Excess Mortality Associated With Functional Tricuspid Regurgitation Complicating Heart Failure With Reduced Ejection Fraction

Giovanni Benfari, Clemence Antoine, Wayne Miller, Prabin Thapa, Yan Topilsky, Andrea Rossi, Hector I Michelena, Sorin Pislaru, Maurice E Sarano

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Functional tricuspid regurgitation (FTR) is common in heart failure with reduced ejection fraction and mostly consequent to pulmonary hypertension. However, the intrinsic clinical implications of FTR are not fully understood. METHODS: The cohort of all Mayo Clinic patients from 2003 to 2011 diagnosed with heart failure stage B-C and ejection fraction<50%, with FTR grading and systolic pulmonary artery pressure estimation by Doppler echocardiography was identified and outcomes were analyzed. Patients with pacemakers/defibrillators, organic valve disease, or previous valve surgery were excluded. The primary outcome measure was overall mortality (censored at implantation of a defibrillator, ventricular assist device, or cardiac transplantation), adjusting for clinical and echocardiographic associates with mortality and major comorbidities. RESULTS: Among 13 026 patients meeting inclusion criteria, FTR was detected in 88% (N=11 507: 33% trivial, 32% mild, 17% moderate, and 6% severe), aged 68±14 years, 35% women, ejection fraction 36±10%, systolic pulmonary artery pressure 41±14 mm Hg with 20% atrial fibrillation. Covariates independently associated with FTR included elevated systolic pulmonary artery pressure, older age, female sex, lower ejection fraction, mitral regurgitation, and atrial fibrillation (all P<0.0001). FTR was independently associated with more dyspnea, impaired kidney function, and lower cardiac output ( P<0.003 for all). For long-term outcome, higher FTR degree compared with trivial tricuspid regurgitation was independently associated with higher mortality (adjusted hazard ratios 1.09 [1.01-1.17] for mild FTR, 1.21 [1.11-1.33] for moderate FTR and 1.57 [1.39-1.78] for severe FTR); hence, 5-year survival was substantially lower with increasing severity of functional FTR, 68±1% for trivial FTR, 58±2% for mild FTR, 45±2% for moderate FTR, and 34±4% for severe FTR. CONCLUSIONS: In this large cohort of patients with heart failure with reduced ejection fraction, FTR was common and independently associated with pulmonary hypertension, atrial fibrillation, and more severe heart failure presentation. Long-term, higher FTR severity is associated with considerably worse survival, independently of baseline characteristics. Given these untoward outcomes associated with FTR in patients with heart failure with reduced ejection fraction, clinical trials should be directed at testing FTR treatment.

Original languageEnglish (US)
Pages (from-to)196-206
Number of pages11
JournalCirculation
Volume140
Issue number3
DOIs
StatePublished - Jul 16 2019

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Tricuspid Valve Insufficiency
Heart Failure
Mortality
Atrial Fibrillation
Pulmonary Artery
Defibrillators
Pulmonary Hypertension
Pressure

Keywords

  • atrial fibrillation
  • heart failure, systolic
  • mitral valve insufficiency
  • prognosis
  • tricuspid valve insufficiency
  • ventricular dysfunction, left

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Excess Mortality Associated With Functional Tricuspid Regurgitation Complicating Heart Failure With Reduced Ejection Fraction. / Benfari, Giovanni; Antoine, Clemence; Miller, Wayne; Thapa, Prabin; Topilsky, Yan; Rossi, Andrea; Michelena, Hector I; Pislaru, Sorin; Sarano, Maurice E.

In: Circulation, Vol. 140, No. 3, 16.07.2019, p. 196-206.

Research output: Contribution to journalArticle

Benfari, Giovanni ; Antoine, Clemence ; Miller, Wayne ; Thapa, Prabin ; Topilsky, Yan ; Rossi, Andrea ; Michelena, Hector I ; Pislaru, Sorin ; Sarano, Maurice E. / Excess Mortality Associated With Functional Tricuspid Regurgitation Complicating Heart Failure With Reduced Ejection Fraction. In: Circulation. 2019 ; Vol. 140, No. 3. pp. 196-206.
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abstract = "BACKGROUND: Functional tricuspid regurgitation (FTR) is common in heart failure with reduced ejection fraction and mostly consequent to pulmonary hypertension. However, the intrinsic clinical implications of FTR are not fully understood. METHODS: The cohort of all Mayo Clinic patients from 2003 to 2011 diagnosed with heart failure stage B-C and ejection fraction<50{\%}, with FTR grading and systolic pulmonary artery pressure estimation by Doppler echocardiography was identified and outcomes were analyzed. Patients with pacemakers/defibrillators, organic valve disease, or previous valve surgery were excluded. The primary outcome measure was overall mortality (censored at implantation of a defibrillator, ventricular assist device, or cardiac transplantation), adjusting for clinical and echocardiographic associates with mortality and major comorbidities. RESULTS: Among 13 026 patients meeting inclusion criteria, FTR was detected in 88{\%} (N=11 507: 33{\%} trivial, 32{\%} mild, 17{\%} moderate, and 6{\%} severe), aged 68±14 years, 35{\%} women, ejection fraction 36±10{\%}, systolic pulmonary artery pressure 41±14 mm Hg with 20{\%} atrial fibrillation. Covariates independently associated with FTR included elevated systolic pulmonary artery pressure, older age, female sex, lower ejection fraction, mitral regurgitation, and atrial fibrillation (all P<0.0001). FTR was independently associated with more dyspnea, impaired kidney function, and lower cardiac output ( P<0.003 for all). For long-term outcome, higher FTR degree compared with trivial tricuspid regurgitation was independently associated with higher mortality (adjusted hazard ratios 1.09 [1.01-1.17] for mild FTR, 1.21 [1.11-1.33] for moderate FTR and 1.57 [1.39-1.78] for severe FTR); hence, 5-year survival was substantially lower with increasing severity of functional FTR, 68±1{\%} for trivial FTR, 58±2{\%} for mild FTR, 45±2{\%} for moderate FTR, and 34±4{\%} for severe FTR. CONCLUSIONS: In this large cohort of patients with heart failure with reduced ejection fraction, FTR was common and independently associated with pulmonary hypertension, atrial fibrillation, and more severe heart failure presentation. Long-term, higher FTR severity is associated with considerably worse survival, independently of baseline characteristics. Given these untoward outcomes associated with FTR in patients with heart failure with reduced ejection fraction, clinical trials should be directed at testing FTR treatment.",
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T1 - Excess Mortality Associated With Functional Tricuspid Regurgitation Complicating Heart Failure With Reduced Ejection Fraction

AU - Benfari, Giovanni

AU - Antoine, Clemence

AU - Miller, Wayne

AU - Thapa, Prabin

AU - Topilsky, Yan

AU - Rossi, Andrea

AU - Michelena, Hector I

AU - Pislaru, Sorin

AU - Sarano, Maurice E

PY - 2019/7/16

Y1 - 2019/7/16

N2 - BACKGROUND: Functional tricuspid regurgitation (FTR) is common in heart failure with reduced ejection fraction and mostly consequent to pulmonary hypertension. However, the intrinsic clinical implications of FTR are not fully understood. METHODS: The cohort of all Mayo Clinic patients from 2003 to 2011 diagnosed with heart failure stage B-C and ejection fraction<50%, with FTR grading and systolic pulmonary artery pressure estimation by Doppler echocardiography was identified and outcomes were analyzed. Patients with pacemakers/defibrillators, organic valve disease, or previous valve surgery were excluded. The primary outcome measure was overall mortality (censored at implantation of a defibrillator, ventricular assist device, or cardiac transplantation), adjusting for clinical and echocardiographic associates with mortality and major comorbidities. RESULTS: Among 13 026 patients meeting inclusion criteria, FTR was detected in 88% (N=11 507: 33% trivial, 32% mild, 17% moderate, and 6% severe), aged 68±14 years, 35% women, ejection fraction 36±10%, systolic pulmonary artery pressure 41±14 mm Hg with 20% atrial fibrillation. Covariates independently associated with FTR included elevated systolic pulmonary artery pressure, older age, female sex, lower ejection fraction, mitral regurgitation, and atrial fibrillation (all P<0.0001). FTR was independently associated with more dyspnea, impaired kidney function, and lower cardiac output ( P<0.003 for all). For long-term outcome, higher FTR degree compared with trivial tricuspid regurgitation was independently associated with higher mortality (adjusted hazard ratios 1.09 [1.01-1.17] for mild FTR, 1.21 [1.11-1.33] for moderate FTR and 1.57 [1.39-1.78] for severe FTR); hence, 5-year survival was substantially lower with increasing severity of functional FTR, 68±1% for trivial FTR, 58±2% for mild FTR, 45±2% for moderate FTR, and 34±4% for severe FTR. CONCLUSIONS: In this large cohort of patients with heart failure with reduced ejection fraction, FTR was common and independently associated with pulmonary hypertension, atrial fibrillation, and more severe heart failure presentation. Long-term, higher FTR severity is associated with considerably worse survival, independently of baseline characteristics. Given these untoward outcomes associated with FTR in patients with heart failure with reduced ejection fraction, clinical trials should be directed at testing FTR treatment.

AB - BACKGROUND: Functional tricuspid regurgitation (FTR) is common in heart failure with reduced ejection fraction and mostly consequent to pulmonary hypertension. However, the intrinsic clinical implications of FTR are not fully understood. METHODS: The cohort of all Mayo Clinic patients from 2003 to 2011 diagnosed with heart failure stage B-C and ejection fraction<50%, with FTR grading and systolic pulmonary artery pressure estimation by Doppler echocardiography was identified and outcomes were analyzed. Patients with pacemakers/defibrillators, organic valve disease, or previous valve surgery were excluded. The primary outcome measure was overall mortality (censored at implantation of a defibrillator, ventricular assist device, or cardiac transplantation), adjusting for clinical and echocardiographic associates with mortality and major comorbidities. RESULTS: Among 13 026 patients meeting inclusion criteria, FTR was detected in 88% (N=11 507: 33% trivial, 32% mild, 17% moderate, and 6% severe), aged 68±14 years, 35% women, ejection fraction 36±10%, systolic pulmonary artery pressure 41±14 mm Hg with 20% atrial fibrillation. Covariates independently associated with FTR included elevated systolic pulmonary artery pressure, older age, female sex, lower ejection fraction, mitral regurgitation, and atrial fibrillation (all P<0.0001). FTR was independently associated with more dyspnea, impaired kidney function, and lower cardiac output ( P<0.003 for all). For long-term outcome, higher FTR degree compared with trivial tricuspid regurgitation was independently associated with higher mortality (adjusted hazard ratios 1.09 [1.01-1.17] for mild FTR, 1.21 [1.11-1.33] for moderate FTR and 1.57 [1.39-1.78] for severe FTR); hence, 5-year survival was substantially lower with increasing severity of functional FTR, 68±1% for trivial FTR, 58±2% for mild FTR, 45±2% for moderate FTR, and 34±4% for severe FTR. CONCLUSIONS: In this large cohort of patients with heart failure with reduced ejection fraction, FTR was common and independently associated with pulmonary hypertension, atrial fibrillation, and more severe heart failure presentation. Long-term, higher FTR severity is associated with considerably worse survival, independently of baseline characteristics. Given these untoward outcomes associated with FTR in patients with heart failure with reduced ejection fraction, clinical trials should be directed at testing FTR treatment.

KW - atrial fibrillation

KW - heart failure, systolic

KW - mitral valve insufficiency

KW - prognosis

KW - tricuspid valve insufficiency

KW - ventricular dysfunction, left

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