Jun 24, 2022 This Week in Cardiology Podcast

John M. Mandrola, MD


June 24, 2022

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 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 June 24, 2022, John Mandrola, MD comments on the following news and features stories.

General Comments, One Announcement

Next week is our July 4th Independence Day holiday. This Week in Cardiology will take a week off and return July 8.

I had the pleasure to give a couple of lectures at the regional Cardiac Society of Australia and New Zealand (CSANZ) meeting via Zoom. Thanks to the organizers for the invite and the kind comments about this podcast. My slides aimed to provoke humility and I’m grateful for the chance to show them.

I have been seeing a few more comments and reviews and I am grateful for these. Remember, if you disagree, please let me know—preferably in the comment section of the |Medscape Cardiology or on Twitter. I learn each week and really appreciate the feedback, even if it is critical.

I also want to let you in on a secret. Any success this podcast has achieved owes a lot to the generosity of my virtual mentors, who I badger with questions. To those who help me better understand things, I want to say thank you. If I started mentioning names, I’d surely miss some. You know who you are.


This week, the Journal of the American Medical Association (JAMA) published the results of the DECAAF II trial, led by friend and colleague Nassir Marrouche, now at Tulane University. DECAAF II studied a novel way to improve the results of ablation of persistent atrial fibrillation (AF). At this moment, there is no general agreement on how best to ablate persistent AF. During panel discussions at AF meetings, there are as many different ablation approaches to persistent AF as there are panelists.

Evidence wise, what we know from an older randomized controlled trial (RCT) called STAR-AF 2 is that the standard pulmonary vein isolation (PVI) lesion set is as good as PVI plus any other add-on ablation. The core idea that Marrouche had was that atrial fibrosis (or scar) was important in the maintenance of AF. And this was more than just an idea—he led the first DECAAF study, published in JAMA in 2014, which found that atrial tissue fibrosis, estimated by delayed enhancement magnetic resonance imaging (MRI), was independently associated with likelihood of recurrent arrhythmia.

Thus, since left atrial fibrosis associates with higher recurrences after AF ablation, it made sense that targeting these areas with ablation in addition to PVI would improve outcomes. You might be wondering why. It’s because areas of scar within heart tissue allow for channels of slow conduction and unidirectional block of wavefronts.

Recall the three components of reentry—multiple pathways; slowed conduction in one or more pathways; and unidirectional block. It's why we ablate entire areas of scar in the ventricle to cure ventricular tachycardia. You ablate the channels. Well then, perhaps it would work in AF.

What I absolutely love about this story is that Marrouche did not promote this procedure because it made sense, and he is a key opinion leader and because his group had seen promising results using it. That would be eminence-based medicine. Instead, he said let’s study in the proper way: with an RCT.

  • The trial was done in 44 centers of excellence in AF in 10 countries.

  • 843 patients with persistent AF were randomly assigned to PVI plus MRI-guided atrial fibrosis ablation vs PVI alone.

  • The primary endpoint was the time to first atrial arrhythmia after a 90-day blanking period.

  • The primary safety composite endpoint was stroke, PV stenosis, bleeding, heart failure (HF), or death.

  • There was no significant difference in atrial arrhythmia recurrence between groups (fibrosis-guided ablation plus PVI patients 43.0% vs PVI-only 46.1 hazard ratio [HR], 0.95 [95% CI, 0.77-1.17]; P = .63).

  • Patients in the fibrosis-guided ablation plus PVI group experienced a higher rate of safety outcomes (9 vs 0 in PVI group; P = .001).  

  • Six patients (1.5%) in the fibrosis-guided ablation plus PVI group had an ischemic stroke compared with none in PVI-only group.

Their conclusion: Among patients with persistent AF, MRI-guided fibrosis ablation plus PVI, compared with PVI catheter ablation only, resulted in no significant difference in atrial arrhythmia recurrence. Findings do not support the use of MRI-guided fibrosis ablation for the treatment of persistent AF.

Comments. While I am sure my friend Nassir wished that the atrial fibrosis guided strategy worked, I want to say this is still one of the most positive stories I can recall this year. It is how medical science should work. They had a good idea, one with plausibility, but instead of reporting and promoting small case series or retrospective reviews, they tested the strategy in a proper RCT.

The RCT unequivocally showed that this approach did not reduce AF over and above standard PVI, and it was associated with a significantly higher rate of complications. Their discussion offered some reasons why fibrosis guided ablation may not have worked but there were no attempts to spin (or distract us from the non-significant primary endpoint); there were no post-hoc analyses.

  • I already had great respect for Nassir and his DECAAF II co-authors. Their rigorous empirical approach to this problem and their clearly written spin-free manuscript only bolsters my respect for them. DECAAF II is like a shining light on how medical science ought to work.

  • We have made great progress in cardiology and electrophysiology in the past two decades and this has set a high bar for new therapies.

  • We should not be surprised when new things don’t work. Not working better than a standard is the norm.

Smoking and Heart Failure

The Journal of the American College of Cardiology (JACC), one of the top journals in cardiology, has published an observational study that aimed to quantify the association of cigarette smoking and its cessation with the incidence of HF —with preserved or reduced ejection fraction (EF).

The investigators used the Atherosclerosis Risk in Communities (ARIC) study, a longitudinal database in four communities. Never smokers comprised the control arm.

What do you think this study found?

  • There was a dose-dependent association between smoking and HF.

  • Smoking cessation was associated with a lower risk of HF.

I highlight this paper for two reasons: Why do we need such a study? And why is a top journal publishing such a study? I mean no offense to the authors or JACC but come on, life is short, attention spans even shorter. It takes time and energy to gather the data, write the manuscript, and answer the peer review queries. Lots of time.

I am not against replication studies. We need more of them. But smoking? Seriously? I mean, smoking is literally the absolute worst thing people can do for their health. We’ve known this for decades. Of course it is associated with HF. Of course stopping smoking is crucial for health.

We don’t need any more studies that find that smoking associates with more of disease x or y. Smoking is terrible and it causes cancer, stroke, coronary disease, chronic obstructive pulmonary disease, erectile dysfunction, bad teeth, and a host of other diseases.

That it also likely increases the odds of HF does not matter, because it already shreds health in every other way possible.

Speaking of Marginal Use of Time and energy: Vitamins

JAMA has published a US Preventive Services Task Force (USPSTF) evidence report, editorial, and patient page on the lack of evidence for benefit of vitamin supplementation in people who don’t have vitamin deficiency. Again, we have known this for years. Thousands of words were written, peer-reviewed, edited, copy-edited, and the conclusions are the same. They are always the same.

  • Vitamin supplements don’t prevent heart disease, stroke, or cancer.

  • Of note, USPSTF recommends against vitamin E because there is strong evidence that it does not prevent heart disease.

  • They recommend avoiding beta-carotene because there is evidence it increases the risk of lung cancer in those already at risk.

Comments. My take of vitamin studies is that we should stop wasting money on such efforts. The world has oodles more pressing health problems that need solving.

I have learned that a large group of vitamin-takers are resistant to evidence. I no longer wrestle with patients about vitamins. I simply say there have been lots of studies and none show benefit. Let’s talk about something important, like getting more exercise, eating fewer Cheetos, and taking the tablets that have passed muster in clinical trials.

Pre-op Testing

JACC has published an observational study looking at the impact of AF on the risk of post-op outcomes after noncardiac surgery. This topic is close to my heart because I bet that I get up to four preop “clearance” requests a day. Before I tell you about the specifics of the study, let’s clear the air about pre-op clearance.

I am emotional about this topic because I believe we literally burn money with pre-op testing. If tomorrow all pre-op testing magically became evidence-based, I bet we would save billions of dollars that could be used to reduce disparities of care. Office visits, then echocardiograms, exercise electrocardiograms, nuclears all waste money before noncardiac surgery. It breaks my heart the money we waste in this endeavor.

Second comment: I hate the term cardiac clearance. No mortal human being can clear a person for surgery. I have probably stopped surgery a handful times in 25 years, and these were patients who had weeks to months to live. I do call surgeons often about high-risk oral anticoagulation (OAC) interruptions such as in patients with prior stroke and a mechanical valve, but I never say a person is not cleared. I say, Hey, are you really sure the benefits outweigh the risk in this person? Many times, the surgeon replies, Oh, that changes things, Iet’s take a less invasive approach. The fact that well-educated professionals have accepted the foolhardy concept of clearance depresses me.

With that as background, here is what the Cleveland Clinic investigators did. They took older adults in a Medicare database who were admitted for non-cardiac surgery from 2015-2019 and divided them into two groups – those with AF and those without AF. Of course, these will be unbalanced groups because AF patients will be sicker. So, they used propensity matching to try to even out baseline differences. The primary outcome was 30-day death rate, myocardial infarction (MI), stroke, and HF. They then examined the incremental utility of using AF in addition to the revised cardiac risk index (RCRI) and CHADSVASC score.

  • This was a large study of 8.6 million older adults; 16% had AF.

  • After matching, AF was associated with a 31% higher risk of mortality and heart failure, a 40% higher rate of stroke, and a 19% lower rate of MI.

  • Results were consistent in subgroup analysis by sex, race, type of surgery, and all strata of RCRI and CHADSVASC score.

  • AF improved the discriminative ability of RCRI (C-statistic 0.73 to 0.76).

  • The lower rate of MI is not obvious. And on further stratification by CHADSVASC score, pre-existing AF was associated with an increased risk of MI for patients with a score of 0 to 1 and a decreased risk for those with a score greater than 1.

The authors concluded that, “Adding pre-existing AF to the RCRI can improve risk prediction of adverse cardiovascular events after noncardiac surgery.”

Comments. I worry first about the internal validity of these findings. Sure, it makes sense that AF ought to associate with greater risk. But why is there a lower risk of MI? And why do the lower CHADSVASC patients have a higher risk while those with higher CHADSVASC have a lower risk?

The authors speculate that we might use OAC more quickly in patients with AF, and that would lower rates of MI, but if that were the case, why would it not also lower stroke rates? Stroke rates were higher in patients with AF.

One more likely explanation in my mind is statistical noise. For instance, they tell us they did not have info on whether patients were on rate vs rhythm control, and they had no data on EF, left atrial size, or subtypes of AF. This is crucial, because AF is defined by its vast variability. A 35 year old runner with two episodes of AF vs a 76 year old man with chronic kidney disease and permanent AF are both in the same category of having AF, but they are as different as can be. This is an existential weakness of the study.

But let’s assume the data are without confounding issues. Let’s assume it is totally accurate. How much did it improve over and above the standard revised cardiac risk index? Well, it improved the discriminative ability of the risk index (C-statistic from 0.73 to 0.76; P < 0.001) to predict 30-day adverse cardiovascular events. What does that mean? It has to be a big deal because the P-value is highly significant. Wrong.

  • The C-statistic, which can be thought of as a concordance index, is a measure of how well a logistic regression model fits for a binary outcome.

  • The C-statistic indicates that a randomly selected subject who experienced the outcome will have a higher predicted probability of having the outcome occur than a randomly selected subject who did not experience the outcome.

  • A C-statistic of 0.5 is random chance—flipping a coin. A C-statistic of 1 is a perfect fit.

  • The difference between 0.73 and 0.76, as in this paper, may be statistically significant, but it is clinically useless.

Dr. Andrew Flapan, a consultant cardiologist in Scotland who graciously took me around Edinburgh, railed against the notion of being “high-risk.” High-risk is not a diagnosis he said.

The notion of being x or y or z percent high-risk pre-operatively is of minimal value because there is scant evidence that it is modifiable. Doing heart catheterization or a percutaneous coronary intervention has not been shown to reduce outcomes. I went back and found no Class Ia (RCT-level guidance) evidence.

In fact, the CARP trial studied a super high-risk group of patients with established coronary artery disease and upcoming vascular surgery. Coronary-artery revascularization before elective vascular surgery did not significantly alter the long-term outcome. On the basis of these data, a strategy of coronary-artery revascularization before elective vascular surgery among patients with stable cardiac symptoms cannot be recommended.

And if revascularization does not benefit, why do we do so many stress evaluations before surgery? Is it to benefit us, or the patients?

I will cite a 2021 observational study in vascular surgery that finds huge variation in pre-abdominal aortic aneurysm stress testing among US hospitals. And no reduction was observed in major adverse cardiac events or 1-year mortality among centers with high stress test usage.

I don’t see quantification here as helpful. Is the surgery necessary? Is it highly likely to improve health or prolong life? If so, then it doesn’t matter if there is .03 diff in a C-statistic. You just do it.


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