Ventricular fibrillation due to pheochromocytoma crisis in a previously asymptomatic patient

Abstract

Pheochromocytomas are catecholamine-producing tumors and a rare cause of sudden cardiac death. We describe the case of a previously healthy 28-year-old man who presented after a ventricular fibrillation out-of-hospital cardiac arrest (OHCA). His clinical investigation, including a coronary evaluation, was unremarkable. A protocolized head-to-pelvis computed tomography (CT) scan was ordered and revealed a large right adrenal mass with subsequent laboratory studies showing markedly elevated urine and plasma catecholamines. This raised suspicion for a pheochromocytoma as the underlying etiology behind his OHCA. He received appropriate medical management, underwent adrenalectomy with subsequent normalization of his metanephrines, and fortunately did not have recurrent arrythmias. This case highlights the first documented case of a ventricular fibrillation arrest as the initial presentation of pheochromocytoma crisis in a previously healthy individual, and how the use of early protocolized sudden death CT scan allowed for the prompt diagnosis and management of a rare cause of OHCA.

Learning objective

We review the typical cardiac manifestations of pheochromocytoma and describe the first case of a pheochromocytoma crisis presenting as sudden cardiac death (SCD) in a previously asymptomatic individual. In young patients with unexplained SCD, it is important to consider pheochromocytoma in the differential diagnosis. We also review why an early head-to-pelvis sudden death computed tomography scan protocol may be helpful in the evaluation of patients resuscitated from SCD without an obvious etiology.

Introduction

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors that have an estimated annual incidence of 2–8 per million [1]. The majority (85–90 %) of pheochromocytomas are in the adrenal gland, whereas the remaining 10–15 % are extra-adrenal [1]. Clinical presentation usually includes the classic triad of headaches, sweating, and tachycardia. However, as cross-sectional imaging becomes more widespread, more patients are being diagnosed in the pre-symptomatic stage [2]. Rarely, patients may experience a pheochromocytoma crisis, which can lead to multi-organ failure including severe cardiovascular complications through both direct cardiotoxic injury and overstimulation of α- and β-adrenoceptors. This can result in profound systemic vasoconstriction, coronary vasospasm, myocardial ischemia, and infarction [3]. More chronically, exposure to these deleterious catecholamine effects can also cause cardiomyopathies or arrhythmias that increase risk for sudden cardiac death.

Case report

A 28-year-old male presented to the hospital after a witnessed ventricular fibrillation (VF) out of hospital cardiac arrest (OHCA). Prior to his presentation, he was asymptomatic and in his usual state of health. The patient worked as a roofer and recalled bending over to lift a heavy object when he experienced sudden-onset right lower back pain followed by light-headedness. He was found unconscious on the floor by his coworkers after an undetermined amount of time. They immediately initiated bystander cardiopulmonary resuscitation.

Emergency medical services arrived and found the patient pulseless in VF (Fig. 1). His initial blood pressure in the field was 218/152 mmHg with heart rate of 128 beats per minute (bpm). After two 200 J shocks, he converted to sinus rhythm with return of spontaneous circulation. Upon arrival to the emergency department, the patient was alert and answering questions appropriately without any neurologic deficits. His vital signs were now 113/87 mmHg, heart rate of 129 bpm, respiratory rate of 12 breaths per min, and pulse oximeter saturation of 99 % on ambient air.

Fig. 1.

Initial electrocardiogram upon emergency medical services arrival demonstrating ventricular fibrillation.

The patient had no prior medical history and was not taking any prescription medications or over-the-counter supplements. He denied any symptoms of headaches, palpitations, elevated blood pressure, presyncope, syncope, or anxiety. He endorsed using occasional marijuana but denied any use on the day of OHCA. He denied any significant alcohol or illicit substance use.

Initial electrocardiogram (ECG) revealed sinus tachycardia without ischemic changes. His initial laboratory studies, including cardiac troponin I, were unremarkable. He underwent a protocolized sudden death head-to-pelvis computed tomography (CT) scan that revealed a large right adrenal mass that measured 6.5 × 4.1 × 4.9 cm (Fig. 2). Transthoracic echocardiogram (TTE) revealed a moderately dilated left ventricle and severely reduced left ventricular ejection fraction (LVEF) of 14 % with global hypokinesis and akinesis of the mid to apical walls of the left ventricle (Video 1). Urine toxicology was only positive for cannabis. Troponin I peaked at 0.93 ng/mL (normal <0.03 ng/mL). There were no dynamic changes on serial ECGs. A coronary CT angiogram showed no evidence of coronary atherosclerosis or stenosis.

Fig. 2.

Axial image of the abdomen from the sudden death computed tomography scan showing a large right adrenal mass measuring 6.5 × 4.1 × 4.9 cm (lines).

Given the large adrenal mass, an endocrinologist was consulted and work up included aldosterone, renin, dehydroepiandrosterone, cortisol, and plasma and urine metanephrines. The plasma metanephrines and normetanephrines were elevated at 0.60 nmol/L (normal <0.49 nmol/L) and 13 nmol/L (normal <0.89 nmol/L), respectively. Urine metanephrines and normetanephrines were also markedly elevated at 463 μg/24 h (44–261 μg/24 h) and 8755 μg/24 h (<390 μg/24 h), respectively. The elevated urine and plasma fractionated metanephrines, in conjunction with the adrenal mass seen on CT, confirmed the diagnosis of a pheochromocytoma.

Thus, a multidisciplinary team consisting of cardiology, electrophysiology, and endocrinology was assembled, and it was concluded that the etiology of the patient's VF OHCA was most likely secondary to a pheochromocytoma crisis. Although, the patient remained normotensive and completely asymptomatic with no arrhythmias detected on telemetry, he had persistent sinus tachycardia despite intravenous fluids. Therefore, the consensus from the multidisciplinary team was to proceed with sympathetic blockade with doxazosin 2 mg daily orally to target a systolic blood pressure of <90 mmHg while standing. After three days, oral carvedilol 3.125 mg twice a day was initiated to address ongoing tachycardia, which improved to 90 bpm. A repeat TTE on day four of his hospitalization demonstrated normalization of his ejection fraction and left ventricular cavity size. A subsequent cardiac magnetic resonance imaging (MRI) study, obtained to assess for an alternative etiology of his arrest, demonstrated a normal left ventricular structure and function with no evidence of myocardial scar, infiltration, or inflammation.

The patient was discharged on alpha and beta blockade as well as with a temporary wearable external defibrillator until definitive surgical removal of the adrenal mass could be performed. Two weeks later, the patient underwent a successful laparoscopic adrenalectomy, and pathologic analysis of the mass was consistent with pheochromocytoma (Fig. 3).

Fig. 3.

Gross pathology of resected right adrenal gland with well circumscribed white to reddish mass consistent with pheochromocytoma.

Repeat metanephrine testing four weeks later demonstrated improvement in plasma metanephrines and normetanephrines to <0.20 nmol/L (normal <0.49 nmol/L) and 1.1 nmol/L (normal <0.89 nmol/L), respectively. At this point, his alpha- and beta-blockade agents were discontinued. Three months after his initial presentation, he remained asymptomatic with normal cardiac function. After shared decision-making, it was decided not to pursue an implantable cardiac defibrillator, given his low risk of recurrent ventricular arrhythmias now that his pheochromocytoma had been definitively treated with surgical excision, and prior evaluation demonstrated a structurally normal heart.

Discussion

Although there have been rare case reports of pheochromocytoma-induced sudden death and cardiomyopathy in the literature [4,5], our case report is notable for several reasons. First, this is the first case report in which a VF arrest was the presenting symptom of a pheochromocytoma. It is atypical that our patient was completely asymptomatic and did not have any symptoms of headaches, palpitations, elevated blood pressure, presyncope, syncope, or anxiety before presenting with cardiac arrest secondary to pheochromocytoma crisis. Second, this case highlighted the integral role of early head-to-pelvis sudden death CT scan (SDCT) after cardiac arrest. The CT results assisted in the timely diagnosis and clinical management of this patient's pheochromocytoma. At our institution, protocolized SDCT are obtained in all OHCA cases without a clear etiology. Prior studies have demonstrated high diagnostic yield of SDCT for cardiac and other causes of OHCA [6]. This is the first report of diagnosis of a pheochromocytoma by SDCT.

The VF arrest was provoked after bending over and lifting a heavy object, which likely resulted in increased intra-abdominal pressure and tumor manipulation leading to a sudden release of catecholamines that precipitated a pheochromocytoma crisis. This phenomenon of direct pressure resulting in the release of catecholamine rich blood from the venous sinusoids has been well described [7]. Although the patient did endorse occasional marijuana use and there are reports of marijuana inducing arrhythmias [8], including VF, this was thought to be less likely since he did not use marijuana on the day of his arrest.

Our patient's initial TTE within hours of resuscitation showed a severely reduced LVEF with a moderately dilated LV with focal areas of akinesis consistent with catecholamine-induced cardiomyopathy in pheochromocytoma (CICMPP). CICMPP is a well-established entity that encompasses three distinct subtypes of dilated, hypertrophic, and stress-induced cardiomyopathies. CICMPP typically resolves after several weeks of treatment and definitive surgical resection of the pheochromocytoma [9,10]. Interestingly, our patient had rapid cardiac recovery with repeat TTE four days post cardiac arrest demonstrating normalization of his left ventricular chamber size, systolic function, and wall motion abnormalities, suggesting this could have been due to cardiac stunning in the setting of his VF arrest rather than a CICMPP. This was corroborated by his cardiac MRI, which did not demonstrate any evidence of myocardial scarring or other suggestion of underlying cardiomyopathy.

Conclusions

We describe a case of a patient with VF OHCA as the first presentation of pheochromocytoma. His VF OHCA was triggered by a pheochromocytoma crisis that we suspect was due to increased abdominal pressure exerted on the adrenal mass. This case highlights the benefit of early sudden cardiac death full body CT scanning to assist in the prompt diagnosis in patients with unknown cause for sudden death.

The following is the supplementary data related to this article.

Video 1

Transthoracic echocardiogram showing an apical four-chamber Definity enhanced image with severely reduced left ventricular ejection fraction, global hypokinesis, and akinesis of the mid to apical walls.

Funding/support

No funding to disclose.

Patient permission/consent statement

None required.

Declaration of competing interest

None.