Citations

Introduction: Valvular heart disease (VHD) poses a growing global burden, particularly in aging populations. While transcatheter interventions have expanded rapidly over the past two decades, the extent to which trial populations reflect real-world demographics—especially age and sex—is unclear. Understanding enrollment trends and representation gaps is essential to ensure equitable, generalizable evidence for clinical decision-making. Methods: We systematically reviewed VHD interventional trials (2000–2024) indexed in PubMed. Surgical and percutaneous trials across aortic, mitral, tricuspid, and pulmonic valves were included. Trial characteristics, demographics, and interventions were analyzed using descriptive and nonparametric statistics. Results: We included 487 trials enrolling 87,412 participants (45% women). Median trial size increased over time (z = 4.98, p < 0.01), and the mean age of participants also rose significantly (z = 10.08, p < 0.01). Trials involving percutaneous (11% to 45%), bioprosthetic (22% to 53%), aortic valve (27% to 62%), and multinational (2% to 16%) interventions increased over time. Older participants were more commonly enrolled in percutaneous, industry-funded, multinational, bioprosthetic, and aortic valve trials. Female representation remained unchanged across time (median 47%, z = -0.48, p = 0.63), but trials enrolling older participants tended to include more women (ρ = 0.196, p < 0.01). Female representation was highest in mitral (59%) and tricuspid (59%) valve trials, and more common in percutaneous (52%) than surgical (42%) interventions. Conclusion: Over the past two decades, VHD trials have expanded in size and geographic scope, with increased enrollment of older adults, particularly in percutaneous and industry-sponsored studies. However, sex disparities and demographic variability persist. Future trials should prioritize inclusive designs to ensure equitable, generalizable evidence for evolving valve interventions.

Background A contemporary, comprehensive risk score for the prediction of in‐hospital fatal and nonfatal adverse events after percutaneous coronary intervention has been recently developed, albeit its external validation in patients with acute coronary syndrome is lacking. The objective of this study is to validate the Mayo Clinic integer risk score in a large cohort of patients with acute coronary syndrome undergoing percutaneous coronary intervention from the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial. Methods The risk score is composed of a common set of 23 clinical and procedural variables (model A) and 18 preprocedural variables (model B). The primary objective was to appraise the receiver‐operator characteristics of both models for in‐hospital mortality, bleeding, contrast‐associated acute kidney injury, and stroke. The impact of risk score categories on 1‐year outcomes was also investigated. Results Among the 6724 patients undergoing percutaneous coronary intervention in the MATRIX trial, the receiver‐operator characteristics—area under the curves for in‐hospital mortality, bleeding, contrast‐associated acute kidney injury, and stroke were 0.88 (95% CI, 0.85–0.91), 0.66 (95% CI, 0.63–0.69), 0.70 (95% CI, 0.67–0.72), and 0.65 (95% CI, 0.52–0.78) for model A and 0.88 (95% CI, 0.84–0.92), 0.63 (95% CI, 0.60–0.66), 0.66 (95% CI, 0.63–0.69), and 0.65 (95% CI, 0.52–0.78) for model B, respectively. Mortality (model A), bleeding, and stroke risks were well calibrated, whereas mortality (model B) and contrast‐associated acute kidney injury risk were underestimated. There was a gradual risk increase for 1‐year mortality and bleeding as a function of the risk score tertile using both models. Conclusions The risk score identifies patients with acute coronary syndrome at incremental risk of in‐hospital mortality, bleeding, contrast‐associated acute kidney injury, and stroke, representing a valuable tool for mitigation of modifiable risk factors. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01433627.

Background We tested whether biologic age, as estimated by deficits, functional impairments, or Age‐Gap or their combination, provide improved estimation of cause‐specific death as compared with chronological age. Methods Cardiovascular and noncardiovascular deficits, functional impairments, and Age‐Gap were prospectively collected in 535 patients aged ≥55 years undergoing percutaneous coronary interventions between August 1, 2014, and March 31, 2018. Age‐Gap was calculated as the difference between chronological age and age estimated by artificial intelligence ECG using a convolutional neural network. The full biological age model included deficits, functional impairments, and Age‐Gap >2 SD. A multivariable reduced model with the least number of variables was also created to provide a comparable C index to the full model. Results The average chronological age was 72.1±9.5 years, and there were 68% of men. During a median follow‐up of 2.61 years, 124 (23%) patients died. There was a modest correlation between Age‐Gap and biological age ( r =0.28 [95% CI, 0.20–0.35]; P <0.001). When modeled with chronologic age as a covariate, Age‐Gap predicted all‐cause (hazard ratio [HR], 1.07 [95% CI, 1.04–1.10]; P <0.001) and cardiovascular (HR, 1.07 [95% CI, 1.04–1.11]; P <0.001) mortality. As compared with chronological age, the full biological age model noted significant improvement in the prediction of long‐term overall (95% CI, 0.65–0.78), cardiovascular (95% CI, 0.69–0.77), and noncardiovascular (95% CI, 0.55–0.86) mortality. In the reduced models, most prognostic information for noncardiovascular mortality (C index: 0.79) was obtained by subjective difficulty in performing tasks, whereas the deficit‐based estimation predicted cardiovascular mortality (C index: 0.72). Conclusions Estimated biological age from deficits and functional impairments was superior to chronological age in predicting long‐term cause‐specific mortality following percutaneous coronary interventions.

Importance There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN. Objective To present the long-term efficacy and safety of patisiran in adults with hATTR-PN. Design, Setting, and Participants This global open-label extension (OLE) of the APOLLO randomized clinical trial and phase 2 OLE study enrolled patients from 43 hospitals or clinical centers across 19 countries between July 2015 and August 2017, with follow-up until November 2022. Of 212 eligible patients with hATTR who completed the phase 3 APOLLO or phase 2 OLE parent studies, 211 enrolled in and 138 completed the global OLE. Intervention Patisiran, 0.3 mg/kg, intravenously once every 3 weeks for up to 5 years. Main Outcomes and Measures Outcomes evaluated at year 5 of the global OLE included disability (polyneuropathy disability [PND] score); polyneuropathy severity (Neuropathy Impairment Score [NIS]), nutritional status (modified body mass index [mBMI]), quality of life (Norfolk Quality of Life–Diabetic Neuropathy [Norfolk QOL-DN]), and Rasch-Built Overall Disability Scale (R-ODS), with no statistical hierarchy. Safety, survival probability, and mortality were also assessed. Results At the global OLE baseline, the mean (SD) age was 61.3 (12.3) years, and 156 patients (73.9%) were male. In 138 patients completing the study, PND scores remained stable or improved in 89 patients (65.0%), NISs showed a mean (SD) change of 10.9 (14.7), and mean (SD) mBMI (calculated as weight in kilograms divided by height in meters squared times serum albumin in grams per liter) increased by 46.4 (120.7) over 5 years from baseline. Norfolk QOL-DN and R-ODS scores showed mean (SD) changes of 4.1 (16.7) and –3.7 (6.2), respectively. Adverse events (AEs) leading to study withdrawal occurred in 47 patients (22.3%). Infusion-related reactions were the most common treatment-related AE (n = 34 [16.1%]). Overall, 41 patients (19.4%) died during the study. Patisiran treatment in the parent study and low familial amyloid polyneuropathy score at parent study baseline were associated with significantly improved survival. Conclusions and Relevance In the longest study of an RNAi therapeutic for any disease, patisiran treatment resulted in modest changes for patients with hATTR-PN with an acceptable safety profile. These results highlight the importance of initiating early treatment for hATTR and the potential of RNAi therapeutics in medicine. Trial Registration ClinicalTrials.gov Identifier: NCT02510261

Introduction: We aim to elucidate the incidence of major complications related to right heart catheterization (RHC) and ascertain if there are unique risks with right ventricular biopsy. Methods: Diagnostic RHC procedures from 1/1/2002 through 12/31/2013 were identified using the clinical scheduling system at Mayo Clinic, Rochester. Major complications were identified through electronic records using International Classification of Diseases, Ninth Revision billing codes. All events were recorded and adjudicated. Analysis was performed on four separate patient categories (RHC/RV angiography alone, RV biopsy alone, multiple RHC procedures, and concurrent RHC/LHC procedures) and the overall group. Primary outcomes are described in Table 1. Outcomes were measured within 7 days of the procedure, except for death (same day events) and tricuspid regurgitation (variable time endpoints). Results: There were 17,696 RHC procedures (5,556 RHC/RV angiography, 3,846 RV biopsy alone, 776 multiple RHC procedures, and 7,518 combined RHC/LHC). Patient population had a mean age of 56.5 years (15.3) and was predominantly male (58.5%). Same-day death related to RHC procedure occurred in 1 procedure or 0.6 of 10,000 RHCs. There was no significant difference in the risk of complications across RHC procedure categories except for worsening tricuspid regurgitation, which was significantly (p<0.001) more prevalent with RV biopsy (392 cases, 6.0%) than without (136 cases, 1.2%). Conclusion: The incidence of major complications related to right heart catheterization is rare. Worsening tricuspid regurgitation is the most frequently identified change with a significantly higher prevalence with biopsies.

Introduction: Survivorship needs to be comprehensively evaluated amongst older adults. We examined follow-up mortality in patients referred to cardiac catheterization laboratory by prospectively examining frailty. Methods: Frailty in 923 patients ≥55 years was determined using Rockwood’s deficit index. The frailty deficit was based on symptoms, signs, disabilities, diseases, and laboratory measurements. The number of deficits was expressed as a proportion of the total measured deficits. Frailty index was grouped into <0.10 (control), 0.10-<0.20, 0.20-<0.30, 0.30+ and age- and gender-adjusted follow-up mortality was determined using a Cox proportional hazards model. Results: There were 180 (20%) with frailty index <0.10, 348 (38%) in 0.10-<0.20, 215 (23%) in 0.20-<0.30 and 177 (19%) with an index of 0.30 or higher. Patients with a frailty index of 0.30+ were significantly older than those with an index <0.10 (75 ± 10 vs 67 ± 8 years; p<0.001) and more likely to be women (50% vs 20%; p<0.001). Patients with frailty index ≥0.20 and ≥0.30 had a significantly higher mortality risk (HR 3.95, 95% CI 1.51-10.3 and HR: 10.3, 95% CI 4.11-25.7, respectively) on follow-up which remained significant following adjustment for age and gender (HR 3.20, 95% CI 1.21-8.45 and HR: 7.99, 95% CI 3.13-20.4). Conclusions: Among older adults refereed to catheterization laboratory, frailty deficit index predicts follow-up mortality.