JAMA cardiology最新文献

Importance: Secondary tricuspid regurgitation (STR) is observed in multiple cardiac and pulmonary diseases. Heart failure with preserved ejection fraction (HFpEF) is a common cause of STR that may be overlooked, along with precapillary etiologies of pulmonary hypertension (PH).

Objectives: To investigate the prevalence of HFpEF and precapillary PH in patients with severe STR of undefined etiology (isolated STR) referred for exercise right heart catheterization (RHC), and to evaluate the performance of noninvasive measures to identify HFpEF.

Design, setting, and participants: This retrospective cross-sectional study included consecutive adults with severe STR in the absence of EF less than 50%, hemodynamically significant left-sided valve disease, congenital heart disease, infiltrative or hypertrophic cardiomyopathy, pericardial disease, or prior cardiac procedures who underwent rest-and-exercise RHC between February 2006 and June 2023 at Mayo Clinic and transthoracic echocardiography less than 90 days prior. Diastolic dysfunction (DD) was defined by at least 3 of 4 or 2 of 3 abnormal diastolic parameters (medial e', medial E/e', tricuspid regurgitation [TR] velocity, left atrial volume index). HFpEF was diagnosed when pulmonary arterial wedge pressure was at least 15 mm Hg at rest, at least 19 mm Hg with feet up, or at least 25 mm Hg during exercise. Data analysis was performed from November 2023 to March 2024.

Main outcomes and measures: The prevalence of HFpEF and precapillary PH in severe isolated STR was determined, and performance of noninvasive measures to identify HFpEF was evaluated.

Results: Overall, 54 patients with severe isolated STR (mean [SD] age, 70.8 [12.5] years; 34 [63%] female) were identified. The primary indication for RHC was evaluation of TR prior to potential intervention in 36 patients (67%), evaluation of PH in 13 (24%), and confirmation of HFpEF in 5 (9%). HFpEF was identified in 40 patients (74%) but was recognized prior to RHC in only 19 patients (35%). Of the 14 remaining patients without HFpEF, precapillary PH was diagnosed in 10 (71%). Guideline-defined DD was absent in 24 patients (60%) who were subsequently diagnosed with HFpEF. Left atrial emptying fraction (area under the receiver operating characteristic curve [AUC] = 0.90; 95% CI, 0.82-0.98) and strain (AUC = 0.91; 95% CI, 0.83-0.99) had robust discrimination for HFpEF.

Conclusions and relevance: The findings suggest that HFpEF is underdiagnosed and should be rigorously evaluated for in patients with severe isolated STR, along with precapillary PH, as both have distinct requirements for management. Resting DD based on current guidelines is insufficiently sensitive in these patients, indicating a pressing need for other noninvasive diagnostic tools, such as left atrial function assessment.

Importance: Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist. However, it is unknown which genetic and cardiovascular risk factors might be AS-specific and which could be shared between AS and CAD.

Objective: To identify genetic risk loci and cardiovascular risk factors with AS-specific associations.

Design, setting, and participants: This was a genomewide association study (GWAS) of AS adjusted for CAD with participants from the European Consortium for the Genetics of Aortic Stenosis (EGAS) (recruited 2000-2020), UK Biobank (recruited 2006-2010), Estonian Biobank (recruited 1997-2019), and FinnGen (recruited 1964-2019). EGAS participants were collected from 7 sites across Europe. All participants were of European ancestry, and information on comorbid CAD was available for all participants. Follow-up analyses with GWAS data on cardiovascular traits and tissue transcriptome data were also performed. Data were analyzed from October 2022 to July 2023.

Exposures: Genetic variants.

Main outcomes and measures: Cardiovascular traits associated with AS adjusted for CAD. Replication was performed in 2 independent AS GWAS cohorts.

Results: A total of 18 792 participants with AS and 434 249 control participants were included in this GWAS adjusted for CAD. The analysis found 17 AS risk loci, including 5 loci with novel and independently replicated associations (RNF114A, AFAP1, PDGFRA, ADAMTS7, HAO1). Of all 17 associated loci, 11 were associated with risk specifically for AS and were not associated with CAD (ALPL, PALMD, PRRX1, RNF144A, MECOM, AFAP1, PDGFRA, IL6, TPCN2, NLRP6, HAO1). Concordantly, this study revealed only a moderate genetic correlation of 0.15 (SE, 0.05) between AS and CAD (P = 1.60 × 10-3). Mendelian randomization revealed that serum phosphate was an AS-specific risk factor that was absent in CAD (AS: odds ratio [OR], 1.20; 95% CI, 1.11-1.31; P = 1.27 × 10-5; CAD: OR, 0.97; 95% CI 0.94-1.00; P = .04). Mendelian randomization also found that blood pressure, body mass index, and cholesterol metabolism had substantially lesser associations with AS compared with CAD. Pathway and transcriptome enrichment analyses revealed biological processes and tissues relevant for AS development.

Conclusions and relevance: This GWAS adjusted for CAD found a distinct genetic risk profile for AS at the single-marker and polygenic level. These findings provide new targets for future AS research.