The Take Home: AHA Scientific Sessions
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The American Heart Association Scientific Sessions were held virtually Nov. 13 to 15. The event included numerous presentations of new data in cardiology.
Healio spoke with several experts to discuss top takeaways from the meeting, including Sana M. Al-Khatib, MD, MHS, FHRS, from Duke University School of Medicine and Duke Clinical Research Institute; Joanna Chikwe, MD, FRCS, from Smidt Heart Institute at Cedars-Sinai; Cardiology Today Editorial Board Member and American College of Cardiology President Dipti Itchhaporia, MD, FACC, FESC, from Hoag Memorial Hospital and the University of California, Irvine; Cardiology Today Editorial Board Member Erin D. Michos, MD, MHS, FACC, FAHA, FASE, from Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease; Cardiology Today Chief Medical Editor Carl J. Pepine, MD, MACC, from the University of Florida; and Roopinder K. Sandhu, MD, MPH, from Smidt Heart Institute at Cedars-Sinai.
Editor’s Note: All coverage from the AHA Scientific Sessions can be found here .
Fitbit Heart Study
Sandhu: The use of wearable technologies for the detection of atrial fibrillation is rapidly rising. It is critical that these technologies are validated, and for this reason the Fitbit Heart Study provides important information.
The study of 445,669 participants with a compatible Fitbit device and a smartphone with the Fitbit app found the positive predictive value of the novel algorithm in Fitbit wearables used to detect an irregular pulse that is confirmed on an ECG patch monitor as AF is very high. Among the 1,057 participants who had an ECG reading after an irregular heart rhythm detection on their Fitbit, 32.2% had AF confirmed (men, 36.3%; women, 27.8%; aged 65 years, 33.4%; aged < 65 years, 31.3%).
The algorithm requires at least 30 minutes of irregular rhythm to detect AF, which means shorter episodes will not be detected. Interestingly, only one-third of the patients with an irregular heart rhythm detection completed a virtual visit with a physician.
This is helpful information for clinicians who may have patients who present with an irregular heart rhythm detection from a Fitbit wearable, but there are still many unanswered questions. Specifically, what is the clinical significance of these AF episodes, how should clinicians manage these events and does treatment, specifically with oral anticoagulation therapy for stroke prevention, provide a net clinical benefit?
We should encourage the use of wearables once we have data to clearly define the optimal patient population, clinical care pathway and management strategy. We have not done that yet.
We need to have more randomized clinical trials that compare wearable technologies to usual care, assess clinical outcomes and potential harms.
CRAVE
Al-Khatib: In CRAVE, 100 healthy volunteers were assigned to consume or avoid coffee every day for 14 days, communicated via daily texts and reminders. In the intention-to-treat analyses, random assignment to consume coffee was associated with a 54% increase in premature ventricular contractions (95% CI, 19-200; P = .001), 1,058 additional Fitbit-measured steps per day (95% CI, 441-1,675; P = .001) and 36 fewer minutes of Fitbit-measured sleep per night (95% CI, 22-50; P < .001). There were no between-group differences in atrial arrhythmias or glucose levels.
To date, data on this topic have been conflicting and have resulted from observational studies. But this is a question that we get asked very frequently by patients. These facts underscore the importance of the CRAVE trial.
The study suggests that coffee consumption does not increase the risk for atrial arrhythmias, but it increases the premature ventricular contraction count. It increases exercise activity and reduces sleep. Despite the importance of the trial, the sample size was relatively small, and the research participants were healthy volunteers. They are very different from the average patient we see in clinical practice. Also, the study included short-term outcomes. I would love to see more data on long-term outcomes, including harder endpoints such as sustained ventricular arrhythmias and sudden cardiac death.
While we still need more data, I think these results should give us some reassurance that coffee consumption does not appear to increase the risk for AF. The association with premature ventricular contractions and ventricular arrhythmias deserves further study.
I like the fact that the researchers effectively utilized a digital health platform to conduct the study. I commend them on the very creative design.
PREPARE-IT 2
Michos: Icosapent acid (Vascepa, Amarin) is an interesting compound. It does lower triglycerides, but in the REDUCE-IT trial, the 25% reduction in major adverse CV events was far greater than what we would expect to see with just triglyceride lowering. There are likely anti-inflammatory and antithrombic effects with icosapent ethyl. Inflammation also plays a causative role in symptomatic COVID-19. An activation of the inflammatory cascade can lead to secondary organ damage, including cardiac injury.
PREPARE-IT 2 was, overall, a null study. It included 2,052 adults aged at least 40 years with a confirmed positive COVID-19 diagnosis no more than 7 days from onset of symptoms and without a clear indication for hospitalization. Compared with placebo, researchers observed fewer COVID-19 hospitalizations or deaths at 28 days among participants in the icosapent ethyl arm (11.16% vs. 13.69%); however, the HR of 0.84 did not reach statistical significance (95% CI, 0.65-1.08; P = .166).
However, for the primary outcome, there was a reduction in COVID-19 hospitalization and death of 16%, so the HR did go in a favorable direction. A factor to keep in mind is these were patients who were COVID-19-positive but not that sick. Anyone already hospitalized was excluded. We have gotten better at treating people with COVID-19 as the pandemic progressed. The rate of hospitalization was lower than what the trial was powered for.
There are some key takeaways. There have been a lot of concerns about AF in these omega-3 fatty acid trials. While this was a 28-day study, there was no increased risk for AF with a loading dose that was twice as high, and no major bleeding. This reaffirms the safety of icosapent ethyl.
Where do we go from here? A larger randomized clinical trial would be needed to see a benefit with icosapent ethyl, but I don’t think that is feasible. This study likely will not affect clinical practice right now. Vaccination remains the best strategy to prevent severe COVID-19.
EMPULSE
Itchhaporia: EMPULSE is yet another study in the compendium of trials that show an early benefit with SGLT2 inhibition.
The trial included 530 patients hospitalized with a primary diagnosis of acute HF, defined as de novo or decompensated chronic HF, regardless of left ventricular ejection fraction and diabetes status. Two-thirds of the patients had reduced EF. After clinical stabilization, patients were randomly assigned to receive once-daily empagliflozin 10 mg (Jardiance, Boehringer Ingelheim/Eli Lilly) or placebo.
The primary outcome was clinical benefit at 90 days, defined as a composite of time to all-cause death, number of HF events (HF hospitalization, urgent and unplanned outpatient HF visit), time to first HF event and an at least 5-point difference in change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score. Patients assigned empagliflozin were 36% more likely to experience clinical benefit at 90 days compared with those assigned placebo (win ratio = 1.36; 95% CI, 1.09-1.68; P = .0054).
All-cause mortality among patients assigned empagliflozin was half that of patients assigned placebo (4.2% vs. 8.3%). HF events occurred in 10.6% and 14.7% of empagliflozin and placebo patients, respectively.
I am not surprised by these findings, as they are consistent with previous trials in this class. If one looks at the primary component endpoints by subgroup, HF status, diabetes status or age did not influence the findings.
The data are consistent. The evidence is clearly there for SGLT2 inhibitors to have a place in HF therapy. Now, we may initiate these therapies earlier, in the hospital. I think most of us have wanted to do that; these data make us feel better that even when patients are acute, yes, HF should be treated.
DREAM-HF
Pepine: Unfortunately, because the DREAM-HF trial did not meet its primary endpoint, the very important novel findings did not receive the attention that I believe it merited.
Briefly, in 537 patients with NYHA class II or III HF with reduced EF, a single dose of allogeneic mesenchymal stem cells (Mesoblast) with standard of care medical therapy did not reduce hospitalizations for worsening HF compared with standard of care alone. However, these cells did reduce new MIs or strokes by 65% among all treated patients (P = .001) and reduced CV death, MI or strokes by one-third (P = .021). Inflammation appeared to be an important predictor of the response to these cells. In those with elevated inflammation (high-sensitivity C-reactive protein 2 mg/L or greater), the cells reduced MIs or strokes by 79% (P < .001).
These provocative new findings support the suggestion that although the cells were injected into heart muscle, they had important vascular anti-inflammatory actions at a distance. This concept (allogeneic mesenchymal stem cell effects on blood vessels at a distance from their heart muscle site of injection) is also consistent with findings from two randomized trials with the same cells given to patients receiving left ventricular assist devices. In those trials, the cells reduced the frequency of gastrointestinal bleeding. This new knowledge should stimulate new trials with intravenous injections of allogeneic mesenchymal stem cells for conditions where inflammation/immune activation is a key mechanism.
AVATAR
Chikwe: The AVATAR trial results are a rather positive finding for early intervention in relatively low-risk patients with asymptomatic severe aortic stenosis.
Among 157 patients, after a mean follow-up of 32 months, those assigned to undergo early surgical aortic valve replacement had a lower rate of the primary composite endpoint, which included all-cause death, MI, stroke or unplanned hospitalization for HF, compared with patients assigned to a conservative strategy of watchful waiting (HR = 0.46; 95% CI, 0.23-0.9; P = .02).
We certainly see a real preponderance of patients who have been observed until they are symptomatic and then referred for surgery. I think a lot of that reflects a natural caution among cardiologists based on older outcomes with surgery. The AVATAR trial had pretty phenomenal outcomes: operative mortality was 1% and the patients did extraordinarily well with surgery. It’s something we see across the board with surgery: Asymptomatic patients with severe valve lesions, and particularly mitral valve regurgitation, are followed until they become symptomatic; generally, most of the data we have suggest that they just do better with an earlier intervention.
One of the caveats is a small number of patients, and the findings are driven by a very few endpoints. For confidence, you have to put the AVATAR trial in the context of the RECOVERY trial, which found broadly similar findings. My bias is that if you’ve got a surgical team that you know can deliver consistently good outcomes and you have a low-risk patient who is asymptomatic, it’s appropriate and probably beneficial to send them for surgery, or at least surgical assessment, before they develop symptoms.
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