By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
SYNOPSIS: This study of U.S. registry of mitral transcatheter edge-to-edge repair data revealed a minority of patients undergoing this procedure experience optimized medical therapy, with wide variations across sites.
SOURCE: Varshney AS, Shah M, Vemulapalli S, et al. Heart failure medical therapy prior to mitral transcatheter edge-to-edge repair: The STS/ACC Transcatheter Valve Therapy Registry. Eur Heart J 2023; Aug 26: ehad584. doi: 10.1093/eurheartj/ehad584. [Online ahead of print].
Mitral transcatheter edge-to-edge repair (M-TEER) has shown substantial benefit when applied to patients with congestive heart failure (CHF) and significant mitral regurgitation (MR) despite medical therapy. The best evidence for this approach comes from the 2018 COAPT trial, in which successful M-TEER led to lower rates of heart failure hospitalization and all-cause mortality rates at two years and five years.1
One of the central points of the COAPT design was the stipulation that patients were enrolled only if they continued to experience at least moderate-to-severe MR and to be symptomatic despite using maximally tolerated doses of guideline-directed medical therapy. To this end, all patients in COAPT were required to be assessed by a heart team that included a heart failure specialist. Unusually, at least for a major trial, enrollment of each patient required review by a central eligibility committee, which confirmed that all criteria were met, including the use of optimized guideline-directed medical therapy (GDMT).
In routine medical practice, achieving optimal GDMT happens less often than in clinical trials. The extent to which patients referred for M-TEER for secondary MR undergo GDMT optimization before their procedures has not been described. Varshney et al studied the U.S.-based Transcatheter Valve Therapy (TVT) database to identify all patients with an ejection fraction (EF) less than 50% undergoing M-TEER for secondary MR between July 2019 and the end of March 2022. There were data available for 4,199 patients across 449 sites at least 30 days after the procedure, while one-year data were available for 2,014 patients across 341 sites. Before the procedure, beta-blockers were prescribed for 85.1% of patients, while other elements of medical therapy were administered less frequently. Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB) were prescribed for 44.4% of patients, and mineralocorticoid receptor antagonists (MRA) for only 28.6%. Angiotensin receptor neprilysin inhibitors (ARNI) were prescribed for 19.9% of patients. Notably, sodium-glucose cotransporter-2 inhibitor use is not captured in the TVT database; therefore, Varshney et al did not report that information in their paper.
Only 19.2% of patients were prescribed each of the three most common pillars of GDMT (referred to as triple therapy: beta-blockers, ACEI/ARB or ARNI, and MRA) at the time of the procedure. A total of 38.2% were prescribed double therapy, 36% were prescribed a single medication, and 6.5% received no GDMT before TEER.
While some patients cannot tolerate GDMT because of low blood pressure, declining kidney function, or side effects, the wide site-level variability observed in the study suggests other factors were at play. For example, using so-called triple therapy varied from 0% to 61% of patients among sites that performed at least 10 procedures per year. At 10 sites, representing 6.9% of the whole, no patients were prescribed triple therapy before TEER.
Outcomes at both 30 days and one year were better among patients taking more optimized GDMT. The composite rate of all-cause mortality or HF hospitalization after TEER was 23.1% in those taking triple therapy, 24.8% in those taking double therapy, 35.7% in those taking a single drug, and 41.1% in those not taking any GDMT before the procedure. The mortality rate alone was more than 24% for patients on zero drugs or a single drug vs. 13.7% and 13.9% in those treated with double and triple therapy, respectively. The authors concluded a low percentage of patients undergoing percutaneous therapy for functional MR were treated with optimized GDMT, with fewer than one-fifth prescribed comprehensive medical therapy. Double and triple therapy, compared with a single drug or no drug, were associated with reduced risks of mortality and HF hospitalization at one year.
COMMENTARY
Transcatheter mitral valve repair has proven efficacious in treating functional MR in patients with HF caused by reduced ejection fraction (HFrEF) when conducted on a background of optimal medical therapy. Those who follow the literature might remember two major trials performed with the MitraClip system in CHF with severe functional MR came to opposite conclusions. COAPT, which mandated aggressive upfront GDMT optimization, showed a reduction in mortality and HF hospitalization rates.1 In contrast, the MITRA-FR trial, did not require such optimization. Those authors reported no difference in the rate of death or HF hospitalizations among patients treated with either the MitraClip or best medical care.2
There are additional differences between these two trials, yet the best available evidence supports medical optimization before proceeding to M-TEER. Current U.S. guidelines give a class IIa recommendation for TEER in patients with severe secondary MR and persistent symptoms despite undergoing treatment with optimal GDMT.3 The limited uptake of GDMT in this U.S.-based registry is consistent with other studies of HFrEF patients without mitral valve disease, showing relative underuse of medical therapy.
All patients with HFrEF will benefit from optimized medical therapy. In addition, some fraction of patients in this category who are relatively undertreated will see improvements in the severity of MR such that they no longer require or qualify for mitral intervention. Some have advocated for a mandated heart team approach in these patients that would dial in the involvement of HF specialists,4 but this is unlikely to be added in the foreseeable future. The central point here is these procedures should be seen as an adjunct to medical therapy, rather than as a replacement for it. Programs offering this therapy should strive as much as possible to provide comprehensive HF care to these patients.
REFERENCES
1. Stone GW, Lindenfeld J, Abraham WT, et al. Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med 2018;379:2307-2318.
2. Obadia JF, Messika-Zeitoun D, Leurent G, et al. Percutaneous repair or medical treatment for secondary mitral regurgitation. N Engl J Med 2018;379:2297-2306.
3. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2021;143:e72-e227.
4. Haydock PM, Flett AS. Management of heart failure with reduced ejection fraction. Heart 2022;108:1571-1579.
This study of U.S. registry of mitral transcatheter edge-to-edge repair data revealed a minority of patients undergoing this procedure experience optimized medical therapy, with wide variations across sites.
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