Background: Treatment for breast cancer (BC) frequently involves radiotherapy. Guidelines recommend screening for cardiac adverse events starting 10 years after radiotherapy. The rationale for this interval is unclear. Methods and Results: We aimed to study cardiovascular event rates in the first decade following curative radiotherapy for BC. We compared mortality and cardiovascular event rates with an age‐ and risk factor‐matched control population. We included 1095 patients with BC (mean age 56±12 years). Two hundred and eighteen (19.9%) women died. Cancer and cardiovascular mortality caused 107 (49.1%) and 22 (10.1%) deaths, respectively. A total of 904 cases were matched to female FLEMENGHO (Flemish Study on Environment, Genes and Health Outcomes) participants. Coronary artery disease incidence was similar (risk ratio [RR], 0.75 [95% CI, 0.48–1.18]), yet heart failure (RR, 1.97 [95% CI, 1.19–3.25]) and atrial fibrillation/flutter (RR, 1.82 [95% CI, 1.07–3.08]) occurred more often in patients with BC. Age (hazard ratio [HR], 1.033 [95% CI, 1.006–1.061], P =0.016), tumor grade (HR, 1.739 [95% CI, 1.166–2.591], P =0.007), and neoadjuvant treatment setting (HR, 2.782 [95% CI, 1.304–5.936], P =0.008) were risk factors for mortality. Risk factors for major adverse cardiac events were age (HR, 1.053 [95% CI, 1.013–1.093]; P =0.008), mean heart dose (HR, 1.093 [95% CI, 1.025–1.167]; P =0.007), history of cardiovascular disease (HR, 2.386 [95% CI, 1.096–6.197]; P =0.029) and Mayo Clinic Cardiotoxicity Risk Score (HR, 2.664 [95% CI, 1.625–4.367]; P <0.001). Conclusions: Ten‐year mortality following curative treatment for unilateral BC was mainly cancer related, but heart failure and atrial fibrillation/flutter were already common in the first decade following irradiation. Mean heart dose, pre‐existing cardiovascular diseases, and Mayo Clinic Cardiotoxicity Risk Score were risk factors for cardiac adverse events. These results suggest a need for early dedicated cardio‐oncological follow‐up after radiotherapy.

BACKGROUND: A formal prognostic staging system in wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM), based on echocardiographic imaging, is lacking. We evaluated the prognostic performance of global longitudinal strain (GLS) staging in a large cohort of patients with ATTRwt-CM, including under tafamidis treatment and relative to National Amyloidosis Center (NAC) biomarker staging. METHODS: A multicentric, international ATTRwt-CM patient cohort with baseline GLS (distribution quartiles), evaluated by echocardiography, was studied, related to all-cause mortality. RESULTS: The study comprised 816 patients with ATTRwt-CM, median age of 81.5 years, 83% males, and 72% tafamidis initiated. During a 2.2-year median follow-up, 29.7% of patients died. GLS worsened with increasing NAC disease stage (I: −14.3%, II: −11.6%, III: −11.4%; P <0.001). Median survival per baseline GLS quartile stage 1 (<−15.8%), 2 (−15.8 to −12.9%), 3 (−12.8 to −10.0%), and 4 (GLS >−10.0%) was not met, 6.7, 4.6, and 3.4 years, respectively ( P <0.001). The median GLS −12.8% cutoff predicted 1-year mortality with 74% sensitivity, 52% specificity (area under the curve, 0.73 [95% CI, 0.66–0.80]; P <0.001). GLS was the only independent echocardiographic and strong mortality predictor, independent of other predictors, including age, New York Heart Association class symptoms, NAC stage, and tafamidis treatment (hazard ratio, 1.08 [95% CI, 1.04–1.12]; P <0.001), also when restricted to 591 tafamidis-treated subjects (hazard ratio, 1.15 [95% CI, 1.08–1.22]; P <0.001). Baseline GLS −12.8% cutoff value provided further prognostic discriminative ability for mortality within each NAC disease stage stratum (all P <0.050). Likelihood ratio test indicated incremental prognostic value of GLS (staging) over baseline NAC staging ( P <0.001). CONCLUSIONS: GLS is a strong, independent mortality predictor in ATTRwt-CM, irrespective of tafamidis treatment, that may be an adjunct or complementary to biomarker staging.

Background: Mitral valve prolapse (MVP) and mitral annular disjunction (MAD) are common valvular abnormalities that have been associated with ventricular arrhythmias (VA). Cardiac magnetic resonance imaging (CMR) has a key role in risk stratification of VA, including assessment of late gadolinium enhancement (LGE). Methods: Single-center retrospective analysis of patients with MVP or MAD who had >1 CMR and >1 24 h Holter registration available. Data are presented in detail, including evolution of VA and presence of LGE over time. Results: A total of twelve patients had repeated CMR and Holter registrations available, of which in four (33%) patients, it was conducted before and after minimal invasive mitral valve repair (MVR). After a median of 4.7 years, four out of eight (50%) patients without surgical intervention had new areas of LGE. New LGE was observed in the papillary muscles and the mid to basal inferolateral wall. In four patients, presenting with syncope or high-risk non-sustained ventricular tachycardia (VT), programmed ventricular stimulation was performed and in two (50%), sustained monomorphic VT was easily inducible. In two patients who underwent MVR, new LGE was observed in the basal inferolateral wall of which one presented with an increased burden of VA. Conclusions: In patients with MVP and MAD, repeat CMR may show new LGE in a small subset of patients, even shortly after MVR. A subgroup of patients who presented with an increase in VA burden showed new LGE upon repeat CMR. VA in patients with MVP and MAD are part of a heterogeneous spectrum that requires further investigation to establish risk stratification strategies.

BACKGROUND: Managing clinically significant primary mitral regurgitation is challenging. Right ventricular–pulmonary arterial coupling, assessed with tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP) ratio, reflects right ventricular adaptability to afterload. This international multicenter cohort study aimed to evaluate the prognostic value of rest TAPSE/sPAP and exercise TAPSE (exTAPSE)/sPAP in primary mitral regurgitation. METHODS: Between January of 2019 and December of 2023, 211 patients assigned to a derivation cohort (64±12 years of age, 40% women) and 146 patients assigned to a validation cohort (66±13 years of age, 39% women), all of whom had moderate or severe primary mitral regurgitation, no or discordant symptoms, and no left ventricular systolic dysfunction or atrial fibrillation, underwent semisupine cycle–ergometry cardiopulmonary exercise testing combined with exercise echocardiography. TAPSE/sPAP was measured at rest and at intermediate (defined as the first ventilatory threshold) and peak exercise. The primary end point was a composite of cardiovascular death, unplanned cardiovascular hospitalizations, and new atrial fibrillation. RESULTS: In the derivation cohort, 48 patients reached the composite outcome (median follow-up, 24 months [interquartile range, 12–51]). Intermediate and peak exTAPSE/sPAP were strongly correlated ( r =0.84; P <0.001), with intermediate exTAPSE/sPAP offering superior feasibility (98% versus 92%) with comparable prognostic accuracy to peak exTAPSE/sPAP (area under the receiver operating characteristic curve, 0.794 [0.730–0.849] versus 0.765 [0.698–0.823]) and therefore was used as the exercise TAPSE/sPAP measure. Patients with a reduced rest TAPSE/sPAP (cutoff 0.8 mm/mm Hg) and intermediate exTAPSE/sPAP (cutoff 0.6 mm/mm Hg) had a lower event-free survival (log-rank P <0.0001). Intermediate exTAPSE/sPAP and percent-predicted peak VO ₂ were independently associated with the primary end point (hazard ratio, 0.64 [0.51–0.80] per 0.1 mm/mm Hg increase [ P <0.001] and hazard ratio, 2.03 [1.05–3.93] if <80% [ P =0.04], respectively) and had incremental prognostic value beyond age, left atrial volume index, mitral regurgitation severity, rest TAPSE/sPAP, and mitral valve intervention (time-dependent covariable). Similar results were found when rest and intermediate exTAPSE/sPAP were included in the multivariable model as categorical measures. Validation in an independent cohort confirmed the consistent and robust performance of both multivariable models, irrespective of whether TAPSE/sPAP was modeled as a continuous or categorical variable. CONCLUSIONS: Exercise right ventricular–pulmonary arterial coupling, particularly intermediate exTAPSE/sPAP, is a robust and feasible measure independently associated with adverse outcomes, and provides prognostic information beyond resting variables and cardiorespiratory fitness, potentially refining risk stratification and guiding management in patients with primary mitral regurgitation.