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.

Aims: To define the hitherto unknown aetiology/mechanism distributions of mitral regurgitation (MR) in the community and the linked clinical characteristics/outcomes. Methods and results: We identified all isolated, moderate/severe MR diagnosed in our community (Olmsted County, MN, USA) between 2000 and 2010 and classified MR aetiology/mechanisms. Eligible patients (n = 727) were 73 ± 18 years, 51% females, with ejection fraction (EF) 49 ± 17%. MR was functional (FMR) in 65%, organic (OMR) in 32% and 2% mixed. Functional MR was linked to left ventricular remodelling (FMR-v) 38% and isolated atrial dilatation (FMR-a) 27%. At diagnosis FMR-v vs. FMR-a, vs. OMR displayed profound differences (all P < 0.0001) in age (73 ± 14, 80 ± 10, 68 ± 21years), male-sex (59, 33, 51%), atrial-fibrillation (28, 54, 13%), EF (33 ± 14, 57 ± 11, 61 ± 10%), and regurgitant-volume (38 ± 13, 37 ± 11, 51 ± 24 mL/beat). Dominant MR mechanism was Type I (normal valve-movement) 38%, Type II (excessive valve-movement) 25%, Type IIIa (diastolic movement-restriction) 3%, and Type IIIb (systolic movement-restriction) 34%. Outcomes were mediocre with excess-mortality vs. general-population in FMR-v [risk ratio 3.45 (2.98–3.99), P < 0.0001] but also FMR-a [risk ratio 1.88 (1.52–2.25), P < 0.0001] and OMR [risk ratio 1.83 (1.50–2.22), P < 0.0001]. Heart failure was frequent, particularly in FMR-v (5-year 83 ± 3% vs. 59 ± 4% FMR-a, 40 ± 3% OMR, P < 0.0001). Mitral surgery during patients’ lifetime was performed in 4% of FMR-v, 3% of FMR-a, and 37% of OMR. Conclusion: Moderate/severe isolated MR in the community displays considerable aetiology/mechanism heterogeneity. Functional MR dominates, mostly FMR-v but FMR-a is frequent and degenerative MR dominates OMR. Outcomes are mediocre with excess-mortality particularly with FMR-v but FMR-a, despite normal EF incurs notable excess-mortality and frequent heart failure. Pervasive undertreatment warrants clinical trials of therapies tailored to specific MR cause/mechanisms.

The impact of tricuspid regurgitation (TR) in patients with left ventricular systolic dysfunction on presentation and clinical outcome is uncertain due to confounding comorbidities and mediocre regurgitation ascertainment. In a cohort of patients with left ventricular systolic dysfunction (ejection fraction, EF < 50%) and functional TR (assessed quantitatively), we matched TR grade-groups for age, sex, EF, and TR velocity. Association of quantified TR (effective regurgitant orifice, ERO, severe if ≥0.4 cm2) to clinical presentation and outcome was analysed. In the 291 cohort patients (age 70 ± 12 years) with left ventricular dysfunction (EF 31 ± 10%), functional TR ERO was 0.26 ± 0.3 cm2. Presentation with right heart failure was strongly related to TR quantified severity [adjusted odds ratios were 4.15 (1.95-8.84), P = 0.0002 for moderate TR and 6.86 (3.34-14.1), P < 0.0001 for severe TR]. Effective regurgitant orifice ≥0.4 cm2 was associated with increased mortality [hazard ratio 1.6 (1.17-2.2), P = 0.003] unadjusted and after comprehensive adjustment [hazard ratio 1.8 (1.16-2.8), P = 0.009]. Furthermore, ERO ≥0.4 cm2 was associated with increased cardiac events (mortality, new atrial fibrillation or heart failure) unadjusted [hazard ratio 1.9 (1.3-2.7), P = 0.002] and after comprehensive adjustment [hazard ratio 2.2 (1.1-4.6), P = 0.02]. Tricuspid regurgitation, even moderate, is associated at diagnosis with more severe heart failure presentation. While moderate TR is associated with heart failure at presentation, our quantitative data show that the threshold associated with reduced survival and more cardiac events is ERO ≥0.4 cm2. These data emphasize the clinical impact of functional TR and warrant large cohort-analysis and clinical trials of treatment of TR associated with left ventricular dysfunction.