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Over the last 20 years, the scientific progresses in molecular biology and genetics in combination with the increasing use in the clinical setting of contrast-enhanced cardiac magnetic resonance (CMR) for morpho-functional imaging and structural myocardial tissue characterization have provided important new insights into our understanding of the distinctive aspects of cardiomyopathy, regarding both the genetic and biologic background and the clinical phenotypic features. This has led to the need of an appropriate revision and upgrading of current nosographic framework and pathobiological categorization of heart muscle disorders. This article proposes a new definition and classification of cardiomyopathies that rely on the combination of the distinctive pathobiological basis (genetics, molecular biology and pathology) and the clinical phenotypic pattern (morpho-functional and structural features), leading to the proposal of three different disease categories, each of either genetic or non-genetic etiology and characterized by a combined designation based on both "anatomic" and "functional" features, i.e., hypertrophic/restrictive (H/RC), dilated/hypokinetic (D/HC) and scarring/arrhythmogenic cardiomyopathy (S/AC). The clinical application of the newly proposed classification approach in the real-world practice appears crucial to design a targeted clinical management and evaluation of outcomes of affected patients. Although current treatment of cardiomyopathies is largely palliative and based on drugs, catheter ablation, device or surgical interventions aimed to prevent and manage heart failure and malignant arrhythmias, better knowledge of basic mechanisms involved in the onset and progression of pathobiologically different heart muscle diseases may allow to the development of disease-specific curative therapy., Competing Interests: Declaration of competing interest No disclosures., (Copyright © 2024. Published by Elsevier B.V.)

Aims: Transvenous lead extraction (TLE) is potentially complicated by significant tricuspid valve regurgitation increase (TRI). However, there are limited data on the effect of the bidirectional rotational mechanical sheaths on significant TRI. The aim of the present study was to investigate the rate of significant changes in tricuspid regurgitation (TR) severity following mechanical rotational TLE and their outcomes., Methods and Results: In 158 patients (mean age 66 ± 16.9 years) undergoing mechanical rotational TLE, acute changes in TR severity were assessed by echocardiography evaluation. A significant acute TRI was defined as an increase of at least one grade with a post-extraction severity at least moderate. A total of 290 leads were extracted (mean implant duration, 93 ± 65 months). Significant TRI was noted in 5.7% of patients, and it was linked to tricuspid valve damage, TLE infection indication, and longer lead implant duration. Univariate predictors of significant TRI included implant duration of all leads [odds ratio (OR) 1.01; 95% confidence interval (CI) 1.003-1.018; P = 0.001] and right ventricular leads (OR 1.01; 95% CI 1.004-1.017; P = 0.002). Severe increase of TR following TLE was an independent predictor of mortality [hazard ratio (HR) 5.20; 95% CI 1.44-18.73; P = 0.012 ] along with severe systolic dysfunction (HR 2.37; 95% CI 1.01-5.20; P = 0.032), and systemic infection (HR 2.28; 95% CI 1.06-4.89; P = 0.035)., Conclusion: Significant TRI was detected in 5.7% of patients following transvenous rotational mechanical lead extraction. The duration of lead implantation emerged as the sole predictor of significant TRI. Physicians engaged in TLE should exercise greater vigilance for this potential complication., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

A 74-year-old man who recently undergone a definitive pacemaker implantation with an apical septal active lead fixation presented to the emergency department because of a new-onset acute chest pain that began soon after cough episodes. Pacemaker interrogation reported an increased bipolar pacing threshold (3.25 V at 1 ms). Contrast-enhanced chest CT scan and percutaneous angiography revealed the sequential perforation of the right ventricular apex and the left internal mammary artery by the ventricular pacemaker lead. Successful percutaneous embolization of the LIMA, blood transfusion and thoracentesis were then performed, and the patient subsequently underwent a percutaneous ventricular lead extraction followed by re-implantation, with an uneventful follow-up after 2 years. This unique case report highlights a potential rare complication of the active fixation of the ventricular lead at the apical interventricular septum and should lead the clinicians to keep in mind right ventricular perforation, even without cardiac tamponade, in patients presenting for cardio-pulmonary symptoms soon after pacemaker implantation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Mitral valve prolapse (MVP) may be associated with ventricular arrhythmias (VA) even in the absence of significant valvular regurgitation. Curling, mitral annulus disjunction (MAD) and myocardial fibrosis (late gadolinium enhancement [LGE]) may account for arrhythmogenesis., Objectives: This study investigated the determinants of VA in patients with MVP without significant regurgitation., Methods: This study included 108 patients with MVP (66 female; median age: 48 years) without valve regurgitation. All patients underwent 12-lead electrocardiography, 12-lead 24-hour electrocardiographic Holter monitoring, exercise stress test, and cardiac magnetic resonance. Patients were divided into 2 groups (arrhythmic and no-arrhythmic MVP), according to the presence of VA with a right bundle branch block pattern., Results: The 62 patients (57%) with arrhythmic MVP showed: 1) higher MAD (median length: 6.0 vs 3.2 mm; P = 0.017); 2) higher prevalence of curling (79% vs 52%; P = 0.012); and 3) higher prevalence of left ventricular LGE (79% vs 52%; P = 0.012). Mediation analysis showed that curling had both a direct (P = 0.03) and indirect effect mediated by LGE (P = 0.04) on VA, whereas the association between MAD and VA was completely mediated by LGE. Patients with severe VA showed more pronounced morphofunctional alterations, in terms of MAD (7.0 vs 4.6 mm; P = 0.004) and presence and severity of curling (respectively, 91% vs 64%; P = 0.010; and 4 vs 3 mm; P = 0.004), compared to those without severe VA., Conclusions: In patients with MVP the occurrence of VA with right bundle branch block morphology is the expression of more severe morphologic, mechanical, and tissue alterations. Curling has both a direct and an indirect effect on VA., Competing Interests: Funding Support and Author Disclosures This study was funded by the University of Padua Project BIRD213179. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular assist devices (LVADs) are an increasingly used strategy for the management of patients with advanced heart failure (HF). Subcutaneous implantable cardioverter defibrillator (S-ICD) might be a viable alternative to conventional ICDs with a lower risk of short- and long-term of device-related complications and infections.The aim of this multicenter study was to evaluate the outcomes and management of S-ICD recipients who underwent LVAD implantation., Methods: The study population included patients with a preexisting S-ICD who underwent LVAD implantation for advanced HF despite optimal medical therapy., Results: The study population included 30 patients (25 male; median age 45 [38-52] years).The HeartMate III was the most common LVAD type. Median follow-up in the setting of concomitant use of S-ICDs and LVADs was 7 months (1-20).There were no reports of inability to interrogate S-ICD systems in this population. Electromagnetic interference (EMI) occurred in 21 (70%) patients. The primary sensing vector was the one most significantly involved in determining EMI. Twenty-seven patients (90%) remained eligible for S-ICD implantation with at least one optimal sensing vector. The remaining 3 patients (10%) were ineligible for S-ICD after attempts of reprogramming of sensing vectors. Six patients (20%) experienced inappropriate shocks (IS) due to EMI. Six patients (20%) experienced appropriate shocks. No S-ICD extraction because of need for antitachycardia pacing, ineffective therapy or infection was reported., Conclusions: Concomitant use of LVAD and S-ICD is feasible in most patients. However, the potential risk of EMI oversensing, IS and undersensing in the post-operative period following LVAD implantation should be considered. Careful screening for EMI should be performed in all sensing vectors after LVAD implantation., Competing Interests: Declaration of competing interest This was an independent study. No external funding was received for this project. CT is a member of Boston Scientific advisory board; FM scientific consultant for Boston Scientific and Cook Medical. RT is a consultant for BostonScientific and received speaker's honoraria from Boston Scientific. Other authors do no report disclosures regarding this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The Petersen' index reflects an excess of myocardial trabeculation which is not a specific morpho-functional feature of left ventricular non-compaction (LVNC) cardiomyopathy, but a "phenotypic trait" even observed in association with other myocardial diseases and over-loading conditions. The present study was designed to evaluate the relation between a critical thinning of compact layer and the development of systolic dysfunction and LVNC cardiomyopathy., Methods: We compared CMR morpho-functional features and measurements of LV wall thickness using a 17 segment model of a cohort of patients fulfilling the Petersen criterion for LVNC with LV systolic dysfunction versus those of a cohort of age- and sex-matched controls with LVNC and preserved LV systolic function. All the study patients had an "isolated" LVNC defined as positive Petersen criterion in the absence of other diseases such as hypertrophic and dilated cardiomyopathy, valvular heart disease, or congenital heart disease and over-loading conditions., Results: he study population included 33 patients with "isolated" LVNC: 11 consecutive index patients with a reduced LV ejection fraction (LVNCrEF) and 22 controls with a preserved LVEF (LVNCpEF). The compact myocardial layer was thinner in patients with LVNCrEF than in those with LVNCpEF patients, both in mid-ventricular and apical LV segments. On linear regression analysis, there was a linear correlation between median thickness of mid-ventricular free wall segments and left ventricular ejection fraction (r = 0.51, p = 0.005). On the ROC curves analysis, ≥2 segments with a compact myocardial layer <5 mm in the free wall mid-ventricular segments showed the best accuracy for reduced LVEF (100% sensitivity and 60% specificity; AUC 0.81, p < 0.01). The negative predictive value for LV systolic dysfunction of <2 free wall mid ventricular segments <5 mm was 100%. On quantitative analysis, the mass of papillary muscles was lower in patients with LVNCrEF [1.2 (0.8-1.4) versus 1.6 (1.1-1.8) g/mq; p = 0.08]., Conclusions: A thinned compact layer of mid-ventricular segments of the LV free wall was associated with a reduced systolic function and "isolated" LVNC cardiomyopathy., Competing Interests: Declaration of Competing Interest No disclosures., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Left ventricular (LV) fibrosis has a key role in arrhythmogenesis in patients with mitral valve prolapse (MVP). Cardiac magnetic resonance identifies LV fibrosis by using late gadolinium enhancement (LGE) technique. LGE assessment and quantification in patients with MVP lacks of standardization protocols., Methods: 66 MVP patients with normal systolic function and without significant regurgitation were enrolled. Semi-automated gray-scale thresholding techniques using full width at half maximum (FWHM) and 2, 3 and 5 standard deviation (SD) above the remote myocardium were used and compared with the visual assessment, considered as the gold standard., Results: LGE was identified in 41 MVP patients (62%) and quantified. The mean quantity of LGE visually assessed was 2.40 ± 1.07% or 1.40 ± 0.82 g. With FWHM, LGE resulted 3.56 ± 1.23% or 1.99 ± 1.13 g. Using thresholding, the mean LGE quantity was 9.2 ± 3.1% or 4.82 ± 2.28 g for 2-SD, 5.72 ± 1.75% or 3.06 ± 1.47 g for 3-SD and 2.36 ± 0.99% or 1.29 ± 0.79 g for 5-SD. The 5-SD measurement in percentage demonstrated a good correlation with LGE quantification visually assessed (2.40 ± 1.07 vs. 2.363 ± 0.9909, p = 0.543). When compared with the gold standard, the 5-SD threshold quantification, both in percentage and in grams, revealed the least intra-observer (respectively, ICC: 0.976 and 0.966) and inter-observer variability (respectively ICC: 0.948 and 0.935)., Conclusion: The 5-SD gray-scale threshold technique in percentage revealed the best correlation with the visual assessment and an optimal reproducibility in MVP patient., (© 2023. The Author(s).)

Background: The Medtronic SelectSecure Model 3830 lumenless lead (Medtronic, Inc., Minneapolis, MN) is commonly used for conduction system pacing (CSP). However, with this increased use, the potential need for transvenous lead extraction (TLE) also will increase. While extraction of endocardial 3830 leads is rather well described especially in pediatric and adult congenital heart disease population, there is very limited data on extraction of CSP leads. In the present study, we reported our preliminary experience on TLE of CSP leads and provided technical considerations., Methods: The study population comprised 6 consecutive patients (67% male; mean age 70 ± 22 years) with CSP leads (3830 leads), including left bundle branch pacing (LBBP) lead (n = 3) and His pacing lead (n = 3) undergoing TLE. Overall target leads were 17. The mean implant duration time of CSP leads was 97 ± 90 months [range 8-193)., Results: Manual traction was successful in 2 cases and mechanical extraction tools were required in the remaining cases. Sixteen leads (94%) were completely extracted, whereas incomplete removal was observed in one lead (6%) among 1 patient. Of note, in the only lead incompletely removed, we observed retention of < 1-cm remnant of lead material consisting of the screw of 3830 LBBP lead into the interventricular septum. No failure of lead extraction was reported and no major complications occurred., Conclusions: Our findings demonstrated that at an experienced center the success of TLE of chronically implanted CSP leads is high in the absence of major complications also when mechanical extraction tools are needed., (© 2023. The Author(s).)

Background: Pulmonary capillary wedge pressure (PCWP) assessment is fundamental for managing dilated cardiomyopathy (DCM) patients. Although cardiovascular magnetic resonance (CMR) has become the gold-standard imaging technique for evaluating cardiac chamber volume and function, PCWP is not routinely assessed with CMR. Therefore, this study aimed to validate the left atrial expansion index (LAEI), a LA reservoir function parameter able to estimate filling pressure with echocardiography, as a novel CMR-measured parameter for non-invasive PCWP estimation in DCM patients., Methods: We performed a retrospective, single-center, cross-sectional study. We included electively admitted DCM patients referred to our tertiary center for further diagnostic evaluation that underwent a clinically indicated right heart catheterization (RHC) and CMR within 24 h. PCWP invasively measured during RHC was used as the reference. LAEI was calculated from CMR-measured LA maximal and minimal volumes as LAEI =  ( (LAVmax-LAVmin)/LAVmin) × 100., Results: We enrolled 126 patients (47 ± 14 years; 68% male; PCWP = 17 ± 9.3 mmHg) randomly divided into derivation (n = 92) and validation (n = 34) cohorts with comparable characteristics. In the derivation cohort, the log-transformed (ln) LAEI showed a strong linear correlation with PCWP (r = 0.81, p < 0.001) and remained a strong independent PCWP determinant over clinical and conventional CMR parameters. Moreover, lnLAEI accurately identified PCWP ≥ 15 mmHg (AUC = 0.939, p < 0.001), and the optimal cut-off identified (lnLAEI ≤ 3.85) in the derivation cohort discriminated PCWP ≥ 15 mmHg with 82.4% sensitivity, 88.2% specificity, and 85.3% accuracy in the validation cohort. Finally, the equation PCWP = 52.33- (9.17xlnLAEI) obtained from the derivation cohort predicted PCWP (-0.1 ± 5.7 mmHg) in the validation cohort., Conclusions: In this cohort of DCM patients, CMR-measured LAEI resulted in a novel and useful parameter for non-invasive PCWP evaluation., (© 2023. The Author(s).)

Unstable and symptomatic complete atrioventricular block represents a potentially fatal condition that requires prompt therapy while waiting for definitive pacemaker implantation. Although transcutaneous pacing is included in acute management, it could be a difficult approach due to its painfulness and the occasional failure of mechanical capture. Drug therapy is a feasible choice, and current guidelines encompass the use of atropine, dopamine, or epinephrine. Isoprenaline has never been investigated in this setting, and no specific indication of its use has been provided despite its potentially more favorable pharmacological profile. The study population included a consecutive series of patients who presented to the emergency department because of unstable third-degree atrioventricular block and were treated with either isoprenaline or dopamine infusion while waiting for definitive pacemaker implantation. Asymptomatic patients or those with reversible causes of complete atrioventricular block were excluded. The clinical response to the drug was deemed poor if, despite achieving a full drug dose, patients remained symptomatic and/or with hemodynamic instability, ventricular rate and rhythm did not improve or worsened, including if ventricular arrhythmias or asystolic pauses and/or irrepressible nausea/vomiting occurred. Isoprenaline infusion has proved to be safe and tolerated with no arrhythmia induction or hypotensive issues. Isoprenaline has also proven to be more satisfactory in achieving an effective clinical response in 84% of patients rather than dopamine (31%, p < 0.001), reducing the need for temporary artificial pacing. Our data point out the efficacy and safety of isoprenaline infusion and its greater tolerability over dopamine in the acute management of unstable third-degree AV block while waiting for definitive pacemaker implantation.

Background: Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy against sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) and left ventricle ejection fraction (LVEF) ≤35% as detected by transthoracic echocardiograpgy (TTE). This approach has been recently questioned because of the low rate of ICD interventions in patients who received implantation and the not-negligible percentage of patients who experienced SCD despite not fulfilling criteria for implantation., Objectives: The DERIVATE-ICM registry (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy; NCT03352648) is an international, multicenter, and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to TTE in patients with ICM., Methods: A total of 861 patients with ICM (mean age 65 ± 11 years, 86% male) with chronic heart failure and TTE-LVEF <50% participated. Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints., Results: During a median follow-up of 1,054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007 [95% CI: 1.000-1.011]; P = 0.05), CMR-LVEF (HR: 0.972 [95% CI: 0.945-0.999]; P = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010 [95% CI: 1.002-1.018]; P = 0.015) were independent predictors of MAACE. A multiparametric CMR weighted predictive derived score identifies subjects at high risk for MAACE compared with TTE-LVEF cutoff of 35% with a NRI of 31.7% (P = 0.007)., Conclusions: The DERIVATE-ICM registry is a large multicenter registry showing the additional value of CMR to stratify the risk for MAACE in a large cohort of patients with ICM compared with standard of care., Competing Interests: Funding Support and Author Disclosures The Italian Ministry of Health, Rome, Italy (RC 2017 R659/17-CCM698) has provided funding for this study. Dr De Cecco has received a grant from Siemens. Dr Pontone has received institutional fees from General Electric, Bracco, Heartflow, Medtronic, Bayer, and Bhoeringher. Dr Schwitter has received research support from Bayer Healthcare Switzerland. Dr Schoepf has received grants from Astellas, Bayer, General Electric, and Siemens Healthcare; personal fees from Guerbet; and speaking honoraria from Heartflow. Dr Varga-Szemes has received grants from Siemens Healthcare and personal fees from Elucid Bioimaging. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: We assessed the feasibility of cardiac magnetic resonance (CMR) and the role of myocardial strain in the diagnostic work-up of patients with acute myocardial infarction (AMI) and a clinical suspicion of cardiac rupture (CR)., Methods and Results: Consecutive patients with AMI complicated by CR who underwent CMR were enrolled. Traditional and strain CMR findings were evaluated; new parameters indicating the relative wall stress between AMI and adjacent segments, named wall stress index (WSI) and WSI ratio, were analysed. A group of patients admitted for AMI without CR served as control. 19 patients (63% male, median age 73 years) met the inclusion criteria. Microvascular obstruction (MVO, P = 0.001) and pericardial enhancement (P < 0.001) were strongly associated with CR. Patients with clinical CR confirmed by CMR exhibited more frequently an intramyocardial haemorrhage than controls (P = 0.003). Patients with CR had lower 2D and 3D global radial strain (GRS) and global circumferential strain (in 2D mode P < 0.001; in 3D mode P = 0.001), as well as 3D global longitudinal strain (P < 0.001), than controls. The 2D circumferential WSI (P = 0.010), as well as the 2D and 3D circumferential (respectively, P < 0.001 and P = 0.042) and radial WSI ratio (respectively, P < 0.001 and P: 0.007), were higher in CR patients than controls., Conclusion: CMR is a safe and useful imaging tool to achieve the definite diagnosis of CR and an accurate visualization of tissue abnormalities associated with CR. Strain analysis parameters can give insights into the pathophysiology of CR and may help to identify those patients with sub-acute CR., Competing Interests: Conflicts of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Most recent cardiac implantable electronic devices (CIEDs) can safely undergo a cardiovascular magnetic resonance (CMR) scan under certain conditions, but metal artifacts may degrade image quality. The aim of this study was to assess the overall diagnostic yield of CMR and the extent of metal artifacts in a multicenter, multivendor study on CIED patients referred for CMR., Methods: We analyzed 309 CMR scans from 292 patients (age 57 ± 16 years, 219 male) with an MR-conditional pacemaker ( n = 122), defibrillator (n = 149), or loop recorder (n = 38); CMR scans were performed in 10 centers from 2012 to 2020; MR-unsafe implants were excluded. Clinical and device parameters were recorded before and after the CMR scan. A visual analysis of metal artifacts was performed for each sequence on a segmental basis, based on a 5-point artifact score., Results: The vast majority of CMR scans (n = 255, 83%) were completely performed, while only 32 (10%) were interrupted soon after the first sequences and 22 (7%) were only partly acquired; CMR quality was non-diagnostic in 34 (11%) scans, poor (<1/3 sequences were diagnostic) in 25 (8%), or acceptable (1/3 to 2/3 sequences were diagnostic) in 40 (13%), while most scans (n = 201, 68%) were of overall good quality. No adverse event or device malfunctioning occurred, and only nonsignificant changes in device parameters were recorded. The most affected sequences were SSFP (median score 0.32 [interquartile range 0.07-0.91]), followed by GRE (0.18 [0.02-0.59]) and LGE (0.14 [0.02-0.55]). ICDs induced more artifacts (median score in SSFP images 0.87 [0.50-1.46]) than PMs (0.11 [0.03-0.28]) or ILRs (0.11 [0.00-0.56]). Moreover, most artifacts were located in the anterior, anteroseptal, anterolateral, and apical segments of the LV and in the outflow tract of the RV., Conclusions: CMR is a versatile imaging technique, with a high safety profile and overall good image quality even in patients with MR-conditional CIEDs. Several strategies are now available to optimize image quality, substantially enhancing overall diagnostic yield.

Background: Outcomes of transvenous lead extraction (TLE) are well reported in the general population, However, data on safety, efficacy of TLE in octogenarians with a long lead dwell time, using powered extraction tools are limited. The aim of this multicenter study was to evaluate the safety, effectiveness of TLE in octogenarians using the bidirectional rotational mechanical sheaths and mid-term outcome after TLE., Methods: The study population comprised 83 patients (78.3% male; mean age 85 ± 3 years; [range 80-94 years]) with 181 target leads. All the leads (mean implant duration 112 ± 77 months [range 12-377]) were extracted exclusively using the Evolution RL sheaths (Cook Medical, Bloomington, IN, USA)., Results: The main indication for TLE was infection in 84.3% of cases. Complete procedural success rate, clinical success rate, per lead were 93.9% and 98.3%, respectively. Failure of lead extraction was seen in 1.7% of leads. The additional use of a snare was required in 8.4% of patients. Major complications occurred in one patient (1.2%). Thirty-day mortality after TLE was 6%. During a mean time follow-up of 22 ± 21 months, 24 patients (29%) died. No procedure-related mortality occurred. Predictors of mortality included ischemic cardiomyopathy (HR 4.35; 95% CI 1.87-10.13; p = .001), left ventricularejection fraction ≤35% (HR 7.89; 95% CI 3.20-19.48; p < .001), and TLE for systemic infection (HR 4.24; 95% CI 1.69-10.66; p = .002)., Conclusions: At experienced centers bidirectional rotational mechanical sheaths combined with different mechanical tools and femoral approach allowreasonable success and safety in octogenarian with long lead dwell time. Patient's age should not influence the decision to extract or not the leads, although the 30-day and mid-term mortality are significant, especially in the present of specific comorbidities., (© 2023 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Acute myocardial edema (AME) is increased water content in the myocardium and represents the first and transient pathophysiological response to an acute myocardial injury. In-vivo and non-invasive evaluation is feasible with cardiac magnetic resonance (CMR), which is a powerful imaging technique capable of tissue characterization. In the clinical setting, early demonstration of AME has a recognized diagnostic value for acute coronary syndromes and acute myocarditis, although its prognostic value is not well established. This article provides a comprehensive narrative review on the clinical meaning of AME in heart diseases. In particular, the available evidence of a possible favourable prognostic value in several clinical scenarios is addressed.

Background: Long-term data on the potential advantages of combining the third-generation subcutaneous implantable cardioverter defibrillator (S-ICD) with modern software upgrade including the "SMART Pass", modern programming strategies and the intermuscular (IM) two-incision implantation technique in arrhythmogenic cardiomyopathy (ACM) with different phenotypic variants are lacking. In this study we evaluated the long-term outcome of patients with ACM who underwent third-generation S-ICD (Emblem, Boston Scientific) and IM two-incision technique., Methods: The study population included 23 consecutive patients [70% male, median age 31 (24-46) years] diagnosed with ACM with different phenotypic variants who received third-generation S-ICD implantation with the IM two-incision technique., Results: During a median follow-up of 45.5 months [16-65], 4 patients (17.4%) received a at least one inappropriate shock (IS), with median annual event rate of 4.5%. Extra-cardiac oversensing (myopotential) during effort represented the only cause of IS. No IS due to T-wave oversensing (TWOS) were recorded. Only one patient (4.3%) experienced device-related complication consisting of premature cell battery depletion requiring device replacement. No device explantation because of need for anti-tachycardia pacing or ineffective therapy occurred. There was no significant difference between patients who did and did not experienced IS with regard to baseline clinical, ECG and technical characteristics. Five patients (21.7%) received appropriate shocks on ventricular arrythmias., Conclusions: According to our findings, although the third-generation S-ICD implanted with the IM two-incision technique appears to be associated with a low risk of complications and IS due to cardiac oversensing, the risk of IS due to myopotential mainly during effort should be considered., Competing Interests: Declaration of Competing Interest All the authors declare that there are no conflict of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background Scar burden with late gadolinium enhancement (LGE) cardiac MRI (CMR) predicts arrhythmic events in patients with postinfarction in single-center studies. However, LGE analysis requires experienced human observers, is time consuming, and introduces variability. Purpose To test whether postinfarct scar with LGE CMR can be quantified fully automatically by machines and to compare the ability of LGE CMR scar analyzed by humans and machines to predict arrhythmic events. Materials and Methods This study is a retrospective analysis of the multicenter, multivendor CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry. Patients with chronic heart failure, echocardiographic left ventricular ejection fraction (LVEF) of less than 50%, and LGE CMR were recruited (from January 2015 through December 2020). In the current study, only patients with ischemic cardiomyopathy were included. Quantification of total, dense, and nondense scars was carried out by two experienced readers or a Ternaus network, trained and tested with LGE images of 515 and 246 patients, respectively. Univariable and multivariable Cox analyses were used to assess patient and cardiac characteristics associated with a major adverse cardiac event (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare model performances. Results In 761 patients (mean age, 65 years ± 11, 671 men), 83 MACEs occurred. With use of the testing group, univariable Cox-analysis found New York Heart Association class, left ventricle volume and/or function parameters (by echocardiography or CMR), guideline criterion (LVEF of ≤35% and New York Heart Association class II or III), and LGE scar analyzed by humans or the machine-learning algorithm as predictors of MACE. Machine-based dense or total scar conferred incremental value over the guideline criterion for the association with MACE (AUC: 0.68 vs 0.63, P = .02 and AUC: 0.67 vs 0.63, P = .01, respectively). Modeling with competing risks yielded for dense and total scar (AUC: 0.67 vs 0.61, P = .01 and AUC: 0.66 vs 0.61, P = .005, respectively). Conclusion In this analysis of the multicenter CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry, fully automatic machine learning-based late gadolinium enhancement analysis reliably quantifies myocardial scar mass and improves the current prediction model that uses guideline-based risk criteria for implantable cardioverter defibrillator implantation. ClinicalTrials.gov registration no.: NCT03352648 Published under a CC BY 4.0 license. Supplemental material is available for this article.

The designation of 'arrhythmogenic cardiomyopathy' reflects the evolving concept of a heart muscle disease affecting not only the right ventricle (ARVC) but also the left ventricle (LV), with phenotypic variants characterized by a biventricular (BIV) or predominant LV involvement (ALVC). Herein, we use the term 'scarring/arrhythmogenic cardiomyopathy (S/ACM)' to emphasize that the disease phenotype is distinctively characterized by loss of ventricular myocardium due to myocyte death with subsequent fibrous or fibro-fatty scar tissue replacement. The myocardial scarring predisposes to potentially lethal ventricular arrhythmias and underlies the impairment of systolic ventricular function. S/ACM is an 'umbrella term' which includes a variety of conditions, either genetic or acquired (mostly post-inflammatory), sharing the typical 'scarring' phenotypic features of the disease. Differential diagnoses include 'non-scarring' heart diseases leading to either RV dilatation from left-to-right shunt or LV dilatation/dysfunction from a dilated cardiomyopathy. The development of 2020 upgraded criteria ('Padua criteria') for diagnosis of S/ACM reflected the evolving clinical experience with the expanding spectrum of S/ACM phenotypes and the advances in cardiac magnetic resonance (CMR) imaging. The Padua criteria aimed to improve the diagnosis of S/ACM by incorporation of CMR myocardial tissue characterization findings. Risk stratification of S/ACM patients is mostly based on arrhythmic burden and ventricular dysfunction severity, although other ECG or imaging parameters may have a role. Medical therapy is crucial for treatment of ventricular arrhythmias and heart failure. Implantable cardioverter defibrillator (ICD) is the only proven life-saving treatment, despite its significant morbidity because of device-related complications and inappropriate shocks. Selection of patients who can benefit the most from ICD therapy is one of the most challenging issues in clinical practice., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Right ventricular systolic dysfunction (RVSD) is an important determinant of outcomes in heart failure (HF) cohorts. While the quantitative assessment of RV function is challenging using 2D-echocardiography, cardiac magnetic resonance (CMR) is the gold standard with its high spatial resolution and precise anatomical definition. We sought to investigate the prognostic value of CMR-derived RV systolic function in a large cohort of HF with reduced ejection fraction (HFrEF)., Methods and Results: Study cohort comprised of patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy registry who had HFrEF and had simultaneous baseline CMR and echocardiography (n = 2449). RVSD was defined as RV ejection fraction (RVEF) <45%. Kaplan-Meier curves and cox regression were used to investigate the association between RVSD and all-cause mortality (ACM). Mean age was 59.8 ± 14.0 years, 42.0% were female, and mean left ventricular ejection fraction (LVEF) was 34.0 ± 10.8. Median follow-up was 959 days (interquartile range: 560-1590). RVSD was present in 936 (38.2%) and was an independent predictor of ACM (adjusted hazard ratio = 1.44; 95% CI [1.09-1.91]; P = 0.01). On subgroup analyses, the prognostic value of RVSD was more pronounced in NYHA I/II than in NYHA III/IV, in LVEF <35% than in LVEF ≥35%, and in patients with renal dysfunction when compared to those with normal renal function., Conclusion: RV systolic dysfunction is an independent predictor of ACM in HFrEF, with a more pronounced prognostic value in select subgroups, likely reflecting the importance of RVSD in the early stages of HF progression., Competing Interests: Conflict of interest: S.J.A. is supported by NIH 2R01 HL12766105 & 1R21 EB030654 and receives royalty fees from Elsevier. Carlo De Cecco received grant by Siemens. G.P. received institutional fees by General Electric, Bracco, Heartflow, Medtronic, Bayer, Bhoeringher. J.S. received research support by Bayer Healthcare Switzerland. U.J.S. received grant by Astellas, Bayer, General Electric, and Siemens Healthcare, personal fees by Guerbet, speaking honorarium by Heartflow. A.V.-S. received grant by Siemens Healthcare and personal fees by Elucid Bioimaging. The other authors have nothing to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Lead dwell time >10 years is a recognized predictor for transvenous lead extraction (TLE) failure and complications. Data on the efficacy and safety of TLE using the bidirectional rotational mechanical sheaths in patients with very old leads are lacking. In this multicenter study, we reported the outcomes of transvenous rotational mechanical lead extraction in patients with leads implanted for ≥10 years., Methods: A total of 441 leads (median: 159 months [135-197]; range: 120-487) in 189 consecutive patients were removed with the Evolution RL sheaths (Cook Medical, Bloomingtom, IN, USA) and mechanical ancillary tools supporting the procedures., Results: The main indication for TLE was infection in 74% of cases. Complete procedural success rate, clinical success rate, per lead were 94.8% and 98.2%, respectively. Failure of lead extraction was seen in 1.8% of leads. The additional use of a snare via the femoral approach was required in 9% of patients. Lead dwell time was the only predictor of incomplete led removal (odds ratio: 1.009; 95% confidence interval [CI]: 1.003-1.014; p = .002). Four major complication (2%) were encountered. During a mean time follow-up of 31 ± 27 months, 21 patients (11%) died. No procedure-related mortality occurred. Predictors of mortality included severe left ventricular systolic dysfunction (hazard ratio [HR]: 8.06; 95% CI: 2.99-21.73; p = .001), TLE for infection (HR: 8.0; 95% CI: 1.04-62.5; p = .045), diabetes (HR: 3.7; 95% CI: 1.48-9.5; p = .005), and previous systemic infection (HR: 3.1; 95% CI: 1.17-8.24; p = .022). Incomplete lead removal or failure lead extraction did not impact on survival during follow-up., Conclusion: Our findings demonstrated that the use of bidirectional rotational TLE mechanical sheaths combined with different mechanical tools and femoral approach allows reasonable success and safety in patients with very old leads at experienced specialized centers., (© 2022 Wiley Periodicals LLC.)

Purpose: The aim of the present study was to evaluate the outcome of patients underwent subcutaneous implantable cardioverter defibrillator (S-ICD) implantation with the intermuscular (IM) two-incision technique during 3-year follow-up., Methods: the study population consisted of 105 consecutive patients (79 male; median 50 [13-77] years) underwent S-ICD implantation with the IM two-incision technique. The composite primary end point of the study consisted of device-related complications and inappropriate shocks (IAS). Secondary end points included the individual components of the primary end point, death from any cause, appropriate therapy, major adverse cardiac events, hospitalization for heart failure, and heart transplantation., Results: According to the PRAETORIAN score, the risk of conversion failure was classified as low in 99 patients (94.3%), intermediate in 6 (5.7%).Ventricular fibrillation was successfully converted at ≤65 J in 97.4% of patients. During a median follow-up of 39 (16-53) months, 10 patients (9.5%) experienced device-related complications, and 9 (8.5%) patients reported IAS. Lead-associated complications were the most common (5 patients, 4.7%), including 2 cases of lead failure (1.9%). Pocket complications were reported in 2 patients (1.9%). Extra-cardiac oversensing (3.8%) represented the leading cause of IAS. No T-wave oversensing episodes were recorded. Twelve patients (11.4%) experienced appropriate shocks. Eight patients (7.6%) died during follow-up. IAS or device-related complications did not impact on mortality., Conclusions: The overall device-related complications and IAS rates over 3 years of follow-up were 9.5% and 8.5%, respectively. According to our findings, the IM two-incision technique allows for optimal positioning of the device achieving a low PRAETORIAN score with a high conversion rate. IM two-incision technique allows low incidence of pocket complications, shifting the type of complications towards lead-related complications, which represent the most common complications. The IM two-incision technique would not seem to impact the occurrence of IAS. Management of complications are safe without impact on the outcome., (© 2023. The Author(s).)

Arrhythmogenic cardiomyopathy (ACM) is a genetically determined heart muscle disease characterized by fibro-fatty myocardial replacement, clinically associated with malignant ventricular arrhythmias and sudden cardiac death. Originally described a disease with a prevalent right ventricular (RV) involvement, subsequently two other phenotypes have been recognized, such as the left dominant and the biventricular phenotypes, for which a recent International Expert consensus document provided upgrade diagnostic criteria (the 2020 "Padua Criteria"). In this novel workup for the diagnosis of the entire spectrum of phenotypic variants of ACM, including left ventricular (LV) variants, cardiac magnetic resonance (CMR) has emerged as the cardiac imaging technique of choice, due to its capability of detailed morpho-functional and tissue characterization evaluation of both RV and LV. In this review, the key role of CMR in the diagnosis of ACM is outlined, including the supplemental value for the characterization of the disease variants. An ACM-specific CMR study protocol, as well as strengths and weaknesses of each imaging technique, is also provided. KEY POINTS: • Arrhythmogenic cardiomyopathy includes three different phenotypes: dominant right, biventricular, and dominant left. • In 2020, diagnostic criteria have been updated and cardiac magnetic resonance has emerged as the cardiac imaging technique of choice. • This aim of this review is to provide an update of the current state of art regarding the use of CMR in ACM, with a particular focus on novel diagnostic criteria, CMR protocols, and prognostic significance of CMR findings in ACM., (© 2022. The Author(s).)

Background: Phantoms accurately mimicking the electromagnetic and thermal properties of human tissues are essential for the development, characterization, and quality assurance (QA) of clinically used equipment for Hyperthermia Treatment (HT). Currently, a viable recipe for a fat equivalent phantom is not available, mainly due to challenges in the fabrication process and fast deterioration., Materials and Methods: We propose to employ a glycerol-in-oil emulsion stabilized with ethylcellulose to develop a fat-mimicking material. The dielectric, rheological, and thermal properties of the phantom have been assessed by state-of-the-art measurement techniques. The full-size phantom was then verified in compliance with QA guidelines for superficial HT, both numerically and experimentally, considering the properties variability., Results: Dielectric and thermal properties were proven equivalent to fat tissue, with an acceptable variability, in the 8 MHz to 1 GHz range. The rheology measurements highlighted enhanced mechanical stability over a large temperature range. Both numerical and experimental evaluations proved the suitability of the phantom for QA procedures. The impact of the dielectric property variations on the temperature distribution has been numerically proven to be limited (around 5%), even if higher for capacitive devices (up to 20%)., Conclusions: The proposed fat-mimicking phantom is a good candidate for hyperthermia technology assessment processes, adequately representing both dielectric and thermal properties of the human fat tissue while maintaining structural stability even at elevated temperatures. However, further experimental investigations on capacitive heating devices are necessary to better assess the impact of the low electrical conductivity values on the thermal distribution.

Purpose: This study aimed to assess the quality of the lucite cone applicator (LCA), the standard applicator for superficial hyperthermia at the Erasmus MC Cancer Institute, using the most recent quality assurance guidelines, thus verifying their feasibility., Materials and Methods: The assessment was conducted on each of the six LCAs available for clinical treatments. The temperature distribution was evaluated using an infrared camera across different layers of a fat-muscle mimicking phantom. The maximum temperature increase, thermal effective penetration depth (TEPD), and thermal effective field size (TEFS) were used as quality metrics. The experimental results were validated through comparison with simulated results, using a canonical phantom model and a realistic phantom model segmented from CT imaging., Results: A maximum temperature increase above 6 °C at 2 cm depth in the fat-muscle phantom for all the experiments was found. A mean negative difference between simulated and experimental data was of 1.3 °C when using the canonical phantom model. This value decreased to a mean negative difference of 0.4 °C when using the realistic model. Simulated and measured TEPD showed good agreement for both in silico scenarios, while discrepancies were present for TEFS., Conclusions: The LCAs passed all QA guidelines requirements for superficial hyperthermia delivery when used singularly or in an array configuration. A further characterization of parameters such as antenna efficiency and heat transfer coefficients would be beneficial for translating experimental results to simulated values. Implementing the QA guidelines was time-consuming and demanding, requiring careful preparation and correct setup of antenna elements.

Arrhythmogenic cardiomyopathy (ACM) is a rare heart muscle disease characterized by a progressive fibro-fatty myocardial replacement, ventricular arrhythmias, and increased risk of sudden cardiac death. The first diagnostic criteria were proposed by an International Task Force of experts in 1994 and revised in 2010. At that time, ACM was mainly considered a right ventricle disease, with left ventricle involvement only in the late stages. Since 2010, several pathological and clinical studies using cardiac magnetic resonance (CMR) imaging have allowed to understand the phenotypic expression of the disease and to reach the current idea that ACM may affect both ventricles. Indeed, left ventricular involvement may parallel or exceed right ventricular involvement. The main limitations of the 2010 criteria included the poor sensitivity for left ventricular involvement and the lack of inclusion of tissue characterization by CMR. The 2020 International criteria (the Padua criteria) were developed to overcome these shortcomings. The most important innovations are the introduction of a set of criteria for identifying left ventricular variants and the use of CMR for tissue characterization. Moreover, criteria for right ventricular involvement were also updated taking into account new evidence. According to the number of criteria for right and/or left ventricular involvement, the 2020 Padua criteria allows diagnosing three ACM phenotypic variants: right-dominant, biventricular and left-dominant. This review discusses the evolving approach to diagnosis of ACM, from the 1994 International Criteria to the 2020 Padua criteria., Competing Interests: The authors declare no conflict of interest. Alessandro Zorzi is serving as one of the Editorial Board members of this journal. We declare that Alessandro Zorzi had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Stefan Peters., (Copyright: © 2022 The Author(s). Published by IMR Press.)

When approaching infected lead removal in cardiac device-related infective endocarditis (CDRIE), a surgical consideration for large (>20 mm) vegetations is recommended. We report our experience with the removal of large CDRIE vegetations using the AngioVac system, as an alternative to conventional surgery. We retrospectively reviewed all infected lead extractions performed with a prior debulking using the AngioVac system, between October 2016 and April 2022 at our institution. A total of 13 patients presented a mean of 2(1) infected leads after a mean of 5.7(5.7) years from implantation (seven implantable cardioverter-defibrillators, four cardiac resynchronization therapy-defibrillators, and two pacemakers). The AngioVac system was used as a venous−venous bypass in six cases (46.2%), venous−venous ECMO-like circuit (with an oxygenator) in five (38.5%), and venous−arterial ECMO-like circuit in two cases (15.4%). Successful (>70%) aspiration of the vegetations was achieved in 12 patients (92.3%) and an intraoperative complication (cardiac perforation) only occurred in 1 case (7.7%). Subsequent lead extraction was successful in all cases, either manually (38.5%) or using mechanical tools (61.5%). The AngioVac system is a promising effective and safe option for large vegetation debulking in CDRIE. Planning the extracorporeal circuit design may represent the optimal strategy to enhance the tolerability of the procedure and minimize adverse events.

Background: The 2020 severe acute respiratory syndrome coronavirus 2 outbreak entailed reduced availability of traditional (in-office) cardiology consultations. Remote monitoring is an alternative way of caring that may potentially mitigate the negative effects of the epidemic to the care of cardiovascular diseases. We evaluated the outcome of implantable cardioverter defibrillator (ICD) carriers followed up remotely in 2020 (epidemic period) versus 2019 (control)., Methods: We included all patients with an ICD who remained remotely monitored from the beginning to the end of each year. The combined end point included: new-onset atrial fibrillation; sustained ventricular tachycardia >170 bpm without ICD intervention; appropriate ICD intervention (either shock or antitachycardia pacing); any-cause death. Multiple events in the same patients were counted separately if occurring ≥48 h apart., Results: In 2020, 52 end points occurred in 37 of 366 (10%) ICD carriers [0.14/patient (95% confidence interval [CI] = 0.11-0.19)] versus 43 end points in 32 of 325 (10%) ICD carriers in 2019 [0.13/patient (95% CI = 0.10-0.18) P  = 0.75]. There was no difference between the distribution of any individual end point in 2020 versus 2019 although a nonsignificant mortality increase was observed (from 2.8% to 4.6%, P  = 0.19). The lowest weekly event rate occurred during the national lock down in spring 2020 but a similar trend occurred also in 2019 suggesting that the effect may not be linked to social distancing measures., Conclusions: We did not observe an increase in a combined end point including arrhythmic events and mortality in ICD carriers who were remotely monitored in 2020, compared to 2019, despite the negative impact of the coronavirus disease 2019 outbreak on the healthcare system., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Introduction: Predictors of late life-threatening arrhythmic events in Brugada syndrome (BrS) patients who received a prophylactic ICD implantation remain to be evaluated. The aim of the present long-term multicenter study was to assess the incidence and clinical-electrocardiographic predictors of late life-threatening arrhythmic events in BrS patients with a prophylactic implantable cardioverter defibrillator (ICD) and undergoing generator replacement (GR)., Methods: The study population included 105 patients (75% males; mean age 45 ± 14years) who received a prophylactic ICD and had no arrhythmic event up to first GR., Results: The median period from first ICD implantation to last follow-up was 155 (128-181) months and from first ICD Implantation to the GR was 84 (61-102) months. During a median follow-up of 57 (38-102) months after GR, 10 patients (9%) received successful appropriate ICD intervention (1.6%/year). ICD interventions included shock on ventricular fibrillation ( n = 8 patients), shock on ventricular tachycardia ( n = 1 patient), and antitachycardia pacing on ventricular tachycardia ( n = 1 patient). At survival analysis, history of atrial fibrillation (log-rank test; P = 0.02), conduction disturbances (log-rank test; P < 0.01), S wave in lead I (log-rank test; P = 0.01) and first-degree atrioventricular block (log-rank test; P = 0.04) were significantly associated with the occurrence of late appropriate ICD intervention. At Cox-regression multivariate analysis, S-wave in lead I was the only independent predictor of late appropriate ICD intervention (HR: 9.17; 95%CI: 1.15-73.07; P = 0.03)., Conclusions: The present study indicates that BrS patient receiving a prophylactic ICD may experience late appropriate intervention after GR in a clinically relevant proportion of cases. S-wave in lead I at the time of first clinical evaluation was the only independent predictor of persistent risk of life-threatening arrhythmic events. These findings support the need for GR at the end of service regardless of previous appropriate intervention, mostly in BrS patients with conduction abnormalities., Competing Interests: VM received an educational grant from the Enrico and Enrica Sovena Fundation, Italy. G-BC received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, Acutus Medical. CA receives research grants on behalf of the center from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, Acutus, and received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Livanova, Boston Scientific, Atricure, Acutus Medical, and Daiichi Sankyo. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Migliore, Martini, Calo', Martino, Winnicki, Vio, Condello, Rizzo, Zorzi, Pannone, Miraglia, Sieira, Chierchia, Curcio, Allocca, Mantovan, Salghetti, Curnis, Bertaglia, De Lazzari, de Asmundis and Corrado.)

Background: Subcutaneous implantable cardioverter defibrillator (S-ICD) is a suitable alternative for transvenous ICD (TV-ICD) patients who have undergone transvenous lead extraction (TLE). Limited data are available on the outcome of S-ICD patients implanted after TLE. We assessed the safety, efficacy, and outcome of S-ICD implantation after TLE of TV-ICD., Methods: The study population consisted of 36 consecutive patients with a median age of 52 (44-66) years who underwent S-ICD implantation after TLE of TV-ICD., Results: Indications for TLE were infection (63.9%) and lead malfunction (36.1%). During a median follow-up of 31 months, 3 patients (8.3%) experienced appropriate therapy and 7 patients (19.4%) experienced complications including inappropriate therapy (n = 4; 11.1%), isolated pocket erosion (n = 2; 5.5%), and ineffective therapy (n = 1; 2.8%). No lead/hardware dysfunction was reported. Premature device explantation occurred in 4 patients (11%). Eight patients (22.2%) died during follow-up, six of them (75%) because of refractory heart failure (HF). There were no S-ICD-related deaths. Predictors of mortality included NYHA class ≥ 2 (HR 5.05; 95% CI 1.00-26.38; p = 0.04), hypertension (HR 22.72; 95% CI 1.05-26.31; p = 0.02), diabetes (HR 10.64; 95% CI 2.05-55.60; p = 0.001) and ischemic heart disease (HR 5.92; 95% CI 1.17-30.30; p = 0.01)., Conclusion: Our study provides evidences on the use of S-ICD as an alternative after TV-ICD explantation for both infection and lead failure. Mortality of S-ICD patients who underwent TV-ICD explantation does not appear to be correlated with the presence of a prior infection, S-ICD therapy (appropriate or inappropriate), or S-ICD complications but rather to worsening of HF or other comorbidities., (© 2022. The Author(s).)

Background: Cerebrovascular accidents (CVAs) can complicate the follow-up of patients with acute myocardial infarction (AMI). Intracavitary blood stasis evaluation can be useful to stratify cardioembolic risk and optimize medical therapy. Cardiac magnetic resonance (CMR) imaging is increasingly used in AMI patients for prognostic purposes. Slow-flow artefact is common on T2-weighted images in presence of left ventricular (LV) blood stasis., Methods and Results: In this observational retrospective study, all patients with AMI undergoing CMR in our hospital were included. T2-weighted images were used to assess the presence of LV blood stasis. Among the 209 patients enrolled (males 72%, mean age 61 ± 12 years), LV blood stasis was detected in 48 (23%) and was significantly more prevalent in patients with extensive anterior or antero-apical AMI, lower LV ejection fraction, greater infarct size and microvascular obstruction. During follow-up (54 months, IQR 41-70), 8 CVAs and 6 cardiovascular deaths occurred. LV blood stasis emerged as a significant risk factor for both endpoints (logRank p < 0.001 and p = 0.008, respectively) and remained independent predictor of CVAs (HR 9.819, 95% CI 1.733-55.617, p = 0.010)., Conclusions: LV blood stasis identified with CMR predicts the occurrence of CVAs in patients with AMI. These results may be helpful to personalize antithrombotic therapy for prevention strategies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The implantable cardioverter defibrillator(ICD) has revolutionized the management of patients with hypertrophic cardiomyopathy (HCM) at risk of sudden cardiac death (SCD). However, the identification of ideal candidates remains challenging. We aimed to describe the long-term impact of the ICD for primary prevention in patients with HCM based on stringent (high SCD risk) vs lenient indications (need for pacing/personal choice)., Methods: Data from two Italian HCM Cardiomyopathy Units were retrospectively analyzed. Only patients >1 follow-up visits were divided into two groups according to ICD candidacy:stringent (high SCD risk) and lenient (need for pacing, patients' choice, physician advice despite lack of high SCD risk). Major cardiac events (composite of appropriate shock/intervention and SCD) was the primary endpoint. A safety endpoint was defined as a composite of inappropriate shocks and device-related complications., Results: Of 2009 patients, 252(12.5%) received an ICD, including 27(1.3%) in secondary prevention and 225(11.2%) in primary prevention (age at implantation 49 ± 16 years; men 65.3%). Among those in primary prevention, 167(74.2%) had stringent, while 58(25.8%) had lenient indications. At 5 ± 4 years, only stringent ICD patients experienced major cardiac events (2.84%/year, 5-year cumulative incidence: 8.1%, 95%CI [3.5-14.1%]). ICD-related complications were similar across stringent and lenient subgroups. However, patients implanted >60 years had a significantly higher risk of adverse events., Conclusion: One third of ICD recipients with HCM in primary prevention received a lenient implantation and had no appropriate intervention. ICD implantation due to systematic upgrade in patients requiring pacing and increased risk perception may offer little advantage and increase complication rates., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Premature ventricular beats (PVBs) in athletes are not rare. The risk of PVBs depends on the presence of an underlying pathological myocardial substrate predisposing the subject to sudden cardiac death. The standard diagnostic work-up of athletes with PVBs includes an examination of family and personal history, resting electrocardiogram (ECG), 24 h ambulatory ECG (possibly with a 12-lead configuration and including a training session), maximal exercise testing and echocardiography. Despite its fundamental role in the diagnostic assessment of athletes with PVBs, echocardiography has very limited sensitivity in detecting the presence of non-ischemic left ventricular scars, which can be revealed only through more in-depth studies, particularly with the use of contrast-enhanced cardiac magnetic resonance (CMR) imaging. The morphology, complexity and exercise inducibility of PVBs can help estimate the probability of an underlying heart disease. Based on these features, CMR imaging may be indicated even when echocardiography is normal. This review focuses on interpreting PVBs, and on the indication and role of CMR imaging in the diagnostic evaluation of athletes, with a special focus on non-ischemic left ventricular scars that are an emerging substrate of cardiac arrest during sport.

Arrhythmogenic Cardiomyopathy (ACM) is a heredo-familial cardiac disease characterized by fibro-fatty myocardial replacement and increased risk of sudden cardiac death. The diagnosis of ACM can be challenging due to the lack of a single gold-standard test: for this reason, it is required to satisfy a combination of multiple criteria from different categories including ventricular morpho-functional abnormalities, repolarization and depolarization ECG changes, ventricular arrhythmias, tissue characterization findings and positive family history/molecular genetics. The first diagnostic criteria were published by an International Task Force (ITF) of experts in 1994 and revised in 2010 with the aim to increase sensitivity for early diagnosis. Limitations of the 2010 ITF criteria include the absence of specific criteria for left ventricle (LV) involvement and the limited role of cardiac magnetic resonance (CMR) as the use of the late gadolinium enhancement technique for tissue characterization was not considered. In 2020, new diagnostic criteria ("the Padua criteria") were proposed. The traditional organization in six categories of major/minor criteria was maintained. The criteria for identifying the right ventricular involvement were modified and a specific set of criteria for identifying LV involvement was created. Depending on the combination of criteria for right and LV involvement, a diagnosis of classic (right dominant) ACM, biventricular ACM or left-dominant ACM is then made. The article reviews the rationale of the Padua criteria, summarizes the main modifications compared to the previous 2010 ITF criteria and provides three examples of the application of the Padua criteria in clinical practice.

Background: Recent studies have shown that Evolution RL bidirectional rotational mechanical sheath (Cook Medical, USA) is an effective and safe technique for transvenous lead extraction (TLE). We reported our experience with the bidirectional rotational mechanical tools using a multidisciplinary approach highlighting the value of a joint cardiac surgeon and electrophysiologist collaboration., Methods: The study population comprised 84 patients (77% male; mean age 65 ± 18 years) undergoing TLE. After a multidisciplinary evaluation, a combined procedure was considered., Results: The main indication for TLE was infection in 54 cases (64%). Overall, 152 leads were extracted with a mean implant duration of 94 ± 63 months (range 12-421). Complete procedural success rate, clinical success rate, and lead removal with clinical success rate were 91.6% (77/84), 97.6% (82/84), and 98.6% (150/152), respectively. Eighteen combined procedures were performed in 12 patients (14%), such as "hybrid approach" (n = 2) or TLE concomitant to: 1) transcatheter aspiration procedure for large vegetation (n = 8); 2) left ventricular assistance device implantation as bridge to cardiac transplantation (n = 1); 3) permanent pacing with epicardial leads (n = 6); 4) tricuspid valve replacement (n = 1). One major complication (1.2%) and 11 (13%) minor complications were encountered. No injury to the superior vena cava occurred and no procedure-related deaths were reported. During a mean time follow-up of 21 ± 18 months, 17 patients (20%) died. They were more often diabetics (p = .02), and they underwent TLE more often for infection (p = .004)., Conclusions: Our results support the finding that excellent outcomes can be achieved in performing TLE of chronically implanted leads by using the Evolution RL bidirectional rotational mechanical sheath and a multidisciplinary team approach involving both electrophysiologist and cardiac surgeon as first line operators., (© 2021 Wiley Periodicals LLC.)

Aims: Left ventricular global longitudinal strain (GLS) by cardiac magnetic resonance feature tracking (CMR-FT) analysis has shown an incremental prognostic value compared to classical parameters in non-ischemic dilated cardiomyopathy (NICM). However, less is known about the role of right ventricular (RV) GLS. Our objective was to evaluate the prognostic impact of RV-GLS by CMR-FT analysis in a population of NICM patients. Methods: In this multicenter study, we examined NICM patients evaluated with a comprehensive CMR-FT study. Major cardiac events (MACEs) were considered as the study primary outcome measure and were defined as a composite of (a) cardiovascular death, (b) cardiac transplant or destination therapy ventricular assist device, (c) hospitalization for life-threatening ventricular arrhythmias or implantable cardiac defibrillator appropriate intervention. Heart failure (HF) related events, including hospitalizations and life-threatening arrhythmia-related events were considered as secondary end-points. Receiver operating time-dependent analysis were used to calculate the possible additional effect of RV-GLS to standard evaluation. Results: We consecutively enrolled 273 patients. During a median follow-up of 39 months, 41 patients (15%) experienced MACEs. RV-GLS and LV late gadolinium emerged as the strongest prognostic CMR-FT variables: their association provided an estimated 3-year MACEs rate of 29%. The addition of RV-GLS significantly improved the prognostic accuracy in predicting MACEs with respect to the standard evaluation including LGE (areas under the curve from 0.71 [0.66-0.82] to 0.76 [0.66-0.86], p = 0.03). On competing risk analysis, RV-GLS showed a significant ability to reclassify overall both HF-related and life-threatening arrhythmia-related events, regardless of LV and RV ejection fraction. Conclusions: In NICM patients, RV-GLS showed a significant prognostic role in reclassifying the risk of MACEs, incremental with respect to standard evaluation with standard prognostic parameters., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cittar, Cipriani, Merlo, Vitrella, Masè, Carrer, Barbati, Belgrano, Pagnan, De Lazzari, Giorgi, Cova, Iliceto, Basso, Stolfo, Sinagra and Perazzolo Marra.)

Background Sudden cardiac arrest (SCA) may be caused by an acute and reversible myocardial injury, a chronic and irreversible myocardial damage, or a primary ventricular arrhythmia. Cardiac magnetic resonance imaging may identify myocardial edema (ME), which denotes acute and reversible myocardial damage. We evaluated the arrhythmic outcome of SCA survivors during follow-up and tested the prognostic role of ME. Methods and Results We included a consecutive series of 101 (71% men, median age 47 years) SCA survivors from 9 collaborative centers who underwent early (<1 month) cardiac magnetic resonance imaging and received an implantable cardioverter-defibrillator (ICD). On T2-weighted sequences, ME was found in 18 of 101 (18%) patients. According to cardiac magnetic resonance imaging findings, the arrhythmic SCA was ascribed to acute myocardial injury (either ischemic [n=10] or inflammatory [n=8]), to chronic structural heart diseases (ischemic heart disease [n=11], cardiomyopathy [n=20], or other [n=23]), or to primarily arrhythmic syndrome (n=29). During a follow-up of 47 months (28 to 67 months), 24 of 101 (24%) patients received an appropriate ICD intervention. ME was associated with a significantly higher survival free from both any ICD interventions (log-rank=0.04) and ICD shocks (log-rank=0.03) and remained an independent predictor of better arrhythmic outcome after adjustment for left ventricular ejection fraction and late gadolinium enhancement. The risk of appropriate ICD intervention was unrelated to the type of underlying heart disease. Conclusions ME on early cardiac magnetic resonance imaging, which denotes an acute and transient arrhythmogenic substrate, predicted a favorable long-term arrhythmic outcome of SCA survivors. These findings may have a substantial impact on future guidelines on the management of SCA survivors.

A type 2 diabetes (T2D) simulator has been recently proposed for supporting drug development and treatment optimization. This tool consists of a physiological model of glucose/insulin/C-peptide dynamics and a virtual cohort of T2D subjects (i.e., random extractions of model parameterizations from a joint parameter distribution) well describing both average and variability realistic T2D dynamics . However, the state-of-art procedure to get a reliable virtual population requires some post-processing after subject extraction, in order to discard implausible behaviors. We propose an improved method for virtual subjects' generation to overcome this burdensome task. To do so, we first assessed a refined joint parameter distribution, from which extracting a number of subjects, greater than the target population size. Then, target-size subsets are undersampled from the large cohort. The final virtual population is selected among the subsets as the one maximizing the similarity with T2D data and model parameter distribution, by means of measurement' outcome metrics and Euclidian distance (Δ), respectively. In the final population, almost all the outcome metrics are statistically identical to the clinical counterparts (p-value>0.05) and model parameters' distribution differs by ~5-10% from that derived from data. The methodology described here is flexible, thus resulting suitable for different T2D stages and type 1 diabetes, as well.Clinical Relevance- A straightforward subjects' generation would ease the availability of tailored in silico trials for testing diabetes treatment in a specific population.

Criteria for diagnosis of arrhythmogenic cardiomyopathy (ACM) were first proposed in 1994 and revised in 2010 by a Task Force. Although the Task Force criteria demonstrated a good accuracy for diagnosis of the original right ventricular phenotype (arrhythmogenic right ventricular cardiomyopathy), they lacked sensitivity for identification of the expanding phenotypic spectrum of ACM, which includes left-sided variants and did not incorporate late-gadolinium enhancement findings by cardiac magnetic resonance. The 2020 International criteria ("Padua criteria") have been developed by International experts with the aim to improve the diagnosis of ACM by providing new criteria for the diagnosis of left ventricular phenotypic features. The key upgrade was the incorporation of tissue characterization findings by cardiac magnetic resonance for noninvasive detection of late-gadolinium enhancement/myocardial fibrosis that are determinants for characterization of arrhythmogenic biventricular and left ventricular cardiomyopathy. The 2020 International criteria are heavily dependent on cardiac magnetic resonance, which has become mandatory to characterize the ACM phenotype and to exclude other diagnoses. New criteria regarding left ventricular depolarization and repolarization ECG abnormalities and ventricular arrhythmias of left ventricular origin were also provided. This article reviews the evolving approach to diagnosis of ACM, going back to the 1994 and 2010 International Task Force criteria and then grapple with the modern 2020 International criteria.

Aims: The aim of this registry was to evaluate the additional prognostic value of a composite cardiac magnetic resonance (CMR)-based risk score over standard-of-care (SOC) evaluation in a large cohort of consecutive unselected non-ischaemic cardiomyopathy (NICM) patients., Methods and Results: In the DERIVATE registry (www.clinicaltrials.gov/registration: RCT#NCT03352648), 1000 (derivation cohort) and 508 (validation cohort) NICM patients with chronic heart failure (HF) and left ventricular ejection fraction <50% were included. All-cause mortality and major adverse arrhythmic cardiac events (MAACE) were the primary and secondary endpoints, respectively. During a median follow-up of 959 days, all-cause mortality and MAACE occurred in 72 (7%) and 93 (9%) patients, respectively. Age and >3 segments with midwall fibrosis on late gadolinium enhancement (LGE) were the only independent predictors of all-cause mortality (HR: 1.036, 95% CI: 1.0117-1.056, P < 0.001 and HR: 2.077, 95% CI: 1.211-3.562, P = 0.008, respectively). For MAACE, the independent predictors were male gender, left ventricular end-diastolic volume index by CMR (CMR-LVEDVi), and >3 segments with midwall fibrosis on LGE (HR: 2.131, 95% CI: 1.231-3.690, P = 0.007; HR: 3.161, 95% CI: 1.750-5.709, P < 0.001; and HR: 1.693, 95% CI: 1.084-2.644, P = 0.021, respectively). A composite clinical and CMR-based risk score provided a net reclassification improvement of 63.7% (P < 0.001) for MAACE occurrence when added to the model based on SOC evaluation. These findings were confirmed in the validation cohort., Conclusion: In a large multicentre, multivendor cohort registry reflecting daily clinical practice in NICM work-up, a composite clinical and CMR-based risk score provides incremental prognostic value beyond SOC evaluation, which may have impact on the indication of implantable cardioverter-defibrillator implantation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Cardiovascular magnetic resonance (CMR) has emerged as an accurate diagnostic technique for the evaluation of patients with cardiac disease in the majority of clinical settings, thanks to an established additional diagnostic and prognostic value. This document has been developed by a joined group of experts of the Italian Society of Cardiology (SIC) and Italian Society of Radiology (SIRM) to provide a summary about the current state of technology and clinical applications of CMR, to improve the clinical diagnostic pathways and to promote its inclusion in clinical practice. The writing committee consisted of members and experts of both societies in order to develop a more integrated approach in the field of cardiac imaging. This section 2 will cover myocarditis, pericardial disease, cardiomyopathies and valvular heart disease., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aims: The aim of this study is to evaluate the clinical features of patients affected by arrhythmogenic cardiomyopathy (AC), presenting with chest pain and myocardial enzyme release in the setting of normal coronary arteries ('hot phase')., Methods and Results: We collected detailed anamnestic, clinical, instrumental, genetic, and histopathological findings as well as follow-up data in a series of AC patients who experienced a hot phase. A total of 23 subjects (12 males, mean age at the first episode 27 ± 16 years) were identified among 560 AC probands and family members (5%). At first episode, 10 patients (43%) already fulfilled AC diagnostic criteria. Twelve-lead electrocardiogram recorded during symptoms showed ST-segment elevation in 11 patients (48%). Endomyocardial biopsy was performed in 11 patients, 8 of them during the acute phase showing histologic evidence of virus-negative myocarditis in 88%. Cardiac magnetic resonance was performed in 21 patients, 12 of them during the acute phase; oedema and/or hyperaemia were detected in 7 (58%) and late gadolinium enhancement in 11 (92%). At the end of follow-up (mean 17 years, range 1-32), 12 additional patients achieved an AC diagnosis. Genetic testing was positive in 77% of cases and pathogenic mutations in desmoplakin gene were the most frequent. No patient complained of sustained ventricular arrhythmias or died suddenly during the 'hot phase'., Conclusion: 'Hot phase' represents an uncommon clinical presentation of AC, which often occurs in paediatric patients and carriers of desmoplakin gene mutations. Tissue characterization, family history, and genetic test represent fundamental diagnostic tools for differential diagnosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)