Brief report

A 2-year-old female with a previous history of a multiple small ventricular septal defects was admitted with concern for episodic hypersomnolence and near-syncopal events. At baseline, the parents reported the child to be active and playful; however, during repeat episodes, she would acutely cease her activities, appear pale, diaphoretic, and rest her head in her caretaker’s lap. These symptoms would typically last between 5 and 10 minutes before resolving without intervention. Episodes had started 2 months prior and increased in frequency to nearly daily occurrences just prior to admission. Of note, there was no known family history of cardiovascular disease. Initial evaluation included age-appropriate vital signs at rest, and basic laboratory evaluation was only notable for an elevated troponin of 295 ng/L (normal < 45 ng/L) and an elevated pro-B-type natriuretic peptide of 2569 pg/ml (normal < 300 pg/ml). ^{Reference Ponikowski, Voors and Anker1} Electrocardiogram analysis at the patient’s baseline revealed sinus rhythm without other abnormalities. An echocardiogram showed the previously described ventricular septal defects in addition to a dilated left ventricle with evidence of non-compaction and an ejection fraction of about 30%. She was admitted to the cardiac ICU and started on milrinone for presumed decompensated systolic heart failure. During her first night of admission, she developed transient ST segment changes (Fig. 1) with an increase in her lactate level that correlated temporally with her symptoms. Diagnostic catheterisation performed the following day showed normal intracardiac pressures with hyper-trabeculated left ventricular endocardium consistent with non-compaction. There was normal coronary artery anatomy without evidence of stenosis or obstruction (Fig. 2). Concurrently, a loop recorder was placed to assess for arrhythmias contributing to her symptomatology.

Figure 1. (Left) Twelve-lead electrocardiogram shortly after vasospastic episode began showing diffuse ST segment depression. (Right) Telemetry strips showing ST depression correlating to ischaemic symptoms (top), about 2 minutes later shortly after sublingual nitroglycerine was given (middle), and 2 minutes later showing normalisation of electrocardiogram (bottom).

Figure 2. (Left) Cardiac catheterisation demonstrating normal coronary artery anatomy. (Right) Graph showing mixed venous oxygen saturation versus lactate levels over time. This demonstrates the acute, transient nature of the ischaemia which occurred intermittently during her admissions.

She was transitioned from milrinone to enalapril but had additional episodes consisting of concurrent ST changes, elevated troponin, and increased lactate levels (Fig. 2). The genetics team was consulted; a cardiomyopathy genetic panel was significant for a de novo likely pathogenic variant in the actin alpha cardiac muscle 1 (ACTC1) gene. This mutation of the actin alpha subunit leads to myofibrillar disarray and degradation of intercalated discs in cardiomyocytes which clinically has been linked to dilated, hypertrophic, and non-compaction cardiomyopathies. ^{Reference Frustaci, De Luca and Guida2}

While this finding clarifies her ventricular non-compaction, it did not explain her acute coronary syndrome episodes. Intravenous nitroglycerine was started with a period of clinical stability and no episodes, which was subsequently transitioned to a calcium channel blocker. Given her persistent systolic dysfunction, profound haemodynamically significant vasospastic episodes, and her uncertain risk of sudden cardiac death, she was evaluated by the transplant team and listed status 1B for heart transplant. Our patient was able to discharge home; however, she had another ischaemic event 5 days after discharge prompting re-admission. During one of these acute episodes, she was promptly given 100 mcg of sublingual nitroglycerine with resolution of her symptoms within 2 minutes and normalisation of her ST segment depression shortly after. With ongoing episodes of ischaemic ST segment changes with concurrent low cardiac output, the presence of angiographically normal coronary arteries, and prompt resolution with administration of nitroglycerine, the diagnosis of vasospastic angina was made. Shortly after she was listed 1A status by exception due to her perceived risk of sudden death.