Please note that the text below is not a full transcript and has not been copyedited. For more insight and commentary on these stories, subscribe to the This Week in Cardiology podcast, download the Medscape app or subscribe on Apple Podcasts, Spotify, or your preferred podcast provider. This podcast is intended for healthcare professionals only.
In This Week’s Podcast
For the week ending January 31, 2025, John Mandrola, MD, comments on the following topics: Another negative AF ablation trial, predicting AF after stroke, the value of RCTs, troponin testing in the ED, and surgical aortic valve choice.
Another Negative AF Ablation Trial
The Adelaide team has once again added to the knowledge base of AF treatment with a clean well conducted RCT looking at another AF ablation strategy. First some background:
About 10 years ago, Canadian investigators published the STAR AF II trial comparing three AF ablation strategies in pts with persistent AF. Pulmonary vein isolation (PVI )alone, PVI + lines, PVI + complex fractionated atrial electrogram (CFAE). The results have stood the test of time. The trial found no difference in AF recurrences.
STAR AF II established that less-is-more. PVI alone performed just as well as PVI plus more ablation outside the PVs. It was a disruptive finding because people believed (and some still do) that because pers AF often associates with atrial structural disease, like fibrosis, dilation etc, that PVI alone would not be enough.
But to date, only two studies of many, have found that extra ablation adds anything to PVI alone—a vein of marshall ethanol ablation and a hybrid surgical and catheter procedure modestly reduced AF. Both of these studies had small effect sizes and were statistically fragile.
The Adelaide group had the idea of studying coronary sinus (CS) isolation added to PVI. They performed a simple RCT. 50 had PVI plus CS isolation and the other group had no CS isolation. Both groups had roofline ablation in addition to PVI.
At 2 years there was no difference in arrhythmia free survival. The Kaplan meier curves were identical. While there were no statistical diff in adverse effects, one stroke and one pericardial effusion occurred in the CS isolation vs 0 in the no CSI group.
Comments:
There is not much to say here, other than a) congratulations to the team for doing a proper RCT, and b) it’s pretty clear that CS isolation does not help. So don’t do it. Some might ask whether there were enough patients and could this be a false negative finding. I’d argue against that thesis, not only was the p-value 0.9, or almost 1, but also, from a Bayesian view, you have STAR AF II, which provides a very pessimistic prior.
The combination of a negative prior plus a negative set a data should lead to a pretty negative posterior.
Finally, this is the way to answer questions in medicine. Don’t look back with retrospective data, prospectively randomize and study outcomes.
Predicting AF after Ischemic Stroke
I don’t know about your hospital, but a lot of post-stroke expensive loop recorders get placed in ours. The purpose, of course, is to detect AF, use oral anticoagulation (OAC), and reduce recurrent stroke. It’s a good purpose. People are well-intentioned.
Yet, the financial incentives are huge. I am not sure how it happened, but the hospital makes money, the doctor makes money, and there is a recurring revenue stream every month when the device is downloaded. Many patients have complained to me that they get monthly co-pays.
Studies, like the famous CRYSTAL AF, show that longer-term monitoring detects more AF than short-term monitoring. But we don’t have outcome data? Does the expense of implantable loop recorder (ILR) use result in fewer strokes? This is an especially relevant question now that we have incredibly persuasive data, from LOOP, NOAH, ARTESIA, that short-duration asymptomatic AF, you know, the kind you pick up on an ILR, confers a very low yearly stroke rate.
What’s more, many patients who receive a post-stroke ILR never have AF detected.
Well, perhaps there is an interim step. Perhaps there are predictors from the clinical features, or ECG, or both that might help enrich the population with patients who will have AF detected. If that happened, post-stroke ILR use could be more cost-effective.
The journal Heart Rhythm has published a meta-analysis of 75 studies with 58 prediction models to try and predict patients who would have AF after a stroke. First author Anna Helbitz, and colleagues from the UK, Canada, and Denmark.
Here I have another short report: Most of the studies included were at high risk of bias, a handful had good discrimination (c-statistic around 0.85) but no model showed excellent discrimination when limited to external validation or studies with > 100 AF events. And no studies considered clinical outcomes.
IOW – none of these combinations of clinical or ECG criteria were usable in clinical practice.
Comments:
The first thing to say is to remember the old saying…that prediction is hard especially about the future.
Post-stroke monitoring I think is a well-intentioned endeavor, but empirical data is weak. This meta-analysis suggests that many people have tried to find a constellation of symptoms that will predict AF, but none are reliable enough to use clinically.
Other people have tested the idea that we should just use oral AC in patients with embolic stroke of unknown origin. This too makes perfect sense, because, when you see an embolic stroke and there is no obvious atherosclerotic source, it must be due to a clot somewhere else and OAC should work. Except it doesn’t. Three RCTs, RESPECT-ESUS (dabigatran), Navigate ESUS, (rivaroxaban) and last year ARCADIA (apixaban) all failed to reduce recurrent stroke.
Therefore, to me, the obvious solution is to randomize stroke patients without an atherosclerotic source to ILR monitoring vs ECG patch recording or even home ECG recording and measure outcomes. It will take a big sample, but it’s doable.
Speaking of RCTs
I read a great review paper titled:
First author Sergio Buccheri and published open access in the BMC journal called Trials. It’s a review paper, but it is excellent.
They describe recent success in doing large simple RCTs using modern IT infrastructure. One was the RECOVERY trial in the UK during COVID-19 pandemic. The other, one of my favorite trials, the TASTE trial of thrombus aspiration during ST-elevation myocardial infarction (STEMI).
TASTE was done as part of the SWEDEHEART program, which stands for “Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies” (SWEDEHEART)
It was launched in 2009 and collects data consecutively on all patients with different cardiac conditions who require specialist medical management or interventional or surgical
Patients are informed about their proposed inclusion in SWEDEHEART when they present to a cardiology service, and they are registered using their personal identification number (PIN), a unique 12-digit number that each Swedish inhabitant receives at birth
SWEDEHEART was used to conduct TASTE which compared manual aspiration of intracoronary thrombus before (PCI) versus standard PCI without thrombus aspiration in patients with AMI undergoing primary PCI
The design of TASTE was kept very simple by employing a minimal set of exclusion criteria and by obtaining the primary endpoint of all-cause mortality by direct linkage with the Swedish Population Registry.
There was also a minimal administrative imposed on investigators by using clinical and follow-up information that was already collected in the SWEDEHEART registry and by avoiding separate monitoring and adjudication of adverse events. Then… All hospitals performing PCI in Sweden, contributed to the screening and randomization of 7244 patients within less than 3 years.
What kills me every time I watch a PCI during a STEMI is that TASTE found absolutely no difference in death or a composite of death, rehospitalization for MI or stent thrombosis at 30 days or one year. How is this possible?
The authors’ point however in discussing TASTE is not to emphasize the shocking findings, or how almost no interventional cardiologist has stopped routinely aspirating thrombus, but that TASTE was made simple by creating a system friendly to RCTs.
When I go around to lecture I am often asked about the next big development in cardiology or medicine. I can’t think of a new device or new medicine that could possibly break our curse of incremental gains of late, but one thing I do think could seriously improve healthcare would be a stronger culture of randomization.
I don’t know about you, but we don’t randomize many patients because there is infrastructure. Yes, we are doing the Left vs Left RCT of CRT vs CSP in CRT-eligible patients, but this is just one specific question. And left vs left trialists got a multi-million dollar grant from PCORI. The trial requires oodles of paperwork, multiple research coordinators. It’s gargantuan in size.
A far better situation is to have a SWEDEHEART like format where you could more easily streamline patients into trials.
The most striking aspect of visiting hospitals in Denmark is that large numbers of patients are in trials. From the hallway, they look like regular patients getting care. But being in a trial massively increases our knowledge base going forward.
Just the fact that thrombus aspiration does not work, should motivate every single doctor—everywhere—to want to randomize more of their patients.
The review paper also warns about something I see too often: you have to have proper RCTs. They need to be large enough to answer questions. Underpowered trials are an ethical disaster—because this means you experimented on humans and could not answer a question.
Another issue discussed is that clinical trials should focus on important outcomes. Reduction of BNP, for instance, is a waste of money and borderline unethical in my opinion. Surrogate outcomes should be used extremely sparing.
Read that paper—I think you will learn a lot. Enough ranting about RCTs.
Troponin Testing in the ED
JAMA-IM has published a research letter from a group at Harvard looking at cardiac biomarker use in the ED. First author, Cian McCarthy. This was mostly troponin measurements.
Few topics in clinical cardiology could be more relevant than dealing with biomarkers. While it should not be, much folly follows from mis-use of biomarker tests.
The study used a sample from National Hospital Ambulatory Medical Care Survey, examining about a 100k ED visits, which was a weighted total of nearly 732 million visits between 2014 and 2022.
Findings:
Overall, enzymes were measured in 7% of all visits. This has not changed over a decade.
Nearly one in three patients get an ECG.
Among those who had enzymes testing, 35% had chest pain, 39% had non–chest pain anginal equivalent symptoms, and 26.0% had no anginal symptoms.
Not surprising was that abnormal vital signs increased the odds of having biomarkers done. Asian vs white race doubled the odds of having an enzyme test as did the presence of cerebrovascular disease.
Only 3% of patients with an enzyme test had an acute coronary syndrome (ACS) diagnosed. Also not surprising was that ACS was more commonly diagnosed in those with chest pain then those with non-chest-pain anginal equivalent or nonanginal symptoms.
The authors concluded that a) two-thirds of the patients who had enzymes measured did not have cardiac symptoms suggest of angina, and b) of those, less than 2% had ACS, which, they write, “threshold below which the harms of evaluating for myocardial infarction may outweigh the benefits.”
Another finding that surprised them, and me, was that 75% of patients with chest pain did not undergo cardiac biomarker testing.
Comments:
I could ramble on about the folly of biomarker testing for many minutes. But I won’t.
My brain plays two movies in regard to troponin testing. One movie says docs should stop ordering these tests when the diagnosis is surely not due to plaque rupture ACS. The classic scenario is the patient with AF or supraventricular tachycardia (SVT). They played pickleball in the heat of the summer with no angina. Later that night, at rest, they go into AF with a RVR. Hours later they come to the ED. They complain of uneasiness in the chest—like many patients with AF. The problem is not an MI due to plaque rupture. It is AF and tachycardia.
Then someone draws a troponin and when it comes back elevated, it breaks the brains of the caregivers. Now the patient is put on a rule out or rule it or whatever it’s called. Instead of getting aggressive rate control of the AF and an EP consult, everyone worries about ischemia. The next day the patient gets angiography, still tachycardic by the way. Then a mid-circ is stented, despite it being totally incidental/ Now we get consulted and to care for the AF, the patient is now taking 2 or 3 antithrombotic meds because of the stent. This happens like all the time. It gives me a rash every time.
So movie number 1 says don’t measure the biomarker, then you won’t start this cascade.
But I have another movie playing in my head. This one says it should not matter whether the enzyme test is done. The test is not the problem; it’s the mis-use of the test.
Now I will self-cite. In 2021, Foy and I attempted to cure the world of troponin misuse in 1000-word editorial in JAMA-IM. We have a table too. It’s titled “Updating our Thinking on Troponin Use and Interpretation.” Sadly it’s only been viewed 6000 times.
Our take is this: If the patient with an elevated troponin is having a clinical scenario c/w Type I MI due to plaque rupture—an ACS, then treat fast with drugs and revascularization. Like you would with any STEMI.
But. But. Every other cause of elevated troponin, whether it is Type 2 MI from tachycardia, shock, anemia, or acute myocardial injury from heart failure or ICD shock or myocarditis, or chronic myocardial ischemia from CKD, or chemotherapy, or critical illness, then the treatment is TO TREAT THE UNDERLYING CAUSE.
So, nobody needs to be confused. This movie says you could do troponin on everyone coming to the ED, and no one should be mis-treated. If the troponin is elevated and it is not due to ACS, no chest pain and no ECG changes, then you just treat the underlying cause. Correct the AF rate, correct the anemia, or hypoxemia.
Help me spread the message: a) don’t measure troponins when you don’t suspect ACS. b) If you do measure troponin, and there is not an ACS, then treat the underlying cause.
Choice of Surgical Aortic Valve
I am glad I have not had aortic stentosis (AS) and had to choose between a mechanical or bioprosthetic surgical aortic valve replacement (AVR). It’s not a hard choice for older patients—who should just choose bioprosthetic valve.
But for the middle-aged person it is tough. A mechanical valve, I call them clickers, go on forever. But you have to take warfarin, which is usually fine, but sometimes isn’t.
Yet choosing a bioprosthetic valve at age 50 means that if you don’t die of a bike wreck or cancer or a 1000 other things, you may need multiple surgeries.
If I had to make this choice, being an evidence-based doctor, I might ask about outcomes. While the valve choice has clear potential pros and cons, can we say which one leads to better survival.
To answer this, you would want to have a massive RCT, which followed patients for a decade or more.
You can probably guess that such an RCT does not exist. In fact, I can’t think of many RCTs that follow patients for more than 5 years. It’s barely feasible due to costs; and patients move.
This week, in JACC, multiple authors attempted to assess survival using observational data. They used the STS-ACSD database.
About 110,000 patients had AVR during 2008-2019. 94K had bioprosthetic and 16K had mechanical AVR.
They report three main findings: one is that mechanical AVR use has declined from 20% to 10%. Second, for patients younger than 60, mechanical AVR was associated with a lower risk of death. Third, extensive sensitivity analyses confirmed mechanical AVR was associated with reduced all-cause mortality after excluding the potential influence of pure aortic insufficiency and intermediate/high surgical risk.
The main KM curves are similar but then diverge in favor of mechanical AVR after about 5 years. The paper has these graphs with age of valve surgery on the x axis and adjusted survival on the y-axis. HR favor mechanical AVR until about age 60-65 but the CI are wide.
Comments:
This is a good-intentioned effort. I mean no malice to the authors, but it is a terrible idea. This is a classic situation where there are oodles of factors that go into the choice of the valve. Some come out on a spreadsheet, like creatine, or diabetes or BP, but many don’t.
It seems blatantly obvious that only the “healthiest” “best” patients receive a mechanical AVR. And surely it those factors that improve survival. There’s just no way to be sure that the observational study is not biased.
Why even do the analysis? Some argue that in the absence of RCTs, such an analysis is better than nothing. I disagree in this case. It’s better just to say I don’t know about survival because it’s impossible to know because such different patients get different valves.
© 2025 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Jan 31, 2025 This Week in Cardiology Podcast - Medscape - Jan 31, 2025.
Comments