Incidence of ventricular arrhythmias related to COVID infection and vaccination in patients with Brugada syndrome: Insights from a large Italian multicenter registry based on continuous rhythm monitoring.

INTRODUCTION: Brugada syndrome (BrS) has a dynamic ECG pattern that might be revealed by certain conditions such as fever. We evaluated the incidence and management of ventricular arrhythmias (VAs) related to COVID-19 infection and vaccination among BrS patients carriers of an implantable loop recorder (ILR) or implantable cardioverter-defibrillator (ICD) and followed by remote monitoring. METHODS: This was a multicenter retrospective study. Patients were carriers of devices with remote monitoring follow-up. We recorded VAs 6 months before COVID-19 infection or vaccination, during infection, at each vaccination, and up to 6-month post-COVID-19 or 1 month after the last vaccination. In ICD carriers, we documented any device intervention. RESULTS: We included 326 patients, 202 with an ICD and 124 with an ILR. One hundred and nine patients (33.4%) had COVID-19, 55% of whom developed fever. Hospitalization rate due to COVID-19 infection was 2.76%. After infection, we recorded only two ventricular tachycardias (VTs). After the first, second, and third vaccines, the incidence of non-sustained ventricular tachycardia (NSVT) was 1.5%, 2%, and 1%, respectively. The incidence of VT was 1% after the second dose. Six-month post-COVID-19 healing or 1 month after the last vaccine, we documented NSVT in 3.4%, VT in 0.5%, and ventricular fibrillation in 0.5% of patients. Overall, one patient received anti-tachycardia pacing and one a shock. ILR carriers had no VAs. No differences were found in VT before and after infection and before and after each vaccination. CONCLUSIONS: From this large multicenter study conducted in BrS patients, followed by remote monitoring, the overall incidence of sustained VAs after COVID-19 infection and vaccination is relatively low.

Mortality after transvenous lead extraction: A risk prediction model for sustainable care delivery.

BACKGROUND AND AIMS: Transvenous lead extraction (TLE) has become a pivotal part of a comprehensive lead management strategy, dealing with a continuously increasing demand. Nonetheless, the literature about the long-term impact of TLE on survivals is still lacking. Given these knowledge gaps, the aim of our study was to analyse very long-term mortality in patients undergoing TLE in public health perspective. METHODS: This prospective, single-centre, observational study enrolled consecutive patients with cardiac implantable electronic device (CIED) who underwent TLE, from January 2005 to January 2021. The main goal was to establish the independent predictors of very long-term mortality after TLE. We also aimed at assessing procedural and hospitalization-related costs. RESULTS: We enrolled 435 patients (mean age 70 ± 12 years, with mean lead dwelling time 6.8 ± 16.7 years), with prevalent infective indication to TLE (92%). Initial success of TLE was achieved in 98% of population. After a median follow-up of 4.5 years (range: 1 month-15.5 years), 150 of the 435 enrolled patients (34%) died. At multivariate analysis, death was predicted by: age (≥77 years, OR: 2.55, CI: 1.8-3.6, p < 0.001), chronic kidney disease (CKD) defined as severe reduction of estimated glomerular filtration rate (eGFR <30 mL/min/1.73 m2 , OR: 1.75, CI: 1.24-2.4, p = 0.001) and systolic dysfunction assessed before TLE defined as left ventricular ejection fraction (LVEF) <40%, OR: 1.78, CI 1.26-2.5, p = 0.001. Mean extraction cost was €5011 per patient without reimplantation and €6336 per patient with reimplantation respectively. CONCLUSIONS: Our study identified three predictors of long-term mortality in a high-risk cohort of patients with a cardiac device infection, undergoing successful TLE. The future development of a mortality risk score before might impact on public health strategy.

Leadless pacemaker technology: clinical evidence of new paradigm of pacing.

Despite continuous technological developments, transvenous pacemakers (PM) are still associated with significant immediate and long-term complications, mostly lead or pocket-related. Recent technological advances brought to the introduction in clinical practice of leadless PM for selected cohort of patients. These miniaturize devices are implanted through the femoral vein and advanced to the right ventricle, without leaving leads in place. Lack of upper extremity vascular access and/or high infective risk in patients requiring VVI pacing are the most common indications to leadless PM. The recently introduced MICRA AV leadless PM also allows ventricular synchronization through mechanical sensing of atrial contraction waves, thus solving the problem of AV synchronization. This review will discuss and summarize available clinical evidence on leadless PM, their performance compared to transvenous devices, current applications and future perspectives.

Pulmonary vein isolation in atrial fibrillation patients guided by a novel local impedance algorithm: 1-year outcome from the CHARISMA study.

BACKGROUND: Highly localized impedance (LI) measurements during atrial fibrillation (AF) ablation have recently emerged as a viable real-time indicator of tissue characteristics and durability of the lesions created. We report the outcomes of acute and long-term clinical evaluation of the new DirectSense algorithm in AF ablation. METHODS: Consecutive patients undergoing AF ablation were included in the CHARISMA registry. RF delivery was guided by the DirectSense algorithm, which records the magnitude and time-course of the impedance drop. The ablation endpoint was pulmonary vein isolation (PVI), as assessed by the entrance and exit block. RESULTS: 3556 point-by-point first-pass RF applications of >10 s duration were analyzed in 153 patients (mean age=59 ± 10 years, 70% men, 61% paroxysmal AF, 39% persistent AF). The mean baseline LI was 105 ± 15 Ω before ablation and 92 ± 12 Ω after ablation (p < .0001). Both absolute drops in LI and the time to LI drop (LI drop/τ) were greater at successful ablation sites (n = 3122, 88%) than at ineffective ablation sites (n = 434, 12%) (14 ± 8 Ω vs 6 ± 4 Ω, p < .0001 for LI; 0.73 [0.41-1.25] Ω/s vs. 0.35[0.22-0.59 Ω/s, p < .0001 for LI drop/τ). No major complications occurred during or after the procedures. All PVs had been successfully isolated. During a mean follow-up of 366 ± 130 days, 18 patients (11.8%) suffered an AF/atrial tachycardia recurrence after the 90-day blanking period. CONCLUSION: The magnitude and time-course of the LI drop during RF delivery were associated with effective lesion formation. This ablation strategy for PVI guided by LI technology proved safe and effective and resulted in a very low rate of AF recurrence over 1-year follow-up.

Cardiac contractility modulation for patient with refractory heart failure: an updated evidence-based review.

Heart failure is the cardiovascular epidemic of the twenty-first century, with poor prognosis and quality of life despite optimized medical treatment. Despite over the last decade significant improvements, with a major impact on morbidity and mortality, have been made in therapy for heart failure with reduced ejection fraction, little progress was made in the development of devices, with the implantable defibrillator indicated for patients with left ventricle ejection fraction ≤ 35% and cardiac resynchronization therapy for those with QRS ≥ 130 ms and evidence of left bundle branch block. Nevertheless, only a third of patients meet these criteria and a high percentage of patients are non-responders in terms of improving symptoms. Nowadays, in patients with symptomatic heart failure with ejection fraction between 25% and 45% and QRS < 130 ms, not eligible for cardiac resynchronization, the cardiac contractility modulation (CCM) represents a concrete therapeutic option, having proved to be safe and effective in reducing hospitalizations for heart failure and improving symptoms, functional capacity, and quality of life. The aim of this review is therefore to summarize the pathophysiological mechanisms, the current indications, and the recent developments regarding the new applications of the CCM for patients with chronic heart failure.

Severity of spleep apnea syndrome and life-threatening tachyarrhythmias in patients with implantable cardioverter defibrillator.

BACKGROUND: Sleep apnea syndrome (SAS) has been reported to be associated with a higher incidence of ventricular arrhythmias. The aim of this study was twofold: (1) to investigate whether in SAS patients receiving an implantable cardioverter defibrillator (ICD) the severity of SAS was associated with the occurrence of ventricular arrhythmias; (2) to assess whether changes in nocturnal apnoic/hypopnoic episodes may favor the occurrence of life-threatening arrhythmias, that is, sustained ventricular tachycardia (VT)/fibrillation (VF), requiring ICD intervention. METHODS: We enrolled 46 patients with documented SAS at polysomnography (apnea/hypopnea index [AHI] > 5) who also had a left ventricle ejection fraction (LVEF) < 35% and, according to primary prevention indications, implanted an ICD (Boston Scientific Incepta) able to daily monitor apnoic/hypopnoic episodes occurring during sleep. Patients were followed at 3-month intervals. RESULTS: At a mean follow-up of 18 months, 21 episodes of sustained VT/FV requiring ICD intervention were documented in eight patients (17.4%). Baseline AHI was significantly higher in patients with compared to those without ICD intervention. ICD interventions, however, were not preceded by any worsening of apnoic/hypopnoic episodes. The respiratory disturbance index (RDI) of the week during the event, indeed, was not different from that recorded during the previous 2 weeks (25.4 ± 11, 25.6 ± 10 and 25.1 ± 10, respectively; p = .9). CONCLUSIONS: In patients with SAS who received an ICD for primary prevention of sudden death, those with ICD interventions showed a more severe form of the disease at baseline. ICD interventions, however, were not preceded by any significant changes in SAS severity.

Early rhythm-control ablation therapy to prevent atrial fibrillation recurrences: Insights from the CHARISMA Registry.

BACKGROUND: An early, comprehensive rhythm-control therapy is needed in order to treat atrial fibrillation (AF) effectively and to improve ablation outcomes. METHODS: A total of 153 consecutive patients from the CHARISMA registry undergoing AF ablation at eight centers were included. Patients with de novo PVI were classified as having undergone early treatment (ET) if the procedure was performed within 6 months after the first AF episode, and as having undergone delayed treatment (DT) if ablation was performed over 6 months after the first AF episode. RESULTS: One-hundred fifty-three patients were enrolled (69.9% male, 59 ± 10 years, 61.4% paroxysmal AF, 38.6% persistent AF). The time from the first AF episode to the ablation procedure was 1034 ± 1483 days. The ET group comprised 36 patients (25.3%), the DT group 60 (39.2%) and Redo cases were 57 (37.3%). During a mean follow-up of 366 ± 130 days, 18 patients (11.8%) suffered an AF/AT recurrence. More DT patients than ET patients suffered recurrences (15.7% vs. 2.2%, p = 0.0452) and the time to AT/AF recurrence was shorter in the group of patients who received an ablation treatment after 6 months (HR = 6.19, 95% CI: 1.7 to 21.9; p = 0.0474). On multivariate Cox analysis, only hypertension (HR = 4.86, 95% CI: 1.6 to 14.98, p = 0.0062) was independently associated with recurrences. Beyond the hypertension risk factor, ET was associated with a low risk of recurrence; recurrence rate ranged from 0% (ET patients without hypertension) to 25.0% (DT patients with hypertension). CONCLUSIONS: An early rhythm-control ablation therapy in the absence of common risk factors was associated with the lowest rate of recurrences.

Sudden Cardiac Death in Athletes in Italy during 2019: Internet-Based Epidemiological Research.

Background and objectives: An Italian nationwide pre-participation screening approach for prevention of sudden cardiac death in athletes (SCD-A) in competitive sportspeople showed promising results but did not achieve international consensus, due to cost-effectiveness and the shortfall of a monitoring plan. From this perspective, we tried to provide an epidemiological update of SCD-A in Italy through a year-long internet-based search. Materials and Methods: One year-long Google search was performed using mandatory and non-mandatory keywords. Data were collected according to prevalent SCD-A definition and matched with sport-related figures from Italian National Institute of Statistics (ISTAT) and Italian National Olympic Committee (CONI). Results: Ninety-eight cases of SCD-A in 2019 were identified (48.0% competitive, 52.0% non-competitive athletes). Male/female ratio was 13:1. The most common sports were soccer (33.7%), athletics (15.3%) and fitness (13.3%). A conclusive diagnosis was achieved only in 37 cases (33 of cardiac origin), with the leading diagnosis being coronary artery disease in 27 and a notably higher occurrence among master athletes. Combining these findings with ISTAT and CONI data, the SCD-A incidence rate in the whole Italian sport population was found to be 0.47/100,000 persons per year (1.00/100,000 in the competitive and 0.32/100,000 in the non-competitive population). The relative risk of SCD-A is 3.1 (CI 2.1-4.7; p < 0.0001) for competitive compared to non-competitive athletes; 9.9 for male (CI 4.6-21.4; p < 0.0001) with respect to female. Conclusions: We provided an updated incidence rate of SCD-A in both competitive and non-competitive sport in Italy. A higher risk of SCD-A among competitive and male athletes was confirmed, thus corroborating the value of Italian pre-participation screening in this population.

Diagnostic Workflow in Competitive Athletes with Ventricular Arrhythmias and Suspected Concealed Cardiomyopathies.

The diagnosis of structural heart disease in athletes with ventricular arrhythmias (VAs) and an apparently normal heart can be very challenging. Several pieces of evidence demonstrate the importance of an extensive diagnostic work-up in apparently healthy young patients for the characterization of concealed cardiomyopathies. This study shows the various diagnostic levels and tools to help identify which athletes need deeper investigation in order to unmask possible underlying heart disease.

Clinical utility of genetic testing in the early diagnosis of Danon disease mimicking hypertrophic cardiomyopathy: a case report.

BACKGROUND: Danon disease (OMIM 300257) is an X-linked lysosomal storage disorder, characterized by hypertrophic cardiomyopathy (HCM), skeletal myopathy, variable intellectual disability, and other minor clinical features. This condition accounts for ~ 4% of HCM patients, with a more severe and early onset phenotype in males, causing sudden cardiac death (SCD) in the first three decades of life. Genetic alterations in the LAMP2 gene are the main cause of this inherited fatal condition. Up to date, more than 100 different pathogenic variants have been reported in the literature. However, the majority of cases are misdiagnosed as HCM or have a delay in the diagnosis. CASE PRESENTATION: Here, we describe a young boy with an early diagnosis of HCM. After 2 episodes of ventricular fibrillation within 2 years, genetic testing identified a novel LAMP2 pathogenic variant. Subsequently, further clinical evaluations showing muscle weakness and mild intellectual disability confirmed the diagnosis of Danon disease. CONCLUSIONS: This report highlights the role of genetic testing in the rapid diagnosis of Danon disease, underscoring the need to routinely consider the inclusion of LAMP2 gene in the genetic screening for HCM, since an early diagnosis of Danon disease in patients with a phenotype mimicking HCM is essential to plan appropriate treatment, ie cardiac transplantation.

Real-life outcome of implantable cardioverter-defibrillator and cardiac resynchronization defibrillator replacement/upgrade in a contemporary population: observations from the multicentre DECODE registry.

AIMS: The benefit of prolonged implantable cardioverter-defibrillator (ICD)/cardiac resynchronization therapy defibrillator (CRT-D) therapy following device replacement is hindered by clinical and procedure-related adverse events (AEs). Adverse events rate is highest in more complex devices and at upgrades, as per the REPLACE registry experience, but is changing owing to the improvement in device technology and medical care. We aimed at understanding the extent and type of AEs in a contemporary Italian population. METHODS AND RESULTS: Detect long-term complications after ICD replacement (DECODE) was a prospective, single-arm, multicentre cohort study aimed at estimating medium- to long-term AEs in a large population of patients undergoing ICD/cardiac resynchronization defibrillator replacement/upgrade from 2013 to 2015. We prospectively analysed all clinical and device-related AEs at 12-month follow-up (FU) of 983 consecutive patients (median age 71 years, 76% male, 55% ischaemic, 47% CRT-D) followed for 353 ± 49 days. Seven percent of the patients died (60.6% for cardiovascular reasons), whereas 104 AEs occurred; 43 (4.4%) patients needed at least one surgical action to treat the AE. Adverse events rates were 3.3/100 years lead-related, 3.4/100 years bleedings, and 1.6/100 years infective. The primary endpoint was predicted by hospitalization in the month prior to the procedure [hazard ratio (HR) = 2.23, 1.16-4.29; 0.0169] and by upgrade (HR = 1.75, 1.02-2.99, 0.0441). One hundred and twelve (11.4%) patients met the combined endpoint of death from any cause, cardiac implantable electronic device (CIED)-related infection, and surgical action/hospitalization required to treat the AE. Hospitalization within 30 days prior to the procedure (HR = 2.07, 1.13-3.81; 0.0199), anticoagulation (HR = 1.97, 1.26-3.07; 0.003), and ischaemic cardiomyopathy (HR = 1.67, 95% confidence interval 1.06-2.63; P = 0.0276) were associated with the combined endpoint during FU. CONCLUSIONS: Adverse events following CIED replacement/upgrade are lower than previously reported, possibly owing to improved patients care. Hospitalization in the month prior to the procedure, upgrade, and clinical profile (anticoagulation, ischaemic cardiomyopathy) hint to increased risk, suggesting an individualized planning of the procedure to minimize overall AEs. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/ Identifier: NCT02076789.

Appropriate implantable cardioverter-defibrillator interventions in cardiac resynchronization therapy-defibrillator (CRT-D) patients undergoing device replacement: time to downgrade from CRT-D to CRT-pacemaker? Insights from real-world clinical practice in the DECODE CRT-D analysis.

Aim: Ventricular tachycardia (VT)/ventricular fibrillation (VF) occurrence after cardiac resynchronization therapy-defibrillator (CRT-D) replacement is unknown; hence, there is no practical guideline to recommend either CRT-D or CRT-pacemaker at the time of device replacement. We observed the 1-year VT/VF occurrence after CRT-D replacement in a subanalysis of the Detect Long-term Complications after ICD Replacement (DECODE) registry. Methods and results: A total of 332 consecutive patients who had undergone CRT-D replacement from 2013 to 2015 were enrolled in 36 Italian centres. The primary endpoint was the number of patients with any appropriate implantable cardioverter-defibrillator (ICD) interventions during 12-month follow-up. The secondary endpoint comprised death from any cause and appropriate ICD interventions. At replacement, 214 (64.5%) patients had a left ventricular ejection fraction ≤ 35% and 138 (41.6%) patients had a secondary prevention indication for ICD. Seventy (21.1%) patients had no longer indication to ICD therapy. During a median follow-up period of 406.5 (362-533) days, VT/VF requiring therapy delivery occurred in 57 (17%) patients, specifically in 7% of those who no longer had an ICD indication. On multivariate analysis, number of criteria for ICD replacement independently predicted appropriate ICD intervention during follow-up [hazard ratio (HR) = 1.62, 95% confidence interval (CI) 1.07-2.46; log-rank P = 0.02]. The combined endpoint of death from any cause or appropriate ICD therapy occurred in 76 (23%) patients. Only NYHA class remained associated with this combined endpoint (HR = 1.97, 95% CI 1.23-3.14; P = 0.005). Conclusions: The DECODE registry showed the 'real-world' experience of CRT-D recipients approaching device replacement, in which 7% of patients who no longer had an indication for ICD therapy experienced appropriate ICD interventions.

Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device: Results From the AATAC Multicenter Randomized Trial.

BACKGROUND: Whether catheter ablation (CA) is superior to amiodarone (AMIO) for the treatment of persistent atrial fibrillation (AF) in patients with heart failure is unknown. METHODS AND RESULTS: This was an open-label, randomized, parallel-group, multicenter study. Patients with persistent AF, dual-chamber implantable cardioverter defibrillator or cardiac resynchronization therapy defibrillator, New York Heart Association II to III, and left ventricular ejection fraction <40% within the past 6 months were randomly assigned (1:1 ratio) to undergo CA for AF (group 1, n=102) or receive AMIO (group 2, n=101). Recurrence of AF was the primary end point. All-cause mortality and unplanned hospitalization were the secondary end points. Patients were followed up for a minimum of 24 months. At the end of follow-up, 71 (70%; 95% confidence interval, 60%-78%) patients in group 1 were recurrence free after an average of 1.4±0.6 procedures in comparison with 34 (34%; 95% confidence interval, 25%-44%) in group 2 (log-rank P<0.001). The success rate of CA in the different centers after a single procedure ranged from 29% to 61%. After adjusting for covariates in the multivariable model, AMIO therapy was found to be significantly more likely to fail (hazard ratio, 2.5; 95% confidence interval, 1.5-4.3; P<0.001) than CA. Over the 2-year follow-up, the unplanned hospitalization rate was (32 [31%] in group 1 and 58 [57%] in group 2; P<0.001), showing 45% relative risk reduction (relative risk, 0.55; 95% confidence interval, 0.39-0.76). A significantly lower mortality was observed in CA (8 [8%] versus AMIO (18 [18%]; P=0.037). CONCLUSIONS: This multicenter randomized study shows that CA of AF is superior to AMIO in achieving freedom from AF at long-term follow-up and reducing unplanned hospitalization and mortality in patients with heart failure and persistent AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00729911.

Presence of 'ghosts' and mortality after transvenous lead extraction.

AIMS: The number of cardiovascular implantable electronic devices has increased progressively, leading to an increased need for transvenous lead extraction (TLE) due to device infections. Previous studies described 'ghost' as a post-removal, new, tubular, mobile mass detected by echocardiography following the lead's intracardiac route in the right-sided heart chambers, associated with diagnosis of cardiac device-related infective endocarditis. We aimed to analyse the association between 'ghosts' assessed by transesophageal echocardiography (TEE) and intracardiac echocardiography (ICE) and mortality in patients undergoing TLE. METHODS AND RESULTS: We prospectively enrolled 217 patients (70 ± 13 years; 164 males) undergoing TLE for systemic infection (139), local device infection (67), and lead malfunction (11). All patients underwent TEE before and 48 h after TLE and ICE during TLE. Patients were allocated to two groups: either with (Group 1) or without (Group 2) post-procedural 'ghost'. Mid-term clinical follow-up was obtained in all patients (11 months, IQR 1-34 months). We identified 30 (14%) patients with 'ghost', after TLE. The significant predictors of 'ghost' were Charlson co-morbidity index (HR = 1.24, 95% CI 1.04-1.48, P = 0.03) and diagnosis of endocarditis assessed by ICE (HR = 1.82, 95% CI 1.01-3.29, P = 0.04). Mortality was higher in Group 1 than in Group 2 (28 vs. 5%; log-rank P < 0.001). Independent predictors of mid-term mortality were the presence of 'ghost' and systemic infection as the clinical presentation of device infection (HR = 3.47, 95% CI 1.18-10.18, P = 0.002; HR = 3.39, 95% CI 1.15-9.95, P = 0.001, respectively). CONCLUSION: The presence of 'ghost' could be an independent predictor of mortality after TLE, thus identifying a subgroup of patients who need closer clinical surveillance to promptly detect any complications.