# Right-Sided Extravalvular Damage: An Overlooked Driver of Risk Model Failure in Low-Flow, Low-Gradient Aortic Stenosis

**Authors:** Yash Prakash, Akarsh Sharma, Lakshay Chopra, Mihir Prakash, Eileen Galvani, Oludamilola Akinmolayemi, Carlo Mannina, Ranbir Singh, Jonathan L. Halperin, Samin K. Sharma, Annapoorna S. Kini, Deepak L. Bhatt, Stamatios Lerakis

PMC · DOI: 10.1016/j.jscai.2025.104116 · 2025-12-30

## TL;DR

This study shows that right-sided heart damage improves risk prediction for aortic stenosis patients undergoing TAVR, especially in moderate-risk groups.

## Contribution

Identifies right-sided extravalvular damage as a novel factor improving mortality prediction in low-flow aortic stenosis patients.

## Key findings

- Right-sided extravalvular damage is independently linked to higher 1-year mortality after TAVR.
- Adding these markers improved model fit and discrimination, particularly in moderate-risk patients.
- The STS-PROM score overestimates mortality, but this can be corrected with right-sided damage markers.

## Abstract

The Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score is guideline-endorsed for estimating procedural risk in aortic stenosis (AS) but tends to overestimate long-term mortality after transcatheter aortic valve replacement (TAVR). This study aimed to evaluate whether markers of right-sided extravalvular damage improve STS-PROM’s performance in predicting 1-year mortality post-TAVR for patients with low-flow, low-gradient AS.

Four hundred ten patients with valve area ≤1.0 cm2, stroke volume index ≤35 mL/m2, and mean gradient <40 mm Hg who underwent TAVR were retrospectively stratified into low (<4%), moderate (4%-8%), and high (>8%) STS-PROM risk groups. Performance of an enhanced logistic regression model incorporating both STS-PROM and right-sided extravalvular damage (defined as moderate+ pulmonary hypertension, moderate+ tricuspid regurgitation, or right ventricular systolic dysfunction) was assessed using receiver operating characteristic curves, net reclassification index (NRI), and integrated discrimination index (IDI).

Right-sided extravalvular damage was independently associated with increased 1-year mortality (OR, 2.45; 95% CI, 1.34-4.46; P < .01). Model fit improved with its addition (Δχ2 = 8.68, P < .01), and discrimination increased (IDI = 0.02, P = .01). NRI analysis showed improved survivor classification (non-event NRI = 0.10, P < .01). The largest gain was in moderate-risk patients (area under the curve, 0.46-0.67; P = .06).

Markers of right-sided extravalvular damage conferred meaningful prognostic value in low-flow, low-gradient AS by correcting the STS-PROM score’s tendency to overestimate post-TAVR mortality. The added value of these markers was most pronounced in moderate-risk patients, for whom existing tools appear least reliable. These markers may improve patient selection for TAVR and merit evaluation in other severe AS phenotypes.

## Linked entities

- **Diseases:** aortic stenosis (MONDO:0042981)

## Full-text entities

- **Genes:** STS (steroid sulfatase) [NCBI Gene 412] {aka ARSC, ARSC1, ASC, ES, SSDD, XLI}, NPPB (natriuretic peptide B) [NCBI Gene 4879] {aka BNP, Iso-ANP}
- **Diseases:** MR (MESH:D008944), Extravalvular Damage (MESH:D020263), pulmonary hypertension (MESH:D006976), frailty (MESH:D000073496), Cardiomyopathy (MESH:D009202), aortic regurgitation (MESH:D001022), cardiac remodeling (MESH:D020257), coronary artery disease (MESH:D003324), LFLG (MESH:D009800), CVA (MESH:D020521), cardiac damage (MESH:D006331), LV systolic dysfunction (MESH:D018487), peripheral artery disease (MESH:D058729), heart failure (MESH:D006333), arrhythmias (MESH:D001145), tricuspid regurgitation (MESH:D014262), AS (MESH:D001024), paravalvular leak (MESH:D019559), PROM (MESH:D005322), chronic kidney disease (MESH:D051436), DM (MESH:D009223), RV dysfunction (MESH:D018497), renal failure (MESH:D051437), CKD (MESH:D012080), diabetes mellitus (MESH:D003920), atrial fibrillation (MESH:D001281), valvular disease (MESH:D006349), hypertension (MESH:D006973), Death (MESH:D003643), hyperlipidemia (MESH:D006949)
- **Chemicals:** creatinine (MESH:D003404), calcium (MESH:D002118), Cr (MESH:D002857), dobutamine (MESH:D004280), Acurate neo (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12923347/full.md

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Source: https://tomesphere.com/paper/PMC12923347