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JACC Cardiovasc Interv. 2015 Apr 20;8(4):588-96. doi: 10.1016/j.jcin.2014.08.019. Epub 2015 Mar 26.

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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Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
Department of Cardiology, Centre Hospitalier Universitaire Limoges, Hôpital Dupuytren, Limoges, France; Institut national de la santé et de la recherche médicale 1094, Faculté de médecine de Limoges, Limoges, France.
Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
Department of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Division of Adult Congenital and Valvular Heart Disease, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany.
Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada. Electronic address:



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).


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


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.


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).


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.


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

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