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Limited data are available on right (RV) and left (LV) ventricular structures and functions in acute heart failure with preserved ejection fraction (AHF-pEF) presenting with hypertensive pulmonary edema (APE) versus predominant peripheral edema (peHF).In a prospective study of consecutive patients with AHF-pEF, 80 patients met inclusion and not exclusion criteria, and underwent echocardiographic and laboratory examination in the emergency ward. The survived (94%) were re-evaluated at the discharge. At admission, systolic, diastolic, pulse blood pressure (BP), and high sensitivity troponin I were higher (all P 0.05) with APE than with peHF while brain-type natriuretic peptide (BNP), hemoglobin and estimated glomerular filtration rate (eGFR) did not differ between the two phenotypes. LV volumes and EF were comparable between APE and peHF, but APE showed lower relative wall thickness (RWT), smaller left atrial (LA) volume, higher pulse pressure/stroke volume (PP/SV), and higher ratio between the peak velocities of the early diastolic waves sampled by traditional and tissue Doppler modality (mitral E/e', all P 0.05). Right ventricular and atrial (RA) areas were smaller, tricuspid anular plane systolic excursion (TAPSE) and estimated pulmonary artery peak systolic pressure (sPAP) were higher with APE than with peHF (all P 0.05) while averaged degree of severity of tricuspid insufficiency was greater with peHF than with APE. At discharge, PP/SV, mitral E/e', sPAP, RV sizes were reduced from admission in both phenotypes (all P 0.05) and did not differ anymore between phenotypes, whereas LV EF and TAPSE did not show significant changes over time and treatments.In AHF-pEF, at comparable BNP and LV EF, hypertensive APE showed eccentric LV geometry but smaller RV and RA sizes, and higher RV systolic function, increased LV ventricular filling and systemic arterial loads. AHF resolution abolished the differences in PP/SV and LV diastolic load between APE and peHF whereas APE remained associated with more eccentric RV and higher TAPSE.

Aims: Sudden cardiac death (SCD) causes high mortality and substantial societal burdens for healthcare systems (HSs). The risk of SCD is significantly increased in patients with reduced left ventricular ejection fraction after myocardial infarction (MI). Current guidelines recommend re-evaluation of cardioverter-defibrillator implantation 40 days post-MI, earliest. Medical therapy alone does not provide sufficient protection against SCD, especially in the first month post-MI, and needs time. Consequently, there is a gap in care of high-risk patients upon hospital discharge. The wearable cardioverter defibrillator (WCD) is a proven safe, effective therapy, which temporarily protects from SCD. Little information on WCD cost-effectiveness exists. We conducted this research to demonstrate the medical need of the device in the post-MI setting defining WCD cost-effectiveness. Methods & results: Based on a randomized clinical trials (RCTs) and Italian and international data, we developed a Markov-model comparing costs, patient survival, and quality-of-life, and calculated the Incremental Cost-Effectiveness Ratio (ICER) of a WCD vs. current standard of care in post-MI patients. The rather conservative base case analysis – based on the RCT intention-to-treat results - produced an ICER of €47,709 per Quality Adjusted Life Year (QALY) gained, which is far lower than the accepted threshold of €60,000 in the Italian National HS. The ICER per Life Year (LY) gained was €38,276. Conclusion: WCD utilization in post-MI patients is clinically beneficial and cost-effective. While improving guideline directed patient care, the WCD can also contribute to a more efficient use of resources in the Italian HS, and potentially other HSs as well.

Background Small amounts of high-sensitivity cardiac troponin (hs-cTn) I and T can be detected in healthy individuals or can occur in the absence of any clinical features of myocardial ischemia (myocardial injury). However, it is not possible to clinically distinguish whether and which increase in hs-cTn are due to which mechanisms. Moreover, predictive data regarding hs-cTnT in an emergency room (ER) setting are scanty. Consequently, with this monocentric retrospective study, we aimed at expanding the knowledge of this biomarker in this setting. Methods Consecutive adult patients presenting at the ER and hospitalized with a first abnormal hs-cTnT value (≥14 ng/L) were enrolled for 6 months. The baseline hs-cTnT value and the ensuing variations were correlated with the clinical presentation and diagnosis. Subsequently, multivariable models were built to assess which clinical and laboratory variables most influenced hospital admissions. Results At a first screening, 4660 patients were considered, and 4149 patients were enrolled (Figure 1). Of these, 1555 (37.5%) had a first hs-cTnT ≥14 ng/L, and 1007 (65%) were hospitalized according to the following diagnoses: acute coronary syndrome (ACS, 182; 18%), non-ACS cardiovascular disease (337; 34%) and non-cardiovascular disease (487; 48%). Higher hs-cTnT values as well as significant hs-cTnT variations were found in the ACS group (p < 0.01). Furthermore, in the latter, the mean percentage of variation of hs-cTnT was higher, while it was intermediate in the non-ACS group, and low in those with non-cardiovascular disease (407.5%, 270.6% and 12.4%, respectively). Only syncope and CRP (OR: 0.08, 95% CI: 0.02–0.39, p Conclusion In our study, differently from the investigated hs-cTnT, only clinical variables predicted hospitalizations in different patients’ subgroups.

Aims Cavotricuspid isthmus ablation is a routine procedure in electrophysiology laboratories. It is mainly performed as treatment for cavotricuspid isthmus-dependent atrial flutter, which is rare in young patients without structural heart disease. Safety and efficacy data regarding this procedure in such patients are scarce. In this case series we present the clinical characteristics and procedure related outcomes of 3 juvenile patients without overt structural heart disease who underwent cavotricuspid isthmus ablation in our Hospital for recurrent typical atrial flutter. Methods and Results Of the 1217 flutter ablation procedures performed in our Hospital from 2003 to 2022, 3 were on juvenile, otherwise healthy patients. The median patient age was 19.3 years old. All of them had a history of recurrent paroxysmal typical atrial flutter, which was initially terminated with electrical cardioversion. Given the young age no pharmacological prophylaxis was initiated, but on the subsequent recurrence we decided for an ablative strategy. Echocardiography and/or MRI excluded structural heart disease. One of them had experienced flutter induced tachycardiomyopathy, while one underwent previous cavotricuspid isthmus ablation with subsequent arrhythmia relapse. All the procedures were conducted using standard electrophysiology equipment successfully, without significant complications. Baseline electric characteristics of cavotricuspid isthmus were recorded and block of conduction was confirmed using standard protocols. Conclusion Recurrent cavotricuspid isthmus-dependent atrial flutter in young Patients without structural heart disease is exceptionally rare, and ablation is seldom performed. In this case series we present 3 patients with such characteristics, and in whom cavotricuspid isthmus radiofrequency ablation was successfully performed.

Background Cardiac myxomas, though uncommon, do represent the most frequent primary cardiac neoplasms in human beings. Their clinical presentation is mainly due to flow obstruction, cytokines hyperincretion or embolism. Coronary embolism related to the tumor is a rare finding. Here we describe the case of a left atrial cardiac myxoma with an acute coronary syndrome presentation. Case presentation A 71 year-old woman referred for chest pain, nausea and vomit. On the previous few months she had developed exertional dyspnea and fatigue. No prior history of cardiovascular diseases was reported. The 12-lead ECG showed no significant alterations. Troponin T values were elevated (224 ng/L, normal assay threshold Conclusion We reported a case of acute coronary syndrome due to left atrial myxoma. Coronary embolization induced by a cardiac myxoma is rare; however, it should be suspected in patients presenting with myocardial infarction without adjunctive coronary risk factors.

Background Dextrocardia is a rare congenital condition with a prevalence of 0.83 per 10000 pregnancies. Its most common configuration is situs inversus totalis, also known as “mirror-image dextrocardia”. This case report presents a clinical case of symptomatic sinus node dysfunction requiring permanent pacemaker implantation (PPI) in a patient with mirror-image dextrocardia. Case summary A 81-year-old female patient with known situs inversus totalis presented with recurrent syncope. Sick sinus syndrome was diagnosed after documentation of critical pauses (>6.3”) at 24-hour Holter monitoring, giving indication to elective PPI. At admission, 12-lead ECG showed sinus bradycardia and right axis deviation on the frontal plane (standard peripheral leads position and precordial leads on the right side of the chest). Transthoracic echocardiography was performed prior to the procedure with the ultrasound probe flipped and placed on the patient's right side of the thorax, thus achieving standard echocardiography windows and images. A preserved biventricular systolic function and the absence of relevant valvular disease or cardiac malformations was documented. The next day, a dual-chamber pacemaker was implanted following standard technique with the operator standing on the right side of the patient and with right subclavian vein puncture; the pacemaker pocket was created in the right pectoral region. The entire procedure was performed under fluoroscopic guidance using horizontally 180° flipped views, therefore obtaining identical images to those of standard PPI procedures, helping the operator identify anatomical structures during lead positioning. [Fig. 1 a - b] Chest X-ray confirmed correct pacemaker lead placement and absence of procedure-related complications. Stable and satisfactory lead parameters were observed at follow-up. Discussion In literature there are only a few case reports on PPI in situs inversus totalis. The symmetrical disposition of the anatomy makes transvenous PPI technically demanding. In this case the challenge was overcome by using flipped fluoroscopy images, to facilitate lead positioning maneuvres. This technique can be considered only in situs inversus totalis and not in other forms of dextrocardia, such as dextroversion and destroposition, because it is the only situation in which the anatomy is the mirror image of the normal one.

Aims The atrial septal pouch (ASP) is an incomplete fusion between septum primum (SP) and septum secundum (SS), resulting in a kangaroo pouch, that has a high prevalence in general populations (47%) and it is a potential site of blood stasis and thrombosis. After the novel coronavirus disease (COVID19) -related thrombotic complications, immunothrombosis has been widely investigated and proposed as key pathogenic mechanism linking coagulation and inflammation, leading sometimes to intracardiac thrombosis. In this paper we describe a case of thrombus in the ASP interestingly developed after COVID19 and made a literature review. Methods and Results A 85 years old woman with a history of hypertension and chronic atrial fibrillation (AF) in therapy with dabigatran, was admitted to our hospital for dyspnea, atypical chest pain and fever. Laboratory exams showed only mild leukocytosis and elevated levels of d-dimer; EKG confirmed AF with a normal ventricular rate and CT scan excluded pulmonary embolism. Transthoracic and transesophageal echocardiogram (TEE) (Figure 1) showed a mobile ovoid mass (13×26 mm) attached to a left-sided ASP mimicking a myxoma, no mass was seen in the left atrial appendage (LAA). Four months earlier she had been hospitalized for idiopathic thrombocytopenia and concurrent COVID19 infection with mild symptoms, therefore dabigatran was discontinued for a month. The patient underwent surgery and histopathology confirmed it was a thrombus. In the PubMed search we conducted for reports demonstrating ASP masses, or alleged thromboembolism (TE) from this site, we found 25 reports, whose characteristics are briefly summarized in Table 1. Interestingly mild thrombocytopenia was described just in one case. Conclusions In addition to the LAA, the atrial septal pouch is a newly described, common anatomic entity of the interatrial septum, that potentially serves as a site of stasis and thrombus formation. Despite its high prevalence, the finding of a thrombus in this site is very rare. According to Virchow triad, we assume that in this case an endothelial injury and hypercoagulability could have played a pivotal role, since the concomitant thrombocytopenia and high levels of d-dimer. This could be the first case of a thrombus in the ASP associated with COVID19-immunothrombosis.

Background Coronary angiography is the gold standard approach to assess coronary artery disease, especially in acute settings. Additional morphological and functional methods such as intravascular ultrasound (IVUS), optical coherence tomography (OCT), and fractional flow reserve or instantaneous wave free ratio (FFR or iFR) are used to confirm hemodynamic relevance of stenoses, to characterise plaque morphology and vessel size and to optimise stent implantation. This abstract presents a clinical case in which intracoronary imaging, in particular OCT, was essential in proper diagnosis and treatment of a patient presenting with acute coronary syndrome (ACS). Case Summary A 43-year-old female patient with no cardiac medical history presented with new onset chest pain occurring at rest from the night before. At admission, a 12-lead ECG showed sinus rhythm with negative T-waves in the precordial leads, hypokinesia of the anterior and apical wall of the left ventricle was found at echocardiography, and high sensitive cardiac troponin was slightly elevated at the first two measurements. The patient was admitted to the Intensive Coronary Unit with the diagnosis of non-ST segment elevation myocardial infarction and underwent coronary angiography within 24 hours of presentation. A slightly inhomogeneous distribution of dye was found at the ostium of left anterior descending artery (LAD). It was interpreted as a possible type 3 spontaneous coronary artery dissection or as the presence of a non obstructive stenoses. No significant findings were observed in the other cardiac vessels. Due to the discrepancy between the clinical presentation and the angiographic findings, additional morphological and functional assessment of LAD was performed. The OCT revealed the presence of an eccentric obstructive plaque on ostial LAD, and the functional study with FFR confirmed the hemodynamic significance of the stenosis. The patient therefore underwent revascularization with drug-eluting stent implantation on left-main/LAD axis; post-angioplasty OCT confirmed the correct stent position. The patient remained hemodynamically stable during the following hospital stay and was discharged on day 7, with a preserved global left ventricular function and persistence of apical wall hypokinesia, slow ECG evolution with regression of negative anterior T-waves and no sign of necrosis was also observed. Discussion There are several angiographically undetectable lesions that can be identified only by IVUS or OCT. In this case the angiographic findings were of difficult interpretation, coronary angiography alone would have been inconclusive and would have led to the diagnosis of myocardial infarction with non-obstructive coronary arteries. This case highlights the importance of intravascular imaging and functional study to guide revascularization also in the acute settings of an ACS.

A real-world analysis among the Italian population has been carried out to estimate the number of atrial fibrillation (AF) patients undergoing catheter ablation and to evaluate their clinical outcome and economic burden. A retrospective analysis on administrative Italian databases has been performed. Between January 2011 and December 2019, all patients diagnosed with AF were considered and those undergoing catheter ablation were identified. Overall, 3084 (3.54%) of AF patients with at least one catheter ablation were included (mean age 63.2, 67.3% males). A significant decrease in the use of AF-related medications and in hospitalizations, mainly related to AF and heart failure, was observed during the 3-year post-ablation period. The average total cost per patient during the 1-year before ablation period was significantly higher compared to the 1-year post-ablation cost (EUR 5248 vs. 4008, respectively; p < 0.001). After propensity score matching, the overall mortality of patients who underwent ablation was significantly lower compared to that assessed in patients not treated with the procedure (9.386/1000 vs. 23.032/1000 person-year, respectively; p < 0.001). Moreover, the mean total costs were significantly higher in patients who did not undergo ablation compared to those who received ablation (EUR 5516 vs. 4008, respectively; p < 0.001). This real-world data analysis shows that in Italy, although catheter ablation is performed in a minority of AF patients, it is associated with significantly better post-procedure clinical outcomes and a significant reduction in healthcare-related costs.

Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory arteriopathy, considered a rare cause of coronary artery disease. Although familial cases have been described, no specific gene association has been detected so far. When the coronary vessels are involved, the main clinical scenarios are stable angina, acute coronary syndromes, left ventricular dysfunction, and sudden death. Specific clinical and angiographic findings may suggest this as the underlying disease, but certain diagnosis histological. The involvement of the lower and upper limbs is unusual; however, it may have decisive clinical implications for the most appropriate revascularization method and the selection of the arterial graft to be used.

Although cryoablation (CA) of septally located accessory pathways (APs) is an established treatment for Wolff-Parkinson-White syndrome, its major limitation is the lack of data regarding long-term follow-up (FU). The present study sought to investigate long-term outcomes of a specific CA protocol targeting para-Hisian (P-H) and mid-septal (M-S) APs.26 patients who previously underwent CA of PH or MS APs from 2004 to 2014, were prospectively considered to receive a follow-up (FU) during 2021. All subjects received an outpatient control visit, performing an exercise stress test and a 24-h ECG Holter monitoring.Acute success was achieved in 22 patients (85%). One case of recurrence was reported at short-term FU. Long-term FU, performed after a mean time of 150 ± 37 months, did not show ventricular preexcitation recurrences, with a success rate of 81%, and without late adverse events. Symptoms reduction (12% vs. 96%, plt;.001) and lower rates of antiarrhythmic drug use (12% vs. 62%, plt;.001) were observed at long term-FU with respect to baseline. This clinical outcome was detected also among patients who underwent unsuccessful CA at baseline.Our CA protocol confirmed remarkable safety and efficacy throughout a longterm FU. Significant clinical improvement in terms of antiarrhythmic therapy discontinuation and symptoms reduction was also shown among patients who experienced acute failure of CA.

Atypical atrial flutters are complex, hard-to-manage atrial arrhythmias. Catheter ablation has progressively emerged as a successful treatment option with a remarkable role played by irrigated-tip catheters and 3D electroanatomic mapping systems. However, despite the improvement of these technologies, the ablation results may be still suboptimal due to the progressive atrial substrate modification occurring in diseased hearts. Hence, a patient-tailored approach is required to improve the long-term success rate in this scenario, aiming at achieving specific procedure end points and detecting any potential arrhythmogenic substrate in each patient.

Atrial flutter is a term encompassing multiple clinical entities. Clinical manifestations of these arrhythmias range from typical isthmus-dependent flutter to post-ablation microreentries. Twelve-lead electrocardiogram (ECG) is a diagnostic tool in typical flutter, but it is often unable to clearly localize atrial flutters maintained by more complex reentrant circuits. Electrophysiology study and mapping are able to characterize in fine details all the components of the circuit and determine their electrophysiological properties. Combining these 2 techniques can greatly help in understanding the vectors determining the ECG morphology of the flutter waveforms, increasing the diagnostic usefulness of this tool.

Atypical atrial flutters are complex supraventricular arrhythmias that share different pathophysiological aspects in common. In most cases, the arrhythmogenic substrate is essentially embodied by slow-conducting areas eliciting re-entrant circuits. Although atrial scarring seems to promote slow conduction, these arrhythmias may occur even in the absence of structural heart disease. To set out the ablation strategy in this setting, three-dimensional mapping systems have proved invaluable over the last decades, helping the cardiac electrophysiologist understand the electrophysiological complexity of these circuits and easily identify critical areas amenable to effective catheter ablation.

Atrial flutter and fibrillation have been inextricably linked in the study of electrophysiology. With astute clinical observation, advanced diagnostic equipment in the Electrophysiology Laboratory, and thoughtful study of animal models, the mechanism and inter-relationship between the 2 conditions have been elucidated and will be reviewed in this article. Though diagnosis and management of these conditions have many similarities, the mechanisms by which they develop and persist are quite unique.

Isthmus-dependent flutter represents a defeated arrhythmia. Possibly one of the most outstanding successes in terms of understanding the mechanism behind it has led to an effective, relatively simple, and safe targeted therapy. Technology, fulfilling a number of the clinical electrophysiologist's dreams, has linked diagnosis and therapy in computerized systems showing real-time imagines of the right atrium, the arrhythmia circuit, and the ablation target. The entire history of clinical electrophysiology is contained in its path and atrial flutter needs to be regarded with immense respect for a large amount of knowledge that its study always engenders."

Ablation of typical atrial flutter has a high safety and efficacy profile, but hidden pitfalls may be encountered. In some cases, a longer cycle length with isoelectric lines is associated with a different or more complex arrhythmogenic substrate, which may be missed if conduction block of the cavotricuspid isthmus is performed in the absence of the clinical arrhythmia. Prior surgery may have consistently modified the atrial substrate and complex or multiple arrhythmias associated with an isthmus-dependent circuit can be encountered. In these cases, electroanatomic mapping is useful to guide the procedure and plan an appropriate ablation strategy.

Aims This report describes the findings of the 2018 Italian Catheter Ablation Registry of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC). Methods The Italian Catheter Ablation Registry systematically collects data on the ablation procedures performed in Italy. Data collection was retrospective. A standardized questionnaire was completed by participating centres. Results We collected data on 15 714 catheter ablation procedures performed in Italy during 2018 in 94 electrophysiology centres. In most centres (75/94, 80%), a single electrophysiology laboratory was available, and a hybrid electrophysiology laboratory was available in 15% (14/94) of centres. In most (93%) centres, at least two electrophysiologists were involved in the catheter ablation procedures. In only 13 out of 94 (14%) electrophysiology laboratories, an anaesthesiologist assists every electrophysiology procedure; in most cases (74/94, 79%), an on-demand anaesthesiology service was available. On-site cardiothoracic surgery was reported in 43 out of 94 (46%) centres.Nonfluoroscopic navigation systems were available in most centres (88/94, 93%). Intracardiac echocardiography was used in 59 out of 94 (63%) electrophysiology laboratories. Atrial fibrillation (31%) was the most frequently treated ablation target, followed by atrioventricular nodal re-entrant tachycardia (20%) and cavo-tricuspid isthmus (15%). In 61.7% of all procedures, a 3D mapping system was used. In about one-third of procedures, a near-zero approach was performed. Conclusion In most Italian electrophysiology centres, a single electrophysiology laboratory was available and at least two electrophysiologists were involved in the ablation procedures. An increasing number of procedures were performed by means of a nonfluoroscopic mapping system with a near-zero approach.

Background. Nowadays, it is still not possible to clinically distinguish whether an increase in high-sensitivity cardiac troponin (hs-cTn) values is due to myocardial injury or an acute coronary syndrome (ACS). Moreover, predictive data regarding hs-cTnT in an emergency room (ER) setting are scarce. This monocentric retrospective study aimed to improve the knowledge and interpretation of this cardiac biomarker in daily clinical practice. Methods. Consecutive adult patients presenting at the ER and hospitalized with a first abnormal hs-cTnT value (≥14 ng/L) were enrolled for 6 months. The baseline hs-cTnT value and the ensuing changes and variations were correlated with the clinical presentation and the type of diagnosis. Subsequently, multivariable models were built to assess which clinical/laboratory variables most influenced hospital admissions in the investigated population analyzed according to the final reason for hospitalization: (1) cardiovascular vs. non-cardiovascular diagnosis, and (2) ACS vs. non-ACS one. Results. A total of 4660 patients were considered, and, after a first screening, 4149 patients were enrolled. Out of 4129 patients, 1555 (37.5%) had a first hs-cTnT ≥14 ng/L, and 1007 (65%) were hospitalized with the following types of diagnosis: ACS (182; 18%), non-ACS cardiovascular disease (337; 34%) and non-cardiovascular disease (487; 48%). Higher hs-cTnT values and significant hs-cTnT variations were found in the ACS group (p < 0.01). The mean percentage of variation was higher in patients with ACS, intermediate in those with non-ACS cardiovascular disease, and low in those with non-cardiovascular disease (407.5%, 270.6% and 12.4%, respectively). Only syncope and CRP (OR: 0.08, 95% CI: 0.02–0.39, p < 0.01 and OR: 0.9988, 95% CI: 0.9979–0.9998, p = 0.02, respectively) or CRP (OR: 0.9948, 95% CI: 0.9908–0.9989, p = 0.01) and NT-proBNP (OR: 1.0002, 95% CI: 1.0000–1.0004, p = 0.02) were independent predictors of a cardiovascular disease diagnosis. On the other hand, only chest pain (OR: 22.91, 95% CI: 3.97–132.32, p < 0.01) and eGFR (OR: 1.04, 95% CI: 1.004–1.083, p = 0.03) were associated with the ACS diagnosis. Conclusions. Differently from the investigated biomarkers, in this study, only clinical variables predicted hospitalizations in different patients’ subgroups.

Background: The Lombardy region, in Northern Italy, suffered a major outbreak of Coronavirus disease 2019 (COVID-19) at the end of February 2020. The health system was rapidly overwhelmed by the pandemic. It became evident that patients suffering from time-sensitive medical emergencies like stroke, cerebral hemorrhage, trauma and acute myocardial infarction required timely, effective and safe pathways to be treated. The problem was addressed by a regional decree that created a hub-and-spoke system for time-sensitive medical emergencies. Methods: We report the re-organizational changes adopted at a hub hospital (despite having already destined to COVID-19 patients most resources), and the number of emergent procedures for medical emergencies on the first 30-day of activity. These data were compared with the hospital activity in the same period of the previous year. Results: Organizational changes were implemented in few hours. Dedicated pathways for non-COVID-19 patients affected by a medical emergency were set up in the emergency department, in the labs and in the operating theater. Ten intensive beds were implemented from a high-dependency unit; two operating rooms were reserved 24 h/day to neurosurgical or trauma emergencies. The number of emergent procedures was not different from that of the previous year, no admission refusal, no treatment delay and no viral transmission to the treated patients were recorded. No viral transmission to health care workers was observed. Conclusions: Re-organization of a hospital in order to adopt a hub-and-spoke model resulted feasible and allowed to face acute coronary syndrome and other time-sensitive medical emergencies timely and safely.

The impact of sudden cardiac death (SCD) in heart failure (HF) patients is important and prevention of SCD is a reasonable and clinically justified endpoint if associated with a reduction in all-cause mortality. According to literature, in HF with reduced ejection fraction, only three classes of agents were found effective in reducing SCD and all-cause mortality: beta-blockers, mineralcorticoid receptor antagonists and, more recently, angiotensin-receptor neprilysin-inhibitors. In the PARADIGM trial that tested sacubitril/valsartan vs. enalapril, the 20% relative risk reduction in cardiovascular deaths obtained with sacubitril/valsartan was attributable to reductions in the incidence of both SCD and death due to HF worsening and this effect can be added to the known positive effect of implantable cardioverter-defibrillators in appropriately selected patients. In order to maximize the implementation of all the available treatments, patients with HF should be included in virtuous networks with a dialogue between all the physician involved, with commitment by all these physicians for appropriate decision-making on application of pharmacological and device treatments according to available evidence, as well as commitment for drug titration before and after device implant, taking advantage from remote monitoring, and with the safety of back up device therapy when indicated. There are potential synergistic effects of drug therapy, with all the therapies acting on neuro-hormonal and sympathetic activation, but specifically with sacubitril/valsartan, and device therapy, in particular cardiac resynchronization therapy, with added incremental benefits on positive cardiac remodelling, prevention of HF progression, and prevention of ventricular tachyarrhythmias.