Available online 3 July 2025

Author links open overlay panel, , , , , , , , , , , , , , , AbstractBackground

Functional tricuspid regurgitation (TR) arises from impaired valve integrity resulting from contractile dysfunction, chamber dilation, or myocardial tissue alterations. Whereas right ventricular (RV) dysfunction is a recognized driver of adverse outcomes in TR, the impact of myocardial tissue injury, particularly nonischemic septal fibrosis (NIsF), remains largely unexplored.

Objectives

This study aims to evaluate the association of NIsF with adverse right-sided chamber remodeling and to assess its incremental prognostic value for mortality in patients with functional TR.

Methods

Patients with advanced (≥ moderate) functional TR underwent comprehensive cardiac magnetic resonance (CMR) evaluation. Late gadolinium enhancement (LGE) was used to identify NIsF, defined as hyperenhancement in the midmyocardial or epicardial regions of the interventricular septum. Cine CMR measured functional and geometric indices of the left and right sides of the heart. Follow-up data were obtained for all-cause mortality.

Results

A total of 663 patients with advanced TR (mean age: 63.8 ± 16.0 years; 53% male) were studied, and 29.4% were found to have NIsF. NIsF was strongly associated with adverse chamber remodeling, including larger left ventricular and RV volumes, reduced systolic function, and increased TR severity (all P < 0.001). TR regurgitant fraction increased stepwise with NIsF extent (no NIsF, 34.9% ± 1.5%; 1 segment, 38.1% ± 13.0%; 2 segments, 40.8% ± 13.8%; P < 0.001). Over a mean follow-up of 4.3 ± 4.3 years, 25.3% of patients died. NIsF was independently associated with mortality (HR: 1.79 [95% CI: 1.26-2.56]; P = 0.001), even after adjusting for conventional risk markers, including age, TR severity, RV dysfunction, and dilation. Kaplan-Meier analysis demonstrated significantly higher mortality risk among patients with NIsF compared with patients without NIsF (P < 0.001).

Conclusions

Among patients with advanced TR, NIsF is an important marker of adverse right-sided chamber remodeling and provides incremental prognostic utility beyond conventional risk markers.

Central IllustrationDownload: Download high-res image (1MB)Download: Download full-size imageSection snippetsStudy group

The study group comprised consecutive patients with advanced functional TR (≥ moderate) who underwent CMR at New York Presbyterian Hospital–Weill Cornell Medicine (New York, New York, USA). Patients with previous tricuspid valve surgery, congenital heart disease, or primary tricuspid valvular disease (prolapse, rheumatic, leaflet perforation) were excluded, as were patients with CMR-evidenced conditions that impeded visualization of NIsF and myocardial infarction, including infiltrative

Study group characteristics

The study cohort included 663 patients with advanced (≥ moderate) functional TR. Nearly one-third (29.4%) of these patients had NIsF identified on LGE CMR. All patients underwent comprehensive multiplanar cine CMR imaging, including contiguous short-axis data sets for quantifying RV function and volumes, as well as 4-chamber long-axis images to confirm the functional cause of TR.

Table 1 summarizes baseline demographic and clinical characteristics, including comparisons between patients with and

Discussion

This study offers novel insights into the prognostic significance of NIsF in patients with functional TR (Central Illustration). Our findings demonstrate that NIsF detected on LGE CMR is not only highly prevalent, affecting more than one-fourth of the study patients but also strongly associated with increased all-cause mortality risk, even after adjusting for conventional risk factors, including age and RV remodeling. Additionally, our data reveal that NIsF is independently associated with

Conclusions

This study demonstrates that among patients with advanced TR, myocardial injury (NIsF) noted on LGE CMR is strongly associated with adverse right-sided chamber remodeling and provides incremental prognostic utility beyond conventional risk factors. Study findings highlight the importance of myocardial tissue characterization in patients with functional TR and lay the foundation for future research to test whether targeted interventions can improve outcomes.

Funding Support and Author Disclosures

This study has received funding from the National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) (grant K23HL140092 to Dr J. Kim and grant R01HL170566 to Drs Weinsaft and Kim). Dr Weinsaft has received funding for this work from NIH/NHLBI. Dr Kim has received funding for this work from NIH/NHLBI. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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© 2025 by the American College of Cardiology Foundation. Published by Elsevier.