LV Diastolic Dysfunction Linked With Higher Mortality Post-TAVR

Advanced left ventricular diastolic dysfunction (LVDD) in patients undergoing TAVR is linked with almost a fourfold increase in risk of postprocedural death as early as 30 days postprocedure, according to new data. The findings could have implications for the timing of TAVR in certain patients, the authors say, although more research is needed.

While the root cause of LVDD can be multifactorial, the degree to which it can be reversed and how much aortic stenosis plays a mechanistic role both remain unclear. Prior research has found conflicting evidence as to the effect LVDD has on TAVR outcomes, and from his experience, senior study author Thomas Pilgrim, MD (Bern University Hospital, Switzerland), told TCTMD “there are some things that you cannot resolve” with TAVR. Looking at reasons for rehospitalization in patients who underwent the procedure, he said that his team thought LVDD could be a culprit.

For the study, published online yesterday ahead of print in JACC: Cardiovascular Interventions, lead author Masahiko Asami, MD (Bern University Hospital, Switzerland), and colleagues looked at a consecutive cohort of 777 patients undergoing TAVR as part of the Swiss TAVI Registry, 70.1% of whom were diagnosed with LVDD at baseline on echocardiography. Specifically, 18%, 36.3%, and 19.1% were categorized as having grade I, II, and III LVDD, respectively.

Rates of all-cause mortality at 1 year increased with rising LVDD grade: compared with patients with normal diastolic function, the risk of dying was twice as high in those with grade I LVDD (adjusted HR 2.32; 95% CI 1.15-4.66), 2.5-fold higher in those with grade II LVDD (adjusted HR 2.58; 95% CI 1.43-4.67), and four times higher in those with grade III LVDD (adjusted HR 4.21; 95% CI 2.25-7.86).

On echocardiographic follow-up through 18 months, LVDD remained unchanged in about half of the 87 patients with available data. The mortality difference between patients with and without LVDD began to emerge 30 days after TAVR and continued through mid-term follow-up, strongly driven by an increased risk of cardiovascular mortality.

According to Pilgrim, an important takeaway from the study is that the effect of LVDD can emerge early after TAVR. “That is an important risk factor also for the periprocedural period,” he noted.

There were no differences with regard to MI or cerebrovascular events, and the mortality results were maintained in both a sensitivity analysis of patients with preserved LVEF as well as an adjusted model including LVEF, LV mass index, and LV stroke volume.

Further, multivariate analysis identified LVDD as an independent predictor of all-cause death at 1 year, with grade III LVDD being the strongest predictor (adjusted HR 3.13; 95% CI 1.87-5.25) followed by diabetes, chronic obstructive pulmonary disease, and peripheral vascular disease.

Patients with and without evidence of LVDD has similar measurements of aortic valve area and mean transvalvular gradient, but those with LVDD had a lower LVEF and more commonly had concomitant mitral or tricuspid regurgitation. Also, patients with LVEF < 50% were more likely to have advanced LVDD and a higher NYHA class.

Takeaways

Commenting on the study for TCTMD, James Flaherty, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), said this research corroborates many of the findings of a study published last year, on which he was senior author. “Specifically, the grade of diastolic dysfunction as graded echocardiographically prior to TAVR correlates with long-term outcomes,” he said. “The greater the severity of diastolic dysfunction, the worse the outcomes were and that mirrored our findings as well.”

In an editorial accompanying the current study, Patricia Pellikka, MD, and Ratnasari Padang, MBBS, PhD (Mayo Clinic, Rochester, MN), write that “baseline diastolic function evaluated by echocardiography provided important prognostic information beyond standard risk factors alone. Because even mild [diastolic dysfunction] at baseline can negatively influence outcome 1-year post-TAVR, the challenge remains to identify which parameters in asymptomatic patients with severe [aortic stenosis] best identify who may benefit from early [aortic valve replacement].”

Flaherty agreed that this is an important question. If aortic stenosis is severe and symptomatic, then the presence of LVDD might not add to the “decision algorithm” of whether to perform TAVR, he said. However, “it may add to prognostication in terms of what you might expect for long-term outcomes.”

Because some diastolic dysfunction may be reversible with treatment, that could be a future avenue of research, Flaherty added. But for asymptomatic patients, “the way that I look at this is it may be worth considering what the level of diastolic function is in deciding on timing of treatment,” he said, noting that the findings should only be considered hypothesis-generating at this time.

LVDD grade will likely never play into the simple decision of whether to offer treatment to a patient, Flaherty said, given that patients with advanced diastolic dysfunction who underwent TAVR “likely had much better outcomes than if they had got no treatment at all. So advanced diastolic dysfunction does not equal futility in this population necessarily.”

Pilgrim, for his part, said he would have written a similar editorial to what Pellikka and Padang produced. “Since diastolic dysfunction is reversible to some degree in early stages, it may be better to perform TAVI before the development of the irreversible status of that particular diastolic dysfunction in order to increase your long-term outcome,” he said.

Also, it’s important to pay attention to the screening method of LVDD, Pilgrim observed, suggesting a role for MRI, looking for fibrosis.

When Is ‘Too Late’?

Pellikka and Padang argue that “potentially lifesaving treatments such as TAVR must be administered before it’s too late”—for example, before myocyte death, myocardial fibrosis, and advanced diastolic dysfunction. Echocardiography will likely “continue to play a central role in guiding therapeutic decisions,” and “continued refinements” to it will enhance patient care, they say.

Future research should include larger, prospective analyses of TAVR patients with LVDD, Pilgrim said. Also, “it would be better to have invasive assessment of left ventricular diastolic dysfunction rather than an echocardiogram” and be able to “differentiate outcomes according to exact etiology” of LVDD, he added.

Flaherty would also like to see a large study looking at diastolic dysfunction “serially after TAVR—what recovery you get—and try to understand if recovery correlates with better outcomes.”

Today “we're learning about a lot of different features of myocardial structure and function that can be seen in patients with aortic stenosis that can impact outcomes even for those that are treated, and TAVR is providing a research vehicle to understand a lot of these mechanisms and the impact of different measurements such as diastolic function on the outcomes after treatment,” he concluded. “Maybe these are things that could help us figure out better the urgency and timing of treatment in certain patients.”

This study will be presented this weekend at the CRT Meeting in Washington, DC.