Tricuspid Regurgitation Across the Spectrum of Heart Failure With Preserved Ejection Fraction
Key result
Ventricular secondary tricuspid regurgitation is linked to ~70% higher mortality or HF hospitalization in HFpEF.
- HR 1.70
- 95% CI 1.10-2.65
- n=1,091
Why the study?
Secondary tricuspid regurgitation is linked to advanced HFpEF with pulmonary vascular disease, but whether it develops at earlier stages remained to be evaluated.
Does the presence and mechanism of secondary tricuspid regurgitation (V-STR vs A-STR) worsen the composite of mortality and heart failure hospitalizations in patients with HFpEF?
Key Points
- To evaluate the prevalence, distribution, and prognostic significance of secondary tricuspid regurgitation mechanisms across the clinical spectrum of heart failure with preserved ejection fraction (HFpEF).
- Evaluated 1,091 patients (median age 65 years, 60.3% women; 669 with HFpEF) using resting and exercise invasive hemodynamics alongside echocardiography.
- Categorized HFpEF by the presence of pulmonary vascular disease (pulmonary vascular resistance >2 WU), filling pressure elevation at rest versus provocation, and mechanism (atrial vs ventricular secondary tricuspid regurgitation).
- Tracked clinical outcomes, including all-cause death and heart failure hospitalization, over a median follow-up of 4.9 years.
- Moderate or greater secondary tricuspid regurgitation occurred in 17.4% of HFpEF patients and increased with pulmonary vascular disease from 6.7% in exercise HFpEF without PVD to 33.7% in rest HFpEF with PVD, while remaining more frequent in exercise-only HFpEF than in non-cardiac dyspnea controls (11.7% vs 6.5%, p=0.047).
- Ventricular secondary tricuspid regurgitation was present in 69.0% of moderate or greater cases and independently predicted the composite endpoint of death or heart failure hospitalization (multivariable HR 1.70, 95% CI 1.10–2.65) and individual mortality (HR 3.41, 95% CI 2.19–5.35, p<0.001).
Study Design
Type
Cohort (n=1,091)
Multicenter
Yes
Structured PICO
Does the presence and mechanism of secondary tricuspid regurgitation (V-STR vs A-STR) worsen the composite of mortality and heart failure hospitalizations in patients with HFpEF?
P
Population
1,091 adult patients undergoing right heart catheterization at rest and exercise, including 669 with HFpEF, median age 65, 60.3% female, followed for a median of 4.9 years.
E
Exposure
Presence of ≥moderate secondary tricuspid regurgitation (STR), classified as ventricular (V-STR) or atrial (A-STR)
C
Comparator
No or mild tricuspid regurgitation
O
Outcome
Composite of all-cause mortality and heart failure hospitalizationshard clinical
Main Result
Hazard Ratio: 1.7 (95% CI 1.1–2.65)
Limitations
- Retrospective study design
- Referral bias from tertiary centers
- Selection bias from routine clinical practice referral for invasive hemodynamic evaluation
- Survival bias affecting prevalence of TR
- Lack of 3-dimensional echocardiographic datasets
- Retrospective design with referral bias from tertiary centers and selection bias due to requirement for invasive hemodynamic evaluation
- Survival bias from evaluating prevalent rather than incident TR
- Small number of patients with HFpEF and ≥moderate A-STR
- Use of ICD codes for comorbidities
Ask about this paper
Answers are grounded in this paper and cite their sources.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“TR is hardly ever just by itself. It's secondary to something else. And one of the most common secondary causes is heart failure with preserved ejection fraction.”
“V-STR patients identified on echo are a population that need to be treated and worked up with urgency (e.g., right heart cath) because V-STR is a more severe phenotype of disease (increased hospitalization and mortality risk).... any lab that prides itself on being a significant referral lab... they should also have the capacity to do exercise hemodynamic testing... because it really is a gold standard test for HFpEF.”
Implication
In patients with HFpEF, ventricular secondary tricuspid regurgitation is the predominant phenotype and is independently associated with increased mortality and heart failure hospitalizations, whereas atrial secondary tricuspid regurgitation is associated only with increased heart failure hospitalizations.
Abstract
Background: Secondary tricuspid regurgitation (STR) in heart failure (HF) and preserved ejection fraction (HFpEF) is linked to more advanced stages with pulmonary vascular disease (PVD), but may also develop at earlier stages of HFpEF, such as those with isolated exercise-induced congestion. Objective: To evaluate the prevalence, distribution, and prognostic significance of STR mechanisms across the spectrum of HFpEF. Methods: Cardiac structure, function, hemodynamics, and clinical outcomes were compared among patients with HFpEF phenotypes categorized according to the presence of PVD (pulmonary vascular resistance>2 WU), elevation in filling pressure at rest vs provocation (leg-elevation or exercise), and according to the presence of atrial or ventricular STR (A-STR, V-STR). Results: Of 1,091 patients (median age 65 years, 60.3% women), 669 (61.3%) had HFpEF [20.2% exercise HFpEF-PVD, 38.6% rest HFpEF-PVD, 15.5% exercise HFpEF+PVD, 25.7% rest HFpEF+PVD]. Moderate/severe STR was present in 17.4% overall, but increased with PVD [6.7%, 11.6%, 18.3%, 33.7%, respectively], though moderate/severe STR was still more common in exercise-only HFpEF vs non-cardiac dyspnea patients (11.7% vs 6.5%, p=0.047). Most STR (69%) fulfilled criteria for V-STR, but these individuals had similar AF prevalence and greater atrial remodeling compared to A-STR. V-STR was independently associated with composite of death or HF hospitalization [multivariable HR 1.70, (95% CI 1.10-2.65)] as well as death and HF hospitalizations each alone, whereas A-STR was associated with increased risk of HF hospitalizations [multivariable Fine-Gray HR 2.21 (1.12-4.37)]. Conclusion: STR in HFpEF is associated with PVD and less strongly with higher resting filling pressure. While V-STR is the more common phenotype of STR in HFpEF, these patients also have substantial atrial myopathy, suggesting a mixed mechanism. TR was more prevalent in exercise HFpEF than non-cardiac dyspnea; with none in the latter group having moderate-severe/severe TR, highlighting the importance of exercise hemodynamics. While V-STR conferred excess mortality and HF hospitalizations, A-STR conferred only excess HF hospitalizations.
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Cite This Study
Naser et al. (2025) conducted a cohort in Heart failure with preserved ejection fraction (HFpEF) (n=1,091). Ventricular secondary tricuspid regurgitation (V-STR) vs. No or mild tricuspid regurgitation was evaluated on Composite of all-cause mortality and HF hospitalizations (HR 1.70, 95% CI 1.10-2.65). Ventricular secondary tricuspid regurgitation was independently associated with an increased risk of the composite of death or heart failure hospitalization (HR 1.70) in patients with HFpEF.