Non-ischemic Primary and Secondary Cardiomyopathy
Charlotte Manisty
Consultant Cardiologist
University College London and Barts Heart Centre
London, England, United Kingdom
Anish N. Bhuva, MD, PhD
Consultant Cardiologist
Barts Health NHS Trust, England, United Kingdom
Satish Ramkumar, MD, PhD
Cardio-Oncology and Cardiac MRI Fellow
Barts Health NHS Trust
London, United Kingdom
Xilin Wu
Department of Endocrinology
Barts Health NHS Trust, United Kingdom
Jessica Artico, MD
Clinical Research Fellow
St Bartholomew's Hospital, England, United Kingdom
Rhodri Davies, MD, PhD
Associate clinical professor
University College London
London, Wales, United Kingdom
Clement Lau, MD
Clinical Pharmacology - William Harvey Research Institute
Queen Mary University of London, United Kingdom
Kate Laycock
Department of Endocrinology
Barts Health NHS Trust, United Kingdom
Samuel M. O'Toole
Department of Endocrinology
Barts Health NHS Trust, United Kingdom
James C. Moon, MD
Clinical Director, Imaging
Barts Heart Centre and UCL
London, England, United Kingdom
Thomas A. Treibel, MD, PhD
Consultant Cardiologist
University College London, England, United Kingdom
Emily Goodchild
Department of Endocrinology
Barts Health NHS Trust, United Kingdom
Giulia Argentesi
Department of Endocrinology
Barts Health NHS Trust, United Kingdom
Jackie Salsbury
Department of Endocrinology
Barts Health NHS Trust, United Kingdom
William M. M. Drake, MD
Department of Endocrinology
Barts Health NHS Trust
London, United Kingdom
Morris J. Brown
Department of Endocrinology
Barts Health NHS Trust, United Kingdom
Primary aldosteronism (PA) is an under-diagnosed, common cause of secondary hypertension. It differs from essential hypertension (EH) as it may be curable with surgery; myocardial remodelling is aldosterone mediated, and cardiovascular events are twice as common. The mechanisms of excess risk and possible reversibility with treatment are poorly understood. We sought to interrogate the underlying pathophysiology in patients with PA, and reversibility comparing medical and surgical interventions.
Methods: PA Patients were recruited over 4 years from the MATCH study (a multicenter prospective study comparing 11C-metomidate PET-CT imaging with adrenal vein sampling for predicting surgical response, NCT02945904).1 Patients underwent assessment at baseline and 12 months post intervention (surgical adrenalectomy or medical treatment including mineralocorticoid receptor antagonists) using CMR and cardiac biomarker measurement. CMR included standard cine and late gadolinium enhancement (LGE), parametric mapping and aortic stiffness (pulse wave velocity and distensibility). Analysis was AI based and fully automated where available. Partial and full clinical cure was defined as per the PASO criteria.3
Results:
51 patients (age 53±11 yrs, n=36 male) underwent follow-up at 12±3 months post intervention (26 surgical, 25 medical).
Baseline: Compared to healthy age and sex matched controls, PA patients had increased indexed LV mass, T1 and ECV with elevated T2 values in 91% patients (Table 1). Scar was noted in 29% PA patients (subendocardial LGE in 5/15 pts.) and 29% had elevated troponin.
Follow-up: BP fell by 8mmHg [95%CI 1-15mmHg] in the overall cohort [13mmHg with surgery and 3mmHg with medical therapy at one year, between group p=0.16]. Structural reverse remodelling was measured in aortic stiffness, LV end-diastolic volume, LV end-systolic volume, and LV mass (% change 10.2%, 7.3%, 6.2% respectively), Table 1 and Figure 1. LV mass reduction was due to falls in both myocyte volume (3.7%) and extracellular volume (5.6%), p< 0.05). Scar mass reduced also at follow-up (median±IQR 2.5±3.3g vs. 1.8±2.2g, p=0.01). Surgical vs medical remodelling: Remodelling was more pronounced for surgical vs medical intervention (numbers small: p< 0.05 for LVEDV, LVESV and aortic stiffness), figure 1b. Patients achieving partial/full cure demonstrated greater reductions in LV and myocyte volumes (p < 0.05) but not aortic stiffness.
Conclusion: Primary aldosteronism demonstrates adverse cardiac remodelling with LV hypertrophy, increased aortic stiffness, myocardial fibrosis and low-grade inflammation. This is the first study to describe at least partial reversibility of these changes following treatment, and the effects of surgery on cardiovascular remodelling appear incremental to the benefits from medical treatment. The effects of aldosterone on the cardiovascular system in PA may extend beyond blood pressure control.