Cardiac Structure and Function in Cushing's Syndrome: A Cardiac Magnetic Resonance Imaging Study

Abstract

Background:Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients.Objectives:The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function.Methods:Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2–12 mo) after the treatment of hypercortisolism.Results:Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P < .001 for all) and increased end-diastolic LV segmental thickness (P < .001). Treatment of hypercortisolism was associated with an improvement in ventricular and atrial systolic performance, as reflected by a 15% increase in the LV ejection fraction (P = .029), a 45% increase in the LA ejection fraction (P < .001), and an 11% increase in the RV ejection fraction (P = NS). After treatment, the LV mass index and end-diastolic LV mass to volume ratio decreased by 17% (P < .001) and 10% (P = .002), respectively. None of the patients had late gadolinium myocardial enhancement.Conclusion:Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism.

Cardiac hypertrophy in Cushing’s syndrome: if not hypertension then what?

“…Overall, this study adds to the scenario that the observed heart abnormalities in patients with CS are not directly related to blood pressure, and other contributing factors have to be considered. In this line, the reversibility of the structural changes did not relate to changes in blood pressure after treatment in two studies [8,9] and, also, hypertension does not seem to be an independent risk factor for long-term mortality in Cushing's disease [4].…”

“…LV mass index, however, is likely to be overestimated in echo-based studies. In a study that applied cardiac magnetic resonance (CMR) [9], subclinical biventricular and left atrium (LA) systolic dysfunction, as well as mainly regional LV wall thickness were found, although clinical LV hypertrophy according to the CMR criteria was detected in only one of the 18 patients. One study using ECG detected subtle abnormalities, LV hypertrophy and prolonged QT-corrected dispersion [10].…”

“…Nevertheless, the increased LV mass and the concentric LV remodeling are independent risk factors for overt heart failure and major cardiovascular events. Of note, some of these abnormalities, such as circumferential and longitudinal LV hypertrophy, biventricular systolic function, diastolic LV dysfunction and LA systolic dysfunction, are reversible after treatment [8,9]. However, the pathophysiology of these heart abnormalities remains largely elusive.…”

“…All these factors have negative impact on the heart, and may promote ventricular hypertrophy, fibrosis and deposition of fat. In fact, a recent study by Kamenicky et al [9] reported that reversibility of some of these cardiac abnormalities after treatment of cortisol excess was, at least partly, related to the improvement of blood glucose levels and BMI.…”

“…In the myocardium, it has been postulated that local HSD2 is insufficient to inactivate cortisol that prevails over aldosterone for the MR and exerts diverse effects through both receptors. MR-mediated myocardial fibrosis, may thus be an important factor, but the data is contradictory, probably due to the use of different methods to assess fibrosis [9,17]. Several other mechanisms include: induction of perivascular inflammation through activation of the MR, production of cytokines that may promote myocardial stiffness and contractile dysfunction by local inflammatory cells mainly the macrophages, reduced expression of eNOS and, potentiation of adrenergic action.…”