Structural
Tricuspid Regurgitation Is Associated With Increased Risk of Mortality in Patients With Low-Flow Low-Gradient Aortic Stenosis and Reduced Ejection Fraction: Results of the Multicenter TOPAS Study (True or Pseudo-Severe Aortic Stenosis)

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Abstract

Objectives

This study sought to examine the impact of tricuspid regurgitation (TR) on mortality in patients with low-flow, low-gradient (LF-LG) aortic stenosis (AS) and reduced left ventricular ejection fraction (LVEF).

Background

TR is often observed in patients with LF-LG AS and low LVEF, but its impact on prognosis remains unknown.

Methods

A total of 211 patients (73 ± 10 years of age; 77% men) with LF-LG AS (mean gradient <40 mm Hg and indexed aortic valve area [AVA] ≤0.6 cm2/m2) and reduced LVEF (≤40%) were prospectively enrolled in the TOPAS (True or Pseudo-Severe Aortic Stenosis) study and 125 (59%) of them underwent aortic valve replacement (AVR) within 3 months following inclusion. The severity of AS was assessed by the projected AVA (AVAproj) at normal flow rate (250 ml/s), as previously described and validated. The severity of TR was graded according to current guidelines.

Results

Among the 211 patients included in the study, 22 (10%) had no TR, 113 (54%) had mild (grade 1), 50 (24%) mild-to-moderate (grade 2), and 26 (12%) moderate-to-severe (grade 3) or severe (grade 4) TR. During a mean follow-up of 2.4 ± 2.2 years, 104 patients (49%) died. Univariable analysis showed that TR ≥2 was associated with increased risk of all-cause mortality (hazard ratio [HR]: 1.82, 95% confidence interval [CI]: 1.22 to 2.71; p = 0.004) and cardiovascular mortality (HR: 1.85, 95% CI: 1.20 to 2.83; p = 0.005). After adjustment for age, sex, coronary artery disease, AVAproj, LVEF, stroke volume index, right ventricular dysfunction, mitral regurgitation, and type of treatment (AVR vs. conservative), the presence of TR ≥2 was an independent predictor of all-cause mortality (HR: 1.88, 95% CI: 1.08 to 3.23; p = 0.02) and cardiovascular mortality (HR: 1.92, 95% CI: 1.05 to 3.51; p = 0.03). Furthermore, in patients undergoing AVR, TR ≥3 was an independent predictor of 30-day mortality compared with TR = 0/1 (odds ratio [OR]: 7.24, 95% CI: 1.56 to 38.2; p = 0.01) and TR = 2 (OR: 4.70, 95% CI: 1.00 to 25.90; p = 0.05).

Conclusions

In patients with LF-LG AS and reduced LVEF, TR is independently associated with increased risk of cumulative all-cause mortality and cardiovascular mortality regardless of the type of treatment. In patients undergoing AVR, moderate/severe TR is associated with increased 30-day mortality. Further studies are needed to determine whether TR is a risk marker or a risk factor of mortality and whether concomitant surgical correction of TR at the time of AVR might improve outcomes for this high-risk population.

Key Words

aortic stenosis
aortic valve replacement
echocardiography
low-flow
low-gradient
outcome
tricuspid regurgitation

Abbreviations and Acronyms

AS
aortic stenosis
AVA
aortic valve area
AVAproj
projected aortic valve area at normal flow rate
AVR
aortic valve replacement
CI
confidence interval
HR
hazard ratio
LF-LG
low-flow, low-gradient
LVEF
left ventricular ejection fraction
OR
odds ratio
RV
right ventricular
SVI
stroke volume index
TR
tricuspid regurgitation

Cited by (0)

This work was supported by grants (#57445 for TOPAS-II and #126072 for TOPAS-III) from the Canadian Institutes of Health Research Ottawa, Canada. Dr. Dahou was supported by a fellowship grant from L’Agence de la santé et des services sociaux de la Capitale Nationale, Québec, Québec, Canada. Dr. Clavel was supported by a post-doctorate fellowship from the Canadian Institutes of Health Research Ottawa, Canada. Dr. Ribeiro is supported by a research PhD grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico-Brazil. Dr. Mathieu is a research scholar from the Fonds de Recherche en Santé du Québec, Montreal, Québec, Canada. Dr. Baumgartner has served as a consultant and proctor for Edwards Lifesciences; has received speaking fees from Edwards Lifesciences and Actelion; and has received travel support from Edwards Lifesciences, Actelion, Abbott, St. Jude Medical, Direct Flow Medical, Medtronic, and Gore. Dr. Rodés-Cabau has served as a consultant for Edwards Lifesciences and St. Jude Medical. Dr. Pibarot holds the Canada Research Chair in Valvular Heart Diseases, Canadian Institutes of Health Research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.