March 15th, 2013
How Good Is Your Eye for Coronary Angiography?
Brahmajee Kartik Nallamothu, MD, MPH and John Ryan, MD
John Ryan interviews Brahmajee Nallamothu, lead author of a new study published in Circulation, comparing the accuracy of visually interpreted coronary angiography with that of quantitative coronary angiography (QCA). Nallamothu discusses the study’s implications for clinical practice.
THE STUDY
Researchers randomly selected 175 patients undergoing PCI at one of seven hospitals in 2011. Percent diameter stenosis as interpreted by visual assessment was compared with percent diameter stenosis determined by QCA. Of 216 lesions, 213 (98.6%) were interpreted to have ≥70% stenosis by visual assessment. QCA identified 56 of those 213 lesions (26.3%) as having <70% stenosis. Mean percent diameter stenosis was 8.2% higher when assessed clinically than when measured by by QCA.
THE AUTHOR RESPONDS
Ryan: Of the lesions deemed to be ≥70% by clinical assessment, more than a quarter were found to be <70% by QCA. This seems like a large number. Did it surprise you?
Nallamothu: It did surprise me a bit, but I’m not exactly sure what we should have expected. Part of the reason this study was so exciting to do was that no one had really looked broadly at this question in several years. However, it is important to emphasize that although we saw this difference, it is unclear how it would have changed a clinical decision or outcome. That remains to be seen.
Ryan: On average, clinical interpretation was 8.2% higher than the lesions’ percent stenosis on QCA. How representative of U.S. cardiology practices do you think these findings are?
Nallamothu: I am not sure. These hospitals were pretty special. The very fact that they were engaged and interested in exploring this aspect of quality separates them from most institutions in my mind. They all had great leadership in their cath labs, so we were able to work with closely with the people there.
Ryan: No lesion was calculated to be <50% on QCA. With all the newspaper reports of cardiologists performing inappropriate interventions, did this surprise you? It certainly seems reassuring.
Nallamothu: It didn’t surprise me, but it should reassure others. I understand the concerns that have been raised, but I strongly believe that these reports are the rare exception and do not reflect the practices of the vast majority of interventional cardiologists who are trying to do their best for their patients each day.
Ryan: Most of the reported values on clinical interpretation were divisible by 10 (i.e., 60%, 70%, 80%, etc.), whereas QCA gives a more precise number. Should cardiac catheterization labs switch to QCA for all their angiograms to avoid this rounding? How would such a change affect outcomes, if at all?
Nallamothu: I’m not sure if turning an interventional cardiologist into a “human QCA machine” (this is Dave Cohen’s expression) is necessarily the answer. I think the real opportunity is to understand why and when discrepancies may occur that would change clinical decision making and outcomes. For example, we have thought about how best to give feedback to hospitals about cases of substantial discrepancy between the clinical interpretation and QCA. In those instances, the hospital and operators could review the case more fully. It might turn out that the clinical decision was completely appropriate and in the patient’s best interest. It also may be that additional studies could have been of value – perhaps fractional flow reserve or stress testing – before deciding to perform PCI. Those are the next steps that we have to consider carefully. Finally, this issue isn’t just important for interventional cardiologists. The reliability of diagnostic-test interpretation also matters in other areas of cardiology, such as echocardiography and nuclear medicine, as well as internal medicine more generally.
March 14th, 2013
Fibrinolysis Now or Primary PCI Later?
Frans Van de Werf, MD,PhD, Richard A. Lange, MD, MBA and L. David Hillis, MD
CardioExchange’s Rick Lange and David Hillis ask Frans Van de Werf, principal investigator for the STREAM study, about his study group’s findings and their implications for clinical practice.
THE STUDY
In the STREAM trial, investigators compared two treatment strategies in STEMI patients presenting early after symptom onset who were unable to undergo primary PCI within 1 hour: (1) prompt fibrinolysis (in a prehospital setting or the emergency room of a community hospital without PCI capability), followed by timely catheterization and appropriate rescue coronary intervention; and (2) transport for primary PCI.
The primary endpoint — a composite of death, shock, congestive HF, and reinfarction within 30 days – occurred in 12.4% of the fibrinolysis group versus 14.3% of the primary-PCI group (relative risk, 0.86; P=0.21. Intracranial hemorrhage was more common with fibrinolysis than with primary PCI (1% vs. 0.2%, P=0.05), especially in the elderly. After the protocol-defined tenecteplase dose was cut in half for patients older than 75, the rate of intracranial hemorrhage was not significantly higher in the fibrinolysis group than in the primary-PCI group (0.5% and 0.3%, P=0.45).
VAN DE WERF RESPONDS
Lange and Hillis: How does this trial differ from other trials of fibrinolysis versus primary PCI (e.g., DANAMI-2, CAPTIM,
Van de Werf: The inclusion of patients presenting much earlier after onset of symptoms and the much earlier start of lytic therapy compared with the invasive procedure are important differences from DANAMI-2. Our population, even after dose reduction of tenecteplase (n=1503), was also much larger than the referral population of DANAMI-2. Other important features of our trial as compared with the other trials are more–up-to-date antithrombotic co-therapy and the requirement of catheterization between 6 and 24 hours after randomization in patients with evidence of reperfusion after lytic therapy.
Lange and Hillis: With comparable efficacy in the two treatment arms but more intracerebral bleeding in the thrombolysis arm, is a recommendation for fibrinolysis difficult to defend?
Van de Werf: It all depends on how much ischemic myocardium you may be able to salvage by earlier reperfusion with a lytic, and thus on the system delay to primary PCI.
By the way, after the protocol amendment, there were more fatal strokes in the primary-PCI arm than in the fibrinolysis arm (4 vs. 3)!
Lange and Hillis: What about patients who present with symptoms more than 3 hours after symptom onset, or those who can undergo primary PCI within the 2-hour period recommended by the European and North American guidelines?
Van de Werf: In our study, we included only patients presenting within 3 hours and unable to undergo prompt primary PCI. I would assume that the benefit of earlier reperfusion in a patient presenting after 3 hours is much smaller. I don’t think these patients should get lytic therapy before transport, unless the ECG suggests that the occlusion occurred more recently than the onset of symptoms did. It is sometimes difficult to pinpoint the onset of a STEMI exactly.
Lange and Hillis: If you had an acute MI, and your local hospital didn’t have primary PCI capability, would you want prehospital fibrinolysis or transportation to a remote facility that is PCI-capable?
Van de Werf: It depends on how much time it would take to get the PCI, and who would do the procedure!
March 13th, 2013
FDA Officials Calm Concerns Over Excessive Bleeding with Dabigatran
Larry Husten, PHD
Concerns over excessive bleeding complications with dabigatran (Pradaxa, Boehringer Ingelheim) as compared with warfarin are most likely due to the heightened sensitivity and vigilance that can accompany a new drug, according to FDA officials in a perspective published online in the New England Journal of Medicine.
“We believe that the large number of reported cases of bleeding associated with dabigatran provides a salient example of stimulated reporting,” write Mary Ross Southworth, Marsha Reichman, and Ellis Unger. “In this case, such reporting provided a distorted estimate of the comparative bleeding rates associated with dabigatran and warfarin in clinical practice.”
Although the pivotal RE-LY trial found no significant difference in bleeding risk between dabigatran and warfarin, postmarketing reports received through the FDA Adverse Event Reporting System (FAERS) raised the possibility that dabigatran may not have been as safe in clinical practice as it had been in clinical trials.
One theory investigated by the FDA is that dabigatran may have been used differently or in different patient populations than had been studied in RE-LY and as indicated by the FDA. However, an FDA review of the FAERS reports found “no indication that dabigatran was not being used in accordance with its labeled directions.”
The FDA then used insurance and administrative data from the FDA Mini-Sentinel database to quantify the relationship between bleeding complications and new use of dabigatran and warfarin. The review found no greater risk for bleeding associated with dabigatran than with warfarin. The authors say that the FDA is conducting additional assessments to examine the issue.
They write that postmarketing surveillance of dabigatran will continue, though their current perspective is upbeat: “We believe that dabigatran provides an important health benefit when used as directed.”
March 13th, 2013
Radiotherapy for Breast Cancer Increases Heart Disease Risk
Larry Husten, PHD
A new study published in the New England Journal of Medicine offers the best look yet at the increased risk for heart disease produced by radiotherapy for breast cancer. Further, this increased risk may just be the tip of the iceberg of more radiation-related problems, warns a cardio-oncologist in an accompanying editorial.
The new study, based on data from Sweden and Denmark of women treated with radiotherapy for invasive breast cancer, found a linear increase in the rate of heart disease associated with the dose of radiation received by the heart. Starting 5 years after radiotherapy, and with no sign of a threshold, the risk for major coronary events increased by 7.4% per gray. The mean dose of radiation was 4 Gy. Although the relative risk was consistent throughout the study, the increase in absolute risk was greatest in women with cardiac risk factors or established heart disease.
Findings from the study, according to the authors, “make it possible to estimate” a patient’s risk for heart disease related to radiation. “This absolute risk can be weighed against the probable absolute reduction in her risk of recurrence or death from breast cancer that would be achieved with radiotherapy.” The authors estimated that for a 50-year-old woman without preexisting risk factors and with a mean radiation exposure of 3 Gy, her risk for death from ischemic heart disease by age 80 would rise from 1.9% to 2.4% and her risk for an acute coronary event would rise from 4.5% to 5.4%. The risk for death by age 80 for an otherwise similar woman with existing risk factors would rise from 3.4% to 4.1%. Women exposed to larger doses of radiation would be exposed to even greater risks.
In the accompanying editorial, Javid Moslehi writes that results of the study suggest that “cardiac risk factors should be assessed and aggressively managed — starting at the time of radiation treatment (or even before) and continuing throughout survivorship.” To make matters worse, the findings “may represent just the tip of the iceberg.” Radiation may also cause increases in pericardial disease, peripheral vascular disease, cardiomyopathy, valvular dysfunction, and arrhythmias, according to Moslehi, and other breast cancer therapies, such as anthracyclines and hormonal therapies, may have “additional cardiotoxic effects.”
Moslehi, who is in the Cardio-Oncology Program at the Dana–Farber Cancer Institute, writes about the emerging new discipline of “cardio-oncology”:
Given the widespread use of radiation therapy in the treatment of breast cancer, and the continually expanding arsenal of novel therapies, the current study calls for greater collaboration between oncologists and cardiologists. An important lesson for the oncologist may be that the time to address concerns about cardiovascular “survivorship” is at the time of cancer diagnosis and before treatment rather than after completion of therapy. Similarly, cardiologists need to assess prior exposure to radiation therapy as a significant cardiovascular risk factor in survivors of breast cancer.
March 12th, 2013
Azithromycin: FDA Issues Cardiac Warning
The antibiotic azithromycin (Zithromax and Zmax) can cause QT interval prolongation and torsades de pointes, the FDA warned on Tuesday.
The agency says that healthcare providers should consider risk for fatal heart rhythms when treating patients already at high cardiovascular risk, including people with known prolongation of the QT interval, torsades de pointes, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure; patients taking drugs that prolong the QT interval; and patients with proarrhythmic conditions (e.g., uncorrected hypokalemia). Older patients and patients with cardiac disease may also be at higher risk.
The warning follows a New England Journal of Medicine study last year that found a higher rate of cardiovascular and all-cause mortality in patients who took 5 days of azithromycin, compared with other antibiotics. (Three experts share their perspective on the NEJM study with CardioExchange
Reprinted with permission from Physician’s First Watch
March 12th, 2013
Sildenafil Does Not Improve Exercise Capacity in HF with Preserved Ejection Fraction
Nicholas Downing, MD
Sildenafil does not improve exercise capacity or clinical status in patients with symptomatic heart failure (HF) and preserved ejection fraction, according to a JAMA study. This finding contrasts with previous research suggesting a potential benefit in such patients.
Some 220 HF patients with ejection fractions of 50% or greater were randomized to receive oral sildenafil or placebo for 24 weeks. Most were already taking diuretics, renin-angiotensin system antagonists, beta-blockers, and statins.
At the end of treatment, there were no significant differences between the groups in peak oxygen consumption, 6-minute walk distance, or a clinical status score based, in part, on time to death or hospitalization.
March 12th, 2013
Too Long, Too Short, or Just Right?
Tariq Ahmad, MD, MPH
Several Cardiology Fellows who are attending ACC.13 in San Francisco this week are blogging for CardioExchange. The Fellows include Tariq Ahmad, Megan Coylewright, Jeremiah Depta, Kumar Dharmarajan, Payal Kohli, and Sandeep Mangalmurti. View the previous post
ACC 2013 was only 3 days. AHA 2012, in comparison, was 5 days.
I figured that since this meeting was far shorter, day 3 would be as packed as day 1.
That was not the case: most of my friends and mentors had left by the morning or afternoon today. Those who stayed in town spent the day exploring the city or visiting Napa Valley. The meeting looked like a ghost town around 2:30 PM.
Is there a better format for these meetings?
Should more of the educational content be online and the meetings be more of an opportunity to interact on a personal level? Should there be time set aside to take advantage of the host city? Should we do away with rigidly formatted oral sessions where interaction is kept to a minimum and most presenters just read off PowerPoint slides?
I would vote yes.
How would you like to see the ACC format of the future?
For more of our ACC.13 coverage of late-breaking clinical trials, interviews with the authors of the most important research, and blogs from our fellows on the most interesting presentations at the meeting, check out our Coverage Headquarters.
March 12th, 2013
More Negative Heart Failure Trials: Blogging from ACC.13
Tariq Ahmad, MD, MPH
Several Cardiology Fellows who are attending ACC.13 in San Francisco this week are blogging for CardioExchange. The Fellows include Tariq Ahmad, Megan Coylewright, Jeremiah Depta, Kumar Dharmarajan, Payal Kohli, and Sandeep Mangalmurti. View the previous post here and the next one
Some important “late breakers” were presented today, the 3rd and last day of ACC.13. I was particularly looking forward to hearing the results of the RELAX trial. Would sildenafil be useful for the treatment of diastolic heart failure? For a disease that appears to have no treatment, the results of this exciting Heart Failure Network study were highly anticipated by patients and physicians alike.
The results of ASTRONAUT were also presented. This looked at the use of aliskiren (direct renin inhibitor) in systolic heart failure.
However, as with most trials in heart failure, the results were negative.
I wonder why we continue to have such terrible luck with therapeutics in heart failure. Perhaps the disease is far too complex for drugs based on single targets to be successful. Or maybe we are viewing the disease process incorrectly and need a paradigm shift in how we describe heart failure.
Is there even such a thing as diastolic and systolic heart failure? Until the 18th century, diseases were described in terms of evil humors, and patients treated accordingly (by bleeding or purging). As might be expected, the treatments were ineffective. We may continue to be victims of inaccurate classifications.
On a more positive note, I found the results of the STOP-HF trial to be quite intriguing. This study looked at the benefit of natriuretic guided screening and treatment in patients with stage A heart failure. The investigators found very significant decreases in heart failure and cardiovascular events.
I am the fellow on the GUIDE-IT trial that just began enrollment. My mentor at DCRI, Mike Felker, is the PI on this trial. We are looking at the effects of natriuretic peptide guided treatment in patients with advanced heart failure.
As we understand more about the molecular biology of heart failure, we may have more tools like the natriuretic peptides that help us define and treat the disease more effectively.
And therapeutics aimed at more accurate definitions of heart failure might result in more positive trial results.
For more of our ACC.13 coverage of late-breaking clinical trials, interviews with the authors of the most important research, and blogs from our fellows on the most interesting presentations at the meeting, check out our Coverage Headquarters.
March 11th, 2013
The Affordable Care Act: The Carrots Are Becoming Sticks
Sandeep Mangalmurti, MD, JD
Several Cardiology Fellows who are attending ACC.13 in San Francisco this week are blogging for CardioExchange. The Fellows include Tariq Ahmad, Megan Coylewright, Jeremiah Depta, Kumar Dharmarajan, Payal Kohli, and Sandeep Mangalmurti. View the previous post here and the next one
I attended an attention-grabbing discussion this morning on the continuing effects of the Affordable Care Act (ACA) on cardiology. Obamacare is here to stay, and it is transforming before our very eyes. Cardiologists and hospitals need to evolve along with it or eventually face financial extinction.
Part of this evolution is deliberately built into the infrastructure of the ACA. The motivation for health reform is well known; health care costs continue to increase at an unsustainable rate. There are multiple drivers of these costs, but the fee-for-service model might be the heart of the problem. As we are all aware, it financially incentivizes volume of care, not quality of care. Since its implementation, the ACA has attempted to change this incentive structure by increasing reimbursement when certain quality goals are met. Some institutions have made these desired changes and have reaped the promised financial rewards. Over the next several years, the rewards will end, and the punishments will begin. Failure to meet these benchmarks will automatically result in a reimbursement cut. In some cases, such as heart failure readmission rates, the magnitude of these cuts will increase with each passing year.
Eventually, a large percentage of cardiology groups will be compensated by Medicare using a model known as “Value Based Purchasing.” Under this model, the government will collect information on quality and performance from providers nationwide and use it to create a “value based modifier” to individually adjust an organization’s compensation from Medicare. Eligible organizations that refuse to participate in the Value Based Purchasing model will be automatically punished with lower reimbursement amounts. There’s that stick again!
Sometimes the ACA doesn’t even need the stick. Take for example, the continuing integration of small cardiology practices into hospitals. One important cause of this integration has been the ACA deliberately setting different reimbursement levels, depending on whether the procedure or visit occurs in a hospital or private office. For example, as mentioned in today’s session, reimbursement levels for echos in a hospital or health network approach $450, compared to $180 in doctor’s offices. Naturally, this carrot is working…more and more cardiology care is moving towards the former. Much of this movement will be permanent; once a private practice integrates with a hospital, it’s hard to un-ring that bell. However, future compensation will likely not have this disparity; everyone will be compensated equally, at the lower rate. Massive cost savings for the government….no stick necessary.
For more of our ACC.13 coverage of late-breaking clinical trials, interviews with the authors of the most important research, and blogs from our fellows on the most interesting presentations at the meeting, check out our Coverage Headquarters.
March 11th, 2013
Two Trials Explore On-Pump Versus Off-Pump Bypass Surgery
Larry Husten, PHD
For more of our ACC.13 coverage of late-breaking clinical trials, interviews with the authors of the most important research, and blogs from our fellows on the most interesting presentations at the meeting, check out our Coverage Headquarters.
Two large trials presented at the American College of Cardiology meeting in San Francisco and published simultaneously in the New England Journal of Medicine provide important new information about the ongoing debate over whether CABG should be performed with or without cardiopulmonary bypass. The combined results suggest that both techniques can be effective, and that surgeons should choose the technique with which they are most familiar and comfortable.
Previous 30-days results from CORONARY (CABG Off or On Pump Revascularization Study), which randomized 4,752 patients to on-pump or off-pump CABG, showed no significant difference in the primary outcome (death, MI, stroke, or new renal failure requiring dialysis) between the two groups. However, patients in the off-pump group required more repeat revascularization procedures, though they had lower rates of bleeding, acute kidney injury, and respiratory complications.
Now, one-year results from CORONARY have found no significant difference in the primary outcome between the groups at 1 year (12.1% in the off-pump group versus 13.3% in the on-pump group (HR 0.91, CI 0.77-1.07, p=0.24). There were also no significant differences in the individual components of the endpoint. In addition, there were no significant differences in recurrent angina (1% versus 0.9%) or the need for repeat revascularization (1.4% versus 0.8%).
A quality of life substudy found no differences between the two groups at any time point in the first year. A neurocognitive substudy found less deterioration in one assessment of neurocognitive function in the off-pump group at discharge but found no significant differences at 30 days or at 1 year. There were no differences at any time between the two groups in two other tests of neurocognitive function.
“The CORONARY study shows that off-pump bypass is just as good as on-pump. Therefore, surgeons should tailor their surgical approach to their technical expertise and expected technical difficulty,” said Andre Lamy, lead author of the study, in an ACC press release.
For more of our ACC.13 coverage of late-breaking clinical trials, interviews with the authors of the most important research, and blogs from our fellows on the most interesting presentations at the meeting, check out our Coverage Headquarters.
In the GOPCABE (German Off-Pump Coronary Artery Bypass Grafting in Elderly Patients) study, 2,539 patients 75 years of age or older were randomized to on-pump or off-pump CABG. The primary endpoint was the composite of death, stroke, MI, repeat revascularization, or new renal-replacement therapy at 30 days and at one year.
At 30 days there was no significant difference in the primary endpoint: 7.8% for the off-pump group versus 8.2% for the on-pump group (OR 0.95, CI 0.71-1.28, p=0.74). However, there were more repeat revascularizations in the off-pump group at 30 days: 1.3% versus 0.4%; OR 2.42; CI 1.03-5.72; p=0.04. At one year there was no significant difference between the groups in the composite endpoint (13.1% versus 14%; HR 0.93; CI 0.76-1.16; p=0.48) or in any of the individual components of the composite endpoint.
The authors write that their trial “does not support the assumption that off-pump CABG can improve the early outcome in high-risk patients.”
During the discussion section of the presentation lead investigators for both studies, Anno Diegeler for GOPCABE and Andre Lamy for CORONARY, emphasized that their results depended on having expert surgeons highly qualified in both techniques.
Choice of the technique, said Diegeler, should depend on clinical characteristics, patient choice, and surgeon experience.
Chris Cannon, a panel discussant, asked the question:”Why would you want to do off-pump since it’s no better and it’s harder to do?” At the ACC news conference, Mark Davies said that “these trials may temper our enthusiasm for off-pump surgery.” In the U.S., with the advent of publicly reported STS (Society for Thoracic Surgeons) scores for individual hospitals and amateurs, there will no room for amateurs. Davies added, “If you’re an amateur at it you should give it up.” Neil Kleiman had a recommendation: “if you’re going to do it you damn well better be good at it… there’s no room for sloppiness.”
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