Vanessa M Ferreira1, Mafalda Marcelino2, Stefan K Piechnik3, Claudia Marini3, Theodoros D Karamitsos3, Ntobeko A B Ntusi3, Jane M Francis3, Matthew D Robson3, J Ranjit Arnold3, Radu Mihai4, Julia D J Thomas5, Maria Herincs5, Zaki K Hassan-Smith6, Andreas Greiser7, Wiebke Arlt6, Márta Korbonits5, Niki Karavitaki8, Ashley B Grossman2, John A H Wass2, Stefan Neubauer3. 1. 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. 2. Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology & Metabolism (OCDEM), Churchill Hospital, University of Oxford, Oxford, United Kingdom. 3. Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. 4. Department of Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. 5. Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom. 6. Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, United Kingdom. 7. Siemens Healthcare GmbH, Erlangen, Germany. 8. 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.
Abstract
BACKGROUND: Pheochromocytoma is associated with catecholamine-induced cardiac toxicity, but the extent and nature of cardiac involvement in clinical cohorts is not well-characterized. OBJECTIVES: This study characterized the cardiac phenotype in patients with pheochromocytoma using cardiac magnetic resonance (CMR). METHODS: 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]). RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: Pheochromocytoma is associated with catecholamine-induced cardiac toxicity, but the extent and nature of cardiac involvement in clinical cohorts is not well-characterized. OBJECTIVES: This study characterized the cardiac phenotype in patients with pheochromocytoma using cardiac magnetic resonance (CMR). METHODS: 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]). RESULTS: 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. CONCLUSIONS: 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: Horacio Medina de Chazal; Marco Giuseppe Del Buono; Lori Keyser-Marcus; Liangsuo Ma; F Gerard Moeller; Daniel Berrocal; Antonio Abbate Journal: J Am Coll Cardiol Date: 2018-10-16 Impact factor: 24.094
Authors: Benjamin B Kenigsberg; Christopher F Barnett; Jeffrey C Mai; Jason J Chang Journal: Curr Neurol Neurosci Rep Date: 2019-11-13 Impact factor: 5.081
Authors: Evan Hann; Iulia A Popescu; Qiang Zhang; Ricardo A Gonzales; Ahmet Barutçu; Stefan Neubauer; Vanessa M Ferreira; Stefan K Piechnik Journal: Med Image Anal Date: 2021-03-11 Impact factor: 8.545
Authors: Matthew K Burrage; Mayooran Shanmuganathan; Qiang Zhang; Evan Hann; Iulia A Popescu; Rajkumar Soundarajan; Kelvin Chow; Stefan Neubauer; Vanessa M Ferreira; Stefan K Piechnik Journal: Sci Rep Date: 2021-06-30 Impact factor: 4.379