September 4th, 2013
Too Much Emphasis on Door-to-Balloon Time?
Larry Husten, PHD
One of the great medical advances in recent years has been the improved treatment of acute myocardial infarction. As the enormous benefits of earlier reperfusion became evident, medical systems in many parts of the world aimed to treat increasing numbers of patients in a shorter time frame. The door-to-balloon (D2B) time as a performance measure has emerged as a key part of this initiative. Now a study published in the New England Journal of Medicine finds that in-hospital mortality for acute MI patients receiving PCI has not fallen despite improvements in the D2B time. But some experts fear this finding may be misinterpreted, as it more accurately reflects a growing and changing population receiving PCI than any shortcomings in the D2B initiative.
Using the CathPCI Registry of the National Cardiovascular Data Registry, Daniel Menees and colleagues analyzed data from almost 100,000 hospital admissions for primary PCI between July 2005 and June 2009.
- Median door-to-balloon times declined over time, from 83 minutes to 67 minutes (p<0.001).
- A greater percentage of patients were treated in 90 minutes or less: from 59.7% to 83.1% (p<0.001).
- No significant change in unadjusted in-hospital mortality: 4.8% and 4.7% (p=0.43 for trend)
- No significant change in adjusted in-hospital mortality: 5.0% and 4.7% (p=0.34).
The authors write that their “findings raise questions about the role of door-to-balloon time as a principal focus for performance measurement and public reporting” and “suggest that additional strategies are needed to reduce in-hospital mortality in this population.” They point out that D2B is only “one component of total ischemic time; as door-to-balloon time is reduced, it becomes a smaller fraction of total ischemic time, making the time before arrival at a hospital a more important factor.”
In an accompanying editorial, Eric Bates and Alice Jacobs write that “the primary opportunity for reducing total ischemic time and time to treatment, and for improving outcomes, now lies in the prehospital STEMI system of care, where logistic challenges remain…. Although door-to-balloon time remains important, it’s time to turn our attention to the further development of systems that address the continuum of STEMI care, from symptom onset through return to the community.”
Another way to view the study results is that they show that the D2B initiative is an apparent victim of its own success by bringing many more difficult-to-treat patients into the system at an earlier period. Harlan Krumholz, a leader of the D2B initiative, explains:
At a patient level shorter times translate into better outcomes and reaffirm the importance of rapid treatment. The paper also reveals the remarkable improvement in care over this period. And overall mortality rates for AMI (not shown in this paper) are dropping impressively. The lack of improvement in mortality over these years for the population of patients undergoing PCI may say more about the changing population of patients being referred for primary PCI over this period (volume grew rapidly – the mortality of those treated in more than 90 minutes increased) than the effectiveness of rapid (as opposed to delayed) reperfusion therapy.
In an interview on CardioExchange, study authors Daniel Menees and Hitinder Gurm propose that
It may be time to move away from D2B time, or at least recognize its limitations and consider its use in the context of other measures. We need to start trying to track total ischemic time (i.e., onset of symptoms) better as well as take a closer look at the false activation rates across different regions and hospital systems. We think this is the real message behind our study – it’s time to look beyond D2B times, and we need start looking at other ways we can favorably impact patient outcomes.
September 4th, 2013
New Dual Biomarker Test Could Speed Rule-Out of MI in the ED
Larry Husten, PHD
Only 1 in 10 patients with acute chest pain in the emergency department turn out to have an acute myocardial infarction, yet many are not released from the hospital until after 6 to 12 hours of cardiac monitoring and multiple ECG and troponin tests. The search for a test that can rule out MI early in the process has proved elusive.
The Biomarkers in Cardiology-8 (BIC-8) trial, presented at the European Society of Cardiology meeting in Amsterdam, was designed to determine the utility of the combination of troponin and copeptin testing. Copeptin is a marker of severe hemodynamic stress. After an acute MI, copeptin levels increase rapidly. In earlier observational studies, the combination test was found to have a negative predictive value of 99%.
Some 902 patients with suspected ACS who were troponin-negative were randomized to standard treatment or an experimental strategy in which those with a negative copeptin test were discharged early. At 30 days, there were no significant differences in the rate of major adverse cardiovascular events (MACE) between the two groups:
- 5.5% in the standard-care group versus 5.46% in the copeptin group. The results fell within the predefined margin of noninferiority.
- Early discharge occurred much more frequently in the copeptin group: 66% versus 12% with standard care (p<0.001).
Twelve physicians treating patients in the copeptin group overruled a negative copeptin test. In a per protocol analysis, the MACE rate was 5.68% in the standard-care group versus 3.18% in the copeptin group.
Lead investigator Martin Möckel said that “patients with a negative troponin and a negative copeptin result at admission can safely be discharged if the final clinical assessment is consistent with this decision, as long as a timely diagnostic work-up is done in the outpatient setting.” However, he said that a negative copeptin test does not mean that physicians should not take into account the clinical assessment of their patients. “If his or her final clinical assessment excludes discharge due to high suspicion of ACS, perhaps due to recurrent symptoms or an updated history, the patient should not be discharged despite negative biomarker results.”
He said the new process was safe and effective and “has the potential to change clinical practice with high patient safety.”
The study received financial support from Thermo Fisher, which has a copeptin test available in Europe.
September 4th, 2013
Something New, or the Same Again?
Paddy Barrett, MB BCh BAO MRCPI MCTI
Several Cardiology Fellows who are attending ESC.13 in Amsterdam this week are blogging for CardioExchange. The Fellows include Paddy Barrett, Louis Handoko, and Amanda Vest. For more of our ESC.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.
Sitting at the gate, everyone is talking a little less, becoming focused on preparations for clinical work in the morning. Another year has passed, another ESC Congress is over, and we return to our respective roles, hopefully somewhat more informed than we were before we departed.
But what have I really learned at the Congress? Something new, or the same thing I learn every year? I think a little of both — but it may be the later that is more important.
Each year, our knowledge is expanded with the presentation of novel trial data and the refreshing of core concepts. And although these are important, I believe the Congress’s real value lies in the people we encounter over the five days.
During these periods we forge new relationships with colleagues the world over but — often more important — build on the relationships with those we work with on a daily basis. The meeting provides a platform to interact with individuals outside one’s normal sphere of exposure, share ideas, and develop connections and collaborations that will grow from year to year.
It is while sitting on a plane, or over a drink in a cafe in a sunny square, far away from the frequently intense clinical environments we work in, that we can really get to know our colleagues. And in doing so, we considerably strengthen the unity among all in our community of cardiovascular disease, both at home and abroad.
The cutting-edge science the Congress serves up each year will no doubt significantly influence how we manage our patients daily, but the relationships we build will define how we will grow as a community over the years and decades to come.
It’s been a great conference, and to all those I met, and indeed to all those that I did not, I hope to see you at the Congress next year.
September 4th, 2013
Same Disease, Different Tools
Amanda Ruth Vest, MBBS
Several Cardiology Fellows who are attending ESC.13 in Amsterdam this week are blogging for CardioExchange. The Fellows include Paddy Barrett, Louis Handoko, and Amanda Vest. For more of our ESC.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.
I sometimes feel frustrated that the available tools in my subspecialty of heart failure fall short of the therapeutic advances achieved in other subspecialties. The standard pharmacological heart-failure cocktail has been largely unchanged since I graduated medical school 8 years ago. Nesiritide held promise in acutely decompensated heart failure until definitive studies failed to demonstrate a mortality or rehospitalization benefit. Cardiac resynchronization therapy and ventricular assist devices have entered the arena for a subset of advanced heart failure patients, but where are the new drugs?
The joint ESC-AHA symposium on challenges in managing heart failure opened my eyes to the differing armamentarium available to European and American clinical cardiologists and to several evolving drug options.
Ivabradine is used by approximately 12% of patients in the European HF registry (as reported by Aldo P. Maggioni) but is not licensed for use in the U.S. It is a negative chronotrope that was approved for treatment of angina in Europe in 2005. The 2010 SHIFT trial demonstrated an ivabradine-associated reduction in heart failure mortality and readmissions for systolic heart failure patients in sinus rhythm with a heart rate above 70 bpm. It has proven particularly useful in patients whose beta-blocker tolerance is limited by hypotension. When session cochair Mariell Jessup asked the audience who routinely considers use of ivabradine for heart failure patients, I was one of only a few attendees who did not raise their hands. European practitioners again raised their hands en masse when asked whether they use levosimendan — a calcium sensitizer approved as inotropic therapy for acutely decompensated heart failure in many European countries. By contrast, far fewer hands were raised when the cochair asked whose home institutions offered percutaneous ventricular assist devices, destination ventricular assist devices, and cardiac transplantation – options that I am far more familiar with as a trainee at a large U.S. institution. I also learnt that the approval of tolvaptan for hyponatremia in the setting of decompensated heart failure is limited to the U.S.; in Europe, SIADH is the only approved indication. These geographic variations in options for heart failure management underscore the challenges faced by guideline writers who seek widely applicable clinical recommendations.
Useful additions to the heart failure toolbox may be on the horizon for cardiologists on both sides of the Atlantic. Serelaxin (recombinant human relaxin-2), which showed encouraging results for relief of dyspnea in in the RELAX-AHF study published earlier this year, was recently granted ‘breakthrough therapy’ designation by the FDA and is currently being considered for European approval. Other promising agents entering phase III evaluation include omecamtiv mecorbl (a cardiac-specific myosin activator) and ularitide (a natriuretic peptide).
This was an ideal session to gain appreciation of the differing strategies for managing heart failure in Europe and America. I left wishing that ivabradine were available to help U.S. cardiologists meet heart rate goals, but feeling encouraged by reports of potentially useful heart failure drugs in development. The international insights gained at my first ESC Congress have added to my clinical toolbox. I recommend this conference to U.S. cardiology fellows-in-training seeking a more global perspective to their clinical practice.
What do you see as the most salient differences in clinical cardiology practice between the U.S. and the rest of the world?
September 3rd, 2013
Echo CRT Trial – Going Narrow Doesn’t Broaden CRT Population
Edward J. Schloss, MD
A once promising indication for cardiac resynchronization therapy (CRT) in selected heart failure patients with narrow QRS intervals has suffered a major blow with the premature termination of the Biotronik sponsored multicenter EchoCRT trial reported today at the European Society of Cardiology in Amsterdam.
Cardiac resynchronization therapy was developed in the late 1990s as a treatment in patients with systolic heart failure. A series of seminal trials including MUSTIC, MIRACLE and COMPANION firmly established biventricular pacing as an effective treatment for advanced systolic congestive heart failure by the early 2000s. The patients in all of these early trials had LVEF <= 35% and wide electrocardiographic QRS complexes (>120 msec or more) as a marker intraventricular dyssynchrony that could be improved with CRT.
Later trials including MADIT CRT and REVERSE showed benefit of CRT in patients with milder symptomatic classes of heart failure, but the study populations still required wide QRS complexes and severe LV dysfunction.
Analysis of these and other studies has suggested that the treatment benefit of CRT may be confined to the left bundle branch block population and the most recent US society guidelines for CRT now reflect this, assigning less weight to the non-LBBB wide QRS population.
For years, investigators have suggested that there may be an unmet need for CRT in patients with systolic heart failure who do not have wide QRS complexes, but appear to have treatable dyssynchrony by echo. Small studies, commonly single center, have shown CRT benefit in this population when pre-procedure screening echocardiography has shown evidence of dyssynchrony. A larger randomized study, RETHINQ, reported in 2007, however, failed to show any benefit in a heart failure population with echocardiographic dyssynchrony and narrow QRS. Some criticized the study for its design, with particular attention to the type of echo parameters used to define dyssynchrony. This past February, however, another randomized trial of CRT in patients with narrow QRS, LESSER-EARTH was terminated prematurely without benefit. This trial, however, did not have any echocardiographic enrollment requirements and was also limited by very slow enrollment (85 patients over 8 years).
One isolated recent bit of supporting evidence for narrow QRS CRT came from the NARROW-CRT trial that was reported this past April. This trial showed benefit of CRT in a small, randomized sample of heart failure patients with narrow QRS and echo criteria for dyssnchrony. They were randomized to CRT-D vs. D-ICD with minimal pacing. The biventricular paced group had a significantly higher proportion of patients that improved their heart failure clinical composite score. (41% vs. 16%) and exhibited a trend toward improvement in survival and heart failure hospitalization.
The best, and possibly last, remaining hope for CRT in the narrow QRS population has rested on the EchoCRT trial, which was reported today at the European Society of Cardiology meeting in Amsterdam and simultaneously published in New England Journal of Medicine. Biotronik sponsored this investigator-initiated, randomized, multicenter trial, which began enrollment in August 2008 with projected enrollment of 2330 patients. Study patients had Class III or IV heart failure with LVEF <=35%, diastolic LV dimension greater than 5.5 cm and QRS duration <130 msec. Prior to enrollment, all patients had echocardiography with modern, advanced dyssynchrony measurements including tissue doppler and speckle tracking imaging. A single core lab at the University of Pittsburgh reviewed all echoes, and patients were enrolled in the trial only if they met predetermined indices for dyssynchrony. Once determined eligible, all patients underwent placement of a biventricular ICD with blinded randomization to active CRT=ON versus CRT=OFF. The primary endpoint was a composite of time to first hospitalization for heart failure or all-cause mortality over a minimum of one year. Duration of the trial was event driven and had been expected to have been completed in December 2012.
On March 13, 2013, the EchoCRT data safety and monitoring committee notified the trial sites that the trial would be terminated prematurely due to futility. There had not been a public disclosure of this news until April of this year when this was discussed in an ACC summary of the NARROW-CRT trial publication and later reported by Cardiobrief. No details of the trial results were available until this week’s report.
The Echo CRT trial enrolled 809 patients over a mean 19.4 months. The composite outcome of death or heart failure admission was reached in 28.7% patients getting CRT vs. 25.2% of the blinded controls. There were 45 deaths in the CRT group and 26 in the control group. Although neither of these values reached statistical significance, it is worth noting that the trial was terminated for futility before comparative power could be reached, and the death data appear to show ongoing curve divergence upon termination of the trial. When analyzed specifically for cardiovascular death, the CRT group did have statistically significant excess death (37 vs. 17, P=0.004). None of the nine pre-specified subgroups showed benefit from CRT, and more procedural harm was demonstrated in the CRT group.
After this extremely discouraging but well run trial, it seems unlikely that there will be a future for CRT in the narrow QRS heart failure population. Given the current strict regulatory environment, off label implants are likely to be heavily scrutinized and discouraged. It also seems unlikely that another large-scale trial in this population will be carried out.
Although the results of EchoCRT likely eliminates the promise of CRT as a primary treatment for narrow QRS systolic heart failure, the overall field of biventricular pacing continues to advance. The positive findings of the BLOCK HF trial published earlier this year may lead to an indication for CRT as a preferred pacing therapy in patients with heart block and LV dysfunction. BIOPACE has a similar design as BLOCK HF and is reported to be in follow up. In addition, the recently initiated MIRACLE EF trial will look at CRT as a primary treatment in heart failure patients with LBBB and mild LV dysfunction. The ongoing PROMPT trial is evaluating LV or biventricular pacing as a treatment to prevent adverse myocardial remodeling early after myocardial infarction.
Reprinted with permission from Edward J. Schloss’s “Left to My Own Devices” blog.
See CardioExchange’s news coverage of EchoCRT
September 3rd, 2013
Renal Denervation: The Next Magic Bullet?
M. Louis Handoko, MD PhD
Several Cardiology Fellows who are attending ESC.13 in Amsterdam this week are blogging for CardioExchange. The Fellows include Paddy Barrett, Louis Handoko, and Amanda Vest. For more of our ESC.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.
For scientific reasons, my attention has recently been drawn to renal denervation. In a landmark paper, the Symplicity HTN-1 study group demonstrated impressive and sustained effects of this procedure on blood pressure reduction in patients with therapy-resistant hypertension. Their findings have been confirmed repeatedly by others. Renal denervation is a relative simple procedure, which has assisted in establishing this novel treatment modality. Just recently, my own institute started to use renal denervation, and the experiences are positive so far.
Soon after that paper was published, pilot studies demonstrated beneficial effects for other indications. These were the main subject of the session I attended this morning. Based on the data provided, I got the impression that renal denervation is the solution for everything. Beside hypertension, it also treats diabetes, acute and chronic heart failure, worsening of renal function, as well as obstructive sleep apnea…. Although these developments are very interesting and exciting, they also sounded too good to be true. And, there must be a reason that we are born with a sympathetic brain-kidney connection….
Fortunately, almost every presenter announced a full-scale, investigator-driven, randomized clinical trial on the specific topic, and hopefully in the near future, these trials will provide more-definite answers on the role of renal denervation. I intend to follow these developments closely. New data at the 2014 ESC meeting? You and I will see in Barcelona next year!
September 3rd, 2013
Hearts and Minds
Paddy Barrett, MB BCh BAO MRCPI MCTI
Several Cardiology Fellows who are attending ESC.13 in Amsterdam this week are blogging for CardioExchange. The Fellows include Paddy Barrett, Louis Handoko, and Amanda Vest. For more of our ESC.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.
Some years back, a good friend of mine continued to smoke despite the persistent requests by his wife that he stop. Being a psychologist, she understood that conventional requests were unlikely to be successful, and she adopted a slightly alternative strategy: She started smoking. Every time he smoked, she did too. She would only quit, when he did. Needless to say, my good friend no longer smokes.
Although successful in its outcome, this strategy clearly can’t be adopted on a larger scale, but it does highlight a very important point. Management of cardiovascular disease is as much a behavioral challenge as it is a basic science one.
There is no doubt that many of the clinical trials presented here will result in therapies that will significantly affect cardiovascular disease. But with the cost of taking a drug to market in the U.S. now estimated to be as high as US$1.7 billion, we must ask whether the degree of benefit justifies the cost.
The announcement of negative, and often staggeringly expensive, cardiovascular outcome drug studies is all too common at these meetings. Yet, we know that achieving most of the seven health metrics, including a normal weight and regular exercise, as outlined by the American Heart Association, substantially reduces not only cardiovascular mortality but also all-cause mortality. Still, the process of implementing them at a population level is costly and lengthy. But, surely, the cost and time benefit accrued must be in favor of behavioral modification.
When increasingly expensive drug trials fail to result in mortality reductions, and behavioral interventions repeatedly do so, maybe we need to rethink our strategies.
This year’s ESC has emphasized behavioral approaches, ranging from the provision of dedicated cycle lanes to and from the conference center, to the presentation of findings of provocative mortality reductions in Tour de France riders.
However, more than anything, we the delegates must first act as advocates and adopters of these behavioral interventions. For the most part, I believe we do. However, with incredulity I have witnessed several delegates avail themselves of the health-conscious option of cycling to the Congress, walk to the main entrance, and promptly light a cigarette. I’m pretty confident that the Tour de France riders studied didn’t celebrate the completion of their stage with a pack of Marlboro Lights.
Achieving the most effective and economical reductions in cardiovascular morbidity and mortality is a much a challenge of the mind as it is of the heart. But as delegates of the Congress, to achieve these benefits of the heart, maybe we need to start by changing our own minds.
How do you see the relative value of behavioral and pharmaceutical approaches? Do you avail yourself of the best “health-conscious options”?
September 3rd, 2013
A Transatlantic Taste
Amanda Ruth Vest, MBBS
Several Cardiology Fellows who are attending ESC.13 in Amsterdam this week are blogging for CardioExchange. The Fellows include Paddy Barrett, Louis Handoko, and Amanda Vest. For more of our ESC.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.
As a British cardiology fellow at a U.S. institution, I’m often asked on patient care rounds, “Would this condition be managed differently in Europe?” I’m embarrassed to admit that I have minimal knowledge of European cardiology practice — I’ve been in the U.S. for the past 7 years of training, and my British cardiology experience is limited to a 4-week medical student rotation in 2004.
In an effort to address this deficit, I submitted an abstract to ESC Congress 2013 and was delighted to have my work accepted as a poster presentation. I was slightly less delighted to discover that the lowest registration fee for this 5-day convention was 600 euros (US$790), leaving me wondering whether it was my scientific or my financial contribution that the ESC was most interested in attracting! The absence of a trainee’s registration fee is disappointing in comparison to the heavily subsidized registration offered to fellows-in-training at the American Heart Association and American College of Cardiology scientific sessions (US$110 for ACC 2013). With the costs of transatlantic flight (US$1500) and accommodation — international conferences are not reimbursed by my department — I began questioning the value of my first European medical conference attendance.
However, I am glad to report that the investment has proven worthwhile thus far. My initial perception is that the ESC is more willing to explore controversial areas; American cardiology conferences might have shied away from the Rapid Fire session “Obesity: Problem or Paradox.” Although obesity continues to be considered as a major modifiable risk factor for cardiovascular disease, there is increasing evidence that excess adiposity may promote survival in some populations with coronary artery disease or heart failure. Aziza Azimi presented data from a cohort of women with coronary artery disease in whom weight gain was associated with a reduced mortality risk, regardless of baseline BMI. Lower BMI was associated with worse outcomes in a Japanese cohort with cardiovascular risk factors (Takanori Nagahiro), and the survival paradox also held true in a post-PCI Japanese cohort (Hidehiro Kaneko). Discussion of a possible mortality benefit conferred by adipokines – cell-signaling proteins secreted by adipose tissue – was balanced by two presentations outlining the positive cardiovascular effects of surgical weight loss. Data presented by Pio Cialdella were particularly compelling in building on existing reports of reductions in left ventricular mass and end-systolic volumes after bariatric surgery.
Although the answer to the ultimate clinical question — should we still encourage cardiovascular patients to lose weight? — proved elusive, I was impressed that the ESC and abstract presenters had tackled this controversial area that sits uncomfortably alongside the weight-loss message central to American cardiovascular public health efforts.
This first taste of European cardiology had left me hungry to learn more about international clinical and research perspectives.
What do you see as the most salient differences in cardiology research between the U.S. and the rest of the world?
September 3rd, 2013
Speedy Tour de France Racers Slower to Die
Larry Husten, PHD
For more of our ESC.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 recent years, concerns have been raised about possible adverse cardiovascular effects of intense endurance exercise. Additional concerns have been raised about sports where performance-enhancing drugs are commonly used. However, a new study shows that despite these potential hazards, elite endurance athletes appear to live longer than their contemporaries.
Xavier Jouven, a triathlete and a researcher at the Sudden Death Expertise Center in Paris, France, gathered mortality information from all 786 French participants in the Tour de France from 1947 through 2012 and compared it with mortality in people of the same age in the French general population. The study was presented at the European Society of Cardiology Congress in Amsterdam and published simultaneously in the European Heart Journal.
By 2012, 208 of the French cyclists had died. They had a 41% reduction in mortality compared with their cohorts in the general population (standardized mortality ratio 0.59, CI 0.51-0.68, p<0.0001). Jouven and colleagues estimated that Tour de France athletes on average gain an extra 6 years of life. The results were consistent across age groups except for those under age 30. In this group, there was a nonsignificant increase in mortality (SMR 1.65). “A particularly high frequency of death related to traffic or race accident was observed in that young age group,” explained the researchers.
The mortality benefit for the cyclists was observed across nearly all causes of death, and included significant reductions in cardiovascular, cancer, respiratory, and digestive disease related deaths. The one exception: a small but nonsignificant excess of deaths due to traumatic causes (SMR 1.06). The most common causes of death among the cyclists were neoplasms (32.2%) and cardiovascular diseases (29%), but these occurred less frequently than in the general population.
“Our results do not allow a detailed assessment of the balance between positive effects of high level sports activity and selection of healthy elite athletes, versus any potential deleterious effects of excessive physical exercise or alleged doping,” said Jouven. “Although our results are reassuring to some extent, since no death has been observed since 1990, we have to remain careful since we cannot directly assess the potential harmfulness of doping through our analyses and results.”
Jouven said the results offered reassurance to physicians who may have been reluctant to endorse their patients’ interest in sports. But Sanjay Sharma, the trial discussant and the co-author of an accompanying editorial in the European Heart Journal, disputed the generalizability of the findings. Among other reasons, “the ability to compete in the most arduous endurance sports may in itself indicate a superior genetic composition with lower disease susceptibility.”
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