Case presentation

We present a 14-year-old African American male with a history of pulmonary artery atresia with intact ventricular septum and right-ventricular-dependent coronary circulation, palliated via bidirectional cavopulmonary anastomosis and Fontan completion at 3 years of age. He developed medically refractory protein-losing enteropathy and underwent orthotopic heart transplantation at 11 years of age. The donor was a similar-aged male who suffered an out-of-hospital cardiac arrest due to a respiratory cause.

For his second annual evaluation (24 months post-transplant), he was on no cardiac medications, and immunosuppression was monotherapy with sirolimus. Baseline transthoracic echocardiography showed a normal left ventricular size (left ventricular end-diastolic diameter 45 mm (z-score = 0.8); left ventricular end-systolic diameter 28 mm (z-score = 0.1)) with ejection fraction of 61% by M-mode, trivial mitral valve regurgitation, and borderline right ventricular size with normal systolic function. Cardiac catheterisation was performed with normal coronary angiography (International Society of Heart and Lung Transplantation Coronary Artery Vasculopathy grade 0), normal cardiac output via Fick estimate, and left ventricular end-diastolic pressure of 11 mmHg. Endomyocardial biopsy was performed, ultimately demonstrating no evidence for antibody- or cell-mediated rejection. He then proceeded to dobutamine stress echocardiography according to an institutional research protocol, recently published by Fine et al. ^{Reference Fine, Greenway and Mulvagh3} Resting electrocardiogram and echocardiogram were normal. Dobutamine was titrated according to protocol, ^{Reference Fine, Greenway and Mulvagh3} starting at a dose of 5 μg/kg/minute, followed by 3-minute stages of increasing doses of 10, 20, and 30 to a maximal dose of 40 μg/kg/minute, to achieve 75% of the age-predicted maximal target heart rate, calculated as 220 minus age in years. Atropine (2 mg) was used to achieve target heart rate. Maximal achieved peak heart rate was 162 beats per minute. At peak stress (40 mcg/kg/minute), ventricular ectopy developed, and dobutamine was immediately discontinued. This was followed by >1 mm ST-segment elevation in anterolateral leads, and ST-segment elevation in inferolateral leads at late recovery (Figure 1). Echocardiography demonstrated left ventricular mid-ventricular hypokinesis and apical akinesis at peak stress, with increased end-systolic volume and acute reduction in the ejection fraction to 35%. At late recovery, left ventricular end-systolic volume further increased, with ejection fraction decreasing to 25% with progression to left ventricular apical and mid-ventricular akinesis (Figure 2; Supplementary Video S1). Emergent catheterisation was performed with coronary angiography demonstrating no coronary artery dissection, vasospasm, or occlusion. Left ventricular end-diastolic pressure was now severely elevated at 28 mmHg with no outflow tract obstruction.

Figure 1 Electrocardiographic abnormalities progression in leads I, aVF, V1, V3 and V6. ECG was normal at baseline. At peak stress, there is ST-segment elevation in leads I, aVL and V3, followed by ST-segment elevation in aVF and V6 at late recovery. Note that corrected QT-segment was normal throughout the study (411 msec at peak stress and 423 msec at late recovery). At 3 weeks after DSE, there is only T-wave inversion in lead I and aVL.

Figure 2 Images were obtained from the apical 4-chamber view at end-diastole (left) and end-systole (right). Note progressive decrease in left ventricular ejection fraction and increase in end-systolic volumes from baseline (1) to peak stress (2) and late recovery (3).

The patient was admitted to the paediatric ICU with mild shortness of breath and bilateral rales on exam. Oxygen saturation was 96%, while on nasal cannula at 2 L/minutes. Chest x-ray was concerning for pulmonary oedema, and echocardiogram 6 hours after dobutamine stress echocardiography showed normal left ventricular size (left ventricular end-diastolic diameter 43 mm (z-score = 0)) with reduced systolic function (left ventricular end-systolic diameter 34mm (z-score = 2.9); ejection fraction of 37% by M-mode (35% by Simpson’s monoplane method), mild mitral valve regurgitation, normal right ventricular size with moderately decrease systolic function, and no pericardial effusion. Troponin-T levels peaked to 610 ng/L (normal ≤15 ng/L) 6 hours after dobutamine stress echocardiography. Given concern for dobutamine-induced Takotsubo syndrome, inotropes were avoided, and the patient was managed conservatively for acute systolic/diastolic heart failure with intermittent intravenous furosemide (1 mg/kg/dose) and nasal continuous positive airway pressure.

Over the ensuing 24 hours, Troponin-T levels decreased to 96 ng/L, chest x-ray findings nearly resolved after one dose of Furosemide, and positive pressure was discontinued. Repeat echocardiogram in the following day demonstrated a normal left ventricular size (left ventricular end-diastolic diameter 43 mm (z-score = 0; left ventricular end-systolic diameter 30 mm (z-score = 1.0)), ejection fraction of 51% (M-mode), dyskinetic left ventricular inferior wall, and significantly improved right ventricular systolic function. The patient was discharged on his home medication regimen 2 days after dobutamine stress echocardiography. Echocardiogram normalised 6 days later, and electrocardiogram 3 weeks after dobutamine stress echocardiography documented regression of ST-segment elevation and T-wave inversion in anterolateral leads (Figure 1).