Clozapine is the antipsychotic of choice for people with treatment-resistant schizophrenia (TRS) but is associated with the uncommon but potentially life-threatening adverse effect of myocarditis. However, there are no criteria for diagnosing clozapine-associated myocarditis (CAM) or global guidelines on detection and risk reduction, or for restarting clozapine after CAM.

To develop criteria for CAM and algorithms for clozapine initiation and clozapine rechallenge after CAM in a multiprofessional consensus process.

We conducted a systematic literature search for cases of clozapine rechallenge following CAM using the PubMed, EMBASE, CINAHL and PsycINFO databases, followed by a multidisciplinary international two-step Delphi consensus process in July and October 2024. The Delphi panel comprised psychiatrists, cardiologists, pharmacists, psychopharmacologists and nurses with expertise on clozapine or myocarditis.

Ninety-three clinicians and academics with experience in prescribing clozapine from six continents participated in the Delphi process. A consensus was reached on a definition of CAM according to modified clinical criteria from the European Society of Cardiology for myocarditis associated with immune checkpoint inhibitors. Titration schemes slower than those given in the Summary of Product Characteristics for clozapine were recommended to minimise CAM risk. Minimum and enhanced requirements for screening and monitoring were developed to account for global perspectives and limited resources in certain healthcare systems, and an approach to clozapine rechallenge was elaborated.

This multidisciplinary project represents the first guidance for CAM and will inform clinicians, other caregivers and patients, as well as facilitating the development of national guidelines on CAM prevention, screening and monitoring and rechallenge after an index episode of myocarditis in individuals taking clozapine.

Parvovirus B19 (PVB19) myocarditis is a life-threatening condition with high morbidity and mortality in children. While electrocardiograms are commonly used in the early assessment of myocarditis, no specific electrocardiogram pattern has been consistently linked to PVB19. The objective of this study is to identify a distinctive electrocardiogram pattern associated with PVB19 myocarditis and evaluate its diagnostic accuracy.

This retrospective case–control study included 77 paediatric patients diagnosed with acute myocarditis at a single centre in Barcelona over 16 years (August 2008–September 2024). Twenty patients had PVB19 myocarditis, confirmed by polymerase chain reaction in blood or endomyocardial biopsy, while 57 patients had myocarditis caused by other viruses. Electrocardiogram were assessed by three cardiologists blinded to the aetiological diagnosis.

A specific electrocardiogram pattern in the limb leads, characterised by peaked P waves, low QRS complex voltages, and altered repolarisation (manifesting as negative or flat T waves, with or without QTc prolongation), was observed in 14 of 20 patients (70%) with PVB19 myocarditis. Two additional patients exhibited low voltages and altered repolarisation without peaked P waves, and all demonstrated repolarisation abnormalities. In contrast, only 1 of 57 patients with myocarditis from other viruses exhibited the full electrocardiogram pattern. The pattern demonstrated a specificity of 98% and a sensitivity of 70% for PVB19 myocarditis.

The identified electrocardiogram pattern shows strong diagnostic specificity for PVB19 myocarditis in paediatric patients and may serve as a useful early diagnostic tool. Further multicentre studies are needed to confirm these findings and explore their clinical implications.

Clozapine is the antipsychotic medication with the greatest efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, clozapine is ceased in approximately 0.2% to 8.5% of people due to concerns about clozapine-associated myocarditis (CAM). The opportunity for clozapine rechallenge is important for people with TRS and CAM, due to limited alternative treatments. However, there is a lack of consensus regarding the optimal process, monitoring, and dose titration to achieve successful clozapine rechallenge. The study aimed to review the process, monitoring, and dose titration within cases of clozapine rechallenge after CAM, to identify features associated with successful rechallenge.

A systematic review of clozapine rechallenge cases following CAM was conducted. PubMed, EMBASE, Cinahl, and PsycINFO were searched for cases. Reference lists of retrieved articles and field experts were consulted to identify additional studies.

Forty-five cases were identified that described clozapine rechallenge, 31 of which were successful. Successful rechallenge cases generally used a slower dose titration regime with more frequent monitoring than standard clozapine initiation protocols; however, this data was not always completely recorded within cases. Six cases referred to published rechallenge protocols to guide their rechallenge.

The process, monitoring, and dose titration of clozapine rechallenge are inconsistently reported in the literature. Despite this, 69% of case reports detailed a successful rechallenge post CAM; noting limitations associated with reliance on case data. Ensuring published clozapine rechallenge cases report standardised data, including titration speed and monitoring frequencies, is required to guide the development and validation of guidelines for clozapine rechallenge.

Myocarditis represents a diverse group of inflammatory diseases affecting the heart muscle, with both infectious and non-infectious etiologies. Among the non-infectious causes, drug-induced hypersensitivity reactions are rare but serious. Isoniazid, a cornerstone in tuberculosis treatment, is known for its hepatotoxicity but has rarely been documented to cause hypersensitivity myocarditis.

We present a case of a 15-year-old girl from Eastern Turkmenistan who was admitted to our emergency department with altered consciousness and seizure activity. She was diagnosed with status epilepticus and treated accordingly. The patient, with no prior medical history, was found to have hypotensive shock and myocarditis upon further examination. A detailed history revealed she had ingested 45 tablets of expired isoniazid in a suicide attempt. She was treated with pyridoxine and supportive therapies, resulting in a gradual recovery.

This case underscores the critical need to consider drug-induced hypersensitivity myocarditis in the differential diagnosis of myocarditis, especially in patients with recent medication use. Prompt recognition and appropriate treatment with pyridoxine, steroid, and supportive cardiac care can be lifesaving. This case also highlights the importance of awareness regarding the potential cardiotoxic effects of isoniazid overdose.

Clozapine-induced inflammation, such as myocarditis and pneumonia, can occur during initial titration and can be fatal. Fever is often the first sign of severe inflammation, and early detection and prevention are essential. Few studies have investigated the effects of clozapine titration speed and concomitant medication use on the risk of clozapine-induced inflammation.

We evaluated the risk factors for clozapine-associated fever, including titration speed, concomitant medication use, gender and obesity, and their impact on the risk of fever and the fever onset date.

We conducted a case-control study. The medical records of 539 Japanese participants with treatment-resistant schizophrenia at 21 hospitals in Japan who received clozapine for the first time between 2010 and 2022 were retrospectively investigated. Of these, 512 individuals were included in the analysis. Individuals were divided into three groups according to the titration rate recommended by international guidelines for East Asians: the faster titration group, the slower titration group and the ultra-slower titration group. The use of concomitant medications (such as antipsychotics, mood stabilisers, hypnotics and anxiolytics) at clozapine initiation was comprehensively investigated. Logistic regression analysis was performed to identify the explanatory variables for the risk of a fever of 37.5°C or higher lasting at least 2 days.

Fever risk significantly increased with faster titration, male gender and concomitant use of valproic acid or quetiapine. No increased fever risk was detected with the use of other concomitant drugs, such as olanzapine, lithium or orexin receptor antagonists. Fever onset occurred significantly earlier with faster titration. Multivariate analysis identified obesity as being a factor that accelerated fever onset.

A faster titration speed and concomitant treatment with valproic acid and quetiapine at clozapine initiation increased the risk of clozapine-associated fever. Clinicians should titrate clozapine with caution and consider both the titration speed and concomitant medications.

Multisystem inflammatory syndrome in children is an inflammatory syndrome related to severe acute respiratory syndrome coronavirus 2 with a high risk of cardiovascular complications (vasoplegia, cardiac shock). We investigated the cardiac outcomes in multisystem inflammatory syndrome in children, focusing on the identification of predictors for late cardiac function impairment.

Clinical characteristics, conventional echocardiography (left ventricle ejection fraction, fractional shortening), 4-chamber left ventricular global longitudinal strain, and cardiac MRI of multisystem inflammatory syndrome in children patients (n = 48) were collected during admission, 6 weeks, 6 months, >12–≤18 months, and >18–≤24 months post-onset. Paired over-time patterns were assessed and multivariable regression analyses were performed to identify predictors for late global longitudinal strain impairment.

In total, 81.3% of patients had acute cardiac dysfunction (left ventricle ejection fraction <50% and/or fractional shortening <28%). The left ventricle ejection fraction and fractional shortening reached a plateau level ≤6 weeks, while the global longitudinal strain continued to decrease in the first 6 months post-onset (median –17.3%, P < 0.001 [versus acute]). At 6 months, 35.7% of the patients still had an abnormal global longitudinal strain, which persisted in 5/9 patients that underwent echocardiography >12–≤18 months post-onset and in 3/3 patients >18–≤24 months post-onset. In a multivariable analysis, soluble troponin T (>62.0 ng/L [median]) was associated with reduced global longitudinal strain at 6 months. Our cardiac MRI findings indicated acute myocardial involvement (increased T1/T2 value) in 77.8% (7/9), which recovered quickly without signs of fibrosis on convalescent cardiac MRIs.

Late global longitudinal strain impairment is seen in some multisystem inflammatory syndrome in children patients up to one-year post-onset. Careful cardiac follow-up in patients with elevated troponin in the acute phase and patients with persistent abnormal global longitudinal strain is warranted until resolution of the global longitudinal strain since the long-term implications of such abnormalities are still unclear.

In pediatric multisystem inflammatory syndrome and isolated viral myocarditis/myopericarditis, autonomic nervous system function can be evaluated by a non-invasive method called heart rate variability. This study aims to evaluate heart rate variability in these two groups by comparing them with each other. This is the first study assessing these values in these two groups of patients.

Patients who are diagnosed with multisystem inflammatory syndrome in children and isolated viral myocarditis/myopericarditis at a university hospital from September 2021 to February 2023 are screened by electrocardiography, echocardiography, and 24-hour Holter monitoring. A healthy control group, compatible in age and gender with the patient groups, was selected from healthy subjects that applied to the hospital for palpitation, murmur, and/or chest pain. Heart rate variability parameters and related laboratory markers were analyzed and compared among the three groups.

There were 30 patients with multisystem inflammatory syndrome in children, 43 patients with isolated viral myocarditis/myopericarditis, and 109 participants in the healthy control group. Statistically significant differences were found in most of the heart rate variability parameters: standard deviation of normal to normal intervals (SDNN), the mean of the 5- minute RR interval standard deviations (SDNNİ), the standard deviation of 5-minute R wave to R wave(RR) interval means (SDANN), the root mean square of successive RR interval differences (RMSSD), and the percentage of the beats with a consecutive RR interval difference of more than 50 ms (pNN50%), very low frequency, high frequency, low frequency, triangular index, and low frequency/high-frequency ratio. Multisystem inflammatory syndrome in children patients had impaired and declined heart rate variability values compared to the other two groups. In patients with myocarditis/myopericarditis, we couldn’t find a significant difference in these parameters with the control group.

Heart rate variability can be used as an important non-invasive autonomic function parameter in determining prognosis and treatment plans, especially in patients diagnosed with multisystem inflammatory syndrome in children. This impairment of autonomic activity could be more prominent in patients with decreased left ventricular systolic functions.

Public interest in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has been rising with regard to associated myocarditis. Thus, the objective of our study was to assess trends in public interest in myocarditis during the course of the pandemic and the SARS-CoV-2 vaccine rollout in the United States.

We conducted a longitudinal assessment of public interest in myocarditis, and its association with actual coronavirus disease 2019 (COVID-19) -related myocarditis during the first wave of the pandemic and SARS-CoV-2 vaccine-related myocarditis following vaccine rollout. To complete this objective, we used data from 3 sources: a report from the Morbidity and Mortality Weekly Report, the Vaccine Adverse Event Reporting database, and from Google Trends.

Results show that Relative Search Interest (RSI) was low before and during the initial phase of the pandemic and peaked in April 2021, during the initial vaccine push. The ratio of myocarditis related to the SARS-CoV-2 vaccines was considerably lower than the ratio of myocarditis from natural infection.

Search interest in myocarditis was low until SARS-CoV-2 vaccines were rolled out, in which media coverage intensely focused on a relatively small number of cases. This study highlights both the benefits of COVID-19 vaccine uptake and the impact of the media on public interest