March 7th, 2012
Software Tool Could Provide Early Warning of ICD Lead Failure
Larry Husten, PHD
In recent years, defects in ICD leads have caused recalls and provoked broad concerns among healthcare professionals and patients alike about the safety and reliability of ICDs and other implanted cardiac devices. Now a key player in these events proposes that a computer software program can better monitor ICD leads and provide earlier warnings of possible malfunctions.
In a paper published in Circulation: Cardiovascular Quality and Outcomes, Robert Hauser and colleagues report on their evaluation of DELTA (Data Extraction and Longitudinal Trend Analysis), a commercially available automated surveillance tool, in simulated analyses of lead survival in a population of 1035 patients with the recalled Sprint Fidelis lead and 1675 patients with the Quattro Secure lead. Lead failures occurred in 8.1% of the Fidelis leads and 1.4% of the Quattro leads during the study.
A simulated analysis of the entire cohort “triggered a sustained alert” for the Fidelis lead 13 months after device approval and a full 2 years before the leads were pulled from the market. A second, propensity-matched analysis triggered an alert 22 months after approval and more than 1 year before withdrawal from the market.
“The results of this multicenter study suggest that an active automated surveillance system could have identified this cardiovascular device problem substantially sooner than was achieved through existing postmarket surveillance methods,” the authors conclude. An earlier alert of the Fidelis problem, the add, “could have spared thousands of patients the consequences of receiving a device prone to failure, including the risks and costs of lead replacement.”
March 6th, 2012
Shared Decision Making in Advanced Heart Failure
Larry Allen, MD, MHS
Larry Allen is the lead author and co-chair of the AHA Scientific Statement on Decision Making in Advanced Heart Failure.
Patient-centered care ensures that clinical decisions are guided by an individual patient’s values, needs, and preferences; shared decision making is the act of putting this type of care into clinical practice by asking health care providers and patients to consider information together and work toward consensus. This process should focus on the outcomes that are most important to the patients, including not only survival but also relief of symptoms, quality of life, and living at home.
High-quality medical decision making for advanced heart failure is becoming particularly important but also increasingly challenging as patients are living longer with their heart disease and treatment options continue to expand– including left ventricular assist devices. Therefore, the American Heart Association has sponsored a Scientific Statement entitled “Decision Making in Advanced Heart Failure, published yesterday, that provides a roadmap for clinicians caring for these complex patients. The statement argues that for patients with advanced heart failure, the decision-making process should be proactive, anticipatory, and patient-centered. This involves talking about goals of care, expectations for the future, and the full range of treatment options, including palliative care. It also requires a team approach.
As the time required for shared decision making is difficult to fit into a regular clinic visit in the middle of a busy clinical practice, we propose an annual review to discuss prognosis, consider reasonable therapies, and clarify the patient’s values, goals and preferences. This review is in addition to, not a replacement for, additional discussions triggered by events such as hospitalizations and other changes in the patient’s health.
March 6th, 2012
Another Round in the Debate on Diabetes and Statins
Yoni Freedhoff, MD
Let me start by saying that I am proud to have Eric Topol as a friend and a trusted advisor over the past 20 years. His work has been an inspiration to cardiovascular health professionals for several decades. His new book, The Creative Destruction of Medicine: How the Digital Revolution Will Create Better Health Care, should be required reading by all physicians and in all medical schools. It is simply that good.
Eric is a strong believer that we need to have more personalized medicine. I agree. I predict that he and his research group will lead the way to help us understand why certain people benefit more from certain medications and others may not. So far, the only ways we have to decide which asymptomatic persons would benefit from statin therapy are the traditional risk factors which make up the Framingham risk score, hsCRP, and coronary calcium measurements. Both of the latter two tests have been given a class IIa indication from the AHA for use in intermediate risk adults (Framingham score of 10-20% risk of an MI over the next decade.)
Eric is concerned about the apparent increased risk of diabetes with statin use. A 2010 meta-analysis in the Lancet found about a 10% increased risk in statin users. Eric rightly points out that the relative risk was higher with the more potent rosuvastatin in JUPITER. Yet, that is where we saw a significant decrease in total mortality and the largest relative risk reduction in CVD events.
Dr. Topol is one of the country’s leading geneticists and thought-leaders. He may be an invited guest to Stockholm in the next decade to accept a great award. If that is the case, I would like to be on his invitation list.
No one is right all the time – just ask my wife. We know that chlorthalidone reduces clinical events and reduces mortality in persons with a systolic blood pressure greater than 160 but it also raises blood sugar. We also know that niacin raised blood sugar in the Coronary Drug Project, but it reduced events and mortality as a single agent.
We don’t know why certain adults go from a glucose of 115-125 and then go over that magic 125 threshold more frequently. Though this has not been published, I have been told by several statin investigators that the vast majority of the persons who crossed the 125 line were clearly insulin resistant with glucoses between 115-125. We are not talking about going from a glucose of 90 to 140!
Before we throw out the NCEP guidelines on primary prevention, I think that we need to be more skeptical of the diabetes fear from statins. The benefit is very clear in high risk primary prevention patients. Please refer to Professor C. Michael Minder’s latest paper on the American Journal of Medicine website. It is a masterpiece. Just like William Shakespeare’s Much Ado About Nothing. My favorite line from that play was “Let every eye negotiate for itself and trust no agent.”
All of us await the ATP guidelines and how to make sense of the benefits and possible risks of the hyperglycemia seen with the more potent statins. In the meantime, please read Dr. Topol’s book. It is fabulous and thought-provoking. And by the way if your statin patient’s glucose goes above 125, simply remind them of the importance of dropping a few pounds and exercising more. Eat Less, eat smarter and move more. A lot more.
I look forward to teeing it up with my friend, and trusted mentor Eric Topol at Torrey Pines and Congressional sometime in 2012! Dr.Topol may prove to be correct on this topic but my view of statins is much more optimistic in high risk primary prevention patients.
March 5th, 2012
Statins and Diabetes: Real Concern or Much Ado About Nothing?
Larry Husten, PHD
In a New York Times Op-Ed piece on Monday, Eric Topol comments on last week’s announcement by the FDA that it was changing the label for statins. Topol focuses on the new warning that statins raise the risk of diabetes. He opens with a provocative statement:
We’re overdosing on cholesterol-lowering statins, and the consequence could be a sharp increase in the incidence of Type 2 diabetes.
Topol does the math and calculates that 20 million Americans taking statins equates to 100,000 new statin-induced diabetics:
Not a good thing for the public health and certainly not good for the individual affected with a new serious chronic illness… If there were a major suppression of heart attacks or strokes or deaths, that might be justified. But in patients who have never had heart disease and are taking statins to lower their risk (so-called primary prevention), the reduction of heart attacks and other major events is only 2 per 100. And we don’t know who the 2 per 100 patients are who benefit or the one per 200 who will get diabetes! Moreover, the margin of benefit to risk is quite narrow.
Topol then concludes that statins are beneficial for secondary prevention in people with a history of heart disease or stroke but for “the vast majority of people who take statins — those who have never had any heart disease — there should be a careful review of whether the statin is necessary, in light of the risk of diabetes and the relatively small benefit that can be derived.”
On his blog on Forbes, pharma reporter Matt Herper writes that with the editorial Topol “has broken ranks with many other heart doctors.” It should be noted, though, that statins for primary prevention have been the subject of intense debate in the past, most recently in an exchange in the Wall Street Journal between cardiologists Rita Redberg and Roger Blumenthal. In addition, the FDA action and Topol’s piece relied on long-available data.
In a comment highlighted by Herper on his blog, Sanjay Kaul looks at the same numbers as Topol and concludes that “the patients who develop diabetes (1 in 200) are more likely to have elevated fasting blood sugar at baseline, and these patients are also likely to benefit from satins (2 in 100).”
In his own blog on Forbes, John LaMattina, who was the president of Pfizer Global Research and Development in Lipitor’s prime, also disputes Topol’s conclusions. He points out the presence of “a very compelling clinical trial showing the value of one statin, Lipitor (atorvastatin), in Type 2 diabetes — the Collaborative Atorvastatin Diabetes Study — known as CARDS.” The study was stopped early when it showed large reductions in acute coronary events and mortality for atorvastatin when compared with placebo in diabetics with no history of cardiovascular disease.
March 5th, 2012
Selections from Richard Lehman’s Weekly Review: Week of March 5th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint selections from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
Week of March 5th
NEJM 1 Mar 2012 Vol 366
Goal-Oriented Patient Care (pg. 777): There is no JAMA this week, and the best things in the New England Journal come right at the start. Whether you are a British GP contemplating another set of humiliating idiotic directives and the imminent destruction of the NHS, or an American physician wondering how your crazy health system can ever be turned into something rational and sustainable, or an academic wondering how much more futile research you have to grind your way through and pretend to be interested in, here is the boost you need. Goal-Oriented Patient Care — An Alternative Health Outcomes Paradigm. For the battle-weary GP, an affirmation of the central value of what you came into medicine to do – to help patients to achieve goals that they choose for themselves, in a continuing dialogue about the possible and the practical. For the American system, a model of care that puts the patient at the centre and emphasizes joined-up, affordable care. For the academic, a new research agenda based on what will best inform shared decision-making with patients and society. Download this article by David Reuben and Mary Tinetti at once and keep it under your pillow.
The NEJM lets you have this free, and also the companion pieces which follow – about shared decision-making and defining patient-centred care. Both good, but the Reuben/Tinetti is a gem.
Arch Intern Med 27 Feb 2012 Vol 172
Stenting vs. Medical Therapy (pg. 312): Doctors and patients love to share simple mechanistic explanations of diseases and cures. Angina pectoris is caused by blocked pipes: unblock the pipes, preferably leaving behind something to keep them open, and you have cured the problem; whereas if you just keep on pushing tablets, you’re just treating the symptoms without dealing with the cause. Most of us shared this belief with cardiologists and with patients, until the COURAGE trial came along in 2007 to prove otherwise (and the trial was nearly never done because many interventional cardiologists considered it unethical). This meta-analysis looks at this and 7 other trials and confirms the counter-intuitive conclusion that “Initial stent implantation for stable CAD shows no evidence of benefit compared with initial medical therapy for prevention of death, nonfatal MI, unplanned revascularization, or angina.” Collusion in mechanistic certainty is one of the great barriers to progress in medicine, and it may cause direct harm to patients, as the next paper illustrates.
Patient Satisfaction and Mortality: There isn’t much else of note in this week’s printed Archives, but hidden in the Online First section awaiting paper publication is a remarkable study of patient satisfaction in relation to outcomes. This is worth spending some time on. In the USA, the highest quartile of patient satisfaction is associated with 9% higher inpatient care and drug costs, and – wait for it – 26% higher mortality. What is killing America’s most satisfied patients? Is there some hidden confounding here (as the editorial hints)? The authors adjust for everything obvious, such as age and health status; so perhaps the kind of medicine these patients are getting really is 26% more dangerous. But this exceeds even the most pessimistic predictions of those of us who have long held that the overprovision that American patients are programmed to demand might be dangerous. Costly, futile, yes: but as lethal as this? I intend to spend an hour with my brilliant group of young overseas doctors at Yale picking over this paper. If nothing else, it will have some lessons on what to avoid in their own health systems. I firmly believe that all health provision should be judged by the experience of patients, but the simple criterion of fulfilled expectation is clearly inadequate, and may be positively dangerous in societies which ratchet up demand for medical services while ignoring costs and harms.
March 5th, 2012
New Insight Into Obesity and Physical Activity in Children
Karen Dorsey, MD, PhD
As obesity has increased among children, a clear link has been established between obesity and cardiovascular risk factors including high cholesterol, high blood pressure, and diabetes. However, less is known about whether being more physically active might protect children from developing these risk factors. Among adults, physical activity has been shown to reduce cardiovascular risk and prolong life regardless of whether a person is obese or non-obese. Less is known about how these factors work together in children.
A recent study in JAMA by Ekelund and colleagues is one of the first to directly address this question of whether physically active children have better cardiovascular health compared with less active children. It is a particularly powerful study because it analyzes the combined results of several studies to include over 6,000 children. The key findings are that moderate and vigorous physical activity (MVPA) is strongly linked to lower cardiovascular risk, that time spent sedentary is not directly linked to cardiovascular risk, and that relatively small differences in physical activity levels can have a profound impact on cardiovascular health. The study also found that physical activity and sedentariness interact in an interesting way. Specifically, children who were the most physically active and the least sedentary had lower cardiovascular risk compared with similarly active but more sedentary children.
This means that interventions that attempt to increase physical activity levels and to decrease sedentariness might have a greater effect on cardiovascular health than attempts to change either behavior alone. In addition, the results suggest that increasing children’s MVPA by only 20 minutes might significantly improve their health regardless of its impact on their weight. Thus, this study provides evidence of the urgent need to identify children who are less physically active and invest in large scale public health efforts to increase active play and reduce sedentariness.
March 2nd, 2012
Four Cardiovascular Societies Release Criteria for TAVR Programs and Operators
Larry Husten, PHD
A newly released statement contains detailed recommendations about the requirements necessary for hospitals and physicians to participate in transcatheter aortic valve replacement (TAVR) programs. The expert consensus document was released jointly by the American College of Cardiology Foundation (ACCF), the Society for Cardiovascular Angiography and Interventions (SCAI), the American Association for Thoracic Surgery (AATS) and the Society for Thoracic Surgeons (STS).
The statement is the latest result of the coordinated effort from medical societies and regulators to effect a smooth introduction of this potentially disruptive new technology. The same four societies earlier released a consensus document that provided a roadmap for the uptake of TAVR in the U.S., which was followed soon thereafter by the release from CMS of details of its proposed national coverage for TAVR.
The document emphasizes “a formal collaborative effort between cardiologists and cardiothoracic surgeons as the cornerstone for establishing a successful program, noting that a program without both specialties would be fundamentally deficient,” according to a press release issued by the societies.
The statement contains specific details about:
- Annual heart (aortic valve) surgery and percutaneous coronary intervention (PCI) volume requirements for institutions.
- Board certification and procedural requirements for both surgeons and interventional cardiologists.
- Monitoring of complication rates and institutional follow up.
- Participation in a national registry that will include enrollment of all patients undergoing TAVR with continued tracking of outcomes.
- Commitment to a heart team concept that is led by the surgeon and interventional cardiologist and made up of a formal collaborative effort among all medical team members. In all TAVR procedures, the interventional cardiologist and surgeon must both be present during the entire procedure ensuring joint participation and optimal patient-centered care.
March 2nd, 2012
Statins and Protease Inhibitors May Interact, Causing Rhabdomyolysis
Physician's First Watch, CardioExchange Staff
The FDA is warning again about interactions between protease inhibitors and certain statins that can lead to rhabdomyolysis. Protease inhibitors are used to treat HIV and hepatitis C.
In a safety communication, the agency published a list of statins that should either be avoided or whose dosing levels should be limited when coadministered with protease inhibitors. Atorvastatin, lovastatin, rosuvastatin, and simvastatin are either listed as contraindicated or have had limits put on dosages.
In particular, lovastatin and simvastatin exposures can increase beyond 10-fold when used with protease inhibitors, and rosuvastatin exposure can increase up to 3-fold, according to the FDA.
Earlier this week, the agency announced several changes to statin labels, including a warning to avoid lovastatin in combination with HIV protease inhibitors.
This post is reprinted from Physician’s First Watch, a part of the Journal Watch family. PFW is a free daily alert on current news that affects your practice — from medical journals, government agencies, scientific conferences, and major media reports.
March 1st, 2012
Is Age Just a Number?
Tariq Ahmad, MD, MPH and James Fang, MD
An 89-year-old woman with severe aortic stenosis is referred to a cardiologist at a major academic center that offers transcatheter aortic valve implantation (TAVI).
A widow for 20 years, the patient lives alone and does well with the assistance of her daughter, who lives nearby. She has two more children in the same town, as well as several grandchildren and great grandchildren. Until five years ago, she worked as a receptionist in the office of her son, who is a dentist.
The patient goes grocery shopping, cooks her own food, is very involved with the local church, and remains socially active. She has never smoked, only drinks socially, has an excellent memory, and reads a book every week.
Her major complaints are angina and shortness of breath on exertion. These symptoms have worsened in the past 2 months, and she had two worrisome episodes of syncope in the past 2 weeks.
Her other medical issues include atrial fibrillation that is rate-controlled, as well as hypothyroidism.
Her exam reveals a blood pressure of 110/70 mm Hg and an irregularly irregular heart rate at 80 bpm. Her venous pressure is normal, and her lungs are clear. A cardiac exam shows no RV lift, but a grade 3/6 crescendo–decrescendo systolic midpeaking murmur, heard throughout the precordium and loudest at the upper sternal border. The aortic-closure sound was audible but diminished. There was no loud pulmonary component, and no diastolic murmurs or gallops were detected. The carotid upstrokes were slightly diminished and delayed, and no separate carotid bruits were audible.
The patient’s abdomen is soft and nontender, with no organomegaly or palpable masses. The distal pulses are 1–2+, and her extremities are warm and well-perfused without edema.
Echocardiography shows a trileaflet aortic valve with decreased mobility; a short-axis planimetry mitral valve area of 0.6 cm2; a peak velocity of 3.8 m/sec, and a mean calculated gradient of 45 mm Hg. The patient has a mildly depressed LV ejection fraction (45%–50%), a nondilated left ventricle, normal RV function, bileaflet mitral valve prolapse with moderate-to-severe mitral regurgitation, and moderate-to-severe tricuspid regurgitation (TR velocity, 3 m/sec).
Cardiac catheterization reveals no obstructive coronary disease. The right-atrial pressure is 8 mm Hg, with a pulmonary-artery pressure of 30/16 mm Hg (mean, 22 mm Hg), and a pulmonary capillary wedge pressure of 13 mm Hg. LV pressure was 190/12 mm Hg, and aortic pressure was 150/65 mm Hg. Cardiac index is calculated at 1.6 L/minute.
Questions:
1. Would you recommend aortic valve replacement? If so, would you favor TAVI or a conventional approach?
2. What other testing would you do to help inform your decision?
3. Should there be an age cutoff for advanced therapies in cardiac disease?
Editor’s Note: For a few hours after initial publication of this post, the values for the patient’s LV pressure and aortic pressure were incorrect. The correct values now appear.
Response:
March 9, 2012
This elderly but very independent and functional woman appears to have symptomatic multivalvular heart disease. Exertional dyspnea, angina, and syncope would all be expected, given the severity of her valvular lesions.
Although significant mitral regurgitation is not uncommon in patients with severe aortic stenosis, this patient’s bileaflet prolapse and unremarkable filling pressures suggest that the MR is an independent lesion. The low-normal ejection fraction is particularly worrisome. Although some evidence has shown that mitral regurgitation can improve after aortic valve replacement (Circ Cardiovasc Imaging 2012; 5:36 and Ann Thorac Surg 2007; 83:1279), the nature of this patient’s MR suggests that it will persist and remain symptomatic.
It is interesting that the right-atrial pressure is only 8 mm Hg, with moderate-to-severe tricuspid regurgitation and normal pulmonary-artery pressures. This would imply longstanding primary TR, not secondary to RV dysfunction. The low cardiac index is indicative of the poor forward-stroke volume as a consequence of MR and aortic stenosis.
The patient’s age and multivalvular heart disease increase her operative risk but are by no means prohibitive. The key issue is the nature of the cardiac surgery support at the institution. Many programs have surgeons who are extremely experienced in this area and could therefore handle such a patient with a very reasonable risk for morbidity and mortality.
TAVI’s role continues to evolve but is currently reserved for patients who are at extremely high or prohibitive risk for conventional surgery. It is not clear to me that this patient has that level of risk. A useful approach would be to calculate an STS score or EuroScore.
Therefore, I would recommend aortic valve replacement and mitral valve repair as a primary strategy. TAVI should be undertaken only after disclosing the caveats of this therapy to the patient and her family.
Further testing does not seem necessary to me. Published evidence is insufficient to suggest using BNP level to guide therapy, although some clinicians might be more comfortable with an elevated value.
In general, medicine has no “age cutoffs.” Age is only one of many criteria that clinicians use to decide on a course of therapy for given patient. In the end, the weight of evidence-based medicine is always tempered by an individualized approach and the exercise of judgment.
Follow-Up:
March 15, 2012
The patient did, as Dr. Fang recommended, undergo “conventional” aortic valve replacement and mitral valve repair. She had been seen in consultation by the cardiac surgeons at our medical center; they determined that her calculated STS score was within an acceptable range for them to proceed with surgery. The risks and benefits were discussed at length with the patient and her family, who felt that she still had “many good years left” and wanted to proceed. Her surgery was successful, and her postoperative course was uneventful. After discharge, she spent some time in cardiac rehab, where she regained her strength. She was seen in follow-up clinic and had no further episodes of chest pain or shortness of breath on exertion.
March 1st, 2012
Decision on Apixaban (Eliquis) Pushed Back By 3 Months
Larry Husten, PHD
Confirming earlier speculation by a Wall Street analyst, Pfizer and Bristol-Myers Squibb announced on Wednesday evening that the FDA had extended by 3 months the action date for the new drug application (NDA) for the highly anticipated oral anticoagulant apixaban (Eliquis). The application is for their important indication of stroke prevention in atrial fibrillation. The FDA had previously granted the application a 6-month priority review, resulting in a March 28th decision date. The new decision date is June 28, 2012.
Sanford Bernstein research analyst Tim Anderson first raised the idea that the decision date might be delayed back on February 10th. On Tuesday Anderson released another note with additional evidence for the delay, based on the release of the tentative FDA advisory committee calendar for 2012, suggesting that the apixaban NDA will be subject to an advisory panel meeting. According to the calendar, the Cardiovascular and Renal Drugs Advisory Committee is scheduled to meet on March 27 and May 23. The agenda for the March 27 session is already set for a discussion of Replagal for Fabry disease. Recall that earlier this week, the FDA granted a priority review to the NDA for rivaroxaban for ACS, resulting in a decision date of June 29. One might speculate then that another day might be added to the May 23rd meeting for consideration of the rivaroxaban and apixaban NDAs.
Anderson wonders why the FDA has suddenly put the brakes on the apixaban approval, which had heretofore seemed uncomplicated. He writes:
Our best guess remains that FDA may be seeking cover, given the safety experience following competing drug Pradaxa’s approval in 2010. Additionally, FDA may be seeking advice on things like product labeling and what claims would be allowed.
We might also note that the approval of rivaroxaban was far more difficult than had been expected. Remember that the ROCKET AF trial had been presented and published with broad approval, but then came under heavy fire from FDA reviewers. It is possible that FDA reviewers may also raise previously unsuspected concerns about the pivotal apixaban trial, ARISTOTLE, though no serious criticisms have been publicly raised so far.
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