Dataset Information

Clozapine-induced myocarditis: Follow-up for 3.5 years after successful retrial.

ABSTRACT: Schizophrenia patients have significantly lower life expectancy than the general population. Clozapine is the most effective antipsychotic to reduce the mortality rate in these patients. Here, we report a schizophrenic patient with clozapine-induced myocarditis and successful retrial. In the first trial, clozapine was discontinued due to myocarditis. In the second trial, the titration rate was slower, and sodium valproate was not coadministered with clozapine. The patient has not developed myocarditis over 3.5 years of observation. It may be possible to take clozapine for a long time even after clozapine-induced myocarditis, and thus improve the life expectancy of schizophrenia patients.

SUBMITTER: Otsuka Y

PROVIDER: S-EPMC6498130 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Clozapine-induced myocarditis: Follow-up for 3.5 years after successful retrial.

Otsuka Yuji Y Idemoto Keita K Hosoda Yutaka Y Imamura Yukitsugu Y Aoki Tsutomu T

Journal of general and family medicine 20190227 3

Schizophrenia patients have significantly lower life expectancy than the general population. Clozapine is the most effective antipsychotic to reduce the mortality rate in these patients. Here, we report a schizophrenic patient with clozapine-induced myocarditis and successful retrial. In the first trial, clozapine was discontinued due to myocarditis. In the second trial, the titration rate was slower, and sodium valproate was not coadministered with clozapine. The patient has not developed myoca ...[more]

PMID: 31065477

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Project description:Clozapine is the most effective antipsychotic drug for schizophrenia, yet it can cause life-threatening adverse drug reactions, including myocarditis. The aim of this study was to determine whether schizophrenia patients with clozapine-induced myocarditis have a genetic predisposition compared with clozapine-tolerant controls. We measured different types of genetic variation, including genome-wide single-nucleotide polymorphisms (SNPs), coding variants that alter protein expression, and variable forms of human leucocyte antigen (HLA) genes, alongside traditional clinical risk factors in 42 cases and 67 controls. We calculated a polygenic risk score (PRS) based on variation at 96 different genetic sites, to estimate the genetic liability to clozapine-induced myocarditis. Our genome-wide association analysis identified four SNPs suggestive of increased myocarditis risk (P < 1 × 10-6), with odds ratios ranging 5.5-13.7. The SNP with the lowest P value was rs74675399 (chr19p13.3, P = 1.21 × 10-7; OR = 6.36), located in the GNA15 gene, previously associated with heart failure. The HLA-C*07:01 allele was identified as potentially predisposing to clozapine-induced myocarditis (OR = 2.89, 95% CI: 1.11-7.53), consistent with a previous report of association of the same allele with clozapine-induced agranulocytosis. Another seven HLA alleles, including HLA-B*07:02 (OR = 0.25, 95% CI: 0.05-1.2) were found to be putatively protective. Long-read DNA sequencing provided increased resolution of HLA typing and validated the HLA associations. The PRS explained 66% of liability (P value = 9.7 × 10-5). Combining clinical and genetic factors together increased the proportion of variability accounted for (r2 0.73, P = 9.8 × 10-9). However, due to the limited sample size, individual genetic associations were not statistically significant after correction for multiple testing. We report novel candidate genetic associations with clozapine-induced myocarditis, which may have potential clinical utility, but larger cohorts are required for replication.

Project description:Myocarditis is a rare complication of the COVID-19 mRNA vaccine. We previously reported a case series of 15 adolescents with vaccine-associated myocarditis, 87% of whom had abnormalities on initial cardiac magnetic resonance (CMR), including late gadolinium enhancement (LGE) in 80%. We performed follow-up CMRs to determine the trajectory of myocardial recovery and better understand the natural history of vaccine-associated myocarditis. Case series of patients age < 19 years admitted to Boston Children's Hospital with acute vaccine-associated myocarditis following the BNT162b2 vaccine who had abnormal CMR at the time of initial presentation, and underwent follow-up testing. CMR assessment included left ventricular (LV) ejection fraction, T2-weighted myocardial imaging, LV global native T1, LV global T2, extracellular volume (ECV), and late gadolinium enhancement (LGE). Ten patients (9 male, median age 15 years) with vaccine-associated myocarditis underwent follow-up CMR at a median of 92 days (range 76-119) after hospital discharge. LGE was persistent in 80% of patients, though improved from prior in all cases. Two patients (20%) had abnormal LV global T1 at presentation, which normalized on follow-up. ECV decreased between acute presentation and follow-up in 6/10 patients; it remained elevated at follow-up in 1 patient and borderline in 3 patients.ConclusionCMR performed ~3 months after admission for COVID-19 vaccine-associated myocarditis showed improvement of LGE in all patients, but persistent in the majority. Follow-up CMR 6-12 months after acute episode should be considered to better understand the long-term cardiac risks.What is known• Myocarditis is a rare side effect of COVID-19 mRNA vaccine. •Late gadolinium enhancement is present on most cardiac magnetic resonance at the time of acute presentation.What is new•Late gadolinium enhancement improved on all repeat cardiac magnetic resonance at 3-month follow-up. •Most patients still had a small amount of late gadolinium enhancement, the clinical significance of which is yet to be determined.

Project description:BackgroundMass COVID-19 vaccination campaigns have helped impede the COVID-19 pandemic. In rare cases, some vaccines have led to vaccine associated myocarditis in a specific subset of the population, usually young males. Cardiac magnetic resonance (CMR) can reliably diagnose vaccine associated myocarditis, but follow-up data of CMR proven acute myocarditis is scarce.Materials and methodsNine patients with acute vaccine associated myocarditis underwent baseline and follow-up CMR examinations and were compared to baseline parameters at initial presentation and to a group of 20 healthy controls. CMR protocol included functional assessment, T1 and T2 mapping, T2 signal intensity ratio, strain feature tracking, and late gadolinium enhancement (LGE).ResultsMyocarditis patients (n = 9, aged 24 ± 6 years, 8 males) underwent CMR follow-up after an average of 5.8 ± 4.3 months. All patients showed a complete resolution of visual myocardial edema while also demonstrating a reduction in overall LGE extent from baseline to follow-up (4.2 ± 2.1 vs. 0.9 ± 0.8%, p < 0.001), although visual LGE was still noted in all patients. Left ventricular ejection fraction was normal at baseline and at follow-up (58 ± 6 vs. 62 ± 4%, p = 0.10) as well as compared to a healthy control group (60 ± 4%, p = 0.24). T1 (1024 ± 77 vs. 971 ± 34 ms, p = 0.05) and T2 relaxations times (57 ± 6 vs. 51 ± 3 ms, p = 0.03) normalized at follow-up. Most patients reported a resolution of clinical symptoms, while two (22%) reported new onset of exertional dyspnea.ConclusionPatients with COVID-19 vaccine associated acute myocarditis showed a complete, uncomplicated resolution of myocardial inflammation on follow-up CMR, which was associated with a near complete resolution of symptoms. Minor, residual myocardial scarring was present on follow-up LGE imaging. The long-term implications of the remaining myocardial scar-tissue after vaccine associated myocarditis remain unknown warranting further studies.

Dataset Information

Clozapine-induced myocarditis: Follow-up for 3.5 years after successful retrial.

Publications

Clozapine-induced myocarditis: Follow-up for 3.5 years after successful retrial.

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