Synthetic HRV assessment of autonomic modulation effects induced by empaglifozin added to optimized therapy in a patient with post-COVID paroxysmal atrial fibrillation-induced heart failure and normal

Abstract Introduction According to ESC guidelines, early administration of SGLT2 inhibitors (SGLT2i) is recommended (class IA) for the management of heart failure (HF) with reduced or preserved ejection fraction (EF) 1. Given the importance of cardiac autonomic modulation (CAM) dysfunction in HF, CAM assessment before and during HF treatment with SGLT2i may provide a better mechanistic understanding of their beneficial effects for HF management. Indeed, early administration of dapagliflozin improved autonomic function in early-onset post-myocardial infarction HF 2. Besides traditional Heart Rate Variability (HRV), mathematical methods for automatic calculation of the parasympathetic (PNSi), sympathetic (SNSi), and Baevsky’s stress (BSTRi) indexes are now available for more synthetic CAM assessment 3,4. Since sympathetic overdrive is a well-recognized mechanism implicated in the pathogenesis and deterioration of HF, the benefit of SGLT2i could be due to direct sympathetic signaling reduction or indirectly, by vagal activation favoring a protective CAM 5. Objective To describe the reproducible PNSi enhancement and SNSi decrement, evidenced by HRV assessment before and during empagliflozin (10 mg q.d.) added to optimized HF treatment, observed in a non-diabetic 80-year-old patient with LBBB, normal coronary angiography, and post-COVID persistent atrial fibrillation-induced HF, during 9-months follow-up. Method HRV analysis of linear (L), non-linear (NL), and time-varying (TV) parameters was performed with Kubios (v3.5), using five 24-hour ECG Holter sessions (two before and three during 9 months of SGLT2i), from short (2-minute) or whole, selected intervals, during daily activity (DA) and non-REM sleep. PNSi, SNSi, and BSTRi were automatically calculated. Results The patient’s EF was normal before a post-COVID persistent AF-induced HF requiring DC-cardioversion. After sinus rhythm recovery and optimized HF therapy, the patient was minimally symptomatic (NYHA II), with improvement of reduced EF from 32% to 40%. During 9 months of empagliflozin treatment, EF increased from 40% to 44%. CAM was characterized by a highly significant increment of PNSi and concomitant reduction of SNSi, with changes of L and NL parameters nonsignificant during DA, but statistically significant during non-REM sleep (Table 1). An example of the automatic TV graphic display of the PNSi and SNSi dynamics is shown in Figure 1. Conclusion PNSi and SNSi provided a synthetic assessment of CAM, highlighting that changes toward enhanced vagal modulation due to a concomitant decrement of sympathetic tone and increment of vagal tone, especially evident during non-REM sleep, may contribute to the beneficial effects of long-term HF treatment with SGLT2i. Further assessment of CAM exploring the effects of SGLT2i during both DA and sleep could be useful for a better mechanistic understanding of SGLT2i's therapeutic efficacy in HF patients.Table 1 PNSi, SNS, and HRV parameters. Figure 1.PNSi and SNSi interacion