1356468 - Titin Cardiomyopathy in a Patient with Multiorgan Sarcoidosis

A 61-year-old African-American woman with a history of pulmonary sarcoidosis presented with severe, shortness of breath. She had family history of inherited cardiomyopathy with her brother and nephew having undergone heart transplantation for Titin related inherited cardiomyopathy.

Patient was initially diagnosed with cardiogenic shock. EKG demonstrated sinus tachycardia and nonspecific T wave changes, high sensitivity troponin T was negative, but she was found to have significantly elevated NT-pro-BNP.

Diagnostic Techniques and Their Most Important Findings:

TTE demonstrated a left ventricular ejection fraction (LVEF) of 32%, impaired right ventricular function.

Left and right heart catheterization revealed elevated filling pressures, reduced cardiac index, no significant coronary artery disease.

Patient underwent a CMR with and without contrast (Figure 1). It showed a normal sized left ventricle with moderately decreased LVEF of 37%. It also demonstrated low indexed left ventricular mass, and late gadolinium enhancement (LGE) in a nonvascular distribution in the basal and mid anterior septum and the basal and mid inferolateral wall, suggestive of cardiac sarcoidosis (CS). There was a global increase in T2 relaxation time on T2 mapping (Figure 2). It also revealed extensive pathology in the lungs with evidence of mediastinal and hilar adenopathy, consistent with a diagnosis of pulmonary sarcoidosis.

To evaluate for CS, the patient underwent an FDG PET study (Figure 3). It revealed no active inflammatory myocardial process, there was extensive abnormal extra-cardiac tracer uptake in various groups of mediastinal nodes, peri-hilar nodes, peri-aortic nodes, and nodes in the porta-hepatis and the spleen, consistent with a diagnosis of systemic sarcoidosis.

The patient improved clinically and was discharged home on milrinone. She underwent outpatient genetic testing, which revealed Titin gene mutation.

Learning Points from this Case:

Titin gene mutation is a common cause of inherited heart disease, present in approximately 25% of familial cases of dilated cardiomyopathy [1,2,3]. Our case describes an unusual presentation of Titin cardiomyopathy in a patient with systemic sarcoidosis. Given the severe extra-pulmonary sarcoidosis and development of acute heart failure, the patient was initially suspected to have CS. The LGE pattern was typical for CS and the T2 values were elevated globally, which indicates increased intracellular and/or extracellular edema. However, the FDG PET study showed no myocardial uptake of tracer, ruling out active CS. It has been shown that there is global elevation in T2 values because of myocardial edema in acute decompensated heart failure from venous congestion [4]. The subsequent diagnosis of Titin gene mutation, along with an unknown recent insult is postulated to be the likely cause for patient’s acute heart failure. However, the presence of late gadolinium enhancement in a pattern typically seen in CS in the absence of FDG uptake on cardiac PET imaging could indicate a prior episode of active CS.