A, Electrocardiogram shows left ventricular hypertrophy with secondary ST-T wave changes. B, Two-dimensional echocardiography (top) shows marked septal hypertrophy with septal wall thickness of 24 mm (yellow arrow) and posterior wall thickness of 15 mm (red arrow). Left ventricular strain image with a preoperative parasternal long-axis view (bottom) shows global longitudinal strain of −12.6%. C, Postadrenalectomy echocardiography (top) shows septal wall thickness of 12 mm (yellow arrowheads) and posterior wall thickness of 8 mm (red arrowheads). Left ventricular strain image (bottom) shows a postoperative global longitudinal strain of −21.0%.
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Wani A, Adil A, Gardezi SAA, et al. Pheochromocytoma Presenting as Hypertrophic Obstructive Cardiomyopathy. JAMA Cardiol. 2021;6(8):974–976. doi:10.1001/jamacardio.2021.0944
Hypertrophic cardiomyopathy (HCM) is clinically diagnosed when there is unexplained left ventricular (LV) wall thickness of 15 mm or greater. However, clinical diagnosis of HCM is neither specific (owing to the presence of phenocopy) nor sensitive (owing to incomplete penetrance of causal variants). Distinguishing HCM from phenocopies is important because treatment may differ substantially.
This case series describes a 33-year-old woman who was 30 weeks pregnant, with 2 prior uncomplicated pregnancies, and was admitted for hypotension. The Advocate Aurora Health institutional review board approved the study, and oral informed consent was obtained from the patient. This study was performed from June 30, 2018, to July 24, 2020, and followed the reporting guideline for case series.
When the patient was admitted to the hospital, she had intractable vomiting, diaphoresis, weight loss, and fatigue of 4 weeks’ duration. Blood pressure was labile, with intermittent episodes of severe hypertension. Cardiac examination revealed a grade 3/6 systolic murmur at the mid upper-left sternal border and pitting edema bilaterally. Laboratory studies showed leukocytosis and metabolic acidosis. Urinalysis showed marked proteinuria. Electrocardiography findings met the criteria for LV hypertrophy (LVH) (Figure, A). Echocardiography findings were suggestive of HCM with systolic anterior motion of the mitral valve leaflet causing an LV outflow tract gradient of 45 mm Hg (Figure, B). Because of a preemptive diagnosis of preeclampsia, an emergency cesarean delivery was performed under epidural anesthesia, which was tolerated well. With an uneventful hospital course, the patient was discharged home on postoperative day 9 with oral antihypertensive treatment.
A month later, the patient was referred to the HCM Center of Excellence at Advocate Aurora Health, where she reported labile blood pressure with nausea and diaphoresis. Echocardiography findings confirmed an HCM phenotype with asymmetric septal hypertrophy (Figure, B). Left ventricular ejection fraction was 66%, with global longitudinal strain reduced at −12.6% (Figure, B). Cardiac magnetic resonance imaging showed septal thickness up to 24 mm without late gadolinium enhancement. Pheochromocytoma was clinically suspected. Catecholamine levels were markedly elevated (Table). Abdominal magnetic resonance imaging showed bilateral adrenal masses, with findings characteristic of bilateral pheochromocytomas. Fundoscopic examination revealed retinal angioma. A hereditary paraganglioma-pheochromocytoma panel revealed MAX gene (heterozygous c.138G>C; p.Leu46Phe) and was negative for the rearranged during transfection (RET), neurofibromatosis type 1, von Hippel-Lindau syndrome, and succinate dehydrogenase type A variants. Despite initiation of phenoxybenzamine and metoprolol treatment, the patient continued to have labile blood pressure.
Three months after diagnosis, the patient underwent bilateral adrenalectomy. Histopathologic findings confirmed pheochromocytoma. Echocardiography 3 months after surgery revealed complete normalization of septal and posterior wall thickness with no residual features of the HCM phenotype (Figure, C). At 8-month follow-up, symptoms had completely resolved. The patient discontinued antihypertensive treatment.
Pheochromocytoma, a rare catecholamine-secreting tumor, is mostly sporadic. Familial cases commonly have bilateral adrenal involvement. Autosomal dominant familial forms include von Hippel-Lindau syndrome, multiple endocrine neoplasia type 2, and neurofibromatosis type 1. The MYC-associated protein X gene variant found in this patient is associated with bilateral adrenal tumors, of which one-fourth can demonstrate malignant behavior.1 Given insidious onset of nonspecific symptoms, the variety of potential diagnoses can delay recognition and treatment.
Pheochromocytoma, similar to stress-induced cardiomyopathy, is attributed to catecholamine excess.2 Van Vliet et al3 described focal myocardial lesions, including focal necrosis of myocardial fibers and diffuse myocardial edema, in 58% of patients with pheochromocytoma on autopsy.
Myocardial hypertrophy in patients with pheochromocytoma has been attributed to systemic hypertension. In 1973, Laks et al4 performed infusions of subhypertensive doses of norepinephrine in 6 dogs, invoking LVH independent of pressure load. Shub et al5 reported cases of pheochromocytoma mimicking obstructive HCM, and tumor removal abated these features. Fouad-Tarazi et al6 demonstrated that LVH developed in a subset of patients with pheochromocytoma-induced hypertension, indicating that factors other than catecholamines and blood pressure may be associated with development of LVH in patients with pheochromocytoma.
This study had limitations. The present study describes the features of pheochromocytoma-induced hypertrophic cardiomyopathy. There could be other possible differentials; however, based on the response to therapy, this was the best working diagnosis. Our longest follow-up was 8 months; hence, we lack long-term follow-up data.
The patient in this case series had high catecholamine levels, severe asymmetric LVH, and dynamic obstruction of the LV outflow tract despite the increased preload state of pregnancy. She experienced persistent symptoms despite appropriate medical therapy and complete regression of LVH after bilateral adrenalectomy.
Accepted for Publication: March 3, 2021.
Published Online: May 12, 2021. doi:10.1001/jamacardio.2021.0944
Corresponding Author: A. Jamil Tajik, MD, Aurora Cardiovascular and Thoracic Services, Aurora Sinai/Aurora St Luke’s Medical Centers, University of Wisconsin School of Medicine and Public Health, 2801 W Kinnickinnic River Pkwy, Ste 880, Milwaukee, WI 53215 (firstname.lastname@example.org).
Author Contributions: Drs Wani and Tajik had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Wani, Tajik.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Wani, Adil.
Critical revision of the manuscript for important intellectual content: Gardezi, Jain, Galazka, Waples, Tajik.
Conflict of Interest Disclosures: None reported.
Meeting Presentation: This paper was presented at the American College of Cardiology Scientific Sessions 2019; March 18, 2019; New Orleans, Louisiana.
Additional Contributions: We thank the patient for granting permission to publish this information. The following individuals from Advocate Aurora Health (Milwaukee, Wisconsin) contributed to the study without compensation: Rahul Sawlani, MD, provided interpretation and opinion regarding the magnetic resonance imaging findings; Valentin Suma, MD, provided interpretation of echocardiograms; and Heather Sanders, ACNP, was the main point of contact with the patient.