Diastolic but Also RV Dysfunction Predict TAVR Survival

Patrice Wendling

March 02, 2018

New research highlights the impact of left ventricular diastolic dysfunction (LVDD) on mortality risk after transcatheter aortic valve replacement (TAVR) but also how deadly right ventricular dysfunction (RVD) can be.

In the first of two papers, Swiss researchers report that baseline LVDD is associated with a two- to fourfold increased all-cause mortality risk at 1 year with advancing stages of diastolic dysfunction and that this effect is independent of systolic LV function.

In the second paper, patients with baseline RVD had nearly three times the risk for cardiovascular death at 1 year as those with normal RV function (20.1% vs 7.1%; adjusted hazard ratio [HR], 2.94; 95% CI, 2.02 - 4.27).

RV function recovered in more than half (57.4%) of patients evaluated a median of 2 days after TAVR, but an increasing risk for death remained in patients with recovered RVD, new-onset RVD, and persistent RVD (adjusted HRs, 2.16, 3.93, and 8.74, respectively).

This gradient of risk observed for both RVD and diastolic dysfunction will need to be corroborated in larger studies with more patients, but it suggests that RV and LV function should be considered in risk assessment before and after TAVR, senior author, Thomas Pilgrim, MD, Bern University Hospital, Switzerland, told theheart.org | Medscape Cardiology.

RVD has been associated with all-cause mortality after cardiac surgery and in patients with heart failure, but smaller trials using inconsistent definitions of RVD have produced mixed results in patients undergoing TAVR.

Pilgrim noted that RVD  has been "a bit neglected in the past" and that part of the impetus for conducting the study was the recent European Society of Cardiology statement on the management of acute RV failure and the American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines for the evaluation of RVD.

"After TAVR, everybody cares about paravalvular regurgitation and procedural gradient, but nobody cares about the right ventricle, and I think this is something that should change once you read this article," he said.

LVDD is widely recognized as a predictor of mortality in surgical patients, but Pilgrim noted that LVDD defined by using the latest echocardiographic guidelines was present at baseline in 70% of patients, far surpassing prior prevalence estimates of about 15%.

Patricia Pellikka, MD, Mayo Clinic, Rochester, Minnesota, coauthor of a related editorial, cautioned in an interview that diastolic dysfunction in these elderly TAVR patients could be related to comorbidities, such as lung disease, pulmonary hypertension, and obstructive sleep apnea, and that just having long-standing LV aortic stenosis could potentiate RV impairment.

Still, Pellikka said the papers underscore the importance of considering all available transthoracic echocardiographic evidence in selecting patients for early, life-saving aortic valve replacement.

"We really need to be careful that we're not offering therapy too late when patients aren't going to derive the maximum benefit because we've waited for symptoms that may be vague in the first place and still vague at follow-up, and meanwhile right ventricular dysfunction and diastolic dysfunction are progressing," she said.

The studies, led by Masahiko Asami, MD, Bern University Hospital, were published online February 28 in JACC: Cardiovascular Interventions and February 14 in JACC: Cardiovascular Imaging, respectively.

Role of RVD

To evaluate the role of RVD, the researchers examined data from 1116 (mean age, 82 years) in the prospective Swiss TAVI registry who underwent TAVR for severe aortic stenosis (AS) at their institution between August 2007 and December 2015 and had transthoracic echocardiographic data.

Cutoff values for abnormal RV function were fractional area change less than 35%, tricuspid annular plane systolic excursion less than 1.7 cm, and systolic movement of the RV lateral wall by tissue Doppler imaging of less than 9.5 cm/s.

RVD was found in 29.1% of patients at baseline. These patients were significantly more likely to be men, to have a history of atrial fibrillation or bypass surgery, and to have a lower LV ejection fraction and transvalvular gradient. They also had higher pulmonary artery pressures and were more likely to have concomitant moderate or severe mitral and tricuspid regurgitation.

A composite of all-cause death, disabling stroke, and myocardial infarction occurred in 29.6% of patients with RVD vs 14.7% of patients with normal RV function (adjusted HR, 2.08; 95% CI, 1.57 - 2.76), driven by a higher rate of all-cause mortality (26.2% vs 11.1%; adjusted HR, 2.48; 95% CI, 1.82 - 3.38). Patients with RVD also had a higher rate of stage 3 kidney injury (adjusted HR, 2.43; 95% CI, 1.28 - 4.61).

The higher mortality risk emerged within the first 30 days of TAVR (9% vs 2.2%; HR, 4.62; 95% CI, 2.51 - 8.50).

In multivariate analysis, RVD was the strongest independent predictor of cardiovascular death at 1 year (HR, 2.51; 95% CI, 1.64 - 3.86).

"You would certainly not perform open-heart surgery in patients with severe right ventricular dysfunction, but I think for TAVR there's not a cutoff where you would think, 'Well, you don't perform TAVR anymore because of right ventricular dysfunction'," Pilgrim said. "You'd still do it, but it gives you a very good picture on the prognosis and on the expected outcomes of those patients."

New-onset RVD was found in 12.1% of patients after TAVR, but exactly why this occurred is unclear. Most of these patients did not have an obvious periprocedural complication that would explain it, although it's possible they had borderline RVD before TAVR and then it just "pushed them over into right ventricular dysfunction," Pilgrim said.

LVDD

The investigators turned to 777 patients from the same Swiss TAVI registry to examine LVDD by using four cutoffs:

  • Annular e' velocity (septal e' < 7 cm/s or lateral e' < 10 cm/s);

  • Average E'  ratio > 14;

  • Left atrium maximum volume index > 34 mL/m2; and

  • Peak tricuspid regurgitation velocity > 2.8 m/s.

LVDD, defined as the presence of more than half of all parameters, was documented in 545 patients and classified as grade 1 in 18%, grade 2 in 36.3%, and grade 3 in 19.1%. In all, 145 patients were excluded from the analysis because they had only one  or two discrepant variables available to grade.

Similar to their RVD counterparts, patients with LVDD were more likely to be male, to have a history of bypass surgery or myocardial infarction, and to have concomitant moderate or severe mitral or tricuspid regurgitation. Patients with LVDD also had a lower LV ejection fraction, but there were no significant differences in aortic valve area or transvalvular gradient.

Compared with patients with normal diastolic function, patients with LVDD had a risk for all-cause death at 1 year that increased with worsening stages of LVDD from grade 1 (16.3%; adjusted HR, 2.32; 95% CI, 1.15 - 4.66) to grade 2 (17.9%; adjusted HR, 2.58; 95% CI, 1.43 - 4.67) to grade 3 (27.6%; adjusted HR, 4.21; 95% CI, 2.25 - 7.86).

The mortality difference emerged as early as 30 days after TAVR in patients with LVDD grade 3 but continued during mid-term follow-up and was strongly driven by differences in cardiovascular death (adjusted HR, 7.53; 95% CI, 3.17 - 17.9).

The effect of LVDD on 1-year mortality was independent of systolic LV function in a sensitivity analysis that included only patients with an LV ejection fraction of 50% or greater (LVDD grade 2 adjusted HR, 2.57; 95% CI, 1.30 - 5.08; LVDD grade 3 adjusted HR, 3.66; 95% CI, 1.46 - 9.18). The data "underscores the applicability of LVDD as a viable tool for risk stratification in AS patients," the authors write.

LVDD grades 1, 2, and 3 independently predicted death at 1 year, with adjusted HRs of 2.36, 2.58, and 4.41, respectively. LVDD grade 3 was the strongest predictor of mortality, followed by body mass index of 20 kg/m2 or less, diabetes, chronic obstructive pulmonary disease, and peripheral vascular disease.

"The long-term effect of LVDD on survival may be related to the protracted regression of LV hypertrophy," while "LV stiffness may further exacerbate the effect of persistent volume overload," the researchers write. Prior studies have suggested an additive effect of LVDD and paravalvular regurgitation after TAVR, while more moderate aortic regurgitation has been independently associated with an increased risk for mortality at 2 years.

In the accompanying editorial, Pellikka and Ratnasari Padang, MBBS, PhD, also from the Mayo Clinic, note that the study included 107 patients with moderate or severe mitral regurgitation, which can induce changes in transmitral Doppler patterns resembling those with advanced DD. Baseline mitral regurgitation is also a known predictor of worse outcome after TAVR and may have confounded the relationship.

In addition, they write, "Significant mitral annulus calcification, a common finding in elderly patients with AS, was not specified, and can lead to reduction in mitral orifice area and restriction of mitral annulus movement with consequent elevation of E/e'. These patients should have been excluded."

Still, Pellikka and Padang conclude that "baseline diastolic function evaluated by echocardiography provided important prognostic information beyond standard risk factors alone."

Pilgrim reported receiving research grants to his institution from Edwards Lifesciences, Symetis, and Biotronik; speaker fees from Boston Scientific; and travel expense reimbursement from St Jude Medical. Asami and Pellikka have disclosed no relevant financial relationships.

JACC Cardiovasc Imaging. Published online February 14, 2018. Abstract

JACC Cardiovasc Interven. Published online February 28, 2018. Abstract, Editorial

Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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