When One Diagnosis Is Not Enough: From Acute Myocarditis to Arrhythmogenic Cardiomyopathy: Hickam’s Dictum in Action

Description of Clinical Presentation: A 36-year-old female with no prior medical history, presented with acute chest pain and dyspnea. Serial troponin rose from 5407 to 6671 ng/L. EKG showed sinus tachycardia. Chest computed tomography (CT) demonstrated bilateral ground-glass opacities. Transthoracic echocardiography showed a left ventricular ejection fraction of 30%. Normal coronary angiography prompted referral for cardiac magnetic resonance (CMR) imaging.

Diagnostic Techniques and Their Most Important Findings: CMR revealed a moderately enlarged left ventricle (LV), moderately decreased LV ejection fraction of (EF)28%, elevated myocardial T2 signal and subepicardial to mid-myocardial late gadolinium enhancement (LGE) in a non-territorial pattern, consistent with acute myocarditis. Right ventricular (RV) size was normal with borderline decreased EF of ~38%. Endomyocardial biopsy confirmed subacute myocarditis with eosinophils. A diagnosis of eosinophilic myocarditis was made. Guideline-directed therapy and corticosteroids were initiated.

Five months later, she re-presented in cardiogenic shock. Repeat CMR demonstrated severe biventricular dysfunction (LV EF ~25%, RV EF ~26%), thrombi in all four chambers, and persistent—though improving—subepicardial LGE, most pronounced in the anterior segments. New circumferential subendocardial RV edema, greatest in the RV outflow tract, was also noted.

The patient deteriorated rapidly, requiring intra-aortic balloon pump support; systemic embolization led to right renal infarction. She underwent urgent orthotopic heart transplantation. Pre-transplant genetic testing revealed desmoplakin-associated cardiomyopathy with arrhythmogenic phenotype. Histopathologic examination of the explanted heart confirmed the genetic diagnosis and further demonstrated superimposed non-necrotizing granulomatous myocarditis, characterized by a brisk perivascular lymphoplasmacytic infiltrate, in continuity with her previously documented eosinophilic myocarditis.

Learning Points from this Case: This case exemplifies Hickam’s dictum: not all clinical findings can be attributed to a single diagnosis. The patient initially manifested eosinophilic myocarditis but was ultimately found to harbor desmoplakin-associated arrhythmogenic cardiomyopathy (DSP-ACM), a condition known to present with myocarditis-like “hot phases.” The LGE distribution reflected dual pathology: subendocardial enhancement with wall thinning and intracavitary thrombi consistent with eosinophilic myocarditis, contrasted with near-circumferential subepicardial to mid-myocardial enhancement characteristic of DSP-ACM with diffuse fibrosis.
CMR proved pivotal, establishing the initial diagnosis, delineating progression with multi-chamber thrombi, and informing the decision for transplantation in the setting of advanced dysfunction and embolic complications. Beyond diagnosis, CMR remains the cornerstone for recognizing overlapping myocardial pathologies, with complementary input from clinical data, histopathology, and genetics to achieve diagnostic precision and optimize outcomes.

4-Chamber LGE with non-territorial distribution with corresponding SAX with LGE and T2 showing edema
Second CMR SAX view showing LV and RV thrombi, with T2 image with corersponding edema
Second CMR: 4 Chamber view with LGE and 3 Chamber view showing both LV and RV thrombi