ICD Interventions Research Articles

Impact of Imaging and Pharmacological Treatment Strategies in Refractory Ventricular Tachycardia in Critically Ill Patients: A Systematic Review.

Ventricular tachycardia (VT) is a life-threatening arrhythmia often leading to sudden cardiac death, particularly in critically ill patients. Refractory VT, characterized by recurrent episodes requiring intervention, poses unique challenges for management, necessitating advanced diagnostic and therapeutic strategies. This systematic review evaluates the impact of imaging and pharmacological treatments in managing refractory VT in critically ill patients. A systematic literature search was conducted using keywords such as "refractory ventricular tachycardia", "critical illness", "imaging techniques", "pharmacological treatments", "antiarrhythmic drugs", "ICD interventions", and "non-invasive therapy". Databases searched included PubMed, Google Scholar, and Cochrane Library, identifying 1590 publications. After screening, 11 studies meeting the inclusion criteria were included in this review. Oral procainamide significantly reduced VT episodes but caused severe side effects in certain patients. Noninvasive interventions such as transcutaneous magnetic stimulation (TcMS) and noninvasive electrophysiology-guided radioablation reduced VT burden and antiarrhythmic drug (AAD) use, with TcMS decreasing VT episodes in the sham group (P < 0.001). Stereotactic body radiation therapy (SBRT) and stereotactic arrhythmia radiotherapy (STAR) reduced VT episodes. Ultrasound-guided stellate ganglion blockade decreased VT episodes (P < 0.001) within 24 hours. Catheter ablation improved composite outcomes, including ICD shocks and heart failure hospitalizations, compared to AAD therapy. Quality of life significantly improved with noninvasive therapies, though SBRT presented rare complications like pneumonitis. Imaging and pharmacological interventions effectively reduce VT burden and ICD interventions while showing varying safety profiles. However, the limited sample sizes, short follow-up durations, and heterogeneity across studies highlight the need for further high-quality research to establish long-term efficacy and safety.

ATrial arrhythmias in inhEriTed aRrhythmIa Syndromes: results from the TETRIS study.

Little is known about the distribution and clinical course of patients with inherited arrhythmia syndrome (IAS) and concomitant atrial arrhythmias (AAs). The aim of the study is (i) to characterize the distribution of AAs in patients with IAS and (ii) evaluate the long-term clinical course of these patients. An international multicentre study was performed and involved 28 centres in 16 countries. Inclusion criteria were (i) IAS and (ii) electrocardiographic documentation of AAs. The primary endpoint was a composite of sudden cardiac death, sustained ventricular arrhythmias (VAs), or appropriate implantable cardioverter defibrillator (ICD) interventions. Strokes, inappropriate ICD shocks due to AAs, and the occurrence of sinus node dysfunction were assessed. A total of 522 patients with IAS and AAs were included. Most patients were diagnosed with Brugada syndrome (n = 355, 68%) and long QT syndrome (n = 93, 18%). The remaining patients (n = 71, 14%) presented with short QT syndrome, early repolarization syndrome, catecholaminergic polymorphic ventricular tachycardia, progressive cardiac conduction diseases, or idiopathic ventricular fibrillation. Atrial fibrillation was the most prevalent AA (82%), followed by atrial flutter (9%) and atrial tachycardia (9%). Atrial arrhythmia was the first clinical manifestation of IAS in 52% of patients. More than one type of AA was documented in 23% of patients. Nine patients (3%) experienced VA before the diagnosis of IAS due the use of anti-arrhythmic medications taken for the AA. The incidence of the primary endpoint was 1.4% per year, with a two-fold increase in patients who experienced their first AA before the age of 20 (odds ratio 2.2, P = 0.043). This was consistent across the different forms of IAS. Inappropriate ICD shock due to AAs was reported in 2.8% of patients, strokes in 4.4%, and sinus node dysfunction in 9.6%. Among patients with IAS and AAs, AA is the first clinical manifestation in about half of the cases, with more than one form of AAs present in one-fourth of the patients. The occurrence of AA earlier in life may be associated with a higher risk of VAs. The occurrence of stroke and sinus node dysfunction is not infrequently in this cohort.

Prospective assessment of risk factors for appropriate ICD intervention in patients with ischemic cardiomyopathy: results of PARCADIA trial

Abstract Background There is still a big unmet need for better risk stratification tools to identify patients at high risk for sudden cardiac death in the era of primary prevention ICD therapy. Scar burden on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging may be a risk marker for the prediction of ventricular arrhythmia in post-myocardial infarction (MI) patients. Purpose The aim of the PARCADIA trial was to assess whether scar characteristics, determined via LGE-CMR, or other baseline risk markers are associated with appropriate ICD therapy. Methods In this prospective, multi-center, clinical trial, we enrolled post-MI patients with an indication for de novo primary prevention ICD. Main exclusion criteria were indication for cardiac resynchronization therapy and NYHA class IV. Prior to the ICD implantation, LGE-CMR was performed to analyze the amount of scar tissue (LGE core mass + grey zone mass) and LV function / volumes. A 24h Holter recording was performed to collect information on potential triggers like premature ventricular beats (PVB) and sympathetic-vagal balance based on heart rate variability (HRV). Follow-ups were performed in-office every 6 months, including remote monitoring. Appropriate ICD therapy was used as primary endpoint and adjudicated by a clinical event committee. Results 199 patients were enrolled at 5 investigational sites in Europe. Patients mean age was 64.3 years, with a mean LVEF of 27.7 %, timing from the index MI was 9.1 years, and 42.7% received a primary PCI on index MI. After a median follow-up duration of 47.7 months, 23.1% of patients received appropriate ICD therapy. In 135 patients (67.8%), quality of LGE-CMR was sufficient for detailed analysis. The mean LGE core mass (20.5 vs. 19,7 g) and grey zone mass (10.5 vs. 11.4 g) was not different in patients with or without appropriate ICD therapy, also not when corrected for LV mass. However, LVEF (28.5 vs. 32.9 %) was lower, while diastolic myocardial mass (141 vs. 125 g), and end-diastolic volume (265.0 vs. 226.7 ml) were significantly higher in patients with appropriate ICD therapy. On 24h Holter the mean PVB burden (3695 vs. 1643 beats), and non-sustained ventricular tachycardia (12 vs. 0.9), were higher in patients with appropriate ICD therapy, while the HRV (96.1 vs. 113.1 SDNN) was lower. In univariate analysis the variables LVEF, timing to index MI, primary PCI on index MI, PVB burden and HRV appeared to be predictors for appropriate ICD intervention, while in multivariate analysis LVEF and PVB burden remained predictive. Conclusion In post-MI patients with appropriate ICD therapy, scar burden was not different from patients without appropriate ICD therapy. Only LVEF and PVB burden were independent predictors of increased arrhythmogenicity. Improved CMR analysis on scar characteristics (conduction channels) to identify potential arrhythmogenic regions might be the topic for future research.

Prognostic role of the progression of late gadolinium enhancement in hypertrophic cardiomyopathy

Abstract Background Late Gadolinium Enhancement (LGE) extent ≥15% of left ventricular (LV) mass is a widely accepted prognostic risk factor in hypertrophic cardiomyopathy (HCM). However, LGE extent increases over time and the clinical role of the progression of LGE (LGE-rate) was not prospectively evaluated in previous studies. Purpose We evaluated the clinical and prognostic role of LGE-rate in HCM. Methods 105 patients with HCM underwent cardiac-MR at baseline (CMR-I) and after ≥2 years of follow-up (CMR-II). LGE extent was measured in both the examinations (LGE was defined using threshold validated method of ≥6 SD exceeding the mean of normal myocardium (1)). LGE-rate was defined as the ratio between the increase of LGE extent (g) and the time interval (months) between CMR-I and CMR-II. A combined endpoint of sudden cardiac death (SCD), resuscitated cardiac arrest, appropriate ICD intervention and sustained ventricular tachycardia was used (hard events). Results The percentage of patients with LGE extent ≥15% increased from 9% to 20% at CMR-II (p=0.03), compared to CMR-I. During a median follow-up of 52 months, 25 hard events were recorded. The presence of LGE≥15% at CMR-II allowed a significant reclassification of the risk of patients than at LGE≥15% at CMR-I (NRI 0.21, p=0.046). At maximally selected rank statistical analysis the optimal prognostic cut-point for LGE-rate was &amp;gt;0.07 g/months. At Kaplan-Meier curve analysis patients with LGE-rate&amp;gt;0.07 had significant worse prognosis than those without (p&amp;lt;0.0001) (figure 1). LGE-rate&amp;gt;0.07 allowed a significant reclassification of the risk compared to LGE≥15% at CMR-I and at CMR-II (NRI 0.49, p=0.003) (figure 2). At Cox regression multivariable analysis, LGE-rate&amp;gt;0.07 was the best independent predictor of hard events. Conclusions LGE-rate is heterogenous among patients with HCM and a follow-up CMR should be performed after 2 years to reclassify the risk of SCD of those patients. High LGE-rate should be considered as a novel prognostic risk factor in HCM.Figure 1Figure 2

Ventricular arrhythmia burden in ICD patients during the second wave of the COVID-19 pandemic

AimCOVID-19 has been associated with cardiovascular complications including ventricular arrhythmias (VA) and an increased number of out-of-hospital cardiac arrests. Nevertheless, several authors described a decrease of VA burden in patients with an implantable defibrillator (ICD) during the first wave of the COVID-19 pandemic. The objective of this study was to determine if these observations could be transferred to later periods of the pandemic as well.MethodsWe retrospectively analyzed a total of 1674 patients with an ICD presenting in our outpatient clinic during the second wave of the COVID-19 pandemic and during a control period for the occurrence of VA requiring ICD interventions.ResultsSeven hundred ninety-five patients with an ICD had a device interrogation in our ambulatory clinic during the second wave of the COVID-19 pandemic compared to eight hundred seventy-nine patients in the control period. There was significant higher amount of adequate ICD therapies in the course of the COVID-19 period. Thirty-six patients (4.5%) received in total eighty-five appropriate ICD interventions during COVID-19, whereas only sixteen patients (1.8%) had sustained VA in the control period (p = 0.01).ConclusionIn contrast to the first wave of COVID-19, which was characterized by a decrease or least stable number of ICD therapies in several centers, we found a significant increase of VA in ICD patients during the second wave of COVID-19. Possible explanations for this observation include higher infectious rates, potential cardiac side effects of the vaccination as well as personal behavioral changes, or reduced utilization of medical services.

ICD outcome in pediatric arrhythmogenic cardiomyopathy

BackgroundArrhythmogenic cardiomyopathy (ACM) is a very rare condition among pediatric patients. Sudden cardiac death (SCD) is the main complication and often requires ICD implantation.Aim of the study is the evaluation of the outcomes of ICD implanted ACM pediatric patients in terms of safety, efficacy and complications. MethodsAll pediatric patients (<18 y.o.) diagnosed with ACM and who were implanted with ICD since 2009 in Our Institution were collected. Implantation was decided according to current recommendations/ guidelines, and outcome was recorded during follow-up. ResultsNineteen consecutive ACM patients were implanted with ICD. Subcutaneous ICDs (S-ICD) were implanted in 15 patients (79%) while transvenous ICDs (TV-ICD) in 4 patients (21%). Mean age at implantation was 14.3 ± 2.1 y.o. ICDs were implanted for secondary prevention in 4 (21%) patients, and for primary prevention in 15 (79%). During the follow-up (5.59 ± 3.4 years), appropriate ICD interventions were delivered in 4 (21%) patients for sustained VTs, [2 implanted in primary prevention (13%) and 2 in secondary prevention (50%)]. No defibrillation failures occurred. Inappropriate shocks occurred in 2 cases (10.5%). Device-related complications requiring device revision occurred in 3 (16%): lead dislodgement, surgical skin erosion and sensing defect. ConclusionsIn a pediatric ACM cohort, appropriate ICD therapies occurred in a minority of primary prevention patients and frequently in secondary prevention patients. The rate of inappropriate shocks and device-related complications were even more rare and mostly wound related. Therefore, ICD therapy in pediatric ACM is effective and safe.

Cardiac magnetic resonance for prophylactic implantable-cardioverter defibrillator therapy international study in ischemic cardiomyopathy: international DERIVATE-ICM Registry

Abstract Funding Acknowledgements Type of funding sources: None. Background Implantable cardioverter–defibrillator (ICD) therapy is the most effective sudden cardiac death (SCD) event prophylactic-strategy in ischemic cardiomyopathy (ICM) patients with transthoracic echocardiographic (TTE) left ventricular ejection fraction (LVEF) ≤35%. This approach has been recently questioned due to the low rate of ICD interventions in patients who received implantation and the not negligible percentage of patients who experienced SCD event despite not fulfilling criteria for implantation. Purpose The DERIVATE-ICM registry (RCT#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 standard of care based on TTE in ICM patients. Methods We enrolled 861 ICM patients (mean age 65±11 years, 86% male) with chronic heart failure and TTE-LVEF&amp;lt;50%. Major adverse arrhythmic cardiac events (MAACE), defined as the combination of SCD, aborted SCD event, and sustained ventricular tachycardia were the primary endpoint. Independent predictors were used to calculate a CMR risk score for each patient. Risk levels were defined as low (quantile 1 [Q1]), medium (Q2 and Q3) and high (Q4). Results During a median follow-up of 1054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007, 95%CI:1.000–1.011, p = 0.050), 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. Based on the multivariable analysis, CMR weighted risk score was developed according to the following equation [0.005 * EDV/BSA (mL/m²) – 0.029 * LVEF (%) + 0.010 * LGE ischemic mass (g)]. Figure 1 (top) shows the Kaplan-Meier curves according to the guidelines-based TTE-LVEF model and the CMR risk score. Moreover, the table of reclassification of the CMR versus TTE predictive model is reported in Figure 1 (bottom). This multiparametric CMR weighted predictive derived score effectively identifies subjects at high risk for MAACE as compared to TTE-LVEF cut-off of 35% with a NRI of 31.7% (p = 0.007). The distribution of CMR predictive score in patients with TTE-LVEF≤35% (panel A) and with TTE LVEF&amp;gt;35% (panel C) is represented in Figure 2, together with the event rate redistribution according to the CMR risk score (panel B and panel D). Conclusions The DERIVATE-ICM study is the first large multicenter registry testing the additional value of CMR to stratify the risk for MAACE in a large cohort of ICM patients as compared to standard of care. This model identifies a large number of patients with TTE-LVEF&amp;lt;35% at low risk of SCD event and on the other side it identifies a subset of patients who are at high risk of MAACE despite TTE-LVEF≥35%. Further randomized trials to test a CMR guided strategy for ICD implantation versus standard of care are now needed.

Left-ventricular non-compaction and ventricular arrhythmias

Abstract Funding Acknowledgements Type of funding sources: None. Background Left ventricular non-compaction (LVNC) is a rare, although underdiagnosed, cardiomyopathy deriving from the incomplete development of myocardial tissue. Its presentations range from heart failure to embolism and arrhythmic events with the latter being the most frequent cause of death. Purpose To define the incidence of arrhythmic complications in LVNC and describe the interplay between systolic dysfunction and ventricular events. Methods This is a retrospective evaluation of a prospectively-collected database including all consecutive patients with a definitive diagnosis of LVNC followed-up at the Cardiomyopathy Clinic of our institution from October 2009 to August 2022. We conducted a follow-up analyzing the possible correlation between baseline characteristics and a composite outcome of ventricular arrhythmias (sustained VT or VF), appropriate ICD interventions and sudden cardiac death (SCD). We also extracted a sample from our population with preserved LVEF and compared global longitudinal strain (GLS) in compacted and non-compacted segments. Results 44 patients (29 males, 65.9%) were enrolled in the study; 36 patients (81.8%) underwent a cardiac MRI and 34 (77.3%) resulted positive for Petersen criteria. 26 patients (59.1%) had positive echocardiographic criteria, while 18 patients (40.9%) were positive for both MRI and echocardiographic criteria. Five patients (11%) experienced an arrhythmic event during a median follow-up of 2 years (1 VT, 1 VF and 3 patients with appropriate ICD interventions). No clinical, ECG or lab predictors were found for arrhythmic events apart from a history of non-sustained or sustained ventricular arrhythmias, which was associated with a 36% increased risk of subsequent VT/VF episodes (RR 1.36; 95% CI 1.01-1.85; p=0.01). Notably, LVEF (which was ≤35% in 11% of the patients) was not able to significantly discriminate arrhythmic risk (50.7±13.0% vs. 50.2±7.8%; p=ns). Out of 9 patients with normal LVEF and normal GLS, the segmental LS resulted better in non-compacted cardiac segments vs. compacted ones (-20.0±4.6% vs. -17.5±4.9%; p=0.03). This was mainly due to an increase deformation of endocardial layers of non-compacted segments (-26.4±6.6% vs. -19.7±6.6%; p≤0.001), while epicardial layers were similar in compacted versus non-compacted segments. Conclusions LVNC represents a poorly understood condition where a mixture of genetic and molecular mechanisms create a fertile substrate for the origin of ventricular arrhythmias. Our population reflects this pattern by showing a high percentage (5.5%/year) of patients experiencing the composite outcome. GLS was higher in non-compacted segments due to an apparent hyperdeformation of endocardial layers. In our opinion, this evidence represents a valid resource and a useful weapon to distinguish LVNC from other differential diagnoses such as, for example, dilated cardiomyopathy.

Age and genetics are associated with ventricular fibrillation but not with monomorphic ventricular tachycardia in Brugada syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background/introduction Brugada syndrome (BrS) is associated with ventricular arrhythmias (VA) in macroscopically normal hearts. VA in BrS can be classified as ventricular fibrillation (VF) and monomorphic ventricular tachycardia (MVT). Although BrS has been initially described in association with VF, MVT is not rare, as it occurs in ≈30% of BrS patients. Purpose The aim of this study is to correlate VF or MVT with the genetic background and other clinical variables. Methods All BrS patients, were prospectively enrolled in a monocentric registry between 1992 and 2022. Inclusion criteria for the study were: 1) BrS diagnosis; 2) Genetic analysis performed for SCN5A; 3) Classification of variants following ACMG guidelines. Patients with a pathogenic/likely pathogenic (P/LP) variant in SCN5A were defined as (P+). Patients without a P/LP variant were defined as (P-). Primary endpoint was VA occurrence, defined as: documented arrhythmic SCD, documented arrhythmic aborted SCD, VF, sustained MVT or appropriate ICD intervention. All VA events were adjudicated as VF or MVT. Results A total of 500 BrS patients were analyzed. A P/LP variant in SCN5A was found in 104 patients (20.8%). After a mean follow-up of 110.9 months, 48 patients (9.6%) experienced a VA, adjudicated as MVT in 18 patients (37.5%) and VF in 30 patients (62.5%). At survival analysis, P- patients had higher VF free survival, compared with P+ patients (96.5% vs 84.6%, Log-Rank p&amp;lt;0.001) with no difference in MVT free survival (Log-Rank p=0.61), Figure 1. BrS patients &amp;gt; 30 years at diagnosis had higher VF free survival, compared with patients ≤ 30 years at diagnosis (95.5% vs 90.3%, Log-Rank p=0.041), with no difference in MVT free survival (Log-Rank p=0.9), Figure 2. Patients &amp;gt; 50 years at index event had higher VF free survival, compared with patients ≤ 50 years at index event (Log-Rank p=0.002), with no significant difference in MVT free survival (Log-Rank p=0.81). At Cox multivariate analysis independent predictors of VF occurrence were as follows: Age at index event ≤ 50 years (HR=2.57, CI 95% 1.01-6.6, p=0.04), P/LP variant in SCN5A (HR= 2.35, CI 95% 1.12-4.92, p=0.02), SND (HR= 2.67, CI 95% 1.01-7.04, p=0.044), history of syncope (HR= 2.14, CI 95% 1.02-4.51, p=0.047) and history of aborted SCD (HR= 18.66, CI 95% 8.87-39.27, p&amp;lt;0.001). Independent predictors of MVT occurrence were the following: history of syncope (HR= 2.71, CI 95% 1.26-5.80, p=0.01), history of aborted SCD (HR= 4.82, CI 95% 2.14-10.85, p&amp;lt;0.001), VA inducibility at EPS (HR= 3.71, CI 95% 1.66-8.31, p=0.001). Conclusion In a large BrS cohort undergoing genetic analysis MVT occurred in 37.5% of patients and VF in 62.5% of patients. P/LP SCN5A carriers and younger BrS population had a higher incidence of VF with no difference in MVT incidence.

Stereotactic Arrhythmia Radioablation (STAR) for refractory ventricular tachycardia (VT) - A preliminary report from the German multicenter RAVENTA study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): The multicenter RAdiosurgery for VENtricular TAchycardia (RAVENTA) study (NCT03867747) is part of the STOPSTORM.eu consortium project Background Stereotactic Arrhythmia Radioablation (STAR) has been shown to be a promising treatment option for refractory ventricular tachycardia (VT) in initial reports of monocentric clinical studies and case series. Methodology The multicenter RAdiosurgery for VENtricular TAchycardia (RAVENTA) study is part of the STOPSTORM.eu consortium project and investigates STAR with 25 Gy in one session for patients with refractory VT without further treatment options. The primary endpoint is to evaluate the feasibility and safety of the procedure with an incidence of ≤ 5% of severe (grade ≥ 3) treatment-related side effects within 30 days after therapy. We now present an analysis after enrolment of 10 of the 20 planned patients. Results Ten patients were included in the RAVENTA study at four treatment centers between 10/2019 and 10/2022. STAR was performed without complications in all patients. To date, there were no acute (≤ 30 days) or late (&amp;gt; 30 days up to one year) grade ≥ 3 side effects which were possibly treatment-associated. Significant reduction in VT burden and ICD interventions was observed in most patients. In 7/10 (70%) of the patients, sustained freedom from VT was achieved up until last follow-up. Conclusion RAVENTA is the world's first multicenter study for STAR of refractory VT. We did not observe any treatment-related severe side effects in the current analysis. Most patients benefited from significant reductions in VT burden.

Genetic testing in children with Brugada syndrome: results from a large prospective registry

Abstract Funding Acknowledgements Type of funding sources: None. Background/introduction A pathogenic/likely pathogenic (P/LP) variant can be found in 20-25% of patients with Brugada syndrome (BrS) and a P/LP variant in SCN5A is associated with a worse prognosis. However, the diagnostic yield and the prognosis of gene testing in pediatric BrS syndrome is unclear. Purpose The aim of this study is to define the diagnostic yield of SCN5A gene testing with ACMG standardized variant classification in a large cohort of pediatric BrS. Furthermore, a correlation between the clinical outcomes and the genetic background of children with BrS in comparison with adult BrS is aimed. Methods All consecutive patients diagnosed with BrS, between 1992 and 2022 were enrolled in a prospective monocentric registry. Inclusion criteria were: 1) BrS diagnosis; 2) Genetic analysis for SCN5A gene and 3) classification of gene variants following current ACMG guidelines. Pediatric patients were defined if ≤ 12 years of age. The primary endpoint was ventricular arrhythmias (VA) occurrence, defined as documented SCD, aborted SCD, ventricular tachycardia or ventricular fibrillation or appropriate ICD intervention. Results A total of 500 BrS patients were included, 41 pediatric patients and 459 adult patients. Among children with BrS, 19 patients (46.3%) had a P/LP variant (P+) in SCN5A gene. No P/LP variants could be identified in 22 (53.7%) pediatric patients (P-). After a mean follow-up of 140.2 months, 3 children (7.3%) experienced a VA, treated with appropriate ICD shock. Inappropriate shocks occurred in 3 pediatric patients (7.3%). At survival analysis, P- pediatric patients had higher VA free survival during the follow-up, compared with P+ pediatric patients (Log-Rank p=0.021), Figure 1. There was no difference in VA free survival between pediatric and adult BrS patients both without (P-), (Log-Rank p=0.19) and with (P+) a P/LP variant (Log-Rank p=0.91), Figure 2. Conclusion In a large BrS cohort, the diagnostic yield for SCN5A P/LP variants in the pediatric population is 46.3%. P+ children with BrS have a worse arrhythmic prognosis.

Prognosis of patients undergoing catheter ablation of arrhythmic storm in patients with and without history of previous ICD interventions

Abstract Funding Acknowledgements Type of funding sources: None. Background Catheter ablation (CA) improves prognosis in patients with electrical storm (ES). However, its effectiveness and timing in patients with ventricular tachycardia and appropriate ICD therapies remain a matter of debate. Purpose Our aim was to investigate whether patients with history of discrete ventricular tachycardia episodes had different clinical features and outcome compared to patients with ES as first arrhythmic occurrence. Methods We enrolled 57 consecutive patients undergoing CA for ES and collected clinical, echocardiographic and electroanatomic mapping data. The primary end point was a composite of death from any cause and recurrences of sustained VT or ventricular fibrillation, appropriate ICD therapy, or ES. Results During a median follow up of 39 months, 28 patients (49%) met the primary end point of arrhythmic recurrence or death from any cause. There were no significant differences between clinical, electrocardiographic and echocardiographic parameters in the two groups. Regarding ICD therapies, patients with who met the primary end point had a higher number of ATP/shock episodes preceding the ES event: 15 (52%) vs 25 (89%), p=0.002. At Cox regression analysis, NIDCM, previous ATP and/or shock and ≥3 ATP were associated with arrhythmic recurrences and/or death. At multivariate analysis, ≥3 ATP was the only predictor that met statistical significance for the primary end point: HR was 30.41, CI 4.42 – 209.12, p=0.001. When dividing our population in patients and without ventricular arrhythmias (VAs) with appropriate device intervention before ES, thoses with VAs arrhythmias before ES had a higher percentage of presence of late potentials (80% vs 55%, p=0.041) and a greater unipolar scar (59.2±41.6 vs 30.2±21.6, p=0.001). At univariate analysis the presence of late potentials was associated with ventricular arrhythmias before ES (OR 3.33, CI 1.03-10.84, p=0.045). Conclusions CA in patients with a long arrhythmia history, recurrent ICD therapies and presence of late potentials at electroanatomic mapping, may yield worse outcomes and therefore our results support an early referral for CA of VT to improve prognosis in these subjects.

Cardiac Magnetic Resonance for Prophylactic Implantable-Cardioverter Defibrillator Therapy in Ischemic Cardiomyopathy: The DERIVATE–ICM International Registry

BackgroundImplantable 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. ObjectivesThe DERIVATE (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy)-ICM registry (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. MethodsA 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. ResultsDuring 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). ConclusionsThe 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.

Long-Term Outcome of ICD Therapy in Patients With Noncompaction Cardiomyopathy Compared With DCM and HCM

BackgroundImplantable cardioverter-defibrillators (ICDs) are frequently used for primary and secondary prevention in patients with cardiomyopathies due to different etiologies. However, long-term outcome studies in patients with noncompaction cardiomyopathy (NCCM) are scarce. ObjectivesThis study summarizes the long-term outcome of ICD therapy in patients with NCCM compared with those with dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM). MethodsProspective data from our single-center ICD registry were used to analyze the ICD interventions and survival in patients with NCCM (n = 68) compared with patients with DCM (n = 458) and patients with HCM (n = 158) from January 2005 to January 2018. ResultsThis NCCM population with an ICD for primary prevention comprised 56 (82%) patients with a median age of 43 years and 52% males, compared with 85% in patients with DCM and 79% in patients with HCM (P = 0.20). During a median follow-up of 5 years (IQR: 2.0-6.9 years), appropriate and inappropriate ICD interventions were not significantly different. Nonsustained ventricular tachycardia during Holter monitoring in patients with NCCM was the only significant risk factor for appropriate ICD therapy in patients with NCCM, with a HR of 5.29 (95% CI: 1.12-24.96). The long-term survival was significantly better in the univariable analysis in the NCCM group. However, there was no difference in multivariable Cox regression analyses between the cardiomyopathy groups. ConclusionsAt 5 years of follow-up, the rate of appropriate and inappropriate ICD interventions in NCCM was comparable to that in DCM or HCM. In multivariable analysis, no differences in survival were found between the cardiomyopathy groups.

Do apical aneurysms predict sudden cardiac death in hypertrophic cardiomyopathy?

The current AHA/ACC HCM guideline recommendation for a primary prevention ICD is based on retrospective series that have important limitations. These include selection bias, the fact that ‘SCD events’ are appropriate ICD interventions for monomorphic VT in the vast majority of cases, and a high prevalence of major confounders in patients with apical aneurysm and SCD events. HCM, hypertrophic cardiomyopathy; SCD, sudden cardiac death; LV, left ventricular; LVEF, left ventricular ejection fraction; VF, ventricular fibrillation; VT, ventricular tachycardia (Lorenzini et al. 2020). Lorenzini M et al. Mortality Among Referral Patients With Hypertrophic Cardiomyopathy vs. the General European Population. JAMA Cardiology 2020; 5:73–80.

770 LONG-TERM PROGNOSIS IN LVNC CARDIOMYOPATHY: A SINGLE-CENTRE EXPERIENCE

Abstract Background left ventricular non-compaction (LVNC) cardiomyopathy is an often underdiagnosed and under-classified disease deriving from the incomplete development of ventricular myocardium. Clinical presentations may be variable and uncommon, ranging from an apparent lack of functional anomalies to heart failure, ventricular arrhythmias and, in some cases, even ischemic stroke. Despite great improvements in diagnostic performance there is still a widespread lack of evidence regarding the prognosis and management of affected patients. Methods all consecutive patients admitted to our Cardiology Institution from October 2009 to August 2022 fulfilling LVNC criteria by echocardiography or cardiovascular magnetic resonance (CMR) or both, were consecutively enrolled. CMR has been performed wherever possible. All patients underwent a complete cardiological visit, a 12-lead ECG and echocardiography at baseline, whereas at follow-up, if a complete visit was not possible, information regarding patients’ endpoints was acquired through telephonic contact. Additional diagnostic exams or implantation of a cardiac device were also performed if indicated. The primary endpoint was a composite of at least one between: sustained ventricular arrhythmias, an appropriate ICD intervention and sudden cardiac death. Secondary endpoints included supraventricular arrhythmias, unplanned cardiac hospitalizations, acute decompensated, chronic heart failure and ischemic stroke. Risk predictor analyses were not performed as the overall event rates were low and the risk for type II error was high. Results forty patients (26 males; age 45±17) were prospectively enrolled and followed up for a median of five years. CMR and echocardiography were overall agreeing on the majority of the diagnoses, with 62.5% of patients meeting the echo criteria and 70% of patients meeting the CMR criteria for LVNC. The incidence of the primary endpoint was 1.8% per years. Male gender and late gadolinium enhancement (LGE) were correlated with an increased incidence of the primary endpoint, while LVEF, NC/C or functional status were not associated with a significantly increased risk of the composite endpoint. HF diagnosis was the most common endpoint (6.1% annual incidence). The annual incidence of supraventricular arrhythmias was 3.0% and the annual incidence of stroke was 0.7%. Twenty-four patients (60%) experienced at least one hospitalization during follow-up. Unplanned hospitalizations represented 20% of all hospitalizations and were mainly HF-related. Planned hospitalizations were performed for elective procedures such as atrial fibrillation cardioversion, ablation, coronary angiography or diagnostic check-ups. Discussion in patients with LVNC, there is an increased incidence of cardiac-related outcomes than in the general population; furthermore, male gender and myocardial fibrosis are associated with increased risk of events. This trend highlights the importance of a prompt diagnosis and, obviously, of a correct knowledge of such disease.

178 ARRHYTHMIC STORM IN ATTR WILD TYPE AMYLOIDOSIS: AN UNUSUAL COMBINATION

Abstract Cardiac amyloidosis (CA) is characterized by extracellular protein fibril deposition in the myocardium leading to restrictive heart failure. Both atrial and ventricular arrhythmias are common in CA. Study have shown up to one half of patients with CA die suddenly. However, the most common cause of sudden death has been historically through to be secondary electromechanical dissociation rather than a lethal ventricular arrhythmia. We present the case of a 84 years old man, with a history of hypertension, dyslipidaemia, and prior smoking. In June 2020 the patient was admitted to the emergency room of our hospital due to an episode of hemodynamically unstable sustained ventricular tachycardia (SVT). The patient underwent electrical cardioversion with restoration of sinus rhythm. An echocardiogram that showed a slightly reduced ejection fraction (FE = 45%), severe concentric hypertrophy, grade 3 diastolic dysfunction with high pressures in the left ventricular (LV) cavity, and a reduced GLS (-13.8%) with a typical apical-sparing aspect. A cardiac magnetic resonance (Fig.1). was performed showing a diffuse area of LGE with a subepicardial pattern involving left ventricular and atrial segments, compatible with myocardial storage disease. In order to complete the diagnostic workout, we performed a bone scintigraphy (Fig.2). (Positive for CA, with Perugini score grade 2), a genetic test (negative for hATTR-CA mutations) and free light chain in serum (negative for AL-CA). The patient was discharged at home after ICD implantation in secondary prevention and prescribed appropriate heart failure therapy. In May 2022 the patient was readmitted in emergency room for dyspnea during an arrhythmic storm characterized by several SVTs and ICD interventions, and atrial fibrillation (FA). After stabilization of clinical parameters, the patient was hospitalized in our ward. We optimized medical therapy with metaprololo 100 mg 1 cp BID, cordarone 600 mg ev and mexiletina 200 mg cp BID. During the hospitalization we succeeded in reducing SVT burden. However, ventricular PVCs and slow SVT remained. For this reason, we decided to perform an electrophysiological study (EPS) followed by catheter ablation. The EPS found two low voltage areas (Fig.3). The first were found under the aortic valve; the second was an area of dense scar and fragmented potentials along the basal-posterior wall. After ablation of the first area we succeeded in removing clinical PVCs. During the ablation of the second area the procedure was complicated by ventricular fibrillation that required advanced life support and many electrical shocks. The patient was discharged at home in absence of further episodes of SVTs with optimized therapy At a three moths follow up no arrhythmic events were recorded.

860 TRICUSPID REGURGITATION RELATED TO CARDIAC IMPLANTABLE DEVICES: A NEW ENTITY?

Abstract Background. The incidence of cardiac implantable electronic device (CIED) implantation is currently growing. Patients who develop a moderate to severe CIED-induced tricuspid regurgitation (TR) are at higher risk of pulmonary hypertension, right heart failure (HR) and have higher mortality. Transthoracic echocardiography (TTE) is the most common method for TR grading, while transesophageal echocardiography (TOE) with three-dimensional (3D) imaging is nowadays gaining importance to reconstruct valve morphology and to determine the TR pathophysiology. Case Summary. We present the case of an 83-year-old man with multiple comorbidities, affected by non-ischemic dilated cardiomyopathy, for which a biventricular defibrillator (ICD-CRT) was implanted in 2007 in primary prevention. Over the years, the patient has been a CRT-responder, with partial recovery of the ejection fraction (40% in 2022 versus 25%). In 2018 he had an episode of acute pulmonary oedema and ventricular fibrillation with ICD intervention; during that hospitalization, the right ventricular catheter (EC) was replaced due to dysfunction. In 2022, the patient presented to our hospital for anasarca due to right HF. TTE and TOE showed new onset of right heart dilation and dysfunction with severe TR, which was predominantly caused from lead impingement of the septal tricuspid valve (TV) leaflet and later from secondary dilation of the TV annulus. The patient responded well to medical therapy and was discharged. Discussion. CIED-related TR is getting more relevant since its growing prevalence and its prognostic impact, even if little is known about why some patients develop moderate-to-severe CIED-related TR. Clinicians should be aware of this entity and follow the patients with TR over the time with periodic echocardiograms. TOE and 3D imaging should always be performed to understand the mechanism of the TR and to select the optimal treatment. Currently, no guidelines nor randomized data are available in order to guide treatment in these patients. Figure 1:4-chamber views with and without color Doppler showing the ventricular EC passing the TV through with the presence of peri-catheter TR.Figure 2:trans-gastric TOE xPlane views showing how the ventricular EC determines a restrictive movement of the septal TV leaflet, causing the severe TR to form.

310 CLINICAL COURSE AND CHARACTERISTICS OF ADVANCED HEART FAILURE ASSOCIATED WITH ARRHYTHMOGENIC CARDIOMYOPATHY

Abstract Background The prevalence and course of heart failure (HF) in arrhythmogenic cardiomyopathy (ACM) is unresolved, and previous studies have mostly focused on the right-dominant variant of the disease, less prone to HF. Conversely, ACM variants with left ventricular (LV) involvement are now increasingly recognized, often initially ‘mis-diagnosed’ as dilated cardiomyopathy. Aim of this study was therefore to describe the prevalence and clinical course of advance HF in the full clinical spectrum of ACM. Methods We retrospectively reviewed records of all ACM patients diagnosed before 2021 from 3 Italian Cardiomyopathy Referral Centres (Azienda Ospedaliero Universitaria Careggi; Policlinico Sant’Orsola; Azienda Ospedaliero Universitaria Sant’Andrea). LV involvement was diagnosed in the presence of subepicardial late gadolinium enhancement (LGE) in at least 3 contiguous segments in the same short-axis slice at cardiac magnetic resonance, independent of whether it fulfilled the 2010 Task Force criteria for right-dominant ACM (biventricular ACM) or not (left-dominant ACM); in this latter case, diagnosis was reached after careful exclusion of other differential diagnosis, and only when at least one of the following features was present: likely pathogenic/pathogenic genetic variant associated with ACM; familial history of ACM; electrocardiographic abnormalities suggestive of ACM with LV involvement. Advanced HF was defined as NYHA functional class III/IV and/or referral for heart transplantation. Median follow-up was 6 years. Results Forty-four out of 174 ACM patients (25%) developed advanced HF: 10 right-dominant ACM and 34 with LV involvement. Twenty ACM patients were initially diagnosed with dilated cardiomyopathy; as such, development of advanced HF in 17 cases preceded the diagnosis of ACM. Five patients were diagnosed with ACM after heart transplantation, by histological examination. In the other 22, median time from ACM diagnosis to advanced HF development was 4 years. As compared to those without, advanced HF patients were more likely to present LV involvement. During clinical course, 20 (46%) advanced HF patients received at least one appropriate ICD intervention, with 13 experiencing an electrical storm. Twenty-six (59%) patients required HF-related hospitalization, and 32 (72%) were referred for heart transplantation with 25 ultimately receiving it. ACM patients with advanced HF, compared to those without, experienced a higher rate of mortality (36% vs. 6%; OR 3.5 [95%CI: 1.4-8.7], p=0.01) and ventricular arrhythmic events (41% vs. 11%; OR 2.4 [95%CI: 1.1-5.0], p=0.02). Conclusions Advanced HF progression in ACM is not rare, and occurs more frequently in variants with LV involvement. Advanced HF is associated with increased mortality and arrhythmic risk.

Abstract 13383: Is Genotype Negative Hypertrophic Cardiomyopathy Really Benign? The Increased Risk of Sudden Death and Advanced Heart Failure in the Absence of Pathogenic Sarcomere Mutations

Introduction: The genetic basis of hypertrophic cardiomyopathy (HCM) is complex, and the genotype-phenotype correlations have not been completely resolved. Patients lacking a pathogenic variant are presumed to have a better prognosis than patients with sarcomeric pathogenic mutations. Aim: We sought to assess the relationship between the genotype status and the adverse clinical events. Methods: Consecutive patients with HCM underwent genetic testing focused on HCM-related genes. Patients with pathogenic or likely pathogenic variants were considered genotype positive (G+), and those without definite disease-causing mutation were considered genotype negative (G-). Patients were followed for 5.2 ±4.9 years for outcomes. Sudden death (SD) events included out-of-hospital cardiac arrests, appropriate ICD interventions, and HCM-related death. Results: Of 988 HCM patients, 212 (21%) were G+, while 776 (79%) were G -. As compared to G-, G+ HCM patients were younger (45 ± 14 vs. 53 ± 13 years), had more extensive LV hypertrophy (maximum wall thickness: 19.6 ± 5 mm vs. 18.4 ± 4 mm, p&lt;0.001), and with no difference in the presence of LVOT obstruction (59% vs. 66%, p=0.06). Despite G- status, 3% of G- patients had extensive scarring on cardiac MRI (≥15% of LV mass; no different from G+, p=0.54). Over follow-up, 66 patients had SD events. While SD events were more common in G+ patients (11.3% vs. 5.4%, p=0.002), the majority of SD events occurred in G- patients (64%). Similarly, end-stage HCM developed 54 patients, more commonly in G+ (9.0% vs. 4.5%, p=0.01), but with majority of events in G- patients (65%). Conclusion: Contrary to certain prevailing views, in this large consecutive genotyped HCM cohort, sarcomere genotype-negative patients (representing a distinctive majority) did not express an entirely benign prognosis. In fact, nearly two-thirds of SD events and end-stage HF progression occurred in G- HCM patients, albeit at somewhat lower rates than in G+ patients. These data do not support that genotype should not be included as a risk marker of adverse arrhythmic and advanced heart failure events.