Cardiac and renal sympathetic nerve activation in early-stage HFpEF: insights from ¹³¹I-MIBG imaging study

While sympathetic overactivity is a well-established driver of disease progression in heart failure with reduced ejection fraction, its role in early-stage heart failure with preserved ejection fraction (HFpEF) remains unclear. In particular, renal sympathetic activity-an important contributor to neurohormonal dysregulation-has not been systematically evaluated in HFpEF. Early-stage HFpEF refers to patients who present with mild symptoms, only modest elevations in B-type natriuretic peptide (BNP), and invasively confirmed elevated left ventricular end-diastolic pressure (LVEDP) but without overt structural remodeling or severe congestion. We conducted a single-center retrospective randomized controlled study including 121 patients with early-stage HFpEF and 44 matched controls. All participants underwent ¹³¹I-metaiodobenzylguanidine (¹³¹I-MIBG) scintigraphy to quantify sympathetic nerve activity in the heart and kidneys. Uptake ratios (15 min and 4 h heart-to-mediastinum [H/Ma] and kidney-to-posterior mediastinum [K/Mp]) and washout rates (Heart Washout Rate [HWR] and Kidney washout Rate [KWR]) were calculated. Correlations with these MIBG parameters and left ventricular end-diastolic pressure (LVEDP) were analyzed. HFpEF patients showed significantly higher cardiac H/Ma and renal K/Mp ratios, and lower HWR and KWR compared with controls (all P < 0.001). In the HFpEF group, both 4-h H/Ma and 4-h K/Mp ratios were positively correlated with LVEDP, while HWR and KWR were inversely correlated with these indices (all P < 0.01). Early-stage HFpEF patients show increased cardiac and renal sympathetic activity, highlighting the renal sympathetic nervous system as a potential therapeutic target and suggesting ¹³¹I-MIBG scintigraphy as a promising tool for risk stratification and early intervention.