Background and Aims: Immune checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this ‘cardiomyotoxicity’ are lacking. The main aim of this study was to determine predictors and construct a risk score associated with negative outcomes in patients admitted for ICI myocarditis. Methods: A multicentre registry collected data retrospectively from 17 countries between 2014 and 2023. A multivariable Cox regression model was used to determine risk factors for the primary composite outcome: time to severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardiomuscular symptoms, diagnostics, and treatments. Time-dependent covariates were used, and missing data were imputed. A point-based prognostic risk score was derived and externally validated. Results: In 748 patients (67% male, age 23–94 years), 30-day incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17%, respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7–7.7), presence of cardiomuscular symptoms (HR 2.6 [1.5–4.2]), low QRS voltage on presenting electrocardiogram (HR for ≤0.5 mV vs >1 mV 1.9 [1.1–3.1]), left ventricular ejection fraction (LVEF) < 50% (HR 1.7 [1.1–2.6]), and incremental troponin elevation (HR 1.8 [1.4–2.4], 2.9 [1.8–4.7], and 4.6 [2.3–9.3], for 20, 200, and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-day primary outcome incidence increased gradually from 4% (risk score = 0) to 81% (risk score ≥ 4). This risk score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low-risk patients who were managed with no immunosuppression resulting in no cardiomyotoxic events. Conclusions: ICI-associated myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low QRS voltage, depressed LVEF, and cardiomuscular symptoms. A risk score incorporating these features performed well. Clinical trial registration: NCT04294771 and NCT05454527.

Aims: It is unclear whether the future risk of cardiovascular events in breast cancer (Bc) survivors is greater than in the general population. This meta-analysis quantifies the risk of cardiovascular disease development in Bc patients, compared to the risk in a general matched cancer-free population, and reports the incidence of cardiovascular events in patients with Bc. Methods and results: We searched PubMed, Scopus, and Web of Science databases (up to 23 March 2022) for observational studies and post hoc analyses of randomized controlled trials. Cardiovascular death, heart failure (HF), atrial fibrillation (AF), coronary artery disease (CAD), myocardial infarction (MI), and stroke were the individual endpoints for our meta-analysis. We pooled incidence rates (IRs) and risk in hazard ratios (HRs), using random-effects meta-analyses. Heterogeneity was reported through the I2 statistic, and publication bias was examined using funnel plots and Egger’s test in the meta-analysis of risk. One hundred and forty-two studies were identified in total, 26 (836 301 patients) relevant to the relative risk and 116 (2 111 882 patients) relevant to IRs. Compared to matched cancer-free controls, Bc patients had higher risk for cardiovascular death within 5 years of cancer diagnosis [HR = 1.09; 95% confidence interval (CI): 1.07, 1.11], HF within 10 years (HR = 1.21; 95% CI: 1.1, 1.33), and AF within 3 years (HR = 1.13; 95% CI: 1.05, 1.21). The pooled IR for cardiovascular death was 1.73 (95% CI 1.18, 2.53), 4.44 (95% CI 3.33, 5.92) for HF, 4.29 (95% CI 3.09, 5.94) for CAD, 1.98 (95% CI 1.24, 3.16) for MI, 4.33 (95% CI 2.97, 6.30) for stroke of any type, and 2.64 (95% CI 2.97, 6.30) for ischaemic stroke. Conclusion: Breast cancer exposure was associated with the increased risk for cardiovascular death, HF, and AF. The pooled incidence for cardiovascular endpoints varied depending on population characteristics and endpoint studied. Registration: CRD42022298741.

Thrombotic event (TE) risk is high in transthyretin amyloid cardiomyopathy (ATTR-CM). The authors sought to explore left atrial (LA) remodeling in ATTR-CM and its association with TE risk in comparison to other phenotypes of left ventricular hypertrophy (LVH). Subjects who underwent speckle tracking echocardiography, Tc-99m pyrophosphate scintigraphy, serum and urine immune electrophoresis, per registry protocol, were retrospectively identified (n = 405). Cardiac magnetic resonance and endomyocardial biopsy were used per clinical indication. Subjects with cardiac amyloidosis other than ATTR-CM were excluded, those with nonamyloid LVH served as controls. Propensity score matching was performed for age, sex, coronary artery disease, and diabetes. Longitudinal follow-up was performed over 5 years for TEs. In all ATTR-CM (n =149) and LVH (n =165) in a propensity matched cohort (104:104), ATTR-CM subjects had decreased left atrial reservoir strain (LASr), smaller left atrial volume index, more intense late gadolinium hyperenhancement, and increased LA stiffness as compared to LVH. In ATTR-CM, LASr correlated poorly with E/e', was severely depressed regardless of the diastolic dysfunction grade (in those with sinus rhythm), and did not correlate with left atrial volume index, in contrast to the LVH group. LASr and LA stiffness were associated with ATTR-CM independently of diastolic dysfunction and atrial fibrillation (AF) (OR: 1.2 and OR: 1.9, respectively; P < 0.001 and P = 0.002). Furthermore, LASr and LA stiffness were independently associated with TEs (n = 20) during follow-up, regardless of CHA₂DS₂-VASc or prevalent AF at baseline, in ATTR-CM. Primary LA cardiopathy seems to be associated with TEs in ATTR-CM, independently of AF, CHA₂DS₂-VASc, and LA dilatation, unlike other LVH phenotypes.

Background: Cardiovascular dysfunction and hypertension can persist postpartum following hypertensive disorders of pregnancy (HDPs). This study hypothesized that activin A, proinflammatory markers and concentric remodeling by echo would be higher 1‐2 years postpartum following HDP with persistent hypertension compared to HDP with normalized blood pressure (BP). We further hypothesized correlations between biomarkers with BP and echocardiographic indices. Methods and Results: This study enrolled participants with HDPs but no prepregnancy hypertension followed 1 to 2 years after delivery. Activin A and inflammatory cytokines, BP, and echocardiograms were obtained. Biomarker concentrations and echocardiographic parameters were compared between HDP with and without persistent hypertension. Individuals with persistent hypertension at a mean of 1.6 years postpartum had significantly higher activin A concentrations (median[interquartile range 25–75] 230.6 [196.0–260.9] versus 175.3 pg/mL [164.3–188.4]; P 0.42, 48% versus 7%; P <0.01), and worse peak left atrial strain (33.4% versus 39.3%; P <0.05) as compared with those whose BP normalized. Higher activin A and interleukin‐6 concentrations correlated with higher systolic (activin A: r =0.43, P =0.01) and diastolic BP (activin A: r =0.58, P <0.01; interleukin‐6: r =0.36; P <0.05), as well as greater left ventricular thickness (activin A and interventricular septal thickness: r =0.41, interleukin‐6 and interventricular septal thickness: r =0.36; both P <0.05). Conclusions: Individuals with HDPs and persistent hypertension had significantly higher activin A and greater concentric remodeling compared with those with HDPs and normalized BP at 1 to 2 years postpartum. Activin A was positively correlated with both BP and echocardiographic indices (left ventricular thickness), suggesting overlapping processes between persistent hypertension and cardiac remodeling.

Background: Many different devices are currently used for percutaneous patent foramen ovale (PFO) closure (pPFOc), aiming to achieve complete occlusion to prevent recurrent embolism. We aimed to reveal the association between residual right-to-left shunt (RLS) after pPFOc and baseline structural features of the PFO determined using transoesophageal echocardiography (TEE) before the procedure. Methods: This is a single-center cross-sectional study. A total of 123 patients who underwent pPFOc for cryptogenic stroke (CS) were screened, consecutively. Patients were compared based on the presence of residual RLS. The association of structural features of the PFO with residual RLS was evaluated using logistic regression analysis. Results: The procedure was successfully completed in a total of 103 patients included in the study after exclusion and 21% had significant residual RLS. During a median follow-up of 18 months, one patient died at 25 months due to malignancy, recurrent CS were observed in 5 (5%) patients, and atrial fibrillation was detected in 3 (3%) patients. No significant difference was observed in the baseline clinical characteristics and laboratory parameters among the patients. In addition to atrial septal aneurysm (ASA), aortic rim, tunnel width and length; inferior vena cava (IVC)-PFO tunnel angle was associated with residual RLS with a cut-off 11.3 (AUC: 0.786, 64% sensitivity, 87% specificity, p < 0.001). In individuals with residual RLS, longer and wider tunnel size, rudimentary aortic rim, acute IVC-PFO tunnel angle, and decreased tunnel length-left disc ratio were observed. Conclusions: IVC-PFO tunnel angle is a novel parameter and provides benefit to detect significant RLS in pPFOc patients.