disease and pulmonary hypertension in January 2016 and had a triple-bypass operation at age 69. Interview was conducted six months post-surgery.
Author: Gail S. Thornton, M.A.
Co-Editor: The VOICES of Patients, HealthCare Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures
Evergreen, Colorado, an idyllic, peaceful community with an elevation of 8,000 feet west of Denver, offers its residents and visitors a beautiful place for arts and culture, summer and winter sporting activities, and scenic beauty. In fact, Ralph Nichols has lived in the town for more than 20 years.
“This past September [2015] was, particularly, challenging for me, where winter begins quite early for us. It became increasingly painful and difficult to breathe in the freezing temperatures. It seemed that my lungs were inflamed and I couldn’t even stand the cold weather. I thought it might be the beginning of a bad cold, and I wasn’t overly concerned that there was anything terribly wrong.”
At that time, Ralph went to his family physician who performed the usual routine examination with no significant results.
“Many years ago, I developed a mild case of scleroderma, a chronic connective tissue disease. I thought that perhaps my symptoms were the result of some type of inflammation in my body that could be managed with prescription medications.”
Scleroderma is known as an autoimmune disease, which adds an inappropriate amount of collagen to various parts of the body, such as the joints, skin, and later stages, various organs, such as the lungs, in Ralph’s case. Scleroderma can cause the organs to shut down and, eventually, cause death.
“I never let this condition stop me from doing anything as it is life-long condition. It was always something I had to tolerate and work through.”
Image SOURCE: Photographs courtesy of Ralph Nichols and Gabriela Contreras. Top left: Ralph today. Top right: Ralph recovering one month after surgery. Bottom left and center: Ralph with his medical team. Bottom right: Ralph in rehabilitation center.
Over the brutal Colorado winter, Ralph’s symptoms were getting worse. He had no idea that his life would dramatically change over the next few months. He went to see his family physician again. During this physical examination, Ralph was referred to pulmonary and cardiovascular specialists for a routine electrocardiogram, echocardiogram and stress test in order to further diagnose his symptoms. He had always been relatively healthy and fit and never been seriously ill or hospitalized.
“On the outside, Ralph was the picture of good health,” said his wife, Gabriela. “On the inside, his body was telling him that something was wrong.”
Three months later in December 2015, Ralph met with Dr. Alexandra Smart, a pulmonologist, who ordered a chest x-ray and other diagnostic tests, including a right heart catheterization. At that point, Ralph’s medical team grew. It was then determined that Ralph needed to see other cardiovascular specialists and undergo more tests. In January 2016, he met with Dr. Sameer Mehta, cardiologist at Cardiac & Thoracic Surgery Associates, in Lakewood, Colorado, who reviewed his tests to date, listened to Ralph’s symptoms, and told him he needed both a right and left heart cardiac catheterization.
“They gave me sedation for the catheterization procedure and went through my neck with a camera to see what was going on with my lungs and heart. We were all singing together on the way to the operating room. During the procedure, my cardiologist found more than he had anticipated.”
The result was not good. Ralph had major blockages in two main arteries that supply blood to his heart muscle compounded by the fact that his lungs were affected by scleroderma.
“The catheterization was alarming. It showed that my arteries were in bad shape. They were both clogged with atherosclerotic plaque; one of them was 99 percent blocked and the other was 85 percent blocked.”
His cardiologist believed that the blockages would not respond to medications quickly or a stent.
“Even though my father had major heart disease and died two years later of cancer at the age of 56, I thought that I would be immune to this particular experience. After all, I was in good health, exercised regularly, lived a reasonable lifestyle and had a great diet.”
Preparing for Life-Saving and Life-Changing Surgery
Unfortunately, surgery was the next step. Ralph was referred to Dr. Mehta’s colleague, Dr. Patrick D. Rudersdorf, cardiothoracic surgeon at Cardiac & Thoracic Surgery Associates.
“I didn’t leave the hospital that day as expected. Instead, I got a visit from Dr. Rudersdorf and couldn’t believe what he was telling me. My only chance to live was having triple bypass surgery which needed to be done immediately. The doctor met with me that same day to explain the procedure, answer my questions and talk through the details of the rehabilitation period after the surgery.”
Dr. Rudersdorf reassured Ralph that he was doing the right thing and calmed my fears.
“He said that I needed this life-saving surgery because I was at high risk for having a major heart attack. I was shocked, at first, at the thought of the intensity of surgery on my body. It’s a situation that no one likes to be in, but I had to make a decision about alleviating the ongoing pain and pressure in my chest along with shortness of breath due to diseased heart arteries. Coronary bypass surgery was my answer to feeling better — and it essentially gave me my life back.”
Dr. Rudersdorf moved his previously planned morning surgery to another day to accommodate me first thing in the morning. Ralph underwent triple bypass surgery at St. Anthony Hospital in Lakewood, Colorado. The procedure was complex and took eight hours. He was in the hospital for a total of 31 days.
“It was an ordeal that I thought I’d never have to experience. I had no time to call anyone, or time to even contemplate life and death…or even being scared. My wife Gabriela spent the entire time in the hospital, supported by our dearest friends, Norma Delaney and Garret Annofsky, in addition to keeping family and friends in other parts of the United States and Mexico updated as well. Once the surgery was over, the medical team woke me up and said the procedure was successful, but I was far from being out of the woods.”
Ralph had some complications because of a condition called pulmonary hypertension, a type of high blood pressure that affects the arteries in the lungs and the right side of the heart. According to the Mayo Clinic’s web site, in one form of pulmonary hypertension, tiny arteries in the lungs, called pulmonary arterioles, and capillaries become narrowed, blocked or destroyed. This makes it harder for blood to flow through the lungs, and raises pressure within the lungs’ arteries. As the pressure builds, the heart’s lower right chamber (right ventricle) must work harder to pump blood through the lungs, eventually causing the heart muscle to weaken and fail. http://www.mayoclinic.org/diseases-conditions/pulmonary-hypertension/home/ovc-20197480
“The pulmonary hypertension limited some of the medications that the doctors would have used during my recovery. It was a tough few days for me in intensive care, hooked up to about 18 monitors. The medical team had to stop and re-start my heart four different times because of atrial fibrillation — finally getting both parts of the heart to dance together in the same rhythm.”
Ralph’s heart was beating abnormally fast and irregular and not functioning the way it should. The doctors restore regular rhythm to the heart by sending an electrical shock to the heart, which is called electrical cardioversion or chemically using antiarrhythmia medications, which is called pharmacologic or chemical cardioversion.
“The doctors shocked my heart first chemically with medications when I was awake. This procedure was the scariest. I was sitting up in bed and felt my heart stop, then the medical team flushed the medication out with saline in order to restart my heart. That procedure was not successful, so that is why the doctors had to shock my heart three more times electrically.
“The reason the doctors stopped my heart was to correct the atrial fibrillation and to get my heart into regular sinus rhythm, which is a wave mode of the heart where everything is synchronized. The doctors did not want me to continue to experience atrial fibrillation because if continued, I would not be able to regain my strength.”
Ralph was finally moved from intensive care to intermediate care after five days and the medical team kept him in intermediate care another 12 days until his heart and lungs got stronger.
“From there, I didn’t go home but instead went to Evergreen Life Center for rehabilitation for two weeks to learn how to walk, climb stairs so that I could access my home on my own, and develop my strength again. The rehab team would let me leave only after making sure I had oxygen in my home.”
After that, Ralph started another phase of his rehabilitation at St. Anthony Cardiac Rehabilitation and Wellness Center. For the next three months, he took part in cardiac rehabilitation three days a week. He passed that with flying colors. Now, he is in another phase of rehabilitation, building his lung capacity two days a week.
Ralph didn’t have the means or even the will to communicate with friends during this tumultuous time, except Gabriela and several close friends who were always at the hospital and rehabilitation center who gave him the strength to continue.
“I finally returned home after many weeks with an enormous feeling of gratitude for each and every one of my friends, as well as the St. Anthony’s hospital team of doctors, nurses, and therapists, who supported me and Gabriela during this exceptional adventure that has certainly changed my life.”
Surely, this experience has been a life-changing experience for Ralph.
Coronary Artery Bypass Facts
Coronary artery bypass grafting (CABG, often pronounced “cabbage”) is a surgical treatment for blocked coronary arteries. Coronary arteries supply blood to the heart muscle and when blockages in these arteries form, chest pain, shortness of breath and heart attacks can occur. Catheter procedures performed by interventional cardiologists address the blockages themselves with stents. Coronary bypass surgery performed by cardiac surgeons reroutes the blood around the blockages to supply better blood supply to the heart muscle and is a better treatment option, although more invasive, for certain patients and more durable for most patients.
Today, Ralph is regaining his strength both in mind and body. He visits the cardiovascular and pulmonary rehabilitation center three times a week for the past few months and walks on their treadmill, lifts weights and pedals the bicycle for one hour, supervised by the therapists. He also sees his medical team for regular check-ups every month, eats healthier with no fat and no salt, and takes a cocktail of medicines daily for his heart and lungs, including amiodarone, furosemide, pitavastatin, and aspirin.
“Almost six months after my surgery, although I am not in the best shape of my life, however, I am in the best spiritual place than ever before. This is a huge milestone for me. I continue to improve my strength, which will make my heart more resilient. There is nothing that I can’t do now, and I am doing everything I can to experience a normal life as far as work and regaining my strength. I find it necessary to move to a warmer climate and lower altitude in order to continue to improve.”
Ralph also is the former lead singer of The Letterman and The Sandpipers, two American easy-listening bands during the 1960-70-80s. He is an entertainer at heart with over 3,000 professional appearances to his credit. He has been performing and recording for over 50 years, traveled the world extensively and performed before members of the Vatican with Pope Pius XII and Royalty with Prince Rainier and Princess Grace Kelly, as well as notables such as Frank and Nancy Sinatra, Tony Bennett, Ronald Reagan, Merv Griffin, Danny Thomas, Shirley Bassey, Rosalind Russell and Bob Hope.
Ralph and his vocal group were dubbed by Billboard Magazine as “the greatest romantic vocal group of all time.” He is also a member of the Vocal Group Hall of Fame, a prestigious honor. He is a true legend as his group has sold more than 20 million recordings, performed live thousands of times, and whose recording of the song “Love” was left by NASA astronauts in a time capsule on the moon.
“I enjoy each and every day and appreciate all that life has to offer.”
Ralph’s next step is to get back to singing and his solo entertainment business, which he holds dear to his heart. That should be a task that he can easily accomplish.
Editor’s note:
We would like to thank Gabriela Contreras, a global communications consultant and patient advocate, for the tremendous help and support that she provided in scheduling time to talk with Ralph Nichols.
Ralph Nichols provided his permission to publish this interview on July 30, 2016.
No evidence to change current transfusion practices for adults undergoing complex cardiac surgery: RECESS evaluated 1,098 cardiac surgery patients received red blood cell units stored for short or long periods
I wish to encourage the e-Reader of this Interview to consider reading and comparing the experiences of other Open Heart Surgery Patients, voicing their private-life episodes in the ER that are included in this volume.
I also wish to encourage the e-Reader to consider, if interested, reviewing additional e-Books on Cardiovascular Diseases from the same Publisher, Leaders in Pharmaceutical Business Intelligence (LPBI) Group, on Amazon.com.
Perspectives on Nitric Oxide in Disease Mechanisms, on Amazon since 6/2/12013
Cardiovascular Diseases, Volume Four: Regenerative and Translational Medicine: The Therapeutics Promise for Cardiovascular Diseases, on Amazon since 12/26/2015
Moderate Ischemic Mitral Regurgitation: Outcomes of Surgical Treatment during CABG vs CABG without Mitral Valve Repair
Curator: Aviva Lev-Ari, PhD, RN
Original Article
Michler RE et al. Two-year outcomes of surgical treatment of moderate ischemic mitral regurgitation. N Engl J Med2016 Apr 3; [e-pub]. (http://dx.doi.org/10.1056/NEJMoa1602003)
Two-year findings do not support widespread adoption of the combined procedure.
When the Cardiothoracic Surgical Trials Network randomized 301 patients with moderate mitral regurgitation to undergo coronary artery bypass grafting (CABG) alone or CABG plus mitral valve repair, the two groups had similar postsurgical ventricular dimensions, survival, and major adverse events at 1 year. However, the combined-procedure group had a significantly lower prevalence of moderate-to-severe mitral regurgitation — but longer postsurgical hospital stays and higher incidences of postoperative supraventricular arrhythmias and serious neurologic events (NEJM JW Cardiol Jan 2015 and N Engl J Med 2014; 371:2178).
We now have the 2-year findings.
The postsurgical left-ventricular end-systolic volume index was again similar between the two groups.
Two-year mortality was slightly, but not significantly, higher with CABG alone than with the combined procedure (10.6% vs. 10.0%)
CABG-alone group had a significantly higher incidence of moderate-to-severe mitral regurgitation (32% vs. 11%).
The two groups had similar rates of hospital readmission and
The two groups had similar major adverse events,
Most quality-of-life scores were similar between the two groups.
except that
serious neurologic events and supra-ventricular arrhythmias were significantly more common with the combined procedure.
SOURCES
Michler RE et al. Two-year outcomes of surgical treatment of moderate ischemic mitral regurgitation. N Engl J Med2016 Apr 3; [e-pub]. (http://dx.doi.org/10.1056/NEJMoa1602003)
Please visit: www.openpediatrics.org OPENPediatrics™ is an interactive digital learning platform for healthcare clinicians sponsored by Boston Children’s Hos…
Medtronic recalled its dual chamber pacemakers (Adapta, Versa, Sensia, Relia, Attesta, Sphera, and Vitatron A, E, G, and Q series) due to a possible software error that can stop pacing.
Steps to minimise replacement of cardiac implantable electronic devices
Much can and should be done to maximise the longevity of existing devices
Imagine spending £3000 on a new watch with a battery embedded in the mechanism that cannot be replaced or recharged. Although the battery is predicted to last 10 years or more, after six years you discover that it is running flat and you’re advised to replace the watch immediately, even though it may keep good time for a year or more.
This mirrors the dilemma faced by all patients with cardiac implantable electronic devices such as pacemakers and implantable cardioverter defibrillators (ICD). But for them the stakes are much higher as replacing the battery exposes them to a risk of serious complications, including life threatening infection.
Over half of all patients with pacemakers require a replacement procedure because the batteries have reached their expected life.1 Some 11-16% need multiple replacements.2 The situation is worse for recipients of an ICD, since the risks of infection at the time of implant and device replacement are higher than with pacemakers and the batteries have a shorter life.3
What is the risk of infection?
With no standard definition or reporting system, infection rates vary widely, and the commonly quoted risk of 0.5% for new implants and 1-5% for replacement procedures may be wrong.4 Infection, even if it seems superficial, usually necessitates extraction of the entire system. Simply treating the infection with antibiotics results in a much poorer outcome.5 The increased risk of infection associated with battery replacement makes it critical that we prolong the life of implantable devices as much as possible. The health economic grounds for minimising the number of replacements are also compelling.6
The current financial model discourages the development of longer life devices. Increasing longevity would reduce profits for manufacturers, implanting physicians, and their institutions. With financial disincentives for both manufacturers and purchasers it is hardly surprising that longer life devices do not exist.
Patients are often assumed to prefer smaller devices, but when offered the choice, over 90% would opt for a larger, longer lasting device over a smaller one that would require more frequent operations to change the battery.7 And given the risks that patients are exposed to during replacement, there is an urgent need to improve longevity by developing longer life batteries and using those in current devices more prudently.
What can be done now?
At present the main drive to improving longevity of pacemakers has been through programming changes aimed at reducing the amount of pacing8 or minimising the drain of current during pacing—for example, using high impedance leads. But devices are usually replaced when there is still substantial life left in the battery. For example, when a pacemaker reaches elective replacement indication, it is usually 3-12 months before it will reach its end of life. And even then, the battery may continue to function for several months. Early replacement may be reasonable for high risk patients (such as those who are entirely dependent on their pacemaker). However, we could delay replacement of the pulse generator until the batteries are virtually depleted in lower risk patients. The increasingly popular innovation of home monitoring of devices would facilitate this.
For ICDs the waste is even more striking; devices reach their elective replacement indication when they are still capable of delivering at least six full energy shocks. Each shock reduces the battery longevity by about 30 days. So for patients who receive no shock therapy we are prematurely discarding a device costing up to £25 000 (€33 000; $36 000), which could last at least another six months (current devices last four to seven years on average). We need to review the timing of replacement of implantable devices in all patients.
Kinderman M, Schwaab B, Berg M, Frohlig G. Longevity of dual chamber pacemakers: device and patient related determinants. Pacing Clin Electrophysiol2001;24:810-5.
Kurtz SM, Ochoa JA, Lau E, et al. Implantation trends and patient profiles for pacemakers and implantable cardioverter defibrillators in the United States: 1993-2006. Pacing Clin Electrophysiol2010;33:705-11.
Ramachandra I. Impact of ICD battery longevity on need for device replacements–insights from a Veterans Affairs database. Pacing Clin Electrophysiol2010;33:314-9.
Boriani G, Braunschweig F, Deharo JC, Leyva F, Lubinski A, Lazzaro C. Impact of extending device longevity on the long-term costs of implantable cardioverter defibrillator therapy: a modelling study with a 15-year time horizon.Europace2013;15:1453-62.
Wild DM, Fisher JD, Kim SG, Ferrick KJ, Gross JN, Palma EC. Pacemakers and implantable cardioverter defibrillators: device longevity is more important than smaller size: the patient’s viewpoint. Pacing Clin Electrophysiol2004;27:1526-9.
CentraCare Heart & Vascular Center is the first in the world to use EchoPixel’s technology both before and during a structural heart procedure. “EchoPixel pre-planning True3D software helped us reduce our procedure times by more than 27% and increase optimal procedure outcome by 20%. EchoPixel-HTG is taking us to the next level,” says Dr. Dutcher. “As one of the world’s largest WATCHMAN implanting sites, we are always looking for new ways to advance and improve patient care, and are proud to be the first center in the world to offer this novel imaging technology.”
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