LAUSR

Systolic heart failure is predominantly related to coronary artery disease followed by idiopathic cardiomyopathy, valvular disease, and hypertensive heart disease. The left ventricular remodeling process owing to permanent increases in volume load plays a critical role in the clinical manifestation and outcome in systolic heart failure patients. This also leads to the systemic and local activation of the renin-angiotensin-system (RAS) associated with some hypertrophic growth, change in the phenotype of the cardiac myocyte due to reappearance of fetal gene program, increasing degeneration of contractile protein, malfunctioning excitation-contracting coupling, interstitial fibrosis, and a decrease in contractile response to beta-adrenergic stimulation. In this respect, numerous clinical investigations have unraveled beneficial effects of RAS blockade with angiotensinconverting enzyme inhibitors, angiotensin II type 1 receptor blockers, and aldosterone antagonists leading to a distinct improvement in symptoms and clinical outcome in systolic heart failure patients. Yet, RAS blockade treatment may not necessarily lead to a beneficial treatment response as a variety in individual responses may exist. The reported inter-individual variability in treatment response to RAS blockade in systolic heart failure patients remains obscure that may be related, at least in part, to differences in race, ethnicity, comorbid conditions, concomitant use of other medications, and certain genetic predispositions. Given the reported variability in myocardial response to medical RAS blockade, apart from suboptimal medical RAS blockade in the myocardium, differences in myocardial contractile responsiveness to sympathetic activation and its interaction with decreased renal function may, at least in part, account for observed variability in treatment responses in heart failure patients. In this issue of the Journal of Nuclear Cardiology, Marsico et al. report of novel and important findings in that patients with renal dysfunction and systolic heart failure have a worse impairment of cardiac sympathetic activity than in those systolic heart failure patients with preserved renal function. The study consisted of 263 patients with mild-to-severe heart failure (NYHA II-III) of ischemic and non-ischemic origin (27% vs. 73%) undergoing I-meta-iodobenzylguanidine (I-MIBG) myocardial scintigraphy assessing cardiac sympathetic activation. The heart-to-mediastinal (H/M) ratio was derived from early and late activities and the wash out rate was calculated. As it was observed, the GFR positively correlated with late H/M ratio (r = 0.215; p\ 0.001), signifying some interaction among reductions in kidney function and an impairment of cardiac sympathetic activity. When the study population was sub-grouped into moderate-to-severe and normal-tomild GFR reduction, a decrease in late H/M ratio was noted in patients with renal dysfunction compared to those without (1.49 ± 0.21 vs. 1.56 ± 0.26, p = 0.03). Importantly, a reduction in glomerular filtration rate (GFR) was indeed an independent predictor of reduced cardiac sympathetic activity, implying indeed a direct Reprint requests: Thomas H. Schindler, MD, PhD, Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway, St. Louis, MO 63110; [email protected], [email protected] J Nucl Cardiol 2021;28:2123–5. 1071-3581/$34.00 Copyright 2019 American Society of Nuclear Cardiology.