Cardiology Digest podcast: Episode #18

See how the CHA2DS2-VASc score could alter anticoagulation decisions in silent atrial fibrillation. Challenge outdated genetic constructs of race in heart failure treatment efficacy. Explore the V142I transthyretin gene variant and implications for targeted genetic screening.

Franz Wiesbauer, MD MPH
Franz Wiesbauer, MD MPH
30th Jun 2024 • 9m read
01:21
Apixaban versus aspirin according to CHA2DS2-VASc score in subclinical atrial fibrillation
03:35
Revisiting race and the benefit of renin-angiotensin system blockade in heart failure
08:14
Cardiovascular burden of the V142I transthyretin variant

What are the latest cardiology studies?

Study #1

We kick things off by exploring exactly where the CHA2DS2-VASc score fits into anticoagulation decisions in patients with silent atrial fibrillation. Building on the main findings from the ARTESiA and NOAH-AFNET 6 trials, this study sparks a thought-provoking discussion on the future of risk stratification. Tune in to hear insights that could shape your clinical practice. 

"This research analyzed data from just over 4000 patients with silent atrial fibrillation who were randomized to receive either apixaban (5 mg twice a day) or aspirin (81 mg once a day). They stratified the results based on patients’ CHA2DS2-VASc scores."

Lopes, RD, Granger, CB, Wojdyla, DM, et al. 2024. Apixaban versus aspirin according to CHA2DS2-VASc score in subclinical atrial fibrillation: Insights from ARTESiA. J Am Coll Cardiol. In Press, Journal Pre-proof. (https://www.sciencedirect.com/science/article/abs/pii/S0735109724071602?via%3Dihub)

Study #2

Next, we break down misconceptions surrounding race and treatment efficacy in heart failure with reduced ejection fraction. This study shines a light on the impacts of renin-angiotensin system inhibition across different racial groups. See how these findings challenge outdated genetic constructs of race, and what they mean for your approach to patient care.

"The primary analysis looked at over 8800 patients’ data from three randomized clinical trials that compared a placebo to renin-angiotensin system inhibitors. None of the patients studied were taking renin-angiotensin system inhibitors at the start of the study. Approximately 1 in 10 patients was Black."

Shen, L, Lee, MMY, Jhund, PS, et al. 2024. Revisiting race and the benefit of RAS blockade in heart failure: A meta-analysis of randomized clinical trials. JAMA. 24: 2094–2104. (https://jamanetwork.com/journals/jama/article-abstract/2819299)

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Study #3

Finally, we turn our focus to the V142I transthyretin gene variant, to evaluate its impacts on cardiovascular health within the U.S. Black population. This research not only highlights the need for targeted genetic screening but also raises important questions about the accessibility of costly treatments for transthyretin amyloidosis.

"The research focused on transthyretin amyloidosis, a condition where misfolded transthyretin proteins accumulate in tissues, potentially leading to symptomatic cardiomyopathy or neuropathy. A risk factor for transthyretin amyloidosis is the V142I variant in the transthyretin gene. That variant is carried by about 3% to 4% of Black individuals in the U.S.… Researchers analyzed data from four large epidemiological cohort studies involving over 23 000 self-reported Black participants."

Selvaraj, S, Claggett, B, Shah, SH,  et al. 2024. Cardiovascular burden of the V142I transthyretin variant. JAMA21: 1824–1833. (https://jamanetwork.com/journals/jama/article-abstract/2818877)

Maurer, MS, Miller, EJ, Ruberg, FL, et al. 2024. Addressing health disparities—the case for variant transthyretin cardiac amyloidosis grows stronger. JAMA21: 1809–1811. (https://jamanetwork.com/journals/jama/article-abstract/2818879)

Yancy, CW. 2024. Heart failure in African American individuals, Version 2.0. JAMA21: 1807–1808. (https://jamanetwork.com/journals/jama/article-abstract/2818878)

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Episode transcript

Please note that these timestamps are auto-generated and may be approximate.

Nora [00:00:06]:

Welcome to Medmastery’s Cardiology Digest, where in less than 15 minutes, we’ll get you up to date on important studies and advancements in cardiology that can impact your clinical practice! I’m your host, Nora, and I’m thrilled to have you tuning in. In today's episode, we cover the results of three recent trials published in top cardiology journals. First up, we kick things off by exploring exactly where the CHA2DS2-VASc score fits into anticoagulation decisions in patients with silent atrial fibrillation. Building on the main findings from the ARTESiA and NOAH-AFNET 6 trials, this study sparks a thought-provoking discussion on the future of risk stratification. Next, we break down a JAMA paper that dives into misconceptions surrounding race and treatment efficacy for heart failure with reduced ejection fraction. See how these findings challenge the outdated genetic constructs of race and what they mean for your approach to patient care.

Nora [00:01:03]:

Finally, we turn our focus to the V142I transthyretin gene variant, to evaluate its impacts on cardiovascular health within the U.S. Black population. Don’t miss a beat—make sure to subscribe to Medmastery’s Cardiology Digest so you never miss an episode. Let's get started! Today’s first study is from the pages of The Journal of the American College of Cardiology, and shows that the CHA2DS2-VASc score can be a valuable tool for risk stratification in patients with silent atrial fibrillation. This study falls into a level three category of evidence, which is right in the middle of our rating scale. Patients with a CHA2DS2-VASc score greater than four and treated with apixaban had 1.28 fewer episodes of stroke or systemic embolism per 100 patient-years, without a notable increase in bleeding risk. On the other hand, for patients who had a CHA2DS2-VASc score of four or less, the reduction in stroke or systemic embolism was not statistically significan

Nora [00:02:02]:

The study is titled "Apixaban versus aspirin according to CHA2DS2-VASc score in subclinical atrial fibrillation: Insights from ARTESiA." Conducted by Lopes and colleagues, this analysis of a subgroup from the ARTESiA trial was published about a month-and-a-half ago in May 2024. This research analyzed data from just over 4000 patients with silent atrial fibrillation who were randomized to receive either apixaban (5 mg twice a day) or aspirin (81 mg once a day). They stratified the results based on patients’ CHA2DS2-VASc scores. To provide some context for why they decided to investigate this issue, several recent trials looked at the pros and cons of anticoagulation for silent atrial fibrillation (also known as atrial high-rate episodes). Based on those trials, it looked like anticoagulation can indeed prevent ischemic events, but because those events are infrequent and offset by the risk of bleeding, anticoagulation didn’t seem to provide much advantage for patients. But this new study’s results added important nuance, showing us how the CHA2DS2-VASc score can be a useful tool for better risk assessment in patients with silent atrial fibrillation. 

Nora [00:03:14]:

Next, we’re diving into an important meta analysis from JAMA. It showed that when patients who have heart failure with reduced ejection fraction are treated with renin-angiotensin system inhibitors, there are no major racial differences in treatment outcomes. This is a critical finding that challenges longstanding misconceptions. Let's explore the study in depth. Titled "Revisiting race and the benefit of RAS blockade in heart failure: A meta-analysis of randomized clinical trials," this analysis by Shen and colleagues was published in May of 2024. This research fits into a level of evidence category one, which is the highest possible rating and reflects its robust methodology.

Nora [00:04:13]:

How was the study done? The primary analysis looked at over 8800 patients’ data from three randomized clinical trials that compared a placebo to renin-angiotensin system inhibitors. None of the patients studied were taking renin-angiotensin system inhibitors at the start of the study. Approximately one in 10 patients was Black. Here are the key findings: First, Black patients had higher rates of death and hospitalizations from heart failure compared to non-Black patients. Second, renin-angiotensin system inhibitors reduced the relative risk of the primary composite outcome (which was first hospitalization due to heart failure or death). This meta analysis showed that there was no statistically significant difference between the decreased risk provided to Black versus non-Black patients. Lastly, instead of looking at outcomes as a composite, they looked at them individually…

Nora [00:05:08]:

… (i.e. first hospitalization due to heart failure, cardiovascular death, and total hospitalizations due to heart failure): For the first hospitalization due to heart failure, there was a statistically significant difference in relative risk reduction: 38% decreased risk in non-Black patients, versus an 11% decreased risk in Black patients. On the other hand, for cardiovascular death, as well as total hospitalizations due to heart failure, there was no statistically significant difference in the degree of risk reduction between Black and non-Black patients. Those findings remained consistent even when the researchers added two studies that used an angiotensin-receptor blocker with an angiotensin-converting–enzyme inhibitor (that is,  an ARB with an ACE inhibitor). An additional important point is that higher baseline event rates for Black individuals mean that similar reductions in relative risk result in larger reductions in absolute risk. Ultimately, this was an important analysis because early trials for renin-angiotensin system inhibitors for heart failure with reduced ejection fraction gave the impression that Black individuals might not benefit from renin-angiotensin system inhibitors as much as their non-Black counterparts.

Nora [00:06:21]:

An expert said that this meta analysis should lay to rest the idea that Black patients who have heart failure with reduced ejection fraction benefit any less from inhibition of the reenin-angiotensin system. It reminds us that race, often misunderstood as a genetic determinant, does not actually influence the efficacy of renin-angiotensin system inhibitors. In other words, Black and non-Black patients who have heart failure with reduced ejection fraction should receive the same treatment. 

Nora [00:07:35]:

So this study came out just last month in JAMA, and showed that Black individuals carrying the V142I transthyretin gene variant have increased long-term risks for hospitalization due to heart failure and mortality. This was a cohort study titled "Cardiovascular burden of the V142I transthyretin variant", and was led by Selvaraj and colleagues. It fits into a level of evidence category three, which is in the middle of our rating scale. However, the study carries substantial weight due to its relatively large sample size and lengthy follow-up.

Nora [00:08:51]:

The research focused on transthyretin amyloidosis, a condition where misfolded transthyretin proteins accumulate in tissues, potentially leading to symptomatic cardiomyopathy or neuropathy. A risk factor for transthyretin amyloidosis is the V142I variant in the transthyretin gene. That variant is carried by about 3% to 4% of Black individuals in the U.S. and was the primary focus of this study. Researchers analyzed data from four large epidemiological cohort studies involving over 23 000 self-reported Black participants—the goal was to understand the clinical risks associated with this genotype. The study's key findings are eye-opening: 3.2% of participants had the V142I variant. The demographic and clinical profiles of the carriers were similar to non-carriers.

Nora [00:09:42]:

The mean age was 61 years, 78% were women, 62% had hypertension, and 21% had diabetes.

Over an average follow-up of 15.5 years, carriers of the V142I variant faced about a 70% higher risk of hospitalization due to heart failure and about a 12% higher risk of all-cause mortality. These risks were markedly age-dependent, starting at age 63 for hospitalization due to heart failure with reduced ejection fraction, and age 72 for all-cause death. Hospitalizations were primarily due to heart failure with reduced ejection fraction. By age 85, carriers experienced a life expectancy reduction of 1.9 to 2.8 years when compared to non-carriers. The estimated cumulative loss of life for the broader U.S. Black population was almost 1 million years. An expert commenting on the study said that these data indicate that the V142I gene variant is not rare among Black people in the U.S. and has a sizable impact on their health and longevity (that increases with age!). The data from this study can guide decision-making regarding genetic testing and suggests a compelling need for genetic screening in the Black population, which could inform the use of expensive but potentially life-saving treatments for transthyretin amyloidosis.

Nora [00:11:05]:

Before we wrap up, make sure you subscribe so you never miss an episode. And if you have any feedback or thoughts about this episode, write to us at [email protected]—we’d love to hear from you! New to Medmastery? We provide internationally accredited CME courses through our digital platform that’s received multiple awards for outstanding digital education. We’re highly commended by the British Medical Association and used by residency programs and universities to train both clinicians and students. Our faculty practices, teaches, and trains at leading universities around the globe. We’re rated excellent on Trustpilot, 21% of our paying members report that Medmastery has helped them save at least one life, and we’d love to help you next! 

Nora [00:11:50]:

Ready to take your skills to the next level?  Use the link in the episode description to grab a free trial at Medmastery.com and check us out. You have nothing to lose and a wealth of knowledge to gain! Thank you so much for tuning in this week. If you’ve found this episode helpful and know any colleagues who’d feel the same, please share this podcast with them. And if you have a few seconds to spare, it would help us a lot if you could leave us a review. That's all for today. Have a fantastic week, and we hope to see you next time!

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