Ten years of subcutaneous defibrillator therapy: Consolidated clinical evidence and future perspectives.

The subcutaneous implantable cardioverter defibrillator (S-ICD) was developed as an alternative to the traditional transvenous implantable cardioverter defibrillator (TV-ICD), aiming to provide easier implantation, simplified detection algorithm of malignant ventricular arrhythmias and prevention from placing components in the cardiovascular system. The S-ICD is implanted subcutaneously or intramuscularly with the generator placed in the left midaxillary line and the lead tunneled subcutaneously in the left para-sternal region. Preimplant electrocardiogram screening is recommended to prevent implantation in patients at high risk of T wave over-sensing. Currently, the S-ICD is unsuitable for patients requiring pacing or cardiac resynchronization. Since the beginning, the S-ICD underwent extensive preclinical investigation until the first prospective multicentre trial demonstrating high efficacy and safety led to market release. While earlier studies focused on younger patients with higher ejection fraction, more recent studies showed favorable outcomes even in patients with comorbidities similar to those typically observed in patients receiving TV-ICD. The development of second and third generation devices has contributed to reduce inappropriate shocks and overcome previous limitations. The aim of this paper is to review the evidence in the literature over the past decade supporting S-ICD as a valid alternative to TV-ICD in terms of safety and efficacy, highlighting the improvements in technology, as well as outcomes.

Efficacy of cryoablation in atrial fibrillation: comparison with antiarrhythmic therapy.

Atrial fibrillation (AF) represents the most common arrhythmia in clinical practice, characterized by irregular atrial electrical activity originating mainly in and around the pulmonary veins. This condition can manifest itself symptomatically or silently but still dangerously. Complications associated with AF include stroke, heart failure, worst clinical outcome in patients with underlying conditions, increased emergency room visits, hospitalizations, and cardiovascular mortality. Currently, according to the main international guidelines, antiarrhythmic therapy is considered the first choice for rhythm control in patients with AF despite modest efficacy and non-negligible side effects. In recent decades, radiofrequency catheter ablation has emerged as an alternative to antiarrhythmic drugs for rhythm control. Cryoablation was developed with the aim of reducing procedural times and reducing complications related to the ablative procedure with radiofrequency without losing efficacy. Recent studies conducted with rigour and scientific solidity have demonstrated on the one hand that the results of this technique are not inferior compare with radiofrequency. This study aims to compare data on the safety and efficacy of cryoablation with those obtained from antiarrhythmic drugs through a review of the most recent scientific evidence.

Prognostic Value of Nonischemic Ringlike Left Ventricular Scar in Patients With Apparently Idiopathic Nonsustained Ventricular Arrhythmias.

BACKGROUND: Left ventricular (LV) scar on late gadolinium enhancement (LGE) cardiac magnetic resonance has been correlated with life-threatening arrhythmic events in patients with apparently idiopathic ventricular arrhythmias (VAs). We investigated the prognostic significance of a specific LV-LGE phenotype characterized by a ringlike pattern of fibrosis. METHODS: A total of 686 patients with apparently idiopathic nonsustained VA underwent contrast-enhanced cardiac magnetic resonance. A ringlike pattern of LV scar was defined as LV subepicardial/midmyocardial LGE involving at least 3 contiguous segments in the same short-axis slice. The end point of the study was time to the composite outcome of all-cause death, resuscitated cardiac arrest because of ventricular fibrillation or hemodynamically unstable ventricular tachycardia and appropriate implantable cardioverter defibrillator therapy. RESULTS: A total of 28 patients (4%) had a ringlike pattern of scar (group A), 78 (11%) had a non-ringlike pattern (group B), and 580 (85%) had normal cardiac magnetic resonance with no LGE (group C). Group A patients were younger compared with groups B and C (median age, 40 vs 52 vs 45 years; P<0.01), more frequently men (96% vs 82% vs 55%; P<0.01), with a higher prevalence of family history of sudden cardiac death or cardiomyopathy (39% vs 14% vs 6%; P<0.01) and more frequent history of unexplained syncope (18% vs 9% vs 3%; P<0.01). All patients in group A showed VA with a right bundle-branch block morphology versus 69% in group B and 21% in group C (P<0.01). Multifocal VAs were observed in 46% of group A patients compared with 26% of group B and 4% of group C (P<0.01). After a median follow-up of 61 months (range, 34-84 months), the composite outcome occurred in 14 patients (50.0%) in group A versus 15 (19.0%) in group B and 2 (0.3%) in group C (P<0.01). After multivariable adjustment, the presence of LGE with ringlike pattern remained independently associated with increased risk of the composite end point (hazard ratio, 68.98 [95% CI, 14.67-324.39], P<0.01). CONCLUSIONS: In patients with apparently idiopathic nonsustained VA, nonischemic LV scar with a ringlike pattern is associated with malignant arrhythmic events.

Collateral injury of the conduction system during catheter ablation of septal substrate in nonischemic cardiomyopathy.

INTRODUCTION: In patients with nonischemic cardiomyopathy (NICM) little is known about the clinical impact of catheter ablation (CA) of septal ventricular tachycardia (VT) resulting in the collateral injury of the conduction system (CICS). METHODS AND RESULTS: Ninety-five consecutive patients with NICM underwent CA of septal VT. Outcomes in patients with no baseline conduction abnormalities who developed CICS (group 1, n = 28 [29%]) were compared to patients with no CICS (group 2, n = 17 [18%]) and to patients with preexisting conduction abnormalities or biventricular pacing (group 3, n = 50 [53%]). Group-1 patients were younger, had a higher left ventricular ejection fraction and a lower prevalence of New York Heart Association III/IV class compared to group 3 while no significant differences were observed with group 2. After a median follow-up of 15 months, VT recurred in 14% of patients in group 1, 12% in group 2 (P = .94) and 32% in group 3 (P = .08) while death/transplant occurred in 14% of patients in group 1, 18% in group 2 (P = .69) and 28% in group 3 (P = .15). A worsening of left ventricular ejection fraction (LVEF) (median LVEF variation, -5%) was observed in group 1 compared to group 2 (median LVEF variation, 0%; P < .01) but not group-3 patients (median LVEF variation, -4%; P = .08) with a consequent higher need for new biventricular pacing in group 1 (43%) compared to group 2 (12%; P = .03) and group 3 (16%; P < .01). CONCLUSIONS: In patients with NICM and septal substrate, sparing the abnormal substrate harboring the conduction system provides acceptable VT control while preventing a worsening of the systolic function.

Prognostic role of serial quantitative evaluation of 18F-fluorodeoxyglucose uptake by PET/CT in patients with cardiac sarcoidosis presenting with ventricular tachycardia.

BACKGROUND: Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) has shown to be useful in diagnosis, staging and monitoring of cardiac sarcoidosis (CS) but its interpretation is not standardized. OBJECTIVES: We sought to investigate the clinical impact of serial quantitative FDG uptake analysis in patients with CS presenting with ventricular tachycardia (VT) treated by catheter ablation (CA). METHODS: We followed 20 patients (51 ± 9 years, 70% males) with CS and VT who underwent CA, with 92 serial FDG-PET scans (3-10 per patient). Myocardial FDG-avid lesions were quantified using three parameters: maximum standardized uptake value (SUVmax), partial-volume corrected mean standardized uptake value (SUVmean) and partial-volume corrected volume-intensity product [lesion metabolic activity (LMA)]. The volume-intensity product of the entire heart [global cardiac metabolic activity (gCMA)] and the background cardiac metabolic activity (bCMA: difference between gCMA and LMA) were also calculated. The primary end-point was the occurrence of major adverse cardiac events (MACE), including death, heart transplant, hospitalization for heart failure and implantable cardioverter defibrillator (ICD) appropriate interventions. Evolution of echocardiographic parameters over follow-up was also assessed. RESULTS: During a median follow-up of 35 (20-66) months, 18 MACE (1 death, 2 heart transplants, 12 ICD appropriate interventions, 3 hospitalizations) occurred in 12 (60%) patients. At univariable analysis, lack of PET improvement (defined by decrease in LMA of at least 25%) was the only variable associated with cardiac events during follow-up. In particular, non-responders had a 20-fold higher risk of MACE at follow-up (HR 18.96, 95% CI 2.26-159.27; p = 0.007). Moreover, a significant linear inverse relationship was observed between changes in LMA and changes in left ventricular ejection fraction over follow-up (ß = -20.11; p = 0.003). CONCLUSIONS: In patients with CS and VT, temporal change in FDG uptake evaluated by a quantitative approach is associated with parallel change in systolic function. Moreover, reduction in FDG uptake is strongly associated with fewer MACE at long-term follow-up.

Malfunction of cardiac devices after radiotherapy without direct exposure to ionizing radiation: mechanisms and experimental data.

AIMS: Malfunctions of cardiac implantable electronical devices (CIED) have been described after high-energy radiation therapy even in the absence of direct exposure to ionizing radiation, due to diffusion of neutrons (n) causing soft errors in inner circuits. The purpose of the study was to analyse the effect of scattered radiation on different types and models of CIED and the possible sources of malfunctions. METHODS AND RESULTS: Fifty-nine explanted CIED were placed on an anthropomorphous phantom of tissue-equivalent material, and a high-energy photon (15 MV) radiotherapy course (total dose = 70 Gy) for prostate treatment was performed. All devices were interrogated before and after radiation. Radiation dose, the electromagnetic field, and neutron fluence at the CIED site were measured. Thirty-four pacemakers (PM) and 25 implantable cardioverter-defibrillators (ICD) were analysed. No malfunctions were detected before radiation. After radiation a software malfunction was evident in 13 (52%) ICD and 6 (18%) PM; no significant electromagnetic field or photon radiations were detected in the thoracic region. Neutron capture was demonstrated by the presence of the (198)Au((197)Au + n) or (192)Ir((191)Ir + n) isotope activation; it was significantly greater in ICD than in PM and non-significantly greater in damaged devices. A greater effect in St Jude PM (2/2 damaged), Boston (9/11), and St Jude ICD (3/6) and in older ICD models was observed; the year of production was not relevant in PM. CONCLUSION: High-energy radiation can cause different malfunctions on CIED, particularly ICD, even without direct exposure to ionizing radiation due to scattered radiation of neutrons produced by the linear accelerator.

Long-term outcome of 'super-responder' patients to cardiac resynchronization therapy.

AIMS: To evaluate the long-term changes of clinical and echocardiographic parameters, the incidence of cardiac events and parameters associated with late cardiac events in 'super-responders' to cardiac resynchronization therapy (CRT) with [CRT defibrillator (CRT-D)] or without defibrillator back-up. METHODS AND RESULTS: In all consecutive patients treated with CRT in two Italian centres (Trieste and Udine) with left ventricular ejection fraction (LVEF) ≤0.35 at implantation (Timp) and LVEF > 0.50 1 and/or 2 years (Tnorm) after implantation, the long-term outcome and the evolution of echocardiographic parameters were assessed; factors associated with a higher risk of cardiac events, defined as hospitalization or death for heart failure (HF), sudden death, or CRT-D appropriate interventions, were also analysed. Among the 259 patients evaluated, 62 (24%) had LVEF ≥ 0.50 at Tnorm (n = 44 with at 1 year, n = 18 at 2 years). During a mean follow-up of 68 ± 30 months, one cardiac death (for HF) and eight cardiovascular events (two hospitalization for HF and six appropriate CRT-D interventions) occurred. At the last echo evaluation (Tfup) performed 51 ± 26 months after Timp, LVEF was <0.50 in five patients (>0.45 in four of them). At univariable analysis, only LV end-systolic volume evaluated at Tfup was associated with a higher risk of cardiac events during follow-up. CONCLUSION: In 'super-responders' to CRT long-term outcome is excellent. However, cardiac events, mainly CRT-D appropriate interventions, can occur despite the persistence of LVEF > 0.50. Early identification of these patients is still an unsolved issue.

Correlation of MRI premature ventricular contraction activation pattern in bigeminy with electrophysiology study-confirmed site of origin.

Although PVCs commonly lead to degraded cine cardiac MRI (CMR), patients with PVCs may have relatively sharp cine images of both normal and ectopic beats ("double beats") when the rhythm during CMR is ventricular bigeminy, and only one beat of the pair is detected for gating. MRI methods for directly imaging premature ventricular contractions (PVCs) are not yet widely available. Localization of PVC site of origin with images may be helpful in planning ablations. The contraction pattern of the PVCs in bigeminy provides a "natural experiment" for investigating the potential utility of PVC imaging for localization. The purpose of this study was to evaluate the correlation of the visually assessed site of the initial contraction of the ectopic beats with the site of origin found by electroanatomic mapping. Images from 7 of 86 consecutive patients who underwent CMR prior to PVC ablation were found to include clear cine images of bigeminy. The visually apparent site of origin of the ectopic contraction was determined by three experienced, blinded CMR readers and correlated with each other, and with PVC site of origin determined by 3D electroanatomic mapping during catheter ablation. Blinded ascertainment of visually apparent initial contraction pattern for PVC localization was within 2 wall segments of PVC origin by 3D electroanatomic mapping 76% of the time. Our data from patients with PVCs with clear images of the ectopic beats when in bigeminy provide proof-of-concept that CMR ectopic beat contraction patterns analysis may provide a novel method for localizing PVC origin prior to ablation procedures. Direct imaging of PVCs with use of newer cardiac imaging methods, even without the presence of bigeminy, may thus provide valuable data for procedural planning.

Polycomb Bodies Detection in Murine Fibromuscular Stroma from Skin, Skeletal Muscles, and Aortic Tissues.

The regulation of chromatin structure depends on a dynamic, multiple mechanisms that modulate gene expression and constitute the epigenome. The Polycomb group (PcG) of proteins are epigenetic factors involved in the transcriptional repression. Among their multilevel, chromatin-associated functions, PcG proteins mediate the establishment and maintenance of higher-order structures at target genes, allowing the transmission of transcriptional programs throughout the cell cycle.In the nucleus, PcG proteins localize close to the pericentric heterochromatin forming microscopically foci, called Polycomb bodies. Here, to visualize the tissue-specific PcG distribution in the aorta, dorsal skin and hindlimb muscles, we combine a fluorescence-activated cell sorter (FACS)-based method with an immunofluorescence staining.