Changes in Cardiac Function Following Fulminant Myocarditis.

BACKGROUND: The natural history of myocardial dysfunction in patients with fulminant myocarditis is poorly understood. This study aims to evaluate changes in cardiac function in patients with fulminant myocarditis using a nationwide registry in Japan. METHODS: This retrospective cohort study included patients with biopsy-proven fulminant myocarditis and available for left ventricular ejection fraction (LVEF). We described the LVEF on admission, at discharge, and 1 year after discharge. We divided patients into 2 groups based on LVEF at discharge (reduced ejection fraction of <50% or preserved ejection fraction of ≥50%) and analyzed changes in LVEF and prognosis according to groups. RESULTS: We included 214 patients (the median [first-third quartiles] age of the cohort was 48 [35-62] years, and 63 [38%] were female). Of 153 patients available for LVEF at 1 year, the median (first-third quartiles) LVEF increased from 33% (21-45%) on admission to 59% (49-64%) at discharge and further to 61% (55-66%) at 1 year. Of 153 patients, 45 (29%) and 22 (14%) had LVEF <50% at discharge and at 1 year, respectively. Comparisons between patients with LVEF <50% and those with LVEF ≥50% demonstrated that the former group had a higher adjusted probability of death or heart transplantation (hazard ratio, 8.19 [95% CI, 2.13-31.5]; P=0.002). CONCLUSIONS: Some patients with fulminant myocarditis had left ventricular dysfunction in the chronic phase. Patients with reduced left ventricular function at discharge had a worse prognosis than those with preserved left ventricular function. REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045352; Unique identifier: UMIN000039763.

Heart failure with preserved ejection fraction phenogroup classification using machine learning.

AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex syndrome with a poor prognosis. Phenotyping is required to identify subtype-dependent treatment strategies. Phenotypes of Japanese HFpEF patients are not fully elucidated, whose obesity is much less than Western patients. This study aimed to reveal model-based phenomapping using unsupervised machine learning (ML) for HFpEF in Japanese patients. METHODS AND RESULTS: We studied 365 patients with HFpEF (left ventricular ejection fraction >50%) as a derivation cohort from the Nara Registry and Analyses for Heart Failure (NARA-HF), which registered patients with hospitalization by acute decompensated HF. We used unsupervised ML with a variational Bayesian-Gaussian mixture model (VBGMM) with common clinical variables. We also performed hierarchical clustering on the derivation cohort. We adopted 230 patients in the Japanese Heart Failure Syndrome with Preserved Ejection Fraction Registry as the validation cohort for VBGMM. The primary endpoint was defined as all-cause death and HF readmission within 5 years. Supervised ML was performed on the composite cohort of derivation and validation. The optimal number of clusters was three because of the probable distribution of VBGMM and the minimum Bayesian information criterion, and we stratified HFpEF into three phenogroups. Phenogroup 1 (n = 125) was older (mean age 78.9 ± 9.1 years) and predominantly male (57.6%), with the worst kidney function (mean estimated glomerular filtration rate 28.5 ± 9.7 mL/min/1.73 m2 ) and a high incidence of atherosclerotic factor. Phenogroup 2 (n = 200) had older individuals (mean age 78.8 ± 9.7 years), the lowest body mass index (BMI; 22.78 ± 3.94), and the highest incidence of women (57.5%) and atrial fibrillation (56.5%). Phenogroup 3 (n = 40) was the youngest (mean age 63.5 ± 11.2) and predominantly male (63.5 ± 11.2), with the highest BMI (27.46 ± 5.85) and a high incidence of left ventricular hypertrophy. We characterized these three phenogroups as atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups, respectively. At the primary endpoint, Phenogroup 1 demonstrated the worst prognosis (Phenogroups 1-3: 72.0% vs. 58.5% vs. 45%, P = 0.0036). We also successfully classified a derivation cohort into three similar phenogroups using VBGMM. Hierarchical and supervised clustering successfully showed the reproducibility of the three phenogroups. CONCLUSIONS: ML could successfully stratify Japanese HFpEF patients into three phenogroups (atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups).

A multicenter prospective randomized study comparing the incidence of periprocedural cerebral embolisms caused by catheter ablation of atrial fibrillation between cryoballoon and radiofrequency ablation (Embo-Abl study): Study design.

BACKGROUND: Although catheter ablation (CA) has become a standard therapeutic approach to atrial fibrillation (AF), it imposes a low but relevant risk of thromboembolic complications of around 0.5%-1%, including ischemic strokes, and has an additional risk of clinically silent cerebral embolisms (SCEs) of 10%-40%. Both cryoballoon (CB) and radiofrequency (RF) ablation are routinely used clinically worldwide, yet there are few prospective data comparing the incidence of cerebral embolism after CA of AF between CB and RF ablation. METHODS: The aim of the Embo-Abl study will be to compare the incidence of cerebral embolisms on 3 T diffusion-weighted image magnetic resonance imaging (MRI) after CA of AF between CB and RF ablation in patients with AF in a prospective, multicenter, open-label, controlled, randomized fashion. The primary endpoint of the Embo-Abl study will be the occurrence of MRI-detected SCE 1-3 days after CA. The patients will be registered and randomly assigned to either the CB or RF ablation group in a 1:1 ratio. The study cohort will include 230 patients with AF from a multicenter in Japan. RESULTS: The results of this study are currently under investigation. CONCLUSION: The Embo-Abl study will be the first to compare the incidence of periprocedural cerebral embolisms caused by CA of AF between CB and RF ablation in a prospective, multicenter, randomized, controlled fashion.

Efficacy of Early Cardiac Rehabilitation After Cardiac Surgery　- Verification Using Japanese Diagnosis Procedure Combination Data.

Background: The current status of cardiac rehabilitation (CR) after cardiac surgery and the introduction of early CR (E-CR) in Japan are not fully understood. In this study, the current status of E-CR and its efficacy were investigated by the Academic Committee of the Japanese Association of Cardiac Rehabilitation. Methods and Results: We examined the rate of introduction of E-CR and its effects among 220,122 patients who underwent major cardiac and thoracic vascular surgery, as registered in the Diagnosis Procedure Combination (DPC) classification system, between April 2012 and March 2018. In this study, E-CR was defined as CR starting within 1 day after surgery. Patients with and without E-CR were propensity score matched and analyzed for clinical outcomes. Of all patients participating in CR after surgery, E-CR was initiated in 52.1%, 56.9%, 47.4%, and 54.1% of patients undergoing coronary artery bypass grafting, valve surgery, aortic surgery, and other cardiovascular surgery, respectively. After propensity score matching, outcomes for E-CR were significantly superior to non-E-CR in terms of in-hospital deaths, Barthel Index score at discharge, length of hospital stay, and hospitalization costs. Conclusions: E-CR after cardiac surgery was effective in terms of prognosis, hospital stay, and medical costs. This study is the first report using big data in Japan. The results indicate that further introduction of E-CR needs to be recommended in the future.

Features and Outcomes of Histologically Proven Myocarditis With Fulminant Presentation.

BACKGROUND: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. METHODS: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. RESULTS: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion (<40%) on admission, and ventricular tachycardia or fibrillation on admission day were associated with worse 90-day survival. Severe histologic damage (damaged cardiomyocytes comprising ≥50% of the total cardiomyocytes) was associated with a worse 90-day prognosis in patients with lymphocytic myocarditis. CONCLUSIONS: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. REGISTRATION: URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000039763.

Contemporary use of SGLT2 inhibitors in heart failure patients with diabetes mellitus: a comparison of DPP4 inhibitors in a nationwide electric health database of the superaged society.

BACKGROUND: There is a lack of recent data reflecting the actual use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for heart failure (HF) and type 2 diabetes (DM) in the superaged society. The present study investigated the association between the use of SGLT2 inhibitors and one-year prognosis in patients hospitalized across a broad spectrum of HF patients with DM in the superaged society using the Nationwide Electric Health Database in Japan. METHODS: The patients hospitalized with the first episode of acute HF were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between April 2014 and March 2019. A cohort of 2,277 users of SGLT2 inhibitors and 41,410 users of the active comparator, dipeptidyl peptidase-4 (DPP4) inhibitors were compared. A propensity score-matched cohort study of 2,101 users of each inhibitor was also conducted. A multivariable multilevel mixed-effects survival model was conducted with adjustments, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. RESULTS: Among 300,398 patients discharged with HF in 4,176 hospitals, 216,016 (71.9%) were 75 years or older, and 60,999 (20.3%) took antidiabetic medications. Among them, the patients treated with SGLT2 inhibitors were younger and had a more severe status than those treated with DPP4 inhibitors. Kaplan-Meier analysis showed that patients treated with SGLT2 inhibitors had a lower mortality risk and HF readmission. In propensity-matched cohorts, SGLT2 inhibitor use was associated with a lower risk of mortality and HF readmission than DPP-4 inhibitor use (HR [95% CI]; 0.70 [0.56, 0.89] and 0.52 [0.45, 0.61], respectively). Very elderly (≥ 75 years) patients showed similar results. Favorable effects were also observed across all age groups, including ≥ 75 years, in patients with coronary artery disease or atrial fibrillation and with concomitant ß-blocker, diuretics, or insulin. CONCLUSION: The use of SGLT2 inhibitors at discharge was associated with a lower risk of one-year mortality and HF readmission in patients across a broad spectrum of HF with DM in the superaged society. The findings further support the benefits of using SGLT2 inhibitors in very elderly HF care and complement the current evidence.

Trends and Factors Associated With Cardiac Rehabilitation Participation　- Data From Japanese Nationwide Databases.

BACKGROUND: Few studies have comprehensively evaluated the trends and factors associated with CR participation across major cardiovascular diseases in Japan.Methods and Results: This study performed a nationwide cross-sectional study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan and the Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination database. This study described the nationwide trends and evaluated patient- and hospital-level associated factors of CR participation for patients with acute heart failure (AHF), acute coronary syndrome (ACS), acute aortic dissection (AAD), peripheral artery disease (PAD), and after cardiovascular surgery using mixed-effect logistic regression analysis. Although the annual number of patients who underwent CR has increased during the study period, the total number of patients participating in outpatient CR was lower than that of inpatient CR. The outpatient CR participation rate was lower for patients with AHF (3.5%), AAD (3.2%), and PAD (1.7%), compared with ACS (7.9%) and after surgery (9.4%). Age, sex, body mass index, Barthel index, Charlson comorbidity index, and institutional capacity were identified as significant associated factors of CR participation in inpatient and outpatient settings. CONCLUSIONS: Participation in outpatient CR was still low, and higher age, multi-comorbidity, and low institutional capacity contributed to the lower outpatient CR participation rate. Identification of the associated factors may help cardiologists to increase CR participation.

The impact of hospital case volume on the outcomes after catheter ablation for atrial fibrillation according to the ablation technology.

INTRODUCTION: The appropriate hospital case volume for catheter ablation (CA) in patients with atrial fibrillation (AF) according to the ablation technology has not been fully examined. This study aimed to investigate the association between the hospital case volume for AF and periprocedural complications and AF recurrence. METHODS: In this retrospective cohort study, we used data from the National Database of Health Insurance Claims and Specific Health Checkups, which covers almost all healthcare insurance claims data in Japan. We included patients with AF who underwent first-time CA from April 2014 to March 2020. Using mixed-effect logistic regression, we analyzed the effect of the annual case volume for AF ablation on acute periprocedural complications and 1-year success rate off antiarrhythmic drugs according to the ablation technology (radiofrequency ablation or cryoballoon ablation). RESULTS: Among 270 116 patients, 207 839 (77%) patients underwent radiofrequency ablation and 56 648 (21%) patients underwent cryoballoon ablation. Of all patients, acute complications occurred in 5411 (2.0%) patients, and the recurrence at 1 year was 71 511 (27%). In the radiofrequency ablation group, acute complications and 1-year AF recurrence according to case volume decreased as the annual case volume increased to up to 150-200 cases/year. However, in the cryoballoon ablation group, these outcomes were similar regardless of the case volumes. CONCLUSION: The case-volume effect was noted in the radiofrequency ablation group, but not in the cryoballoon ablation group. Our results may affect the selection of ablation technology, especially in smaller case-volume hospitals.

Catheter ablation of ganglionated plexi in patients with adenosine triphosphate-induced atrial fibrillation after pulmonary vein isolation.

Intravenous ATP may induce atrial fibrillation (AF). ATP shares similar receptor-effector coupling systems with acetylcholine. However, the association between an ATP injection and the hyperactivity of the intrinsic cardiac autonomic nervous system, known as ganglionated plexi (GPs), is not well understood. We describe a series of patients with non-pulmonary vein (PV) trigger sites provoked by an ATP injection, and assess the feasibility of a ganglionated plexus (GP) ablation. We retrospectively analyzed 547 patients (69% male; mean age 67.4 ± 10.4 years; 38.5% non-paroxysmal AF) who underwent a total of 604 ablation procedures. Intravenous ATP was administered with an isoproterenol infusion during sinus rhythm after a pulmonary vein isolation in 21.3%, Box isolation in 78.6%, and SVC isolation in 52.0% of the procedures, respectively. We reviewed the incidence, the distribution of the foci, and the ablation outcomes in patients with ATP-induced AF. A total of seven patients (1.3%) had ATP-induced AF. Foci were identified in the coronary sinus (CS) in six patients, right atrial posterior wall (RAPW) adjacent to the interatrial groove in two, mitral annulus in two, ligament of Marshall in one, right septum below the foramen ovale in one and left atrial posterior wall in one, respectively. Among these trigger foci, we confirmed the vagal response by high-frequency stimulation in the CS and RAPW in six and two patients, respectively. After a median RF time of 2.9 min (range 2.5-11.3) targeting these foci, in five of six patients who received a repeat ATP injection, the AF became non-inducible. ATP-provoked trigger foci were distributed among certain sites that overlapped with the distribution of the GPs. The GP ablation was effective for this rare, but challenging situation.

A Cardiac Variant of Fabry Disease Diagnosed with Chance Urinary Mulberry Cells.

Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A and is classified into two types: classical and variant. The classical type exhibits classic manifestations, but the variant type does not and is therefore difficult to identify sometimes. A 73-year-old woman with a first episode of heart failure was admitted to our hospital. Her left ventricular wall motion was mildly reduced without hypertrophy. Urine sediment revealed mulberry cells, leading to the diagnosis of Fabry disease. In cases without typical clinical findings, urinary mulberry cells may help diagnose Fabry disease.