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In the growing therapeutic armamentarium for heart failure (HF) management, vericiguat represents an innovative therapeutic option. The biological target of this drug is different from that of other drugs for HF. Indeed, vericiguat does not inhibit neuro-hormonal systems overactivated in HF or sodium–glucose co-transporter 2 but stimulates the biological pathway of nitric oxide and cyclic guanosine monophosphate, which is impaired in patients with HF. Vericiguat has recently been approved by international and national regulatory authorities for the treatment of patients with HF and reduced ejection fraction who are symptomatic despite optimal medical therapy and have worsening HF. This ANMCO position paper summarises key aspects of vericiguat mechanism of action and provides a review of available clinical evidence. Furthermore, this document reports use indications based on international guideline recommendations and local regulatory authority approval at the time of writing.

Sodium–glucose cotransporter 2 inhibitors (SGLT2-is) have recently been included among the first-line drugs for the treatment of heart failure with reduced ejection fraction. International guidelines recommend SGLT2-i use in association with neuro-hormonal modulators (renin–angiotensin blockers, beta blockers, and aldosterone antagonists). Although SGLT2-is are well tolerated, it is important to know potential side effects and conditions that may lead to an increased risk of adverse events in order to maximize clinical benefits. The aim of this Italian Association of Hospital Cardiologists document is to briefly report clinical evidence that supports SGLT2-i use in patients with heart failure and provide practical indications for clinical implementation.

Gut microbiota impacts host health by mediating beneficial physiological processes. However, growing evidence supports the potential role of microbiota in disease development and progression. In this review, we report current knowledge on pathophysiologic processes mediated by gut microbiota that may be implicated in atherosclerosis development and progression. We also summarize findings provided by clinical studies that indicate an association between gut microbiota composition and/or function and atherosclerotic cardiovascular diseases. Finally, we discuss potential strategies to impact gut microbiota composition and/or function in order to reduce the atherosclerotic cardiovascular risk.

Sodium-glucose cotransporter 2 inhibitors (SGLT2-i), initially developed as glucose-lowering agents for the treatment of type 2 diabetes, based on significant clinical benefits shown in patients with heart failure, have recently been included among the first-line drugs for the treatment of heart failure with reduced ejection fraction. International guidelines recommend SGLT2-i use in association with neuro-hormonal modulators (renin-angiotensin blockers, beta-blockers, and aldosterone antagonists). Although SGLT2-i are well tolerated, for an appropriate use and to maximize clinical benefits, it is important to know potential side effects and conditions that may lead to an increased risk of adverse events. The aim of this ANMCO document is to briefly report clinical evidence that support SGLT2-i use in patients with heart failure and provide practical indications for clinical implementation.

Background Sporadic high impedance values without other anomalies detected by remote monitoring of hybrid cardiac implantable electronic device systems have been described recently. The clinical significance and related hazard of this phenomenon are not fully understood. Objective The purpose of this study was to describe the prevalence, management, and outcomes associated with hybrid implantable cardioverter-defibrillator (ICD) systems. Methods We collected data on patients with sporadic high lead impedance alert on remote monitoring who had undergone implantation with a hybrid ICD system between January 2015 and December 2019. Pacing thresholds, sensing and impedance values, and temporal pattern of impedance values were collected by remote monitoring, at implantation, and during an in-office visit. Results Among 92 patients receiving a hybrid ICD, 15 (16.3%) had high impedance alert on remote monitoring (14 Boston Scientific and 1 St. Jude Medical ICD canisters paired with Medtronic or Biotronik DF-1 leads). Four patients had a cardiac resynchronization therapy–defibrillator (CRT-D), 7 a dual-chamber ICD, and 4 a single-chamber ICD. Three patients presented with high atrial lead impedance, 7 high right ventricular lead impedance, 1 high left ventricular impedance, and 2 high shock impedance values. All patients underwent follow-up by remote monitoring. Sporadic high impedance values were not associated with an adverse outcome or need for revision in all but 1 patient, who had continuously increasing pacing thresholds due to lead microfracture. Conclusion In the absence of clear signs of lead fracture or connection issues, sporadic high pacing and shock impedance in hybrid implantable defibrillator systems can be safely managed by close follow-up.

In 2007, great concern arose regarding failure of implantable cardioverter defibrillator (ICD) leads from several manufacturers. Of this analysis was to evaluate the incidence and predictors of Sprint Fidelis lead failure in order to find the best clinical strategy to prevent lead-related adverse events. Four hundred fourteen patients (357 male, 67 ± 12 years) with ICD equipped with right ventricular Sprint Fidelis leads were followed up in our institution. Over a median follow-up of 35 months (25th–75th percentile = 27–47 months) and a total follow-up of 1,231 patient-years, lead failures occurred in 40 of 414 (9.7%) patients. The annual rate was 3.2% per patient-year. Thirty-five (87.5%) failures were caused by pacing–sensing connector fracture. The risk of lead fracture was higher in patients younger than 70 years (odds ratio = 2.31; 95% confidence interval = 1.14–4.68, p = 0.02). Among 30 patients with pacing–sensing conductor failure and available device diagnostics for failure alerting, the diagnostic parameter which first responded to lead failure was the sensing integrity counter in 15 of 30 (50%), pacing impedance in 12 of 30 (40%), and non-sustained ventricular tachycardia in 3 of 30 (10%). The median time (25th–75th percentile) between diagnostics alert and lead failure-related adverse events or failure acknowledgment was 2.2 (0.3–13.0) days. Twenty-two patients suffered inappropriate shocks due to lead failure. In 50% of patients, daily monitoring by device diagnostics would have alerted physicians to impending lead failure at least 1 day in advance. Automatic algorithms based on device diagnostics may detect impending lead failure in nearly 50% of cases. Remote monitoring may prevent failure-related adverse events.

Aims Despite not being uncommon, limited evidence exists about predisposing factors for venous obstruction in patients with implantable electronic devices. We aimed to assess the prevalence of severe venous obstruction in patients with intravenous devices and identify predictor factors. Methods and results A total of 184 patients underwent venography to detect venous obstruction associated with the inserted lead. Vessel obstruction was graded as venous occlusion (complete flow interruption), severe obstruction (narrowing >90%), or mild–moderate obstruction (narrowing 50–90%). Severe venous obstruction/occlusion prevalence was 11.4% ( n = 21) and was always asymptomatic. Collateral circulation was found in 80.9% of patients with severe obstruction/occlusion. Twelve patients (6.5%) had 3 leads. The rates of patients with secondary prevention of sudden cardiac death as indication for implantable devices and of those of patients with 3 leads were significantly greater in the group with severe obstruction/occlusion than in the non-severe obstruction/occlusion group (respectively, P = 0.004 and P = 0.03). Logistic analysis adjusted for venous thromboembolic risk factors confirmed that secondary prevention of sudden cardiac death as indication for implantable devices [odds ratio (OR), 7.1; 95% confidence interval (CI): 1.4–35.3; P = 0.017] and the presence of 3 leads (OR, 8.5; 95% CI: 1.75–41.35; P = 0.008) were predictors of severe obstruction/occlusion. Conclusion In patients with implantable devices, severe venous obstruction prevalence is not negligible and the lack of symptoms does not exclude it. The presence of three leads and sudden cardiac death as indication for implantable devices seem to be associated with the presence of severe venous obstruction/occlusion.

We examined the effects of sleep microstructure, ie, the cyclic alternating pattern (CAP), on heart rate (HR)- and blood pressure (BP)-regulating mechanisms and on baroreflex control of HR in healthy humans and tested the hypothesis that sympathetic activation occurring in CAP epochs during non-rapid eye movement (non-REM) sleep periods is buffered by the arterial baroreflex. Ten healthy males underwent polysomnography and simultaneous recording of BP, ECG, and respiration. Baroreflex sensitivity (BRS) was calculated by the sequences method. Autoregressive power spectral analysis was used to investigate R-R interval (RRI) and BP variabilities. During overall non-REM sleep, BP decreased and RRI increased in comparison to wakefulness, with concomitant decreases in low-frequency RRI and BP oscillations and increases in high-frequency RRI oscillations. These changes were reversed during REM to wakefulness levels, with the exception of RRI. During CAP, BP increased significantly in comparison to non-CAP and did not differ from REM and wakefulness. The low-frequency component of BP variability was significantly higher during CAP than non-CAP. RRI and its low-frequency spectral component did not differ between CAP and non-CAP. BRS significantly increased during CAP in comparison to non-CAP. BRS was not different during CAP and REM and was greater during both in comparison with the awake state. Even during sleep stages, like non-REM sleep, characterized by an overall vagal predominance, phases of sustained sympathetic activation do occur that resemble that occurring during REM. Throughout the overnight sleep period, the arterial baroreflex acts to buffer surges of sympathetic activation by means of rapid changes in cardiac vagal circuits.

We examined the effects of the various sleep stages on baroreflex sensitivity (BRS), and heart rate and blood pressure (BP) variability, and tested the hypothesis that there is a different behavior of the baroreflex control of the sinus node in response to hypertensive and hypotensive stimuli and in relation to different cycles of the overnight sleep.Polygraphic sleep recordings were performed in 10 healthy males. The BP and the RR interval were continuously recorded during sleep.BRS was calculated by the sequences method. Autoregressive power spectral analysis was used to investigate the RR-interval and BP variabilities.During rapid eye movement (REM) sleep BRS significantly increased in response to hypertensive stimuli in comparison with non-rapid eye movement (NREM) sleep and the awake state, whereas it did not change in response to hypotensive stimuli. In the first sleep cycle, BRS significantly increased during NREM in comparison with wakefulness, whereas during REM BRS in response to hypertensive stimuli did not show significant changes as compared with the awake state and/or with NREM. During REM occurring in the sleep cycle before morning awakening, BRS showed a significant increase in response to hypertensive stimuli in comparison with both NREM and the awake state.During sleep, arterial baroreflex modulation of the sinus node is different in response to hypotensive and hypertensive stimuli particularly during REM. Furthermore, baroreflex control of the sinus node shows a non-uniform behavior during REM occurring in different nocturnal sleep cycles. These findings suggest that the arterial baroreflex is more effective in buffering the increased sympathetic activation associated with REM at the end of sleep than in the early night.

Oral anticoagulation is a widely used treatment and atrial fibrillation (AF) is the most frequent indication. We review the therapeutic options on an important clinical challenge: rapid reversal anticoagulation in the setting of an urgent invasive procedure. We report a case of a 71-year-old man treated with warfarin who was over-anticoagulated when presented to the emergency department for syncope due to severe bradiarrhythmia and needed temporary pacing. Intravenous infusion of vitamin-k was not adequate for rapid reversal over anticoagulation whereas the administration of a Prothrombin Complex Concentrate (PCC) was able to quickly reverse anticoagulant activity and allowed the performance of an urgent invasive procedure without hemorrhagic complication. The aim of this paper is to draw attention to possible therapeutic strategies to reduce the risk of bleeding related to over-anticoagulation with vitamin-K antagonists (VKAs) in case of urgent invasive procedure, emphasizing the role of PCC in keeping with national and international guidelines.

Aim The aim of this multicentre, observational, transversal study was to evaluate pacemaker (PM) choice and setting in a large number of patients, in order to understand their relationship with the patients’ clinical characteristics. Methods and results The study enrolled a total of 1858 patients (71 ± 14 years, 54% male), consecutively evaluated during scheduled PM follow-up visits in 7 Italian cardiac arrhythmia centres. To evaluate the appropriateness of PM choice in relation to the patients’ clinical characteristics, we analysed their rhythm disorders at the time of device implantation and the characteristics of the devices implanted. To evaluate the appropriateness of device setting, current rhythm disorders and device setting at the time of enrolment were analysed. In the overall study population, 64.3% of the patients received a PM with all of the features required for their rhythm disorder [80.8% in persistent atrioventricular (AV) block, 76.5% in atrial fibrillation needing pacing, 71.0% in sinus node disease, 58.7% in non-persistent atrioventricular block (AVB), 52.7% in neuro-mediated syncope]. The most frequent cause of inappropriate PM choice was the lack of an algorithm to promote intrinsic AV conduction in non-persistent AVB patients (38.1%). In 76.2% of the patients with an appropriate PM ( n = 1301), the PM was optimally set for their rhythm disorder. Conclusions In the present ‘real-world’ registry, a large number of patients (35.7%) did not receive an optimal PM for their rhythm disorders. Moreover, one-fourth of appropriate PMs were not programmed according to the patients’ clinical characteristics.

Atrioventricular junction (AVJ) ablation followed by biventricular pacing is an established strategy for improving symptoms and morbidity in patients with permanent atrial fibrillation (AF), reduced left ventricular ejection fraction (LVEF), and uncontrolled ventricular rate. There is no clear evidence that such patients benefit from rate-responsive (RR) pacing.This prospective, randomized, single-blind, multicentre study was designed as an intra-patient comparison and enrolled 60 patients (age 69.5 ± 11.8 years, males 63.3%, NYHA 3.0 ± 0.6) with refractory AF and reduced LVEF (mean 32.4 ± 8.3%) treated with AVJ ablation and biventricular pacing. Two 6-minute walking tests (6MWT) were performed 1 week apart: one during VVI 70/min biventricular pacing and the other during VVIR 70-130/min biventricular pacing; patients were randomly and blindly assigned to Group A (n = 29, first 6MWT in VVIR mode) or B (n = 31, first 6MWT in VVI mode). Rate-responsive activation determined an increase of 18.8 ± 24.4 m in the distance walked during the 6MWT (P0.001). The increase was similar in both groups (P = 0.571). A5% increase in the distance walked was observed in 76.7% of patients. The increase in the distance walked was linearly correlated with the increase in heart rate recorded during the 6MWT in the VVIR mode (r = 0.54; P0.001).In permanent AF patients with uncontrolled rate and reduced LVEF who had undergone AVJ ablation and biventricular pacing, RR pacing yields a significant gain in exercise capacity, which seems to be related to the RR-induced frequency during effort.

AimsEvaluation of ambulatory blood pressure monitoring (ABPM), two-dimensional (2D) echo and clinical variables in predicting cardiac death and acute decompensated heart failure in patients with ischaemic cardiomyopathy and receiving a cardioverter-defibrillator implantation.Methods and resultsWe st

Cardiologists often are called to explain electrocardiograms of pacemaker/ implantable cardioverter (PMK/ICD) patients during arrhythmic events. The most frequent arrhythmia is atrial fibrillation (AF) whether in PMK or in ICD patients. Generally, it is not difficult to diagnose, it can affect the quality of life of this subgroup because it can generate inappropriate and painful therapies. Arrhythmias as atrioventricular block or other bradyarrhythmias can show a particular way of presentation specially for the device's intervention using specific algorithms that cardiologists should know to adequately interpret the phenomenon. For example, Rate Drop Response algorithm (to prevent syncope) or other antiarrhythmic functions for atrial tachyarrhythmias (Post Mode Switching Overdrive Pacing (PMOP) or Atrial Rate Stabilization) can alter surface electrocardiogram after AF or atrial ectopic beats. Ventricular arrhythmias in ICD patients are frequent. Burst, ramp and shock are therapies with a high percentage of efficacy. However, sometimes, supraventricular arrhythmias (SVT) can induce inappropriate interventions. In other cases appropriate burst, ramp or shock (during a ventricular tachycardia (VT)) can degenerate it in a fast ventricular tachycardia or in ventricular fibrillation with consequent shocks. Wavelet, onset, stability, and other algorithms, specifically in dual chamber ICDs, are used to discriminate SVT from VT assuring more specific interventions.

Endothelial function is impaired in first-degree relatives (FDRs) of patients with type 2 diabetes. Many states characterized by endothelial dysfunction are associated with increased cardiovascular sympathetic outflow. In this study, we investigated endothelial and autonomic nervous system (ANS) functioning in FDRs and tested the hypothesis that in basal condition, impaired endothelial function is associated with impaired cardiovascular ANS regulation. Flow-mediated endothelium-dependent and -independent vasodilation of the brachial artery was measured with high-resolution ultrasound in 27 otherwise healthy FDRs (14 men and 13 women; mean age 32 years) with normal oral glucose tolerance and in 15 age- and gender-matched control subjects. Cardiovascular ANS regulation was investigated by means of spectral analysis of heart rate and systolic blood pressure (SBP) variability. Baroreflex sensitivity was assessed by the spontaneous baroreflex sequences technique. Flow-mediated endothelium-dependent vasodilation was 9.4±1.0% in FDRs and 17.0±2.3% in control subjects ( P =0.001). Low-frequency oscillations in SBP variability were 8.6±2.8 and 2.8±0.6 mm Hg in FDRs and controls, respectively ( P =0.04). Baroreflex sensitivity was significantly less in FDRs than controls (22.8±2.7 versus 37.0±5.8, respectively; P =0.01). Change in vessel diameter was inversely correlated with the low-frequency component of SBP variability ( r =−0.40; P =0.014). In healthy FDRs of diabetic patients there is a concomitant, possibly related, impairment in endothelial and ANS functioning, which manifests, indirectly, with increase in vascular sympathetic outflow and a depressed baroreflex, vagal, control of heart rate.