1

Case presentation

A 63-year-old woman presented with recurrent syncope and typical angina. She had undergone cardiac transplantation two years prior and had been free from rejection or donor specific antibodies. The patient’s initial syncopal episode was precipitated by chest pain, nausea, and diaphoresis, followed by a five-minute loss of consciousness without postictal confusion. An initial electrocardiogram, telemetry, blood work, echocardiogram, EEG, and head CT were reportedly unremarkable. She was discharged home following observation, and a second syncopal episode occurred the following week with another negative workup at an outside hospital. One week later, the patient experienced a third syncopal episode in which her husband heard a “crash” in the bathroom and found the patient unresponsive on the bathroom floor. She regained consciousness after two minutes and was brought to the hospital for evaluation.

Upon admission, the patient noted that she had been experiencing episodes of severe chest pain at rest, described as “an elephant sitting on her chest.” She denied palpitations or heart failure symptoms, and her patient’s past medical history was only notable for left-sided mastectomy for breast cancer and depression. Her home medications included tacrolimus, prednisone, low dose aspirin, venlafaxine, coleselevam, docusate, and zolpidem. She denied any smoking, alcohol, or drug use. Admission vitals were within normal limits and physical examination was unremarkable. The patient’s baseline electrocardiogram demonstrated sinus tachycardia at 100 beats per minute with non-specific ST-T wave abnormality. A chest radiograph and full laboratory workup were unremarkable.

During her inpatient stay, the patient experienced a few episodes of brief chest discomfort, associated with sinus tachycardia at a rate of 110–115 beats per minute, which would resolve within ten minutes. The patient additionally had an episode of more severe chest pain and was noted to have ST elevations inferiorly on telemetry ( Fig. 1 ). Her symptoms and the ST-elevations resolved within minutes on their own. Coronary angiography, right heart catheterization, and endomyocardial biopsy were performed. Right heart catheterization was unremarkable with mean pulmonary artery pressure of 14 mmHg, pulmonary capillary wedge pressure of 6 mmHg, pulmonary artery saturation of 68%, and cardiac index of 3.05 l per minute per meter squared. Coronary angiography revealed normal left main, left anterior descending, and circumflex arteries. Upon engagement of the right coronary artery, the patient complained of crushing chest pain, similar to her previous episodes. Severe and diffuse vasospasm of the right coronary artery (beyond the ostium, and with slow flow in the entire vessel) was noted with concurrent ST-elevations ( Fig. 2 ), which completely resolved with administration of intracoronary nitroglycerin ( Fig. 3 A and B ). Endomyocardial biopsy was also performed, which was negative for cellular and antibody mediated rejection. The patient was initiated on diltiazem for Prinzmetal’s angina. She was discharged home on event monitor and noted to have transient complete heart block for which a permanent pacemaker was placed to allow for further uptitration of the diltiazem, after which she had no further episodes of chest pain or syncope.

Telemetry strip demonstrating transient ST elevations in leads II and III at the time of chest pain during patient’s hospitalization.

ECG tracing during engagement of right coronary artery demonstrating ST elevations in leads III and avF.

Coronary angiography of right coronary artery demonstrating (A) severe coronary vasospasm and (B) resolution of vasospasm with administration of intracoronary nitroglycerin.

2

Discussion

Our patient presented with severe vasospasm of the right coronary artery associated with crushing chest pain and intermittent ST-elevations, two years following her cardiac transplantation. This case illustrates that, although rare, vasospasm is a reversible cause of significant cardiac ischemia in the post-transplant population. The presumption that the donor heart remains denervated is primarily based on the absence of appropriate neural reflex-mediated changes in heart rate [ , ]. However, there is extensive evidence of sympathetic reinnervation after cardiac transplantation in animal models [ ] and growing evidence in human models [ , ].

In 1959, Prinzmetal et al. [ ] originally described 32 cases of angina occurring at rest, reporting unique clinical characteristics of these patients, particularly that [ ] the angina did not occur with exertion and exercise, [ ] stress tests were typically negative, [ ] ST segment elevation rather than ST depression occurred during chest pain episodes, [ ] the angina episodes often recurred at the same time, frequently awaking the patient from sleep, and [ ] the episodes may be associated with arrhythmias and/or progress on to a myocardial infarction. At the time, Prinzmetal speculated that the angina was secondary to vasospasm or an “increased coronary tonus.” Significant advances in our understanding of Prinzmetal ‘ s angina have taken place since then with occlusive spasm of an epicardial coronary artery serving as the main pathophysiologic mechanism. Select patients with Prinzemetal’s angina can present with syncope and sudden cardiac arrest [ ]. Diltiazem has been demonstrated to be a highly effective agent in the treatment of Prinzemetals’ angina for the past several decades [ ].

To date, the majority of the literature describing coronary artery spasm in cardiac transplant patients has been anecdotal or has consisted of small case series of patients [ ]. The largest observational study in the post-transplant population involved 247 patients undergoing coronary angiography following cardiac transplantation [ ] – of which 12 (4.9%) were noted to have coronary artery spasm, defined by the presence of localized and reversible narrowing of the coronary lumen. The authors described several characteristics of coronary artery spasm in this population, including a documented occurrence in the first 1–3 years after heart transplant, with a predilection for a single coronary artery to be affected, both findings noted in our patient. Of note, in this series, the right coronary artery appeared to be more commonly affected (8 out of 12 patients), with the left anterior descending artery as a close second (6 out of 12 patients). The severity of coronary luminal narrowing ranged from mild to nearly complete occlusion and often appeared as a single tubular smooth and concentric stenosis.

While symptoms may vary, syncope has been previously described as the presenting symptom in two cardiac transplant patients with coronary artery spasm [ ]. It has been proposed that coronary spasm may be related to accelerated atherosclerosis in the transplanted heart and may be associated with early rejection [ ]. Among heart transplant patients with spasm, the presence of multiple areas of coronary artery spasm, seen in roughly 25% of coronary artery spasm cases following transplantation, portends a poor prognosis [ , ]. Autonomic innervation of the heart is not essential in all cases of coronary artery spasm; circulating catecholamines and metabolic and hormonal products may play an important role [ ].