Moderate Aortic Stenosis and HFrEF Combo Portends Poor Survival, Study Finds

Valve replacement, particularly TAVI, showed promise as an early intervention, but a randomized trial is ongoing.

Moderate Aortic Stenosis and HFrEF Combo Portends Poor Survival, Study Finds

Accumulating data make clear the detrimental effect of moderate aortic stenosis (AS) in patients who have heart failure with reduced ejection fraction (HFrEF), a new study suggests, and they point toward the potential for improving survival after TAVI.

Compared with patients who had HFrEF but not moderate AS, those with the combination of both had greater risk for mortality at 3 years (HR 2.98; 95% CI 2.08-4.31), as well as for the composite of HF hospitalization and mortality (HR 2.34; 95% CI 1.72-3.21). Additionally, those who had TAVI over the follow-up period survived longer than those on medication alone.

Senior author Marie-Annick Clavel, PhD (Laval University, Quebec, Canada), said the while there is consensus that moderate aortic stenosis is not benign, optimal management for the subset of patients with both HF and moderate aortic stenosis is unclear. However, she said current thinking seems to be moving away from “wait-and-see” approaches to intervention, despite AVR not currently being recommended in the clinical practice guideline for valvular heart disease.

“We know that left untreated, they are going to have an abysmal prognosis. If they go to intervention, they may have very high operative mortality. Even with a conservative procedure they have higher mortality rates because they are really sick patients.” she told TCTMD. The current study, published this week in the Journal of the American College of Cardiology, add to prior data by Clavel and colleagues showing that at 4 years, 61% of patients with HFrEF and moderate aortic stenosis died, were hospitalized for HF, or required AVR.

“It raises an important question: should we do something? It makes sense that transcatheter intervention would be better as opposed to surgical intervention and that is what our study shows,” Clavel said.

LV Dysfunction + Moderate AS = Bad Combination

For the new study, Clavel and colleagues led by Guillaume Jean, MD (Laval University), examined data on 262 patients with moderate aortic stenosis that was diagnosed on the basis of aortic valve area of 1.0-1.5 cm2 and peak transaortic velocity of 2-4 m/s at rest or after dobutamine stress echocardiography. These patients, who also had LVEF < 50%, were compared with 262 patients with HFrEF but no aortic stenosis. Medication use was comparable in both groups, with the exception of more calcium antagonist prescribing in the group with moderate aortic stenosis. That group also had a higher rate of PCI than the HFrEF-only group (34% vs 24%; P = 0.01).

We know that left untreated, they are going to have an abysmal prognosis. Marie-Annick Clavel

At 3 years, all-cause mortality (the primary outcome) occurred in 35% of patients with HFrEF plus moderate aortic stenosis and in 23% of those with HFrEF only (P < 0.0001). HF hospitalization, the secondary endpoint, occurred in 29% of patients with HFrEF plus moderate aortic stenosis and 18% with HFrEF only.

Of 44 patients who underwent AVR at a median of 10.9 months of follow-up (15 TAVI and 29 surgical), TAVI was associated with improved survival compared with optimal medical management (adjusted P = 0.05), while surgical AVR was not (adjusted P = 0.92).

The researchers say it is likely that worsening of valvular obstruction imposes pressure overload on the left ventricle, which is particularly problematic for patients with HFrEF. They also suggest that one reason why TAVI may be better than SAVR in this patient population is that it has been shown to be associated with less patient-prosthesis mismatch. Numerous studies, including an analysis from the PARTNER trial, have indicated that patient-prosthesis mismatch poses heightened mortality risks for patients with HFrEF, Clavel noted to TCTMD.

TAVR-UNLOAD Expected to Provide More Clarification

In an accompanying editorial, Sammy Elmariah, MD, and Nilay K. Patel, MD (both from Massachusetts General Hospital, Boston), note that while the sample sizes in the study are small and thus prevent definitive conclusions from being drawn, “the analyses provide strong evidence of the detrimental clinical impact of moderate AS in patients with diseased ventricles.”

Elmariah and Patel agree say that while retrospective studies indicate poor clinical outcomes for patients with LV systolic dysfunction and moderate aortic stenosis, it is unclear whether it is “singularly tied to LV dysfunction or if the AS confers additive risk.” Furthermore, they say the need for high-quality data on the optimal timing of AVR in patients with HFrEF and moderate aortic stenosis is urgent.

One ongoing, international RCT that is expected to provide some of those answers is TAVR-UNLOAD, which is comparing TAVI and optimal HF therapy versus optimal HF therapy alone in approximately 300 patients with moderate AS and advanced HF defined by: NYHA class ≥ 2, NT-proBNP > 900pg/mL (or BNP > 200 pg/mL), or HF hospitalization within the previous 2 years.

“We don't have the answer yet,” Clavel said. “If TAVR-UNLOAD is positive, then transcatheter AVR may become an option for these patients even if the stenosis is moderate.”

  • Jean and Patel report no relevant conflicts of interest.
  • Clavel reports a CT core laboratory research contract with Edwards Lifesciences and a research grant from Medtronic.
  • Elmariah reports research grants from Edwards Lifesciences, Medtronic, and Abbott Vascular and consulting fees from Edwards Lifesciences.