Cardiology Digest podcast: Episode #17

Study #1

First up, what happens when a seemingly promising ablation strategy for nonparoxysmal atrial fibrillation disappoints? We're diving into why early nonrandomized trials can often give us hope, but the real story unfolds when randomized trials are performed. How does pulmonary vein isolation stack up against additional treatments, and is there a role for the routine use of left atrial appendage ligation in atrial fibrillation ablation? 

"This paper only came out a couple of months ago, and we love to see that it was a prospective, multicenter, randomized, controlled trial. They included just over 600 patients. Roughly two-thirds of them underwent both left atrial appendage ligation and pulmonary vein isolation. The remaining third only had pulmonary vein isolation done."

Lakkireddy, DR, Wilber, DJ, Mittal, S, et al. 2024. Pulmonary vein isolation with or without left atrial appendage ligation in atrial fibrillation: The aMAZE randomized clinical trial. JAMA. 13: 1099–1108. (https://jamanetwork.com/journals/jama/article-abstract/2816924)

Study #2

Next, can early rhythm control in atrial fibrillation significantly reduce dementia risk? Our second study reveals compelling associations that persist even after rigorous sensitivity analyses. We explore the aggressive use of antiarrhythmic medications in treating new-onset atrial fibrillation, and see what recent research suggests about this approach.

"Early rhythm control was previously linked to lower dementia risk in atrial fibrillation patients. However, this association hadn’t been explored specifically in patients with a prior stroke, which is of interest because stroke is also known to raise dementia risk."

Lee S-R, Choi, E-K, Lee, S-W, et al. 2024. Early rhythm control and incident dementia in patients with atrial fibrillation and prior stroke. JACC Clin Electrophysiol. Online ahead of print. (https://www.sciencedirect.com/science/article/abs/pii/S2405500X24001889)

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Study #3

Lastly, we turn our attention to older adults who’ve had an acute myocardial infarction, and what to do about lipid-lowering therapy—what's the latest evidence? This new study provides welcome insights, especially given the previous exclusion of this age group from randomized trials. How do high-intensity therapies fare in older patients compared to their younger counterparts, and what potential confounders should we keep in mind? See how these findings impact clinical practice!

"This study is important because older age increases the risk of mortality after an acute MI, yet, as I alluded to earlier, most randomized controlled trials exclude patients older than 80 years of age, leaving us with uncertainty regarding how best to treat them."

Fayol, A, Schiele, F, Ferrières, J, et al. 2024. Association of use and dose of lipid-lowering therapy post acute myocardial infarction with 5-year survival in older adults. Circ Cardiovasc Qual Outcomes. 5: e010685. 

https://www.ahajournals.org/doi/10.1161/CIRCOUTCOMES.123.010685

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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 the latest cardiology research from top journals that impacts clinical practice! I'm Nora, your host, and today we’re diving into the results of three recent trials. First up, what happens when a seemingly promising ablation strategy for nonparoxysmal atrial fibrillation disappoints? Early nonrandomized trials gave us hope, but the real story unfolded via randomized trials. We’ll look at a JAMA paper evaluating whether there’s a role for the routine use of left atrial appendage ligation in atrial fibrillation ablation. Next, can early rhythm control in atrial fibrillation significantly reduce dementia risk? A new study reveals compelling associations. Join me to explore the aggressive use of antiarrhythmic medications in treating new-onset atrial fibrillation! Lastly, we’ll turn our attention to older adults who’ve had an acute myocardial infarction, and see what to do about lipid-lowering therapy.

Nora [00:01:09]:

The latest research provides welcome insights for clinical practice, especially given the previous exclusion of this age group from randomized trials. Stay tuned for the full breakdown, and make sure to subscribe so you never miss an episode. Also, help us spread the word by sharing this episode with your colleagues! Now, let's jump into the data! Our first study is a recent JAMA paper looking at treatment of atrial fibrillation. They rigorously examined whether there’s any benefit to doing left atrial appendage ligation in addition to pulmonary vein isolation. The results? They found no additional benefit from doing the extra procedure. Now let’s examine the details of how they came to that conclusion.

Nora [00:01:49]:

This study is titled “Pulmonary vein isolation with or without left atrial appendage ligation in atrial fibrillation: The aMAZE randomized clinical trial”. It was spearheaded by Lakkireddy and colleagues. This paper only came out a couple of months ago, and we love to see that it was a prospective, multicenter, randomized, controlled trial. They included just over 600 patients. Roughly two-thirds of them underwent both left atrial appendage ligation and pulmonary vein isolation. The remaining third only had pulmonary vein isolation done. This paper fits into a Level of Evidence rating #2. So it’s pretty solid, even though it’s not the gold standard, which would be level 1. The study was funded by the manufacturer of the device used for the ligation procedure (i.e., LARIAT), which is not FDA-approved for this particular use-case. 

Nora [00:02:37]:

The primary endpoint: in the year after pulmonary vein isolation, no atrial arrhythmias lasting longer than 30 seconds. A slightly higher percentage of one group achieved the primary endpoint. Any guesses on which one it was? Remember, one group had left atrial appendage ligation and pulmonary vein isolation. The other group only had pulmonary vein isolation. I’ll give you a couple of seconds to make your guess! Well, about 64% of patients who had left atrial appendage ligation plus pulmonary vein isolation achieved the primary outcome. Whereas only 60% of patients who had pulmonary vein isolation alone achieved the primary outcome. But ultimately that difference wasn’t statistically significant. Additionally, the acute success rate for the procedures, defined as isolation of all pulmonary veins, was the same in both groups.

Nora [00:03:28]:

Lastly, the defined safety endpoint was met: only 3.4% of the left atrial appendage ligation group experienced serious adverse events within a month of the procedure. An expert remarked that although an earlier non-randomized trial made the combination of left atrial appendage ligation and pulmonary vein isolation appear promising, it’s now clear that it offers no additional benefits beyond pulmonary vein isolation alone. This fits a recurring pattern of preliminary non-randomized trials sparking optimism regarding ablation for atrial fibrillation, but then those hopes are dashed by subsequent trials that are more rigorous and show no advantage of additional treatments beyond pulmonary vein isolation. Our expert concludes that we shouldn’t routinely use left atrial appendage ligation in atrial fibrillation ablation. Onwards to study number 2! This one is really encouraging, showing that if a stroke survivor develops atrial fibrillation, early rhythm control was correlated with a reduced risk of developing dementia. Let’s dive into the details!

Nora [00:04:33]:

This research was published last month in JACC: Clinical Electrophysiology and is titled "Early rhythm control and incident dementia in patients with atrial fibrillation and prior stroke." It was led by Lee and colleagues and falls under a Level 3 category of evidence—so fairly solid, and right in the middle of our rating scale. Providing context for this study, early rhythm control was previously linked to lower dementia risk in atrial fibrillation patients. However, this association hadn’t been explored specifically in patients with a prior stroke, which is of interest because stroke is also known to raise dementia risk. The investigators looked at national insurance data in South Korea to identify over 41 000 stroke survivors who later developed atrial fibrillation. The average age was 70. About a quarter of those patients received early rhythm control (primarily via anti-arrhythmic medications), but the rest did not. Then the two groups were compared to see whether or not early rhythm control made any difference to the risk of developing dementia. 

Nora [00:05:37]:

The median follow-up period was 2.7 years. The fact that the early rhythm control group had a notably lower weighted incidence of dementia diagnoses is striking because the usual standard of care was no early rhythm control. How much of a difference did it make? Looking at the incidence of dementia per 100 person-years, the risk of any dementia was reduced by 17%, the risk of Alzheimer’s dementia was reduced by 17%, and the risk of vascular dementia was reduced by 20%! These results held up after propensity scoring, and were confirmed by multiple sensitivity analyses. So, an expert said that based on these findings, combined with the results of other randomized, controlled trials, we ought to treat new-onset atrial fibrillation aggressively. 

Nora [00:06:46]:

Now I have another question for you. If I were to ask you whether intensive lipid-lowering therapy after an acute myocardial infarction improves survival in patients aged 80 and above, what would your best guess be? Ready for the answer? Well, a recent study showed that the answer is a resounding yes, providing much-needed data for this underrepresented age group.

Nora [00:08:03]:

This new study was a large observational study titled "Association of use and dose of lipid-lowering therapy post acute myocardial infarction with 5-year survival in older adults." Conducted by Fayol and colleagues, it was published in the April 2024 issue of Circulation: Cardiovascular Quality and Outcomes. In terms of the level of evidence, this study ranks in the middle of our rating scale, at a Level 3! This study is important because older age increases the risk of mortality after an acute myocardial infarction, yet, most randomized controlled trials exclude patients older than 80 years of age, leaving us with uncertainty regarding how best to treat them. The researchers used data from a nationwide registry in France. They identified over 2200 adults who were discharged after an acute myocardial infarction and were 80 years of age or older (the average age was 85, and about half were female).

Nora [00:08:57]:

They looked at how high-intensity lipid-lowering therapy affected 5-year mortality. High-intensity therapy was defined as atorvastatin greater than or equal to 40 mg daily, or, any combination of a statin and ezetimibe. Then they looked at the 5-year survival rates. For every 20 patients, about 7 out of 20 would survive if on no lipid-lowering therapy. But about 12 out of 20 would survive if taking high-intensity lipid-lowering therapy. What about conventional lipid-lowering therapy? Well, almost half of patients survived, but the difference compared to no lipid-lowering therapy wasn’t statistically significant. An expert commenting on the study remarked that it’s important to consider potential confounders. The patients who received high-intensity therapy were generally younger, with fewer comorbidities, and more frequently presented with ST-segment myocardial infarction. Of course, the study’s analysis adjusted for these variables, but nonetheless, residual confounding remains a possibility.

Nora [00:10:03]:

Additionally, the study couldn't account for negative side effects linked to the therapy. Nonetheless, the study’s authors wrote that “These results suggest that high-intensity lipid-lowering therapy should not be denied to patients on the basis of old age.” And the expert commenting on the study agreed, saying that despite potential confounders, this study provides confidence that we can prescribe high-intensity lipid-lowering therapy to our older patients, just like we do for our younger patients. So, what do you think? Was there anything about today’s research papers that surprised you? Is any of what you heard today going to change your treatment approach for certain patients? If you have any feedback or comments to share, please write to us at [email protected] and we may feature it in a future episode! And can I ask you for a quick favor? If this episode was helpful to you, please help us reach more people by sharing it with a colleague. And if you have a few seconds to spare, could you leave a review for this podcast? That would mean the world to us! Next, are you new to Medmastery? If so, here’s the lowdown! Medmastery is a multiple award-winning medical education provider that’s been highly commended by the British Medical Association.

Nora [00:11:15]:

We offer internationally accredited CME courses that are trusted by clinicians, residency programs, and universities around the world. Rated excellent by 100 on Trustpilot, you can trust that you're learning from the best. Our faculty members practice, teach and train at reputable universities worldwide. Having taught hundreds of thousands of clinicians, Medmastery has a proven track record. And 21% of our paying members say we've helped them save at least one life. We'd love to help you do the same. Use the link in the episode description to grab a trial account at medmastery.com and get started today. Thank you so much for tuning in, and please join me next time for more of the latest cardiology research. We offer internationally accredited CME courses that are trusted by clinicians, residency programs, and universities around the world. Rated excellent by hundreds on Trustpilot, you can trust that you're learning from the best—our faculty members practice, teach, and train at reputable universities worldwide. Having taught hundreds of thousands of clinicians, Medmastery has a proven track record, and 21% of our paying members say we’ve helped them save at least one life. We’d love to help you do the same! Use the link in the episode description to grab a trial account at Medmastery.com, and get started today! Thank you so much for tuning in, and please join me next time for more of the latest cardiology research. And, you know what I’m going to say, right? Don’t forget to subscribe so you never miss an episode!