Implantable Cardioverter-defibrillator Therapy Research Articles

LVNC or hyper-trabeculated LV, are we missing something?

Abstract Introduction LVNC is a heterogeneous poorly understood entity characterized by prominent myocardial trabeculation.(1) It often overlaps with other phenotypes such as DCM, HCM.(2) Incidence of SCD is highly variable, however it may account for about 50% of all mortality in LVNC.(3) Risk stratification of SCD is a complex matter. Despite that current guidelines recommend following the same principles of 1ry prevention as in DCM based on similar CV mortality risk, it seems of utmost importance to identify additional features which could be specifically associated with LVNC and contributing to a higher risk of adverse events particularly ventricular arrhythmia (VA). Purpose To identify possible high risk features for prediction of ventricular arrhythmia in the form of documented NSVT, VT, or VF in LVNC. Methods This is a retrospective single centre cohort study of patients fulfilling the LVNC defining criteria from 2018 to 2023. Patients’ data were reviewed for family history of cardiomyopathies or SCD, clinical presentation, ECGs data in the form of QRS duration, QTc interval and Tp-e, Holter analysis, CIEDs interrogation if present and MRI data including LVEF, volumes, fibrosis burden and distribution, NC/C ratio, NC / LV global mass ratio, global longitudinal strain"GLS", global circumferential strain "GCS" , global radial strain "GRS" , extent of hypertrabeculation, RV involvement in the form of EF, volumes, hypertrabeculation. Results A total of 42 patients were included (34+/- 17 years of age, 57% males). 5 patients of our cohort were pediatrics. Mean LVEF 45%. LGE was detected in 14% of cases, RV involvement in 38 %. Ventricular arrhythmia were present in 15 patients (35%), of which 6 patients had malignant ventricular arrhythmia. LVEF, NC/LV global mass ratio, LVGLS, LVGCS were found to be significantly correlated with the occurrence of VA with cut-off values of <43%, >31%, <-15 and <-13.5 respectively. While positive FH, RV involvement, pattern, burden of LV fibrosis and ECG parameters didn’t significantly increase the incidence of VA. In a multivariate regression analysis NC to LV global mass ratio was the sole independent predictor of VA ( p value=0.024). ICDs were implanted in 10 cases, 8 were for 1ry prevention based on clinical judgement, 4 of them received appropriate ICD therapy. Conclusion LVNC is associated with increased risk of VA. In addition to clinical assessment and LVEF, CMR can add a different insight for risk stratification. Interestingly, LGE wasn’t associated with significantly increased risk of VA "taking into consideration LGE was found only in 14% of cases" highlighting the potential role the trabeculated myocardium in the pathophysiology of VA by altering the electrical stability of the heart. Finally, these findings could contribute in answering an ongoing question; Should LVNC with its unique characteristics be treated as a special entity with its own high-risk criteria for VA and SCD?LV NC/global mass ration and GLSDemographic,clinical,ECG and MRI data

Impact of taurolidine use during cardiac electronic implantable device implantation in heart failure patients

Abstract Background Cardiac Implantable Electronic Device (CIED) infections represent a critical health threat with potentially fatal consequences. The TauroPace™ is an innovative solution that contains taurolidine specifically formulated to eradicate environmental microbial contamination on the surface of CIEDs. To date, scarce data are available in literature about Taurolidine’s effect on preventing CIED infections. Aims To investigate the ability of the TauroPace™ to reduce major CIED infections through 12 months follow-up in fragile patients such as heart failure (HF) patients. Methods This prospective cohort study included patients with HF and an ejection fraction ≤ 35%, who were referred for de novo implantation, upgrading or battery replacement of Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy with defibrillator (CRT-D), to the EP labs of two tertiary care hospitals. Patients with previous CIED infections were excluded. During the procedures, the catheters were submerged in the TauroPace™ solution and the pocket was irrigated with taurolidine. Starting from the main risk factors for the development of CIED-related infections as identified in the literature (including individuals with heart failure, diabetes, chronic kidney disease, and those undergoing defibrillators implantation, especially upgrades or revisions procedure), we conducted a meta-analysis and meta-regression to evaluate the relationship between the treatment effect's magnitude and various predictors. To estimate the incidence of CIED infections in high-risk subgroups, we utilized the percentage of patients with diabetes, chronic renal failure, or those undergoing replacement, upgrade, or revision procedures, along with other risk factors for CIED infections, as continuous variables and we were able to modify our comparison parameters based on the real percentage of risk factors that we obtained. Results The study included 69 consecutive patients (53 male [76.8 %], 34 ischemic [49,3 %], median [IQR] age 68 [59-73] years, 19 diabetic [27.5 %] and 34 [49.2 %] with chronic renal failure), of whom 39 (56.5 %) received ICD and 30 (43.5 %) CRT-D, with 28 (40.6 %) replacement procedures, 2 (2.9 %) upgrades, and 39 (57%) de novo implantations. During the one-year follow-up period, 1 [1.45 (Standard Error, SE 0.014) %] patient undergoing a CRT replacement developed an infection. The available data from the literature estimate an incidence rate of 6% (SE 0.0106) when considering a selected patient population with a very high risk of infection similar to our population. This is significantly higher than our cohort (z-score -2.5447, p value = 0.011). Conclusions Taurolidine has yielded promising results, demonstrating a low incidence rate of infections within our cohort of high-risk patients, which is below that reported in the literature. Further data will be necessary to validate and confirm these initial findings.

Systematic review and meta-analysis comparing cardiac resynchronization therapy with versus without defibrillation in patients with non-ischemic cardiomyopathy

Abstract Background Cardiac resynchronization therapy (CRT) stands as a notable medical breakthrough for individuals with heart failure and electrical desynchrony. This intervention aims to alleviate symptoms, diminish hospitalization rates, and enhance overall survival, both in conjunction with and without implantable cardioverter-defibrillator (ICD) therapy. Despite these advancements, the role of defibrillator therapy in addition with CRT for patients with non-ischemic cardiomyopathy (NICM) remains a topic of debate. Objective To assess and compare the outcomes of individuals diagnosed with NICM who have underwent CRT with implantable cardioverter-defibrillator (CRT-D) against those who received CRT with a pacemaker only (CRT-P). Methods We conducted a systematic search of PubMed, Embase and Cochrane database during August 2023 for studies comparing CRT-P and CRT-D in patients with nonischemic cardiomyopathy. Results Thirteen studies, including two randomized clinical trials, were incorporated, with a total of 61,326 patients providing 16,446 pooled death events (9,108 in CRT-D and 7,338 in CRT-P). The meta-analysis revealed that CRT-D was associated with a significantly lower risk of all-cause mortality compared to CRT-P (pooled HR 0.74; 95% CI: 0.62-0.88; I2=84%). Subgroup analysis focusing on propensity score-matched studies yielded consistent findings (pooled HR 0.82; 95% CI: 0.77-0.87; I² = 0%, P<0.001). However, subgroup analysis for patients older than 75 years suggested no statistically significant difference in mortality risk within this specific age group (pooled HR 0.96; 95% CI: 0.811-1.15; I² = 39%, P<0.001). Regarding the secondary endpoint of cardiovascular mortality, no significant risk reduction with CRT-D was observed (pooled HR 0.70; 95% CI: 0.49-1.01; I² = 92%), albeit with high heterogeneity. Conclusion Our study suggests that the addition of defibrillator therapy significantly reduces all-cause mortality in CRT-eligible patients with NICM, although results were not observed for patients older than 75 years.All-cause MortalityPatients older 75 years old

Clinical performance and safety of a two-lead cardiac resynchronization therapy system with a floating atrial sensing dipole

Abstract Background The incidence of complications after implantable cardioverter-defibrillator (ICD) and cardiac resynchronisation therapy (CRT-D) implantations is dependent on the number of implanted leads. The majority of CRT-D patients have unimpaired sinus node function and do not require atrial pacing. A two-lead CRT-D system with a floating atrial sensing dipole mounted on the right ventricular lead ((CRT-DX) allows dual chamber tachyarrhythmia detection, and atrio-ventricular sequential pacing with a reduced amount of implanted material. Purpose This study investigated the clinical efficacy and safety of the CRT-DX system. Methods This multicentre, single-arm study observed patients after de novo implantation of a CRT-DX system for 12 months. Patients were eligible for the study when chronotropic competence was proven by heart rates ≥100 bpm during exercise, premature ventricular contractions rate of < 5%/h and absence of atrioventricular block ≥ II. Intraoperatively measured p-wave amplitude of ≥ 1 mV was recommended. The primary safety endpoint was the additional implantation of a right atrial (RA) lead after the initial implantation. As indicators of efficacy, we report the changes in left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) class over the follow-up period. Results Overall, 110 patients were implanted with the complete CRT-DX system. Mean age of study participants was 62 ± 12 years and 77 (70%) were male. The underlying heart disease was non-ischemic in 66 (60%) patients and 103 (93%) had a left bundle branch block. NYHA class was II in 60 (54.5%) and III in 50 (45.5%) patients. ICD placement was performed in 13 (11.8%) patients for the secondary prevention of sudden cardiac death. A total of 104 patients completed the follow-up, 2 patients died, 1 had the system explanted for infection, 2 withdrew consent and 1 was lost to follow-up. The primary endpoint of RA lead implantation was met in 2 (1.8%) participants (Figure 1). One patient required atrial pacing and one patient, who had shown a p-wave amplitude < 1 mV at implantation, lost atrial sensing. The mean RA sensing amplitude remained stable during follow-up (4.6 ± 1.8 mV, 4.9 ± 1.8 mV and 4.6 ± 1.8 mV at 1, 6 and 12 months, respectively; Figure 2). The LVEF improved by 14.7% ± 11.0%, from 26.3% ± 6.9% to 40.8% ± 10.7% (p < 0.00001). Changes in NYHA class were available in 87 patients with 35 (40.2%) improved by one class and 13 (14.9 %) by two classes. Thirty-four (39.1%) had no change and 5 (5.7%) worsened by one class (global p < 0.00001). Conclusion The two-lead CRT-DX system showed a low requirement of subsequent RA lead implantations (1.8%) and stable RA sensing amplitudes. Our results suggest a CRT response similar to that of conventional three-lead CRT-D systems. CRT-DX systems appear to be a feasible alternative for patients with chronotropic competence.Kaplan-Meier curve for primary endpointDaily mean RA sensing amplitude

Clinical practice and outcome of S-ICD replacement: results from the multicenter rhythm detect registry

Abstract Background Subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy is expanding rapidly. However, there are few data on the S-ICD replacement procedure. Objective The aim of this analysis was to describe the procedure and outcome of S-ICD replacement in clinical practice. Methods From 2013 to 2022, consecutive patients undergoing de-novo implantation of an S-ICD were enrolled at 66 Italian centers of the Rhythm Detect Registry. We analyzed consecutive patients who required S-ICD replacement. Results 319 S-ICD generators (49 Cameron, 270 Emblem) were replaced for battery depletion. All the procedures were performed in electrophysiology laboratories, by one or two expert operators. In 118 (37%) cases, the replacement was performed as outpatient procedure. The procedure was performed under local anesthesia with or without conscious sedation in 297 patients (93%). The previous S-ICD generator was in an intermuscular pocket in 195 (61%) patients, and in a subcutaneous pocket in the remaining 124 (39%). 39 (31%) generators were shifted from subcutaneous to intermuscular pocket, and their PRAETORIAN score improved from 43±20 to 34±13 (p=0.007). In most cases (308 (97%)), the defibrillation test was not performed after replacement, but the overall PRAETORIAN score was very low (37±28). The S-ICD system was successfully replaced in all patients and no complications were reported; the procedure duration was 39±16 min and was comparable in the case of generator re-implanted in the same pocket or in case of shift to a new pocket. Conclusions S-ICD replacement was safe and easy to perform, with no peri-operative complications. In clinical practice the replacement procedure is often an opportunity to optimize the position of the generator

Cardiac magnetic resonance to predict appropriate therapies in secondary prevention

Abstract Introduction Implantable cardioverter-defibrillator (ICD) therapy plays a pivotal role in the management of patient’s survivors of life-threatening ventricular arrhythmias (secondary prevention). Risk of recurrence may be related to presence of myocardial scar and its components (including core mass, border zone (BZ) mass, and BZ channels) assessed with late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Purpose Our study aims to analyze the role of imaging in predicting the risk of recurrent ventricular arrhythmias and improving the risk stratification for appropriate ICD therapy in patients receiving an ICD for secondary prevention. Methods From 2015 to 2020, a total of 111 patients with LGE-CMR before ICD implantation for secondary prevention. Scar tissue including core, BZ and BZ channels were automatically detected by specialized investigational software in patients with LGE-CMR. Patients were followed until a new event was detected. Results The mean age was 65.4 ± 11.4 years; 87% were men; 55% had ischemic cardiomyopathy. The mean left ventricular ejection fraction was 37.8 % ± 14.31%. Patients were followed for a median of 3.26 years (IQR 1.4-4.9). Within the first year of follow-up 22% of patients had received an appropriate therapy, 39% within 3 years and 53% within 6 years. Chronic kidney disease and New York Heart Association (NYHA) class were associated with the primary endpoint [HR 1.94(1.06-3.55), P-value 0.032)] and [HR 1.86 (1.19-2.91), P-value 0.006)], respectively. Regarding CMR characteristics, BZ percentage was also associated with appropriate ICD therapy in the follow up [HR 1.04(1-1.08), P-value 0.048)]. Other CMR parameter, such as BZ mass, BZ core %, BZ core mass and core mass showed a trend to predict ICD therapies during follow-up. ROC curve analysis with Youden’s index defined an optimal BZ percentage cutoff value for recurrence prediction of 9.5% [HR 0.49 (0.28-0.85)]. Conclusion In patients receiving an ICD for secondary prevention, chronic kidney disease, NYHA class and BZ percentage analyzed by LGE-CMR were predictors of recurrent ventricular arrhythmia. A cutoff of BZ of 9.5% could be used to select patients with high risk of recurrence.

Skeletal muscle index as a prognostic marker for sudden cardiac death in heart failure patients with reduced ejection fraction

Abstract Background The association between sarcopenia and sudden cardiac death remains unclear. Therefore, this study aimed to explore the association between sarcopenia, sudden cardiac death, and all-cause mortality in heart failure (HF) patients with reduced ejection fraction based on the skeletal muscle index (SMI) predicted by a formula. Methods A total of 300 patients with heart failure who were admitted to our Hospital, National Center for Cardiovascular Diseases, between March 2013 and November 2015 and met the inclusion criteria were retrospectively analyzed. Baseline SMI was divided into two groups: lower than or equal to the median (n=151) and higher than the median (n=149). The primary endpoints were a composite outcome of sudden cardiac death (SCD) or an equivalent event (sustained ventricular events, or appropriate implantable cardioverter-defibrillator (ICD) therapy).The secondary end point was all-cause mortality. Results The average follow-up period was 24.40 ± 14.07 months. Atotal of 42 patients (42/300,14.0%) experienced sudden cardiac death or an equivalent event, and 97 patients (97/300, 32.2%) experienced all-cause mortality. Analysis of the Kaplan–Meier survival curves showed that patients with an SMI lower than or equal to the median had a higher risk of sudden cardiac death (P=0.0015) and all-cause mortality (P<0.0001). Multivariate Cox analysis showed that an SMI lower than the median was an independent risk factor for sudden cardiac death (hazard ratio (HR): 2.837, 95% confidence interval (CI): 1.009–7.980, P=0.048) and all-cause mortality (HR: 2.597, 95% CI: 1.384–4.871, P=0.003). Conclusions Decreased SMI significantly increased the risk of sudden cardiac death and all-cause mortality in patients with HF and reduced ejection fraction. In a HF population with reduced ejection fraction, attention should be paid to the effect of sarcopenia on prognosis, and active intervention is expected to improve the prognosis of patients.

Mid-term outcomes after stereotactic arrhythmia radioablation for refractory ventricular tachycardia

Abstract Introduction stereotactic arrhythmia radioablation (STAR) is used as a rescue treatment for refractory ventricular tachycardia (VT) originating from unreachable myocardial substrate following unsuccessful radiofrequency catheter ablation (RFCA). The mid-term outcomes of STAR, however, remain poorly known. Objective to report the mid-term efficacy and safety outcomes in our series of 21 patients (pts) treated by STAR over 6 years. Methods Inclusion of consecutive pts treated by STAR with a Cyberknife system between 2017 and 2023. 3D-electroanatomical maps (EAM) of the VT substrate during unsuccessful RFCA were used to delineate the planned target volumes (PTV) on a 4D CT scan. Patients were followed up at least every 6 months by echocardiography and ICD interrogation at the outpatient clinic. Results 21 pts [16 (76 %) male, age 66±8 years] with a mean LVEF of 40±15% were included. The underlying substrate was ischemic in 7 (33 %); non-ischemic dilated in 7 (33 %); inflammatory in 4 (19%); hypertrophic in 1 (5%); neoplasic in 1 (5%); and malignant mitral valve prolapse in 1 (5%). A dose of 21±2 Gray was delivered to the PTV (26 ml, IQR 18-43 ml). After a median follow-up of 39 [IQR, 14-48] months, 12 pts (57%) remained in stable condition, 1 (5%) underwent a heart transplantation, 1 (5%) a left ventricular assistance device, 1 (5%) was in an incessant slow VT and 6 (29%) pts died (3 from end stage heart failure). 15 (71%) pts presented VT recurrences [7 (33%) ATPs; 3 (14%) shocks; 4 (19%) VT storm and 1 (5%) with a well-tolerated slow VT (100 bpm) with an LVAD till transplantation, of whom 9 (43%) required redo RFCA. The median value of total ventricular arrhythmic burden (defined as any arrhythmia requiring ICD therapies) decreased significantly from 31 (IQR, 4-100) to 7 (IQR, 1-23) (p<0.05); for nsVT from 57 (IQR, 1.5- 1196) to 41 (IQR, 0.5-584) (p ns); or ICD shocks from 1.5 (IQR, 0-5.5) to 0 (IQR, 0-2) (p<0.05); for ATPs from 21 (IQR, 2.5-94) to 4 (IQR, 0.5-13) (p<0.05). Figure 1 shows a graphic representation of arrhythmic burden before and after STAR. Conclusion in this cohort of highly selected pts with refractory VT, STAR significantly reduced the arrhythmic burden by a factor of 4 over a 3-year follow-up. Death rate remained high (29%), mostly by terminal heart failure. Nevertheless, a high proportion of pts had VT recurrences that were successfully managed by redo RFCA.VT burden before and after STAR

Prognostic relevance of global work index and global constructive work in patients with non-ischemic dilated cardiomyopathy

Myocardial work (MW) derived from pressure-strain loops is a novel non-invasive tool to assess left ventricular (LV) function, incorporating global longitudinal strain (GLS) by speckle tracking echocardiography and non-invasively assessed blood pressure. Studies on the role of MW in dilated cardiomyopathy (DCM) are still limited. Therefore, the aim of this study was to evaluate the potential value of MW for predicting adverse outcomes in patients with DCM. 116 consecutive patients with DCM who underwent heart catheterization were retrospectively recruited from June 2009 to July 2014. 34 patients (30%) met the composite endpoints for major adverse cardiac events (MACE) of cardiac transplantation, need for implantable cardioverter-defibrillator (ICD) therapy, heart failure hospitalization and all-cause mortality. Patients with DCM were followed up for a mean of 5.1 years (IQR: 2.2–9.1 years). Global work index (GWI) and global constructive work (GCW) were not only independent predictors but also provided incremental predictive values (Integrated discrimination improvement [IDI] > 0) of MACE in multivariate Cox models. Furthermore, Patients with GWI < 788 mm Hg% (HR 5.46, 95%CI 1.66–17.92, p = 0.005) and GCW < 1,238 mm Hg% (HR 4.46, 95%CI 1.53–12.98, p = 0.006) had higher risks of MACE. GWI and GCW assessed by strain imaging echocardiography may have an additional value beyond LV-EF and GLS for predicting adverse outcomes in DCM.

Catheter ablation as an adjunctive therapy to ICD implantation in Brugada syndrome.

Brugada Syndrome (BrS) is a life-threatening cardiac arrhythmia disorder associated with an increased risk ventricular arrhythmias (VAs) and sudden cardiac death (SCD). Current management primarily relies on implantable cardioverter-defibrillators (ICDs), but patients may experience ICD shocks. Catheter ablation (CA) has emerged as a potential intervention to target the arrhythmogenic substrate. This systematic review aims to evaluate the safety and efficacy of catheter ablation in BrS patients. Studies with BrS patients undergoing catheter ablation for VAs were included. 14 studies that involved a total population of 709 BrS patients, with catheter ablation performed in 528 of them, were included. Catheter ablation resulted in non-inducibility of VAs in 91% (95% CI: 83-99, I2=76%) and resolution of Type 1 ECG Brugada pattern in 88% (95% CI: 81-96.2, I2=91%) of the patients. After a mean follow-up of 30.7 months, 87% (95% CI: 80-94, I2=82%) of patients remained free from VAs. The incidence of VAs during follow-up was significantly lower in the ablation cohort in comparison to the group receiving only ICD therapy (OR=0.03, 95% CI: 0.01-0.12, I2=0%). Catheter ablation shows potential as a therapeutic approach to reduce VAs and improve outcomes in BrS patients. While further research with long follow-up period is required to confirm these findings, it represents a valuable tool as an add-on intervention to ICD implantation in BrS patients with high burden of VAs.Protocol registration: CRD42024506439.

The impact of hyperbaric oxygen treatment for cardiovascular implantable electronic devices.

The safety of hyperbaric oxygen treatment (HBO2) in patients with cardiovascular implanted electronic devices (CIED) remains unclear. We conducted a retrospective analysis of seven CIED patients (median age 79 [73-83] years, five males [71.4%]), including five with pacemakers and two with implantable cardioverter defibrillators (ICD), who underwent HBO2 between June 2013 and April 2023. During the initial session, electrocardiogram monitoring was conducted, and CIED checks were performed before and after the treatment. In addition, the medical records were scrutinized to identify any abnormal CIED operations. All seven CIED patients underwent HBO2 within the safety pressure range specified by the CIED manufacturers or general pressure test by the International Organization for Standardization (2.5 [2.5-2.5] atmosphere absolute × 18 [5-20] sessions). When comparing the CIED parameters before and after HBO2, no significant changes were observed in the waveform amplitudes, pacing thresholds, lead impedance of the atrial and ventricular leads, or battery levels. All seven patients, including two with the rate response function activated, exhibited no significant changes in the pacing rate or pacing failure. Two ICD patients did not deactivate the therapy, including the defibrillation; however, they did not experience any arrhythmia or inappropriate ICD therapy during the HBO2. CIED patients who underwent HBO2 within the safety pressure range exhibited no significant changes in the parameters immediately after the HBO2 and had no observable abnormal CIED operations during the treatment. The safety of defibrillation by an ICD during HBO2 should be clarified.

Safety, efficacy, and reliability evaluation ofa novel small-diameter defibrillation lead: Global LEADR pivotal trial results

BackgroundImplantable cardioverter-defibrillators last longer, and interest in reliable leads with targeted lead placement is growing. The OmniaSecure defibrillation lead is a novel, small-diameter, catheter-delivered lead designed for targeted placement, based on the established SelectSecure SureScan MRI Model 3830 lumenless pacing lead platform. ObjectiveThis trial assessed safety and efficacy of the OmniaSecure defibrillation lead. MethodsThe worldwide LEADR pivotal clinical trial enrolled patients indicated for de novo implantation of a primary or secondary prevention implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator, all of whom received the study lead. The primary efficacy end point was successful defibrillation at implantation per protocol. The primary safety end point was freedom from study lead–related major complications at 6 months. The primary efficacy and safety objectives were met if the lower bound of the 2-sided 95% credible interval was >88% and >90%, respectively. ResultsIn total, 643 patients successfully received the study lead, and 505 patients have completed 12-month follow-up. The lead was placed in the desired right ventricular location in 99.5% of patients. Defibrillation testing at implantation was completed in 119 patients, with success in 97.5%. The Kaplan-Meier estimated freedom from study lead–related major complications was 97.1% at 6 and 12 months. The trial exceeded the primary efficacy and safety objective thresholds. There were zero study lead fractures and electrical performance was stable throughout the mean follow-up of 12.7 ± 4.8 months (mean ± SD). ConclusionThe OmniaSecure lead exceeded prespecified primary end point performance goals for safety and efficacy, demonstrating high defibrillation success and a low occurrence of lead-related major complications with zero lead fractures.

IMPLANTABLE LOOP RECORDER IN BRUGADA SYNDROME: INSIGHTS FROM A SINGLE–CENTER EXPERIENCE

Abstract Brugada syndrome (BrS) is characterized by a “coved” ST segment elevation of ≥2 mm in the right precordial electrocardiographic (ECG) leads, either spontaneously or drug–induced. Risk stratification in individuals with BrS remains challenging. Currently, miniaturized and remotely monitored implantable loop recorders (ILRs) are available, providing physicians with a diagnostic tool that can help guide intervention or therapy decisions for these patients. The objective of this study was to investigate the characteristics and outcomes of patients diagnosed with BrS who underwent ICM insertion during routine clinical activity. This is a retrospective single center cohort study. We screened 147 consecutive patients who were diagnosed with BrS based on the presence of spontaneous or drug–induced type 1 ECG pattern between January 2009 and May 2023. Once this comprehensive diagnostic pathway was completed, we engaged in detailed counseling with patients to discuss the potential need for ICD implantation or ILR insertion, if deemed indicated. Compared to patients who did not receive a device, those who received an ILR had a higher prevalence of suspected arrhythmic syncope (43% vs. 22%, p=0.012) and tended to be younger (median age 38 years, IQR 30–52, vs. 43 years, IQR 35–55, p=0.044) and with a higher presence of SCN5A gene mutations (17% vs. 6%). On the other hand, compared to patients who received an ICD, those with an ICM underwent programmed ventricular stimulation less frequently (40% vs. 85%, p=0.010) and, as a result, had a lower frequency of positive result of this test (0% vs. 91%, p&amp;lt; 0.001). During a median follow–up period of 14.7 months (IQR, 4.7–44.8), no deaths occurred among the patients with ILR. Eight individuals (19%) were diagnosed with arrhythmic findings through continuous ILR monitoring. Among these findings, three patients experienced AF (including one case of new–onset AF), two patients exhibited symptomatic asystolic pauses lasting 16 seconds and 3.6 seconds respectively, two patients had non–sustained ventricular tachycardia, and one patient had episodes of paroxysmal supraventricular tachycardia. Except for a history of AF, no significant differences were observed between patients with arrhythmic findings and those without any events. In the ICD group, the median follow–up period was 32.2 months (IQR, 23.2–95.0). During this period, no deaths occurred and no appropriate or inappropriate ICD therapies were delivered.

New York Heart Association functional class and implantable cardioverter-defibrillator in non-ischaemic heart failure with reduced ejection fraction: Extended follow-up of the DANISH trial.

Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy in patients with heart failure, a left ventricular ejection fraction of ≤35%, and New York Heart Association (NYHA) class II-III. However, the evidence regarding the benefit of primary prevention ICD is less consistent in patients with NYHA class III. We investigated the long-term effects of primary prevention ICD implantation according to NYHA class in an extended follow-up study of the DANISH trial. The DANISH trial randomized 1116 patients with non-ischaemic heart failure with reduced ejection fraction (HFrEF) to ICD implantation or usual care. Outcomes were analysed according to NYHA class at baseline (NYHA class II and III/IV). The primary outcome was all-cause mortality. Of the 1116 patients randomized in the DANISH trial, 597 (53.5%) were in NYHA class II at baseline, 505 (45.3%) in NYHA class III, and 14 (1.3%) in NYHA class IV. During a median follow-up of 9.5 years, NYHA class III/IV, compared with NYHA class II, were associated with a greater long-term rate of all-cause mortality (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.20-1.93) and cardiovascular death (HR 1.95 [1.47-2.60]). ICD implantation, compared with usual care, did not reduce the long-term rate of all-cause mortality (all participants: HR 0.89 [95% CI 0.74-1.08]; NYHA class II: HR 0.85 [0.64-1.13]; NYHA class III/IV: HR 0.89 [0.69-1.14]; pinteraction = 0.78) or cardiovascular death (all participants: HR 0.87 [95% CI 0.70-1.09]; NYHA class II: HR 0.78 [0.54-1.12]; NYHA class III/IV: HR 0.89 [0.67-1.19]; pinteraction = 0.58), irrespective of NYHA class. Similarly, NYHA class did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (all participants: HR 0.60 [95% CI 0.40-0.92]; NYHA class II: HR 0.73 [0.40-1.36]; NYHA class III/IV: HR 0.52 [0.29-0.94]; pinteraction = 0.39). In patients with non-ischaemic HFrEF, ICD implantation, compared with usual care, did not reduce the overall mortality rate, but it did reduce sudden cardiovascular death, regardless of baseline NYHA class. ClinicalTrials.gov NCT00542945.

Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy

BackgroundDesmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce. ObjectivesThis study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort. MethodsWe collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed in vitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM. ResultsOf 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n = 7) or heart failure death (HFd)/heart transplantation (HTx) (n = 4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n = 5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n = 10). Male sex (P = 0.004), nonsustained ventricular tachycardia (P = 0.017) and LV ejection fraction ≤50% (P = 0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. In vitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants. ConclusionsDES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals.

Competing risks of monomorphic vs. non-monomorphic ventricular arrhythmias in primary prevention implantable cardioverter-defibrillator recipients: Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) study.

Ablation of monomorphic ventricular tachycardia (MMVT) has been shown to reduce shock frequency and improve survival. We aimed to compare cause-specific risk factors for MMVT and polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF) and to develop predictive models. The multicentre retrospective cohort study included 2668 patients (age 63.1 ± 13.0 years; 23% female; 78% white; 43% non-ischaemic cardiomyopathy; left ventricular ejection fraction 28.2 ± 11.1%). Cox models were adjusted for demographic characteristics, heart failure severity and treatment, device programming, and electrocardiogram metrics. Global electrical heterogeneity was measured by spatial QRS-T angle (QRSTa), spatial ventricular gradient elevation (SVGel), azimuth, magnitude (SVGmag), and sum absolute QRST integral (SAIQRST). We compared the out-of-sample performance of the lasso and elastic net for Cox proportional hazards and the Fine-Gray competing risk model. During a median follow-up of 4 years, 359 patients experienced their first sustained MMVT with appropriate implantable cardioverter-defibrillator (ICD) therapy, and 129 patients had their first PVT/VF with appropriate ICD shock. The risk of MMVT was associated with wider QRSTa [hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.01-1.34], larger SVGel (HR 1.17; 95% CI 1.05-1.30), and smaller SVGmag (HR 0.74; 95% CI 0.63-0.86) and SAIQRST (HR 0.84; 95% CI 0.71-0.99). The best-performing 3-year competing risk Fine-Gray model for MMVT [time-dependent area under the receiver operating characteristic curve (ROC(t)AUC) 0.728; 95% CI 0.668-0.788] identified high-risk (> 50%) patients with 75% sensitivity and 65% specificity, and PVT/VF prediction model had ROC(t)AUC 0.915 (95% CI 0.868-0.962), both satisfactory calibration. We developed and validated models to predict the competing risks of MMVT or PVT/VF that could inform procedural planning and future randomized controlled trials of prophylactic ventricular tachycardia ablation. URL:www.clinicaltrials.gov Unique identifier:NCT03210883.

Sex differences among subcutaneous implantable cardioverter-defibrillator recipients: a propensity-matched, multicentre, international analysis from the i-SUSI project.

Women have been historically underrepresented in implantable cardioverter-defibrillator (ICD) trials. No data on sex differences regarding subcutaneous ICDs (S-ICD) carriers have been described. Aim of our study was to investigate sex-related differences among unselected S-ICD recipients. Consecutive patients enrolled in the multicentre, international i-SUSI registry were analysed. Comparisons between sexes were performed using a 1:1 propensity matching adjusted analysis for age, body mass index (BMI), left ventricular function, and substrate. The primary outcome was the rate of appropriate shocks during follow-up. Inappropriate shocks and other device-related complications were deemed secondary outcomes. A total of 1698 patients were extracted from the i-SUSI registry; 399 (23.5%) were females. After propensity matching, two cohorts of 374 patients presenting similar baseline characteristics were analysed. Despite similar periprocedural characteristics and a matched BMI, women resulted at lower risk of conversion failure as per PRAETORIAN score (73.4% vs. 81.3%, P = 0.049). Over a median follow-up time of 26.5 [12.7-42.5] months, appropriate shocks were more common in the male cohort (rate/year 3.4% vs. 1.7%; log-rank P = 0.049), while no significant differences in device-related complications (rate/year: 6.3% vs. 5.8%; log-rank P = 0.595) and inappropriate shocks (rate/year: 4.3% vs. 3.1%; log-rank P = 0.375) were observed. After controlling for confounders, sex remained significantly associated with the primary outcome (aHR 1.648; CI 0.999-2.655, P = 0.048), while not resulting predictor of inappropriate shocks and device-related complications. In a propensity-matched cohort of S-ICD recipients, women are less likely to experience appropriate ICD therapy, while not showing higher risk of device-related complications. ClinicalTrials.gov Identifier: NCT0473876.

The axillary vein puncture for implantable cardiac defibrillator implantation: 14 years of experience. Analysis of the results

BackgroundAxillary vein puncture (AVP) is a valid alternative to Subclavan vein puncture for leads insertion in cardiac implantable electronic device implantation, that may reduce acute and delayed complications. Very few data are available about ICD recipients.A simplified AVP technique is described. MethodsAll the patients who consecutively underwent “de novo” ICD implantation, from March 2006 to December 2020 at the University of Verona, were considered.Leads insertion was routinely performed through an AVP, according to a simplified technique. Outcome and complications have been retrospectively analyzed. ResultsThe study population consisted of 1711 consecutive patients. Out of 1711 patients, 38 (2.2%) were excluded because they were implanted with Medtronic Sprint Fidelis lead.Out of 1673 ICD implantations, 963 (57.6%) were ICD plus cardiac resynchronization therapy, 434 (25.9%) were dual-chamber defibrillators, and 276 (16.5%) were single-chamber defibrillators, for a total of 3879 implanted leads. The AVP success rate was 99.4%. Acute complications occurred in 7/1673 (0.42%) patients. Lead failure (LF) occurred in 20/1673 (1.19%) patients. Comparing the group of patients with lead failure with the group without LF, the presence of three leads inside the vein was significantly associated with LF, and the multivariate analysis confirmed three leads in place as an independent predictor of LF. ConclusionAVP, according to our simplified technique, is safe, effective, has a high success rate, and a very low complication rate. The incidence of LF was exceptionally low.The advantages of AVP are maintained over time in a population of ICD recipients.

Efficacy and safety of implantable cardioverter-defibrillator implantation in the elderly—The I-70 Study: A randomized clinical trial

There is conflicting evidence on the efficacy of primary prevention implantable cardioverter-defibrillator (ICD) implantation in the elderly. The purpose of this study was to determine the efficacy and safety of ICD implantation in patients 70 years and older. Patients (n = 167) aged 70 years or older and eligible for ICD implantation were randomly assigned (1:1) to receive either optimal medical therapy (OMT) (n = 85) or OMT plus ICD (n = 82). Of the 167 participants (mean age 76.4 years; 165 men), 144 completed the study protocol according to their assigned treatment. Average participant follow-up was 31.5 months. Mortality was similar between the 2 groups: 27 deaths in OMT vs 26 death in ICD (unadjusted hazard ratio 0.92; 95% confidence interval 0.53-1.57), but there was a trend favoring the ICD over the first 36 months of follow-up. Rates of sudden death (7 vs 5; P = .81) and all-cause hospitalization (2.65 events per participant in OMT vs 3.09 in ICD; P = .31) were not statistically significantly different. Eleven participants randomized to ICD received appropriate therapy. Five participants received an inappropriate therapy that included at least 1 ICD shock. The study did not recruit to target sample size, and accumulated data did not show benefit of ICD therapy in patients 70 years or older. Future studies similar in design might be feasible but will need to contend with patient treatment preference given the large number of patients who do not want an ICD implanted. Further research is needed to determine whether the ICD is effective in prolonging life among elderly device candidates.

Impact of preventive substrate catheter ablation on implantable cardioverter-defibrillator interventions in patients with ischaemic cardiomyopathy and infarct-related coronary chronic total occlusion.

Primary prevention patients with ischaemic cardiomyopathy and chronic total occlusion of an infarct-related coronary artery (CTO) are at a particularly high risk of implantable cardioverter-defibrillator (ICD) therapy occurrence. The trial was designed to evaluate the efficacy of preventive CTO-related substrate ablation strategy in ischaemic cardiomyopathy patients undergoing primary prevention ICD implantation. The PREVENTIVE VT study was a prospective, multicentre, randomized trial including ischaemic patients with ejection fraction ≤40%, no documented ventricular arrhythmias (VAs), and evidence of scar related to the coronary CTO. Patients were randomly assigned 1:1 to a preventive substrate ablation before ICD implantation or standard therapy with ICD implantation only. The primary outcome was a composite of appropriate ICD therapy or unplanned hospitalization for VAs. Secondary outcomes included the primary outcome's components, the incidence of appropriate ICD therapies, cardiac hospitalization, electrical storm, and cardiovascular (CV) mortality. Sixty patients were included in the study. During the mean follow-up of 44.7 ± 20.7 months, the primary outcome occurred in 5 (16.7%) patients undergoing preventive substrate ablation and in 13 (43.3%) patients receiving only ICD [hazard ratio (HR): 0.33; 95% confidence interval (CI): 0.12-0.94; P = 0.037]. Patients in the preventive ablation group also had fewer appropriate ICD therapies (P = 0.039) and the electrical storms (Log-rank: P = 0.01). While preventive ablation also reduced cardiac hospitalizations (P = 0.006), it had no significant impact on CV mortality (P = 0.151). Preventive ablation of the coronary CTO-related substrate in patients undergoing primary ICD implantation is associated with the reduced risk of appropriate ICD therapy or unplanned hospitalization due to VAs.