Eosinophilic myocarditis during treatment with olanzapine - report of two possible cases

BACKGROUND: Drug-induced eosinophilic myocarditis is a life-threatening and frequently overlooked condition. The prevalence of myocarditis in clozapine-treated patients may be as high as 3 %. An association between olanzapine and myocarditis has not previously been described, but given the chemical similarity between olanzapine and clozapine, we hypothesized the existence of such an association. We searched the spontaneous adverse drug reports database of the Danish Health and Medicines Authority for olanzapine and myocarditis in the period from October 21, 1996 to – June 03, 2015. We identified two fatal cases of eosinophilic myocarditis associated with the use of olanzapine. CASE PRESENTATION: Case 1 was a 39-year-old Caucasian man with known substance abuse and schizophrenia. He was found dead in his home. Olanzapine was prescribed at day -54, and dose at time of death was 40 mg/day. Post-mortem toxicological examination demonstrated presence of olanzapine, morphine, venlafaxine and oxazepam. Syringes indicating substance abuse were found in his home. Case 2 was a 36-year-old Caucasian man diagnosed with schizophrenia was found dead unexpectedly. There was no history of substance abuse. Current treatment was olanzapine 20 mg/day +5 mg as PRN (prescribed for almost 4 years), aripiprazole 30 mg/day (prescribed for 6 months) and mirtazapine 30 mg/day (prescribed for 6 months). Both cases of eosinophilic myocarditis were confirmed by autopsy findings and both patients received olanzapine in doses exceeding the recommendations. CONCLUSION: Olanzapine may have contributed to and/or worsened the two reported fatal cases of myocarditis. Additional studies are required to establish a causal link between olanzapine and eosinophilic myocarditis

MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome.

Long QT syndrome (LQTS) is a genetic cardiac condition associated with prolonged ventricular repolarization, primarily a result of perturbations in cardiac ion channels, which predisposes individuals to life-threatening arrhythmias. Using DNA screening and sequencing methods, over 700 different LQTS-causing mutations have been identified in 13 genes worldwide. Despite this, the genetic cause of 30-50% of LQTS is presently unknown. MicroRNAs (miRNAs) are small (∼ 22 nucleotides) noncoding RNAs which post-transcriptionally regulate gene expression by binding complementary sequences within messenger RNAs (mRNAs). The human genome encodes over 1800 miRNAs, which target about 60% of human genes. Consequently, miRNAs are likely to regulate many complex processes in the body, indeed aberrant expression of various miRNA species has been implicated in numerous disease states, including cardiovascular diseases. MiR-1 and MiR-133A are the most abundant miRNAs in the heart and have both been reported to regulate cardiac ion channels. We hypothesized that, as a consequence of their role in regulating cardiac ion channels, genetic variation in the genes which encode MiR-1 and MiR-133A might explain some cases of LQTS. Four miRNA genes (miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2), which encode MiR-1 and MiR-133A, were sequenced in 125 LQTS probands. No genetic variants were identified in miR-1-1 or miR-133a-1; but in miR-1-2 we identified a single substitution (n.100A> G) and in miR-133a-2 we identified two substitutions (n.-19G> A and n.98C> T). None of the variants affect the mature miRNA products. Our findings indicate that sequence variants of miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2 are not a cause of LQTS in this cohort

Unrecognised myocardial infarction in patients with schizophrenia

ObjectiveSchizophrenia is associated with a reduction of the lifespan by 20 years, with type II diabetes and cardiovascular disease contributing the most to the increased mortality. Unrecognised or silent myocardial infarction (MI) occurs in ~30% of the population, but the rates of unrecognised MI in patients with schizophrenia have only been sparsely investigated.MethodElectrocardiograms (ECG) from three psychiatric hospitals in Denmark were manually interpreted for signs of previous MI. Subsequently, ECGs were linked to the National Patient Registry in order to determine whether patients had a diagnosis consistent with previous MI.ResultsA total of 937 ECGs were interpreted, 538 men (57.4%) and 399 women (42.6%). Mean age at the time of ECG acquisition was 40.6 years (95% CI: 39.7–41.5, range: 15.9–94.6). We identified 32 patients with positive ECG signs of MIs. Only two of these patients had a diagnosis of MI in the National Patient Registry. An additional number of eight patients had a diagnosis of MI in the Danish National Patient Registry, but with no ECG signs of previous MI. This means that 30 out of 40 (75%) MIs were unrecognised. Only increasing age was associated with unrecognised MI in a stepwise multiple logistic regression model compared with patients with no history of MI, OR: 1.03 per year of age, 95% CI: 1.00–1.06, p=0.021.ConclusionUnrecognised MI is common among patients with schizophrenia and may contribute to the increased mortality found in this patient group.</jats:sec