A framework incorporating disease-specific echocardiographic thresholds for tricuspid regurgitation showed greater prognostic discrimination than European and US guideline definitions among patients with transthyretin amyloid cardiomyopathy in a study published in JAMA Cardiology.
Investigators enrolled 1,124 consecutive adult patients with newly diagnosed transthyretin amyloid cardiomyopathy at 8 high-volume tertiary referral centers in Austria, Italy, Germany, and the Netherlands from January 2016 to February 2026. The median age was 80 years and 260 patients (23%) were female. Patients with prior tricuspid valve intervention or severe aortic stenosis or aortic regurgitation were excluded.
At baseline, patients underwent standardized transthoracic echocardiography with centralized, blinded core laboratory assessment of tricuspid regurgitation using vena contracta width, effective regurgitant orifice area, and regurgitant volume. The derivation cohort included 745 patients from Austria and Germany, and the validation cohort included 379 patients from Italy and the Netherlands. All-cause mortality was the primary end point, and time to first heart failure hospitalization was the secondary end point.
Restricted cubic spline analyses identified intermediate-risk thresholds of 3 mm for vena contracta width, 0.15 cm² for effective regurgitant orifice area, and 10 mL for regurgitant volume. High-risk thresholds were 5 mm, 0.25 cm², and 20 mL, respectively, and extreme-risk thresholds were 8 mm, 0.50 cm², and 40 mL. Investigators established the cut points in the derivation cohort, with their prognostic significance subsequently confirmed in the validation cohort.
“Importantly, prognostic [tricuspid regurgitation] thresholds in [transthyretin amyloid cardiomyopathy] are substantially lower than the conventional cutoffs in current guideline and [Tricuspid Valve Academic Research Consortium] definitions,” wrote lead author Laurenz Hauptmann, MD, of the Clinical Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna in Vienna, Austria, and colleagues.
During a median follow-up of 25 months, 324 patients (29%) died and 251 (22%) experienced at least 1 heart failure hospitalization. The framework classified 413 patients (37%) as low risk, 377 (34%) as intermediate risk, 234 (21%) as high risk, and 100 (9%) as extreme risk. Kaplan-Meier analyses showed stepwise separation in mortality across the 4 categories in the overall, derivation, and validation cohorts.
Overall, 334 patients (30%) met high- or extreme-risk criteria under the proposed framework, compared with 130 (12%) classified as having severe tricuspid regurgitation under the guideline-based and Tricuspid Valve Academic Research Consortium schemes. Following full adjustment for clinical and echocardiographic factors, the proposed framework remained independently associated with mortality and heart failure hospitalization and the highest point estimates among the grading schemes.
Time-dependent analyses showed significantly greater discrimination with the framework compared with European and US guideline definitions at all assessed time points in the overall and derivation cohorts and with American Society of Echocardiography and Tricuspid Valve Academic Research Consortium schemes from 36 months onward. In the validation cohort, the framework showed significantly greater discrimination than European and US guideline definitions from 24 months onward, while differences compared with American Society of Echocardiography and Tricuspid Valve Academic Research Consortium schemes did not reach statistical significance.
The investigators cautioned that the thresholds were developed for prognostic assessment rather than to determine eligibility for tricuspid valve intervention. They noted that causal conclusions could not be drawn from the observational study and that residual confounding remained possible. Tricuspid regurgitation measurements were limited to baseline, without evaluation of longitudinal or treatment-related changes. The investigators also noted that the high feasibility of quantitative assessment reflected standardized core laboratory acquisition and measurement that may be less reproducible in routine practice.
Disclosures: Several study authors reported financial relationships, including grants, personal or consulting fees, advisory board or speaker fees, educational support, proctor fees, congress support, or clinical trial involvement, with companies including Alnylam, Bayer, Pfizer, AstraZeneca, Edwards Lifesciences, Abbott, Medtronic, Novartis, and others. Full disclosures can be found in the published study.
Source: JAMA Cardiology
