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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]

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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]