Myocarditis, Typhoid

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Diagnosis and reasoning

This patient has presented with acute retrosternal pain radiating to his left shoulder, which is worsened by exertion and associated with dyspnea; this is an acute coronary syndrome (ACS) until proven otherwise. An ECG confirms the clinical suspicion by revealing ST-segment elevations in the anterolateral leads, i.e. this is an ST-elevation myocardial infarction (STEMI). As soon as a STEMI is diagnosed, the very first action taken should be administration of aspirin; time is muscle and each and every second counts. In addition, the 2013 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline for the management of STEMI recommends primary percutaneous coronary intervention (PCI) in all such patients who have symptoms of less than 12 hours' duration. However, angiography reveals pristine coronary arteries, forcing us to second-guess our diagnosis! Re-evaluating the findings so far, the presence of ST-elevations indicates that there is definitely some type of cardiac pathology. Acute pericarditis can also give rise to ST-elevations; however, these are typically downwardly convex. Aortic dissection can also give rise to ST-elevations, if the dissection spreads to encompass the coronary os; however, this would have been detected upon angiography. Focal myocarditis (which is an uncommon variant of acute myocarditis) can also give rise to ST segment elevations; if so, an echocardiogram would be expected to reveal supportive features. And the echocardiogram does indeed display findings suggestive of myocarditis: hypokinetic segments in the anterior and lateral walls with classical 'jerky' movements, along with left ventricular dilatation and a reduced ejection fraction. The minimally elevated cardiac enzymes (which are far lower than what one would expect in a STEMI) lend further credence to this diagnosis. The question now arises: what might be the underlying cause for the myocarditis? Note the history of watery diarrhea, starting soon after his return from Brazil. This hints that the myocarditis might be secondary to an infection; the diagnosis of typhoid infection in his father provides the final clue as to the likely etiology. Salmonella typhi infection is well known to cause Myocarditis, although the vast majority of such patients are asymptomatic. Where this is suspected, immediate treatment with IV antibiotics (i.e. Ceftriaxone) is indicated, after obtaining blood and stool cultures. Other key aspects of the management include supportive and pharmacological management of the myocarditis; ACE Inhibitors play a critical role here. As he is likely to be bed-bound for some time, DVT prophylaxis is also essential. Considering the patient in this case; blood cultures turned out to be negative, but stool cultures were positive for S. typhi. His symptoms resolved rapidly after treatment with IV Ceftriaxone; he was discharged home after 2 weeks in hospital.


Discussion

The emergence of multiresistant strains of Salmonella typhi has resulted in a high prevalence of typhoid fever in developing nations worldwide; endemic regions include South Asia, South-East Asia, China, Africa, and Central and South America. Salmonella spp. have the ability to adhere to damaged endothelium, predisposing individuals to complications rarely seen with other Gram-negative organisms; myocarditis is one of these complications, with its association with S. typhi first described in 1884. It is interesting to note that myocarditis in typhoid fever may be more common than suspected; for example, in an Indian series of 100 patients with bacteriologically or serologically proven typhoid fever, 7 cases were found to have clinical evidence of myocarditis, and 46 cases had ECG evidence of myocarditis. Similar to other patients with acute myocarditis, these individuals may manifest chest pain, shortness of breath, fainting spells, reduced functional capacity, fatigue and malaise, and new-onset atrial or ventricular arrhythmias. If the pericardium is also involved (myopericarditis), signs and symptoms suggestive of pericarditis may also be present. Due to the concurrent typhoid infection, they may also manifest fever, malaise, headache and abdominal pain; diarrhea is present in the initial stage of the illness, but later on, constipation may become prominent. Most current vaccines against typhoid are not completely effective in preventing infection (especially if bacterial counts are high); thus vaccination does not necessarily exclude this diagnosis. The diagnosis of typhoid induced myocarditis requires detection of both myocarditis as well as typhoid fever (and where necessary, exclusion of other likely causative etiologies for the myocarditis). Considering the myocarditis, the ECG and echocardiographic findings in these patients are similar to those encountered in myocarditis due to other causes. In case series of these patients, the commonest ECG abnormality encountered was prolongation of the QT interval; nonspecific ST-T changes, bundle branch blocks, first degree atrioventricular block and arrhythmias were also noted. The echocardiographic findings ranged from global hypokinesis and dilation, to segmental wall motion abnormalities which mimicked the findings of an infarction. Where ECGs and echocardiography are equivocal, Cardiac MRI may help by identifying areas of cardiac edema, hyperemia, and necrosis. Endomyocardial biopsy is rarely necessary. The diagnosis of typhoid fever revolves around isolation of the organism; this may require blood, stool and/or urine cultures. While bone marrow cultures are the most sensitive test, this is rarely performed, owing to its invasive nature. Note that the Widal test has a low sensitivity and specificity in endemic areas; thus, it is not generally recommended now. Most of these patients recover with pharmacologic therapy alone, and have a good prognosis; their management is similar to that of patients with other forms of myocarditis, with the addition of antibiotic therapy to treat the typhoid infection.


Take home messages

  1. Typhoid fever is a rare cause of acute myocarditis.
  2. Focal myocarditis can mimic the clinical and ECG findings of a STEMI.
  3. Cardiac MRI is a useful tool for the diagnosis of acute myocarditis where other evidence is equivocal.
  4. Most patients with acute (typhoid) myocarditis have an excellent long-term prognosis.

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