Pheochromocytoma Is characterized by catecholamine-mediated myocarditis, focal and diffuse myocardial fibrosis, and myocardial dysfunction

Vanessa Ferreira, Mafalda Marcelino, Stefan Piechnik, Claudia Marini, Theodoros Karamitsos, Ntobeko Ntusi, Jane Francis, Matthew Robson, Ranjit Arnold, Radu Mihai, Julia Thomas, Maria Herincs, Zaki Hassan-Smith, Andreas Greiser, Wiebke Arlt, Marta Korbonits, Niki Karavitaki, Ashley Grossman, John Wass, Stefan Neubauer

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Abstract

Background: Pheochromocytoma is associated with catecholamine-induced cardiac toxicity, well-described in autopsy and animal studies. The extent and nature of cardiac involvement in clinical cohorts is not well-characterized.

Objectives: To characterize the cardiac phenotype in patients with pheochromocytoma using cardiovascular magnetic resonance (CMR). 

Methods: We studied 125 subjects (patients with newly-diagnosed pheochromocytoma n=29 pre- and post-surgical resection; previously-diagnosed surgically-cured pheochromocytoma n=31; hypertension (HTN) n=14; normal controls n=51) using CMR (1.5T) cine, strain imaging by myocardial tagging, late gadolinium enhancement (LGE) and T1-mapping (ShMOLLI). 

Results: Cardiac involvement was common in patients newly-diagnosed with pheochromocytoma. This included reduced global LV function (LVEF 44-56% in 38%), peak systolic circumferential strain (-15.8±2.9, normal -18.5±1.4, HTN 17.3±8.1s-1; p<0.05), and diastolic strain rate (72.8±22.4, normal 128.7±29.3, HTN 104.7±25.1s-1; p<0.05). Tissue characterization showed higher myocardial T1 (974±25, normal 954±16, HTN 958±23ms, p<0.05) with evidence of myocarditis (median 22% LV with T1>990ms, normal 1%, HTN 2%; p<0.05) and focal fibrosis (59% demonstrated non-ischemic LGE, HTN 14%, patients previously-diagnosed pheochromocytoma 19%). Impaired LVEF typically normalized after tumor resection, but impaired systolic and diastolic strain parameters persisted. Further, areas of focal fibrosis on LGE (median 5% LV myocardium) remained. Myocardial T1, despite regression, did not completely normalize (median 12% LV myocardium), which may suggest the development of diffuse fibrosis. Patients with previous surgically-cured pheochromocytoma, despite normal LVEF, also had impaired diastolic strain rate (62.8±16.2, normal 133.5±25.5, HTN 104.7±25.1; p<0.001) and myocardial T1 abnormalities (median 12% LV, normal 2%, HTN 2%; p<0.05). Interestingly, LV mass index was increased in HTN compared to normal (61±12 vs. normal 51±9 g/m2; p<0.05) but not in the two pheochromocytoma groups (LV mass index 56±12 and 49±9 g/m2).

Conclusions: This first systematic CMR study to characterize the cardiac phenotype in pheochromocytoma showed that cardiac involvement is frequent, including myocarditis, global LV dysfunction, systolic and diastolic dysfunction, focal and diffuse fibrosis, some of which persisted. These effects are beyond those of hypertensive heart disease alone, supporting a direct role of catecholamine toxicity that may result in subtle but long-lasting myocardial alterations.
Original languageEnglish
Pages (from-to)2364–2374
Number of pages11
JournalJournal of the American College of Cardiology
Volume67
Issue number20
Early online date16 May 2016
DOIs
Publication statusPublished - 24 May 2016

Keywords

  • pheochromocytoma
  • cardiovascular magnetic resonance
  • myocarditis
  • catecholamine toxicity
  • ShMOLLI T1-mapping

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