Importance
Acute myocarditis, defined as a sudden inflammatory injury to the myocardium, affects approximately 4 to 14 people per 100 000 each year globally and is associated with a mortality rate of approximately 1% to 7%.


Observations
The most common causes of myocarditis are viruses, such as influenza and coronavirus; systemic autoimmune disorders, such as systemic lupus erythematosus; drugs, such as immune checkpoint inhibitors; and vaccines, including smallpox and mRNA COVID-19 vaccines. Approximately 82% to 95% of adult patients with acute myocarditis present with chest pain, while 19% to 49% present with dyspnea, and 5% to 7% with syncope. The diagnosis of myocarditis can be suggested by presenting symptoms, elevated biomarkers such as troponins, electrocardiographic changes of ST segments, and echocardiographic wall motion abnormalities or wall thickening. Cardiac magnetic resonance imaging or endomyocardial biopsy are required for definitive diagnosis. Treatment depends on acuity, severity, clinical presentation, and etiology. Approximately 75% of patients admitted with myocarditis have an uncomplicated course, with a mortality rate of approximately 0%. In contrast, acute myocarditis that is complicated by acute heart failure or ventricular arrhythmias is associated with a 12% rate of either in-hospital mortality or need for heart transplant. Approximately 2% to 9% of patients have hemodynamic instability, characterized by inability to maintain adequate end-organ perfusion, and require inotropic agents, or mechanical circulatory devices, such as extracorporeal life support, to facilitate functional recovery. These patients have an approximately 28% rate of mortality or heart transplant at 60 days. Immunosuppression (eg, corticosteroids) is appropriate for patients who have myocarditis characterized by eosinophilic or giant cell myocardial infiltrations or due to systemic autoimmune disorders. However, the specific immune cells that should be targeted to improve outcomes in patients with myocarditis remain unclear.


Conclusions and Relevance
Acute myocarditis affects approximately 4 to 14 per 100 000 people per year. First-line therapy depends on acuity, severity, clinical presentation, and etiology and includes supportive care. While corticosteroids are often used for specific forms of myocarditis (eg, eosinophilic or giant cell infiltrations), this practice is based on anecdotal evidence, and randomized clinical trials of optimal therapeutic interventions for acute myocarditis are needed.

Diagnosis and Treatment of Acute Myocarditis: A Review.

Intrauterine pressure was monitored in vivo in oestrogen-treated ovariectomized ewes before, during and after treatment with progesterone (50 mg s.c./day for 3 days). Progesterone reversibly reduced the frequency and amplitude of myometrial activity and abolished uterine reactivity to oxytocin (i.v.) and PGF-2alpha (intrauterine infusion). The rate of rise of intrauterine pressure during active pressure cycles was significantly reduced. These results confirm that the action of progesterone on the ovine myometrium is comparable to the classic progesterone 'block'. The intrauterine infusion of PGF-2alpha (10 microgram/min), which elicited a marked mechanical response in the control animals, failed to stimulate the progesterone-'blocked' uterus, suggesting that the inhibition produced by progesterone is due to a direct action of the hormone on the uterine muscle and not to an indirect mechanism operating through endometrial prostaglandin output.

/pdf/demonstration-that-progesterone-blocks-uterine-activity-in-2qz2ka5h15.pdf

Demonstration that progesterone 'blocks' uterine activity in the ewe in vivo by a direct action on the myometrium.

A multifactorial approach was attempted to establish the sequence of events that lead to parturition in the miniature pig. Uterine electrical activity recorded with chronic electrodes implanted in the uterine muscle was correlated with concurrent maternal plasma levels of progesterone, estrone, estradiol-1713 and oxytocin. In 7 sows that farrowed at normal term the period of observation covered the last 3 weeks of pregnancy up to the end of parturition. During late pregnancy the uterine electromyographs (EMGs) consisted of irregular episodes ( 3.5 mm duration) which occurred close to electrodes that had been implanted on uterine segments containing a fetus. Empty parts of the uterus remained relatively inactive. There were no significant changes in the mean plasma steroid concentrations and myometrial activity over the last 3 weeks of gestation. Plasma oxytocin concentrations remained below 1.2 pU/mI in 6 animals that were sampled between 12 and 2 days prior to parturition. Between -24 and -10 h before expulsion of the first piglet, mean concentrations of progesterone had significantly fallen and those of estrogens had increased. This coincided with behavioral changes of the sow (nest-building) but myometrial activity at this stage was similar to that recorded on the previous days. It was only between -9 and -4 h before the first piglet was born that the pattern of the EMG5 changed and regular phases of electrical discharges appeared with increasing frequency (7-12/h) in all part of the uterus. At the same time oxytocin concentrations in peripheral plasma were elevated. During delivery of the piglets the mean frequency of the phases of electrical discharges increased further (18-20/h), their duration being significantly shorter than in the previous few hours. Oxytocin concentrations reached highest values at this stage, estrogen concentrations were already falling and progesterone had reached values below 4 nglml in all sows.

/pdf/myometrial-electrical-activity-and-plasma-concentrations-of-5biltc8g4o.pdf

Myometrial electrical activity and plasma concentrations of progesterone, estrogens and oxytocin during late pregnancy and parturition in the miniature pig.

The neurohypophysial hormones

In the past decade there has been a growing interest in understanding sex and gender differences in myocarditis and dilated cardiomyopathy (DCM), and the purpose of this review is to provide an update on this topic including epidemiology, pathogenesis and clinical presentation, diagnosis and management. Recently, many clinical studies have been conducted examining sex differences in myocarditis. Studies consistently report that myocarditis occurs more often in men than women with a sex ratio ranging from 1:2–4 female to male. Studies reveal that DCM also has a sex ratio of around 1:3 women to men and this is also true for familial/genetic forms of DCM. Animal models have demonstrated that DCM develops after myocarditis in susceptible mouse strains and evidence exists for this progress clinically as well. A consistent finding is that myocarditis occurs primarily in men under 50 years of age, but in women after age 50 or post-menopause. In contrast, DCM typically occurs after age 50, although the age that post-myocarditis DCM occurs has not been investigated. In a small study, more men with myocarditis presented with symptoms of chest pain while women presented with dyspnea. Men with myocarditis have been found to have higher levels of heart failure biomarkers soluble ST2, creatine kinase, myoglobin and T helper 17-associated cytokines while women develop a better regulatory immune response. Studies of the pathogenesis of disease have found that Toll-like receptor (TLR)2 and TLR4 signaling pathways play a central role in increasing inflammation during myocarditis and in promoting remodeling and fibrosis that leads to DCM, and all of these pathways are elevated in males. Management of myocarditis follows heart failure guidelines and there are currently no disease-specific therapies. Research on standard heart failure medications reveal important sex differences. Overall, many advances in our understanding of the effect of biologic sex on myocarditis and DCM have occurred over the past decade, but many gaps in our understanding remain. A better understanding of sex and gender effects are needed to develop disease-targeted and individualized medicine approaches in the future.

/pdf/sex-and-gender-differences-in-myocarditis-and-dilated-1z17agm5.pdf

Sex and gender differences in myocarditis and dilated cardiomyopathy: An update

/pdf/electrophysiological-observations-of-uterine-motility-during-1e7bzs57r2.pdf

Electrophysiological observations of uterine motility during the oestrous cycle in sheep.

Investigate trends in myocarditis incidence and prognosis in Sweden during 2000-2014. Little data exist concerning population-trends in incidence of hospitalizations for myocarditis and subsequent prognosis. Linking Swedish National Patient and Cause of Death Registers, we identified individuals ≥ 16 years with first-time diagnosis of myocarditis during 2000-2014. Reference population, matched for age and birth year (n = 16,622) was selected from Swedish Total Population Register. Among the 8 679 cases (75% men, 64% < 50 years), incidence rate/100,000 inhabitants rose from 6.3 to 8.6 per 100,000, mostly in men and those < 50 years. Incident heart failure/dilated cardiomyopathy occurred in 6.2% within 1 year after index hospitalization and in 10.2% during 2000-2014, predominantly in those ≥ 50 years (12.1% within 1 year, 20.8% during 2000-2014). In all 8.1% died within 1 year, 0.9% (< 50 years) and 20.8% (≥ 50 years). Hazard ratios (adjusted for age, sex) for 1-year mortality comparing cases and controls were 4.00 (95% confidence interval 1.37-11.70), 4.48 (2.57-7.82), 4.57 (3.31-6.31) and 3.93 (3.39-4.57) for individuals aged < 30, 30 to < 50, 50 to < 70, and ≥ 70 years, respectively. The incidence of myocarditis during 2000-2014 increased, predominantly in men < 50 years. One-year mortality was low, but fourfold higher compared with reference population. 

/pdf/trends-in-myocarditis-incidence-complications-and-mortality-ttfkaxjj.pdf

Trends in myocarditis incidence, complications and mortality in Sweden from 2000 to 2014

Elektrophysiologische Untersuchungen über die Uteruskontraktionen des Schafes während der Trächtigkeit und der Geburt

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Electrophysiological observations of uterine motility during the oestrous cycle in sheep.

Trends in myocarditis incidence, complications and mortality in Sweden from 2000 to 2014

Elektrophysiologische Untersuchungen über die Uteruskontraktionen des Schafes während der Trächtigkeit und der Geburt