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Higher frequencies of inflammatory adverse effects of clozapine have been reported in Japan. As the international titration protocol for Asians has set slower dose titration than the Japanese package insert, we hypothesized that a dose titration speed slower than the recommendation of the guideline would be associated with fewer inflammatory-related adverse events. The medical records of all 272 patients who were first started on clozapine at seven hospitals between 2009 and 2023 were studied retrospectively. Of those, 241 were included in the analysis. The patients were divided into two groups regarding whether the titration speed was faster or slower than the guideline for Asians. The incidence of inflammatory adverse events with clozapine was compared between the groups. The frequency of inflammatory adverse events was 34 % (37/110) in the faster titration group and 13 % (17/131) in the slower titration group, and a significant difference was observed by Fisher exact test (odds ratio 3.38; 95 % confidence interval 1.71–6.91; p < 0.001). Serious adverse effects, fever for more than five days, and clozapine discontinuation were significantly more frequent in the faster titration group. Logistic regression analysis indicated significantly more inflammatory adverse events in the faster titration group (adjusted odds ratio 4.01; 95 % confidence interval 2.02–7.87; p < 0.001) considering age, sex, body mass index, concomitant valproic acid, and smoking as confounding factors. Clozapine-induced inflammatory adverse events were less frequent in Japanese individuals when a titration rate was more gradual than the protocol recommended in the Japanese package insert. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: We developed an international registry to examine cardiovascular complications of COVID-19. Methods: A REDCap form was created in March 2020 at Mayo Clinic in collaboration with the International Society of Cardiomyopathy, Myocarditis and Heart Failure (ISCMF) and data were entered from April 2020 through April 2021. Results: Of the 696 patients in the COVID-19 Registry, 411 (59.2%) were male and 283 (40.8%) were female, with a sex ratio of 1.5:1 male to female. In total, 95.5% of the patients were from Japan. The average age was 52 years with 31.5% being >65 years of age. COVID-19 patients with a history of cardiovascular disease (CVD) had more pre-existing conditions including type II diabetes (p < 0.0001), cancer (p = 0.0003), obesity (p = 0.001), and kidney disease (p = 0.001). They also had a greater mortality of 10.1% compared to 1.7% in those without a history of CVD (p < 0.0001). The most common cardiovascular conditions in patients with a history of CVD were hypertension (33.7%), stroke (5.7%) and arrhythmias (5.1%). We found that troponin T, troponin I, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), C-reactive protein (CRP), IL-6 and lambda immunoglobulin free light chains (Ig FLC) were elevated above reference levels in patients with COVID-19. Myocarditis is known to occur mainly in adults under the age of 50, and when we examined biomarkers in patients that were ≤50 years of age and had no history of CVD we found that a majority of patients had elevated levels of troponin T (71.4%), IL-6 (59.5%), creatine kinase/CK-MB (57.1%), D-dimer (57.8%), kappa Ig FLC (75.0%), and lambda Ig FLC (71.4%) suggesting myocardial injury and possible myocarditis. Conclusions: We report the first findings to our knowledge of cardiovascular complications from COVID-19 in the first year of the pandemic in a predominantly Japanese population. Mortality was increased by a history of CVD and pre-existing conditions including type II diabetes, cancer, obesity, and kidney disease. Our findings indicate that even in cases where no abnormalities are found in ECG or ultrasound cardiography that myocardial damage may occur, and cardiovascular and inflammatory biomarkers may be useful for the diagnosis. [ABSTRACT FROM AUTHOR]

An influenza pandemic occurred in 2009. We performed a retrospective national questionnaire survey about H1N1pdm2009 myocarditis to compare influenza A H1N1pdm2009 myocarditis in the pandemic (2009/2010) and postpandemic seasons (2010/2011) by collecting data from 360 hospitals. The diagnosis of myocarditis was performed using the guidelines for Diagnosis and Treatment of Myocarditis published by the Japanese Circulation Society (JCS 2009). Twenty-nine patients with influenza A H1N1pdm2009 myocarditis were reported, with 25 from the 2009/2010 season and only 4 patients from the 2010/2011 season. Morbidity and mortality was 28 % (8/29) among all the myocarditis patients. Six patients with myocarditis were complicated by pneumonia. Myocarditis was proved by endomyocardial biopsy or autopsy in 9 patients, although histological findings showed mild myocarditis even in clinically defined fulminant myocarditis cases. Seventeen patients were diagnosed with fulminant H1N1pdm2009 myocarditis with fatal arrhythmias or varying degrees of cardiogenic shock. Fifteen fulminant myocarditis patients were seen in the 2009/2010 season and only 2 in the 2010/2011 season. Ventilators were used in 16 patients. Mechanical circulatory support with intraaortic balloon pumping or percutaneous cardiopulmonary support (IABP/PCPS) was emergently inserted in 13 patients. Of these, 9 patients were rescued with mechanical circulatory support, and 4 patients died. Four fulminant myocarditis patients treated without IABP/PCPS died. We described the clinical features of patients with myocarditis associated with influenza H1N1pdm2009 in the pandemic and postpandemic seasons and demonstrated the high prevalence of fulminant myocarditis (17/29, 59 %). The number of patients with myocarditis associated with influenza A virus seemed to increase in the pandemic season. [ABSTRACT FROM AUTHOR]

To clarify the cause of deaths associated with pandemic (H1N1) 2009 among children in Japan, we retrospectively studied 41 patients <20 years of age who had died of pandemic (H1N1) 2009 through March 31, 2010. Data were collected through interviews with attending physicians and chart reviews. Median age of patients was 59 months; one third had a preexisting condition. Cause of death was categorized as unexpected cardiopulmonary arrest for 15 patients, encephalopathy for 15, and respiratory failure for 6. Preexisting respiratory or neurologic disorders were more frequent in patients with respiratory failure and less frequent in patients with unexpected cardiopulmonary arrest. The leading causes of death among children with pandemic (H1N1) 2009 in Japan were encephalopathy and unexpected cardiopulmonary arrest. Deaths associated with respiratory failure were infrequent and occurred primarily among children with preexisting conditions. Vaccine use and public education are necessary for reducing influenza-associated illness and death. [ABSTRACT FROM AUTHOR]

Mechanical circulatory support for acute biventricular failure is challenging. Given that durable VAD is available only for LV support as bridge-to-transplantation in Japan, the treatment options for this pathology are limited to extracorporeal biventricular assist device (BiVAD) support first, which can be subsequently upgraded to durable LVAD in cases having recovery of RV function and transplant candidacy. The purpose of this study was to review the outcomes of extracorporeal BiVAD and to explore factors associated with the outcomes. This study enrolled an institutional consecutive series of 39 cases who underwent extracorporeal BiVADs implantation for acute biventricular failure between April 2014 and October 2020. The etiological diagnosis was myocarditis in 27 cases, acute MI in 6 cases, and dilated cardiomyopathy (DCM) in 6 cases. The cases were assigned into the two groups according to the BiVAD support less than 7 days (n=18, Short group) or 7 days or more (n=21, Long group). The Long group consisted of 6 cases of acute MI (100%), 13 cases (48%) of myocarditis, two cases of DCM (33%). There was no case who deceased within 7 days after BiVAD implantation. In the Short group, extracorporeal LVAD was weaned-off in 11 cases (61%) or upgraded to durable LVAD in 6 cases after withdrawal of RV support within 7 days. The remaining one case deceased under extracorporeal LVAD. In the Long group, RV support was discontinued in 10 cases in the median support of 60 days (IQR; 24.2-76.8), while two cases were on BiVAD support at October 2020. The remaining nine cases (43%) deceased under BiVAD support in-hospital. Survival and VAD-free survival at 1 year were 79% and 56% in the Short group versus 48% and 20% in the Long group, respectively. Outcomes of extracorporeal BiVAD support for acute biventricular failure were dependent on recovery of RV function. Targeting approach for RV function would be warranted for poor biventricular function. [ABSTRACT FROM AUTHOR]

Background: Fulminant type 1 diabetes mellitus (FT1D) is a newly established subtype of type 1 diabetes. Its etiology has not been fully elucidated. Several cases with FT1D have exhibited pancreatitis or myocarditis. Case presentation: We report a 31-year-old Japanese woman who showed upper abdominal pain and was admitted to a local hospital. She was initially diagnosed with acute pancreatitis based on serum amylase elevation and swelling of the pancreas on computed tomography. Four days after admission, she developed diabetic ketoacidosis and was transferred to our hospital. Her symptoms and laboratory findings met the FT1D criteria. On the 3rd hospital day, electrocardiography (ECG) showed ST-segment elevation, and serum cardiac enzymes were markedly elevated. Because she exhibited late gadolinium enhancement in the apical wall on contrast-enhanced cardiac magnetic resonance imaging, she was diagnosed as acute myocarditis. Abnormal ECG findings and elevations of biomarkers associated with myocarditis showed improvement on the next day. Conclusions: This is the first case of FT1D accompanied by both pancreatitis and myocarditis and suggests that the pathophysiology of FT1D is related to the common etiology of acute pancreatitis and myocarditis. [ABSTRACT FROM AUTHOR]