November 7th, 2012
Closing Remarks from AHA
Amit Shah, MD, MSCR
Several Cardiology Fellows who are attending AHA.12 in LA this week are blogging together for CardioExchange. The Fellows include Tariq Ahmad, Reva Balakrishnan, Megan Coylewright, Eiman Jahangir, Amit Shah, and John Ryan (moderator). Read the previous post here. For related CardioExchange content, go to our AHA 2012 Headquarters page.
It’s a few hours before my flight; people are busy with their noses buried in their smartphones, reading and talking about the election. While my mind is on that topic as well, I figured I would take a moment to consolidate my impressions about AHA this year. Overall, it was a relatively tamer conference than in previous years, perhaps due to a combination of the location and Hurricane Sandy. The exhibition hall seemed smaller and less crowded as well. Some good science was presented, as usual, and I enjoyed good conversation with friends and collaborators.
I wanted to highlight some of my thoughts about the late-breaking trials, as well as some of the other studies…
Late-Breaking Trials
FREEDOM. I was not very surprised about the main outcome, with CABG showing superiority over PCI in diabetics with 3-vessel disease. Nonetheless, it was interesting how a 29% reduction in total deaths from CABG equated to 1.27 total life-years gained. It would give patients some perspective. We can counsel them, “Studies show that if we do open heart surgery, you will live an average of 1.27 years longer.” The cost-effectiveness aspect of the study was also fascinating — $8,123 per QALY is cheap compared to other interventions!
Physicians’ Health Study II. Personally, I was always on the fence about multivitamins, but it seems like these findings support that notion. While the findings were mostly negative, I appreciate the silver linings: a 39% relative risk reduction in MI death (p=0.048) and 8% (p=0.04) reduction in total cancer. It is an impressive study on a population I can identify with, but I sometimes wonder about the problem of multiple comparisons when performing secondary analysis on several different outcomes.
OPERA. Fish oil does not prevent post-CABG Afib — an interesting negative study that seemed initially to have held a lot of promise for a highly prevalent issue. Nonetheless, another silver lining was found; the odds ratio for arterial thromboembolism was 0.37, p=0.047, in favor of PUFA. Is this enough evidence to give high-dose PUFAs to reduce arterial thromboembolism risk? Or should we wait for a dedicated trial on arterial thromboembolism? Is it possible that, over a longer follow-up, we would see any other omega-3 benefits unfold?
Take-Home Tweets about Other Studies
- Walnuts lower non-HDL cholesterol by about 10 mg/dL.
- Dark chocolate, albeit relatively devoid of nutrients once processed, has promise as a potent antioxidant and may even help reduce blood pressure. Beware, lovers of white chocolate!
- With regards to CAC scoring, counting the number of calcified vessels gives additional predictive capacity — although the question of whether CAC in the left main is more dangerous than CAC in other vessels is still up for debate.
- Antioxidant fruits such as pomegranates and grapes work by neutralizing free radicals in the gut, as opposed to disseminating in the bloodstream and destroying radicals elsewhere in the body. Maybe the next time you have a steak, have some wine, grapes, or pomegranate juice with it.
- While CAC is superior to carotid IMT in predicting MI, carotid IMT is superior regarding stroke prediction.
Overall, a good few days, despite the 1-hour commute time. Until next year!
November 7th, 2012
Better Evidence, More Comparators Needed in Device Research
Sanjiv Shah, MD
Medical devices play an important role in cardiac care and have helped many of our patients. As many cardiac devices are considered high-risk and are often implanted, it is essential to establish that they are safe and effective and better than the alternative before physicians can recommend their use and understand the best role for new devices on our patients. In a research letter published in JAMA, my colleagues and I looked at the last twelve years of cardiac device premarket approvals. We found that less than half (58 out of the 121) of devices were approved based on at least one study involving an active control, and 35% (42 of 121) were approved based on a single arm study without a control group or based on objective performance criteria or goals, which also don’t have any control group. Another 17% used a control group from a different study, known as historical controls. These findings mean that the majority of cardiac devices are approved without data showing that they are better than an alternative treatment.
These findings highlight an important opportunity to improve the evidence required to support high-risk medical devices. Clearly, we want to approve devices expeditiously when they can improve patient outcomes. However, we do not want to approve and start using devices that have not been shown to be better than already available devices or current medical therapy and in fact may be harmful. Comparative effectiveness studies are essential to allow us to be confident that the benefits outweigh the harms for new devices. This information is critically important as many devices are permanently implanted and removal can only be done at great risk to our patients. The quality of the evidence needs to keep pace with the technologic advances in and proliferation of new devices.
November 7th, 2012
Science, with a Little Bit of Flash
Tariq Ahmad, MD, MPH
Several Cardiology Fellows who are attending AHA.12 in LA this week are blogging together for CardioExchange. The Fellows include Tariq Ahmad, Reva Balakrishnan, Megan Coylewright, Eiman Jahangir, Amit Shah, and John Ryan (moderator). Read the previous post here. Find the next one here. For related CardioExchange content, go to our AHA 2012 Headquarters page.
At the Late-Breaking Clinical Trials session on management of LV dysfunction, I had the distinct feeling that I’ll be telling people a decade from now that “I was there” when studies on therapies that they have come to take for granted were first presented.
I found the story of RELAX-AHF to be particularly compelling. For the first time in decades, a medication appeared to improve symptoms and reduce mortality in acute heart failure. How amazing that the medication is the synthetic analog of a peptide made during pregnancy. Dr. John Teerlink, who presented the data, put it quite well when he stated, “All good things come from women.” It appeared during the presentation that the humanities and sciences were coming together to offer a new medication to patients. However, as Dr. John McMurray (the discussant) noted, we should see whether these results are replicable.
The aspect of these presentations that I have found most intriguing is the simultaneous online publication in top journals. It certainly adds an extra level of ceremony to the presentation. People seated around me were hitting their computers’ reload buttons for the New England Journal of Medicine, Circulation, and Lancet websites so that they would be able to read the simultaneously released papers during the 10-minute presentation of those results at AHA.
I am one of those who enjoy this aspect of the late breakers. I would love to be a “fly on the wall” when the decisions are made, as I’m curious about what occurs behind the scenes during these simultaneous publications. How much time do the authors and editors have to arrive at a mutually agreed-upon manuscript? What if the reviewers have major concerns? Does it ever influence the quality of the paper? Do people feel that this is too over the top and unnecessary?
November 7th, 2012
Risk Prediction and Translation to Clinical Practice
Amit Shah, MD, MSCR
Several Cardiology Fellows who are attending AHA.12 in LA this week are blogging together for CardioExchange. The Fellows include Tariq Ahmad, Reva Balakrishnan, Megan Coylewright, Eiman Jahangir, Amit Shah, and John Ryan (moderator). Read the previous post here. Find the next one here. For related CardioExchange content, go to our AHA 2012 Headquarters page.
The many sessions on epidemiology and prevention that I have attended over the last few days have had a unifying theme — risk prediction of CVD. In fact, my own study looked at risk prediction. Some may even call it the holy grail of cardiology. The discussions have been quite interesting….
Whether via a biomarker, imaging test, or other measure, there are many novel ways to predict risk. As to the current standard, there is something remarkable about traditional risk factors like high blood pressure and dyslipidemia; they have sound biologic mechanisms and are cheap and easy to measure. Also, many, many interventions have been proven to both improve these levels and reduce CVD mortality.
Will another measure ever compare to these? Clearly, coronary calcium has incredible predictive power. Nonetheless, it has the disadvantages of not being directly modifiable, of having some cost not routinely covered by insurance, and of radiation exposure. Biomarkers related to inflammation and oxidation also show promise, as with JUPITER, but showing the preventive value of interventions such as anti-inflammatory and antioxidant drugs has been challenging. The book is still open, however; hopefully, the Cardiovascular Inflammation Reduction Trial (CIRT) will give us some insight.
On another angle, however, we can appreciate the psychological benefit of risk predictors that can reduce risk by motivating behavioral change. Blood pressure is a silent killer and difficult for patients to grasp, but calcium on the heart may sound the alarm! If it can, for example, convince a patient to eat less fast food or drink less soda, then it can in fact be useful to get to the underlying risk of CHF. That to me is powerful.
We clearly have a lot to learn on this front. What are other people’s reactions to all of the risk prediction studies? Are we focusing on it too much? Or not enough?
November 6th, 2012
Poster Sessions: Better to Present or Observe?
Eiman Jahangir, MD
Several Cardiology Fellows who are attending AHA.12 in LA this week are blogging together for CardioExchange. The Fellows include Tariq Ahmad, Reva Balakrishnan, Megan Coylewright, Eiman Jahangir, Amit Shah, and John Ryan (moderator). Read the previous post here. Find the next one here. For related CardioExchange content, go to our AHA 2012 Headquarters page.
Today, I had my poster presentation session. I was excited and had worked hard on the poster. When it came time to print it, I decided to use the AHA printing service. This service is a great resource as they not only print the posters at competitive prices but also will deliver it to the conference and set it up for you.
So this morning, I woke up and hurriedly went to the convention hall to ensure my poster was there. A small part of me was worried that it might not show up or had been lost in the mix. When I showed up, I gave a sigh of relief. There was my poster, and it was set up and ready to go.
Relaxed and ready to present knowing all I had to do was show up!
The session was good but not that busy. There were only four interested people who stopped to chat. One was a reporter, two were from industry outside of the U.S., and one was a rheumatologist. Not a single cardiologist to speak of.
So after 90 minutes, I left my poster to see how others were doing. I ran into my co-fellow from Vanderbilt University, Sandeep Goyal (see picture below), who had done interesting work in atrial fibrillation and sleep apnea. We talked a while about his work before I moved on. By the end of the session, while I enjoyed talking to the few individuals who stopped to talk about my poster, I found my interactions with other poster presenters more fulfilling.
What part of the poster session do you find most intriguing — presenting or observing?
Sandeep Goyal, MD presenting work on atrial fibrillation and sleep apnea
November 6th, 2012
Ultrafiltration Fails to Show Benefit in Acute Heart Failure
Larry Husten, PHD
Although ultrafiltration (UF) in recent years has become increasingly popular as an alternative to intravenous diuretics for patients with acute decompensated heart failure with acute cardiorenal syndrome (type 1), the first clinical trial to test its value shows that it is inferior to standard drug therapy.
The results of CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) were presented at the AHA scientific session in Los Angeles by Bradley Bart and published simultaneously in the New England Journal of Medicine. The study compared UF with standard drug care in 188 patients with acute decompensated heart failure, worsening renal function, and persistent congestion.
UF was inferior to standard pharmacologic therapy as assessed by the primary endpoint of the trial, which was the bivariate change in serum creatinine and weight measured at 96 hours. Weight loss was similar between the groups (5.5 kg in the drug treatment group and 5.7 kg in the UF group ((p=0.58), but creatinine was significantly higher in the UF group:
- -0.04 mg/dL in the drug group versus +0.23 mg/dL in the UF group (p=0.003)
At 60 days, there was no difference in the rate of death or rehospitalization between the groups, but a serious safety signal emerged as more UF patients had a serious adverse event (57% vs. 72%, p=0.03).
The authors conclude:
Given the high cost and complexity of ultrafiltration, the use of this technique as performed in the current study does not seem justified for patients hospitalized for acute decompensated heart failure, worsened renal function, and persistent congestion.
In an accompanying editorial, W.H. Wilson Tang writes that “it is difficult to argue that ultrafiltration provides ‘diuretic sparing’ benefits in patients with acute cardiorenal syndrome when a well-managed pharmacologic approach provided equivalent clinical outcomes with fewer serious adverse effects.” He left hope that “a slower but steady ultrafiltration rate” might yet prove beneficial. Further, it is possible that aggressive therapy in order to reduce length of stay “may actually result in an increased incidence of the acute cardiorenal syndrome and cause unwanted consequences. Perhaps slow and steady may ultimately win the race after all.”
For related CardioExchange content, go to our AHA 2012 Headquarters page.
November 6th, 2012
A New Era in ICD Therapy — Get with the Programming!
Arthur J. Moss, MD
Dr. Moss, principal investigator of the MADIT-RIT trial, comments on the clinical implications of his study group’s research.
THE STUDY
In a trial funded by implantable cardioverter-defibrillator (ICD) manufacturer Boston Scientific, researchers randomized 1500 patients with a primary indication to receive an ICD programmed in one of three ways:
- high-rate therapy: a 2.5-second delay before therapy initiation at a heart rate of ≥200 bpm
- delayed therapy: a 60-second delay at 170–199 bpm, a 12-second delay at 200–249 bpm, and a 2.5-second delay at ≥250 bpm
- conventional therapy: a 2.5-second delay at 170–199 bpm and a 1-second delay at ≥200 bpm
During a mean follow-up of 1.4 years, both the high-rate and delayed-therapy groups had significantly lower rates of a first occurrence of inappropriate therapy than did the conventionally treated group (4%–5% vs. 20%). The all-cause mortality rate was 7% in the conventionally treated group — significantly higher than in the high-rate group (3%) and nonsignificantly higher than in the delayed-therapy group (4%).
THE EXPERT RESPONDS
Q: Do the findings from your trial effectively sound the death knell for conventional programming of ICDs? Will clinicians who continue to use conventional programming be considered remiss?
Moss: The findings from the randomized trial are very strong, so it is likely that clinicians involved in implanting and following patients with ICDs will reprogram the ICDs to the safer, more effective mode. That is how medicine is practiced.
Q: Should clinicians simply focus on high-rate programming rather than delayed programming?
Moss: Yes, that would be my recommendation. High-rate therapy was not statistically superior to delayed therapy, but high-rate therapy is much simpler to program. And patients in the trial who received high-rate therapy fared best overall.
Q: Is it time for ICD programming guidelines to be changed? Or do these results need to be confirmed in other trials that test devices made by other manufacturers?
Moss: The programming ICD guidelines need to be updated. We always like confirmation by another randomized trial or equivalent study.
Q: Are we entering an era when expertise and care in programming an ICD will become as important as expertise in implanting it? In effect, do we need to dedicate more clinical focus to the technical details of programming?
Moss: Our findings significantly simplify ICD programming and should result in less focus on the technical details of device programming.
Offer your reflections on the clinical implications of the MADIT-RIT trial.
For related CardioExchange content, go to our AHA 2012 Headquarters page. For Dr. Mark Link’s perspective on MADIT-RIT, click over to Journal Watch here.
November 6th, 2012
RELAX-AHF Stirs Interest in Novel Drug for Acute Heart Failure
Larry Husten, PHD
A new drug modeled on a hormone active in pregnancy may prove beneficial to patients with acute decompensated heart failure. Serelaxin is a recombinant form of human relaxin-2, which is known to mediate the hemodynamic changes that occur during pregnancy. The drug is under development by Novartis for use in acute heart failure.
In the REALX-AHF trial, 1161 patients were randomized to serelaxin or placebo in the first hours of acute decompensated heart failure. Results of the trial, presented by John Teerlink at the American Heart Association meeting in Los Angeles and published simultaneously in the Lancet, have sparked considerable interest in the heart failure community, since few options have proven successful in this setting.
RELAX-AHF had co-primary endpoints. For the first primary endpoint, dyspnea relief through day 5 (as measured by the visual analog scale area under the curve), serelaxin was associated with a statistically significant 19% improvement compared with placebo, resulting in a mean difference of 448 mm per hour (p=0.007). The trial therefore reached the prespecfied criterion for efficacy. However, there was no significant difference in the other primary endpoint, dyspnea relief at 24 hours. There were also no significant differences in the secondary endpoints of cardiovascular death or hospital readmission for heart failure or renal failure through day 60.
At 6 months, however, cardiovascular deaths were significantly reduced in the serelaxin group:
- 9.5% (55) in the placebo group versus 6% (35) in the serelaxin group (HR 0.63, CI 0.41-0.96, p=0.028, NNT=29)
The investigators also reported that serelaxin was associated with significant reductions in the signs and symptoms of congestion at day 2, fewer patients with worsening heart failure, and the use of lower doses of IV diuretics.
The results, concluded the authors, “provide supportive evidence for a beneficial effect of serelaxin improving symptoms and other clinical outcomes in selected patients with acute heart failure.” The trial discussant, John McMurray, said that he believed serelaxin “does improve dyspnea and other symptoms and signs of congestion” but wondered about the clinical significance of the magnitude of the improvement and, also, whether the single trial would be sufficient to gain marketing approval.
A Surprising Reduction in Mortality
McMurray, along with trial investigators and other heart failure experts present at the AHA, expended considerable energy thinking about the reduction in mortality. The Lancet authors acknowledged that the findings of a 6-month survival benefit “for a drug given for 48 h with a moderate number of death events (107 total) raises the question of whether this benefit is due to chance and whether another, confirmatory trial should be done.” McMurray noted that if only two deaths had moved from one group to the other, then the mortality finding would not have been significant.
But at an AHA news conference, Milton Packer emphasized that “if the mortality effect is true then this trial changes the way we do things.” If confirmed, he said, it would mean that cardiologists would need to treat acute heart failure patients like ACS patients and deliver immediate treatment. Other heart failure cardioloigsts, including Mariel Jessup and Greg Fonarow, agreed that the mortality finding, if confirmed, would mean that serelaxin treatment would represent a genuine breakthrough in the treatment of acute heart failure. But, said Packer, “the real question is whether the mortality difference seen in this trial is true and replicable.”
For related CardioExchange content, go to our AHA 2012 Headquarters page.
November 6th, 2012
AHA — There’s an App for That!
Amit Shah, MD, MSCR
Several Cardiology Fellows who are attending AHA.12 in LA this week are blogging together for CardioExchange. The Fellows include Tariq Ahmad, Reva Balakrishnan, Megan Coylewright, Eiman Jahangir, Amit Shah, and John Ryan (moderator). Read the previous post here. Read the next one here. For related CardioExchange content, go to our AHA 2012 Headquarters page.
Oftentimes, we have a love-hate relationship with technology. While at times I feel that it helps me to be more efficient, other times I feel the whole day is wasted trouble shooting.
Admittedly, I have geared up with technology during this conference with a smartphone, tablet, and ultra-portable laptop (total weight approx. 4 pounds). I would like to think that these tools allow me to be more time-efficient. When I reflect back, however, I think that old-fashioned pen and paper would have been just fine, if not better, in certain cases. So then are they just toys?! I think that would be an interesting debate….
Here are some of my favorite tech-related moments/tricks at AHA. Feel free to share some of yours!
- Letting go of my AHA program book “brick.” This thing probably only weighs 2 pounds, but it certainly feels like 10. The AHA app has been excellent; at any time, I can quickly pull up the 10 different sessions happening simultaneously and bookmark the ones I want to attend.
- Real-time article downloads. Often, someone will present an excellent point that happens to be referenced in Circulation or an open-access journal. The slide is up for about 10 seconds, which give me just enough time to perform a Google (or Google Scholar) search for the article with the author name, year, journal, and one key word. The article is usually one of the first items that appears; I quickly find the PDF link and open it on my mobile device. Then, I open the document with Dropbox (a free app), which saves it to my online storage account and downloads automatically to my computers at home. Now, whether or not I will actually get around to reading the articles is another question….
- Note-taking with Evernote (another free app). I like taking notes at these conferences, but find that organizing them can be a challenge. Sometimes I like to take notes on my computer and other times on my phone or tablet. I appreciate using an app like Evernote, which allows me to take notes on any of my devices and sync it with my online account. If I am on the go, I can take some quick notes on my phone. Then, if I find a seat and plant down, I can open up my laptop and continue the same note from where I left off.
- Office time on the bus. One challenge at AHA has been the commute. My hotel is in Universal Studios, and the commute has been approximately an hour. I have really appreciated being able to set up a mobile office on my commute with internet access through my phone. It really succeeds in the clutch for taking care of time-sensitive work on my laptop…like blogging!
Is there any particular tech trick, app, or aspect of the AHA app that you have found particularly useful?
November 6th, 2012
Breadth vs. Depth at AHA
Tariq Ahmad, MD, MPH
Several Cardiology Fellows who are attending AHA.12 in LA this week are blogging together for CardioExchange. The Fellows include Tariq Ahmad, Reva Balakrishnan, Megan Coylewright, Eiman Jahangir, Amit Shah, and John Ryan (moderator). Read the previous post here. Find the next one here. For related CardioExchange content, go to our AHA 2012 Headquarters page.
This year’s AHA seems to have everything for every kind of cardiologist. My colleagues, ranging from purely clinical interventionists to basic scientists, seem giddy all day with excitement. What I notice, however, is that most have kept to their area of interest.
At last year’s AHA, I was still at an early stage of differentiation into a heart failure fellow, and attended a wide variety of talks, ranging from the benefits of GWAS, to choosing patients for TAVI. I learnt quite a bit, but it seemed that I had sacrificed gaining meaningful insights into a few questions for knowing a little about many.
This year I decided to go for depth rather than breadth.
So far, this seems to have been a good decision. I have spent many hours looking at the posters focused on the use of biomarkers in heart failure and the management of advanced heart failure. The posters don’t seem to get as much attention as the oral sessions, but I found them to be incredibly interesting, especially in terms of giving me new ideas for research.
An especially interesting session I attended last night was on acute decompensated heart failure. It was titled “Why Have We Failed?” It included discussions by some of the most prominent cardiologists of our day, including Drs. Milton Packer, Adrian Hernandez, and Lynne Stevenson. Dr. Eugene Braunwald chaired the session. Each discussant gave their perspective on why the majority of our trials in ADHF have failed. They approached it from the perspective of not choosing the right patient, using the wrong endpoints, giving patients the wrong medications, and having wrong strategies and execution. The room was packed, and the attendees appeared spellbound by the discussion.
In many ways, this session epitomized, for me, the best of AHA. I left it with questions on my mind and many ideas for research: it “recharged” my inner investigator.
Today is especially exciting for those interested in heart failure. The results of RELAX-AHF (Relaxin in Acute Heart Failure) and CARRESS-HF (UF vs. usual care in Acute Heart Failure) are being presented. Initial reports released by Novartis suggest that Relaxin may have a benefit, and I’m quite excited to hear about the actual findings, as it may represent a novel treatment for acute heart failure.
Have others employed a specific strategy for getting the most out of these meetings? I’m especially curious to get input from those who do not have a specific subspecialty interest. How do you approach a meeting of this size?
