Persistent Low-Flow Aortic Stenosis After TAVR Linked With Higher 1-Year Mortality

One-third of patients with low-flow aortic stenosis undergoing transcatheter aortic valve replacement fail to regain normal flow at 6 months, and these patients have significantly worse outcomes when compared with those who achieve moderate or normal flow following the procedure, according to the results of a new study.

In an analysis restricted to PARTNER patients treated with TAVR who had low-flow aortic stenosis at baseline, individuals with a severely reduced left-ventricular stroke volume index (LVSVI) upon discharge had a significantly increased risk of death at 1 year compared with those classified as having moderate low flow or normal flow postprocedure. In a multivariate risk model, individuals with persistently severe low flow after TAVR had a 61% higher risk of death compared with those with moderate and normal flow.   

“We’ve learned over the years that aortic stenosis comes in several different flavors,” Howard Herrmann, MD (Perelman School of Medicine at the University of Pennsylvania, Philadelphia), one of the study’s lead investigators, told TCTMD. “Most patients with aortic stenosis have high gradients due to the valve obstruction, normal left ventricular function, and they maintain their flow through the valve despite the fact that it’s obstructed. That’s the classic group of patients with aortic stenosis. We’ve learned, though, that there are patients who have low flow—low stroke volume is really what we’re talking about—and that can be for a variety of different reasons.”

Severe aortic stenosis is usually defined by an aortic valve area (AVA) < 1.0 cm² and a mean transvalvular gradient ≥ 40 mm Hg in symptomatic patients. Low-flow aortic stenosis is often observed in patients with reduced ejection fraction (< 50%) and/or low transvalvular gradient. Patients with low-flow aortic stenosis can have reduced flow resulting from concomitant myocardial disease or left ventricular systolic dysfunction, said Herrmann. Those with normal ejection fractions and a reduced LVSVI are often referred to as paradoxical low-flow aortic stenosis patients.

The results of the study, with first author Venkatesh Anjan, MD (Perelman School of Medicine at the University of Pennsylvania), were published online June 15, 2016, in JAMA Cardiology.

Identifying Aortic Stenosis in Patients with Normal Gradients

To TCTMD, Herrmann noted that low flow has been previously shown to be a strong predictor of clinical outcomes in patients undergoing TAVR. For example, in a paper published in Circulation in 2013, he and others showed that low-flow aortic stenosis patients had a 50% higher risk of death after TAVR and surgical aortic valve replacement compared with patients with normal flow. Overall, Herrmann said the stroke volume index—and identification of low flow—before TAVR is a better prognostic marker of outcomes than ejection fraction and transvalvular gradient, but that it is harder to measure on echocardiography and is not routinely used by physicians. 

In this latest post hoc analysis of PARTNER, which included patients at high risk (cohort A) and those ineligible (cohort B) for surgery in the randomized trial as well as those in the continued access registry, the researchers analyzed 984 patients with low-flow aortic stenosis (defined as LVSVI ≤ 35 mL/m²) who underwent TAVR and stratified them into three groups based on their discharge LVSVI. 

Prior to the procedure, the mean LVSVI was 27.6 mL/m². Following TAVR, patients were classified as having severe low-flow, moderate low-flow, and normal flow. In the three groups, the mean LVSVI at discharge was 23.1, 31.7, and 43.1 mL/m², respectively.

Approximately one-third of patients with low-flow aortic stenosis did not improve after TAVR. For patients with severely reduced LVSVI at discharge, these individuals had persistent low flow at 6 months and 1 year whereas those with moderate-flow aortic stenosis at discharge had a normalized LVSVI by 6 months.

Overall, the 1-year rate of all-cause mortality was 22.1% among the patients undergoing TAVR. For those with persistently low-flow aortic stenosis at discharge, the 1-year all-cause mortality rate was 26.5%. In contrast, the 1-year mortality rate among patients with moderate low flow and normalized flow after TAVR was 20.1% and 19.6%, respectively. Compared with the normalized-flow patients, those with persistently severe low flow had a 45% increased risk of death at 1 year. The risk of death was more than 60% higher among the persistently severe low-flow patients compared with the two other groups combined.    

At baseline, 424 patients had classic low-flow aortic stenosis—reduced ejection fraction and LVSVI ≤ 35 mL/m²—and 559 patients had paradoxical low-flow aortic stenosis. The overall time course for improvement in flow after TAVR was similar in both groups, but for patients with classic low-flow aortic stenosis, there was no significant difference in mortality based on discharge LVSVI. Among the paradoxical low-flow aortic stenosis patients, 24.7% of individuals with persistently severe low-flow aortic stenosis had died at 1 year. 

To TCTMD, Herrmann said LVSVI and the characterization of left ventricular flow are important prognostic tools that he hopes physicians will begin considering in addition to transvalvular gradient and ejection fraction. “We have identified a high-risk group for the procedure, and now we’ve found a group of those patients who remain high-risk after TAVR,” he noted. “The question is if there is anything else we can do to help improve the outcomes of these patients. That wasn’t the purpose of the study, but it does suggest there is a subgroup that we can start to look at more carefully.”

Related Stories:

• Low-Flow, Low-Gradient Patients More Likely to Die, Less Likely to Undergo AVR
• Patients with Low Aortic Valve Gradient May Be Less Likely to Reap TAVR’s Benefits
• LV Flow After TAVR Predicts Late Mortality