New-onset or persistently low LV outflow following TAVR signals higher mortality risk, according to a small retrospective study published online June 2, 2015, ahead of print in Heart. However, normalization of a low preprocedural stroke volume index appears to carry a good prognosis.

“[M]easurement of early postprocedural [stroke volume index] is useful to assess the immediate hemodynamic benefit of TAVR and to predict the risk of late mortality, write Philippe Pibarot, DVM, PhD, of Quebec Heart and Lung Institute (Quebec City, Canada) and colleagues. They suggest that patients with low flow, whether persistent or new onset, “should receive particular attention with close follow-up and optimization of medical therapy.”

The investigators looked at echocardiographic and clinical data on 255 patients (mean age 80 years; 41.6% men) who underwent TAVR with a balloon-expandable valve at their center between May 2007 and October 2012.

Patients were divided into 4 groups according to whether their baseline and early postprocedural stroke volumes indexed to body surface area were at least 35 mL/m² (normal flow) or less (low flow). Groups included:

• Maintained normal flow (n = 76)
• New-onset low flow (n = 49)
• Normalized flow (n = 41)
• Persistent low flow (n = 89)

At a median follow-up of 1 year, one-third of patients had died. Mortality was higher among the 54.1% of patients who had low flow shortly after the procedure compared with those having normal flow (18.6% vs 12.7%; P = .003).

The impact of flow was also analyzed according to stroke volume status before and early after TAVR. Patients whose low baseline flow was normalized by treatment had half the mortality risk of those with persistently low flow. Patients whose flow was newly or persistently low after TAVR had almost double the mortality risk of those whose normal flow was maintained. No difference in risk was seen for patients who had normal flow at baseline and continued to do so (table 1).

On multivariate analysis, predictors of increased mortality were male sex, permanent A-fib/flutter, transapical approach, early postprocedural low flow, and moderate/severe postprocedural aortic and mitral regurgitation. There were no interactions between early post-TAVR flow and postprocedural moderate/several aortic or mitral regurgitation with regard to mortality.

In a Cox regression model, baseline low flow (P < .001), permanent A-fib/flutter (P = .02), and transapical approach (P < .001) were all associated with early postprocedural low flow. Conversely, after adjustment, early postprocedural moderate/severe aortic stenosis was linked with higher early postprocedural stroke volume index.

In 182 patients with complete data, there was no difference between preprocedural and early postprocedural flow, but by late follow-up, flow had increased from baseline (35 mL/m² vs 38 mL/m²; P < .001). However, in the 50% of patients with low baseline flow (28 ± 4 mL/m²), stroke volume index increased early after the procedure (32 mL/m²) and even further at late follow-up (35 mL/m²; both P < .001).

TAVR approach also influenced stroke volume index. A difference between baseline and early postprocedural flow was seen only in the transfemoral group (mean of 35.3 mL/m² vs 37.7 mL/m²; P = .02). The evolution of stroke volume index was similar between patients with classical (LVEF < 50%) and paradoxical low flow (LVEF ≥ 50%).

Tool to Gauge TAVR Response

In a telephone interview with TCTMD, Ted Feldman, MD, of Evanston Hospital (Evanston, IL), commented: “The new learning point for me is that we can further understand low-flow, low-gradient patients in terms of their response to therapy.”

He said he was surprised to see that normalizing baseline low flow imparted such a good prognosis. “Until I saw this paper, I would walk into a case thinking a patient is not going to do so well, and I didn’t think any further,” he noted. “Now postprocedure I can look to see what happened [to stroke volume] and have a better handle on whether a patient will bounce in and out of the hospital after TAVR or will really sail.”

However, Dr. Feldman expressed skepticism about the clinical usefulness of using baseline stroke volume index as tool to guide treatment. “What we get from this study is prognostic—it’s very difficult to base therapy decisions on what is concluded here,” he said.

Moreover, the predictors of postprocedural low flow may not be causal, he cautioned. Besides, Dr. Feldman added, “we do our best with A-fib, we try to avoid the transapical approach anyway, and we’ve done many things to try to minimize paravalvular leak. So identifying patients as high risk wouldn’t really change the energy with which we already try to optimize every aspect of the procedure.”

Improved Outflow Goes to the Heart of TAVR

Philippe Généreux, MD, of Columbia University Medical Center (New York, NY), welcomed the findings. “The aim of TAVR is to restore normal flow, so looking at stroke volume makes a lot of sense,” he told TCTMD in a telephone interview.

As a risk marker, stroke volume is intertwined with many other factors, including A-fib, prior mitral regurgitation, aortic insufficiency, and low ejection fraction, making it difficult to single out its individual influence, he noted. On the other hand, stroke volume is more sensitive to the severity of aortic stenosis and its impact on myocardial work than ejection fraction alone, he added.

“What is most interesting clinically is to quantify stroke volume before and after TAVR to see if you benefited the patient,” Dr. Généreux commented. “It will be interesting to apply [this metric] in larger studies.”

Meanwhile, “everything we can do to improve stroke volume both before and after the procedure will be key,” he continued. “Not only to remove the [aortic] obstruction but to manage other factors that affect stroke volume, such as mitral regurgitation and A-fib.”

As to how TAVR improves stroke volume, Dr. Généreux explained that “by removing the [aortic] obstruction, you change dramatically the pressure load on the left ventricle, allowing the muscle to ‘breathe’ and function more efficiently.” This may have several salutary side effects, such as decreasing mitral regurgitation, making A-fib easier to manage, and improving forward stroke volume, he observed, adding, “There is every reason to believe that this will result in decreased symptoms and improved functional capacity.”

The goal now will be to determine which patients are more or less likely to respond to TAVR, Dr. Généreux said, because in those with advanced disease the heart muscle may already be “burned out” and/or highly fibrotic, inhibiting myocardial recovery.

Evaluation of stroke volume index is already routine in many cath labs, Dr. Généreux reported, where it is employed not only to quantify flow but also to gauge a patient’s overall condition, as it factors in all comorbidities.

The authors suggest use of various noninvasive imaging techniques before TAVR to help identify patients who may be at higher risk of persistent low flow after the procedure. In addition, they recommend more aggressive treatment of A-fib before and after TAVR and use of new, smaller valve delivery systems to enable transfemoral rather than transapical implantation.

Le Ven F, Thébault C, Dahou A, et al. Evolution and prognostic impact of low flow after transcatheter aortic valve replacement. Heart. 2015;Epub ahead of print.

Disclosures:

• The study was funded by a research grant from the Canadian Institutes of Health Research.
• Dr. Pibarot reports receiving a research grant from Edwards Lifesciences.
• Dr. Feldman reports receiving research grants and consulting fees from Abbott Vascular, Boston Scientific, and Edwards Lifesciences.
• Dr. Généreux reports receiving speaker fees from Edwards Lifesciences.

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