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.

Validity of Diagnostic Algorithms for Cardiovascular Diseases in Japanese Health Insurance Claims.

BACKGROUND: We aimed to validate a claims-based diagnostic algorithm to identify hospitalized patients with acute major cardiovascular diseases (CVDs) from health insurance claims in Japan.Methods and Results: This retrospective multicenter validation study was conducted at 4 institutes, including Japanese Circulation Society-certified and uncertified hospitals in Japan. Data on patients with CVDs in departmental lists or with International Classification of Diseases, 10th Revision (ICD-10) codes for CVDs hospitalized between April 2018 and March 2019 were extracted. We examined the sensitivity and positive predictive value of a diagnostic algorithm using ICD-10 codes, medical examinations, and treatments for acute coronary syndrome (ACS), acute heart failure (HF), and acute aortic disease (AAD). We identified 409 patients with ACS (mean age 70.6 years; 24.7% female), 615 patients with acute HF (mean age 77.3 years; 46.2% female), and 122 patients with AAD (mean age 73.4 years; 36.1% female). The respective sensitivity and positive predictive value for the algorithm were 0.86 (95% confidence interval [CI] 0.82-0.89) and 0.95 (95% CI 0.92-0.97) for ACS; 0.74 (95% CI 0.70-0.77) and 0.79 (95% CI 0.76-0.83) for acute HF; and 0.86 (95% CI 0.79-0.92) and 0.83 (95% CI 0.76-0.89) for AAD. CONCLUSIONS: The validity of the diagnostic algorithm for Japanese claims data was acceptable. Our results serve as a foundation for future studies on CVDs using nationwide administrative data.

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.

Transthyretin Amyloid Cardiomyopathy: Impact of Transthyretin Amyloid Deposition in Myocardium on Cardiac Morphology and Function.

BACKGROUND: Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is increasingly being recognized as a cause of left ventricular (LV) hypertrophy (LVH) and progressive heart failure in elderly patients. However, little is known about the cardiac morphology of ATTR-CM and the association between the degree of TTR amyloid deposition and cardiac dysfunction in these patients. METHODS: We studied 28 consecutive patients with ATTR-CM and analyzed the relationship between echocardiographic parameters and pathological features using endomyocardial biopsy samples. RESULTS: The cardiac geometries of patients with ATTR-CM were mainly classified as concentric LVH (96.4%). The relative wall thickness, a marker of LVH, tended to be positively correlated with the degree of non-cardiomyocyte area. The extent of TTR deposition was positively correlated with enlargement of the non-cardiomyocyte area, and these were positively correlated with LV diastolic dysfunction. Additionally, the extent of the area containing TTR was positively correlated with the percentage of cardiomyocyte nuclei stained for 8-hydroxy-2'deoxyguanosine, a marker of reactive oxygen species (ROS). ROS accumulation in cardiomyocytes was positively correlated with LV systolic dysfunction. CONCLUSION: Patients with ATTR-CM mainly displayed concentric LVH geometry. TTR amyloid deposition was associated with cardiac dysfunction via increased non-cardiomyocyte area and ROS accumulation in cardiomyocytes.

Incidence of epicardial connections between the right pulmonary vein carina and right atrium during catheter ablation of atrial fibrillation: A comparison between the conventional method and unipolar signal modification.

BACKGROUND: When performing an electrical isolation of ipsilateral pulmonary veins (PVs) for atrial fibrillation, physicians often need additional radiofrequency (RF) ablation in the carina region between the superior and inferior PVs to achieve a right PV isolation because of intercaval bundles between the right PVs and right atrium (RA). We compared the efficacy of a high-power and short-duration ablation guided by unipolar signal modification (UM) with the conventional method (CM) for ablating epicardial connections between the right PV carina and RA. METHODS: The study subjects consisted of patients who underwent an initial box isolation of atrial fibrillation from January 2015 to December 2019 at Nara Medical University Hospital. Among these patients, 94 and 65 patients who met the criteria were assigned to the CM and UM groups, respectively. We retrospectively analyzed the anterior ablation line of the right PV using an electroanatomical mapping system. Patients whose initial ablation line included the right PV carina were excluded. RESULTS: Six and seven patients were, respectively, excluded from the CM and UM groups. Among 88 CM group patients, 21 needed additional right PV carina ablation, while among 58 UM group patients, 30 needed additional right PV carina ablation (p = .001). No anatomical factors were associated with the additional right PV carina ablation. CONCLUSIONS: Compared to the CM group, a box isolation was less achievable without RF ablation at the right PV carina in the UM group. We should consider a long-duration ablation for epicardial connections between the right PV carina and RA.

Outcomes of catecholamine and/or mechanical support in Takotsubo syndrome.

OBJECTIVE: This study aimed to reveal the clinical characteristics of patients with severe Takotsubo syndrome (TTS) who needed catecholamine support (CS) or mechanical support (MS) and to identify factors associated with serious illness and in-hospital mortality. METHODS: This was a nationwide retrospective study that used claims data from the Japanese registry of all cardiac and vascular diseases and the diagnosis procedure combination registry, from April 2012 to March 2016. The patients with TTS were divided into severe TTS and mild TTS groups. The severe group was defined as patients who needed CS and/or MS. RESULTS: Among 6169 patients with TTS, 1148 (18.6%) had severe TTS. No significant difference in age was found between the two groups; however, the number of female patients was significantly lower in the severe group than in the mild group. Among 130 patients who underwent MS, 22 and 108 patients required MS alone and both MS and CS, respectively. The 30-day mortality rate was significantly higher in the severe group than in the mild group (11.4% vs 2.6%, p<0.01) and increased with age. Of the patients with severe TTS, 65.6% died within 7 days. Multivariable analysis showed that male sex (OR 1.22, p=0.03), higher Charlson scores (OR 1.11, p<0.01), comorbid pneumonia (OR 1.68, p<0.01), comorbid sepsis (OR 6.02, p<0.01) and ambulance use (OR 2.01, p<0.01) were associated with severe TTS. CONCLUSIONS: The rate of severe TTS was 18.6% among 6169 patients registered in the Japanese nationwide database, and the 30-day mortality was higher in patients with severe TTS than in those with mild TTS (11.4% vs 2.6%).

Association of short-term exposure to air pollution with myocardial infarction with and without obstructive coronary artery disease.

BACKGROUND: Air pollution including particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) increases the risk of acute myocardial infarction. However, whether short-term exposure to PM2.5 triggers the onset of myocardial infarction with nonobstructive coronary arteries, compared with myocardial infarction with coronary artery disease, has not been elucidated. This study aimed to estimate the association between short-term exposure to PM2.5 and admission for acute myocardial infarction, myocardial infarction with coronary artery disease, and myocardial infarction with nonobstructive coronary arteries. DESIGN: This was a time-stratified case-crossover study and multicenter validation study. METHODS: This study used a nationwide administrative database in Japan between April 2012-March 2016. Of 137,678 acute myocardial infarction cases, 123,633 myocardial infarction with coronary artery disease and 14,045 myocardial infarction with nonobstructive coronary arteries were identified by a validated algorithm combined with International Classification of Disease (10th revision), diagnostic, and procedure codes. Air pollutants and meteorological data were obtained from the monitoring station nearest to the admitting hospital. RESULTS: In spring (March-May), the short-term increase of 10 µg/m3 in PM2.5 2 days before admission was significantly associated with admission for acute myocardial infarction, myocardial infarction with nonobstructive coronary arteries, and myocardial infarction with coronary artery disease after adjustment for meteorological variables (odds ratio 1.060, 95% confidence interval 1.038-1.082; odds ratio 1.151, 1.079-1.227; odds ratio 1.049, 1.026-1.073, respectively), while the association was not significant in other variables. These associations were also observed after adjustment for other co-pollutants. The risk for myocardial infarction with nonobstructive coronary arteries (vs myocardial infarction with coronary artery disease) was associated with an even lower concentration of PM2.5 under the current environmental standards. CONCLUSIONS: This study showed the seasonal difference of acute myocardial infarction risk attributable to PM2.5 and the difference in the threshold of triggering the onset of acute myocardial infarction subtype.

Current Status and Effect of Outpatient Cardiac Rehabilitation After Percutaneous Coronary Intervention in Japan.

Background: Although cardiac rehabilitation (CR) has been reported to be associated with better clinical outcomes in patients with cardiovascular diseases, there are few nationwide studies about CR participation by patients with coronary artery disease in Japan. Methods and Results: We performed a nationwide retrospective cohort study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan between April 2014 and March 2018. Patients were divided into 2 groups (acute coronary syndrome [ACS] and stable coronary artery disease [sCAD]), and the rates of participation in in- and outpatient CR after percutaneous coronary intervention (PCI) were investigated. Propensity score-matched analysis was performed and the association between outpatient CR participation and all-cause mortality 3 months after PCI was examined. Overall, 616,664 patients (ACS, n=202,853; sCAD, n=413,811) were analyzed. The participation rates of CR increased annually. The participation rate was higher for inpatient than outpatient CR in both the ACS (52% vs. 9%, respectively) and sCAD (15% vs. 3%, respectively) groups. Prognosis was better for patients with than without outpatient CR in both the ACS (hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.47-0.59) and sCAD (HR 0.72; 95% CI 0.65-0.80) groups. Conclusions: Outpatient CR was associated with a better prognosis in patients with ACS or sCAD. The participation rates of outpatient CR following PCI were extremely low in Japan.

Prognosis and Outcomes of Clinically Diagnosed Cardiac Sarcoidosis Without Positive Endomyocardial Biopsy Findings.

Background: Diagnosis of cardiac sarcoidosis (CS) is sometimes difficult due to a low positive rate of epithelioid granulomas by endomyocardial biopsy (EMB). Accordingly, Japanese guidelines can allow the CS diagnosis using clinical data alone without EMB results (clinical CS) since 2006. However, little is known about prognosis and outcome of clinical CS. Objectives: Purpose of this study was to analyze the prognosis, outcomes, and response to corticosteroid of clinical CS using large-scale cohort survey. Methods: Overall, 422 CS patients (mean age 60 ± 13 years, 68% female, median follow-up period of 5 years), including 345 clinical CS and 77 EMB-positive patients, histologically diagnosed CS (histological CS) by Japanese guidelines, were enrolled and examined. Results: Clinical profile (age, sex, initial cardiac arrhythmias, and abnormal uptake of gallium-67 scintigraphy or 18F-fluorodeoxyglucose positron emission tomography in heart) was similar in both groups. Although clinical CS had better prognosis (P = 0.018) and outcome (all-cause death, appropriate defibrillator therapy, and heart transplantation; P = 0.008), multivariate Cox hazard analysis revealed that left ventricular ejection fraction (LVEF) and sustained ventricular tachycardia history were independently associated with outcome (P < 0.001 and P = 0.002, respectively), but not with the diagnosed CS category. Moreover, similar LVEF recovery after corticosteroid was observed in both groups with low LVEF (≤35%) at the 1-year follow-up period (P < 0.001). Conclusions: In clinical CS according to the Japanese guideline, prophylactic implantable-cardioverter-defibrillator and immunosuppressive therapy are important in patients with low LVEF or ventricular tachycardia history, similar to histological CS.

Role of climatic factors in the incidence of Takotsubo syndrome: A nationwide study from 2012 to 2016.

AIMS: This study aimed to investigate the influence of climatic factors on the onset of Takotsubo syndrome (TTS). METHODS AND RESULTS: We performed a retrospective nationwide study among patients registered in the Japanese Registry of All Cardiac and Vascular Diseases and Diagnosis Procedure Combination (JROAD-DPC) discharge database, between 2012 and 2016. Before the analysis, a multicentre validation study was conducted for assessing the accuracy of the JROAD-DPC classification for TTS. First, we investigated the seasonal variation of incidences of TTS. Second, we analysed the associations between the incidence of TTS and climatic factors using the hierarchical Poisson regression modelling, and we also investigated the associations between typhoon landfalls and hospitalization for TTS, using the fixed-effects conditional Poisson regression model. The sensitivity and specificity for diagnosis were 83% and 100%, respectively. Then we analysed 5643 patients with TTS. The mean patient age was 74 (standard deviation ± 11) years; 79% were female. TTS was diagnosed significantly more frequently in the summer and early autumn. The incidence of TTS was related to higher temperatures; adjusted incidence rate ratios were 1.46 [95% confidence interval (CI): 1.33-1.60, P < 0.01] and 1.47 (95% CI: 1.34-1.62, P < 0.01) for temperatures of 20-25°C and >25°C, respectively. The incidence rate ratio for the first 2 days after a typhoon landfall was 1.85 (95% CI: 1.07-3.19; P = 0.03). CONCLUSIONS: This study demonstrates distinct patterns of seasonal variation in the incidence of TTS, as well as a significant association between its onset and climatic factors, including typhoon landfalls.