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Fulminant but Not Fatal

      Presentation

      Myocarditis is an inflammatory disease of the myocardium that can present in myriad ways, ranging from an insidious course to a fulminant form resulting in cardiogenic shock. The diagnosis of this disease is challenging and relies heavily on clinical suspicion, as diagnostic studies have relatively low sensitivity and specificity.
      A 23-year-old Caucasian woman with no past medical history first noted palpitations during chemistry class. The following morning she felt substernal pressure. Later that day she developed pleuritic chest pain and had several episodes of nonbloody, nonbilious emesis. She also began to experience dyspnea with minimal activity and bilateral lower extremity swelling; therefore, she presented to the Emergency Department. She denied paroxysmal nocturnal dyspnea, orthopnea, lightheadedness, or dizziness.
      The patient was a social drinker and an occasional marijuana smoker. She had no history of pregnancy, sexually transmitted infections, and was monogamous with one male partner. She had vacationed in Mexico 1 month previously and had hiked in Northern California 5 days prior to presentation. Her family medical history was unremarkable. A review of systems was negative for arthralgias, syncope, cough, rash, or photosensitivity.

      Assessment

      On examination, the patient was nontoxic, heart rate was 48 beats per minute, and blood pressure was 110/70 mm Hg. Her respiratory rate was 15 breaths per minute, and oxygen saturation was 99% on ambient air. Her jugular venous pulse was elevated to 12 cm with bibasilar pulmonary rales. The cardiac point of maximal impulse was nondisplaced, heart rate was bradycardic and regular with no murmurs, rubs, or gallops. She had normoactive bowel sounds with mild epigastric tenderness and mild bilateral lower extremity edema. There were no skin lesions.
      An electrocardiogram showed complete heart block with a junctional escape rhythm at 45 beats per minute with nonspecific interventricular conduction delay and evidence of septal infarct (Figure 1). Chest radiograph showed a normal cardiac silhouette with increased vascular markings bilaterally. Laboratory data were notable for: white blood cell count 16,900/mm3, hemoglobin 12.4 g/dL, troponin I 18.0 ng/mL (ref < 0.05), and a urine toxicology screen and urine pregnancy test were both negative. Erythrocyte sedimentation rate 68 (ref 0-20) and C-reactive protein 17.6 mg/dL (ref 0-0.8 mg/dL) were markedly abnormal.
      Figure thumbnail gr1
      Figure 1Complete heart block with junctional escape rhythm, nonspecific interventricular conduction delay, fusion beats, and septal infarct.
      A transvenous pacemaker was placed on admission because of severe conduction system disease. A transthoracic echocardiogram revealed a left ventricular ejection fraction of 40% with mild global hypokinesis and no valvular abnormalities. The right ventricle was mildly dilated and hypokinetic. Comprehensive viral and bacterial studies were negative.
      On the third morning of hospitalization the patient had an acute loss of consciousness. Telemetry showed torsades de pointes and subsequent ventricular fibrillation (Figure 2). The patient received immediate direct current external defibrillation, which restored sinus rhythm, and she regained consciousness. An intravenous infusion of lidocaine and high-dose steroids were initiated and coronary angiography was urgently performed, which revealed normal coronary arteries including no evidence of coronary dissection. During cardiac catheterization, multiple biopsy specimens of right ventricular myocardium were obtained.
      Figure thumbnail gr2
      Figure 2Torsades de pointes with subsequent ventricular fibrillation.
      Intravenous immunoglobulin (IVIG) therapy for viral-mediated fulminant myocarditis was initiated based on the patient's history, clinical presentation, and progressive decline. Cardiac computed tomography showed no evidence of delayed enhancement with gadolinium; therefore, infiltrative myocardial disease was unlikely. Right ventricular endomyocardial biopsy revealed profuse lymphocytic infiltration and myocytolysis consistent with fulminant viral myocarditis (Figure 3). Polymerase chain reaction studies on the cardiac biopsy specimens were negative for a wide range of pathogens, including enteroviruses and herpes viruses.
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      Figure 3Endomyocardial biopsy with infiltrating lymphocytes and myocytolysis, diagnostic of myocarditis.

      Diagnosis

      Fulminant myocarditis is defined by clinical features of myocarditis with severe hemodynamic compromise or arrhythmias. Diagnosis of viral myocarditis is challenging because there is no widely available noninvasive test. Thus, diagnostic evaluation for the cause of fulminant myocarditis can vary widely based on the patient's clinical presentation, risk factors, exposure, and physical examination.
      In this country the most common cause of myocarditis is viral. Patients commonly present with a preceding viral prodrome that can progress to myocardial involvement with chest pain, heart failure, or cardiogenic shock. The more common viral etiologies are enteroviruses (eg, Coxsackie B virus), parvovirus B19, human herpesvirus 6, adenovirus, and cytomegalovirus.
      • Kuhl U.
      • Pauschinger M.
      • Noutsias M.
      • et al.
      High prevalence of viral genomes and multiple viral infections in the myocardium of adults with “idiopathic” left ventricular dysfunction.
      While patients with acute, nonfulminant myocarditis can have an insidious and variable clinical presentation, fulminant myocarditis presents with dramatic symptoms of cardiovascular collapse, which include rapid onset of severe heart failure, life-threatening arrhythmias, end-organ damage, and cardiogenic shock. The clinical evaluation includes an electrocardiogram, which may demonstrate nonspecific changes, low voltage due to associated pericardial effusion or myocardial edema, interventricular conduction delays, tachyarrhythmias and bradyarrhythmias, or even a pseudoinfarction pattern.
      • Kindermann I.
      • Barth C.
      • Mahfoud F.
      • et al.
      Update on myocarditis.
      • Biesbroek P.S.
      • Beek A.M.
      • Germans T.
      • Niessen H.W.
      • van Rossum A.C.
      Diagnosis of myocarditis: current state and future perspectives.
      Echocardiography is an essential diagnostic tool for detection of other causes of heart failure such as valvular disease, myocardial infarction, infiltrative processes, and congenital anomalies. Fulminant myocarditis patients often have normal cardiac chamber sizes with increased septal thickness secondary to acute myocardial edema and severe systolic dysfunction.
      • Kindermann I.
      • Barth C.
      • Mahfoud F.
      • et al.
      Update on myocarditis.
      Laboratory findings may show evidence of end-organ failure such as elevated blood urea nitrogen, creatinine, or transaminases, compared with nonfulminant myocarditis. Elevated cardiac biomarkers indicate cardiac myonecrosis. Cardiac magnetic resonance imaging is considered the most accurate noninvasive modality for diagnosing myocarditis.
      • Gupta S.
      • Markham D.W.
      • Drazner M.H.
      • Mammen P.P.
      Fulminant myocarditis.
      Magnetic resonance imaging can detect acute regional myocardial necrosis, microvascular obstruction (by late gadolinium enhancement), edema, and hemorrhage.
      • Ashrafpoor G.
      • Andreoletti L.
      • Bruneval P.
      • et al.
      Fulminant human herpesvirus 6 myocarditis in an immunocompetent adult: role of cardiac magnetic resonance in a multidisciplinary approach.
      Endomyocardial biopsy remains the gold standard diagnostic test for myocarditis. A positive biopsy has a high positive predictive value; however, because of the patchy infiltrative nature of myocarditis, a negative biopsy has a low negative predictive value.
      • Ginsberg F.
      • Parrillo J.E.
      Fulminant myocarditis.
      Evidence of infiltrating lymphocytes and myocytolysis confirms the diagnosis of viral myocarditis based on Dallas criteria.
      • Kindermann I.
      • Barth C.
      • Mahfoud F.
      • et al.
      Update on myocarditis.
      Our patient's biopsy was consistent with lymphocytic myocarditis showing abundant infiltrative lymphocytes, interstitial edema, and myocytolysis (Figure 3).

      Management

      The mainstay of therapy for fulminant myocarditis is supportive care. Our patient was treated with diuretic therapy to lower ventricular filling pressures and placed on an angiotensin-converting enzyme inhibitor to decrease cardiac afterload and provide neurohormonal blockade. Beta-blockade to reduce myocardial oxygen demand was withheld due to the patient's bradycardia and evidence of complete heart block. An external wearable defibrillator was utilized to protect from malignant ventricular arrhythmias during recovery.
      Patients with acute fulminant myocarditis, compared with those who have acute nonfulminant myocarditis, are more likely to have a full recovery of left ventricular function. Fulminant myocarditis has been deemed to be an independent predictor of survival when compared with patients with acute nonfulminant myocarditis.
      • McCarthy 3rd, R.E.
      • Boehmer J.P.
      • Hruban R.H.
      • et al.
      Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis.
      Optimal treatment of our patient relied heavily on supportive care with both heart failure and arrhythmia management. However, as she continued to deteriorate, reflected by malignant arrhythmias, additional immunosuppressive therapy with intravenous immunoglobulin (IVIG) was administered. Although there are only limited studies on the efficacy of immunosuppressive therapy in fulminant myocarditis, several reports favor its use. IVIG has resulted in decreased incidence of both ventricular arrhythmias and atrioventricular block, as well as improved left ventricular function.
      • Yu D.Q.
      • Wang Y.
      • Ma G.Z.
      • et al.
      Intravenous immunoglobulin in the therapy of adult acute fulminant myocarditis: a retrospective study.
      • Kato S.
      • Morimoto S.
      • Hiramitsu S.
      • et al.
      Successful high-dose intravenous immunoglobulin therapy for a patient with fulminant myocarditis.
      • Goland S.
      • Czer L.S.
      • Siegel R.J.
      • et al.
      Intravenous immunoglobulin treatment for acute fulminant inflammatory cardiomyopathy: series of six patients and review of literature.
      • Kim H.S.
      • Sohn S.
      • Park J.Y.
      • Seo J.W.
      Fulminant myocarditis successfully treated with high-dose immunoglobulin.
      On follow-up 4 months later, the patient's ejection fraction had increased to low normal (50%) and she was asymptomatic. Ten months later she had no cardiac symptoms but was being treated for severe anxiety for fear of repeat cardiac arrest. In conclusion, viral myocarditis is a diagnostic challenge with widely varying clinical presentations. It warrants consideration in a young person with new-onset acute cardiac failure, arrhythmias, and a recent viral prodrome.

      References

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        • Pauschinger M.
        • Noutsias M.
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        Diagnosis of myocarditis: current state and future perspectives.
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