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Natural History of Functional Tricuspid Regurgitation
Study Questions:
What is the relationship between functional tricuspid regurgitation (TR) and mortality among patients with heart failure with reduced ejection fraction (HFrEF), and is there a prognostic value of quantitative measures (effective regurgitant orifice area [EROA], regurgitant volume [RV]) of TR severity?
Methods:
In a single-center, observational, noninterventional study, 382 consecutive euvolemic and clinically stable adult patients with HFrEF (left ventricular ejection fraction <40%) presenting to the outpatient HF clinic at a single European tertiary referral center and optimized on guideline-based medical therapy were studied. Echocardiography/Doppler included assessment of TR EROA and RV. The primary endpoint was all-cause mortality during 5-year follow-up, using data obtained from a national Death Registry.
Results:
TR severity was associated with HFrEF phenotype, with more symptoms (p = 0.004), higher neurohumoral activation (p < 0.001), progressive right ventricular dilatation (p < 0.001), and impaired functional class (p = 0.01). Cox regression showed a strong association between quantitative measures of TR with mortality (all p < 0.001). Quantitative metrics of TR severity consistently were associated with mortality with a hazard ratio of 1.009 (95% confidence interval [CI], 1.004-1.013; p < 0.001) per 0.01 cm2 increase in EROA, and of 1.013 (95% CI, 1.007-1.020; p < 0.001) per 1-ml increase in RV. Results remained unchanged after bootstrap- or clinical confounder-based adjustment. A spline curve pattern illustrated the association between TR severity and mortality, with thresholds for EROA ≥0.2 cm2 and RV ≥20 ml, with sustained excess mortality thereafter.
Conclusions:
This single-center observational study demonstrates an association between quantitative Doppler/echo measures of TR severity and all-cause mortality among patients with HFrEF. Because the thresholds for TR EROA and RV associated with increased mortality in this study fell within current ranges of nonsevere TR, the authors suggest that the results might affect therapeutic decision making, including the timing of intervention.
Perspective:
This study demonstrates an association between quantitative Doppler/echo measures of functional TR severity and all-cause mortality among patients with compensated, medically treated HFrEF. Functional mitral regurgitation (MR) also is found and is known to be associated with a worse prognosis among patients with ischemic and nonischemic cardiomyopathy. The present study does not test whether intervention on functional TR affects prognosis, and (data from the COAPT trial notwithstanding) the idea that intervention on functional MR affects prognosis are controversial. For the time being, and pending a prospective trial testing the effect of intervention on outcomes, it might be best to consider functional TR to be a marker, but not necessarily a cause, of adverse prognosis among patients with HFrEF.
Clinical Topics: Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Valvular Heart Disease, Acute Heart Failure, Echocardiography/Ultrasound, Mitral Regurgitation
Keywords: Cardiomyopathies, Diagnostic Imaging, Dilatation, Echocardiography, Doppler, Heart Failure, Heart Valve Diseases, Mitral Valve Insufficiency, Outpatients, Stroke Volume, Tertiary Care Centers, Tricuspid Valve Insufficiency, Ventricular Function, Left
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