Funding, Deals & Partnerships: BIOLOGICS & MEDICAL DEVICES; BioMed e-Series; Medicine and Life Sciences Scientific Journal – http://PharmaceuticalIntelligence.com
Researchers at Lawrence Livermore National Laboratory discovered interesting ways to advance the capabilities of two-photon lithography, a high-resolution 3D printing technique capable of producing nanoscale features which unleashes the potential for X-ray computed tomography to analyze stress or defects noninvasively in embedded in 3D printed medical devices or implants. Two-photon lithography stereotypically requires a thin glass slide, a lens and an immersion oil to help the laser light focus to a fine point where curing and printing occurs. The findings were published in the journal of ACS Applied Material and Interfaces.
In the paper, researchers describe cracking the code on resist materials improved for two-photon lithography and forming 3-D microstructures with features less than 150 nanometer which is better in comparison to previous techniques which build structures from ground up, limiting the height of the objects.
According to LLNL researcher James Oakdale, “In this paper, we have unlocked the secrets to making custom materials on two-photon lithography systems without losing resolution”, because the laser light refracts as it passes through the photoresist material, the cornerstone is discovering how to match the refractive index of the resist material to the immersion medium of the lens so the laser could pass through unimpeded.
Investigators can now use X-ray computed tomography as an analytical tool to copy the inside parts without cutting them open and to investigate 3D printed objects by fine-tuning the material’s x-ray absorption. The only limiting factor is the time it takes to build, so the researchers are investigating how to speed up the process.
These techniques could be used to harvest and probe the internal structure of targets for the National Ignition Facility, as well as optical and mechanical metamaterials and 3D-printed electrochemical batteries.
FDA Recalls GE’s Infinia Hawkeye 4 Nuclear Medicine System used in Nuclear Medicine Imaging for Detection of Radioisotope Tracer Uptake in the Patient’s body
Hospital patients face delays after 120 nuclear medicine machines were recalled across Australia following the death of a patient in the US. Authorities ordered hospitals across Australia to stop using the nuclear medicine imaging systems, preventing patients from being scanned while the machines are checked for safety. A 66-year-old patient being scanned in a veterans’ hospital in New York was crushed when a GE Healthcare Infinita Hawkeye 4 system collapsed when bolts securing the machine came loose.
HOSPITAL patients face delays after 120 nuclear medicine machines were recalled across Australia following the death of a patient in the US.
Authorities ordered hospitals across Australia to stop using the nuclear medicine imaging systems, preventing patients from being scanned while the machines are checked for safety.
A 66-year-old patient being scanned in a veterans’ hospital in New York was crushed when a GE Healthcare Infinita Hawkeye 4 system collapsed when bolts securing the machine came loose.
The recall notice was sent to Australian hospitals including the Women’s and Children’s Hospital more than a month later on July 9.
Six of 91 systems in Australian centres checked so far require repair to prevent a similar collapse, according to federal health officials, with 29 still to be checked.
Ten were operating in South Australian hospitals including two at the Royal Adelaide Hospital and one each at the Women’s and Children’s, the Queen Elizabeth Hospital and Lyell McEwin Hospital, with the others in private clinics.
GE Healthcare inspectors have inspected seven of these so far and not found any problems,.
SA Health, however, so far has only released one at the RAH and one at the QEH for use.
It released a statement to The Advertiser saying it had “a fleet of gamma cameras across South Australian public hospitals.”
“Five were identified as being in scope of the review,” the statement says. “Use of these five cameras was suspended immediately and GE is currently in the process of reviewing the machines. Two cameras have already been cleared and have resumed scanning.
“SA Health is working with GE Healthcare to minimise the impact on patients during this review.
“However some patient appointments have required rescheduling or rebooking on a different camera. There have been no incidents involving SA Health cameras.”
The systems, estimated to be worth from $300,000 to $800,000 depending on the model, track radiation emitted by radioactive fluids injected into patients to build images of organs and deep tissue to diagnose a range of diseases.
Information generated can pinpoint diseases before anatomical changes in organs and has some advantages over some other scanning techniques such as MRI and CAT scans.
Patients lie on their back with lead encased panels housing gamma cameras above and around them to track the radiation, and the entire machine can weigh in excess of 2000kg.
No deaths or injuries related to the safety issue have been reported in Australia.
The Therapeutic Goods Administration released a statement over the recall, advising patients to speak to their health professional if they have concerns.
“Due to the prevalence of affected nuclear medicine imaging systems in Australia and the need to have such systems inspected regarding this issue before use, there may be delays in accessing some diagnostic scan services,” the statement says.
In its letter to hospital officials GE Healthcare chief medical office Dr Douglas Hansell says: “Please be assured that maintaining a high level of safety and quality is our highest priority.’
Products: Infinia Nuclear Medicine Systems, VG and VG Hawkeye Nuclear Medicine Systems, Helix Nuclear Medicine Systems, Brivo NM615, Discovery NM630, Optima NM/CT640, Discovery NM/CT670
Models: Infinia 3/8, Infinia-II 3/8, Infinia VC, Infinia II VC, Infinia 3/8 Hawkeye, Infinia VC Hawkeye, Infinia II 3/8 Hawkeye, Infinia II VC Hawkeye, Infinia II 3/8 HE4, Infinia II 5/8 HE4, Infinia II VC HE4, Varicam, Millennium VG 3/8, Millennium VG 5/8, Millennium VG 3/8 Hawkeye, Millennium VG 5/8 Hawkeye, Discovery VH, Helix nuclear medicine systems, Brivo NM615, Discovery NM630, Optima NM/CT640, Discovery NM/CT670
These affected products were distributed from October, 1992 through June, 2013.
Use: These Nuclear Medicine systems are used to perform general Nuclear Medicine imaging procedures for detection of radioisotope tracer uptake in the patient’s body, using a variety of scanning modes supported by various acquisition types and optional imaging features designed to enhance image quality in Oncology, Cardiology, Neurology and other clinical diagnostic imaging applications. The scanning modes include planar (Static, Multi-gated, Dynamic, Whole body scanning) and tomographic (SPECT, Gated SPECT, Whole body SPECT, Camera based PET – also known as Coincidence Detection). Acquisition types include single and multi-isotope/multi-peak frame/list mode single-photon and positron imaging. Optional imaging-enhancement features include assortment of collimators, gating by physiological signals, real-time automatic body contouring, and CT-based attenuation correction and functional anatomic mapping.
Recalling Firm:
GE Healthcare, LLC
3000 N Grandview Blvd.
Waukesha WI 53188-1615
Manufacturer:
GE Medical System Israel Ltd
4 Hayozma St.
Tirat Hacarmel, Israel
Reason for Recall: GE Healthcare became aware of an incident at a VA Medical Center facility in the US. A patient died due to injuries sustained while being scanned on an Infinia Hawkeye 4 Nuclear Medicine System. On July 03, 2013 GE notified hospitals that they were recalling several Nuclear Medicine Imaging Systems because serious injuries or deaths could occur due to the failure mode associated with this recall. GE advised hospitals that they cease use of their Nuclear Medicine systems until GE can complete an inspection of the system. In the second notification, GE included all Nuclear Medicine Systems.
Public Contact: For questions about this recall contact GE Healthcare Service Representative at 1-800-437-1171
FDA District: Minneapolis District Office
FDA Comments:
On June 17, 2013 GE sent an Urgent Medical Device Correction letter to all affected customers. The letter identified the affected product, recommended that qualified service personnel maintain the equipment and that Preventative Maintenance procedures were executed according to labeling. In addition, the Safety Chapter Sections should be re-reviewed with personnel to ensure proper operation of the equipment.
On July 03, 2013 GE notified customers again via an Urgent Medical Device Recall letter (including confirmation of delivery for US customers) and follow-up telephone calls. Healthcare facilities are instructed to cease use of their Nuclear Medicine system until a GE Healthcare Field Engineer is able to do a complete inspection of the system and perform any necessary repairs at no cost. A GE Healthcare representative will contact the hospitals to arrange for the inspection.
Physicians: No action is required beyond the recommendations provided in the Urgent Medical Device Recall letter.
Kavitha Chinnaiyan, M.D., FACC, FSCCT, associate professor, Oakland University, William Beaumont School of Medicine, Royal Oak, Mich. She presented at the Society of Cardiovascular Computed Tomography (SCCT) 2018 meeting.
Clinical studies of coronary anatomy by computed tomography use equipment with various numbers of concurrent slices through the heart: 1, 4, 16, 32, 64, 128, and recently 256 or more. Like interventional catheterization, iodine is injected to make the inside of the coronary arteries opaque to xray transmission, to create contrast (otherwise the xray of the coronary tree would be like a photograph of a white polar bear in a snow storm; the contrast acts like spray paint). Computed tomographic angiography (CTA) uses a similar or higher dye load than catheterization, and provides generally lower imaging quality than catheterization but with 3-dimensional reconstruction instead of flat projection (hundreds of linear views at different angles versus one or two image planes at a time). The results from CTA are generally deemed qualitative: whther or not there are potentially flow-limiting lesions in the major branch arteries that supply the heart (with exception: the posterior descending artery to the inferior wall of the heart is not reliably seen). Catheter-based projection coronary angiography sees smaller branches with finer ability to measure the degree of lumen narrowing. However, other imaging methods show greater promise in identifying plaque character. The following examines initial enthusiasm for improvements in CTA which offer better results compared to current clinical CTA and hope to offer advantages over catheter-based methods beyond the avoidance of catheters.
I. Cardiac CT Challenging Functionality of SPECT and Angiogram
Noninvasive computed tomography (CT) perfusion imaging added to CT angiography accurately identifies flow-limiting coronary lesions that need to be treated, results of the CORE320 trial show.
Dr João AC Lima (Johns Hopkins University, Baltimore, MD) presented results of the 381-patient, 16-center trial, which showed that stress CT myocardial perfusion analysis (CTP) significantly improves the diagnostic power of rest CT angiography (CTA) alone. The study also showed that the CTA+CTP strategy has about the same power to identify patients who need revascularization within 30 days as the current standard strategy of invasive angiography plus a single photon-emission computed tomography (SPECT) myocardial perfusion imaging (MPI) test.
Lima explained that the potential advantage of the CT-based approach is that it can obtain information on myocardial perfusion and coronary flow in two scans about 10 minutes apart and is noninvasive.
All patients in the study had been referred for an invasive angiogram to investigate suspected or known coronary artery disease (CAD), but all patients underwent a rest CTA, stress CTP, and SPECT-MPI test in addition to the invasive angiogram. Invasive angiography alone identified apparently obstructive coronary disease in 59% of patients, but adding the SPECT-MPI information reduced that number to 38%.
The accuracy of the CTA+CTP approach was measured as the area under the receiver-operating-characteristic curve. When 50% greater stenosis on invasive angiography was set as the reference standard for a flow-limiting stenosis, the accuracy of the CTA+CTP approach for detecting flow-limiting CAD was 0.87 on a per-patient basis. When the standard was >70% stenosis, the accuracy of the CTA+CTP approach was 0.89.
VIEW VIDEO on CORE320 with Dr João Lima
Flow Limiting Lesion (low perfusion) vs. Anatomic Stenosis Severity
“I think it’s a potential game-changer, because for the first time you have the ability to look at coronary stenosis and ischemia simultaneously, [and] you have the ability to pinpoint the lesion that is causing the ischemia,” DISCOVER FLOW senior investigator Dr James Min (Cedars-Sinai Medical Center, Los Angeles, CA) told heartwire. “You can imagine a scenario where somebody has an abnormal stress test and then you go in and you do an angiogram and see four or five stenoses, but you don’t really know which one caused the ischemia.” But this new “virtual fractional flow reserve” process—or FFRCT—can quantify the fractional flow reserve for each lesion with the data taken from a CCTA, thereby revealing which stenoses are causing ischemia and ought to be treated, as well as which stenoses do not need to be treated. “We’ve never before had this one-stop shop to . . . pinpoint the lesions that cause the ischemia noninvasively.”
As reported by heartwire at EuroPCR 2011, in DISCOVER FLOW, Dr Bon-Kwon Koo (Seoul National University Hospital, Korea) and colleagues used computation of FFRCT to assess 159 vessels in 103 patients undergoing CCTA. Results of the study are published in the November 1, 2011 issue of the Journal of the American College of Cardiology.
All of the patients also underwent invasive CCTA and invasive catheter FFR imaging. Ischemia was defined as an FFR of <0.80 and anatomically obstructive coronary disease was defined as stenosis >50% as measured on the CCTA scan. The diagnostic performance of FFRCT and CCTA were assessed against invasive FFR as the reference standard. Of the patients in the study, 56% had at least one vessel with an FFR of <0.80.
Because only about half of stenoses over 50% actually cause ischemia, the specificity of traditional assessment of a stenosis by CCTA is below 50%. “The concern there is that you identify some high-grade stenoses that are angiographically confirmed, but the lesions don’t actually cause ischemia.” Fractional flow reserve measures how much of the blood flow is being blocked by a lesion, so it is about 25% more accurate than traditional CCTA at picking out lesions that cause ischemia, Min explained.
Per vessel diagnostic accuracy FFRCT and CCTA (reference for both was invasive FFR)
Imaging technology
Accuracy(%)
Sensitivity(%)
Specificity(%)
Positive predictive value (%)
Negative predictive value (%)
FFRCTa
84.3
87.9
82.2
73.9
92.2
CCTAb
58.5
91.4
39.6
46.5
88.9
a. Ischemic defined as <0.80
b. Ischemia defined as stenosis >50%
FFRCT can assess stenoses from any CCTA scan—prospectively gated or retrospectively gated—without any additional imaging techniques or changes to the acquisition parameters. Just as computational fluid dynamics can predict the behavior of an airplane wing under different environmental parameters, FFRCT can measure the flow of blood through a stenotic coronary based on the specific geometry of the patient’s coronaries and myocardium.
At the American Heart Association meeting in Orlando next month, Min will present results of a substudy from DISCOVER FLOW looking specifically at intermediate-grade stenoses (40%-69%), which present the most difficult treatment decisions. “If somebody sees a 90% stenosis or 10% stenosis, they are comfortable with what to do with that. But when you hit that 40% to 70% range—it’s possible that those lesions are ischemic, but you don’t know until you actually assess them,” Min said.
DISCOVER FLOW was designed to evaluate the accuracy of FFRCT on a per-vessel basis, but the more important demonstration of its value will be its ability to guide treatment decisions for each patient. TheDEFACTO trial, which finished enrollment at 17 centers about three weeks ago, is evaluating FFRCT per patient. “That’s the big one,” Min said. “DEFACTO will be the pivotal trial.” Specifically, the 285-patient DEFACTO trial is assessing the ability of CCTA plus FFRCT to determine the presence or absence of at least one hemodynamically significant coronary stenosis in each trial subject. Invasive catheter FFR is the reference standard. Min expects that study to be completed in the first quarter of 2012.
DrMatthew Budoff (Los Angeles Biomedical Research Institute, CA), a longtime researcher in the use of cardiac CT, described what he believes to be the most important uses for CT today [1].
First, CT angiography is emerging as “a single tool that gives us [information about] function and anatomy,” he told the audience.
Second, it is now known that patients are more likely to have a cardiovascular event if they have low-attenuation plaque (soft plaque), positive remodeling, and spotty calcification, he explained. If a clinician were limited to looking only at plaque or stenosis, he would advise him or her to “just read the CTA for plaque and plaque characteristics and [don’t] read it for stenosis severity, and you’ll probably serve your patients better in predicting risk” of a cardiovascular event. “I think in future we’re going to be using plaque characterization in every case,” he added. “I certainly don’t advocate stenting these patients [who have vulnerable plaque] yet, but . . . I do treat these patients more aggressively.”
“With perfusion imaging, TAVR, and plaque assessment leading the way, the increased utilization of CTA is certain,” Budoff concluded. “However, more validation work is needed to ensure that industry and payers accept these applications.”
Speaking to heartwire, Budoff singled out TAVR as “an easy launching point for doctors to get familiar with” CT angiography. He also believes that using CT for “heart-failure assessment or even plaque assessment . . . will really add value to their practice.” CT also allows clinicians to “start getting a handle on what’s causing stenosis [in a patient], what it looks like, and . . . how severe the stenosis is.”
In a separate presentation [2], Dr James KMin (Cedars-Sinai, Los Angeles, CA) identified the same three clinical applications as Budoff in his “top 10 things to watch” in coronary CT in the coming year. He identified his “up-and-coming areas to watch” in the following order:
Dual-energy CT scanners. This hardware, when combined with new software, is producing enhanced image quality that allows, for example, a “plaque biopsy,” which provides detailed information about plaque characteristics.
Myocardial CT perfusion. “We’ve looked at this for seven years, and I think it’s starting to become ready for prime time,” said Min. In the next year, he expects investigators to figure out exactly how to use CT to look at coronary flow reserve.
Computational fluid dynamics. Exciting work is being done, for example, using a virtual stent to see how a real stent would potentially resolve a patient’s ischemia.
Plaque. Coronary CT can do more than identify how many vessels are blocked, he said, echoing Budoff’s words. It is enabling investigators to study the pathogenesis of atherosclerosis. “We’re going to be able to identify plaque characteristics beyond stenosis for the prediction of acute MI,” Min said.
Structural heart disease. CT is already being used to help guide TAVR to reduce postsurgery complications.
Radiation-dose reduction. Min weighed in and said, “I think it’s becoming a nonissue.” He noted that during the past year, investigators reported how coronary CT angiography can be used with radiation doses as low as 0.01 mSv, (should be 1mSv) whereas a screening mammogram exposes a woman to 0.05 mSv of radiation. (1/5 of mammography)
Contrast-agent reduction.”I think we will see improvements—we will get to the 10-cc scan,” Min predicted.
Appropriate-use criteria. Physicians are continuing to identify which patients benefit from cardiac CT, as the technology is advancing.
Two trials. Among the many ongoing trials in the field, Min identified two to watch. The PROMISEstudy is comparing functional vs anatomic testing to identify heart disease. The Coronary Computed Tomographic Angiography for Selective Cardiac Catheterization (CONSERVE) trial is looking at using CT as a “gatekeeper” to the cath lab, to identify which patients should be sent for invasive coronary angiography and which ones have only have mild stenosis and could be sent home and treated with medical therapy .
Worldwide growth in CT. Collaboration with investigators around the world is growing, and the SCCT meetings next year in Hawaii and China will offer more opportunities for this.
Budoff has received research/grant support from HeartFlow, study funding from Wakunaga of America and GE Healthcare and has been a consultant and speaker for GE Healthcare.Min has received research/grant support fromGE Healthcare, Phillips Healthcare, and Vital Images and study funding from Astellas. He has been a consultant for GE Healthcare and Arineta and on the speaker’s bureau for GE Healthcare. He holds equity interest in TC3 and MDXX.
Sources
Budoff MJ. Emerging Clinical applications for cardiac CT. Society of Cardiovascular Computed Tomography 2013 Annual Scientific Meeting; July 12, 2013; Montreal, QC.
Min JK. The future of cardiac CT. What will the next 12 months bring? Society of Cardiovascular Computed Tomography 2013 Annual Scientific Meeting; July 12, 2013; Montreal, QC.
IV. Stress CT Perfusion matches SPECT for detecting Myocardial Ischemia
Montreal, QC – In stress testing using regadenoson (Lexiscan, Astellas), detection rates of myocardial ischemia were similar with less invasive computed-tomography (CT) perfusion imaging compared with the reference method, single-photon-emission CT (SPECT) imaging, in a phase 2 trial [1].
Regadenoson, a selective adenosine-receptor agonist that produces coronary vasodilation in patients unable to undergo exercise stress testing, is the most common agent used to induce pharmaceutical stress in SPECT tests in the US; it was used off-label for the CT imaging.
To heartwire, Cury noted that this trial established noninferiority of regadenoson stress CT perfusion to the reference method, regadenoson SPECT, to detect or exclude myocardial ischemia, which was the primary study outcome.
“This is the second multicenter trial validating [regadenoson] stress CT perfusion, which [builds on the accumulating supporting data from] many single-center studies,” he said, adding that it is still too early, however, to implement these findings into clinical practice.
To heartwire, session moderator Dr John Hoe (Parkway Health Radiology, Singapore) commented that “this is quite an important multicenter trial . . . and the results look very good.” Echoing Cury, he added that “this [research] is slowly [progressing] along the path to validate [regadenoson] CT perfusion as a technique to assess myocardial ischemia.”
In study, 39% of patients had suspected CAD
This was a crossover study conducted at 11 sites in the US, using six types of CT scanners, including 64-, 128-, 256-, and 320-slice machines.
A total of 124 individuals with known (39%) or suspected CAD were randomized to either rest and stress SPECT using regadenoson on day 1, followed by rest and combined stress CT perfusion using regadenoson and coronary CT angiography on day 2; or the same tests in the reverse order.
At baseline, the subjects had a mean age of about 62 and an average body-mass index (BMI) of close to 30. Their average heart rate increased from 64 to 84 beats per minute with the stress-CT perfusion test.
Myocardial ischemia was defined as having two or more reversible defects.
High agreement, specificity, and sensitivity
When it came to detecting myocardial ischemia, CT perfusion imaging agreed with the findings of the reference method, SPECT, 87% of the time (95% CI 0.77-0.97).
“This was well above the specified primary end point for the agreement rate between SPECT and CT perfusion for the detection of ischemia,” Cury said.
Stress CT perfusion imaging also had a high specificity (84%) and sensitivity (90%) for detecting or excluding myocardial ischemia.
Similarly, when it came to detecting the presence or absence of one or more fixed myocardial defects, CT perfusion imaging agreed with the results of the reference method, SPECT, 86% of the time (95% CI 0.74-0.98).
Again, stress CT perfusion imaging had a high specificity (95%) and sensitivity (77%) for detecting or excluding fixed defects.
Used alone, compared with the reference standard of SPECT, stress CT perfusion diagnosed or excluded ischemia accurately in 85% of cases, whereas CT angiography alone made the correct diagnosis in 69% of cases. Thus, “stress CT perfusion may add significant [diagnostic] value to CT angiography alone,” Cury noted.
Regadenoson was well tolerated, and the most common adverse events were flushing or headache.
The study was funded by Astellas. Cury is a consultant for Astellas andhas received research grants from Astellas and GEHealthcare. Hoe has received grant and research support and travel funding fromToshiba Medical Systems and is on its speaker’s bureau.
V. New Protocol Limits Use Of SPECT MPI For Angina
Article Date: 07 May 2013 – 1:00 PDT
A new stress test protocol that investigates reducing the use of perfusion imaging in low risk patients undergoing SPECT myocardial perfusion imaging for possible anginasymptoms was found to be diagnostically safe, revealed a US retrospective analysis. The study, reported as an abstract¹ at the International Conference on Nuclear Cardiology and Cardiac CT (ICNC11) May 5 to May 8 in Berlin, Germany, predicted that using exercise ECG stress testing alone in patients with high exercise capacity would have had no adverse effects on their prognosis at five years.
“Our results are reassuring in that there are few patients whose diagnosis of coronary artery disease (CAD) would be missed,” said Milena Henzlova, the first author of the study. “Not only would widespread adoption of this approach reduce radiation exposure, it would also save considerable amounts of time and money.”
Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has been used for over 30 years to detect ischemia in patients with suspected CAD. In SPECT MPI patients are injected with radioactive agents (such as Tc-99m or Thallium 201) whose passage through the heart is viewed with a SPECT camera. By comparing the heart’s blood flow at rest and during stress (patients exercise on a treadmill, cycle ergometers or undergo pharmacological stress with vasodilators or dobutamine), cardiologists can determine if the myocardium receives sufficient blood supply, as well as the location and extent of underlying CAD.
“Because it’s non invasive and many patients with a chest pain syndrome don’t have coronary disease, SPECT MPI is often viewed as a ‘gate keeper’ to coronary angiography,” explained Lane Duvall, an investigator in the study.
While SPECT MPI represents a well established technique, the main disadvantage is that patients are exposed to diagnostic levels of radiation. In recent years intensive efforts have been made to reduce ionizing radiation associated with cardiac imaging due to concerns that it damages DNA in cells and may ultimately give rise to cancer. Indeed, extrapolating data from the survivors of the Hiroshima and Nagasaki atomic bombs, Andrew Einstein, from Columbia University Medical Center, New York, has estimated that the low levels of radiation encountered during medical imaging might lead to a 2% excess relative risk for future cancers.
Other studies have suggested that exercise treadmill testing alone may be sufficient to predict CVD outcome without use of SPECT MPI in low risk patients. In 2011, Bourque and colleagues from the University of Virginia, Charlottesville, reported that patients who exercise at >10 metabolic equivalents (METS), [the unit used to estimate the amount of oxygen used by the body during physical activity] during stress testing had a very low prevalence of significant ischemia and very low rates of cardiac events during follow-up².
The advantage of exercise treadmill testing is that it offers a quicker study that involves no radiation exposure, with prognostic information provided via a variety of treadmill scores, most notably the Duke Treadmill score. “This has led to investigators questioning the added value of SPECT MPI over exercise testing alone. There’s growing recognition that patients need to be treated as individuals and that those in whom the CVD risks are considered negligible shouldn’t be undergoing the risks of radiation exposure,” said Duvall.
In the current abstract, Henzlova, Duvall and colleagues, from the Mount Sinai School of Medicine, New York, US, set out to investigate retrospectively if a provisional injection protocol in which patients where they met certain criteria were converted to exercise treadmill tests without imaging maintained diagnostic accuracy and prognostic ability. For the retrospective study, data was reviewed from a total of 24,689 patients who had undergone SPECT MPI between February 2004 and June 2010. After exclusion of patients older than 65 years of age, who had known CAD and uninterruptable resting ECGs, 5,352 subjects were identified for analysis.
Subjects were divided into those who would have met all the criteria for not undergoing SPECT MPI (the No injection group n= 1,561 [29.2%]) and those who met the criteria for undergoing SPECT MPI (the Yes injection group, n=3,791, [70.8%]). For the study the criteria laid down for patients considered eligible for not undergoing SPECT MPI included achieving a maximal predicted heart rate >85%, > 10 METs of exercise, no symptoms of chest pain or significant shortness of breath during stress, and no ECG changes (ST depression or arrhythmia). Outcomes for the two groups at five years were then compared based on their actual myocardial perfusion imaging results and all-cause mortality that had been retrospectively identified from the National Death Index.
At a mean follow-up of 60.6 months, 1.1% of patients had died in the No-injection cohort compared to 2.2% Yes injection cohort (P=.01). Furthermore perfusion results were abnormal in 5.9% of the No injection group compared to 14.4% in the Yes injection group (P<.0001). The risk adjusted survival at the end of the follow up was 98.8% in the No injection group compared to 97.2% for patients found to have normal perfusion in the Yes injection group (P=0.009).
“Withholding isotope injections in these selected patients was found to be diagnostically safe with a small percentage of ‘missed’ abnormal perfusion studies, a very low rate of significant stress perfusion defects and left ventricular ischemia, and a prognosis which was better than their counterparts who were injected with the isotope,” said Duvall.
Eliminating the need for imaging in 6% of the 9 million SPECT MPI studies performed annually in the US, the authors added, would result in significant cost savings and the total test time would be halved from three hours to roughly one hour. “There’s a need to accept that less can be more. By individualizing therapy we can reduce radiation exposure and costs without jeopardizing the quality, the diagnostic utility or missing something important,” said Henzlova.
REFERENCES
1. M Henzlova, EJ Levine, S Moonthungal, et al. A protocol for the provisional use of perfusion imaging with exercise stress testing. Abstract no 70123.
2. Bourque JM, Charlton GT, Holland BH, et al. Prognosis in patients achieving >10 METS on exercise stress testing: was SPECT imaging useful? J Nucl Cardiol 2011, 2 230-7. European Society of Cardiology
VI. Contemporary Stress Echo good for Risk Stratification in Chest-Pain Units
12/20/2012, Lisa Nainggolan
London, UK – Doctors in a London chest-pain unit have shown that employing contemporary stress echocardiography in patients with suspected acute coronary syndrome (ACS) but normal ECG and negative troponin is a successful approach for risk stratification [1].
Stress echo is feasible and safe and allows early triage and rapid discharge of patients, plus it is a good predictor of hard events, say Dr Benoy N Shah (Royal Brompton Hospital, London, UK) and colleagues in their paper published online December 18, 2012 in Circulation: Cardiovascular Imaging. Those with an abnormal stress echo had a 13- to15-fold increased risk of MI or death compared with those who had a normal stress echo, they report.
“Stress echo is a very effective gatekeeper for patients undergoing further risk stratification,” senior author Dr Roxy Senior (Royal Brompton Hospital) told heartwire. “It helps select patients for coronary angiography [those with a positive stress echo] and allows immediate discharge of those patients with a negative result.”
Stress echo is perceived to be a technique that is difficult, but that is a misconception.
But Senior says his chest-pain unit is the only one in the UK using this approach. “It is perceived to be a technique that is difficult, but that is a misconception. We have nine stress-echo operators, and it’s easy to train people. With contemporary techniques, which employ contrast in around 50% of cases, the images are quite clear and quick and easy to interpret. It’s very user-friendly. We want to show people around the world that it’s a very doable technique, so why don’t you use it?”
Stress echo also compares favorably with other tests used or proposed for risk stratification of such patients, he says. Exercise ECG is perhaps the most basic technique, “and we have shown that the downstream costs are lower with stress echo than with exercise ECG,” given that the latter provides such equivocal results [2], he explained. And with regard to other imaging modalities that have been employed in this way, computed tomography coronary angiography (CTCA) and single-photon-emission computed tomography (SPECT) require the use of ionizing radiation and have other drawbacks, he notes.
Nevertheless, he and his colleagues say that further, multicenter studies comparing stress echo with CTCA, SPECT, and other imaging techniques for this purpose “will help determine the most cost-effective means of investigating this acute patient population.”
Stress echo performed within 24 hours of admission
Shah and colleagues say that after they showed in 2007 that stress echo was more cost-effective than exercise ECG, they have been employing the former in day-to-day practice in their unit to assess patients who come in with severe chest pain, but whose troponin is negative at 12 hours and whose ECG is “nondiagnostic” (ie, does not suggest any abnormality or shows only minor changes).
The current study is a retrospective look at the patients they have seen so far and is the first evaluation of the clinical impact of incorporating stress echo in a real-world chest-pain unit for the assessment of both short- and long-term prediction of hard events, they say.
“This was sort of an audit; we wanted to know, ‘Is this right? Or are we overcalling it?’ ” Senior explains.
He says the stress echos are performed, for the most part, “within 24 hours” of admission to the chest-pain unit, from 9 am-5 pm Monday to Friday. Those admitted on a weekend will wait slightly longer for a stress echo, he acknowledged. The stress echo is performed on a treadmill if the patient is capable of exercise; if not, a pharmacological stress test is performed using dobutamine. Approximately 30% of the patients in this study performed the test on a treadmill, Senior noted.
Results of the stress echo are available quickly and, if negative, the patient is discharged immediately. If they are positive, the patient is investigated further.
Event rate much higher for those with a positive stress echo
In the study, 839 consecutive patients were assessed; 802 were available for follow-up. Approximately 75% of them had a normal stress echo and were discharged.
“The 30-day readmission rate for all patients was extremely low,” Senior notes, but for those with a negative stress echo it was exceedingly low (at 0.3% compared with 1.1% for those with an abnormal stress echo).
A normal stress echo carried a 99.7% event-free survival for death and 99.5% event-free survival for all hard events in the first year of follow-up; these event rates increased 15-fold and 13-fold respectively if the stress echo was abnormal.
There were 15 “hard” events, 0.5% in the normal stress echo group and 6.6% in the abnormal stress echo group in the first year. At two years, 2.3% of those in the normal stress echo group had died or had a nonfatal MI compared with 9.6% in the stress echo abnormal group, and at three years these figures were 5.1% and 21.1%, respectively. The median follow-up for the study was 27 months.
“For the patients who had a positive stress echo, the event rate was much higher,” Senior notes. Of these 184 patients, 98 had ischemia and most of these underwent coronary angiography, with 57 demonstrating flow-limiting coronary artery disease and 30 subsequently undergoing revascularization.
Among all prognostic variables, only abnormal stress echo (hazard ratio 4.08) and advancing age (HR 1.78) predicted hard events in multivariable regression analysis.
Stress echo should be much more widely used in chest-pain units
“This study demonstrates the excellent feasibility and safety of stress echo in a real-world chest-pain-unit setting, with rapid early triaging and discharge and accurate risk stratification,” the researchers say.
“The two most important outcomes for patients reassured and discharged from the emergency department are that they do not suffer early mortality or early readmission with the same complaint. Our study highlights the excellent negative predictive value of stress echo and very low 30-day readmission rate.”
In addition, the results show that stress echo “appropriately influences the use of coronary angiography and subsequent revascularization” and overall support the wider use of this technique in chest-pain units, they conclude.
Senior has previously received consultancy fees from Lantheus Medical.The coauthors report they have no conflicts of interest.
REFERENCES
Sources
Shah BN, Balaji G, Alhajiri A, et al. The incremental diagnostic and prognostic value of contemporary stress echo in a chest pain unit: mortality and morbidity outcomes from a real-world setting. Circ Cardiovasc Imaging 2012; DOI:10.1161/CIRCIMAGING.112.980797. Available at: http://circimaging.ahajournals.org.
Jeetley P, Burden L, Stoykova B, Senior R. Clinical and economic impact of stress echocardiography compared with exercise electrocardiography in patients with suspected acute coronary syndrome but negative troponin: a prospective randomized controlled study. Eur Heart J. 2007; 28:204-211.
VII. PET Perfusion Imaging Improves Risk Estimates
12/5/2012 Reed Miller
Boston, MA – New data from a large multicenter registry suggest that positron-emission-tomography (PET) myocardial perfusion imaging (MPI) can greatly improve the accuracy of risk estimation in coronary disease patients compared with a model based on traditional risk factors [1].
Only small single-center studies have demonstrated the prognostic value of PET MPI in predicting which patients are at greatest risk for coronary disease events. So Dr Sharmila Dorbala (Brigham and Women’s Hospital, Boston) and colleagues analyzed outcomes from 7061 patients from four centers who underwent a clinically indicated rest/stress rubidium-82 PET MPI test.
Results of the study are published online December 5, 2012 in the Journal of the American College of Cardiology. “The results of the current study are critical to advance the field and guide more effective use of PET MPI in clinical practice,” Dorbala et al state.
Median follow-up was 2.2 years. During follow-up, there were 169 cardiac arrests and 570 all-cause deaths. Net reclassification improvement and integrated discrimination analyses showed that the risk-adjusted hazard of cardiac death increases as the percentage of abnormal myocardium increases. A mildly abnormal stress test is associated with a 2.3 times greater risk of cardiac death than a normal test. The hazard ratio for a severely abnormal test is 4.9.
The addition of PET MPI measurements of myocardial ischemia and myocardial scarring to traditional clinical information improves the performance of a risk prediction model based on traditional risk factors (C statistic 0.805-0.839) as well as risk reclassification for cardiac death, with small improvements in risk assessments for all-cause death. The assessment of the magnitude of ischemia and scar added to the reclassification of risk for cardiac death in one in every nine patients who underwent clinical PET MPI in the study.
Unlike computed-tomography (CT) coronary angiography, perfusion imaging provides information about myocardial blood flow and accounts for underlying coronary disease, collateral flow, and myocardial adaptation to wall stress and can be used in patients with renal insufficiency, the authors point out. Compared with single-photon-emission computed tomography (SPECT) perfusion imaging, PET MPI offers better image quality, test specificity for the diagnosis of obstructive coronary disease, and identification of scar and ischemia, according to Dorbala et al, and PET MPI uses a lower effective radiation dose. However, while the prognostic value of SPECT MPI has been described in tens of thousands of patients, the prognostic value of PET MPI has been studied in only a few thousand patients.
Does more risk information help?
The value of the prognostic information offered by PET MPI is not yet clear, according to an accompanying editorial by Drs Paul Schoenhagen and Rory Hachamovitch (Cleveland Clinic, OH) [2]. “Rather than assessing whether a test yields improvement in risk assessment, the focus [should be] shifted to whether a test can identify which patients will gain a benefit from a specific therapeutic approach,” they write. “The role of testing [should be] defined in the context of a specific intervention and whether the effectiveness of the intervention is improved by the use of an imaging study to identify optimal candidates for treatment.
“However, this process is neither simple nor inexpensive and will require prospective randomized clinical trials, validating the results and hypotheses generated by observational data,” the editorialists conclude.
Commenting on the study, Dr Kavitha Chinnaiyan (William Beaumont Hospital, Royal Oak, MI) toldheartwire, “While the details of downstream management of these patients are unclear in this paper, the association of ischemia with mortality is clear, as is the reclassification of risk. The next step in terms of management of ischemic patients is really the question here.” She also pointed out that the ongoingISCHEMIA trial, comparing angiography and revascularization plus optimal medical therapy with optimal medical therapy only, may provide more insights on the best option for patients who show more than mild ischemia on stress studies.
Dorbala has received research grants from Astellas Pharmaand Bracco Diagnostics; has served on advisory boards for Astellas Pharma; and hasreceived honoraria from MedXcel. Disclosures for the coauthors are listed in the paper.Schoenhagen and Hachamovitch report that they have no relationships relevantto the contents of this paper to disclose. Chinnaiyan has no relevant disclosures.
REFERENCES
Dorbala S, Di Carli M, Beanlands RS, et al. Prognostic value of stress myocardial perfusion positron emission tomography. J Am Coll Cardiol 2013; DOI:10.1016/j.jacc.2012.09.044. Available at:http://content.onlinejacc.org.
Schoenhagen P and Hachamovitch R. Evaluating the clinical impact of cardiovascular imaging: Is a risk-based stratification paradigm relevant. J Am Coll Cardiol 2013; DOI:10.1016/j.jacc.2012.09.044. Available at:http://content.onlinejacc.org.
I shadowed Dr. Cambria in the Operating Room at MGH in January 2005 while he performed Carotid EndarterectomyfollowingAortic Valve Replacement performed by Dr. Jennifer D. Walker in a sequence, first the Valve replacement, then the Endarterectomy.
This word has a Greek origin from the terms [aneurusma], composed of [ana] meaning “complete or throughout”, and [eurus] meaning “wide”, a “complete widening or dilation”. It is used to refer to the dilation of an artery. Aneurysms can be formed in any artery, although they have some preferred sites. The most common aneurysms are found in the aorta, arterial circle of Willis, the root of the cerebral arteries, and internal carotid arteries.Biomechanical studies suggest that once an aneurysm forms it will generally progress in its dilation until aneurysmal rupture. Because of turbulent flow within the aneurysm large clots are usually formed, which in turn can cause emboli.The image shows an excised infrarenal aortic abdominal aneurysm (AAA). The two common iliac arteries can be seen. If you click on the image you will be able to see the same aneurysm opened through its posterior wall and the clot that was contained inside.Photography by D.M.Klein
It is true that abdominal aortic aneurysms (AAA) are mostly asymptomatic, until they rupture. By luck, some are identified. An example was a AAA found in Albert Einstein by Dr. Nissen when Einstein went for abdominal surgery for something completely unrelated! In my experience, I have found many AAA’s in individuals who had a totally different cause of death.
Dr. Richard Cambria describes an Aortic Aneurysm and recalls the numerous risk factors associated with the condition.
Dr. Cambria:
An aortic aneurysm can be most simply thoughts of as a weakening or ballooning of the aorta which is the body’s major and largest blood vessel. That’s important because this ballooning or weakening can eventually lead to the aneurysm bursting, which is usually a fatal event.
Aneurysms have been referred to as the ‘silent killer’ because in most cases these aortic aneurysms cause no symptoms or problems prior to bursting. Most aortic aneurysms occur in older patients, but there are a clearly defined set of risk factors which makes certain patients at higher risk of developing aortic aneurysms. These include, most importantly, a family history of aortic aneurysm disease, and by family history I mean, if your mother or father or a brother or sister had an aortic aneurysm, you are clearly at increased risk of developing an aneurysm.
20% of the patients that we treat for aortic aneurysms have a positive family history of aneurysm disease. You are also at higher risk for developing an aortic aneurysm if you are female, if you have a history of high blood pressure, if you have been a cigarette smoker, and if you have chronic obstructive pulmonary disease or emphysema, which is in turn related to long-term cigarette smoking.
If you are at risk for developing an aortic aneurysm there are simple diagnostic x-ray studies such as ultrasounds and CAT scans to accurately diagnose number one, whether or not an aneurysm is present, and more importantly, if it is present, to measure just how large it is because that’s the single most important factor in determining whether or not your aneurysm needs to be treated.
It’s important to detect and monitor aortic aneurysms before they reach the stage of bursting because treatment is then usually successful with an expected excellent recovery. Treatment of aortic aneurysms today is very effective and involves replacing the aneurysm with an artificial blood vessel.
There are a variety of different surgical treatments, some of them including minimally invasive operations known as stent grafts, which are applied today in many patients.
Mass General has been a leader in the northeast in the successful management of aortic aneurysms. More than a decade ago, we formed the Mass General Thoracic Aortic Center, which is a team-approach of vascular surgeons, cardiac or heart surgeons, and cardiologists to effectively manage thoracic aneurysms which are often the most challenging and clinically complex to treat.
About Dr. Richard Paul Cambria, M.D.:
Richard P. Cambria, M.D. is Professor of Surgery at Harvard Medical School and Chief, Division of Vascular/Endovascular Surgery at Massachusetts General Hospital. Dr. Cambria received his medical degree from the College of Physicians and Surgeons, Columbia University, in 1977. He trained in general and vascular surgery at Massachusetts General Hospital.
Giant Cell Aortitis of the Ascending Aorta Without Signs or Symptoms of Systemic Vasculitis is Associated with Elevated Risk of Distal Aortic Events.
Date
February 2012
Journal
Arthritis and Rheumatism
Title
Long-term Outcomes of Patients Undergoing Endovascular Infrainguinal Interventions with Single-vessel Peroneal Artery Runoff.
Date
May 2011
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
The Effects of Systemic Hypothermia on a Murine Model of Thoracic Aortic Ischemia Reperfusion.
Date
August 2010
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Long-term Outcomes of Diabetic Patients Undergoing Endovascular Infrainguinal Interventions.
Date
August 2010
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Preoperative Variables Predict Persistent Type 2 Endoleak After Endovascular Aneurysm Repair.
Date
August 2010
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Surgical Management of Descending Thoracic Aortic Disease: Open and Endovascular Approaches: a Scientific Statement from the American Heart Association.
Date
August 2010
Journal
Circulation
Title
Balloon Expandable Stents Facilitate Right Renal Artery Reconstruction During Complex Open Aortic Aneurysm Repair.
Date
March 2010
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Preoperative Functional Status Predicts Perioperative Outcomes After Infrainguinal Bypass Surgery.
Date
March 2010
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Intermediate-term Outcomes of Endovascular Treatment for Symptomatic Chronic Mesenteric Ischemia.
Date
February 2010
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
A Multicenter Clinical Trial of Endovascular Stent Graft Repair of Acute Catastrophes of the Descending Thoracic Aorta.
Date
December 2009
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Aortic Remodeling After Endovascular Repair of Acute Complicated Type B Aortic Dissection.
Date
September 2009
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Thoracoabdominal Aneurysm Repair: Hybrid Versus Open Repair.
Date
July 2009
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Successful Use of Bivalirudin for Combined Carotid Endarterectomy and Coronary Revascularization with the Use of Cardiopulmonary Bypass in a Patient with an Elevated Heparin-platelet Factor 4 Antibody Titer.
Functional Outcome After Thoracoabdominal Aneurysm Repair.
Date
December 2008
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Outcomes Following Endovascular Abdominal Aortic Aneurysm Repair (evar): an Anatomic and Device-specific Analysis.
Date
August 2008
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Spinal Cord Complications After Thoracic Aortic Surgery: Long-term Survival and Functional Status Varies with Deficit Severity.
Date
August 2008
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Five-year Results of Endovascular Treatment with the Gore Tag Device Compared with Open Repair of Thoracic Aortic Aneurysms.
Date
June 2008
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Journal of the American College of Radiology : Jacr
Title
International Controlled Clinical Trial of Thoracic Endovascular Aneurysm Repair with the Zenith Tx2 Endovascular Graft: 1-year Results.
Date
March 2008
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Long-term Durability of Open Abdominal Aortic Aneurysm Repair.
Date
November 2007
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Commentary On: Mas Jl, Chatellier G, Beyssen B, Et Al. Endarterectomy Versus Stenting in Patients with Symptomatic Severe Carotid Stenosis. N Engl J Med. 2006;355:1660-1671.
Date
November 2007
Journal
Perspectives in Vascular Surgery and Endovascular Therapy
Defining the High-risk Patient for Carotid Endarterectomy: an Analysis of the Prospective National Surgical Quality Improvement Program Database.
Date
October 2007
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Persistent Type 2 Endoleak After Endovascular Repair of Abdominal Aortic Aneurysm is Associated with Adverse Late Outcomes.
Date
July 2007
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Restenosis After Eversion Vs Patch Closure Carotid Endarterectomy.
Date
July 2007
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Surgical Revascularization Versus Endovascular Therapy for Chronic Mesenteric Ischemia: a Comparative Experience.
Date
July 2007
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Comparison of Risk-adjusted 30-day Postoperative Mortality and Morbidity in Department of Veterans Affairs Hospitals and Selected University Medical Centers: Vascular Surgical Operations in Men.
Stent-graft Versus Open-surgical Repair of the Thoracic Aorta: Mid-term Results.
Date
January 2007
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Intermediate Results of Percutaneous Endovascular Therapy of Femoropopliteal Occlusive Disease: a Contemporary Series.
Date
October 2006
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Commentary on “extra-anatomic Visceral Revascularization and Endovascular Stent-grafting for Complex Thoracoabdominal Aortic Lesions”.
Date
May 2006
Journal
Perspectives in Vascular Surgery and Endovascular Therapy
Title
Multi-institutional Pivotal Trial of the Zenith Tx2 Thoracic Aortic Stent-graft for Treatment of Descending Thoracic Aortic Aneurysms: Clinical Study Design.
Date
May 2006
Journal
Perspectives in Vascular Surgery and Endovascular Therapy
Aortic Dissection: Perspectives in the Era of Stent-graft Repair.
Date
March 2006
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Title
Current Results of Open Surgical Repair of Descending Thoracic Aortic Aneurysms.
Date
March 2006
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Title
Late Results of Combined Carotid and Coronary Surgery Using Actual Versus Actuarial Methodology.
Contemporary Results of Angioplasty-based Infrainguinal Percutaneous Interventions.
Date
November 2005
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Safety and Efficacy of Reoperative Carotid Endarterectomy: a 14-year Experience.
Date
July 2005
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Determinants of Carotid Endarterectomy Anatomic Durability: Effects of Serum Lipids and Lipid-lowering Drugs.
Date
May 2005
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Early Outcomes of Endovascular Versus Open Abdominal Aortic Aneurysm Repair in the National Surgical Quality Improvement Program-private Sector (nsqip-ps).
Date
May 2005
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Endovascular Treatment of Thoracic Aortic Aneurysms: Results of the Phase Ii Multicenter Trial of the Gore Tag Thoracic Endoprosthesis.
Date
March 2005
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Preservation of Renal Function with Surgical Revascularization in Patients with Atherosclerotic Renovascular Disease.
Date
February 2004
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Durability of Aortouniiliac Endografting with Femorofemoral Crossover: 4-year Experience in the Evt/guidant Trials.
Date
June 2003
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Late Aortic and Graft-related Events After Thoracoabdominal Aneurysm Repair.
Date
February 2003
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Evolving Experience with Thoracic Aortic Stent Graft Repair.
Date
July 2002
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Clinical Failures of Endovascular Abdominal Aortic Aneurysm Repair: Incidence, Causes, and Management.
Date
July 2002
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Regarding “analysis of Predictive Factors for Progression of Type B Aortic Intramural Hematoma with Computed Tomography”.
Date
July 2002
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Title
Contemporary Management of Aortic Branch Compromise Resulting from Acute Aortic Dissection.
Date
July 2001
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Endovascular Repair of Abdominal Aortic Aneurysms: Current Status and Future Directions.
Date
August 2000
Journal
Ajr. American Journal of Roentgenology
Title
Epidural Cooling for Spinal Cord Protection During Thoracoabdominal Aneurysm Repair: A Five-year Experience.
Date
July 2000
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Utility and Reliability of Endovascular Aortouniiliac with Femorofemoral Crossover Graft for Aortoiliac Aneurysmal Disease.
Date
July 2000
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Surgical Renal Artery Reconstruction Without Contrast Arteriography: the Role of Clinical Profiling and Magnetic Resonance Angiography.
Date
January 2000
Journal
Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Cambria RP, Brewster DC, Lauterbach SR, Kaufman JA, Geller SC, Fan CM, Greenfield A, Hilgenberg A, Clouse WD. Evolving experience with thoracic aortic stent-graft repair. J Vasc Surg 2002:35:1129-36.
Cambria, RP, Clouse WD, Davison JK, Dunn PF, Corey M, Dorer D. Thoracoabdominal aneurysm repair: Results with 337 operations performed over a 15 year interval. Ann Surg 2002;236-471-79.
Cambria RP and Black JH. Aortic dissection perspectives for the vascular/endovascular surgeon. In Rutherford (ed) Comprehensive Vascular and Endovascular Surgery 6 th , W. B. Saunders, Inc. (in press, 2004).
Cambria RP, Marone LK, Cloud WD, Dorer, DJ, Brewster, DC, LaMuraglia, GM, Watkins, MT, Kwolek, CJ. Preservation of renal functions with surgical revascularization in patients with atherosclerotic renovascular disease. J Vasc Surg 2004; 10.023.
An aneurysm is defined as a focally dilated segment of an artery that is 1.5 times its normal diameter and involves all three arterial walls (intima, media and adventitia). Aneurysms can be found in the common femoral and popliteal arteries in the lower extremities, the splenic, mesenteric, and renal arteries in the abdomen, and also in the intracranial vessels. However, the most common is an abdominal aortic aneurysm (AAA) involving the aorta and iliac arteries.
Abdominal aortic aneurysms are generally asymptomatic and are discovered accidentally either by physician palpation or by a radiologic examination such as a chest or abdominal X-ray. The risk factors that increase the probability of developing a AAA are primarily smoking and family history. An abdominal aortic aneurysm can rupture and, according to the Centers for Disease Control and Prevention, ruptured AAA was the 10th leading cause of death in males between the ages of 65-74 in the United States in 2000.
The preferred method of screening for AAA is diagnostic ultrasound. According to the Journal of Vascular Surgery, diagnostic ultrasound performed by a registered vascular technologist has a sensitivity of 100 percent and a specificity of 96 percent for the detection of an infrarenal AAA. The abdominal aorta is considered aneurysmal when it measures >3.0 cm.
Because of its accuracy, diagnostic ultrasound not only has become an integral part in diagnosing AAA but is also an integral part in the evaluation of disease progression, the preoperative AAA evaluation, and the follow-up of AAA surgical repair. It is important to note that a rupture of an AAA is a surgical emergency and is difficult to evaluate with ultrasound due to the inability to easily demonstrate abdominal free fluid. If a rupture is suspected, it is recommended that other imaging modalities such as CT be employed to better demonstrate the ruptured aneurysm and any intra-abdominal free fluid.
Case Study –
Abdominal Aortic Aneurysm – A 77 year-old male
Angela Rodriguez-Wong, MD, RVT, RPVI
Lois Eliassi, BS, RVT
Figure 1 Distal abdominal aortic aneurysm with mural thrombus.
Figure 2 Bifurcation of the aorta.
Case Study: A 77 year-old male with a past medical history of diabetes, hypertension, arthritis, aortic valve disease and heavy smoking was referred to Eastern Vascular Diagnostic Center with a 4.2 centimeter aneurysm. The patient denied any family history of aneurysm and is allergic to intravenous contrast. A physical exam found the patient alert with a blood pressure of 100/60 mmHg, a pulse of 58 and respiration of 16. Auscultation found a bruit in the left carotid artery, clear lungs, and a regular heart rhythm with an aortic systolic murmur. The patient had a well healed sub-costal incision on his abdomen. The physician was unable to palpate the aneurysms. The patient had an aortic valve replacement in 2007 and also a cholecystectomy. On May 12, 2012, a magnetic resonance imaging (MRI) scan without contrast was performed on the patient’s abdomen. The MRI found an AAA measuring greater than 3 cm with extensive plaque near the bifurcation. The aneurysm extended into the right common iliac artery (CIA) measuring 4.2 cm and into the left CIA measuring 3.1 cm. The MRI exam did not include the pelvis, so the extent of the iliac aneurysms was not clear. On July 31, 2012, the ultrasound was performed, demonstrating normal ankle brachial index (right-1.2, left-1.1) and a AAA measuring 3.9 cm which extended into the right and left CIA. The maximum diameter of the right CIA measures 4.1 cm with mural thrombus creating a residual lumen of 2.0 cm. The maximum diameter of the left CIA measures 4.3 cm, there is also mural thrombus noted but without significant appreciable diameter reduction within the vessel. A computed tomography (CT) scan of the abdomen and pelvis without contrast was performed on July 18th confirming the infrarenal AAA with extension into the iliac arteries bilaterally.
Surgery is recommended when an AAA reaches 5.0-5.5 cm in a male and 4.5-5.0 cm in females. Surgery, depending on the aneurysm, can be an open repair or an endovascular repair. In this patient, despite the size of the AAA being 4.1 cm, the disease also involved the bilateral common iliacs prompting the need for surgical intervention. The patient was cleared by cardiology and on July 31st had an AAA and bilateral Iliac aneurysm resection with a re-implantation of the inferior mesenteric artery and an Aorta to right Hypogastric bypass to maintain pelvic perfusion.
The U.S. Preventive Services Task Force has released a statement summarizing recommendations for screening for AAA. It states that screening benefits patients who have a relatively high risk for dying from an aneurysm; major risk factors are age 65 years or older, male sex, and smoking at least 100 cigarettes in a lifetime. The guideline recommends one-time screening with ultrasound for AAA in men 65 to 75 years of age who have ever smoked. No recommendation was made for or against screening in men 65 to 75 years of age who have never smoked, and it recommended against screening women. Men with a strong family history of AAA should be counseled about the risks and benefits of screening as they approach 65 years of age.
Angela Rodriguez-Wong, MD, RVT, RPVI
awong@navixdiagnostix.com
Lois Eliassi, BS, RVT
leliassi@navixdiagnostix.com
Figure 3 Sagittal image of the right common iliac artery demonstrating the measurement of the aneurysm and the true lumen.
Figure 4 Coronal view of the left common iliac artery.
The expert consensus document explains that CCT may emerge in the field of interventional cardiology as no longer “a mere diagnostic tool,” as it was when first introduced into clinical practice more than 15 years ago.
According to the writing group, led by Daniele Andreini, MD, PhD, FSCCT of Centro Cardiologico Monzino in Milan, Italy, the potential value of CCTA to plan and guide interventional procedures lies in the wide information it can provide, including its accuracy for plaque and calcium characterization.
Andreini and his co-authors explain that, with its 3-dimensional nature and physiological assessment, CCTA is the only non-invasive imaging modality to assess Syntax Score and Syntax Score II, which enable the Heart Team to select the mode of revascularization (PCI or CABG) for patients with complex disease based on long-term mortality.
Additionally, CCTA may help in identifying anatomical characteristics of chronic total occlusions (CTO) that are associated with increased complexity of CTO percutaneous coronary intervention (PCI).
Before PCI, CCTA has the potential to be used to overcome some limitations of conventional invasive coronary angiography (ICA), including vessel foreshortening and difficulties in selecting optimal projections, with particular importance in bifurcation and ostial lesions.
A new CT scanner exposes patients to less radiation while providing doctors with clearer images to help with diagnoses, according to researchers at the National Institutes of Health.
“CT” stands for Computerized Tomography, which involves combining lots of x-ray images taken from different angles into a three-dimensional view of what’s inside the body. The technology can be especially useful for diagnoses in emergency situations, and the number of CT scans in recent years has increased dramatically, says Marcus Chen, a cardiovascular imager at the National Heart, Lung and Blood Institute, in Bethesda, Maryland. But the increase in the use of CT scans raises concerns about the amount of radiation to which patients are exposed, says Chen.
The risk of developing cancer from the radiation delivered by one CT scan is low, but the large number of scans performed each year—more than 70 million—translates to a significant risk. Researchers at the National Cancer Instituteestimated that the 72 million CT scans performed in the U.S. in 2007 could lead to 29,000 new cancers. On average, the organ studied in a CT scan of an adult receives around 15 millisieverts of radiation, compared with roughly 3.1 millisieverts of radiation exposurefrom natural sources each year.
This concern has led researchers to seek ways to reduce the amount of radiation exposure a patient receives in a scan. They are working to improve both hardware, to make the scans go faster and need less repetition, and software, to process the x-ray data better (see “Clear CT Scans with Less Radiation”).
The new CT scanning system, from Toshiba Medical, combines several improvements to reduce radiation exposure. The overall body of a CT scanner is shaped like a large ring. An x-ray tube and a detector spin separately in the ring, opposite one another, and a patient lies in the center. X-rays travel through the patient as they are delivered by the tube and captured by the detectors. The new Toshiba machine has five times as many detectors as most machines, which means that more of an organ can be captured at a time, decreasing the number of passes of the scanner required.
The x-ray components in the new system also spin faster—it takes only 275 milliseconds for them to complete a rotation, instead of 350 millisesconds—which means a patient gets irradiated for less time. In cases where doctors are looking at a moving organ such as the heart, the faster spinning also reduces the number of times a doctor may need to try to get a good image. “It’s like having faster film in your camera,” says Chen. Changes to the way the system generates x-rays and computes the images also mean patients spend less time getting hit with radiation.
Chen and colleagues at the National Heart Lung and Blood Institute used the Toshiba system to examine 107 adult patients of different ages and sizes for plaque buildup and cardiovascular problems. Patient size matters because more x-rays are required to image a larger person. “A lot of imaging centers will use one setting for all patients,” says Chen. “You get beautiful image quality on everybody, but the downside is that some patients get more radiation than they probably should.” In his study, the system takes a quick preliminary scan that uses low-dose x-rays to figure out how big a patient is and how much radiation will be needed for the diagnostic image.
Most patients who got a scan in the new Toshiba machine received 0.93 millisieverts of radiation, and almost every patient received less than 4 millisieverts. Radiation exposure was decreased by as much as 95 percent relative to other CT scanners currently in use.
The reader is advised to review Alternative #3 in the following article, published on 3/10/2013, including the Editorial in NEJM by Dr. Redberg, UCSF, included in the article, prior to reading the content, below — as background on this important topic having the potential to change best practice and standard of care in the ER/ED.
May 14, 2013 — One of the largest studies yet comparing medical resource use and outcomes among chest pain patients found that coronary CT angiography (CCTA) reduced medical resource utilization compared to standard care, generating fewer hospital admissions and shorter emergency room stays, researchers reported in the Journal of the American College of Cardiology.
The retrospective study compared matched cohorts of nearly 1,000 patients presenting with chest pain before and after implementation of routine CCTA evaluation. The study team from Stony Brook, NY, and two other institutions found that patients receiving the standard workup for chest pain — which is to say, mostly observation — were admitted to the hospital almost five times as frequently as patients receiving CT. The standard workup patients also had significantly longer stays when admitted.
The rates of invasive angiography without revascularization and recidivism were also much higher for patients receiving standard care (JACC, May 14, 2013).
“I think the take-home message is that CT done correctly by experts with the resources to do it correctly on a routine basis is not only safe and feasible, but reduces healthcare resource utilization,” said lead author Dr. Michael Poon, from Stony Brook Medical Center, in an interview with AuntMinnie.com.
More than $10 billion in costs
Caring for chest pain is an expensive proposition in the U.S., costing upward of $10 billion a year for some 6 million emergency department (ED) visits. To reduce the problem of overcrowded emergency rooms, some hospitals have implemented chest pain evaluation units, but the care isn’t comprehensive or necessarily all that helpful, Poon said.
“It has been a problem and a major dilemma for emergency rooms because for most patients, it’s a false alarm,” he said. “I would say nine out of 10 are false alarms, but how to pick out that one is very tricky and costly. So what most hospitals tend to do is a one-size-fits-all policy where everybody gets blood tests and an electrocardiogram, and they keep patients in the ED for an extended period of time. So if you come in Friday, you may stay until Monday.”
Coronary CTA has been shown to be safe and cost-effective for acute chest pain evaluation in several smaller studies and in three smaller multicenter trials, but those studies have been limited by a lack of CT availability outside of weekdays and office hours, while EDs must operate 24/7, Poon said.
“All of those studies were done in a randomized, controlled fashion and in an artificial environment,” where each patient was randomized to either a stress test or CT during weekday office hours, Poon said. “But in real life, there is no such thing; it cannot be done.”
More often, chest pain patients get a couple of tests and several hours of observation before they are sent home.
Poon and colleagues from Stony Brook, William Beaumont Hospital, and the University of Toronto wanted to do a “real-world” observational study to show that CT remained cost-effective and efficient for triaging chest pain patients.
The study sought to compare the overall impact of CT on clinical outcomes and efficacy, when comparing CCTA and the hospital’s standard evaluation for the triage of chest pain patients, with CCTA available 12 hours a day, seven days a week.
From a total of 9,308 patients with a chest pain diagnosis upon admission, the study used a matched sample of 894 patients without a history of coronary artery disease and without positive troponin or ischemic changes on an electrocardiogram.
Patients undergoing CT were scanned on a 64-detector-row scanner (LightSpeed VCT, GE Healthcare) following administration of iodinated contrast and metoprolol as a beta-blocker for those with heart rates faster than 65 beats per minute (bpm).
Those with a body mass index (BMI) less than 30 were scanned at 100 kV, while those with a BMI between 30 and 50 were scanned at 120 kV. Retrospective gating was reserved for patients whose heart rates remained above 65 bpm. Obstructive stenosis was defined as 50% or greater lumen narrowing.
CT choice faster, more efficient
The results showed a lower overall admission rate of 14% for CCTA, compared with 40% for the standard of care (p < 0.001). In fact, patients undergoing standard evaluation were 5.5 times more likely to be admitted (p < 0.001) than CCTA patients.
The length of stay in the ED was 1.6 times longer for standard care (p < 0.001) than for CCTA. For patients undergoing CCTA, the median radiation dose was 5.88 mSv.
“We also showed that the recidivism rate is higher for standard of care, meaning that they come back within one month with recurrent chest pain,” Poon said. The odds of returning to the ED within 30 days were five times greater for patients in the standard evaluation group (odds ratio, 5.06; p = 0.022).
“In the era of Obamacare, this is a penalty to the hospital; you don’t want the patient returning within one month with the same diagnosis,” he said. When that happens, “you’re not only not getting paid, you have to pay a penalty. It’s a double whammy. We also show that downstream invasive coronary angiography is significantly less in the CCTA arm.”
More invasive angiography
Patients receiving standard care were seven times more likely to undergo invasive coronary angiography without revascularization (odds ratio, 7.17; p ≤ 0.001), while neither patient group was significantly more likely to undergo revascularization.
“Many physicians use [catheterization] as a way of getting patients in and out of the hospital,” Poon said. However, the cost is more than $10,000 per procedure.
The high rate of angiography without revascularization in the standard care group was not seen in the Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) I and II trials, where all patients in the standard care group underwent stress testing before angiography was considered, he said.
Poon credited the ROMICAT trials’ routine use of stress tests with diminishing CT’s relative advantage in resource use. “In the real world, that is not available,” he said. The present study, in which only about 20% of the standard care patients underwent stress tests, is more realistic.
Finally, Poon and colleagues showed no difference in rates of myocardial infarction between CT and the standard of care within the first 30 days of follow up. However, that is changing as patients are followed for longer time periods, he noted.
“We see a trend starting to diverge in our next report, which follows [patients] for six months,” he said. “You see a lot more acute myocardial infarction in the standard care arm, and we’re going to extend it for a year.”
The authors concluded that using CCTA to rule out acute coronary syndromes in low-risk chest pain patients is likely to improve doctors’ ability to triage patients with the common presentation of chest pain. The result of this approach appears to be fewer hospital admissions, shorter stays, less recidivism, less invasive angiography, and better patient outcomes.
In any case, Poon said, the study method is permanent at Stony Brook University, where the standard of care now incorporates CCTA.
“We didn’t stop doing it after the study,” he said. “If you look at some of the randomized, controlled studies, they actually went back to the standard of care.” They had to because those kinds of protocols are only practical with a grant.
Other related articles on this Open Access Online Scientific Journal include the following:
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
Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems
Larry H Bernstein, MD, FACP and Aviva Lev-Ari, PhD, RN, Curator, 5/15/2013
Maddux PT et al. – The purpose of this study is to determine whether coronary artery anomalies can be detected on noncontrast computed tomography (CT) coronary artery calcium scoring (CCS) studies. Benign and malignant coronary artery anomalies can be detected with relatively high accuracy on noncontrast–enhanced CCS studies. CCS studies should be reviewed for signs of coronary artery anomalies in order to identify malignant variants with possible impact on patient management.
Methods
A total of 126 patients (mean age 62 years; 35 women) underwent noncontrast CCS and contrast enhanced coronary CT angiography (cCTA).
Thirty–three patients were diagnosed with a coronary anomaly on cCTA, whereas coronary anomalies were excluded in 93.
Two observers (reader 1 [R1] and reader 2 [R2]), blinded to patient information independently evaluated each CCS study for: 1) visibility of coronary artery origins, 2) detection of coronary anomalies, and 3) benign or malignant (ie, interarterial) course.
Using cCTA as the reference standard, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CCS studies for detecting coronary anomalies were calculated.
Results
Of the 33 coronary anomalies, 16 were benign and 17 malignant.
Based on noncontrast CCS studies, R1 and R2 correctly identified the left main origin in 123/126 (97.6%) and 121/126 (96%) patients; the left anterior descending origin in 125/126 (99.2%) and 122/126 (96.8%); the circumflex origin in 120/126 (95.2%) and 105/126 (83.3%); and the right coronary artery origin in 117/126 (92.9%) and 103/126 (81.7%), respectively.
R1 and R2 identified 34 and 27 coronary anomalies and classified 19 and 15 as malignant, respectively.
Interobserver reproducibility for detection of coronary anomalies was good (k = 0.76).
Interobserver agreement for detection of malignant variants was even stronger (k = 0.80).
On average, coronary artery anomalies were diagnosed with 85.2% sensitivity, 96.4% specificity, 90.5% PPV, and 94.1% NPV on noncontrast CCS studies.
April 12, 2013 — Automated plaque assessment in coronary CT angiography (CCTA) is a promising new way to evaluate a patient’s plaque burden quickly and noninvasively — but it won’t be quick or accurate without the use of advanced iterative reconstruction, according to researchers from Massachusetts General Hospital in Boston.
Automated techniques are still in their infancy, but once they become more reliable they promise to greatly improve risk assessment and management compared with, for example, calcium scoring, by precisely quantifying the amount of coronary artery plaque — fibrotic, lipid core, and calcium — that is present.
“We know the plaque volume and characteristics … are at least as important as the presence of calcium,” said Dr. Stefan Puchner in an interview with AuntMinnie.com. “If we could make plaque assessment more accurate, we could implement all this stuff in our daily practice.”
The process isn’t accurate today. Automated plaque quantification requires significant time for radiologists to fix the incorrectly drawn vessel wall boundaries, making it impractical for routine use. Manually drawing the boundaries would actually take about a day’s work for each patient, so automation is the only way forward, Puchner said. The group wanted to determine if an advanced reconstruction algorithm might produce fewer errors and make semiautomated plaque estimation practical.
In a study that reconstructed ex vivo coronary vessel segments using three different reconstruction methods, the study team found that, indeed, accuracy in plaque quantification depended on the reconstruction algorithm, as well as vessel size and the extent of calcifications. Using advanced reconstruction, fewer corrections were needed to the vessel wall segmentation, Puchner reported at the 2013 European Congress of Radiology (ECR) in Vienna. Specifically, they compared the use of automated vessel assessment using model-based iterative reconstruction (MBIR, GE Healthcare) compared with an earlier IR algorithm, advanced statistical iterative reconstruction (ASIR, GE), or conventional filtered back projection (FBP) reconstruction.
Cross section of a noncalcified plaque reconstructed with the three different algorithms (left to right: FBP, ASIR, MBIR). No significant differences can be seen between the three algorithms in terms of correct delineation of the plaque borders. All images courtesy of Dr. Stephan Puchner.
For subjects, the group examined three ex vivo human hearts imaged with CCTA and reconstructed with FBP, ASIR, and MBIR. An automated plaque quantification tool (Vitrea Cardiac Solutions, Vital) was applied to each of the three reconstruction algorithms to fit the outer and inner vessel wall boundaries in nine “triplets” constituting 27 vessels. Only the first 40 mm of the contrast-filled vessels was used for analysis.
Each coronary cross section for which the software assigned incorrect boundaries was tallied and corrected in a blinded manner. The group then compared the number of vessel wall corrections between the different reconstruction algorithms using a Chi-square test.
Cross ection of a calcified plaque reconstructed with the three different algorithms (left to right: FBP, ASIR, MBIR). In this case, FBP shows an incorrect delineation of the inner vessel wall boundary, including parts of the calcified plaque. In contrast, the vessel wall boundaries in the cross sections reconstructed with ASIR and MBIR are correctly delineated by the software.
“Our analysis included the percentage of corrections between the three algorithms, and a per-vessel comparison of the percentage of corrections between the three algorithms,” Puchner said in his presentation.
In all, the study comprised 2,295 cross sections in 0.5-mm increments from nine coronary vessels, combined into 765 coregistered triplets evaluated with the three algorithms. Overall, 31% of the cross sections needed boundary corrections, he said. Outer vessel wall boundary corrections were needed in 400 cross sections, and inner vessel boundaries were needed in 381 cross sections.
Cross section of a calcified plaque reconstructed with the three different algorithms (left to right: FBPR, ASIR, MBIR). In this case, FBP and ASIR show an incorrect delineation of the inner vessel wall boundary, including the whole or parts of the calcified plaque. Only in the cross section reconstructed with MBIR are the boundaries correctly delineated by the software.
The percentage of corrected cross sections was lower for MBIR (24.1%) versus ASIR (32.4%, p = 0.0003) and FBP (36.6%, p < 0.0001) — but the differences were only marginal between ASIR and FBP, he said.
“We found that MBIR works much better than the conventional algorithms … significantly reducing the number of corrections needed compared to FBP and ASIR, whereas the difference between the two other algorithms was not significant,”Puchner said.
The use of MBIR significantly reduced the need for vessel wall boundary corrections compared with other reconstruction algorithms, particularly at the site of calcifications.
Automated segmentation is certainly faster than manual processing, Puchner said. Just on the three cases used in the study and in the analysis of the proximal 40 mm of each vessel, use of the software saved about three hours compared with what manual segmentation would have required. There is significant processing time required to create MBIR reconstructions, he acknowledged, but in those cases, it’s the technologists, not the physicians, who are spending the additional time, he said.
“The next step will be to look at it in an in vivo environment, to see this application in a beating heart,”Puchner told AuntMinnie.com. And to test other applications and other iterative reconstruction schemes, of course.
“I’m pretty sure that the other newer algorithms will have similar effects, because overall some studies have shown that the use of newer algorithms reduces blooming effects and other stuff that makes it difficult for the software to delineate it correctly,” he said. With manual segmentation, radiologists tend to overcorrect for older reconstruction algorithms and undercorrect for newer techniques, “but if the software does it, the software is much more dependent on image quality, and it makes a difference if it was reconstructed with the newer algorithms or the older algorithms.”
Automated plaque measurements will also have to be compared with assessments in other modalities such as intravascular ultrasound, and even to histology using the donor hearts, he said.
It is well known that taking a good history and physical, getting a non-ischemic EKG, and serial cardiac biomarkers, results in a risk of death/AMI of <5% in 30 days. Patients, in whom you still suspect have CAD, should undergo provocative testing within the next 72 hours based on the AHA/ACC guidelines. Their guidelines deem provocative testing as including:
Exercise treadmill stress test,
Myocardial perfusion scan,
Stress echocardiography, and/or
Coronary CT angiography (CCTA).
Myocardial perfusion scans and stress echos have a sensitivity of 85–90% and specificity of 75–80%. In contrast, CCTA’s have been shown to have a sensitivity of 93-97% and specificity of 80-90%.
Recently two landmark trials were published in NEJM discussing the use of CCTA in the emergency department.
ACRIN-PA Trial: Litt HI, et al. CT angiography for safe discharge of patients with possible acute coronary syndromes. N Engl J Med. 2012 Apr 12;366(15):1393-403. PMID: 22449295
What they did:
Non-inferiority study
5 Pennsylvania EDs
1,370 patients, Age > 30 years
Inclusion criteria: TIMI score of 0–2, EKG without ischemic changes, and negative first set of Cardiac Biomarkers
Randomized 2 patients to CCTA arm (908 patients) for every 1 patient to Standard Stress arm (462 patients)
Primary Outcome:
MI or Death from CAD at 30 days
Secondary Outcomes:
Rate of discharge from ED
Length of stay (LOS) in ED
Rate of detection of CAD
Resource utilization
What they found:
640/908 pts (70.5%) who underwent CCTA had coronary stenosis of <50% and none had MI or death due to CAD at 30 days
Discharge from ED 49.6% with CCTA vs 22.7% with standard stress arm
ED LOS 18 hr in CCTA arm vs 24.8 hr in standard stress arm
Conclusion: CCTA allows early discharge of low to intermediate risk patients presenting to the ED with possible ACS.
ROMICAT II Trial: Hoffmann U, et al; ROMICAT-II Investigators. Coronary CT angiography versus standard evaluation in acute chest pain. N Engl J Med. 2012 Jul 26;367(4):299-308.PMID: 22830462
What they did:
Randomized controlled trial
9 EDs in the US
1,000 patients with acute chest pain with ages 40–74 years
CCTA (501 patients) versus Standard Evaluation (499 patients)
Primary Outcome:
Hospital length of stay
Secondary Outcomes:
Cardiovascular events at 28 days
Rate of discharge from ED
Time to diagnosis
Cost
Utilization of resources
What they found:
Hospital LOS decreased by 7.6 hr in CCTA group
Rate of discharge from ED 47% in CCTA arm vs 12% in Standard Evaluation Arm
No difference in cardiovascular events at 28 days
Cost was similar between two groups $4,289 CCTA vs $4,060 in Standard arm
Conclusion: CCTA decreases length of stay without an increase in rate of cardiovascular events.
Some discussion points worth mentioning:
CCTA with 0 lesions is NEGATIVE: These patients can certainly be discharged home with primary care follow up with a nearly 100% NPV for ACS/AMI.
CCTA with <50% lesion is NOT NEGATIVE: This patient has CAD. It may not be clinically significant, but we can see plaques. 2/3 of AMIs occur from plaques that have <50% stenosis. Certainly we can start risk factor modification with beta blockers, ASA, and statins, but there are no studies looking at how this group of patients will do long term.
CCTAs are anatomic studies and not functional studies. Identified lesions will lead to more diagnostic tests, which is one of the big arguments against CCTA. CCTA identifies CAD more often than standard stress modalities, which leads to more heart catheterizations and PCIs.
As the number of CT slice increases, radiation dose decreases:
A 64 slice CT = 10 – 15 mSv of radiation
A 128 slice CT = 5 – 10 mSv of radiation
A 256 slice CT = 1 – 5 mSv of radiation
In contrast, a single-view CXR = 0.02 mSV of radiation
There is currently an ongoing National Heart, Lung, and Blood Institute-funded trial called the PROMISE (Prospective Multi-center Imaging Study for Evaluation of Chest Pain) Study with 10,000 patients. Patients with symptoms suggestive of CAD will be randomized to a CCTA vs usual care with a functional test. What’s interesting about this study is it is being performed in the offices of primary care physicians and cardiologists rather than EDs. The study authors hypothesize that medically optimizing patients identified, as having non-obstructive CAD will yield improved long-term outcomes.
It is well known that in low risk patients, doing a good H&P, having a negative EKG (no ischemic changes), and negative serial cardiac biomarkers gives us about 99% NPV & 99% sensitivity for ACS/AMI. This is even without additional testing, such as CCTAs.So are CCTAs worth the cost and potential harms in this low-risk group to add another 1% to the 99% NPV and 99% sensitivity rates? In my opinion, that answer is NO.
Goldstein JA. A Randomized Controlled Trial of Multi-Slice Coronary Computed Tomography for Evaluation of Acute Chest Pain. JACC 2007;49: 863 – 71. PMID: 17320744
Goldstein JA. The CT-STAT (Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment) Trial. JACC 2011 Sept; 58: 1414 – 22. PMID: 21939822
Hulten E. Outcomes After Coronary Computed Tomography Angiography in the Emergency Department: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials. JACC 2013 Feb; 61: 880 – 92. PMID: 23395069
Universal Testing for Lp(a): What Are We Waiting For?
Dennis R. Leahy, MD
February 01, 2023
Lp(a) was associated with atherosclerotic cardiovascular disease (ASCVD), but whether an elevated blood level was a biomarker or a causal factor proved difficult to determine.
Lp(a) comprises an apoB particle bonded to an apo(a) particle. Apo(a) is complex and has a number of isoforms that can result in large heterogenicity in apo(a) size between, as well as within, individuals. This contributes to controversy about the ideal assay and whether Lp(a) levels should be expressed as mass (mg/dL) or number of particles (nmols/L). This should not, however, deter universal testing.
Universal Lp(a) testing would spotlight this pervasive and important risk factor that was referred to as the “horrible” cholesterol in a recent review.
To date, trials of an antisense oligonucleotide and a small interfering RNA molecule targeting hepatic LPA messenger RNA have confirmed that plasma Lp(a) levels can be significantly and safely lowered. If the ongoing Lp(a) HORIZON and OCEAN(a) phase 3 trials have positive outcomes in patients with known ASCVD, this would spawn a host of clinical trials to explore the possibilities of these therapies in primary prevention as well. These will require tens of thousands of enrollees, and universal testing would expand the pool of potential participants.
Recent data from the United Kingdom suggest that attainment of specific LDL-C levels may offset the risk for vascular events in those with high Lp(a) levels.
People carrying this single nucleotide polymorphism (SNP) had a doubling of the risk of valve calcification on computer tomography (CT) compared with those without the variation. The same SNP has previously been identified as a risk factor for increased Lp(a) levels and coronary artery disease (CAD). Findings Could Reawaken Interest in Therapies Targeting Lp(a)
A Single Nucleotide Polymorphism is a change of a nucleotide at a single base-pair location on DNA. Created using Inkscape v0.45.1. (Photo credit: Wikipedia)
Advances in medicine, especially imaging technology have made the identification of small Acoustic Neuromas (AN) possible. After routine auditory tests reveal loss of hearing and speech discrimination (i.e. “I can hear sound in that ear, but can’t understand what’s being said”) a special test for hearing which records responses from the brain-stem called the auditory brainstem response test (ABR, BAER, BSER) maybe done. The results of this test detect the cause of a poorly functioning 8th nerve. If an abnormality in the ABR test suggests an AN, imaging is done to confirm the diagnosis. I do not perform the ABR test in all patients to diagnose an acoustic neuroma because imaging techniques (MRI/CT scans) are the gold standard for diagnosis. CT scan has proven to be a powerful tool in locating AN’s. The only drawback is that small tumors confined to the internal auditory canal (IAC) may not show on plain CT scan. Such cases require air or contrast materials to be introduced into the body in order to enhance the tumor. Therefore, the MRI, a more recently developed diagnostic test, has become the gold standard for diagnosis of AN. Gadolinium is the contrast material used to define & enhance the tumor.
Small tumorsA small tumor is also called intracanalicular because it is confined within the bony internal auditory canal (figure). A patient with such a tumor may have hearing loss, ringing in the ear or ear noise, and vertigo or dizziness.
Medium tumorsA medium sized acoustic neuroma is one that has extended from the bony canal into the brain cavity, but has not yet produced pressure on the brain itself (figure). Patients with such tumors have worsening of their hearing, difficulty in balance, in addition to dizziness, and occasionally, the onset of headaches due to irritation of the lining of the brain called dura. Some patients may experience numbness of the mid-face or diminished sensation in the eye during the later stages.
Large tumorsA large tumor is one that is extended out of the internal auditory canal in to the brain cavity and is sufficiently large to produce pressure on the brain and disturb vital centers in the brain (figure). During this stage, all previous symptoms worsen; facial twitch and weakness may occur, and finally patient may develop hydrocephalus due to the blockage of the cavity which contains CSF-the resultant symptoms are headache, visual loss and double vision.
Microscopy
The AN usually arises within the nerve trunk of the vestibular part of the 8th nerve. It gradually grows out of the nerve as it increases in size and assumes a peripheral position. The AN’s usually arise halfway along the length of the vestibular nerve, which corresponds to the transition zone of the nerve structure. The typical microscopic appearance of AN’s has two distinct features of arrangement of the cells-either tightly packed (Antoni A) or loosely packed (Antoni B) fibers. The distinction of these two cell types is of no clinical importance. Indeed, regions of Antoni A and B may coexist in the same tumor. As the tumor grows, it follows the direction of least resistance, usually towards the brain (cerebellopontine angle) and may reach considerable size. Thus, most tumors consist of 2 parts: a stalk or stem within the internal auditory canal (IAC) and another portion near the brain region. Microscopic investigations into the effect of AN’s on adjacent facial or 7th nerve have shown tumor involvement in some cases. This involvement may not be recognized by the surgeon during removal of the AN.
This picture shows the microscopic appearance of a normal vestibular (8th) nerve passing through the internal auditory canal (IAC) to supply the organ of balance. The facial (7th) nerve runs along with the 8th nerve in the IAC. The organ of hearing (cochlea) is also seen in this picture.
This picture shows an AN tumor arising from the 8th nerve, within the IAC.
This is a higher magnification of the above picture showing the junction of the tumor and the VII nerve. The arrows indicate the sheath (covering layer) of the tumor.
This picture is a high magnification of the same tumor showing the arrangement of the fibers within the AN. The arrow indicates a whorled appearance of the fibers while the upper part of the tumor shows loosely packed (Antoni B) fibers.
Origin and Cause
ACOUSTIC NEUROMA-THE BASIC FACTS
Origin and Cause
What is an acoustic neuroma?
An acoustic neuroma (sometimes also termed a neurinoma or vestibular schwannoma) is a benign or non-cancerous growth that arises from the 8th or vestibulo-cochlear nerve. The 8th nerve is actually 2 separate nerves, the vestibular nerve and the cochlear nerve. The vestibular nerve is responsible for balance while the cochlear nerve is responsible for hearing. The vestibular nerve has 2 parts-the superior vestibular nerve (SVN) and the inferior vestibular nerve (IVN).These nerves lie adjacent to each other as they pass through a bony canal, from the inner ear to the brainstem. This bony canal is called the internal auditory canal (IAC) and it varies in length from 0.4 to 1.2 cm. We have two figures of a temporal bone (that part of the skull which has the ear in it) dissection to the right.The first figure is a view from the top showing the middle ear and the internal auditory canal (IAC) with the nerves passing through it. The organ of hearing (cochlea) and the dura lining the IAC can be seen clearly.The second figure is a magnification of the IAC region showing the different nerves passing through it. This figure also demonstrates clearly, the cochlear nerve supplying the cochlea. Acoustic neuromas usually arise from the cells of the VIII nerve within the internal auditory canal (third figure).
The third figure is a schematic drawing showing an acoustic neuroma arising from the vestibular nerve within the IAC. The facial or 7th nerve that is responsible for facial movement, along with important blood vessels, also passes with the 8th nerve in the canal (figures).
The cause of acoustic neuroma is unknown. A small percentage of individuals have a hereditary condition called neurofibromatosis type 2 (NF-2). These patients may have an acoustic neuroma on both sides with an aggressive growth pattern and often involve adjacent nerves.
What is the growth pattern?
Acoustic neuromas usually grow very slowly over a period of many years. Once the tumor fully occupies the internal auditory canal, it often begins to erode the walls of the canal and enlarges it. This bony erosion however, does not always occur. They typically remain within their capsule or lining and displace the surrounding nerves and brain tissue very slowly. This is why the body has ample time to accommodate the abnormal growth. The tumor first distorts the 8th nerve, and then presses on the adjacent 7th nerve. The 7th nerve is gradually stretched into a ribbon like structure over the enlarging tumor (figure; cross section of the 7th nerve is shown in the right half of the figure). As the tumor slowly enlarges towards the brain, it protrudes from the internal auditory canal into an area of the skull called cerebello-pontine angle. The tumor is now pear or mushroom shaped with the smaller end within the canal and the larger part towards the brain (figure). It is at this stage that the tumor presses adjacent nerves like the trigeminal or 5th nerve responsible for facial sensation. Ultimately, with increasing tumor size, it can press on the brainstem which can be life threatening.
How often do acoustic neuromas occur?
Acoustic neuromas have been known to occur in all areas of the world without any predilection for individuals of any ethnic background. Small AN’s without any symptoms, have been found on autopsy in 2.5% of the general population. Estimates of symptomatic AN range from 1 in every 3,500 to 5 in every million people. It appears that women are more affected than men and most AN’s are diagnosed between the ages of 30 & 60 years.
Symptoms
Early symptoms of AN can occur in other conditions of the ear that can be easily overlooked. Early diagnosis of AN is quite challenging because there is no typical pattern. However, there are symptoms that act as indicators to the possibility if an AN. Patients with “inner ear” problems should be completely evaluated to rule out AN as a cause of these symptoms. It is possible that Meniere’s disease or hardening of the bone of the middle ear (otosclerosis) could be causing these symptoms. Patients with AN may present the following symptoms:
Hearing loss
Ringing in the ears (tinnitus)
Dizziness (vertigo)
Difficulty in balance (imbalance or dysequilibrium)
Fullness or pressure in the ears
Facial numbness or paralysis (for very large tumors)
HEARING LOSS
In over 90 percent of the patients with AN, the first symptom is a reduction in hearing in one ear due to involvement of the VIII nerve. This is usually accompanied by ringing in the ears or ear noise-also called “tinnitus”. The hearing loss is usually subtle and worsens very slowly over a period of time. In some cases, the hearing loss may be sudden. Some patients may experience a sense of fullness in the affected ear. Unfortunately, since hearing loss is often mild and there is no pain, patients tend to ignore the change in hearing and merely shift the phone to the opposite ear or make other compromises for the one-sided hearing loss rather than seek medical attention.
VERTIGO & IMBALANCE The tumor usually arises from the vestibular or balance nerve. As a result, unsteadiness or balance problems may be one of the earlier symptoms in the growth of the tumor. Since the remainder of the balance system compensates for this loss, balance problems may be forgotten after some time.
If the tumor grows larger in size it may start to press on other nerves, mainly the trigeminal nerve, causing facial sensation to become affected. Patients may then experience constant or intermittent numbness and facial tingling. Patients may also have facial tics or spasms. If the tumor grows larger and presses on the brainstem raised intracranial pressure may cause headaches, facial weakness, vertigo and an unsteady gait to ensue.
Treatment There are 3 treatment options available for AN
1) Observation
2) Microsurgical removal (partial or total)
3) Stereotactic radiation therapy (radiosurgery)
Observation AN are occasionally discovered incidentally while evaluating another problem or when the tumor is very small with subtle symptoms. Since AN are benign tumors and produce symptoms due to pressure on surrounding structures, careful observation over a period of time may be appropriate for some patients. For instance, a small tumor diagnosed in an elderly patient may only require observation to study the growth rate of the tumor if acute symptoms are not present. If it appears that the tumor will not need to be treated during the patient’s normal life expectancy, treatment and its potential risks and complications maybe avoided. In these patients, MRI is performed periodically to monitor growth of the tumor. If there is no growth, observation is continued. On the other hand, if the tumor shows increase in size, treatment may become necessary. Another group of patients for whom observation is preferred is in patients who have a tumor in their only or better hearing ear, particularly if it is a size where hearing preservation is unlikely. In such cases, periodic MRI is done to monitor growth and surgery is considered only if the hearing is lost or the tumor size becomes life threatening.
Microsurgical removal At the present time, the only treatment that can cure the patient is removal of the tumor by surgery. Within the last 2 decades, microsurgical techniques have been pioneered and refined. Use of the operating microscope, finely scaled surgical instruments, alternate cutting & tumor reducing tools, and better anesthesia, have reduced the death rate extremely. In addition, results have improved as surgeons have gained experience in the delicate removal process of the tumor.
Three main surgical approaches are used depending upon the location, tumor size and hearing level of the patient. They are- middle fossa (MF), sub-occipital (SO), and the trans-labyrinthine (TL) approach. Surgery for AN’s is done under general anesthesia using an operating microscope. Postoperatively, one to several days may be spent in the intensive care with careful monitoring. Problems that may develop in the immediate postoperative period including headache, dizziness, imbalance, vomiting and decreased mental alertness due to the development of a blood clot causing obstruction to the flow of cerebrospinal fluid (CSF).
Other early complications may include cerebrospinal fluid leak and meningitis, an infection controlled with antibiotics that will require a longer hospitalization. Some patients and their surgeons prefer incomplete removal of an AN in order to reduce the risk of complications, realizing that further surgery maybe needed in the future. Occasionally in cases with large tumors, disturbances in the vital brain centers during surgery require ending the surgery prior to complete tumor removal. In these cases, the tumor which was left behind is followed with MRI scans and if tumor growth is demonstrated, further surgery maybe necessary to remove the growing tumor. On the other hand, if the tumor shows no growth, observation is continued. Partial tumor removal maybe also be required in a patient with an only hearing ear such as a Neurofibromatosis-2 (NF 2) patient. Unfortunately, partial removal may result in substantial hearing loss in these patients and this risk must be considered.
Small tumor
If the hearing is still preserved in such tumors, a middle fossa approach, incision for which is in front of the ear (figure) may be considered. A small square piece of bone from the side of the skull is then removed (blue shaded area in the figure). The tumor is removed completely in most cases. On rare occasions, partial removal is possible. This approach attempts to preserve the hearing in all cases while removing the tumor. In about half of the patients, the tumor involves the hearing nerve or the artery supplying the inner ear and in such cases, total loss of hearing occurs in the operated ear. In addition, the risk to the facial nerve is far greater in this approach/
Medium tumor
The operation for medium sized tumors is performed by the sub-occipital and/or the trans-labyrinthine approach. The incision for these approaches is behind the ear, overlying the mastoid, the bony projection felt behind the ear (figures). The mastoid and the inner ear structures are removed to expose the tumor, and remove it completely. The opening created in the mastoid bone is closed with fat taken from the abdomen. The translabyrinthine approach sacrifices the hearing and balance mechanism since the inner ear is entered. Consequently, the ear is made permanently deaf. In such cases, the balance mechanism of the opposite ear compensates for the non-functioning operated ear and provides stabilization for the patient within few weeks to months.
Large tumor
Surgery for large tumors requires extensive removal of bone to properly expose the tumor and control the large blood vessels that make access to the tumor difficult. For this reason, special studies of the arteries (arteriograms) may be required in addition to the other investigations, in order to diagnose and establish the size of the acoustic tumor. The operation for large tumors is performed by the TL-SO approach as described for medium tumors. The figure to the right shows the area of the skull approached via the TL and the SO approaches. In these patients, total removal is attempted unless changes in vital signs occur. If there are changes in blood pressure, pulse rate, or respiratory rate, the surgery must be terminated even if the tumor has not been totally removed. The opening in the mastoid is closed with abdominal fat. For large tumors, it is often necessary to monitor the patient’s general status by inserting a small tube (arterial line) into an artery in the arm or leg. In these cases, occasionally a blood clot may form in the artery following surgery. In case this complication occurs, further surgery maybe required to remove the blood clot. A very rare complication of this arterial line monitoring is the loss of a finger, toe, or even a hand or a foot.
Stereotactic Radiation Therapy (Radiosurgery): This is a technique based on the principle that a single relatively high dose of radiation delivered precisely to a small area will arrest or kill the tumor while minimizing injury to the surrounding nerves & brain tissue. The source of radiation is from either radioactive cobalt (called gamma ray) or a linear accelerator (LINAC). The treatment team consists of a neurosurgeon, radiophysicist and a radiation oncologist working together to develop a treatment plan based on the size & shape of the tumor. Radiation, even at relatively high doses such as those used in radiosurgery, does not kill or injure cells immediately. Some tumor cells die in weeks while others die more gradually over 6-18 months after radiation. This treatment usually arrests growth of the tumor and some tumors shrink, but they rarely disappear.
Follow-up of these patients is important because approximately 20% of tumors continue to grow after radiosurgery or at some time in the future. A tumor that has been irradiated and grows may be more difficult to remove than an un-radiated tumor. Symptoms such as dizziness & disturbances in balance typically improve earlier after microsurgical tumor removal than after radiosurgery. This is because effects of radiosurgery may require up to 18 months. Residual dizziness & imbalance may be less after microsurgical treatment. The side effects of radiosurgery may be headache, dizziness, nausea, facial numbness, or rarely, cranial nerve paralysis. In the long term requires follow-up MRI’s over the years and there is a potential for additional treatment in cases of continued growth or later re-growth.
Microsurgery requires follow-up MRI’s suggested at perhaps 1 and 5 years if the tumor has been completely removed. Radiosurgery may be considered in selected patients in whom the risk of surgery is excessive because of advanced age or pre-existing health problems, patients having small to moderate sized tumors or patients with tumors on both sides, or in the only hearing ear.
Postoperative
Microsurgery of an AN is a complex and delicate procedure. The smaller the tumor at the time of surgery, the fewer the chances are for complications. As the tumor size increases, the chances of complications become greater. Thus, there may be problems with the cranial nerves affected by the tumor (like facial paralysis or hearing loss) following surgery that may or may not have been present before tumor removal. Here is a list of some of the more common post-operative issues and problems encountered.
Residual problems
This period is the days or perhaps weeks following surgery. There is a possibility of fatigue or tiredness and increased drowsiness, although some patients may experience “survival euphoria” and a renewed sense of energy and vigor. A period of emotional lows is common as the patient adjusts to physical changes. One symptom that may occur after discharge is a nasal drip of clear colorless fluid, which is particularly noticeable when bending over. This may indicate a cerebrospinal fluid leak and should be reported to the surgeon right away due to the risk of infection.
Follow-up period :After being discharged from the hospital, patients operated for an AN are followed up regularly (every 2-3 months for the first year, every 6 months for the 2nd year, and every year thereafter). These follow up visits are important to monitor the hearing (in patients operated by the MF or SO approach), facial nerve paralysis if any and for recurrence of tumor.
HEARING LOSS With small tumors, it may be possible to save hearing. In larger tumors, especially those that have extended into the brain cavity, the hearing has usually been partially or totally lost and cannot be restored. This loss means the patient will continue having problems locating sound, hearing on the deaf side and understanding speech over high background noise. Consultation with an audiologist is required for these patients for amplification options like traditional hearing aids or a CROS hearing aid (a device which crosses sound over from the operated ear to the opposite ear) or a BAHA.
TINNITUS Ear noises usually remain the same as before surgery, though in a few cases noises may increase or begin after surgery. A masking device may help some people affected by tinnitus.
FACIAL WEAKNESS OR PARALYSIS Since the facial nerve which controls muscles of facial expression is in close proximity with the AN, it is usually necessary to manipulate and at times remove the portion of the nerve. In some cases however, even though the nerve is intact after surgery, nerve damage or swelling may cause temporary or in some cases permanent facial paralysis. Regrowth of the nerve is a slow process that may take up to a year for recovery to be noticeable. If recovery is not observed by 1 year, a second operation may be required to connect the healthy portion of the facial nerve to a nerve in the neck usually the one supplying one side of the tongue. This procedure is called the hypoglossal-facial nerve anastamosis and can restore some but not all facial movement. Spontaneous movements like laughing are asymmetric. There may be loss of tongue function. There are some other procedures that adapt available muscles and nerves to help in toning or reanimating the sagging face. If it becomes necessary to remove a portion of the facial nerve during surgery, the facial nerve may be reconnected directly or by inserting a nerve graft. Usually, the result is asymmetric but will provide some spontaneous movement.
EYE PROBLEMS
Studies have shown that at least half of those who have had an acoustic neuroma removed develop long term eye discomfort and other eye problems, particularly if the tumor was medium or large. Loss of eyelid function and/or altered tear production can cause irritation and scratchiness in the eye because it is dry & unprotected. To deal with this problem, there are various surgical procedures that can be done to protect the cornea. They include canthoplasty (bringing together tendons in either or both corners of the eye), a spring implantation in the upper lid, an elastic prosthesis secured around the upper and lower lids, a gold weight implant in the upper lid; and a tarsorapphy (sewing the lids together). Artificial tears or eye lubricants maybe needed for a short time or permanently. Taping part of the lids together, using protective glasses and moisture chamber, using bandage contact lenses and avoiding eye irritants may be helpful. In a few patients, double vision may be present due to pressure on the 6th cranial nerve that controls the muscles that move the eyes.
TASTE DISTURBANCE AND MOUTH DRYNESS OR EXCESSIVE SALIVATION There maybe some changes in taste and amount of saliva secretion for a short time following surgery. In some cases this may be prolonged. In the others, increased salivation occurs while chewing or there maybe increased tearing while eating. The appetite maybe affected for some time.
SWALLOWING, THROAT AND VOICE PROBLEMS In a small number of patients, AN surgery affects the nerves which control the throat, swallowing and voice production leading to hoarseness & difficulty in swallowing. These symptoms usually improve slowly over time.
BALANCE PROBLEMS The vestibular portion of the VIII nerve is almost always removed during surgery. Usually this part of the nerve is non-functional and has already been destroyed because of the AN. Dizziness is common following surgery and maybe severe for a time. After a while, the balance apparatus of the opposite or normal ear compensates for this loss, and balance improves. This compensation may not be perfect, particularly in darkness, when the patient is fatigued, when there is a sudden change in body position, or while walking on uneven surfaces. Maintaining a good general physical health through proper diet and moderate exercise, can improve balance & general vitality to a great extent.
FATIGUE Fatigue sometimes remains a prolonged problem for some patients after some of the other symptoms have subsided. It is important in such patients to adjust their pace of life in harmony with their energy level.
HEADACHE
Headaches can be a problem for some patients while still in the hospital. This maybe related to tension from holding the head rigidly, changes in intracranial pressure, muscle spasm, or anxiety. Headaches are almost never related to tumor recurrence. Treatment is with analgesics & muscle relaxation. If severe headaches persist after hospital discharge, medical help should be sought.
DENTAL CARE If the patient has facial paralysis, food tends to get lost in the mouth on the affected side and can lead to dental problems. Washing and rinsing the mouth is therefore necessary, as well as brushing & flossing the teeth several times a day is important.
PROTECTING THE OTHER EAR It is important to provide sensible protection to the opposite or good ear that has the remaining hearing apparatus. This is done by avoiding extreme or sudden exposure to loud noises like firearms or some cordless phones near the good ear. Some physicians suggest follow-up MRI scans and/or audiograms for some time following AN removal.
PSYCHOLOGICAL COPING For some patients, adjustment to a new self after AN removal can be a challenging task. This is because in addition to changes in hearing, the appearance may now be altered along with the presence of other impairments. Return to normal activity may be slow. Concentrating on strengths rather than on weaknesses will help such patients to return to all former activities and also expand their abilities in new areas.
Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA. damien.weber@psi.ch
Abstract
OBJECTIVE:
We sought to determine the tumor control rate and cranial nerve function outcomes in patients with vestibular schwannomas who were treated with proton beam stereotactic radiosurgery.
METHODS:
Between November 1992 and August 2000, 88 patients with vestibular schwannomas were treated at the Harvard Cyclotron Laboratory with proton beam stereotactic radiosurgery in which two to four convergent fixed beams of 160-MeV protons were applied. The median transverse diameter was 16 mm (range, 2.5-35 mm), and the median tumor volume was 1.4 cm(3) (range, 0.1-15.9 cm(3)). Surgical resection had been performed previously in 15 patients (17%). Facial nerve function (House-Brackmann Grade 1) and trigeminal nerve function were normal in 79 patients (89.8%). Eight patients (9%) had good or excellent hearing (Gardner-Robertson [GR] Grade 1), and 13 patients (15%) had serviceable hearing (GR Grade 2). A median dose of 12 cobalt Gray equivalents (range, 10-18 cobalt Gray equivalents) was prescribed to the 70 to 108% isodose lines (median, 70%). The median follow-up period was 38.7 months (range, 12-102.6 mo).
RESULTS:
The actuarial 2- and 5-year tumor control rates were 95.3% (95% confidence interval [CI], 90.9-99.9%) and 93.6% (95% CI, 88.3-99.3%). Salvage radiosurgery was performed in one patient 32.5 months after treatment, and a craniotomy was required 19.1 months after treatment in another patient with hemorrhage in the vicinity of a stable tumor. Three patients (3.4%) underwent shunting for hydrocephalus, and a subsequent partial resection was performed in one of these patients. The actuarial 5-year cumulative radiological reduction rate was 94.7% (95% CI, 81.2-98.3%). Of the 21 patients (24%) with functional hearing (GR Grade 1 or 2), 7 (33.3%) retained serviceable hearing ability (GR Grade 2). Actuarial 5-year normal facial and trigeminal nerve function preservation rates were 91.1% (95% CI, 85-97.6%) and 89.4% (95% CI, 82-96.7%). Univariate analysis revealed that prescribed dose (P = 0.005), maximum dose (P = 0.006), and the inhomogeneity coefficient (P = 0.03) were associated with a significant risk of long-term facial neuropathy. No other cranial nerve deficits or cancer relapses were observed.
CONCLUSION:
Proton beam stereotactic radiosurgery has been shown to be an effective means of tumor control. A high radiological response rate was observed. Excellent facial and trigeminal nerve function preservation rates were achieved. A reduced prescribed dose is associated with a significant decrease in facial neuropathy.
The Proton Beam Unit was founded in 1962 and has the largest experience with stereotactic radiosurgery of any center in the United States. Information regarding non-invasive proton beam radiosurgery and fractionated radiosurgery for brain and spinal tumors and arteriovenous malformations.The Purpose of this Center is to provide a complete range of services for the diagnosis, and treatment with non-invasive proton beam radiosurgery and fractionated radiosurgery for brain and spinal tumors and arteriovenous malformations. Patients may be referred for consultation only, care in partnership with referring physician, or complete management.
Bragg Peak Proton Beam Radiosurgery Unit – The Proton Beam Unit was founded in 1962 and has the largest experience with stereotactic radiosurgery of any center in the United States. Proton beam offers certain theoretical advantages over other modalities of stereotactic radiosurgery (i.e. gamma knife and linear accelerators) because it makes use of the quantum wave properties of protons to reduces doses to surrounding tissue beyond the target to a theoretical minimum of zero. In practice, the proton facility offers advantages for the treatment of unusually shaped brain tumors and arteriovenous malformations. The homogeneous doses delivered also makes fractionated therapy possible. Proton beam radiosurgery also has the ability to treat tumors outside of the cranial cavity. These properties make it the ideal post-resection therapy for many chordomas and certain chondrosarcomas of the spine and skull base as well as an excellent mode of therapy for many other types of tumors.
NPTC: Information, proton radiosurgery treatments and support services have been transfered to the new The Northeast Proton Therapy Center (NPTC). Located on the main hospital campus of the Massachusetts General Hospital (MGH), the NPTC represents the forefront of technological advancement in radiation therapy. The construction of the facility was jointly funded by the hospital and the National Cancer Institute to meet the increasing medical demand for high precision radiation therapy provided by proton therapy. The program builds on more than forty years of pioneering work and experience gained by the physicians, physicists, and clinical support personnel at Harvard University’s Cyclotron Laboratory where more than nine thousand patients were treated with proton therapy from 1961 to it’s closing in 2002.
Rabinov JD, Brisman JL, Cole AJ, Lee PL, Bussiere MR, Chapman PH, Loeffler JS, Cosgrove GR, Chaves T, Gonzalez RG.: MRI changes in the rat hippocampus following proton radiosurgery. Stereotact Funct Neurosurg. 2004;82(4):156-64.
Brisman JL, Cole AJ, Cosgrove GR, Thornton AF, Rabinov J, Bussiere M, Bradley-Moore M, Hedley-Whyte T, Chapman PH.: Radiosurgery of the rat hippocampus: magnetic resonance imaging, neurophysiological, histological, and behavioral studies. Neurosurgery. 2003 Oct;53(4):951-61; discussion 961-2.
Weber DC, Chan AW, Bussiere MR, Harsh GR 4th, Ancukiewicz M, Barker FG 2nd, Thornton AT, Martuza RL, Nadol JB Jr, Chapman PH, Loeffler JS.: Proton beam radiosurgery for vestibular schwannoma: tumor control and cranial nerve toxicity. Neurosurgery. 2003 Sep;53(3):577-86; discussion 586-8.
Barker FG 2nd, Butler WE, Lyons S, Cascio E, Ogilvy CS, Loeffler JS, Chapman PH.: Dose-volume prediction of radiation-related complications after proton beam radiosurgery for cerebral arteriovenous malformations. J Neurosurg. 2003 Aug;99(2):254-63.
Harsh GR, Thornton AF, Chapman PH, Bussiere MR, Rabinov JD, Loeffler JS.: Proton beam stereotactic radiosurgery of vestibular schwannomas. Int J Radiat Oncol Biol Phys. 2002 Sep 1;54(1):35-44.
Barker FG 2nd, Amin-Hanjani S, Butler WE, Lyons S, Ojemann RG, Chapman PH, Ogilvy CS.: Temporal clustering of hemorrhages from untreated cavernous malformations of the central nervous system. Neurosurgery. 2001 Jul;49(1):15-24; discussion 24-5.
Chapman PH, Tarbell: Proton beam therapy. In: Pediatric Neurosurgery. Surgery of the Developing Nervous System, 4th ed. Ed: McLone DG: WB Saunders: Philadelphia, pp. 1255-1262, 2001.
Loeffler JS, Singer RJ, Chapman PH, Ogilvy CS: Proton-beam radiation therapy. In: LINAC and Gamma Knife Radiosurgery. Ed: Germano IM. The American Association of Neurological Surgeons: Park Ridge, IL, pp. 71-74, 2000.
Harsh G, Loeffler JS, Thornton A, Smith A, Bussiere M, Chapman PH: Stereotactic Proton Radiosurgery. Neurosurg Clin N Am 1999; 10:243-256.
Tatter SB, Butler WE, Chapman PH. Technical and clinical aspects of proton-beam stereotactic radiosurgery. In: Textbook of Stereotactic and functional Neurosurgery. Eds: Gildenberg PL, Tasker RR. McGraw-Hill, New York pp. 705-710, 1998.
Serago CF, Thornton AF, Urie MM, Chapman P, Verhey L, Rosenthal SJ, Gall KP, Niemierko A: Comparison of proton and x-ray conformal dose distributions for radiosurgery applications. Med Phys 22:2111-16, 1995.
Butler WE, Ogilvy CS, Chapman PH, Verhy L , Zervas NT. “Stereotactic alignment for Bragg peak radiosurgery.” In Radiosurgery: Baseline and Trends, ed. L. Steiner. 85-91. New York: Raven Press, 1992.
Chapman PH, Ogilvy CS , Butler WE. “A new stereotactic alignment system for charged-particle radiosurgery at the Harvard Cyclotron Laboratory, Boston.” In Stereotactic Radiosurgery, ed. Eben Alexander III, Jay S. Loeffler, and L. Dade Lunsford. 105-108. New York: McGraw-Hill, 1993.
De Salles AA, Asfora WT, Abe M, Kjellberg RN: Transposition of target information from the magnetic resonance and computed tomography scan images to conventional X-ray stereotactic space. Applied Neurophysiology 50: 23-32, 1987.
Gall KP, Verhey LJ, Wagner M: Computer-assisted positioning of radiotherapy patients using implanted radiopaque fiducials. Medical Physics 20: 1153-9, 1993.
Kjellberg RN, Hanamura T, Davis KR, Lyons SL , Adams RD: Bragg-peak proton-beam therapy for arteriovenous malformations of the brain. New England Journal of Medicine 309: 269-74, 1983.
Kjellberg RN, Shintani A, Frantz AG, Kliman B: Proton-beam therapy in acromegaly. New England Journal of Medicine 278: 689-95, 1968.
Urie MM, Fullerton B, Tatsuzaki H, Birnbaum S, Suit HD, Convery K, Skates , Goitein M: A dose response analysis of injury to cranial nerves and/or nuclei following proton beam radiation therapy. International Journal of Radiation Oncology, Biology, Physics 23: 27-39, 1992.
Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA. murphye3@ccf.org
Abstract
Vestibular schwannomas are slow-growing tumors of the myelin-forming cells that cover cranial nerve VIII. The treatment options for patients with vestibular schwannoma include active observation, surgical management, and radiotherapy. However, the optimal treatment choice remains controversial. We have reviewed the available data and summarized the radiotherapeutic options, including single-session stereotactic radiosurgery, fractionated conventional radiotherapy, fractionated stereotactic radiotherapy, and proton beam therapy. The comparisons of the various radiotherapy modalities have been based on single-institution experiences, which have shown excellent tumor control rates of 91-100%. Both stereotactic radiosurgery and fractionated stereotactic radiotherapy have successfully improved cranial nerve V and VII preservation to >95%. The mixed data regarding the ideal hearing preservation therapy, inherent biases in patient selection, and differences in outcome analysis have made the comparison across radiotherapeutic modalities difficult. Early experience using proton therapy for vestibular schwannoma treatment demonstrated local control rates of 84-100% but disappointing hearing preservation rates of 33-42%. Efforts to improve radiotherapy delivery will focus on refined dosimetry with the goal of reducing the dose to the critical structures. As future randomized trials are unlikely, we suggest regimented pre- and post-treatment assessments, including validated evaluations of cranial nerves V, VII, and VIII, and quality of life assessments with long-term prospective follow-up. The results from such trials will enhance the understanding of therapy outcomes and improve our ability to inform patients.
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