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Abstract Lymphocytic myocarditis (LM) is primarily triggered by various factors including viral infections and subsequent immune responses. While rare, some patients with LM experience recurrence with a life‐threatening fulminant form. Although combining steroids and immunosuppressants, such as azathioprine and mycophenolate mofetil, has demonstrated favourable outcomes in patients with LM, their efficacy is limited to the chronic phase. Indeed, various immunosuppressants have been used for LM with fulminant manifestation; however, their evidence remains lacking. In our case series, two patients with LM experienced fulminant relapses during steroid tapering, and another presented persistent cardiac enzymes elevation despite steroid therapies. Consequently, we initiated calcineurin inhibitors alongside steroids, resulting in well‐controlled clinical courses without further recurrence of LM and significant adverse effects. Our cases suggest calcineurin inhibitors as therapeutic options for managing steroid‐resistant LM with fulminant relapse.

Abstract Background The risk of subsequent cardiovascular disease (CVD) is high in cancer survivors. Although metabolic syndrome is an established risk factor for CVD, its association with cancer survivors has not yet been established. This study aimed to clarify whether metabolic syndrome is associated with subsequent CVD risk in patients with cancer using a nationwide epidemiological dataset. Methods We retrospectively analysed 53 510 patients with a history of breast, colorectal, or stomach cancer, which is reportedly a major site for developing cancer in Japan. Study participants were categorized into two groups based on the presence of metabolic syndrome, defined using the Japanese criteria (high waist circumference and ≥2 metabolic parameters including elevated blood pressure, elevated triglycerides, reduced high‐density lipoprotein cholesterol, or elevated fasting plasma glucose). The clinical outcomes were collected between 2005 and 2021. The primary endpoint was defined as the composite CVD outcome, including myocardial infarction, angina pectoris, stroke, and heart failure. Results The median patient age was 54 years, and 37.5% of the patients were men. Metabolic syndrome was observed in 5558 (10.4%) patients. Over a mean follow‐up period of 973 ± 791 days, 3085 composite CVD outcomes were recorded. Multivariable Cox regression analyses showed that metabolic syndrome was associated with a greater risk of developing CVD events (HR = 1.29, 95% CI = 1.15–1.45). Metabolic syndrome was also associated with an increased risk of CVD in patients with a follow‐up period ≥1 year (HR = 1.33, 95% CI = 1.15–1.53). This relationship was also observed when metabolic syndrome was defined according to the International Diabetes Federation criteria (HR = 1.34, 95% CI = 1.21–1.49) and the National Cholesterol Education Program Adult Treatment Panel III criteria (HR = 1.32, 95% CI = 1.19–1.46). Subgroup analyses showed that the relationship between metabolic syndrome and incident CVD was more pronounced in the non‐obese participants than in the obese participants. Conclusions Metabolic syndrome is associated with a greater risk of developing CVD, even among cancer survivors.

Key Clinical Message Genetic variants associated with hereditary TAAD may contribute to nonsyndromic TAAD. We present the case of a 72‐year‐old man with nonsyndromic TAAD undergoing prophylactic surgery after a gene panel test revealed a pathogenic variant in TGFBR1, but the indication for genetic testing in such elderly‐onset cases still warrants further discussion. Abstract Hereditary thoracic aortic aneurysm and dissection (TAAD) is a serious clinical condition resulting in a fatal outcome. Recently, variants in causative genes for syndromic hereditary TAAD, such as Marfan syndrome and Loeys–Dietz syndrome (LDS), have been reported to predispose to the development of nonsyndromic TAAD; however, genetic testing for patients with elderly‐onset nonsyndromic TAAD warrants further discussion. We present a 72‐year‐old nonsyndromic Japanese man with moderate‐sized aortic annulus ectasia (AAE) with moderate aortic regurgitation and ascending to distal arch aortic dilatation (maximum diameter: 46 mm). He had been treated for hypertension and dyslipidemia for 7 years, and his eldest son had AAE at 33 years old and type A aortic dissection at 43 years old. Surgical repair was considered a treatment option because the patient potentially had a nonsyndromic hereditary aortic disease, and genetic panel testing for TAAD identified a pathogenic missense variant in TGFBR1 (c.934G > A, p.[Gly312Ser]), previously reported in patients with LDS type 1. He was diagnosed with nonsyndromic TGFBR1‐related aortopathy and underwent prophylactic surgery using a modified Bentall operation and total arch replacement with open stent graft implantation. Genetic testing was useful in guiding the treatment strategy, but further analysis is warranted to establish the clinical value in the treatment plan for patients with elderly‐onset nonsyndromic TAAD.

Background There are few data on sex differences in the association between schizophrenia and the development of cardiovascular disease (CVD). We sought to clarify the relationship of schizophrenia with the risk of developing CVDs and to explore the potential modification effect of sex differences. Methods and Results We conducted a retrospective analysis using the JMDC Claims Database between 2005 and 2022. The study population included 4 124 508 individuals aged 18 to 75 years without a history of CVD or renal replacement therapy. The primary end point is defined as a composite end point that includes myocardial infarction, angina pectoris, stroke, heart failure, atrial fibrillation, and pulmonary thromboembolism. During a mean follow‐up of 1288±1001 days, we observed 182 158 composite end points. We found a significant relationship of schizophrenia with a greater risk of developing composite CVD events in both men and women, with a stronger association observed in women. The hazard ratio for the composite end point was 1.63 (95% CI, 1.52–1.74) in women and 1.42 (95% CI, 1.33–1.52) in men after multivariable adjustment (P for interaction=0.0049). This sex‐specific difference in the association between schizophrenia and incident CVD was consistent for angina pectoris, heart failure, and atrial fibrillation. Conclusions Our analysis using a large‐scale epidemiologic cohort demonstrated that the association between schizophrenia and subsequent CVD events was more pronounced in women than in men, suggesting the clinical importance of addressing schizophrenia and tailoring the CVD prevention strategy based on sex‐specific factors.

Nonsyndromic hereditary thoracic aortic aneurysm and dissection (TAAD) is an autosomal dominant disease; however, it is frequently difficult to identify the causative genes. We report in this study a 33-year-old Japanese male with TAAD (Stanford type A) that is complicated with severe aortic regurgitation. There was no family history of aortic diseases in the patient nor any specific clinical features suggestive of connective tissue diseases, such as Marfan syndrome. Genetic testing identified candidate causative variants in two different genes: MYLK (c.4819G > A, p.[Gly1607Ser]) and FBN1 (c.365G > A, p.[Arg122His]). Familial cosegregation analysis revealed that the novel de novo MYLK variant was present only in the proband, and the FBN1 variant was also found in his nonaffected mother, and thus the MYLK variant was classified as likely pathogenic. MYLK is a causative gene for nonsyndromic TAAD that requires careful management; however, the number of reports is limited. Accumulating data on the pathogenicity of rare variants by performing a comprehensive pedigree analysis would help establish better treatment strategies for life-threatening hereditary TAAD cases.

The generalization of deep neural network algorithms to a broader population is an important challenge in the medical field. We aimed to apply self-supervised learning using masked autoencoders (MAEs) to improve the performance of the 12-lead electrocardiography (ECG) analysis model using limited ECG data. We pretrained Vision Transformer (ViT) models by reconstructing the masked ECG data with MAE. We fine-tuned this MAE-based ECG pretrained model on ECG-echocardiography data from The University of Tokyo Hospital (UTokyo) for the detection of left ventricular systolic dysfunction (LVSD), and then evaluated it using multi-center external validation data from seven institutions, employing the area under the receiver operating characteristic curve (AUROC) for assessment. We included 38,245 ECG-echocardiography pairs from UTokyo and 229,439 pairs from all institutions. The performances of MAE-based ECG models pretrained using ECG data from UTokyo were significantly higher than that of other Deep Neural Network models across all external validation cohorts (AUROC, 0.913-0.962 for LVSD, p < 0.001). Moreover, we also found improvements for the MAE-based ECG analysis model depending on the model capacity and the amount of training data. Additionally, the MAE-based ECG analysis model maintained high performance even on the ECG benchmark dataset (PTB-XL). Our proposed method developed high performance MAE-based ECG analysis models using limited ECG data.