title: Pheochromocytoma Is Characterized by Catecholamine-Mediated Myocarditis, Focal and Diffuse Myocardial Fibrosis, and Myocardial Dysfunction.
abstract: Pheochromocytoma is associated with catecholamine-induced cardiac toxicity, but the extent and nature of cardiac involvement in clinical cohorts is not well-characterized.
  
  
  
  This study characterized the cardiac phenotype in patients with pheochromocytoma using cardiac magnetic resonance (CMR).
  
  
  
  A total of 125 subjects were studied, including patients with newly diagnosed pheochromocytoma (n = 29), patients with previously surgically cured pheochromocytoma (n = 31), healthy control subjects (n = 51), and hypertensive control subjects (HTN) (n = 14), using CMR (1.5-T) cine, strain imaging by myocardial tagging, late gadolinium enhancement, and native T1 mapping (Shortened Modified Look-Locker Inversion recovery [ShMOLLI]).
  
  
  
  Patients who were newly diagnosed with pheochromocytoma, compared with healthy and HTN control subjects, had impaired left ventricular (LV) ejection fraction (<56% in 38% of patients), peak systolic circumferential strain (p < 0.05), and diastolic strain rate (p < 0.05). They had higher myocardial T1 (974 ± 25 ms, as compared with 954 ± 16 ms in healthy and 958 ± 23 ms in HTN subjects; p < 0.05), areas of myocarditis (median 22% LV with T1 >990 ms, as compared with 1% in healthy and 2% in HTN subjects; p < 0.05), and focal fibrosis (59% had nonischemic late gadolinium enhancement, as compared with 14% in HTN subjects). Post-operatively, impaired LV ejection fraction typically normalized, but systolic and diastolic strain impairment persisted. Focal fibrosis (median 5% LV) and T1 abnormalities (median 12% LV) remained, the latter of which may suggest some diffuse fibrosis. Previously cured patients demonstrated abnormal diastolic strain rate (p < 0.001), myocardial T1 (median 12% LV), and small areas of focal fibrosis (median 1% LV). LV mass index was increased in HTN compared with healthy control subjects (p < 0.05), but not in the 2 pheochromocytoma groups.
  
  
  
  This first systematic CMR study characterizing the cardiac phenotype in pheochromocytoma showed that cardiac involvement was frequent and, for some variables, persisted after curative surgery. These effects surpass those of hypertensive heart disease alone, supporting a direct role of catecholamine toxicity that may produce subtle but long-lasting myocardial alterations.
authors.affiliation: Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. Electronic address: vanessa.ferreira@cardiov.ox.ac.uk.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Ferreira
authors.affiliation: Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology & Metabolism (OCDEM), Churchill Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Marcelino
authors.affiliation: Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Piechnik
authors.affiliation: Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Claudia
authors.initials: C
authors.lastname: Marini
authors.affiliation: Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Theodoros D
authors.initials: TD
authors.lastname: Karamitsos
authors.affiliation: Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Ntobeko A B
authors.initials: NAB
authors.lastname: Ntusi
authors.affiliation: Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Francis
authors.affiliation: Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Robson
authors.affiliation: Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: J Ranjit
authors.initials: JR
authors.lastname: Arnold
authors.affiliation: Department of Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
authors.forename: Radu
authors.initials: R
authors.lastname: Mihai
authors.affiliation: Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Julia D J
authors.initials: JDJ
authors.lastname: Thomas
authors.affiliation: Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Herincs
authors.affiliation: Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, United Kingdom.
authors.forename: Zaki K
authors.initials: ZK
authors.lastname: Hassan-Smith
authors.affiliation: Siemens Healthcare GmbH, Erlangen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Greiser
authors.affiliation: Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, United Kingdom.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
authors.affiliation: Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
authors.affiliation: Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology & Metabolism (OCDEM), Churchill Hospital, University of Oxford, Oxford, United Kingdom; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, United Kingdom.
authors.forename: Niki
authors.initials: N
authors.lastname: Karavitaki
authors.affiliation: Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology & Metabolism (OCDEM), Churchill Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Grossman
authors.affiliation: Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology & Metabolism (OCDEM), Churchill Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: John A H
authors.initials: JAH
authors.lastname: Wass
authors.affiliation: Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D016022:Case-Control Studies; D002395:Catecholamines / Q000378:metabolism*; D003971:Diastole; D005260:Female; D005355:Fibrosis; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000209:etiology*; D009206:Myocardium / Q000473:pathology*; D010490:Pericardial Effusion / Q000209:etiology; D010673:Pheochromocytoma / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D011446:Prospective Studies; D013318:Stroke Volume; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000209:etiology
chemical_list: D002395:Catecholamines
keywords: T(1) mapping; cardiac magnetic resonance; catecholamine toxicity