Epicardial adipose tissue is a distinct fat depot with local and systemic effects. Distinguished from other visceral fat depots by a number of anatomical and metabolic features, this tissue exhibits increased fatty acid metabolism and a unique transcriptome enriched for genes associated with inflammation and endothelial function. As epicardial fat and the heart share an unobstructed microcirculation, it is suggested that these tissues may interact. Under normal physiological conditions, epicardial fat exhibits metabolic and thermogenic properties similar to those of brown fat, as well as mechanical properties that provide cardioprotection. However, the development of pathological conditions could cause the phenotype of epicardial fat to become detrimental to the myocardium and coronary arteries. The balance between the protective and detrimental effects of this tissue is fragile. The expression of the epicardial fat-specific transcriptome is downregulated in severe and advanced coronary artery disease. Improved local vascularisation, weight loss and targeted drugs can restore the protective physiological functions of epicardial fat. Accurate measurement of epicardial fat thickness or volume has several important clinical applications, as it correlates with visceral adiposity, coronary artery disease, metabolic syndrome, fatty liver disease, cardiac changes, arrhythmias and ventricular dysfunction. Due to the simplicity of this clinical assessment, epicardial fat is a reliable marker of cardiovascular risk and an attractive surrogate for evaluating the efficacy of drugs that modulate adipose tissue. In this article, we review the rapidly emerging evidence suggesting a specific role for epicardial adipose tissue as a marker of cardiac risk and an active player in the development of cardiac pathology, as well as a potentially modifiable therapeutic target for new drugs, even in high-risk populations.

BACKGROUND:Out-of-hospital cardiac arrest remains a significant public health challenge, characterized by poor overall survival. Early defibrillation is crucial to manage fatal arrhythmias. The use of automated external defibrillators is a promising tool in minimizing time to defibrillation and enhancing survival. METHODS:PV (Progetto Vita) in Piacenza pioneered the first community-based automated external defibrillator project in Europe. We present survival data spanning 23 years for all cases of out-of-hospital cardiac arrest managed under both PV and standard emergency medical services interventions. RESULTS:A total of 6996 out-of-hospital cardiac arrests were recorded. Among these, 156 cases were managed by PV volunteers (PV group). The PV group managed a significantly higher proportion of shockable rhythms than the emergency medical services group (69.9% versus 10.9%). Mean time to arrival was shorter (5.7 versus 10.2 minutes), and survival rates better with favorable neurological outcomes (46.2% versus 2.9%, overall). Survival rates declined with time. However, a higher proportion of patients in the PV -group demonstrated favorable neurological outcomes, even up to 9 minutes from the call, compared with the EMS group. Over the study period, the increasing number of automated external defibrillators in fixed public places coincided with a substantial rise in ventricular fibrillation survival in the PV group patients (22% for 2003-2012 to 73% for 2013-2022, P<0.001). Both time from call to arrival and PV-group intervention emerged as independent predictors of survival (odds ratio 1.08 and 0.28, respectively). CONCLUSIONS:Our simplified automated external defibrillator-focused training for community has shown higher survival rates and emerges as a highly successful strategy in a small city.

Abstract Background The HeartLogic algorithm integrates data from various implantable defibrillator (ICD) sensors to predict impending heart failure (HF) decompensation. The algorithm computes worsening in its sensors and weighs them based on a risk level. These sensors include accelerometer-based first (S1) and third (S3) heart sounds, intrathoracic impedance (TI), respiration rate (RR), the ratio of respiration rate to tidal volume (RSBI), and night heart rate (NHR). Objective This study assessed the relative worsening of ICD sensors at the onset of HeartLogic alerts, their association with patient characteristics and subsequent outcomes. Methods The HeartLogic feature was activated in 568 ICD patients (410 with CRT-D) across 26 centers, with a median follow-up of 26 months [25th–75th percentile: 16–37]. Results During the follow-up, 1200 HeartLogic alerts were recorded in 370 patients. The sensor with the highest worsening (SHW) at the alert onset was S3 (27% of alerts), followed by S3/S1 (25%), TI (16%), RR (15%), and NHR (11%), RSBI (6%). Patients with atrial fibrillation (AF) at implantation and those with chronic kidney disease (CKD) had higher alert prevalence (AF 84% vs. no-AF 58%, CKD 72% vs. no-CKD 59%; both p <0.05) and higher alert rates (AF 1.51/patient-year vs. no-AF 0.88/patient-year, CKD 1.30/patient-year vs. no-CKD 0.89/patient-year; both p <0.05). AF patients had alerts with every sensor as SHW, while CKD patients had alerts primarily with TI, RR, and RSBI as SHW (Figure). In 85% of cases among 247 patients with >1 alert, the SHW changed between successive alerts. Of the 88 (7%) alerts resulting in HF hospitalizations or deaths, a greater proportion featured RR or RSBI (11%) and NHR (11%) as SHW, followed by heart sounds (5%) (both p <0.05). Clinical events were more common with the first alert (12.6%) than subsequent alerts (5.2%, p <0.001). Conclusion HeartLogic alerts are predominantly associated with the highest worsening in heart sounds. Nevertheless, recurrent alerts often involve other sensors, suggesting varied HF progression mechanisms and potential divergent outcomes. The frequency of alerts and the pattern of worsening in ICD sensors are linked to patient characteristics.

Background The HeartLogic algorithm (Boston Scientific, St Paul, MN) integrates data from implantable cardioverter-defibrillator (ICD) sensors to predict heart failure (HF) decompensation: first (S1) and third (S3) heart sounds, intrathoracic impedance, respiration rate, ratio of respiration rate to tidal volume (RSBI), and night heart rate. Objective This study assessed the relative changes in ICD sensors at the onset of HeartLogic alerts, their association with patient characteristics, and outcomes. Methods The study included 568 patients with HF carrying ICDs (CRT-D, n = 410) across 26 centers, with a median follow-up of 26 months. HeartLogic alerts triggered patient contact and potential treatment. Results A total of 1200 HeartLogic alerts were recorded in 370 patients. The sensor with the highest change at the alert’s onset was S3 in 27% of alerts, followed by S3/S1 (25%). Patients with atrial fibrillation (AF) and chronic kidney disease (CKD) at implantation had higher prevalence of alerts (AF, 84% vs no AF, 58%; CKD, 72% vs no CKD, 59%; P < .05) and rate (AF, 1.51 per patient-year vs no AF, 0.88 per patient-year; CKD, 1.30 per patient-year vs no CKD, 0.89 per patient-year; P < .05). During follow-up, 247 patients experienced more than 1 alert; in 85%, the sensor with the highest change varied between successive alerts. Of the 88 (7%) alerts associated with HF hospitalization or death, respiration rate or RSBI (11%, P = .007 vs S3/S1) and night heart rate (11%, P = .031 vs S3/S1) were more commonly the sensors showing the highest change. Clinical events were more common with the first alert (12.6%) than subsequent alerts (5.2%, P < .001). Conclusion HeartLogic alerts are mostly triggered by changes in heart sounds, but clinical events are more linked to respiration rate, RSBI, and night heart rate. Recurrent alerts often involve different sensors, indicating diverse mechanisms of HF progression.

AIMS:Globally, nearly 20% of cardiovascular disease deaths were attributable to air pollution. Out-of-hospital cardiac arrest (OHCA) represents a major public health problem; therefore, the identification of novel OHCA triggers is of crucial relevance. The aim of the study was to evaluate the association between air pollution (short-, mid-, and long-term exposures) and OHCA risk, during a 7-year period in a highly polluted urban area in northern Italy, with a high density of automated external defibrillators (AEDs). METHODS AND RESULTS:Out-of-hospital cardiac arrests were prospectively collected from the 'Progetto Vita Database' between 1 January 2010 and 31 December 2017; day-by-day air pollution levels were extracted from the Environmental Protection Agency stations. Electrocardiograms of OHCA interventions were collected from the AED data cards. Day-by-day particulate matter (PM) 2.5 and 10, ozone (O3), carbon monoxide (CO), and nitrogen dioxide (NO2) levels were measured. A total of 880 OHCAs occurred in 748 days. A significant increase in OHCA risk with a progressive increase in PM2.5, PM10, CO, and NO2 levels was found. After adjustment for temperature and seasons, a 9% and 12% increase in OHCA risk for each 10 μg/m3 increase in PM10 (P < 0.0001) and PM2.5 (P < 0.0001) levels was found. Air pollutant levels were associated with both asystole and shockable rhythm risk, while no correlation was found with pulseless electrical activity. CONCLUSION:Short- and mid-term exposures to PM2.5 and PM10 are independently associated with the risk of OHCA due to asystole or shockable rhythm.

During the last decades, many improvements have been made regarding the treatment of atrial fibrillation in terms of risk prevention, anti-coagulation strategies, and gain in quality of life. Among those, anti-arrhythmic drugs (AADs) have progressively fallen behind and overtaken by technological aspects as devices as procedures are now the standards of care for many patients. But is this it? Are AADs doomed to be relegated to an obscure and rarely read paragraph of the European recommendations? Or could they be still employed safely and effectively? In the present paper, we will discuss contemporary evidence in order to define where AADs still play a pivotal role, how should AADs be used, and whether a tailored approach can be the way to propose the right treatment to the right patient.

There is strong evidence that remote monitoring in cardiac implantable electronic devices can detect device malfunctions earlier than conventional monitoring and that it can be useful for detecting cardiac arrhythmias, while little data are available for an improved management of heart failure (HF). HeartInsight is a new remote monitoring algorithm developed and validated in the SELENE HF study that combines information from a diverse set of sensors integrated into one alert to detect worsening HF with promising accuracy. However, the shift from detecting technical issues or arrhythmia episodes to early predicting clinical events underscores the need to understand how to properly integrate these tools into the clinical workflow by defining an organizational model and shared guidelines for the management of HF alerts. Here, we critically discuss issues that will be raised by the implementation of this 'enhanced' remote monitoring approach to HF care in daily clinical practice.

Atrial fibrillation progression: a clinical consequence of atrial fibrillation burden, concomitant comorbidities, and their duration.

Background: Atrial fibrillation (AFIB), the most frequent cardiac arrhythmia, is a major risk factor for stroke, heart failure, and death. Because of the recent advances in AFIB management and the availability of new oral anticoagulants (OACs), there is a need for a systematic and predefined collection of contemporary data regarding its management and treatment. Methods: The objective of the ongoing ITALY-AFIB registry is to evaluate the long-term morbidity and mortality in patients with AFIB and to verify the implementation of the current guidelines for stroke prevention in these patients. The registry includes consecutive in- and out-patients with first diagnosed, paroxysmal, persistent, or permanent AFIB. In patients in sinus rhythm at entry, the qualifying episode of AFIB, confirmed by ECG diagnosis, had to have occurred within 1 year before entry. The clinical record form is web-based and accessible by personal keyword. Results: Enrolment into the registry started in the year 2013. In a current cohort of 2470 patients (mean age 75 ± 11 years, males 56%), the mean CHA2DS2-VASc score was 3.7 ± 1.8, and the mean HAS-BLED was 1.6 ± 0.9. There were no significant sex differences in the AFIB subtypes. At the end of the inclusion visit and after receiving knowledge of the web-based electronic estimate of risk for stroke and bleeding, the proportion of patients discharged with OACs was 80%. After exclusion of patients with first diagnosed AFIB (n = 397), the proportion of patients with prescription of OACs rose from 66% before the visit to 82% on discharge (p < 0.0001). Prescription of aspirin or other antiplatelet drugs fell from 18% before the visit to 10% on discharge (p < 0.0001). Conclusions: A web-based management of AFIB with automated estimation of risk profiles appears to favorably affect adherence to AFIB guidelines, based on a high proportion of patients treated with OACs and a substantial decline in the use of antiplatelet drugs.

INTRODUCTION:The Respiratory Disturbance Index (RDI) computed by an implantable cardioverter defibrillator (ICD) algorithm accurately identifies severe sleep apnea (SA). In the present analysis, we tested the hypothesis that RDI could also predict atrial fibrillation (AF) burden.METHODS:Patients with ejection fraction ≤35% implanted with an ICD were enrolled and followed up for 24 months. One month after implantation, patients underwent a polysomnographic study. The weekly mean RDI value was considered, as calculated during the entire follow-up period and over a 1-week period preceding the sleep study. The endpoints were as follows: daily AF burden of ≥5 min, ≥6 h, ≥23 h.RESULTS:Here, 164 patients had usable RDI values during the entire follow-up period. Severe SA (RDI ≥ 30 episodes/h) was diagnosed in 92 (56%) patients at the time of the sleep study. During follow-up, AF burden ≥ 5 min/day was documented in 70 (43%), ≥6 h/day in 48 (29%), and ≥23 h/day in 33 (20%) patients. Device-detected RDI ≥ 30 episodes/h at the time of the polygraphy, as well as the polygraphy-measured apnea hypopnea index ≥ 30 episodes/h, were not associated with the occurrence of the endpoints, using a Cox regression model. However, using a time-dependent model, continuously measured weekly mean RDI ≥ 30 episodes/h was independently associated with AF burden ≥ 5 min/day (hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.24-3.65, p = .006), ≥6 h/day (HR: 2.75, 95% CI: 1.37-5.49, p = .004), and ≥23 h/day (HR: 2.26, 95% CI: 1.05-4.86, p = .037).CONCLUSIONS:In heart failure patients, ICD-diagnosed severe SA on follow-up data review identifies patients who are from two- to three-fold more likely to experience an AF episode, according to various thresholds of daily AF burden.

Abstract Background The association between sleep apnea (SA) and atrial fibrillation (AF) has been well described. However, it remains unclear whether the association is causative or primarily dependent on shared comorbidities such as obesity. The Respiratory Disturbance Index (RDI) computed by an implantable cardioverter defibrillator (ICD) algorithm accurately identifies severe SA, whether central or obstructive in origin. Purpose In the present analysis we studied in patients with heart failure the contribution of obesity in the relationship between SA, measured by RDI, and AF. Methods Patients with ejection fraction ≤35% implanted with an ICD endowed with an algorithm (ApneaScan) that calculates the RDI each night, were enrolled and followed-up for 24 months. The weekly mean RDI value was considered, as calculated during the entire follow-up period. The endpoint was daily AF burden of ≥6 hours. Results 164 patients (age 67±10 years, 75% male, ejection fraction 29±5%) had usable RDI values during the entire follow-up period. Body mass index (BMI) was <25 kg/m2 in 62 patients (normal), 25.0–29.9 kg/m2 in 66 patients (overweight), ≥ 30 kg/m2 in 36 patients (obese). When compared with normal patients (31±11 episodes/h), the average RDI value calculated during the entire follow-up period did not differ in overweight patients (35±13 episodes/h, p=0.114), but was significantly higher in obese patients (39±12 episodes/h, p=0.002). During follow-up, AF burden ≥6 hours/day was documented in 48 (29%) patients (BMI ≥ versus <25 kg/m2; HR: 1.47, 95% CI: 0.83–2.60, p=0.197; BMI ≥ versus <30 kg/m2; HR: 0.98, 95% CI: 0.46–2.09, p=0.963). Based on the ROC curve analysis, average RDI ≥37 episodes/h maximized sensitivity and specificity for the prediction of AF (Area under the curve: 0.63, 95% CI: 0.55–0.70, p=0.011). Device-detected RDI ≥37 episodes/h was associated with the occurrence of AF on univariate analysis (HR: 3.88, 95% CI: 2.02–7.44, p<0.001), as well as after correction for either BMI ≥25 kg/m2 (HR: 3.76, 95% CI: 1.94–7.26, p<0.001), or BMI ≥30 kg/m2 (HR: 4.15, 95% CI: 2.15–8.04, p<0.001). Conclusions In heart failure patients, we confirmed the association between ICD-detected SA and AF, an association that persisted independent of patient body habitus. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The study is supported by a research grant from Boston Scientific

Abstract Introduction Cardiovascular diseases is one of the most important public health problems; are among the main causes of morbidity, disability and mortality. Those who survive to an acute form become chronically ill with repercussions on the quality of life and on the economic and social costs. Secondary prevention through an intervention aimed to modify risk factors, in particular the sedentary lifestyle could be effective in the improvement of functional abilities. In this observational study carried out at the ABCardio company in Bologna (Italy), a personalized program of Physical Activity was performed through the innovative Biocircuit technology (Technogym®), on outpatients with a prevalent diagnosis of chronic ischemic heart disease. Methods We have analyzed 31 patients (M / F, 25/6) with a mean age of 61 years, and BMI of 26.4 kg / m2. Patients followed a two–month personalized physical activity program consisting in functional assessment at baseline (T0) and at the end of the program (T1) and of 2 weekly training sessions. Evaluation included: lower and upper limb isokinetic test to measure muscle strength, 500–meter moderate walking test to estimate maximum oxygen uptake (VO2max). Results The results obtained from the comparison between T0 and T1 in the 31 patients in study show significant improvements in the muscle strength of the lower limbs: Leg press +32.9 kg (p = 0.0003), Leg curl +11.8 kg (p < 0.0001), Leg extension +15.8 kg (p = 0.0002); as well as in upper limb muscle strength: Low Row +10.5 kg (p = 0.0005), Chest press +5.7 kg (p = 0.0007), Shoulder press +6.2 kg (p = 0, 0005). Estimated VO2max was also significantly improved from 26.2 mL / kg / min (T0) to 36.3 mL / kg / min (T1), with a mean increase of 10.1 mL / kg / min (p = 0, 0001). No adverse events occurred during supervised training sessions. Conclusions The program, safe and well tolerated by the patients in study, has proved to be effective in increasing exercise capacity in terms of both muscle strength and aerobic capacity. This secondary prevention intervention can be considered useful in reducing residual cardiovascular risk as it induced a significant increase in VO2max.

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 CostEffectiveness 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 euro47,709 per Quality Adjusted Life Year (QALY) gained, which is far lower than the accepted threshold of euro60,000 in the Italian National HS. The ICER per Life Year (LY) gained was euro38,276. 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.

Aims Cardiac resynchronization therapy (CRT) is indicated in patients with systolic heart failure (HF), severe left ventricle (LV) dysfunction and interventricular dyssynchrony. In prospective observational research, we aimed to evaluate whether CRT-induced LV reverse remodelling and occurrence of ventricular arrhythmias (VT/VF) independently contribute to prognosis in patients with CRT defibrillators (CRT-D). Methods In 95 Italian cardiological centres, after a screening period of 6 months, patients were categorized according to VT/VF occurrence and CRT response, defined as LV end-systolic volume relative reduction >15% or LV ejection fraction absolute increase >5%. The main endpoint was death or HF hospitalizations. Results Among 1308 CRT-D patients (80% male, mean age 66 years), at 6 months, follow-up 71% were identified as CRT responders and 12% experienced appropriate VT/VF detections. The main endpoint was significantly and independently associated with previous myocardial infarction, New York Heart Association Class, VT/VF occurrence and with CRT response. CRT nonresponder patients who suffered VT/VF in the screening period had a risk of death or HF hospitalizations [HR = 7.82, 95% confidence interval (CI) = 3.95–15.48] significantly ( P < 0.001) higher than CRT responders without VT/VF occurrence. This risk is mitigated without VT/VF occurrence (HR = 3.47, 95% CI = 2.03–5.91, P < 0.001) or in case of CRT response (HR = 3.11, 95% CI = 1.44–6.72, P = 0.004). Conclusion Our data show that both CRT response and occurrence of VT/VF independently contribute to the risk of death or HF-related hospitalizations in CRT-D patients. Early VT/VF occurrence may be identified as a marker of disease severity than can be mitigated by CRT response both in terms of all-cause mortality and long-term VT/VF onset. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00147290 and NCT00617175

Aims: To assess the effect of pharmacological therapy on long-term prognosis of patients with MINOCA. Methods and results: In this retrospective multicentre cohort study involving 9 Hub Hospitals across Italy we enrolled consecutive patients 18 years and older with diagnosis of MINOCA discharged from 1st March 2012 to 31st March 2018. Data on baseline characteristics and pharmacological therapy at discharge (ACEI/ARB, angiotensinconverting enzyme inhibitors/angiotensin receptor antagonists; ASA, acetylsalicylic acid; beta-blockers; CCB, calcium-channel blockers; DAPT, dual anti-platelet therapy; statins), were collected systematically. The primary endpoint (PE) of the study was a composite of all cause death or acute myocardial infarction or acute coronary syndrome or heart failure leading to hospitalization or stroke. A total of 621 patients were included (mean [SD] age 65.1 [13.9] years; 344 [55.4%] female), of whom 106 (17.1%) experienced PE, including 27 patients (4.3%) who died. Multivariable analysis, after correction for all baseline differences, showed a significant association between pharmacological therapy at discharge and an increased risk of PE for aspirin (HR[95%CI] = 2.47[1.05-5.78], adjusted p = 0.04), whereas beta-blockers were associated with a significant benefit (HR[95%CI] = 0.49 [0.31-0.79], adjusted p = 0.02). Conclusion: The use of beta-blockers was significantly associated to a less frequent occurrence of adverse outcomes at long-term follow-up among patients with MINOCA, whereas ASA displayed a potentially harmful impact on prognosis. The findings in the study may be relevant for the design of future studies which should take into account possible heterogeneity among MINOCA patients. (c) 2020 Elsevier B.V. All rights reserved.

Background: Ventricular arrhythmias (VAs) represent a critical issue in regard to sports eligibility assessment in athletes. The ideal diagnostic evaluation of competitive and leisure-time athletes with complex VAs has not been clearly defined.Objective: To assess the clinical implications of invasive electrophysiological assessments and endomyocardial biopsy among athletes with VAs.Methods: We evaluated 227 consecutive athletes who presented to our institutions after being disqualified from participating in sports because of VAs. After noninvasive tests, electrophysiology study (EPS), electroanatomical mapping (EAM), and EAM- or cMRI-guided endomyocardial biopsy (EMB) were performed, following a prespecified protocol. Sports eligibility status was redefined at 6-month follow-up.Results: From our sample, 188 (82.8%) athletes underwent EAM and EPS, while 42 (15.2%) underwent EMB. In this latter subset, the invasive diagnostic workup allowed diagnostic reclassification of half of athletes (n=21, 50%). Reclassification was particularly common among subjects without definitive findings after noninvasive evaluation (n=23; 87% reclassified), especially in the presence of cMRI-proven left ventricular (LV) nonischemic scar (n=13; 92% reclassified). History of syncope, abnormal echocardiogram, presence of late gadolinium enhancement, and abnormal EAM were linked to sports ineligibility at six-month follow-up, whereas performance of catheter ablation was associated with sports eligibility.Conclusions: A comprehensive invasive workup provided additional diagnostic elements and could improve the sports eligibility assessment of athletes presenting with VAs. The presented extensive invasive evaluation could be routinely performed when noninvasive tests show unclear findings and/or LV nonischemic scar in order to inform athletes' management.