April 19th, 2011
Non-Evidence-Based ICD Implants: The Debate Continues
Larry Husten, PHD
A controversial study published earlier this year in JAMA that found that nearly a quarter of all ICD implantations did not meet evidence-based criteria is the subject of further debate this week in the letters section of JAMA.
In the first letter, Jeanne Poole and George Crossley take issue with the designation by the authors of ICD implantations within 3 months of a new HF diagnosis as being non-evidence based. They point out that current guidelines “do not specify a 3-month wait from HF diagnosis before ICD implantation for any etiology of HF.” In response, Sana Al-Khatib and colleagues argue that “recommendations for primary prevention ICDs apply only to patients whose left ventricular ejection fraction remains low despite optimal medical therapy” and that “achieving optimal medical therapy in patients with newly diagnosed HF is an iterative process” that has required more than 3 months to demonstrate full benefits in clinical trials.
In the second letter, Kathleen Blake and Charles Swerdlow write that the NCDR data “is not designed to determine the medical necessity of ICD implants that do not meet evidence-based guidelines.” They describe several scenarios in which non-evidence-based implants may be medically justified. Al-Khatib et al agree that some non-evidence-based implants can be “clinically appropriate” but, they write, “the important question is how many.” They point out that non-evidence-based implantations in hospitals in their study ranged from 0% to 60%, and write that “the proportion of such cases should generally not be high, and if it is, additional investigations are needed to identify reasons.”
In the third letter, Steven Zweibel, Christopher Clyne, and Eric Crespo question the accuracy of the NCDR registry, since “the registry relies on busy clinicians… who may not be completely familiar with the subtleties of clinical care and decision making for patients with cardiovascular disease.” They cite numerous deficiencies in the data collection for the registry at their own institution. In their response, Al-Khatib et al say that the NCDR has numerous mechanisms to ensure the quality of its data, and that a professional audit found a 90% agreement between hospital records and registry data. CMS reimbursement for ICDs requires participation in the registry, “and penalties may be levied if inaccurate data are knowingly submitted.”
April 18th, 2011
100 Is the New 150: AHA Lowers Optimal Triglyceride Level
Larry Husten, PHD
In a newly released scientific statement on triglycerides, the AHA recommends that 100 mg/dL replace 150 mg/dL as the upper limit for the “optimal level” for triglycerides. But, the statement acknowledges, the cut point should not be used as a therapeutic target for drug therapy, “because there is insufficient evidence that lowering triglyceride levels” can improve risk. Instead, the statement puts a large emphasis on lifestyle changes, especially with diet and exercise, to cut triglycerides and reduce risk.
The new statement “is not intended to serve as a specific guideline,” according to the AHA, but instead “will be of value” to the Adult Treatment Panel IV (ATP IV) of the National Cholesterol Education Program, which will be available for public review and comment this fall and is expected to be published in the spring of 2012.
“The good news is that high triglycerides can, in large part, be reduced through major lifestyle changes,” said the chair of the committee, Michael Miller, in an AHA press release. “In contrast to cholesterol, where lifestyle measures are important but may not be the solution, high triglycerides are often quite responsive to lifestyle measures that include weight loss if overweight, changes in diet, and regular physical activity.”
The statement includes specific recommendations for reducing added sugar, fructose, saturated fat, trans fat, and alcohol for those with elevated triglycerides. According to the statement, 31% of U.S. adults have triglyceride levels greater than 150 mg/dL.
April 15th, 2011
Beyond Fellowship: Academia or Private Practice?
John Ryan, MD and Susan Cheng, MD
Published literature maintains that 20% of cardiology fellows continue into academic careers, with the remainder going into private practice. Fellowship Training Co-Moderator John Ryan, a second-year cardiology fellow in Chicago, and Associate Editor Susan Cheng, a fifth-year fellow in Boston, answer CardioExchange’s questions about the transition from fellowship to the next level – whatever that may be.
Q. Are you surprised that so few fellows choose to remain in academia?
JR: It does surprise me. We spend ten years of training in an almost exclusively academic setting, so at first I would assume we are almost ill equipped to go into private practice because we are simply not exposed to it.
SC: This figure used to seem quite low to me, too. More recently, with research funding being very tight and some academic centers having instituted hiring freezes, it seems that academic opportunities are just not as numerous as outside jobs. Also, the pay difference is often enough to drive many people away from academia after they graduate. John’s point about being prepared to go into private practice is important: I think that the ideal fellowship program for most people offers good training for pursuing either an academic or private-practice position or something in between. However, I can imagine that this would be hard for programs to achieve because the ends of each spectrum can look very different.
Q: Why do you think the number is so low?
JR: I believe it comes down to mentorship. As I get further along in my training, I am beginning to see the skill sets that are required for a career in academics. To acquire those skills, I think someone needs a dedicated mentor who will show how to write papers, apply for grants, and carve out a niche. Patient care is never easy; however, it is second nature to us by the end of our fellowship. Complementing these skills with an area of expertise — be it research, teaching, whatever — that is the hard part.
SC: There are probably several reasons and I agree with John that one of the biggest factors is a lack of mentorship, as well as prior experience. I realize these two go hand-in-hand. A challenge is that good mentorship is difficult to come by for a variety of reasons, including that it takes hard work and a lot of effort on behalf of the mentor – and mentoring skills are not taught in any structured way. All this probably translates into fewer really good mentors and, in turn, fewer people in training who get high-quality mentoring.
Q: How could this number be increased?
JR: I’d expect that providing dedicated time during fellowship for uninterrupted research would produce the highest yield. However, that typically extends training, which is already seen by many as too long. Also, there may be some selection bias, as the fellows who do these two- to three-year research programs are presumably the ones most interested in academics. And there is only so long that we can stretch out our training before reality settles in and we need to start earning a salary.
SC: I have no choice but to agree with John, since I’m now finishing up what will be my third year of dedicated research time – as an overall fifth-year fellow! One can take all the courses in the world, but nothing replaces the hands-on experience of spending large, dedicated amounts of time working on research projects under the right type of mentorship. The issue is that it does take time. Most of the people I know who are moving into academic positions out of fellowship have spent a solid two, three, or more years doing clinical, translational, or basic research – regardless of whether or not they had a bunch of experience or even PhD training prior to cardiology fellowship (science is changing that quickly). I wonder if this reality should be made more clear to fellows entering cardiology and, perhaps, if there should be different tracks for people depending on their career preferences – if they happen to be aware of their preferences that early on.
Q: Could programs better prepare their fellows for private practice?
JR: If we could spend more time in private-practice settings that would be beneficial; however, I am not sure how that would work out from an ACGME perspective. I suspect that developing more familiarity would likely increase the number of graduates going into private practice (although I have no data to support my suspicion).
SC: I can imagine several things that could help better prepare fellows for private practice, such as seminars on providing quality care in a high-volume setting, managing a practice as a well-run business, appropriate billing practices, human-resources management, maintaining certification, continuing medical education, and probably many more areas that I don’t know much about. As far as helping fellows figure out what type of career is right for them, wouldn’t it be great to get a bunch of private practitioners and academicians (and people who have careers that are something in between) together to talk to first- and second-year fellows about their jobs, what they like, what they dislike, and what they would do differently if they could? Maybe we could do something like that online, though I realize that’s another topic altogether…
Q: How important is salary in determining whether fellows stay in academics?
JR: It is likely a major factor, but at least some literature suggests it is not the sole deciding issue. At least in this study of medical students regarding their career choice, the most important aspects were educational experiences, the nature of patient care, and lifestyle. Whether we can extrapolate these data all the way to graduating fellows, I am unsure.
SC: I bet it becomes a more important factor as people get further into their training, as loans accumulate, and they start to build families. It is at this point that I see people around my level of training start to rethink their decision to pursue an academic career. It’s sort of like “the daycare test” – they look at the cost of daycare and then decide that things will be okay the way they are, that things will hopefully get better soon, or that there now needs to be a major change in plan.
April 15th, 2011
Harnessing the Power of the EMR for Clinical Research Recruiting
Peter B Berger, MD
The days of passively recruiting for outpatient clinical trials by having a research coordinator in a clinic manually review charts to determine which patients are eligible will soon be over. How soon is hard to tell, but institutions like Geisinger Medical Center in Pennsylvania, where I am Director of the Center for Clinical Studies (and an interventional cardiologist), have already demonstrated a much more efficient approach, as recently highlighted in the Wall Street Journal.
Because of its longstanding use of electronic medical records (about 13 years now) and its stable patient population, Geisinger is able to programmatically identify large numbers of patients with chronic conditions who meet the eligibility requirements for a given clinical trial, whether in orthopedics or vascular disease, endocrinology or neurology, etc. And because patients in north central Pennsylvania are so beneficent, large percentages respond favorably to letters from their healthcare providers inviting them to learn more about trials for which they appear to qualify. As a result, when it comes to trials targeting outpatients with ongoing or chronic conditions, Geisinger can enroll more individuals than any other institution I’ve ever heard of.
Our approach to recruitment is clearly in the best interests of the study sponsors: it can reduce the number of sites needed for a given trial, speed the completion of the trial, reduce the overall costs associated with the trial, and, ultimately, help bring a drug to market more rapidly. Yet commercial research organizations (CROs) and, at times, sponsors themselves have been reluctant to reimburse us for the upfront, “atypical” costs associated with our approach — for example, EMR programming, letter mailing campaigns, and a call center.
Why the hesitation? CROs use a “one size fits all” paradigm for reimbursement (in which all sites are paid per enrolled patient and generally reimbursed the same amounts), and they are resistant to treating sites differently from one another, even those as unique as Geisinger. Furthermore, even though our approach serves the best interests of the sponsors, it may not do the same for CROs.
So, now the question arises: Are the interests of CROs and sponsors truly so aligned? Can CROs, pharma, and other study sponsors be flexible enough to take advantage of the power of the EMR to transform recruiting for clinical trials?
April 15th, 2011
FDA Offers Cautious Support for Olmesartan (Benicar)
Larry Husten, PHD
The FDA announced on Thursday that it had reviewed the results of the ROADMAP and ORIENT trials and had determined that the benefits of olmesartan (Benicar, Daiichi Sankyo) “continue to outweigh its potential risks” when used as indicated for the treatment of high blood pressure. In June 2010 the FDA had announced that it was conducting a safety review of the drug based on the unexpected finding of a greater number of deaths from cardiovascular causes associated with olmesartan in the two trials.
The FDA also said that it was working with Daiichi Sankyo to perform additional studies and conduct additional analyses of completed studies “to obtain more complete information about the cardiovascular risks or benefits” of the drug.
April 14th, 2011
FDA Officials Offer Explanation for Absence of Low-Dose Dabigatran
Larry Husten, PHD
Following the approval last October of dabigatran, some observers criticized the FDA’s decision not to approve the lower 110 mg dose of the drug in addition to the higher 150 mg dose. Now, in a perspective in the New England Journal of Medicine, 3 FDA officials — B. Nhi Beasley, Ellis Unger, and Robert Temple — explain that their decision “was based on our inability to identify any subgroup in which use of the lower dose would not represent a substantial disadvantage.”
The FDA officials acknowledge that there were several good reasons for approving the lower dose, including the finding of safety and efficacy and the ability to individualize treatment. However, the FDA review team was unable to identify a patient population in which the lower dose might be superior to the higher dose, including older patients, patients with renal function, and patients with previous bleeding episodes.
The authors also express concern about physicians and patients who fear the bleeding risk of warfarin and dabigatran: “we concluded that encouraging the ‘play it safe’ option for patients and physicians represented an undesirable stimulus to use a less-effective regimen and would lead to unnecessary strokes and disability.”
April 14th, 2011
Sugar Is Not So Sweet
Larry Husten, PHD
You may want to skip your Sunday sweet this week. On Sunday, the New York Times magazine section will publish a major assault on sugar by the veteran and often controversial journalist Gary Taubes. In a long and detailed feature article, Taubes outlines the case for the prosecution against sugar, along with its nearly identical and ubiquitous cousin, high-fructose corn syrup, which he argues may well be a chronic toxin that can cause not only obesity, cardiovascular disease, and diabetes, but also cancer. Taubes writes:
It very well may be true that sugar and high-fructose corn syrup, because of the unique way in which we metabolize fructose and at the levels we now consume it, cause fat to accumulate in our livers followed by insulin resistance and metabolic syndrome, and so trigger the process that leads to heart disease, diabetes and obesity. They could indeed be toxic, but they take years to do their damage. It doesn’t happen overnight. Until long-term studies are done, we won’t know for sure.
Regarding cancer, Taubes follows the scientific trail linking insulin and insulin-like growth factor to many human cancers. He writes:
If it’s sugar that causes insulin resistance… then the conclusion is hard to avoid that sugar causes cancer — some cancers, at least — radical as this may seem and despite the fact that this suggestion has rarely if ever been voiced before publicly.
Taubes acknowledges that the evidence isn’t perfect, but wryly concludes with the words: “Officially I’m not supposed to worry because the evidence isn’t conclusive, but I do.”
Readers may be interested to learn that Taubes’s perspective aligns closely with that of Robert Lustig, a pediatric endocrinologist at UCSF. Lustig has a YouTube video lecture about sugar that has received more than 800,000 views (and will probably get a whole lot more views after Sunday).
April 13th, 2011
Increasing Disparity Found in Stroke Mortality in Europe and Central Asia
Larry Husten, PHD
The difference in stroke mortality among countries in Europe and Central Asia is large and, somewhat surprisingly, is growing larger, according to a new analysis of data from the World Health Organization.
In a paper published online in the European Heart Journal, Josep Redon and colleagues examine recent 15-year trends from 39 countries. They report that, in general, western European countries, which already had very low child and adult mortality rates, had the lowest rates of stroke mortality and the greatest declines over time. By contrast, countries in Eastern Europe and central Asia, which already had higher adult and child mortality levels than western European countries, had now experienced “a further unprecedented increase” in stroke-related death.
“The striking conclusion that emerges is that stroke mortality has entered a period of rapidly increasing inequality between countries,” the authors write.
The investigators point to differences in blood pressure as the likely most important cause of the geographical variation, but other factors, including low income, other socioeconomic variables, and psychosocial and dietary factors, may also play significant roles. “If we assume that stroke mortality can serve as a proxy for average BP in a population,” they write, “the data presented here clearly demonstrate the necessity to adopt actions to increase the diagnosis, treatment and hypertension control in the countries where the burden of hypertension sequelae is still growing.”
April 13th, 2011
Which Chest-Pain Patients in the ED Are “Low Risk”?
Martin Than, MBBS
CardioExchange welcomes Dr. Martin Than, lead author of the Lancet article on ASPECT, an observational study of a 2-hour diagnostic protocol to assess chest pain in the emergency department. CardioExchange’s Dr. James de Lemos asks Than about the nuances of the protocol. We welcome you to offer your own questions and opinions.
Background: The accelerated diagnosis protocol (ADP) evaluated in ASPECT was designed to identify which chest-pain patients in the ED have low short-term risk for a major adverse cardiac event (MACE) and, therefore, may be suitable for early discharge. The protocol comprises the TIMI score, ECG, and a point-of-care biomarker panel of troponin, creatine-kinase MB, and myoglobin. Of 3582 consecutive chest-pain patients at 14 EDs in the Asia-Pacific region, 9.8% had negative results on all 3 tests and were therefore classified by the ADP as “low risk.” The MACE rate was 11.8% in the entire population, versus 0.9% in the ADP-identified low-risk group — yielding a sensitivity of 99.3%, a negative predictive value of 99.1%, and a specificity of 11.0% for the ADP.
de Lemos: The integration of risk scoring with ECG and biomarkers is a logical approach to countering overuse of resources in low-risk chest-pain patients. A downside might be that only about 10% of assessed patients would be eligible for early discharge. Did you evaluate whether the cost savings of shortening the observation period by 4 hours in this subgroup made up for the additional laboratory costs of applying your strategy to the larger group of patients? And in your hospital, are you using all three biomarkers or a different biomarker approach?
Than: We believe that the ADP should be used only for patients with a TIMI score of 0 and no new ECG-identified ischemia. Based on the ASPECT cohort, that would mean doing biomarker testing in only 13% of patients at 0 and 2 hours. The ADP would still require testing of three point-of-care (POC) biomarkers for some patients (with some resultant increased cost). A preplanned ASPECT subanalysis revealed that if only the POC troponin was used, the sensitivity was 98.5%.
We have observationally tested other biomarkers in ASPECT. For example, in the Christchurch Hospital cohort (1000 patients), use of just our central laboratory’s contemporary troponin assay (99th percentile at 0.028 µg/L) within the protocol would have yielded a sensitivity of 99.6%. This analysis has persuaded us that a contemporary troponin-only approach would work best in Christchurch. As a consequence, we have begun local implementation as part of a 500-patient, pragmatic randomized controlled trial aimed at testing the effectiveness (early discharge rate and cost utility) of the strategy in real-world practice. The primary outcome is the safe discharge rate at 6 hours after hospital admission. We are approaching the trial’s halfway point, and the early-discharge rate in the experimental arm is about 17%.
de Lemos: At UT Southwestern in Dallas, most of the “action” with the biomarkers is at the first draw. Did you evaluate whether the 2-hour draw was necessary? I suspect that the rate of “rule in” at the 2-hour draw would be low among those with a TIMI risk score of 0, negative baseline markers, and no ECG changes. Could the second measurement be eliminated in low-risk patients?
Than: We definitely found that the initial investigation provided most of the value, but there were 11 false negatives (sensitivity, 97.4%) when the 2-hour set of biomarkers was not used. There were still extra false negatives even if a high-sensitivity troponin assay was used. So, for now, we believe that a second draw is required.
de Lemos: Did you explore other definitions of “low risk”? That might expand the pool of patients who are eligible for early discharge, if the negative predictive value were still high.
Than: The primary hypothesis was based on the TIMI score, but we did test other risk tools (Vancouver Chest Pain Rule, a chest-pain rule for young adults from Marsan and colleagues, GRACE, and PURSUIT). As it happens, using a TIMI score of 0 with the ECG and other biomarkers had the best sensitivity. We are currently working with the dataset to produce a risk tool more focused on a rule-out strategy for “all comers to the ER with chest pain.”
de Lemos: One concern for cardiologists will be what to do with patients identified as “not low risk.” An isolated abnormal-myoglobin test, in particular, will present a conundrum. What, if any, evaluation do you recommend when the myoglobin result is abnormal?
Than: The ADP evaluated in ASPECT is a screening tool that may allow “screen out” and early discharge (or next test — e.g., stress test) for 10% to 15% of patients. If any of the protocol parameters are abnormal, then investigations should continue as usual, following a conservative “late” approach (≥6 hours for the second troponin). We would not advocate extra investigations for an elevated myoglobin level if troponins remained normal. If CK-MB is used, then we advise that further investigations are required for a positive result, because CK-MB is a specific marker of myocardial necrosis. In fact, in Christchurch Hospital we had been provided for many years (until recently) with myoglobin, in addition to troponin, results. I can’t remember anyone ever acting on the results!
April 12th, 2011
Particle Trap Reduces Harmful Diesel Emissions, Could Be Cardioprotective
Larry Husten, PHD
A commonly available particle trap can dramatically reduce harmful emissions from diesel engines and may prevent adverse cardiovascular effects from the emissions, according to a new study published in Circulation. In a randomized, double-blind, three-way crossover trial, Andrew Lucking and colleagues compared the effects of filtered air to diesel exhaust with or without a particle trap for 1 hour in 19 healthy male volunteers.
They report that the particle trap reduced both the number of particle emissions (by more than a factor of 1000) and their size (from 320 to 7.2 µg/m3). This was associated with increased vasodilatation, reduced thrombus formation, and increased tPA release. No adverse effects appeared to be associated with the particle trap. The authors conclude: “Given these beneficial effects on biomarkers of cardiovascular health, the widespread use of particle traps on diesel-powered vehicles may have substantial public health benefit and reduce the burden of cardiovascular disease.”
In an accompanying editorial, Robert Brook and Jeffrey Brook (chair and author, respectively, of the AHA’s scientific statement on air pollution and cardiovascular disease) write that “given the paucity of human data, these new findings carry substantial weight” and “support ongoing efforts to reduce particle pollution through programs targeting diesel emissions.”
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