The male patient was born spontaneously at term after an uneventful pregnancy despite the detection of cardiac tumors at 36 weeks by fetal echocardiography. After birth, he was diagnosed as having TSC based on the diagnostic criteria of white leaf-shaped hypomelanotic macules, a subependymal nodule, and a retinal hamartoma. Multiple intramural cardiac tumors of 5-25 mm in diameter were found by transthoracic echocardiography (Fig. 1a, b). Soon after birth, the boy exhibited numerous episodes of premature supraventricular contractions (PSVC), multifocal premature ventricular contractions (PVC), and non-sustained ventricular tachycardia (NSVT). Mexiletine treatment was commenced at 1 month of age (Fig. 2a). Since a maximum NSVT of 14 beats at a rate of 269 bpm was detected by Holter electrocardiography (ECG) at the age of 5 months, we added disopyramide to his therapy regime, which resulted in a decline in NSVT frequency. The tumors gradually diminished in size, but his frequent PSVC and tachycardia persisted.
At 20 months of age, the patient's cardiac function was preserved; echocardiography revealed a left ventricular end-diastolic diameter (LVDd) of 30.8 mm (Z-score: 0.5) and a left ventricular fractional shortening (LVFS) of 28 %.
At 23 months of age, he was admitted to our hospital due to cardiac dysfunction. His body height and weight were 85 cm (+0.1 SD) and 11.5 kg (+0.1 SD), respectively. Blood pressure was 88/47 mmHg. Heartbeat was irregular at 134 bpm without extra heart sounds or murmurs. Neither hepatomegaly nor pretibial edema was observed. Laboratory data including blood cell counts, electrolytes, CRP, CK-MB, troponin T, glucose, ammonia, lactic and pyruvic acid, and thyroid function showed no abnormalities. However, brain natriuretic peptide (BNP) and human atrial natriuretic peptide levels were markedly increased at 619 pg/ml (normal range: < 20 pg/ml) and 654 pg/ml (normal range: < 43 pg/ml), respectively. There were no significant increases of viral antibody titers in his serum, including those for the Coxsackie virus, adenovirus, or echovirus. His cardiothoracic ratio was 64 % on a chest radiograph. Twelve-lead ECG revealed irregular tachycardia (139 bpm) and sporadic PSVC without ST abnormality or wide QRS duration (Fig. 3). According to Holter ECG, the patient's total number of heartbeats (THB) was 195,807 per day and mean heart rate was 136 bpm. Frequent multifocal PVC (20,883 beats per day; 10.7 % of THB) and PSVC (29,733 beats per day; 15.2 % of THB) were also noted. Echocardiography revealed cardiac dilatation and diffuse hypokinesis, LVDd of 45.2 mm (Z-score: 3.0), and LVFS of 15 % (Fig. 1c). Severe mitral insufficiency caused by the expansion of the mitral annulus was detected as well. His coronary arteries were normal. Surprisingly, his cardiac tumors had diminished in size and were recognizable as a small bright area in the posterior mitral valve (Fig. 1d).
Diuretics and angiotensin converting enzyme inhibitor were administered as anti-heart failure therapies. To control tachycardia and reduce afterload on the failing heart, we also commenced oral administration of carvedilol at 0.15 mg/day (0.01 mg/kg/day) that was gradually increased to 3.0 mg/day (0.3 mg/kg/day) 3 months later. Although frequent PSVC persisted, the boy's mean HR gradually decreased and the incidence of PVC and its short run became markedly diminished (Fig. 2a). BNP gradually decreased to within normal range. The abnormal values of LVFS and LVDd persisted for 1 year after the initiation of carvedilol treatment, but both parameters eventually improved to normal levels (34 % and 35.8 mm [Z-score: 0.8], respectively) by the age of 4 years (Fig. 2b).