Importance:Bilateral internal thoracic artery grafting has been proposed to improve survival compared to standard single internal thoracic artery grafting during coronary artery bypass graft (CABG) surgery, but any survival benefit may emerge only with longer-term follow-up. Objective:To report 15-year extended follow-up of a randomized clinical trial of bilateral vs single internal thoracic artery grafting for CABG. Design, Setting, and Participants:This is a secondary analysis of an unblinded randomized clinical trial that took place at 28 cardiac surgery centers in 7 countries between June 2004 and December 2007, with 15-year follow-up reported after 2025. Patients scheduled for CABG on clinical grounds were eligible. Those requiring only single grafts or concomitant valve surgery, as well as those with a history of previous CABG, were excluded. All 3102 patients in the original trial provided data for this analysis, while 3042 completed the full 15-year follow-up. Data were analyzed from January to March 2026. Intervention:If patients fulfilled all the eligibility criteria and provided written informed consent, they were randomly assigned to bilateral or single internal thoracic artery grafts with vein or radial artery grafts used in both groups as clinically indicated. Main Outcomes and Measures:All-cause mortality at 15 years. The composite of all-cause mortality, myocardial infarction, or stroke was a secondary outcome. Results:A total of 1548 patients were randomized to bilateral internal thoracic artery grafts and 1554 to single internal thoracic artery grafts. The mean (SD) age was 64 (9) years and 446 (15%) were female. In the bilateral graft group, 215 (14%) received only a single arterial graft, while in the single graft group, 359 (23%) also received a radial artery graft. At 15 years, vital status was known for 3039 patients (98%). There were 585 deaths (37.8%) in the bilateral graft group and 584 (37.6%) in the single graft group (hazard ratio [HR], 1.00; 95% CI, 0.89-1.12; P = .97). Secondary outcome event rates were 43.9% and 45.8%, respectively (HR, 0.94; 95% CI, 0.85-1.05). Conclusions and Relevance:There was no difference in all-cause mortality at 15 years between patients undergoing CABG who were randomized to bilateral vs single internal thoracic artery grafts in an intention-to-treat analysis. Given the high rate of potential postrandomization confounders (eg, crossovers and use of radial arteries), the multiple arterial graft hypothesis still needs to be tested in randomized clinical trials. Trial Registration:isrctn.org Identifier: ISRCTN46552265.
This case report discusses a diagnosis of Carney complex type 1 after genetic testing of a male patient aged 36 years with multiple atrial myxomas, bilateral testicular calcification, and a history of recurrent skin masses since childhood.
Importance Bilateral internal thoracic artery grafting has been proposed to improve survival compared to standard single internal thoracic artery grafting during coronary artery bypass graft (CABG) surgery, but any survival benefit may emerge only with longer-term follow-up. Objective To report 15-year extended follow-up of a randomized clinical trial of bilateral vs single internal thoracic artery grafting for CABG. Design, Setting, and Participants This is a secondary analysis of an unblinded randomized clinical trial that took place at 28 cardiac surgery centers in 7 countries between June 2004 and December 2007, with 15-year follow-up reported after 2025. Patients scheduled for CABG on clinical grounds were eligible. Those requiring only single grafts or concomitant valve surgery, as well as those with a history of previous CABG, were excluded. All 3102 patients in the original trial provided data for this analysis, while 3042 completed the full 15-year follow-up. Data were analyzed from January to March 2026. Intervention If patients fulfilled all the eligibility criteria and provided written informed consent, they were randomly assigned to bilateral or single internal thoracic artery grafts with vein or radial artery grafts used in both groups as clinically indicated. Main Outcomes and Measures All-cause mortality at 15 years. The composite of all-cause mortality, myocardial infarction, or stroke was a secondary outcome. Results A total of 1548 patients were randomized to bilateral internal thoracic artery grafts and 1554 to single internal thoracic artery grafts. The mean (SD) age was 64 (9) years and 446 (15%) were female. In the bilateral graft group, 215 (14%) received only a single arterial graft, while in the single graft group, 359 (23%) also received a radial artery graft. At 15 years, vital status was known for 3039 patients (98%). There were 585 deaths (37.8%) in the bilateral graft group and 584 (37.6%) in the single graft group (hazard ratio [HR], 1.00; 95% CI, 0.89-1.12; P = .97). Secondary outcome event rates were 43.9% and 45.8%, respectively (HR, 0.94; 95% CI, 0.85-1.05). Conclusions and Relevance There was no difference in all-cause mortality at 15 years between patients undergoing CABG who were randomized to bilateral vs single internal thoracic artery grafts in an intention-to-treat analysis. Given the high rate of potential postrandomization confounders (eg, crossovers and use of radial arteries), the multiple arterial graft hypothesis still needs to be tested in randomized clinical trials. Trial Registration isrctn.org Identifier: ISRCTN46552265
Importance:In transthyretin amyloid cardiomyopathy (ATTR-CM), tricuspid regurgitation (TR) severity may be underestimated by conventional (semi-)quantitative echocardiographic criteria derived from nonamyloid populations, given the restrictive, low-flow hemodynamics characteristic of the disease. Objectives:To derive and validate disease-specific prognostic, quantitative TR risk thresholds in ATTR-CM and to compare their prognostic performance with current guideline definitions and the Tricuspid Valve Academic Research Consortium (TVARC) 5-grade extension. Design, Setting, and Participants:This international, multicenter cohort study was conducted from January 2016 to February 2026 at 8 high-volume tertiary referral centers across Austria, Italy, Germany, and the Netherlands, with data analysis February to May 2026. Patients with newly diagnosed ATTR-CM were enrolled and underwent standardized transthoracic echocardiography with blinded core laboratory quantitative analysis of echocardiography TR severity parameters (vena contracta width [VCW], effective regurgitant orifice area [EROA], and regurgitant volume [RegVol]). Exposures:TR severity defined by VCW, EROA, and RegVol from blinded core laboratory quantitative analysis and TR severity according to 2025 European Society of Cardiology/European Association for Cardio-Thoracic Surgery, 2020 American Heart Association/American College of Cardiology, 2017 American Society of Echocardiography, and 2023 TVARC grading schemes. Main Outcomes and Measures:Outcomes were all-cause mortality (primary end point) and time to first heart failure hospitalization (HFH; secondary end point). Results:A total of 1124 patients with newly diagnosed ATTR-CM were enrolled (derivation cohort: n = 745; validation cohort: n = 379). Median (IQR) patient age was 80 (75-84) years, and 260 patients (23.1%) were female. Over a median (IQR) follow-up of 25.2 (12.2-43.2) months, 324 patients (28.8%) died and 251 (22.3%) experienced HFH. All TR metrics independently predicted both end points. Spline-derived thresholds delineated intermediate (VCW ≥3 mm; EROA ≥0.15 cm2; RegVol ≥10 mL), high (≥5 mm; ≥0.25 cm2; ≥20 mL), and extreme risk (≥8 mm; ≥0.50 cm2; ≥40 mL), with stepwise Kaplan-Meier separation in both cohorts. Whereas the guideline-based and TVARC schemes each classified 130 patients (11.6%) as having severe TR, the proposed framework classified 334 patients (29.7%) as having at least high or extreme risk (P < .001 for comparison to all other definitions). The framework was independently associated with both end points, with the highest point estimate among the schemes (mortality: hazard ratio [HR], 1.41; 95% CI, 1.23-1.62; HFH: HR, 1.31; 95% CI, 1.12-1.54), and showed superior discrimination over guideline definitions, particularly at later time points. Conclusions and Relevance:In this multicenter cohort study among patients with ATTR-CM, a validated, risk-based conceptual framework of echocardiographic parameters to quantify TR improved prediction of mortality and HFH over standard classification of TR severity, better reflecting restrictive low-flow pathophysiology and supporting disease-specific TR grading in ATTR-CM.
Importance:The fourth universal definition of myocardial infarction (UDMI) distinguishes type 1 from type 2 myocardial infarction (MI), but this framework does not fully capture the heterogeneity of underlying mechanisms and prognosis. Objective:To characterize the distribution and clinical features of MI causal endotypes in a large contemporary cohort with a descriptive assessment of associated 1-year outcomes. Design, Setting, and Participants:Consecutive patients from the prospective, multicenter AMIPE registry with an adjudicated diagnosis of MI according to the fourth UDMI were included between January 1, 2017, and December 31, 2023. Follow-up was 1 year; patients with available 1-year follow-up or who died within the first year were included. Type 3, 4, and 5 MI and nonischemic myocardial injuries were excluded. These data were analyzed from June 2025 to May 2026. Exposures:Patients were classified according to the primary etiologic mechanism of MI into 4 causal endotypes: cardiac/coronary, cardiac/noncoronary, systemic, or indeterminate. Main Outcomes and Measures:The main measures were the distribution of causal endotypes and underlying etiologies. One-year outcomes included all-cause death, major adverse cardiovascular events ([MACE] cardiovascular death or recurrent MI), cardiovascular death, and recurrent MI. Cox and Fine-Gray models used the cardiac/coronary group as reference. Results:Among 6282 patients, mean (SD) age was 69.8 (13.5) years and 2013 (32.0%) were women. Overall, 5330 patients (84.9%) had a cardiac/coronary cause, including 5158 with acute atherothrombosis and 172 with nonatherothrombotic coronary mechanisms, 302 had a cardiac/noncoronary cause (4.8%), most commonly tachyarrhythmia, 503 had a systemic cause (8.0%), and 147 had an indeterminate cause (2.3%). At 1 year, all-cause mortality was 9.8% in cardiac/coronary MI, 15.9% in cardiac/noncoronary MI, 25.8% in systemic MI, and 1.4% in indeterminate MI. Compared with cardiac/coronary MI, adjusted hazard ratios for all-cause death were 1.46 (95% CI, 1.08-1.96) for cardiac/noncoronary MI, 2.50 (95% CI, 2.05-3.05) for systemic MI, and 0.22 (95% CI, 0.06-0.89) for indeterminate MI. Higher mortality in systemic and cardiac/noncoronary MI was largely related to noncardiovascular death. MACE rates differed less markedly across endotypes, whereas recurrent MI was less frequent in cardiac/noncoronary and systemic MI than in cardiac/coronary MI. Conclusions and Relevance:In this study, a causal endotype-based classification of MI identified distinct underlying mechanisms and clinical profiles that were not fully captured by the type 1/type 2 framework. This approach may complement the UDMI by improving characterization of MI heterogeneity.
This case report discusses intravascular lithotripsy and resultant ventricular fibrillation in a man in his 70s with severely calcified right coronary artery stenosis.
Importance Left atrial (LA) dysfunction may play an important role in the pathophysiology of transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and is driven by LA remodeling and amyloid infiltration. Objectives To evaluate the prognostic significance of LA structure and function among patients with ATTR-CM and to assess the effects of vutrisiran on these parameters. Design, Setting, and Participants Post hoc analyses were conducted of the HELIOS-B phase 3 randomized clinical trial, which enrolled patients with ATTR-CM between December 2019 and August 2021 at 87 sites in 26 countries. Median (IQR) follow-up was 36 (33-36) months. Data were analyzed from July through November 2025. Interventions Vutrisiran (25 mg subcutaneously every 3 months) vs placebo. Main Outcomes and Measures The primary outcome was all-cause mortality (ACM) and recurrent cardiovascular events. LA structure (LA volume index [LAVi]) and function (LA reservoir [LASr], conduit [LAScd], and contractile strain [LASct]) were assessed, including the effect of vutrisiran on these measures at 30 months. Results A total of 655 patients were enrolled. Among 644 patients with measurable LA strain (median [IQR] age, 77 [72-80] years; 48 female patients [7.5%]; 569 (88.4%) with wild-type ATTR), mean (SD) LA strain measures were substantially below normal (LASr: 9.5% [6.0%]; LAScd: 6.9% [3.9%]; LASct: 4.2% [4.0%]). Patients with worse LASr had more advanced disease, more atrial fibrillation, and more left ventricular systolic and diastolic dysfunction. LASr and LASct were independently associated with ACM and recurrent cardiovascular events (LASr: hazard ratio [HR] per 5% worsening, 1.37; 95% CI, 1.13-1.68; P = .002; LASct: HR per 5% worsening, 1.53; 95% CI, 1.08-2.17; P = .02), recurrent heart failure hospitalizations (LASr: HR, 1.66; 95% CI, 1.22-2.25; P = .001; LASct: HR, 2.23; 95% CI. 1.46-3.71; P < .001), and incident atrial fibrillation (LASr: HR, 1.30; 95% CI, 1.03-1.63; P = .03; LASct: HR, 2.02; 95% CI, 1.38-2.96; P < .001). In contrast, LAVi was not associated with these outcomes. LA strain measures at baseline did not modify the treatment effect of vutrisiran on ACM and recurrent cardiovascular events (LASr: P value for interaction = .60; LAScd: P value for interaction = .58; LASct: P value for interaction = .47). Vutrisiran attenuated worsening in LA strain vs placebo at month 30 (LASr: +1.2%; 95% CI, +0.4% to +1.9%; LAScd: +0.8%; 95% CI, +0.3% to +1.4%; LASct: +0.8%; 95% CI, 0% to +1.6%). Conclusions and Relevance Per the results of this secondary analysis of the HELIOS-B randomized clinical trial, LA dysfunction is common among patients with ATTR-CM and portends a worse prognosis. Consistent with its beneficial effects on other measures of cardiac structure and function, vutrisiran attenuated worsening in LA strain at 30 months, supporting the importance of LA function in the pathophysiology of ATTR-CM and the ability of silencer therapy with vutrisiran to attenuate worsening atrial myopathy in amyloid heart disease. Trial Registration ClinicalTrials.gov Identifier: NCT04153149
This Viewpoint explores the evidence gap around maternal cardiovascular disease and advocates for a more coordinated, patient-centered, and longitudinal approach to research to address this gap.
Importance:Transthyretin amyloid cardiomyopathy (ATTR-CM) is caused by extracellular myocardial ATTR amyloid infiltration. Vutrisiran, an RNA interference therapeutic that suppresses hepatic TTR production, met its primary end point in the HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy) trial. Multiparametric cardiovascular magnetic resonance (CMR) imaging provides high-fidelity structural and functional assessment, including tissue characterization metrics, namely extracellular volume (ECV) mapping, that can track cardiac amyloid load. Objective:To analyze the association between treatment with vutrisiran and changes in cardiac structure, function, and amyloid burden by CMR imaging. Design, Setting, and Participants:This was a retrospective post hoc analysis of CMR data from participants in the UK HELIOS-B trial. This was a single-center study conducted at the UK National Amyloidosis Centre (NAC). The study population comprised participants from the HELIOS-B trial at the NAC who underwent CMR imaging at baseline and 1-, 2-, and 3-year time points as part of routine clinical care. Study data were analyzed March to April 2025. Exposure:CMR imaging during the HELIOS-B trial between April 2020 and August 2024. Main Outcomes and Measures:CMR parameters of cardiac structure, volumetrics, function, and amyloid burden were assessed. Amyloid regression and progression were defined as absolute reductions and increases in ECV of 5% or greater, respectively. Analysis was blinded to treatment allocation. Changes in CMR parameters between baseline and follow-up were evaluated; a mixed-model analysis was used to assess treatment effect. Sensitivity analyses were conducted using the last observation carried forward. Results:A total of 43 patients (mean [SD] age, 75.0 [5.7] years, 41 male [95.3%]) underwent baseline CMR imaging (21 [48.8%] received vutrisiran; 22 [51.2%] received placebo). Thirty-nine patients (21 received vutrisiran, 18 received placebo), 26 (14 received vutrisiran, 12 received placebo), and 17 (9 received vutrisiran, 8 received placebo) underwent 1-, 2-, and 3-year CMR imaging, respectively. Baseline parameters were comparable between groups. No patients received background tafamidis. Treatment with vutrisiran was associated with statistically significant and directionally favorable changes in biventricular ejection fractions (left ventricular ejection fraction least-squares mean difference, 19.18%; 95% CI, 11.76%-26.60%; P < .001; right ventricular ejection fraction, 16.28%; 95% CI, 9.58%-22.97%; P < .001) and stroke volumes (left ventricular stroke volume, 27.82 mL; 95% CI, 13.40-42.23 mL; P < .001; right ventricular stroke volume, 23.69 mL; 95% CI, 8.06-39.32 mL; P = .003), as well as reductions in left ventricular mass (-23.58 g; 95% CI, -38.78 to -8.39 g; P = .002) and ECV (-6.56%; 95% CI, -10.10% to -3.01%; P < .001). At 36 months, amyloid regression was observed in 2 of 9 patients (22%) taking vutrisiran, and no patients receiving placebo experienced regression. Conversely, 5 of 8 patients (63%) receiving placebo demonstrated progression vs 1 of 9 patients (11%) taking vutrisiran. Conclusions and Relevance:Results of this selected ATTR-CM cohort study show that treatment with vutrisiran was associated with favorable changes in parameters relating to cardiac structure, function, and amyloid burden.
Importance:Left ventricular structural assessment is fundamental in heart failure (HF). However, the independent prognostic value of left ventricular size beyond its association with ejection fraction remains poorly defined in real-world, large-scale populations. Objective:To investigate the association between left ventricular dimension and mortality risk within a large, nationwide cohort with HF. Design, Setting, and Participants:This was a nationwide cohort study using data from the Chinese Cardiovascular Association Database-Heart Failure Center Registry. Patients were enrolled from January 1, 2018, to May 31, 2022. The multicenter study involved 723 centers across 31 provincial-level administrative regions in mainland China. The study included patients hospitalized with HF. Patients were categorized into groups with a small, normal, or large left ventricle (LV) according to American Society of Echocardiography criteria for LV end-diastolic diameter (LVEDD). Data analysis was conducted from March to June 2025. Exposure:LVEDD measured by echocardiography. Main Outcomes and Measures:The primary and secondary end points were all-cause mortality and cardiovascular mortality, respectively. Results:A total of 273 921 patients (median [IQR] age, 71.0 [62.0-79.0] years; 161 589 male [59.0%]) hospitalized with HF were included in this study. A significant U-shaped association was found between LVEDD and both all-cause and cardiovascular mortality (P for nonlinearity <.001). Both a small LV (adjusted HR [aHR], 1.32; 95% CI, 1.28-1.37; P < .001) and a large LV (aHR, 1.38; 95% CI, 1.35-1.40; P < .001) were independently associated with elevated all-cause mortality. Sex-specific optimal LVEDD thresholds were identified (47 mm for male patients, 43 mm for female patients), with each 1-mm deviation associated with a significant increase in mortality risk. These findings were consistent across prespecified subgroups and were further corroborated by analysis of LVEDD indexed to body surface area and by extensive sensitivity analyses, including competing risk models and complete-case analyses. Conclusions and Relevance:This large-scale study established that a U-shaped association exists between LVEDD and mortality in HF, suggesting that both abnormally small and abnormally large ventricles signify high risk, likely through distinct mechanisms. These findings support the integration of LV size assessment into routine risk stratification to guide personalized management.
