Medical News & Perspectives
March 20, 2023
Highlights From the American College of Cardiology’s 2023 Scientific Session: the Ketogenic Diet and Cardiac Events, a Wearable Sensor to Predict Troponin Levels, Bempedoic Acid for Statin Intolerance, and More
Melissa Suran
JAMA. Published online March 20, 2023. doi:10.1001/jama.2023.0156
The annual conference of the American College of Cardiology and World Congress of Cardiology, held in early March, spotlighted a range of late-breaking science—from nonstatin cholesterol-busting treatments to minimally invasive procedures for heart valve repair.
JAMA spoke with Conference Chair Douglas Drachman, MD, an interventional cardiologist at Massachusetts General Hospital, where he is also director of education in the cardiology division. The following is an edited version of that conversation.
JAMA:To start off, let's discuss new research on taking statins to reduce heart dysfunction from anthracycline chemotherapy.
Dr Drachman:In this study, the investigators enrolled 300 patients with lymphoma to receive high-dose anthracycline therapy as part of their chemotherapeutic regimen. These individuals were randomized to receive either atorvastatin 40 mg daily or a placebo over the course of 12 months. The primary end point was left ventricular ejection fraction reduction of greater than or equal to 10% with a reduction of the left ventricular ejection fraction below 55%. This occurred in 9% of those who received atorvastatin vs 22% of those in the placebo group.
What this means is that while taking a statin, one is less inclined to have a reduction in left ventricular function after receiving anthracycline chemotherapy. Interestingly, when compared with the placebo control, there was no difference in reports of muscle pain, liver function abnormalities, or myositis, which are sometimes associated with statin therapy. So the investigators concluded that patients with lymphoma who will undergo anthracycline chemotherapy would benefit from taking a statin.
JAMA:There was a JAMA study presented about a multifaceted intervention for patients with diabetes and heart disease. Preventive care, especially when it came to medication prescriptions, was coordinated among cardiologists, endocrinologists, and primary care clinicians.
Dr Drachman:The investigators developed a multipronged intervention to provide information regarding prescription of 3 major groups of guideline-directed medical therapies that are beneficial for patients with diabetes mellitus: high-intensity statin therapy; ACE [angiotensin-converting enzyme] inhibitor or ARB [angiotensin receptor blocker] therapy; and also SGLT-2 [sodium-glucose cotransporter-2] inhibitor or GLP-1 [glucagon-like peptide 1] receptor antagonist therapies. What the investigators did in the intervention arm was provide an assessment of clinic-specific barriers to guideline-directed medical therapies. They provided tools to coordinate care among the clinicians, as well as educational tools both for the clinicians and patients. Clinicians also received feedback on their prescribing practices.
The study’s primary end point was the percentage of patients prescribed all 3 classes of major guideline-directed medical therapy at 6 and 12 months. And 37.9% of patients in the intervention group, when compared with only 14.5% of patients in the usual care group, were receiving the guideline-directed medical therapies. The investigators found that the difference was largely driven by the prescription of SGLT-2 inhibitors and GLP-1 receptor antagonists. So the study showed that providing information to prescribing clinicians as well as patients could improve the delivery of care according to our guideline-directed medical therapy and best practices.
JAMA:Another JAMA study assessed whether a pacemaker to enhance heart rate during exercise would improve exercise performance in patients who had heart failure with preserved ejection fraction. Unfortunately, it looked like the pacemaker didn't work. Why is that?
Dr Drachman:The primary end point was a change in the Vo2 at the anaerobic threshold: that's a measurement of oxygen consumption and functional efficiency of individuals at the time of peak exertion. The secondary end points included individuals’ quality of life. This small study involved 29 patients who had pacemakers, and the researchers examined these individuals during exercise over 2 separate occasions. Half of the patients started with the atrial pacing function turned off on the pacemaker, and the other half started with the pacemaker function turned on, and then they switched groups.
The V̇o2 at anaerobic threshold was nearly identical between these 2 performance programs. For individuals with heart failure and preserved ejection fraction, it may be that a faster heart rate reduces stroke volume. Maybe that prevents potential gains in cardiac output and therefore does not allow for a higher V̇o2 and anaerobic threshold. So the investigators concluded that pacing does not help improve output or symptoms in heart failure with preserved ejection fraction in chronotropic incompetence.
JAMA:Let's also review a phase 2 trial for MK-0616, an experimental pill to reduce cholesterol. The results appear promising.
Dr Drachman:The investigators enrolled 381 participants at risk for atherosclerotic cardiovascular disease with an LDL [low-density lipoprotein] cholesterol level between 70 and 160 [mg/dL]. These participants were randomized to receive either a placebo or 1 of 4 escalating doses of an oral PCSK9 [proprotein convertase subtilisin/kexin type 9 serine protease] inhibitor that was under investigation. The primary end point was the LDL level at 8 weeks, after which point the drug was stopped, and then clinical outcomes at 16 weeks to see if there was any impact of this intervention with therapy.
The treatment reduced LDL cholesterol 41.2% at the lowest dose and 60.9% at the highest dose. The adverse event rate was similar across all treatment groups when compared with the placebo group at 16 weeks. And there was really no difference in premature discontinuation rates between those who were taking the oral PCSK9 inhibitor when compared with placebo. While this is thought provoking, we'll need larger, longer-term studies to determine the role that this oral PCSK9 inhibitor will have in our contemporary arsenal to address atherosclerotic cardiovascular disease in those with elevated LDL cholesterol levels.
JAMA:A handful of research was presented on minimally invasive transcatheter procedures to repair heart valves. Two studies focused on the mitral valve, and one study was about the tricuspid valve. Taken together, what are your thoughts on the findings?
Dr Drachman:This is an era in which percutaneous treatment of valvular therapies has really come to the forefront as an important therapeutic option. The first of the 3 studies was a real-world registry outcome study examining more than 19 000 patients who had severe mitral regurgitation. Of the individuals treated with a MitraClip for their severe mitral regurgitation, there was a very low rate of in-hospital death—about 1%. About three-quarters who underwent the treatment had New York Heart Association class III to IV heart failure on presentation, and this was reduced to about 16% at 1 month. This was a profoundly successful intervention for these patients of complex backgrounds and complex comorbid conditions.
The second study is an update to information received 2 years after 614 patients with heart failure and grade 3+ to 4+ mitral regurgitation—despite optimal medical therapy—were treated with a MitraClip compared with only guideline-directed medical therapy. At 5 years, hospitalizations occurred in 57.2% of those treated with guideline-directed medical therapy alone, and this was reduced to 33.1% with the MitraClip plus guideline-directed medical therapy. Death or heart failure hospitalizations occurred in 91.5% of those treated with guideline-directed medical therapy alone, and this was reduced to 73.6% in those treated also with the MitraClip. Two years after randomization, those who were initially enrolled in the guideline-directed medical therapy arm could cross over to the MitraClip. Those who received the MitraClip 2 years later did equivalently to those who had received the clip upfront. However, nearly half of the control group died prior to when they could have crossed over. So for those with severe symptomatic mitral regurgitation and heart failure, early therapy considering a MitraClip can be a very important part of treatment.
In the third study, investigators randomized 350 patients with severe tricuspid regurgitation to receive either edge-to-edge clip repair or guideline-directed medical therapy. The primary end point was death, tricuspid valve surgery, heart failure hospitalization, or improvement in quality of life. The significant difference strongly in favor of the tricuspid clip procedure was primarily driven by an improvement in quality of life. And at 30 days, tricuspid regurgitation was less than moderate in 87% of those who underwent the clip procedure and in only 4.8% of those in the control group. So the use of a clip procedure to treat severe tricuspid regurgitation can dramatically reduce the degree of tricuspid regurgitation and can improve quality of life.
JAMA:Another study that stood out was about using artificial intelligence, or AI, to determine how much someone should lower their cholesterol or blood pressure to overcome their inherited risk of coronary artery disease. It seems pretty futuristic.
Dr Drachman:The investigators used randomized data collected from clinical trials in genetic studies. They then trained a causal AI system to estimate the effect of blood pressure and LDL on the incidence of major adverse cardiovascular events. Following this process, they calculated the polygenic risk scores for 445 000 participants in the UK Biobank and used causal AI to determine how much the above-average risk participants would need to reduce their blood pressure, LDL, or both to achieve an average polygenic risk score. The researchers validated this system's accuracy by comparing its estimates with outcomes observed through mendelian randomization. The AI system was accurate, but family history was also a strong predictor of adverse events and should be incorporated into future models. So as you said, this is pretty futuristic, and it's interesting to see how the use of AI may help us titrate what we recommend to our patients.
JAMA:There was also a study on how a ketogenic diet low in carbohydrates and high in fats may be associated with an increased risk of heightened LDL cholesterol and heart disease.
Dr Drachman:Conducting diet research can be confounded by many factors—how a person leads their life or difficulty ascertaining if someone is adhering to a specific diet during a study. In this one, the investigators examined UK Biobank data and identified 305 participants who reported consuming a low-carbohydrate and high-fat keto diet, and they then matched the outcomes of these individuals against 1220 participants on a standard diet. They had an average of 11.8 years of follow-up data. Those who self-reported being on a keto diet had a higher LDL level and a 2-fold higher risk of major adverse cardiovascular events than those on a standard diet. But a limitation of this study is a self-reported diet at 1 point in time that was used to identify people who consumed a keto diet over many years.
JAMA:One study described an experimental bracelet-like sensor used to predict troponin I levels in obstructed arteries. It's 90% accurate and can make predictions within 5 minutes. And the study's data came from real-world clinical settings. Can you explain how this wearable sensor could expedite the time it takes to diagnose a heart attack?
Dr Drachman:The study was conducted in India, and 238 patients in an emergency department setting who presented with acute coronary syndromes received a wrist-worn system. The system uses infrared light to determine the chemical composition of elements circulating in the bloodstream. And the investigators specifically were looking to measure troponin I, which is a marker of myocardial infarction or myocardial necrosis that can predict or help to confirm an ongoing acute coronary syndrome. Often in emergency department settings, even if blood tests are returned rapidly, it might take between 50 and 60 minutes or even longer, depending on assay access. So a transdermal sensor that can indicate if individuals are in the throes of or about to suffer a heart attack could be very important to direct their therapy.
When these participants with elevated troponin I were compared to those without elevated troponin I using the wrist-worn sensor, there was a 4-fold increase in obstructed coronary arteries. One important caveat is that the ability of the infrared light to penetrate may be somewhat subject to skin tone, so the generalizability of the findings may be difficult to confirm as we consider the diverse backgrounds of patients in hospitals.
JAMA:One other study that I'd like to mention explored using bempedoic acid to lower cholesterol and reduce the risk of adverse cardiovascular events in patients with a statin intolerance.
Dr Drachman:In this study, 13 970 subjects who had either known atherosclerotic cardiovascular disease or were at high risk were randomized to receive either bempedoic acid or a placebo. Bempedoic acid is a therapeutic agent that works upstream of the HMG-CoA [β-hydroxy-β-methylglutaryl-CoA] reductase, which is the target of statin therapies and the biochemical pathways of lipid synthesis. So in individuals who are intolerant of statin, if they suffer with myositis or liver function abnormality, could this be an alternative?
A major adverse cardiovascular event was identified in 11.7% of those taking bempedoic acid compared with 13.3% of those on the placebo. In addition, bempedoic acid lowered LDL cholesterol by about 21.1 percentage points at 6 months compared with a 0.8–percentage point LDL reduction in the placebo group. So bempedoic acid seems to have impact analogous to a moderate intensity statin and could present an alternative to individuals who are intolerant of taking statin therapy.
