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Sympathetic activation has been long appreciated exclusively as a fundamental compensatory mechanism of the failing heart and, thus, welcome and to be supported. In the initial clinical phases of heart failure (HF), the sympathetic nervous system overdrive plays a compensatory function aimed at maintaining an adequate cardiac output despite the inotropic dysfunction affecting the myocardium. However, when the sympathetic reflex response is exaggerated it triggers a sequence of unfavourable remodelling processes causing a further contractile deterioration that unleashes major adverse cardiovascular consequences, favouring the HF progression and the occurrence of fatal events. Eventually, the sympathetic nervous system in HF was demonstrated to be a ‘lethality factor’ and thus became a prominent therapeutic target. The existence of an effective highly specialized intracardiac neuronal network immediately rules out the old concept that sympathetic activation in HF is merely the consequence of a drop in cardiac output. When a cardiac damage occurs, such as myocardial ischaemia or a primary myocardial disorder, the adaptive capability of the system may be overcame, leading to excessive sympatho-excitation coupled with attenuation till to abolishment of central parasympathetic drive. Myocardial infarction causes, within a very short time, both a functional and anatomical remodelling with a diffuse up-regulation of nerve growth factor (NGF). The subsequent nerve sprouting signal, facilitated by a rise in the levels of NGF in the left stellate ganglion and in the serum, triggers an increase in cardiac nerve density in both peri-infarct and non-infarcted areas. Finally, NFG production decreases over time, supposedly as an adaptative response to the prolonged exposure to sympathetic overactivity, leading in the end to a reduction in sympathetic nerve density. Accordingly, NGF levels were markedly reduced in patients with severe congestive heart failure. The kidney is the other key player of the sympathetic response to HF as it indeed reacts to under-perfusion and to loop diuretics to preserve filtration at the cost of many pathological consequences on its physiology. This vicious loop ultimately participates to the chronic and disruptive sympathetic overdrive.In conclusion, sympathetic activation is the natural physiological consequence to life stressors but also to any condition that may harm our body. It is the first system of reaction to any potential life-threatening event. However, in any aspect of life over reaction is never effective but, in many instances, is, actually, life threatening. One for all is the case of ischaemia-related ventricular fibrillation which is, strongly facilitated by sympathetic hyperactivity. The take home message? When, in a condition of harm, everybody is yelling failure is just around the corner.

Pharmacological treatment of heart failure with reduced ejection fraction has undergone considerable development in recent years. Type 2 sodium–glucose co–transporter inhibitors represent the most recent class of drugs that has been shown to reduce hospital admissions for heart failure and deaths from cardiovascular causes and have immediately entered in the most recent international guidelines for the treatment of HFrEF patients. The objective of this survey, which involved various cardiologists from Puglia, Molise and Abruzzo, was to analyze the clinical characteristics and therapeutic associations of patients in whom SGLT2i therapy was prescribed. Into the REINFORCE project, each of the cardiologists participating in the survey was asked to provide anonymised data of patients who were initiated on SGLT2i therapy. Each cardiologist provided information on the main clinical and therapeutic characteristics of the patients. Data relating to 788 patients on SGLT2i therapy (98.8% dapagliflozin) were analysed. 71% of patients were male, with a mean age of 69.5 years. Approximately 53.5% of the cases had an ischemic heart failure aetiology, 73% had arterial hypertension and 40.6% had type 2 diabetes mellitus. Of these, 83.9% had HFrEF, the 12.3% from HFmrEF and 3.9% from HFpEF. 38.8% of patients had presented an episode of hospitalization for heart failure (in the previous 6 months). At the time of the visit, 23.2% of patients had a serum creatinine value >1.3 mg/dL. 47% of patients were in NYHA Class I–II, while 53% had an advanced class (NYHA III). The analysis of concomitant drug therapies using SGLT2i showed that: 93.4% of the patients were on therapy with a renin angiotensin system inhibitor (40.5% ACEI/ARBs and 52.8% ARNI), 65.9% were on MRA and 91.5% beta blockers. 86.1% of patients were on concomitant diuretic therapy with furosemide.

Sodium–glucose co–transporter type 2 inhibitors are the new class of drugs that have been shown to reduce heart failure hospitalizations and cardiovascular deaths in patients with HFrEF with a class of recommendation IB for the treatment of patients with HFrEF in the most recent international guidelines. The objective of this observational study was to analyze the main clinical characteristics, therapeutic associations and any adverse events highlighted in outpatients in which SGLT2i therapy was added. Data from 42 patients on SGLT2i therapy (98.2% dapagliflozin) were analysed. 71% of patients were male, with a mean age of 70.5 years. Approximately 52% of cases had an ischemic heart failure aetiology, 54% had arterial hypertension, and 27% had type 2 diabetes mellitus. Of these, 76% had HFrEF, 14% had HFmrEF and the remaining 9% from HFpEF. At the time of the visit, 11.9% of patients had a serum creatinine value > 1.3 mg/dL. Thirty–one percent of patients were NYHA Class III. The analysis of concomitant drug therapies with the use of SGLT2i showed that 76% of patients were on therapy with a renin angiotensin system inhibitor (62% ACEI/ARBs and 14% ARNI), 71% were on MRA and 91% % beta blockers. 82% of patients were on concomitant diuretic therapy with furosemide. ARNI therapy was suspended due to hypotension in 5% of cases (2 patients). No patient had significant renal deterioration requiring discontinuation of SGLT2i.

In recent years, the pharmacological treatment of HFrEF has undergone considerable development. Two pharmacological classes in particular have been shown to significantly reduce cardiovascular events and hospitalizations: ARNI and SGLT2i. The objective of this observational study was to provide "real word" data on the effective use of these drugs, the efficacy, safety and tolerability of their simultaneous administration. We analyzed 82 patients admitted to our clinic over a period of 6 months and reported their clinical characteristics and the effective therapies administered. The data of 82 patients, 64% male, with an average age of 70.5 years were analysed. 49% with ischemic heart disease, 54% hypertension and 31% type 2 diabetes mellitus. Of these, 47.5% with HFrEF, 21% with HFmrEF, and the remaining 30% with HFpEF. At the time of visit, 19.5% of patients had a GFR <59 mL/min/1.73m2. 31% of the patients were in NYHA Class III. We then analyzed the drug therapies provided. Assuming that a very high percentage of patients were taking beta blockers and MRA (91% and 79% respectively), we found that about 72% of patients were on concomitant therapy with a renin angiotensin system inhibitor (51% ARNI, 21% ACEI/ARBs). Among the 51% of patients in ARNI, as many as 32% took the minimum dose of the drug (24/26mg bid), 11% the intermediate dose (49/51mg bid) and only the 8% the maximum recommended dosage (97/103 mg bid). In the group of patients with HFrEF, 10% were not on ARNI therapy or this drug had been discontinued during the follow–up (92% for hypotension, 8% for ARF on IRC). As for gliflozines, 46% of the patients analyzed were on SGLT2i therapy (and of these, approximately 70% had HFrEF). 30% of the total patients were in concomitant therapy with ARNi and SGLT2i (62% of patients affected by HFrEF).

Renal resistance index (RRI) is a parameter which is easily evaluable by the echo Doppler technique and which has been demonstrated to predict worsening of renal function (WRF) in patients affected by chronic heart failure as well as among those undergoing coronary angiography. The aim of this study was designed to evaluate the role of the RRI in predicting WRF after cardiac surgery.

Worsening of renal function (WRF) is frequently observed after cardiac surgery and it is associated with both short– and long–term worse outcome. Among the pathophysiological conditions favoring the occurrence of WRF, the abnormalities in renal blood flow could play a key role. The aim of this study was to evaluate the changes in renal resistance index (RRI), a parameter reflecting renal parenchymal and hemodynamic parameters, after cardiac surgery.