Highlights
1. RV-PA coupling improves significantly with GDMT up-titration in HFrEF patients.
2. TAPSE/sPAP ratio <0.65 mm/mm Hg at follow-up predicts adverse outcomes independently.
3. RV-PA coupling adds incremental prognostic value beyond LVEF and other traditional markers.
Background
Heart failure with reduced ejection fraction (HFrEF) remains a major global health burden, with high morbidity and mortality despite advances in guideline-directed medical therapy (GDMT). While the benefits of GDMT on left ventricular (LV) function are well-established, its impact on right ventricular (RV) function, particularly RV to pulmonary artery (PA) coupling, has been less studied. This gap is clinically significant given the prognostic importance of RV dysfunction in HFrEF.
Study Design
This retrospective study included 291 consecutive HFrEF patients (LVEF <50%) followed in a dedicated HF clinic at a tertiary center from January 2019 to June 2022. All patients underwent echocardiography at baseline (before GDMT up-titration) and at follow-up (end of up-titration). The primary endpoint was a composite of all-cause death or hospitalization for acute HF over 2 years.
Key Findings
The median patient age was 65 years, with 24% females and 47% having ischemic cardiomyopathy as the HF etiology. Baseline LVEF was severely reduced at 30%. After 2 years, 17% of patients reached the primary endpoint.
GDMT up-titration led to significant improvements in RV size and function parameters (all p<0.001). Most notably, RV-PA coupling (measured as TAPSE/sPAP ratio) improved from 0.62 to 0.81 mm/mm Hg (p<0.001).
A follow-up TAPSE/sPAP ratio <0.65 mm/mm Hg strongly predicted adverse outcomes after adjusting for:
- Comorbidities (HR 5.9, 95% CI 2.8-12.1)
- Clinical and biological severity (HR 6.4, 95% CI 2.4-17.8)
- Echocardiographic parameters (HR 3.6, 95% CI 1.6-8.4)
Importantly, TAPSE/sPAP provided incremental prognostic information beyond traditional predictors, including LVEF (C-index improvement, p<0.01).
Expert Commentary
These findings suggest several important clinical implications:
1. RV-PA coupling represents a measurable treatment target in HFrEF management.
2. Echocardiographic assessment of TAPSE/sPAP could help identify high-risk patients who may need more intensive follow-up or advanced therapies.
3. The results support a more comprehensive approach to HFrEF evaluation that includes right heart assessment alongside traditional LV-focused parameters.
Study limitations include its single-center retrospective design and potential selection bias inherent to tertiary center populations. Future prospective multicenter studies are needed to validate these findings.
Conclusion
This study establishes RV-PA coupling as an independent predictor of outcomes in HFrEF during GDMT optimization. The TAPSE/sPAP ratio provides clinically meaningful prognostic information beyond traditional markers, suggesting its potential role in guiding HFrEF management strategies. These findings highlight the importance of comprehensive right heart assessment in HFrEF patients undergoing GDMT up-titration.
Funding and ClinicalTrials.gov
The study was conducted as part of routine clinical follow-up in a tertiary HF clinic. No specific funding was reported. The original study can be identified via PubMed ID 41500258.