Background: A gradual worsening of autonomic control of cardiovascular function accompanies the progression of heart failure. Exercise training modulates autonomic balance, and may affect the prognosis of the disease. Aims: The sympathovagal balance was studied after 3 months of low-intensity rehabilitation compared with conventional therapy in 45 patients with heart failure (52% ischemic, 48% idiopathic), of whom 30 underwent rehabilitation and 15 did not. In 11 rehabilitated patients we also studied the effects on autonomic profile of 6 additional months of home-based training. Rehabilitated and non-rehabilitated patients had similar NYHA class, ejection fraction, exercise pVO2; 50% assumed carvedilol (39±5 mg/day). Methods and results: Autoregressive power spectral density of RR intervals variability were assessed during 10 min of: (1) supine rest and free breathing; (2) supine rest and breathing at 20 acts/min (- vagal stimulus); (3) standing (- sympathetic stimulus). During each period, the ratio LF/HF of the individual autospectrum indicated the sympathovagal balance. After 3 months of rehabilitation, pVO2 increased (20%); LF/HF at rest was unchanged (8.7±1.2 vs. 9.2±1.2); it decreased with controlled breathing (−18%) and increased during standing (+79%) (P<0.05). These changes were more evident after 6 months of home-based training, when pVO2 was still high: LF/HF at rest was reduced (5.4±0.9 vs. 8.5±2.1), decreased during controlled breathing (−17%) and increased during standing (87%) (P < 0.05). No changes in any variable were seen in non-rehabilitated patients. Conclusions: A low intensity rehabilitation program restores autonomic tone and reactivity to vagal and sympathetic stimuli. Some of these effects are already evident after the initial hospital-based phase.

The role of repeated infusions of Levosimendan (LEVO) in patients with chronic advanced heart failure is still unclear. Thirty-three patients with chronic heart failure presenting clinical deterioration were randomized 2:1 to receive monthly infusions of LEVO (n = 22) or Furosemide (Controls, n = 11). At the first drug's administration, noninvasive hemodynamic evaluation was performed; before and after each infusion, we assessed NYHA class, systolic and diastolic function, functional mitral regurgitation, and brain natriuretic peptide (BNP) levels. Noninvasive hemodynamic in the LEVO group showed vasodilation and decrease in thoracic conductance (index of pulmonary congestion), whereas in Controls, only a reduced thoracic conductance was observed. In the LEVO group, systolic and diastolic function, ventricular volumes, severity of mitral regurgitation, and BNP levels improved over time from baseline and persisted 4 weeks after the last infusion (P < 0.01). In Controls, no change developed over time in cardiac function and BNP levels. In LEVO-treated patients, 1-year mortality tended to be lower than in those treated with Furosemide. In conclusion, serial LEVO infusions in advanced heart failure improved ventricular performance and favorably modulated neurohormonal activation. Multicenter randomized studies are warranted to test the effect of LEVO on long-term outcome.

Background: Heart rate variability (HRV) is a reliable and convenient method to assess autonomic function. Cross-sectional studies have established a link between HRV and cognition. Longitudinal studies are an emerging area of research with important clinical implications in terms of the predictive value of HRV for future cognition and in terms of the potential causal relationship between HRV and cognition. However, they have not yet been the objective of a systematic review. Therefore, the aim of this systematic review was to investigate the association between HRV and cognition in longitudinal studies. Methods: The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Embase, PsycINFO and PubMed databases were searched from the earliest available date to 26 June 2023. Studies were included if they involved adult human subjects and evaluated the longitudinal association between HRV and cognition. The risk of bias was assessed with the Newcastle–Ottawa Scale for Cohort Studies. The results were presented narratively. Results: Of 14,359 records screened, 12 studies were included in this systematic review, with a total of 24,390 participants. Two thirds of the studies were published from 2020 onwards. All studies found a longitudinal relationship between HRV and cognition. There was a consistent association between higher parasympathetic nervous system (PNS) activity and better cognition, and some association between higher sympathetic nervous system activity and worse cognition. Also, higher PNS activity persistently predicted better executive functioning, while data on episodic memory and language were more scant and/or controversial. Conclusions: Our results support the role of HRV as a biomarker of future cognition and, potentially, as a therapeutic target to improve cognition. They will need confirmation by further, more comprehensive studies also including unequivocal non-HRV sympathetic measures and meta-analyses.

Modifiable risk factors, including life-style habits and psychological variables, have been increasingly demonstrated to have an important role in influencing morbidity and mortality in cardiovascular patients, and to account for approximately 90% of the population risk for cardiac events.