title: 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).
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Abdellaziz
authors.initials: A
authors.lastname: Dahou
authors.affiliation: 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.
authors.forename: Julien
authors.initials: J
authors.lastname: Magne
authors.affiliation: Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Marie-Annick
authors.initials: MA
authors.lastname: Clavel
authors.affiliation: Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Romain
authors.initials: R
authors.lastname: Capoulade
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Philipp Emanuel
authors.initials: PE
authors.lastname: Bartko
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Jutta
authors.initials: J
authors.lastname: Bergler-Klein
authors.affiliation: Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Sénéchal
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Mundigler
authors.affiliation: Department of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Burwash
authors.affiliation: Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Henrique B
authors.initials: HB
authors.lastname: Ribeiro
authors.affiliation: Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Kim
authors.initials: K
authors.lastname: O'Connor
authors.affiliation: Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mathieu
authors.affiliation: Division of Adult Congenital and Valvular Heart Disease, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Baumgartner
authors.affiliation: Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Jean G
authors.initials: JG
authors.lastname: Dumesnil
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Raphael
authors.initials: R
authors.lastname: Rosenhek
authors.affiliation: Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Larose
authors.affiliation: Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Josep
authors.initials: J
authors.lastname: Rodés-Cabau
authors.affiliation: 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: philippe.pibarot@med.ulaval.ca.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pibarot
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging / Q000401:mortality* / Q000601:surgery; D002423:Cause of Death; D015150:Echocardiography, Doppler / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D019918:Heart Valve Prosthesis Implantation / Q000379:methods / Q000401:mortality*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000502:physiology*; D016019:Survival Analysis; D014262:Tricuspid Valve Insufficiency / Q000000981:diagnostic imaging / Q000401:mortality* / Q000601:surgery
keywords: aortic stenosis; aortic valve replacement; echocardiography; low-flow; low-gradient; outcome; tricuspid regurgitation