BACKGROUND:Patients with hypertrophic cardiomyopathy (HCM) who progress to left ventricular systolic dysfunction (LVSD) are at an increased risk of lethal arrhythmias and end-stage heart failure. Early identification of this high-risk subpopulation is crucial; however, current risk stratification remains insufficient. OBJECTIVES:The objective of the study was to investigate the association of myocardial strain parameters with progression to LVSD in genotyped HCM patients. METHODS:Sarcomere positive was defined as harboring pathogenic or likely pathogenic variants in sarcomere-encoding genes. Speckle-tracking echocardiography was used to measure left ventricular global longitudinal strain (LVGLS) and left atrial reservoir strain (LARS). The primary endpoint was progression to LVSD (ejection fraction <50%) and the secondary endpoint was a composite of progression to LVSD, heart-failure hospitalization, and all-cause death. RESULTS:A total of 101 patients (23.8% sarcomere positive) were included and followed up for 5.0 (IQR: 2.4-8.7) years. No significant association was observed between genotype and strain parameters. Sarcomere positive (subdistribution HR [sHR]: 5.07; 95% CI: 1.25 to 20.6; P = 0.023) and lower LARS (sHR: 1.10 per 1% decrease; 95% CI: 1.02-1.18; P = 0.015), but not LVGLS, were significantly associated with the primary endpoint. Sarcomere-positive patients with reduced LARS faced markedly elevated incidence for the primary endpoint (sHR: 8.31; 95% CI: 2.25-30.7; P = 0.001). Consistent findings were observed in terms of the secondary endpoint (HR: 4.76; 95% CI: 1.59-14.2; P = 0.005). CONCLUSIONS:LARS was associated with progression to LVSD in HCM, potentially reflecting the preclinical stage of LVSD, whereas LVGLS was not. In this exploratory study, integrating left atrial strain analysis with genotyping may have potential value in risk stratification, with implication for early detection of vulnerable individuals.

Pulmonary hypertension due to left heart disease (PH-LHD) in heart transplantation (HTx) candidates is associated with increased post-transplant mortality. Although guidelines recommend acute vasodilator challenge (AVC) with nitroprusside or milrinone, the safety and utility of inhaled nitric oxide (iNO) for AVC in this setting remain unclear.We retrospectively reviewed 18 patients with PH-LHD referred for HTx who underwent AVC with iNO. While arterial oxygen saturation decreased after AVC (95.4 ± 2.6 to 94.1 ± 2.7%, P = 0.013), there were no significant changes in mean aortic pressure (74.5 ± 9.8 versus 74.0 ± 8.0 mmHg, P = 0.680), and no respiratory or circulatory adverse events occurred. Both mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) significantly decreased (mPAP: 36.1 ± 8.0 to 33.2 ± 7.5 mmHg, P = 0.007; PVR: 5.2 ± 2.9 to 2.9 ± 1.3 Wood Units [WU], P < 0.001). Nine patients subsequently underwent left ventricular assist device (LVAD) implantation. At 1 month after implantation, PVR decreased from pre-AVC levels (4.0 ± 1.6 to 2.9 ± 1.3 WU, P = 0.049). The percent change in PVR from pre-AVC to post-LVAD correlated with the percent change from pre-AVC to post-AVC (r = 0.76, P = 0.029).Our preliminary findings suggest that AVC with iNO may be a useful method for evaluating the reversibility of elevated PVR and could indicate the hemodynamic response to LVAD implantation in patients with PH-LHD.

Aims Circulating microRNAs (miRNAs) are informative markers of heart failure (HF); however, sex differences in HF-associated miRNA changes remain unclear. We performed sex-stratified analyses to assess whether HF-associated circulating miRNA changes differ by sex in HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).Methods and results In this prospective multicentre cohort study in Japan, we analysed 235 participants, including 82 controls (41 males and 41 females), 76 patients with HFpEF (39 males and 37 females), and 77 patients with HFrEF (54 males and 23 females). Unbiased whole-blood miRNA sequencing detected 1767 unique miRNAs, of which 229 were retained for the primary analysis after abundance filtering. Age- and body mass index (BMI)-adjusted differential-expression analyses identified 50 miRNAs in males with HFpEF and 59 miRNAs in males with HFrEF, whereas no miRNAs reached statistical significance in females with either HF phenotype. Importantly, HF-associated log2 fold changes in males and females were positively correlated for both HF phenotypes, although the absolute magnitudes of change were greater in males than in females, indicating partly shared directions of change between sexes. Age- and BMI-adjusted permutational multivariate analysis of variance revealed more pronounced phenotype-associated differences in global miRNA profiles in males than in females; these findings were consistent across alternative abundance filters.Conclusion Sex-stratified analyses of circulating miRNAs in HFpEF and HFrEF showed that HF-associated expression changes were consistently more pronounced in males than in females. These findings highlight the importance of sex stratification when interpreting circulating miRNA alterations in HF.Trial registration number UMIN000052673 (UMIN Clinical Trials Registry; observational study)

Background In patients with hypertrophic cardiomyopathy (HCM), genetic testing is crucial for cascade screening and risk stratification. However, it remains limited by financial and logistical constraints, necessitating prioritization. The Mayo HCM Genotype Predictor Score, based on clinical and echocardiographic variables, estimates genotype positivity with acceptable performance. Although sarcomeric variants are also associated with electrophysiological abnormalities, ECG parameters were not incorporated into this model. This study aimed to enhance genotype prediction in HCM by integrating ECG parameters. Methods We retrospectively analyzed 466 patients with HCM from a Japanese multicenter cohort. Genotype positivity was defined as harboring pathogenic/likely pathogenic variants in sarcomere‐encoding genes. Candidate ECG variables were selected via multivariable logistic regression with bootstrap aggregation. A point‐based novel score was developed and internally validated using cross‐validation. Model performance was assessed by the area under the receiver operating characteristic curve and Akaike’s information criterion. Results Genotype‐positive patients (30.3%) more frequently exhibited atrial fibrillation, intraventricular conduction disturbance, lower prevalence of high voltage, and abnormal T‐wave inversion in precordial leads than genotype‐negative patients and thus were incorporated into the novel Mayo‐ECG score. This score stratified genotype positivity from 7.1% (score ≤−1) to 91.4% (score ≥4), and its discriminative performance (area under the receiver operating characteristic curve, 0.81 [95% CI, 0.77–0.85]) outperformed the Mayo score (area under the receiver operating characteristic curve, 0.76 [95% CI, 0.71–0.81]; P =0.005) with better overall model fit (Akaike’s information criterion: 439 versus 479). Internal validation yielded consistent results with good calibration. Conclusions The Mayo‐ECG improves genotype prediction, outperforming the conventional model. Given its simplicity, this model has the potential to prioritize genetic testing in HCM.

Atrial fibrillation management is challenging, and traditional cardiac rehabilitation often overlooks respiratory issues. We aimed to evaluate the safety and efficacy of cardiac rehabilitation with inspiratory muscle training to enhance respiratory and cardiac functions after atrial fibrillation catheter ablation. This prospective, single-center observational study, conducted at the University of Tokyo Hospital between February 2019 and January 2020, included 5 men (average age 68.4 ± 2.58 years) who underwent initial ablation for symptomatic paroxysmal (n = 1) or non-paroxysmal (n = 4) atrial fibrillation. The participants underwent inspiratory muscle training alongside standard cardiac rehabilitation (intensity: 20% of the maximal inspiratory pressure, adjusted weekly). The pre- and post-intervention ejection fraction, left atrial volume index, and brain natriuretic peptide levels were evaluated. Inspiratory muscle training integration was associated with improvements in respiratory muscle strength and pulmonary function. The average ejection fraction improved from 62.0% to 64.4%, the left atrial volume index decreased from 39.4 mL/m2 to 27.0 mL/m2, and brain natriuretic peptide levels reduced from 112.28 pg/mL to 20.98 pg/mL. The anaerobic threshold increased from a mean of 12.3 to 14.2, and the mean peak oxygen uptake increased from 16.72 mL/kg/min to 18.12 mL/kg/min. Over a 4-year follow-up, atrial fibrillation recurrence was observed in only 1 of the 5 patients. Inspiratory muscle training, when integrated with cardiac rehabilitation, could potentially improve respiratory and cardiac function in patients with post-atrial fibrillation ablation and may help reduce the likelihood of atrial fibrillation recurrence. This pilot study supports the potential of inspiratory muscle training in enhancing standard rehabilitation protocols, warranting further investigation in larger randomized trials to substantiate these findings and explore long-term benefits.

Takayasu arteritis (TAK) is a chronic, refractory large-vessel vasculitis designated as a Designated Intractable Disease in Japan. The Japanese diagnostic criteria for TAK, last revised in 2017, have been updated to the 2026 version as part of the Japanese Circulation Society 2026 guidelines on the management of large vessel vasculitis, and are presented here in English for the first time. The revision was conducted through a 3-round modified Delphi process involving a panel of 21 experts, supplemented by email discussion and an in-person meeting. The updated criteria incorporate 3 major changes: new symptoms were added and a qualifying statement introduced in Section A; pulmonary artery involvement was elevated to a main criterion in Section B; and IgG4-related periaortitis, Cogan syndrome, and drug-induced aortitis were added in Section C. These updates reflect advances in imaging technology and international classification frameworks, with an emphasis on improving diagnostic sensitivity to reduce missed diagnoses.

Abstract Cardiac rehabilitation (CR) improves exercise capacity, but frequent cardiopulmonary exercise testing (CPET) is impractical. The AESCULON mini enables non‐invasive hemodynamic monitoring, though its role in CR remains unclear. Eleven patients (6 myocardial infarction, 3 angina pectoris, 2 dilated cardiomyopathy) undergoing outpatient CR at the University of Tokyo Hospital were studied. Hemodynamics were measured using the AESCULON mini before and after 20 min of aerobic exercise at the anaerobic threshold. CPET and brain natriuretic peptide (BNP) were assessed within 2 weeks. Stroke volume, cardiac output, and cardiac index tended to increase, and thoracic fluid content (TFC) decreased post‐exercise. TFC before (r = 0.767, p = 0.006) and after (r = 0.711, p = 0.014) correlated with BNP. Changes in stroke volume and cardiac output correlated with peak VO2, percent predicted peak VO2, and ΔVO2/ΔWR. Patients with increased cardiac output during exercise had higher peak VO2 and ΔVO2/ΔWR. Non‐invasive hemodynamic data from the AESCULON mini correlated with BNP and exercise capacity, suggesting its usefulness for detecting heart failure progression and estimating exercise capacity in CR.

Patients with heart failure present with various symptoms, and comprehensively identifying and accurately documenting them in clinical registries or structured databases requires substantial manual effort. Locally deployed large language models (LLMs), which process data entirely within institutional infrastructure, have enabled automated extraction of structured information from unstructured clinical text. However, symptom-specific extraction performance and reasoning-trace analyses of the underlying decision-making process remain largely unexplored. We utilized multiple locally deployed LLMs for symptom extraction from cardiology discharge summaries, examining how extraction performance varied across individual symptoms and characterizing the inferential processes through reasoning traces. Ten Japanese-language clinical summaries of patients with advanced heart failure evaluated for heart transplantation listing were included to assess the feasibility of locally deployed LLMs for automated symptom extraction, yielding 80 reference-standard symptom-case labels (10 cases × 8 symptoms). Gemma3-27b and Qwen3.5-9b were run locally on a single GPU to extract the presence or absence of eight symptoms required for transplant listing in Japan. Two prompting conditions were evaluated: (1) extraction of all symptoms from the full summary, and (2) an additional instruction to disregard symptoms unrelated to the index hospitalization. Phase 1 evaluated four non-reasoning conditions, and phase 2 added chain-of-thought reasoning to each condition. Results are reported descriptively, without formal statistical testing. Overall accuracy across the four no-reasoning conditions ranged from 87.5% to 91.3%, with Qwen3.5 showing greater sensitivity to prompt modification than Gemma3. In symptom-specific evaluation across all conditions, palpitations and fatigability showed the highest false-positive rates (25% and 38%, respectively). Review of the reasoning outputs showed that, in some cases, both models inferred palpitations from electrocardiographic findings or documented tachycardia, and fatigability from the underlying diagnosis of heart failure, despite the absence of explicit symptom documentation. Symptom extraction performance varies according to the linguistic and clinical characteristics of individual symptoms. Reasoning-trace analysis further showed that LLMs could infer symptom presence from objective clinical findings rather than relying solely on explicitly documented patient complaints.

Everolimus (EVR), which is widely used in heart transplant recipients, has been associated with drug-induced lung injury. Although EVR-associated lung injury has been reported in patients with malignancies and recipients of other solid organ transplants, its incidence and risk factors in heart transplant recipients remain unclear. Krebs von den Lungen-6 (KL-6) is a serum biomarker widely used in the assessment of interstitial lung diseases and may reflect pulmonary involvement, including drug-induced lung injury. This study aimed to determine the incidence and risk factors for KL-6 elevation after EVR administration in heart transplant recipients. This retrospective observational study included patients who received a heart transplant at the University of Tokyo Hospital from June 2006 to April 2021. The patients were categorized into two groups: those who received EVR after heart transplantation (EVR group) and those who did not (non-EVR group). Multivariable logistic regression analysis was performed in the EVR group to identify independent risk factors for KL-6 elevation (defined as a peak level ≥ 500 U/mL). Receiver operating characteristic (ROC) analysis was used to determine optimal cutoff values, and a composite risk score was constructed. Event-free survival was evaluated using the Kaplan–Meier method. Seventy-three patients were included (58 in the EVR group and 15 in the non-EVR group). Peak serum KL-6 levels were significantly higher in the EVR group than in the non-EVR group (320 [235–509] vs. 157 [127–263] U/mL, p = 0.002). KL-6 elevation occurred in 27.6

Aims Non-ischaemic dilated cardiomyopathy (DCM) is frequently characterized by the presence of pathogenic germline variants, and genotype positivity predicts poor prognosis. Despite its importance, genetic testing remains underutilized in the current era. Therefore, we aimed to develop a deep learning model to predict genotype positivity using echocardiographic videos.Methods and results We included patients who were diagnosed with DCM and had genetic testing at the University of Tokyo Hospital, Japan, consecutively from 2014 to 2022. The apical four-chamber views of echocardiographic videos were collected. First, we developed a deep learning model based on the EchoNet-Dynamic model, and the area under the curve (AUC) was computed. Second, we calculated the Madrid genotype score (clinical scoring system) for each case. Third, we developed a logistic regression model that combined the Madrid genotype score and the deep learning model. Finally, we compared the AUC of the combined model with that of the Madrid genotype score alone by DeLong's test. Out of the 258 patients, 117 patients (45.3%) had genetic variants, and 141 (54.7%) did not. TTN (30.8%) was the most common genotype, followed by LMNA (18.8%). The deep learning model yielded an AUC of 0.64. The Madrid genotype score was well validated and achieved an AUC of 0.73. The combined model yielded an AUC of 0.76 with a significant improvement from the Madrid genotype score alone (P = 0.03).Conclusion The deep learning model demonstrated modest discriminative ability to predict genotype positivity using echocardiographic videos. The accuracy of the clinical scoring system improved when combined with the deep learning model.

Chronic kidney disease (CKD) is a major long-term complication following heart transplantation (HT). The safety and efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) for HT recipients with CKD remains unclear. We retrospectively reviewed the records of HT recipients who were followed up between April 2017 and December 2024 at our hospital; those with CKD who initiated SGLT2i at least 6 months after HT and had available follow-up data for 6 subsequent months were included. Among 91 patients who initiated SGLT2i, 45 were eligible (median age: 50 [47-59] years; 11 (24.4%) female). The median estimated glomerular filtration rate (eGFR) at SGLT2i initiation was 42.9 [33.8-50.6] mL/minute/1.73 m2. All patients continued SGLT2i without adverse events. Relative change in eGFR improved significantly from -9.1% in the 6 months before SGLT2i to +3.7% in the 6 months after (P = 0.043). Uric acid and hemoglobin levels improved (P < 0.001 and 0.002, respectively). Patients were stratified into 2 groups based on the relative change in eGFR to identify factors associated with improvement: those with a positive change (n = 23) and those without (n = 22). In logistic regression analysis adjusting for age and sex, lower eGFR (odds ratio: 1.09, 95% confidence interval: 1.02-1.15, P = 0.013) and non-ischemic etiology of heart failure (odds ratio: 18.9, 95% confidence interval: 1.66-215.0, P = 0.018) were associated with eGFR improvement after SGLT2i initiation. SGLT2i use appears safe and helps prevent CKD progression in HT recipients with CKD.

Sarcoidosis is a systemic infiltrative disease characterized by non-caseating granuloma formation, and its cardiac phenotype is an important prognostic factor.1 Sarcoidosis affecting the heart without extracardiac involvement is termed isolated cardiac sarcoidosis (CS). Isolated CS was once thought to be a rare manifestation of sarcoidosis because of the diagnostic challenge arising from the low sensitivity of endomyocardial biopsy (EMB).2 Considering that the importance of early diagnosis and treatment are critical in managing CS,3 the Japanese Circulation Society (JCS) updated its guidelines to allow a clinical diagnosis of CS using multimodal imaging techniques, such as fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), even in the absence of histological evidence of non-caseating granulomas.4 Under the situation in which isolated CS can be clinically diagnosed without histological findings, we should pay more attention to differentiating isolated CS from other cardiomyopathies. Here, we describe a 50-year-old male who was clinically diagnosed with isolated CS and prescribed with prednisolone without much effect, and subsequent genetic analysis revealed pathogenic variants in LMNA and TNNT2, representative genes for cardiomyopathy. A 48-year-old man with hypertension and dyslipidaemia presented to a hospital with advanced atrioventricular block (AVB) pointed out during his annual health check-up. He had no family history of heart disease or sudden death, and his electrocardiogram (ECG) 2 years earlier showed a first-degree AVB and left axis deviation (Figure 1A). ECG in the first hospital presentation shows high-degree AVB and multiple morphologically distinct premature ventricular contractions (Figure 1B), and ambulatory ECG monitoring revealed advanced AVB with the longest pause being 1.57 seconds accompanied by escape rhythms. Transthoracic echocardiography (TTE) demonstrated normal cardiac chamber size and function without any regional wall motion abnormalities. He remained asymptomatic and declined further investigation or regular outpatient follow-up. At the age of 50, he complained of mild dyspnoea on exertion, categorized as New York Heart Association Class II, and was diagnosed with atrial fibrillation and complete AVB and referred to our hospital (Figure 1C). He started receiving edoxaban 60 mg/day. Blood test revealed elevated levels of B-type natriuretic peptide at 290.5 pg/mL and high-sensitivity cardiac troponin I at 30.9 pg/mL. Soluble interleukin-2 receptor and angiotensin-converting enzyme levels were within normal ranges. His chest X-ray indicated cardiomegaly. TTE showed a reduced left ventricular ejection fraction of 38% and hypokinesis of the septal and posterior walls of the left ventricle, without regional wall thinning or ventricular aneurysms (Figure 2A and Video S1). Non-contrast computed tomography did not depict any enlarged lymph nodes, pulmonary nodules or other organ abnormalities, and ophthalmologic and dermatologic examinations were unremarkable. Ambulatory ECG detected non-sustained ventricular tachycardia (NSVT). Coronary computed tomographic angiography showed intact coronary arteries. Cardiac magnetic resonance imaging demonstrated a linear pattern of late gadolinium enhancement (LGE) in the mid-wall of the septum, with a reduced ejection fraction and a dilated left ventricle (Figure 2B and Videos S2 and S3). T2-weighted imaging revealed a high signal in the mid-wall of the septum, corresponding to the region of LGE, indicative of myocardial inflammation (Figure S1). Subsequently, a whole-body FDG-PET scan after 18 h of fasting showed a focal FDG uptake in the ventricular septum, typical pattern for CS, but no uptake in other organs (Figure 2C). The multimodal imaging findings and the presence of arrhythmia such as AVB and NSVT were typical for CS, and we clinically diagnosed the patient with isolated CS without performing EMB, as the patient met criteria (a), (c), (d) and (e) in the JCS guideline4 (Table 1). Following his admission, we initiated prednisolone 30 mg (0.5 mg/kg)/day, but continuous ECG monitoring showed frequent NSVTs with multiple morphologies (Figure 2D). The heart team concluded that semi-urgent defibrillator implantation was necessary, and he received a cardiac resynchronization therapy device with defibrillator (CRT-D) while taking prednisolone 25 mg daily and was discharged 7 days after the implantation. However, 10 days after discharge, the wound was partly detached and bleeding, forcing the patient to be readmitted to the hospital. He was treated with prophylactic antibiotics and surgical site compression for 7 days and was discharged with prednisolone 15 mg/day. Despite the initiation of prednisolone therapy, his symptoms and cardiac dysfunction did not improve much, and NSVTs continued to occur. We performed whole-exome sequencing analysis to evaluate the risk of inherited cardiomyopathies and identified two missense variants in TNNT2 (chr1:201364335(hg38), NM_001001430.3, c.422G>A, p.Arg141Gln) and LMNA (chr1:156136096(hg38), NM_170707.4, c.1132A>C, p.Lys378Gln) (Figure 3). The TNNT2 variant has been previously reported as pathogenic in multiple patients with idiopathic cardiomyopathies (ClinVar accession number: VCV000043637.14). In contrast, the LMNA variant is novel and located in exon 6, a known hot-spot region. This region corresponds to part of the coil 2 domain within the central rod domain of lamin A/C and is related to multiple pathogenic missense variants.5 This variant has not been identified in the general population according to the gnomAD and Tohoku Medical Megabank databases and was predicted to be pathogenic by multiple in silico analyses with a Combined Annotation Dependent Depletion score of 26.6 and a Polymorphism Phenotyping v2 score of 0.999. According to the American College of Medical Genetics and Genomics guidelines,6 LMNA p.Lys378Gln was classified as likely pathogenic (PM1, PM2, PP2 and PP3). Therefore, we hypothesized that these variants were involved in the progressive conduction defects and worsened cardiac function. We describe a patient initially diagnosed with isolated CS using a multimodality imaging approach and treated with prednisolone. He had not improved with steroid therapy and was later found to have two likely pathogenic variants in cardiomyopathy-causing LMNA and TNNT2 genes. Although the possibility of an overlap of CS and genetic cardiomyopathy cannot be excluded, this case underscores the importance of early genetic analysis to reconsider an optimal therapeutic strategy for treatment-resistant patients. As patients with CS are at high risk of malignant arrhythmias,7 delays in diagnosis and intervention might worsen the patient's prognosis.3 Despite this, the diagnosis of isolated CS, characterized by the absence of extracardiac involvement,8 is basically challenging due to the low sensitivity of EMB, which is only up to 20%.2 This difficulty had been hindering early and appropriate management of isolated CS. To address this issue, the JCS guidelines proposed clinical diagnostic criteria for isolated CS without histological evidence,4 which enables timely diagnosis and treatment. Since then, clinical data based on the guideline-recommended diagnostic criteria have been accumulated.9 However, like the present case, there are patients fulfilling the clinical criteria for isolated CS, but the presence of pathogenic variants in cardiomyopathy-related genes might actually cause cardiac dysfunction or be a risk factor for exacerbation of the clinical condition. We clinically diagnosed this case as isolated CS without performing EMB because of concerns about possible procedural complications and the fact that a negative biopsy result would not change the management strategy. His clinical course and multimodal imaging findings, including FDG-PET, were strongly suggestive of isolated CS. However, previous studies have shown that cardiomyopathies, such as arrhythmogenic cardiomyopathy, can exhibit FDG uptake in the heart.10 Lal et al. reported that cardiomyopathy-related genetic variants can be identified in patients previously diagnosed with CS.11 Considering the steroid-unresponsiveness and the fact that cardiomyopathy caused by pathogenic LMNA variant can also produce a variety of abnormalities,12 the appropriate diagnosis for this case was dilated cardiomyopathy rather than CS. The CS diagnostic criteria in JCS guidelines4 contribute to improved sensitivity in the diagnosis; however, recent reports, including this case, have highlighted that the criteria might sacrifice diagnostic specificity. To prevent overdiagnosis of CS with improved diagnostic accuracy, genetic analysis could bridge the gap. In this case, high disease activity estimated from high FDG uptake and frequent NSVTs led to early implantation of CRT-D while taking high-dose prednisolone. Unfortunately, this patient suffered from the surgical site complication. He was at high risk of postoperative pocket haematoma due to the need for both CRT-D implantation and anticoagulant.13 Additionally, haematoma and steroid administration are significant risk factors for device infection, which could lead to serious adverse events.14 Although he recovered with conservative management, he remained exposed to a high risk of device infection. Early genetic assessment prior to the strategic decision-making might have provided a rationale for precision medicine, potentially preventing surgical complications. Furthermore, as laminopathy caused by pathogenic LMNA variants has high penetrance, genetic cascade screening can profoundly contribute to high-quality management of family members. TNNT2 encodes the cardiac isoform of troponin T, and LMNA encodes lamin A/C, which provides structural support with the nucleus. Both genes are strongly associated with genetic cardiomyopathy. Because his cardiac phenotypes such as progressive conduction disturbance and atrial fibrillation are often observed in laminopathy,12 his cardiac abnormalities might be caused by the LMNA variant. FDG uptake has also been reported in some cases of LMNA-related cardiomyopathy,11, 15 but not in those with TNNT2 variants. The mechanism of FDG uptake in laminopathy still remains elusive but is possibly explained by (1) myocardial inflammation and associated apoptosis reflecting rapid disease progression and/or (2) activated glucose metabolism in failing myocardium, which warrants further clarification. In conclusion, caution should be exercised when diagnosing isolated CS clinically without a myocardial biopsy, and genetic analysis might be useful for achieving an accurate diagnosis. We thank R. Nakanishi, I. Sakamoto, N. Matsuzaki, T. Miyoshi, Y. Kaneko, Y. Yokota, Y. Chiba, K. Akiba, A. Okamoto and M. Yoshitake for providing support with analysis. None declared. This work was supported by grants from the SENSHIN Medical Research Foundation (to S.N.), the Japan Foundation for Applied Enzymology (to S.N. and Z.D.), the Kanae Foundation for the Promotion of Medical Science (to S.N.), the MSD Life Science Foundation, Public Interest Incorporated Foundation (to S.N.), the Tokyo Biomedical Research Foundation (to S.N.), the Astellas Foundation for Research on Metabolic Disorders (to S.N.), the NOVARTIS Foundation (Japan) for the Promotion of Science (to S.N.), the Japanese Circulation Society (to S.N.), the Takeda Science Foundation (to S.N.), the Cell Science Research Foundation (to S.N.), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to S.N.) and the Daiichi Sankyo Foundation of Life Science (to S.N.); a Grant-in-Aid for Scientific Research (A) (to S.N.); a Grant-in-Aid for Scientific Research (S) (to I.K.); the UTEC-UTokyo FSI Research Grant Program (to S.N.); the JST FOREST Program (Grant JPMJFR210U) (to S.N.); a Japan Society for the Promotion of Science Grant-in-Aid for Japan Society for the Promotion of Science fellow (23KJ0434) (to Z.D.); and the Japan Agency for Medical Research and Development (AMED) (JP20ek0109487, JP18km0405209, JP19ek0109406, JP21ek0109543, JP21ek0109569, JP21tm0724601, JP22ama121016, JP22ek0210172, JP22ek0210167, JP22bm1123011, JP23tm0724607, JP23gm4010020, JP23tm0524004, JP23tm0524009, JP23jf0126003, JP24ek0109755 and JP24ek0210205) (to S.N. and I.K.). Figure S1. T2-weighted imaging of cardiac magnetic resonance imaging. The mid-wall of the septum shows high signal intensity, corresponding to the region of late gadolinium enhancement (red arrows). Video S1. Transthoracic echocardiogram. Video S2. Cardiac magnetic resonance imaging. Video S3. Late gadolinium enhancement in short-axis and long-axis four-chamber views. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

BACKGROUND:Implantable cardioverter defibrillator (ICD) lead dysfunction after left ventricular assist device (LVAD) implantation can occur, but only short-term outcomes have been reported. OBJECTIVES:We aimed to evaluate the long-term incidence, characteristics, and predictors of persistent ICD lead dysfunction after LVAD implantation. METHODS:This was a retrospective multicenter study. All patients with a transvenous ICD lead at the time of LVAD implantation between January 1, 2011, and December 31, 2023, were enrolled. The primary endpoint was lead dysfunction. Risk factors for persistent compared to temporary lead dysfunction using a logistic analysis were determined. RESULTS:A total of 170 patients (mean age: 48.0 ± 12.7 years) were analyzed. The median follow-up period was 46.2 (Q1-Q3: 32.3-61.4) months. Lead dysfunction was observed in 124 leads (72.9%), of which 60.4% (N = 75) occurred within a year after LVAD implantation. Of the 124 lead dysfunctions, 84 (67.7%) showed persistent dysfunction and 40 (32.3%) were temporary. Lead dysfunction occurring later than 2.1 months after LVAD implantation was a risk factor for persistent lead dysfunction (area under the curve: 0.673). Multivariable analysis identified lead dysfunction occurring later than 2.1 months after LVAD implantation as an independent risk factor for persistent lead dysfunction (OR: 4.67; 95% CI: 2.05-10.94; P < 0.001). CONCLUSIONS:In patients undergoing LVAD implantation, ICD lead dysfunction was observed in 72.9% after a mean follow-up of 46.2 months, of which two-thirds had persistence lead dysfunction. Later occurrence of lead dysfunction (>2 months after implant) may be a risk factor for persistent lead dysfunction.