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COMMENTARY

Mar 07, 2025 This Week in Cardiology Podcast

John M. Mandrola, MD

Disclosures

March 07, 2025

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In This Week’s Podcast

For the week ending March 7, 2025, John Mandrola, MD, comments on the following topics: Listener feedback on asymptomatic aortic stenosis (AS), transcatheter aortic valve replacement (TAVR) vs surgical aortic valve replacement (SAVR), coronary artery calcium (CAC), and revascularization for patients with ischemic LV dysfunction.

Listener Feedback Number 1. On Feb 14, I misspoke about the NOAH and ARTESIA trials. I said NOAH was rivaroxaban vs placebo, but of course NOAH was edoxaban vs placebo. Two listeners noted that and I will change the transcript. Sorry for the mistake.

The second listener feedback is worth expanding a bit, based on new papers published in JACC.

Listener Feedback Asymptomatic AS

I received a note this week from a doctor for whom I have the highest respect for. He was in fact one of my mentors at Indiana and he was instrumental in me choosing cardiology as a career. I offer this to you because I put this person in the 99% of doctors I have worked with in the past three decades.

He did not agree with my opposition to operating on asymptomatic patients with severe aortic stenosis (AS). I felt the evidentiary support was weak, severe AS is not so simple to diagnose, and a change in practice pattern would lead to even more low-risk patients getting transcatheter aortic valve replacement (TAVR).

My mentor wrote: While I have been a loyal listener of TWIC, I was disappointed with your view on the timing of aortic valve intervention in patients with asymptomatic aortic stenosis.

I do agree with several of your points:

  • The asymptomatic patient with aortic stenosis is often not asymptomatic when the physician takes a careful history. My experience has been that when carefully questioned, patients with aortic valve areas of 0.75 cm2 or less are frequently symptomatic.

  • I also worry that increasing the indications for AV replacement, particularly TAVR, will result in an explosion of TAVR procedures.  I also agree that the consequences of AV block requiring pacemaker implantation is an under-recognized issue.

And here’s a list of what he disagreed with:

  • Secondary cardiac damage impacts adversely on the prognosis of patients with AS and starts before the onset of symptoms or impaired left ventricular (LV) ejection fraction.

  • Accumulating clinical evidence supports the earlier timing of AVR with asymptomatic severe AS and those with upstream cardiac damage secondary to AS.

  • The use of cardiac magnetic resonance (CMR) to evaluate for late gadolinium enhancement may help to identify higher risk patients who need earlier intervention.

  • Several studies (i.e., DANAVR) are excluding patients with very severe AS - Vmax > 5 meters/second from randomization.

  • Unless asymptomatic patients are followed closely, the LV remodeling may lead to upstream sequelae including mitral regurgitation, left atrial enlargement, atrial fibrillation (as you know a very difficult condition to treat in the presence of severe AS), pulmonary hypertension, RV dilatation and tricuspid regurgitation (TR).

  • AS is not a benign disease.  In a large US database of almost 600,000 adults from 24 hospitals, the untreated mortality of patients with mild AS was 24%, 34% for moderate AS, and 45% for severe AS.  An Australian population database of over 25,000 patients showed similar results.

You and I grew up under the mentorship of Dr. Charles Fisch, who recommended a conservative approach to management of cardiac patients. 

In general, this approach served me well during my career.  However, I have changed my opinion with regards to early intervention for severe asymptomatic AS.  Given the availability of excellent cardiac surgeons or interventional cardiologists, consideration of earlier intervention seems warranted.

Overuse of TAVR

Regarding the overuse of TAVR, especially in young patients, I want to make note of two papers recently published in the TAVR vs SAVR space.

One is an “updated” meta-analysis of RCTs of TAVR vs SAVR in low-risk patients. First author was Robin Reddy.

The attempt was to pool trials to assess outcomes. New trials have been published and older low-risk trials have reported longer term follow-up.

This meta-analysis included Partner-3, EVOLUT-low-risk, UK TAVI, NOTION, DEDICATE, and NOTION 2.

The main finding, published in JACC, was that about 5300 lower-risk patients were randomized 1-1 TAVR vs SAVR and at 5 years in the pooled survival analyses of reconstructed time-to-event analysis, TAVR was associated with a 20% reduction in the hazard of all-cause death (hazard ratio [HR]: 0.80; 95% CI: 0.66-0.97; P = .02) and a 19% reduction in the hazard of all-cause death or disabling stroke (HR: 0.81; 95% CI: 0.68-0.96; P = .01) compared with SAVR.

There was no difference in stroke (HR: 0.97; 95% CI: 0.74-1.26; P = .80).

The authors concluded:

In lower-risk patients, TAVR was associated with a reduced hazard of death and death or disabling stroke compared with SAVR, while rates of stroke were equivalent.

However, even they note in the next sentence that:

Most patients have not yet undergone 5-year follow-up, and so these findings may change as further longer-term data become available. The present data are informative for lower-risk patients and treating clinicians, but further randomized trials and longer-term follow-up are required, particularly in younger patients.

Comments

I find this is a troubling study. Though the authors offer the duration of follow-up caveats there are many other caveats.

First, at least two of the included trials included intermediate risk patients. It’s an age-old problem with meta-analyses because you simply have to be cautious about what studies are included.

Second issue was that the authors did not have individual patient-level data and instead used a procedure with software to extract the coordinates of the published Kaplan-Meier survival curves, along with information on the number of patients at risk and the total number of events.

Their aim was to reconstruct the underlying time-to-event data for each treatment group. They then used these reconstructed data to generate, and pool estimates of survival probabilities and HRs.

While this software-heavy technique has been published and has been used, there are substantial limitations—many of which are beyond the scope of my methodologic limitations. JACC does offer a nice accompanying editorial from Joshua Wallach and David Cohen which describe some of these. I guess my point would be if you had trials with similar duration of follow-up and similar patients and you could make an individual patient analysis, you could simply pool data rather than extrapolating things from graphs from PDFs.

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