Catecholamine‐Induced Cardiomyopathy Rapidly Reversed With β‐Blocker Therapy

A 45-year-old man with history of a nonoperable metastatic neuroendocrine tumor, suspicious for a paraganglioma based on needle biopsy and plasma catecholamines, developed acute shortness of breath, tachypnea, and tachycardia while receiving his first dose of chemotherapy with cisplatin and etoposide. He was found to be saturating 67% on room air by pulse oximetry and treated with intravenous dexamethasone, diphenhydramine, and furosemide in the chemotherapy suite prior to transport to the emergency department. In the emergency department he appeared alert and oriented but in mild respiratory distress. He was afebrile with a heart rate of 144 beats per minute, blood pressure of 115/74 mm Hg, respiratory rate of 36 respirations per minute, and oxygen saturation of 85% using a nonrebreathing mask. His head–eye–ear–nose–throat examination was unremarkable. Neck examination was significant for the absence of jugular venous distension and a large left-sided nonmobile mass that had not changed per the patient. The heart examination revealed tachycardia and an active precordium with a grade 3 of 6 systolic ejection murmur heard best at the left lower sternal border. Lungs were diffusely coarse on auscultation. Abdomen was unremarkable. Extremities were free of clubbing, cyanosis, or edema. Electrocardiogram confirmed sinus tachycardia with heart rate >150 beats per minute. Portable chest radiography showed cardiomegaly as well as diffuse interstitial abnormalities and parenchymal opacities consistent with pulmonary edema. He was placed on bilevel positive airway pressure 10/5 mm Hg with improvement in oxygen saturation and respiratory distress. He received additional therapy with intravenous furosemide and morphine sulfate, followed by continuous infusions of nitroglycerin and heparin. Brain natriuretic peptide level on admission was 151 pg/mL (normal, 0–100 pg/mL). Serial cardiac enzymes were monitored with a troponin-I peak of 0.53 ng/mL (normal, 0.0–0.1 ng/mL). A 2-dimensional transthoracic echocardiogram was performed and identified generalized left ventricular hypokinesis with an estimated ejection fraction of 20%. As tachycardia was the most pressing issue, he was started on metoprolol tartrate 75 mg twice a day and discharged home 2 days later after additional diuresis. Four days later he presented to the emergency department with continuous chest pain for 1 day, generalized weakness, and decreased urine output. He was found to be in acute renal failure thought to be secondary to cisplatin toxicity or dehydration from recent diuresis. Serial cardiac enzymes were again followed, with a peak troponin-I of 0.14 ng/mL; however, a brain natriuretic peptide level was not measured. A 2-dimensional transthoracic echocardiogram was repeated, this time demonstrating only mild left ventricular hypokinesis with an estimated ejection fraction of 50%. Resting/supine plasma catecholamines were found to be elevated, specifically epinephrine <10 pg/mL (normal, 10–200 pg/mL), norepinephrine 6387 pg/mL (normal, 80–520 pg/mL), and dopamine 93 pg/mL (normal, 0–20 pg/mL). His renal failure was treated with hydration, and he was discharged home a short time after presentation. Unfortunately, his disease rapidly progressed and he decided to enroll in hospice, passing away a few weeks later. Pheochromocytomas are rare neuroendocrine neoplasms, found in less than 0.2% of patients with hypertension.1 Most are located within the abdomen, with approximately 90% arising from one or both adrenal glands.2, 3 Paragangliomas, or extraadrenal pheochromocytomas, comprise approximately 10% of cases and are collections of specialized neural crest cells that have migrated throughout the body.3 The most common destination is within the pelvis; however, tumors can arise from sympathetic ganglia located anywhere from the neck to the bladder as well as the carotid body, vagal body, mediastinum, aorta, and organs of Zuckerkandl.2, 3 Fewer than 10% are malignant, which is determined by local invasion and distant metastases rather than histologic appearance.3, 4 Regardless of their location, these neoplasms are capable of releasing large amounts of norepinephrine, epinephrine, dopamine, or several other hormones. Clinical signs and symptoms depend on the predominant catecholamine secreted, the receptor status, the interaction with the autonomous nervous system, and the effects of other hormones.4 Hypertension, either paroxysmal or sustained, is the most common manifestation, occurring in 90% to 100% of patients.2, 3 Other paroxysmal symptoms such as headaches, palpitations or tachyarrhythmias, diaphoresis, and anxiety are considered “classic.”2-4 Less common, patients present with hypotension and shock related to acute hemorrhagic necrosis of the tumor, dilated or hypertrophic cardiomyopathy, acute myocardial infarction, myocarditis, unstable arrhythmias, or acute pulmonary edema.3-5 Deleterious effects of catecholamines on myocardium have been described including inflammatory cell infiltration, contraction band necrosis, edema, and interstitial fibrosis.2-4 Studies have also suggested that cardiomyopathy associated with pheochromocytoma is mediated by α-adrenergic receptor stimulation by high concentrations of norepinephrine.6, 7 The pathophysiology is thought to be multifactorial: catecholamine-induced overstimulation and vasospasm leading to hypoxia, changes in the permeability of the sarcolemmal membrane resulting in increased calcium influx, and even toxic effects by the oxidized products of catecholamines.2, 6, 8-10 Reversal of cardiac dysfunction has been reported after both surgical and medical therapy of pheochromocytomas as shown in the Table.5, 11-20 Medical treatment includes α-adrenergic blockade for initial blood pressure control, followed by β-adrenergic blockade and inhibitors of catecholamine synthesis. Success in reversal of cardiac dysfunction seems to be dependent on the time of intervention; it must be early in the process before extensive replacement fibrosis has occurred. Unlike our case, a majority of these cases took weeks to months for improvement in cardiac function to be recognized, with the most dramatic results occurring after surgical resection of the tumor. Catecholamine-induced cardiomyopathy as a result of pheochromocytoma is uncommon; however, the importance of aggressive medical therapy is well recognized. To our knowledge, our case represents the most rapidly reversed catecholamine-induced cardiomyopathy presented with recovery of left ventricular ejection fraction in just 7 days.