Validation of the Kansas City Cardiomyopathy Questionnaire in Patients with Tricuspid Regurgitation: The Tri-QOL Study

Importance: Improving patients' health status is a key goal of treating tricuspid regurgitation (TR). The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a heart-failure disease specific health status measure that has been used to capture the health status impact of TR and the benefit of transcatheter tricuspid valve intervention (TTVI), but its validity in this clinical setting is unknown. Objective: To evaluate the psychometric properties of the KCCQ in patients with TR. Design, Setting, Participants: Data were pooled from patients with severe TR enrolled in 11 manufacturer-sponsored trials of TTVI. The data were transferred to the FDA to harmonize and anonymize prior to analysis by an independent center. Prespecified analyses included evaluation of internal consistency, reproducibility, responsiveness, construct validity, and prognostic validity. Results: The study cohort comprised 2693 patients (mean age 79 +/- 8 years, 62% women, mean baseline KCCQ Overall Summary [KCCQ-OS] score 50 +/- 23), enrolled in either single-arm (n=1517) or randomized (n=1176) investigations of TTVI. There was strong internal consistency within individual domains (Cronbach's alpha 0.77-0.83). Among clinically stable patients between 1 and 6 months, there were small mean changes in KCCQ domain and summary scores (differences of -0.1 to 1.9 points), demonstrating reproducibility. In contrast, domain and summary scores of patients who underwent TTVI showed large improvements at 1-month after treatment (mean changes 12.1-21.4 points), indicating excellent responsiveness. Construct validity was moderately-strong to strong when the domains were compared with best available reference measures (Spearman correlations 0.47-0.69). The KCCQ-OS was strongly associated with clinical events, with lower scores being associated with an increased risk of mortality (HR 1.34 per 10-point decrement, 95% CI 1.22-1.47) and heart failure hospitalization (HR 1.24 per 10-point decrement, 95% CI 1.17-1.31). Conclusions and Relevance: The KCCQ has strong psychometric properties, including reliability, responsiveness, and validity in patients with severe TR. These data support its use in clinical investigations of TTVI as a measure of the impact of treatment on patients' symptoms, function, and quality of life. ### Competing Interest Statement John Spertus owns the copyright to the KCCQ and has served as a consultant for Abbott and Edwards Lifesciences. David Cohen received institutional research grants from Abbott, Edwards Lifesciences, Boston Scientific, NHLBI, and the FDA; consulting income from Abbott, Edwards Lifesciences, and Medtronic. The other authors have no potential conflicts to disclose. ### Funding Statement This research was funded by an investigator-initiated contract from the US Food and Drug Administration (Award #75F40122C00183). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: These analyses were approved by the Advarra central institutional review board, and a waiver of informed consent was granted, given the anonymized nature of the data transferred to the analytic center. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Research data are not shared