Sustained Ventricular Arrhythmias Research Articles

A novel tool for arrhythmic risk stratification in desmoplakin gene variant carriers.

Pathogenic desmoplakin (DSP) gene variants are associated with the development of a distinct form of arrhythmogenic cardiomyopathy known as DSP cardiomyopathy. Patients harbouring these variants are at high risk for sustained ventricular arrhythmia (VA), but existing tools for individualized arrhythmic risk assessment have proven unreliable in this population. Patients from the multi-national DSP-ERADOS (Desmoplakin SPecific Effort for a RAre Disease Outcome Study) Network patient registry who had pathogenic or likely pathogenic DSP variants and no sustained VA prior to enrolment were followed longitudinally for the development of first sustained VA event. Clinically guided, step-wise Cox regression analysis was used to develop a novel clinical tool predicting the development of incident VA. Model performance was assessed by c-statistic in both the model development cohort (n = 385) and in an external validation cohort (n = 86). In total, 471 DSP patients [mean age 37.8 years, 65.6% women, 38.6% probands, 26% with left ventricular ejection fraction (LVEF) < 50%] were followed for a median of 4.0 (interquartile range: 1.6-7.3) years; 71 experienced first sustained VA events {2.6% [95% confidence interval (CI): 2.0, 3.5] events/year}. Within the development cohort, five readily available clinical parameters were identified as independent predictors of VA and included in a novel DSP risk score: female sex [hazard ratio (HR) 1.9 (95% CI: 1.1-3.4)], history of non-sustained ventricular tachycardia [HR 1.7 (95% CI: 1.1-2.8)], natural logarithm of 24-h premature ventricular contraction burden [HR 1.3 (95% CI: 1.1-1.4)], LVEF < 50% [HR 1.5 (95% CI: .95-2.5)], and presence of moderate to severe right ventricular systolic dysfunction [HR 6.0 (95% CI: 2.9-12.5)]. The model demonstrated good risk discrimination within both the development [c-statistic .782 (95% CI: .77-.80)] and external validation [c-statistic .791 (95% CI: .75-.83)] cohorts. The negative predictive value for DSP patients in the external validation cohort deemed to be at low risk for VA (<5% at 5 years; n = 26) was 100%. The DSP risk score is a novel model that leverages readily available clinical parameters to provide individualized VA risk assessment for DSP patients. This tool may help guide decision-making for primary prevention implantable cardioverter-defibrillator placement in this high-risk population and supports a gene-first risk stratification approach.

Arrhythmic Risk Stratification in Cardiac Amyloidosis: A Review of the Current Literature

Cardiac amyloidosis is the most frequent infiltrative disease caused by the deposition of misfolded proteins in the cardiac tissue, leading to heart failure, brady- and tachyarrhythmia and death. Conduction disorders, atrial fibrillation (AF) and ventricular arrhythmia (VA) significantly impact patient outcomes and demand recognition. However, several issues remain unresolved regarding early diagnosis and optimal management. Extreme bradycardia is the most common cause of arrhythmic death, while fast and sustained VAs can be found even in the early phases of the disease. Risk stratification and the prevention of sudden cardiac death are therefore to be considered in these patients, although the time for defibrillator implantation is still a subject of debate. Moreover, atrial impairment due to amyloid fibrils is associated with an increased risk of AF resistant to antiarrhythmic therapy, as well as recurrent thromboembolic events despite adequate anticoagulation. In the last few years, the aging of the population and progressive improvements in imaging methods have led to increases in the diagnosis of cardiac amyloidosis. Novel therapies have been developed to improve patients’ functional status, quality of life and mortality, without data regarding their effect on arrhythmia prevention. In this review, we consider the latest evidence regarding the arrhythmic risk stratification of cardiac amyloidosis, as well as the available therapeutic strategies.

Mitral Annulus Disjunction: A Comprehensive Cardiovascular Magnetic Resonance Phenotype and Clinical Outcomes Study.

Clinical importance of mitral annulus disjunction (MAD) is not well established. Characterize a population of MAD all-comers diagnosed by cardiac magnetic resonance imaging (MRI). Retrospective. MAD confirmed in 222 patients, age of 49.2 ± 19.3 years, 126 (56.8%) males. 1.5 T and 3 T/steady-state free precession and inversion recovery. Clinical history, outcomes, imaging, and arrhythmia data. MAD defined as a separation ≥2 mm between left ventricular myocardium and mitral annulus. Presence and pattern of late gadolinium enhancement (LGE) were analyzed. LGE in the papillary muscles and adjacent to MAD were identified as MAD related. Ventricular arrhythmias (VA) were grouped into non-sustained ventricular arrhythmias (NSVA) or sustained. Cardiovascular death assessed. Differences between baseline characteristics were compared. Univariate regression was used to investigate possible associations between ventricular arrhythmia and cardiovascular death with characteristics associated with the severity of MAD. A multivariable logistic regression included significant variables from the univariate analysis and was performed for MAD-related and global LGE. MAD extent 5.0 ± 2.6 mm. MV annulus expanded during systole for MAD ≥6 mm. Systolic expansion associated with prolapse, billowing, and curling. LGE present in 82 patients (36.9%). Twenty-three patients (10.4%) showed MAD-related LGE by three different observers. No association of LGE with MAD extent (P = 0.545) noted. Follow-up 4.1 ± 2.4 years. No sustained VA observed. In univariable analysis, NSVA was more prevalent in patients with MAD ≥6 mm (33.3% vs. 9.9%), but this was attenuated on multivariate analysis (P = 0.054). The presence of NSVA was associated with global LGE but not MAD-related LGE in isolation (P = 0.750). Three patients died of cardiovascular causes (1.4%) and none had MAD-related LGE. None died of sudden cardiac arrest. In patients referred for cardiac MRI, mitral valve dysfunction was associated with MAD severity. Scar was not related to the extent of MAD, but associated with NSVA. The risk of sustained arrhythmias and cardiovascular death was low in this population. 4 TECHNICAL EFFICACY: Stage 2.

Diagnostic and Prognostic Value of Right Ventricular Fat Quantification from Computed Tomography in Arrhythmogenic Right Ventricular Cardiomyopathy.

Background: In arrhythmogenic right ventricular cardiomyopathy (ARVC) non-invasive scar evaluation is not included among the diagnostic criteria or the predictors of ventricular arrhythmias (VA) and sudden death (SD). Computed tomography (CT) has excellent spatial resolution and allows a clear distinction between myocardium and fat; thus, it has great potential for the evaluation of myocardial scar in ARVC. Objective: The objective of this study is to evaluate the feasibility, and the diagnostic and prognostic value of semi-automated quantification of right ventricular (RV) fat replacement from CT images. Methods: An observational case-control study was carried out including 23 patients with a definite (19) or borderline (4) ARVC diagnosis and 23 age- and sex-matched controls without structural heart disease. All patients underwent contrast-enhanced cardiac CT. RV images were semi-automatically reconstructed with the ADAS-3D software (ADAS3D Medical, Barcelona, Spain). A fibrofatty scar was defined as values of Hounsfield Units (HU) <-10. Within the scar, a border zone (between -10 HU and -50 HU) and dense scar (<-50 HU) were distinguished. Results: All ARVC patients had an RV scar and all scar-related measurements were significantly higher in ARVC cases than in controls (p < 0.001). The total scar area and dense scar area showed no overlapping values between cases and controls, achieving perfect diagnostic performance (sensitivity and specificity of 100%). Among ARVC patients, 16 (70%) had experienced sustained VA or aborted SD. Among all clinical, ECG and imaging parameters, the dense scar area was the only one with a statistically significant association with VA and SD (p = 0.003). Conclusions: In ARVC, RV myocardial fat quantification from CT is feasible and may have considerable diagnostic and prognostic value.

Leaky RyR2 channels as pro-arrhythmic trigger in the PKP2-deficient atrial myocardium

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): American Heart Association National Institutes of Health Introduction Atrial arrhythmias, like atrial fibrillation, occur in 20–40% of patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). Atrial fibrillation in ARVC patients is often associated with an increased risk of sustained ventricular arrhythmias and inappropriate ICD shocks. However, the pathophysiology behind the development of atrial arrhythmias in ARVC is far from clear. A genome-wide association study, based on UK-biobank data, revealed a link between atrial fibrillation and variants in the desmosomal gene plakophilin-2 (PKP2). Previous studies show that PKP2 is necessary to maintain the transcription of genes that control intracellular calcium (Ca2+) cycling and that loss of PKP2 expression in adult mouse ventricular tissue leads to disruption of intracellular Ca2+ homeostasis. In this study, we test the hypothesis that loss of PKP2 expression leads to pro-arrhythmic changes in atrial myocytes. Methods Experiments were carried out using a cardiac-specific, tamoxifen (TAM)-activated PKP2 knockout murine model (PKP2-cKO). Cre-negative, flox-positive, TAM-injected littermates were used as controls. We used RNA sequencing, quantitative imaging modalities, as well as biochemical and electrophysiological methods to study the functional and structural properties of atrial PKP2cKO tissue. Studies were carried out 21 days post-tamoxifen injection, a time point at which an arrhythmogenic cardiomyopathy of right ventricular predominance is manifest. Results In contrast to the previously-reported observations in PKP2cKO ventricular myocytes, atrial PKP2cKO myocytes presented no significant differences in Ca2+ transient dynamics, SR load and action potential duration. However, PKP2cKO atrial myocytes showed an increased frequency and amplitude of Ca2+ sparks, in combination with increased diastolic Ca2+ levels as well as an increase in cellular ROS levels. RNAseq data showed an under-representation of mRNA for Integrinα7, a stabilizer of Ryr2 that reduces its phosphorylation. Separate studies showed that PKP2cKO atrial myocytes present impaired relaxation and enhanced sarcomere shortening, a finding consistent with a downregulation in the expression of Myosin Binding Protein C. Isoproterenol (ISO) exposure further increased the frequency of Ca2+ sparks and the levels of diastolic Ca2+, and these effects were reversed by acute (30 minute) in vivo treatment with Ryanodex (medical grade Dantrolene), a known RyR blocker. Conclusion Loss of PKP2 expression affects cellular Ca2+ handling and electrophysiology differently in the atrial versus ventricular myocardium. We speculate that an increased probability of opening of Ryr2 channels, caused by ROS-induced RyR2 oxidation and/or Integrinα7-induced RyR2 phosphorylation, serve as pro-arrhythmic trigger in the PKP2-deficient atrial myocardium, that these effects can be amplified by a catecholaminergic input and that RyR blockers can dampen these pro-arrhythmic effects.

Adverse myocardial and vascular side effects of immune checkpoint inhibitors: a prospective multimodal cardiovascular assessment.

Immune checkpoint inhibitors (ICIs) can induce cardiovascular toxicities. To prospectively assess the incidence of major cardiovascular events (MACE) on ICIs in solid cancer patients: myocarditis, pericarditis, acute coronary syndrome, heart failure, high-degree conduction abnormalities or sustained ventricular arrhythmias, or cardiovascular death at 6weeks (early MACE), including asymptomatic clinical changes by an independent adjudication committee using current recommended diagnostic criteria. The secondary objective was the incidence of the above-mentioned events adding atrial fibrillation (AF) at 6months (late MACE). Participants underwent pre-ICIs and repeated multimodality cardiac imaging (echocardiogram, cardiac magnetic resonance (CMR)), serum biomarkers (ultrasensitive troponin I), and rhythm surveillance (ambulatory ECG monitoring) at 6weeks and 6months. Forty-nine patients (38 (77.6%) male; mean age 64.3 (SD 11.0) years old) were included (June 2020-December 2021). Early MACE were observed in 9 (18.4%) patients at mean 40.1 (SD 5.9) days, with heart failure (HF) in 5 (10.2%), ventricular arrhythmias, or new conduction disorders in 4 (8.2%) patients. History of AF (HR 4.49 (CI 1.11-18.14), P = 0.035) predicted early MACE. At 6months follow-up, 18 MACE were observed in 15/49 (31%) patients, with 6 (12.2%) HF events, 5 (10.2%) significant ventricular arrhythmias, or conduction disorders, and 4 (8.2%) AF. There was a significant decline in LVEF (P < 0.001) in patients with no MACE (P = 0.003) or HF (P = 0.0028). Higher creatinine at inclusion (HR 0.99 [0.98-1.00], P = 0.006) predicted HF on multivariate analysis. There were no significant T1 or T2 mapping changes in our study cohort on repeated CMR. Cardiotoxicity on ICIs is more frequent than previously described when using a thorough detection strategy, consisting mainly in HF and asymptomatic rhythm disorders.

Use of class IC antiarrhythmic drugs in patients with structural heart disease and implantable cardioverter defibrillator

Abstract Background Due to suspected pro-arrhythmic effects and increased mortality associated with class-IC antiarrhythmic drugs (AADs) in previous trials, AAD-therapy in structural heart disease (SHD) is mainly restricted to amiodarone. In the presence of diagnostic and therapeutic advancements in cardiovascular medicine, it remains unclear if previous studies adequately reflect contemporary patients. In clinical practice, class-IC-AADs are occasionally used in individual cases, particularly in patients with an implantable cardioverter defibrillator (ICD). Methods This study retrospectively investigated outcome in ICD-carriers with SHD in whom class-IC-AADs were used as an individualized therapy due to failure, side effects, or unacceptable risk of alternative therapeutic options. Results Fifty patients from four tertiary centers were included (median age 48.5 years; 52% female). The most common underlying SHD were dilated (42%) or ischemic cardiomyopathy (26%) (median LVEF=45%). Indications for AAD were sustained ventricular arrhythmias (VA) (58%), symptomatic premature ventricular contractions (26%), or atrial arrhythmias (16%). Median follow-up was 27.8 months. Freedom from sustained VA was 72%, freedom from ICD-therapy was 80%. In 19 patients (38%) AAD-therapy was terminated. The most common reason was insufficient efficacy (n=8). Pro-arrhythmia was suspected in three patients. Five patients died during follow-up (10.0%), two of cardiovascular cause (4.0%). Conclusion In a multicenter cohort of ICD-carriers with SHD, class-IC-AADs were associated with a low rate of pro-arrhythmic effects or cardiovascular mortality. The majority of patients remained free from sustained VA during a follow-up of &amp;gt;2 years. Further efforts should be made to evaluate the safety of class-IC-AADs in SHD-patients receiving contemporary cardiovascular therapy.

Long-term risk assessment in athletes with ventricular arrhythmias: the key roles of arrhythmia morphology, complexity, and substrate

Abstract Background Ventricular arrhythmias (VAs) are an important source of concern among athletes. Purpose To determine the prognostic role of non-invasive and invasive diagnostic assessments among athletes with complex VAs. Methods We included 215 athletes (83% male; 28 [19-43] years) with complex VAs in a prospective, multi-center cohort study. At baseline, each athlete underwent a prespecified comprehensive diagnostic workup, which included cardiac magnetic resonance (CMR) in 202 subjects, and electrophysiology study (EPS)/electroanatomical mapping (EAM) in 190. The primary study endpoint was the occurrence of sudden death or sustained VAs during long-term follow-up. Results During a median follow-up of 6.2 (4.4-8.1) years, 16 (7%) athletes had a primary outcome event, including one sudden cardiac death. In univariable Cox models, sustained VAs at presentation (p&amp;lt;0.001), uncommon VA morphology(p=0.004), syncope(p=0.005), abnormal ECG (p=0.003), VAs induction/persistence at exercise testing(p=0.021), late gadolinium enhancement (LGE;p=0.006), low-voltage areas (p=0.003) and late potentials (p&amp;lt;0.001) at EAM, and sustained VA induction by EPS (p&amp;lt;0.001) were all associated with increased risk of primary outcome events. The association of late potentials and EPS inducibility with primary outcome events was confirmed after controlling for all non-invasive predictors at univariable analysis, and the incorporation of findings of invasive tests allowed improved prediction of primary outcome events over clinical/non-invasive findings in isolation (log-likelihood ratio for nested models, p=0.043). Younger age (p=0.032), being a professional athlete (p=0.006), and absence of LGE (p=0.029) were independently associated with higher odds of uninterrupted competitive sports practice until last follow-up. Conclusions A comprehensive diagnostic assessment integrating clinical/ECG findings with CMR and EPS/EAM in selected cases may provide important prognostic information among athletes with complex VAs.

Utilization of implantable cardiac monitors in detecting type 1 patterns in brugada syndrome

Abstract Introduction In individuals with Brugada syndrome, the presence of the type 1 pattern (BP1) is linked to an elevated risk of severe arrhythmias. However, the identification and measurement of BP1 can be challenging due to its intermittent nature. Implantable cardiac monitors (ICMs) provide extended continuous monitoring, potentially overcoming the limitations of intermittent ambulatory ECG monitoring in detecting spontaneous BP1. Nevertheless, their specific application for this purpose remains unevaluated. Methods From November 2022 to September 2023, all patients presenting with pharmacologically induced BP1 were enrolled at our centre. An ICM was surgically placed in the left second intercostal space at a 45° angle, enabling readings with a morphology similar to the right precordial ECG leads during ajmaline testing (AT). Patients were remotely monitored, and in addition to routine automatic transmissions, each patient was provided with a remote control to transmit in case of fever or symptomatic events. Transmissions were scrutinized to detect: 1) ST-segment elevation; 2) ventricular arrhythmias; 3) burden of ventricular extrasystoles (PVC). A reading was classified as positive for BP1 if it bore a similar morphology to that recorded during AT. The frequency of BP1-positive transmissions was evaluated across four hourly intervals. Results The ICM was successfully implanted in 21 patients (male-to-female ratio 1.62:1, mean age 43.9±13.1 years). Over an average follow-up of 168±70.6 days, a total of 7818 transmissions were received, evenly spread across hourly intervals (minimum of 1296 transmissions per interval). Among these, 173 transmissions were identified as BP1 positive (2.2%), originating from 6 patients (28.6% of the total, all newly diagnosed with spontaneous BP1). The median duration between implantation and the diagnosis of spontaneous BP1 was 16.5 days (range 2-23). The median number of days with at least one positive transmission was 30.2 (range 13.4-73.9). The evening period (6 pm to midnight) displayed a significantly higher rate of positive transmissions compared to the morning (p=0.04) and afternoon (p=0.01); however, not in contrast to the nighttime (p=0.8). No sustained ventricular arrhythmias were observed, and there were no significant differences in PVC burden among patients. Conclusions The utilization of ICM for continuous monitoring in patients with pharmacologically induced BP1 led to the identification of spontaneous BP1 patterns in almost 30% of cases during an approximately 6-month follow-up. Evening and nighttime periods exhibited the highest incidence of BP1. This methodology shows promise in quantifying BP1 incidence and could serve as a tool for stratifying arrhythmic risk in individuals with Brugada syndrome.

Absence of late gadolinium enhancement and outcomes of cardiac resynchronization therapy in non-ischemic dilated cardiomyopathy

Abstract Background Among patients with non-ischemic dilated cardiomyopathy (DCM) with indication for cardiac resynchronization therapy (CRT), there are no clear recommendations about who should receive a CRT-defibrillator (CRT-D) and who should have CRT-pacemaker (CRT-P). Absence of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has a high negative predictive value for ventricular arrhythmias (VA) and sudden death (SD) in DCM and is a predictor of reverse remodelling in several scenarios. Purpose To evaluate the association between absence of LGE and VA/SD or echocardiographic response to CRT in DCM patients treated with CRT. Methods Multicenter retrospective observational cohort study including consecutive DCM patients with de-novo CRT implant and with available CMR. The primary endpoints were: 1) a combined arrhythmic endpoint including appropriate defibrillator therapies, sustained VA and sudden death. 2) echocardiographic response to CRT, intended as an increase ≥10% in left ventricular ejection fraction (LVEF). Results We included 167 patients, 55% males, with median QRS duration of 160ms and median LVEF of 25%. LGE was present in 46% of cases (LGE+). A CRT-D was implanted in 73% of patients. Median follow-up was 63 months. Of note, among patients without LGE (LGE-) we did not record any event of the combined arrhythmic endpoint. The cumulative incidence of the arrhythmic endpoint was significantly higher in LGE+ than in LGE- patients (25% vs 0%, p&amp;lt;0.001) and LGE was an independent predictor of this endpoint (adjusted HR 42, p&amp;lt;0.001). The proportion of responders to CRT was significantly higher in LGE- than in LGE+ cases (81% vs 53%, p&amp;lt;0.001); absence of LGE was the strongest predictor of echocardiographic response to CRT at multivariate analysis (adjusted OR 4.1, p=0.001). Super-responders (i.e. those with LVEF≥50% at follow-up) were also more frequent among LGE- than LGE+ patients (46% vs 21%, p=0.001) and absence of LGE was an independent predictor of LVEF normalization (HR 2.6, p=0.03). Conclusions Among DCM patients who receive CRT, those without LGE have an extremely low (or null in this case) arrhythmic risk and, at the same time, they have a high probability of echocardiographic response to CRT. Thus, LGE- patients could be ideal candidates for CRT-P instead of CRT-D.

Cryoablation of ventricular tachycardia using ultra-low temperature technology: acute success and insights from the post-interventional CMR

Abstract Background Radiofrequency catheter ablation (RFCA) has good acute and long-term success rates in idiopathic and ischemic ventricular arrhythmia (VA). Drawbacks of the RFCA are reversibility of the edema and limited penetration of the RF energy into the tissue which explain a worse effectiveness in midmyocardial substrates. In comparison to RFCA, the lesions produced by ultra-low temperature cryoablation (ULTC) which uses near-critical nitrogen cryogen at -1960C can be both deeper and irreversible, depending on the duration of the freeze. Purpose We aimed to evaluate the acute effectiveness of a new ULTC technology for VA by examining post-interventional cardiac magnetic resonance images (CMR) with late gadolinium enhancement (LGE), as a part of multi-center Cryocure-VT study. Methods Between December 2022 and May 2023, we ablated 6 patients (age 63±16%; 5 male) with sustained VA and structural heart disease. Three patients had previous myocardial infarction; 1 cardiac sarcoidosis, 1 LMNA/C dilated cardiomyopathy and 1 post-myocarditis VA. LGE-CMR was available in all patients before the ULTC. At first, electro-anatomical mapping and VA induction were performed followed by ULTC using transseptal access. Each application consisted of freeze-thaw-freeze cycle with freeze duration at operator’s discretion based on manufacturer-recommended duration-depth curve. At the end, induction protocol was repeated to assess the acute success. Additionally, LGE-CMR was performed after ablation as an attempt to visualize the cryo-lesions. Results Median of 6 applications (IQR 4.75-7.5) of cryo-energy were applied per patient. Median procedure time was 180 min (IQR 97-180), and median fluoroscopy time of 20 min (IQR 15-26). Septal VA exits were detected in 3/6 patients; in 1 the exit was at aorto-mitral continuity; in 2 – basal inferior. After ablation, no VAs were inducible in 5/6 (83%) patients. The only patient with failure to ablate all VAs had fewer applications (n=4) and shorter freeze duration of 30 sec., as compared to the rest. Post-procedural CMR revealed new LGE with up to 75% transmurality in 5/6 patients; microvascular obstruction in 4/6 patients. Only LV edema, but no LGE was observed in the patient with shortest freeze time, who also had intra-hospital recurrence. No complications occurred. Conclusions Cryoablation of VA using a new ultra-low temperature technology is effective and safe to ablate VT even in patients with mid-septal substrates. New LGE in result of ULTCA can be observed in CMR and the lesions depth depends on the duration of application.

The impact of comorbidities and substance use on heart failure events and major ventricular arrhythmias in phospholamban p.(Arg14del) positive individuals

Abstract Background Patients with the phospholamban (PLN) p.(Arg14del) variant can develop a severe cardiomyopathy, characterized by progressive heart failure (HF) and major ventricular arrhythmias (VA). However, there is a marked variability in disease expression among affected individuals. There is still a considerable gap of knowledge regarding the influence of comorbidities and substance use on disease progression. Purpose The aim of this study is to investigate whether specific comorbidities and substance use are associated with HF events or major VA events in PLN p.(Arg14del) positive individuals. Method Logistic regression analysis was conducted was conducted in a retrospective cohort of 880 PLN p.(Arg14del) positive individuals (N=847 without heart failure at baseline, N=810 without major arrhythmia at baseline and N=780 without both). Comorbidities and substance use at baseline were assessed in univariable and multivariable models with respect to HF events, major VA events, and a composite endpoint of these two referred to as ‘severe phenotype’. Heart failure was defined as heart failure hospitalization, left ventricle assist device implantation, heart transplantation or HF-related death. Major VA was defined as sustained VA, appropriate implantable cardioverter defibrillator intervention, or (aborted) sudden cardiac death. Results Of all tested comorbidities, only renal dysfunction defined as an eGFR (CKD-EPI) &amp;lt;60 ml/min per 1.73 m² was significantly and independently associated with all endpoints (p&amp;lt;0.001). In the substance use analysis, prior history of smoking was associated with heart failure and a severe phenotype (p&amp;lt;0.002 and p&amp;lt;0.021), however actively smoking was not associated with both endpoints. Conclusion Renal dysfunction and a history of smoking were the only factors identified to be associated with worse outcomes in PLN p.(Arg14del) positive individuals. Whether renal dysfunction signifies a risk factor or an early manifestation of disease has to be further elucidated.

Initial experience with ablation of ventricular arrhythmias using a pulsed-field system

Abstract Introduction Catheter ablation using radiofrequency (RF) current is a well-established method of treatment of ventricular arrhythmias (VA). However, RF ablation may fail to eliminate deeply located arrhythmogenic substrate. Pulsed-field (PF) is a novel energy source with a potential to create deeper lesions, especially in scar tissue. Purpose This study aims to present the data on safety and efficacy (acute outcome data) of VA ablation using PF. Methods The population consists of 15patients (5 women, age: 61 ± 19years) after previously failed RF ablation of VA. The underlying condition was nonischemic cardiomyopathy (53%), coronary artery disease (13%), and congenital heart disease (13%), respectively. No structural heart disease was present in 20% of cases. The mean left ventricular ejection fraction was 39 ± 13%. Eighty percent of patients had sustained VA, the remaining patients presented with frequent ventricular ectopy. Ablation was performed using a conventional irrigated 4-mm tip catheter in a combination with commercially available PF generator. Peripheral venous blood samples for the assessment of the plasmatic levels of high-sensitivity troponin T (hsTnT) were obtained the next day (usually 18-24hours) after the procedure. Results A mean of 17±12 PF applications (25A) per patient were delivered. In 5 patients (33%), an additional RF ablation (4±9 applications) was performed. Acute success as assessed by non-inducibility of VA or elimination of ectopic focus was achieved in all but one patient (93%). In 4 cases (27%), PF energy was applied within the great cardiac vein and subsequent coronary angiography did not reveal any abnormality. On the other hand, transient conduction system block occurred in 3 cases (20%) during PF application on the lateral LV wall remotely from the LV septum (complete AV block in one, LBBB in two patients). These events resolved in all cases within one hour. Ablation using PF did not result in excessive increase of hsTnT (657±482ng/l, with upper reference level of 14ng/l). Conclusion Initial experience with PF for the treatment of VA indicates high acute efficacy. The long-term effect is to be determined. PF applications in the ventricle may be associated with unexpected but transient conduction system damage, even when applications are performed remotely from the interventricular septum. The postprocedural increase in plasma troponin levels is only moderate.

Safety and efficacy of a temperature-controlled ablation system for ventricular tachycardia: first results from the TRAC-VT study

Abstract Background Catheter ablation using radiofrequency (RF) energy, is a well-recognized treatment option for patients with ventricular arrhythmias. However, procedural complications may be high, and efficacy is often suboptimal with high recurrence rates. Purpose The TRAC-VT study evaluated safety and efficacy of the DiamondTemp Ablation (DTA) System for the treatment of patients with ventricular arrhythmias by catheter ablation. Methods A temperature-controlled, irrigated RF catheter (with six thermocouples and an internal network of diamond coatings) was utilized to treat subjects with either sustained monomorphic ventricular tachycardia (VT) and structural heart disease or with frequent monomorphic symptomatic ventricular premature beats (VPBs) and normal hearts. Patients were enrolled at five hospital centers in five European countries and were followed for 6 months. Ablation was performed in temperature-control mode with an irrigation flow of 8 mL/min for all power deliveries. The target temperature was set to 55 or 60 °C with a power output limited to 50 Watts. RF energy was applied for a maximum of 45 seconds per target site, depending on impedance drop and electrogram abatement. Results The study enrolled 49 subjects (age 67±12 years, 80% male) in total (38 with sustained monomorphic VT and structural heart disease and 11 with symptomatic VPBs). In all cases, mapping and navigation was used with EnSite systems (Abbott). The average ablation time (defined as time from the insertion of the DTA catheter until removal from body) was 87 ± 44 minutes. During this time, RF energy was applied for an average of 28.2 ± 10.2 seconds with a power of 44.0 ± 7.0 W and a temperature of 50.9 ± 3.9 °C during 35.0 ± 23.2 applications. Acute procedural success was 100% (93%-100%), and it was defined as the elimination of VPBs or non-inducibility for sustained VT (using solely the DTA catheter). The primary safety procedure-related endpoint was an evaluation of cardiovascular-related death, stroke / TIA, cardiac tamponade/perforation, bleeding complication, myocardial infarction, thromboembolism, and pulmonary edema. In total review of the primary safety endpoint, one subject had a confirmation of a stroke / TIA event. Regarding longer term procedural efficacy, the 6-month follow-up was completed in 92% of subjects. For the whole study population chronic success from recurrence of ventricular arrhythmia (faster than 100 beats/min after 6 months) was 73.4% (58.6%-83.6%) for non-sustained ventricular arrhythmias (≥3 beats) and 87.7% (74.7%-94.3%) for sustained ventricular arrhythmias (≥30 sec). Conclusions VT/VPBs ablation using a temperature-controlled irrigated RF catheter was safe and effective with low VT recurrence at 6 months of follow-up.

Electrocardiographic characteristics and catheter ablation of premature ventricular complex- mediated ventricular fibrillation

Abstract Background Premature ventricular contractions (PVCs) can trigger ventricular fibrillation (VF) in patients with/or without structural heart disease. There are limited data on coexisting electrocardiographic (ECG) features and catheter ablation outcomes in these patients which could suggest the concomitant presence of an abnormal electrical and structural substrate. Purpose We investigated ECG and electroanatomic characteristics and clinical outcomes in patents who underwent catheter ablation of PVCs triggering VF. Methods We analyzed data from a consecutive series of patients who underwent catheter ablation between 08/2019 and 04/2023 for PVCs triggering VF. On the 12-lead ECG, we assessed the following abnormalities: (a) Early repolarization (ER) pattern in either inferior or lateral leads (Figure 1), or (b) QRS Notching of either the native sinus beat or PVC (Figure 2). Post-ablation follow up outcomes were collected using a combination of ICD interrogation, remote transmission and clinical follow up. Results The cohort included 15 patients: age 52.1±16.8 years, 46.7% females, and 26.7% presenting with VF storm. On average, there were 3.8 HV shocks/per patient from an ICD prior to the index ablation procedure (range: 0-19 shocks). On the 12-lead ECG, the mean coupling interval of the PVC leading to VF was 204±82 ms, and an overall narrow PVC morphology with a mean QRS duration of 107±17 ms. We observed early repolarization (ER) in 6 (40%) of the cohort. In most patients (n=11; 73.3%), at least one of the 2 ECG abnormalities were present. An endocardial-only approach was adequate in all patients, and during catheter ablation, Purkinje potentials were targeted in 10 (66%) of the patients. Based on activation and pace-mapping, the PVCs were localized to the following sites: (a) left ventricular (LV) septum in 11 (73.3%), (b) papillary muscles in 2 (13.3%), and (c) other sites such as the Moderator band and right ventricular outflow tract in the remaining 2 (13.3%) patients. The ablation locations on the LV septum extended from basal to mid-septum. After an average of 1.7 ablation procedures targeting PVC-triggering VF, 12 (80%) patients remained free of sustained ventricular arrhythmias and ICD shocks, over a mean follow up of 479±395 days. Conclusion In most patients with PVCs-triggering VF, there was an evidence of an ECG abnormality either in the form of an ER pattern or notching of either the Sinus QRS or the PVC complex on pre-ablation ECG. During ablation, Purkinje potentials and PVCs were mapped to and ablated in the region of the LV interventricular septum and papillary muscles. Over long-term follow up, catheter ablation seemed durable and effective in reducing VF episodes and ICD shocks.Presence of Early Repolarization patternPresence of a notching pattern in the Si

Renal denervation for the management of refractory ventricular arrhythmias

Abstract Background While catheter ablation (CA) has proven effective in managing ventricular arrhythmias (VA) associated with structural heart disease, a portion of patients continue to experience refractory VA despite medical treatment and multiple CA procedures. In such cases, additional techniques, such as autonomic neuromodulation, have been explored. Renal denervation (RDN), traditionally performed for the treatment of resistant arterial hypertension, inhibits the afferent renal sympathetic pathway, leading to reduced efferent sympathetic overactivation on a systemic level. Due to this mechanism, it has also been studied for the management of arrhythmias, including atrial fibrillation and VA, with favorable results. Objective To assess the effectiveness and safety of RDN for the management of refractory VA storms in high-risk patients. Methods A retrospective analysis of RDN procedures for electrical storms, conducted at a tertiary center between February 2020 and September 2023. We analyzed baseline patient characteristics, procedural details, and acute complications. Recurrence of VA after RDN was assessed at one and six months. Results A total of 7 patients underwent RDN for the treatment of refractory VA. The mean age was 56 ± 10 years (6 male). The primary diagnosis was ischemic cardiomyopathy (n=5), with a mean left ventricular ejection fraction (LVEF) of 20 ± 5%, and no history of resistant arterial hypertension. All patients had an implantable cardioverter-defibrillator (ICD) (two with concomitant resynchronization therapy). Five patients had undergone previous endocardial VA ablation. Of the two patients without prior VA ablation, one had a contraindication because of a large left ventricle thrombus, and the other was submitted to an electrophysiological study, but without inducible ventricular tachycardia. In the four weeks before RDN, patients exhibited a mean of 12 ± 18 sustained VA episodes, meeting the criteria for electrical storm (3 ≥ episodes in 24h). During the procedure, there was a mean of 7 ± 8 radiofrequency applications in the right renal artery and 6 ± 10 in the left renal artery. No acute complications were observed. One month after the procedure, VA episodes were reduced to a mean of 0 ± 1, with only two patients experiencing recurrent VA. After six months, the absence of VA recurrence remained consistent, with only one patient experiencing new episodes. There were no deaths during this period. Conclusion In our pilot study, RDN appeared to be a safe and effective treatment for the management of VA.VA episodes before and after RDN

ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY AND CARDIAC SARCOIDOSIS: THE GREY ZONE

Abstract Cardiac sarcoidosis (CS) is a rare multisystem disorder characterized by granulomatous infiltration of the myocardium, whose clinical manifestations can be extremely heterogeneus. We report the case of a 47–year–old man with a previous diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVD). In history he had a marked arrhythmic pattern with multiple episodes of sustained ventricular arrhythmias, biventricular disfunction (LVEF 37%, RVEF 32%) and extensive biventricular transmural late–gadolinium enhancement (greater than 50%) at cardiac RMN. At EKG epsilon wave mainly seen in precordial leads. In November 2022 he was implanted with bicameral defibrillator and in March 2023 he underwent ablation procedure for ventricular tachycardia with RF with endo–epicardial approach. In May 2023 he arrived at our Centre for acute decompensated heart failure. At restored hemodynamic stability, screening for the possible inclusion in transplant list was started. Right heart catheterization (RHC) showed low cardiac index with no pulmonary hypertension. Chest CT unexpectedly showed the presence of multiple micronodules with perilymphatic distribution with confluent appearance compatible with pulmonary sarcoidosis. In consideration of this result, the transplant program was temporarily postponed and investigations for possible cardiac involvement of an inflammatory nature were started. 18F–FDG PET–CT showed pulmonary, splenic, lymphonodal and especially cardiac uptake in the mid–distal segment of the lateral wall of the left ventricle and in the inferior–apical site suspicious for inflammatory pathology. Unfortunately, both lymphonodal and cardiac biopsies were inconclusive because of insufficient material. Nevertheless, the clinical scenario satisfied the Japanese criteria for possible CS; therefore, treatment with prednisone 1 mg/kg was started and a 18F–FDG PET–CT was planned after 3 months of steroid therapy. CS can disguise as a phenocopy of arrhythmogenic right ventricular cardiomyopathy because of several common characteristics, especially arrhythmic presentation. Due to these similarities, a careful overall evaluation of each patient with ARVD is mandatory as several transplant centers have reported cases of CS in explanted heart with a pretransplant misdiagnosis of ARVD or dilated cardiomiopathy. Performing a chest CT in all ARVD patients as part of transplant screening may be considered.

STEMI antiplatelet pretreatment strategy - national multicenter registry experience

Abstract Funding Acknowledgements None. Background/Introduction Antiplatelet therapy is the cornerstone treatment for ST-segment elevation myocardial infarction (STEMI). Dual antiplatelet therapy (DAPT) including aspirin and a potent P2Y12 inhibitor (P2Y12i) is recommended as the default strategy. However, the timing of DAPT remains controversial: European Cardiology Society (ESC) guidelines ceased recommending pretreatment with P2Y12i in STEMI, based on ATLANTIC trial results. Purpose This study aims to evaluate the effect of DAPT with potent P2Y12i pretreatment DAPT in STEMI patients, comparing with DAPT with clopidogrel and aspirin only pretreatment. Methods We have analyzed the antiplatelet pretreatment strategy results of a retrospective cohort of 2283 STEMI patients, from a multicenter national registry, from 2011 till 2019. We compared 3 groups: DAPT with potent P2Y12i, DAPT with clopidogrel and aspirin only. Primary endpoints were death, major adverse cardiovascular events (MACE), including reinfarction, heart failure, sustained ventricular arrhythmia, cardiogenic shock, mechanical complication and stroke, and successful PCI. Safety endpoint was major hemorrhagic events between different strategies. Results A total of 2283 STEMI patients where included, with a mean age of 66±13 years and 27% (n=627) were female. The population was divided in 3 groups, according with pretreatment strategy: DAPT with potent P2Y12i, DAPT with clopidogrel and aspirin only. 334 patients undergone DAPT with potent P2Y12i, and 86% (n=296) had a successful PCI, 21% (n=69) had a MACE and 9% (n=31) died in hospital. The group of patients submitted to DAPT with clopidogrel were 1815, and 80% (n=1448) had a successful PCI, 29% (n=527) had a MACE and 11,5% (n=209). The group pretreated only with aspirin were 124 patients, of which, only 14% (n=17) had a successful PCI, 38% (n=47) had a MACE and 39% (n=49) died. Regarding safety outcomes, 1,5% (n=5) patients with DAPT with potent P2Y12i had a significant hemorrhage, comparing with 3% (n=53) of patients with DAPT with clopidogrel and 3% (n=4) of aspirin only group of patients. There was a statistically significant higher rate of successful PCI with DAPT with potent P2Y12i (p&amp;lt;0,05 OR 2), a statistically significant lower number of MACE (p&amp;lt;0,05 OR 0,6) and in hospital deaths (p=0,04 OR 0,67), comparing with DAPT with clopidogrel and aspirin only groups. There was no statistically significant difference between groups in terms of hemorrhagic events (p=0,7). According to our retrospective multicenter national registry, pretreatment with potent P2Y12i is associated with better results, namely higher rate of successful PCI, less MACE and in hospital death, contrary to recent trials. Our study has some bias: the pretreatment with DAPT was standard of care during the registry, and the choice for aspirin only strategy might be due to higher risk patients, as the choice was not randomized.Antiplatelet treatment comparison

The Spatial Ventricular Gradient Is Associated With Inducibility of Ventricular Arrhythmias During Electrophysiology Study

BackgroundMyocardial electrical heterogeneity is critical for normal cardiac electromechanical function, but abnormal or excessive electrical heterogeneity is proarrhythmic. The spatial ventricular gradient (SVG), a vectorcardiographic measure of electrical heterogeneity, has been associated with arrhythmic events during long-term follow-up, but its relationship with short-term inducibility of ventricular arrhythmias (VAs) is unclear. ObjectiveThis study was designed to determine associations between SVG and inducible VAs during electrophysiology study. MethodsA retrospective study was conducted of adults without prior sustained VA, cardiac arrest, or implantable cardioverter-defibrillator who underwent ventricular stimulation for evaluation of syncope and nonsustained ventricular tachycardia or for risk stratification before primary prevention implantable cardioverter-defibrillator implantation. The 12-lead electrocardiograms were converted into vectorcardiograms, and SVG magnitude (SVGmag) and direction (azimuth and elevation) were calculated. Odds of inducible VA were regressed by logistic models. ResultsOf 143 patients (median age, 69 years; 80% male; median left ventricular ejection fraction [LVEF], 47%; 52% myocardial infarction), 34 (23.8%) had inducible VAs. Inducible patients had lower median LVEF (38% vs 50%; P < .0001), smaller SVGmag (29.5 vs 39.4 mV·ms; P = .0099), and smaller cosine SVG azimuth (cosSVGaz; 0.64 vs 0.89; P = .0007). When LVEF, SVGmag, and cosSVGaz were dichotomized at their medians, there was a 39-fold increase in adjusted odds (P = .002) between patients with all low LVEF, SVGmag, and cosSVGaz (65% inducible) compared with patients with all high LVEF, SVGmag, and cosSVGaz (4% [n = 1] inducible). After multivariable adjustment, SVGmag, cosSVGaz, and sex but not LVEF or other characteristics remained associated with inducible VAs. ConclusionAssessment of electrical heterogeneity by SVG, which reflects abnormal electrophysiologic substrate, adds to LVEF and identifies patients at high and low risk of inducible VA at electrophysiology study.

Right heart strain in arrhythmogenic right ventricular cardiomyopathy: Implications for cardiovascular outcome.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive myocardial dysfunction and associated with an increased risk of major cardiovascular events. To determine right heart strain (ventricular and atrial global longitudinal strain (RVGLS and RAGLS)) in patients with definite ARVC and its association with adverse events during follow-up. RVGLS and RAGLS were analysed in focused right heart apical views from 70 patients using TomTec ImageArena and association with a composite endpoint (sustained ventricular arrhythmia and cardiovascular death) was determined. Over a median follow-up duration of 4.9 years, 26 (37%) patients met the endpoint. RVGLS was significantly impaired in the event group (-11.5 [-13.3 - -10.2]%) versus the no-event group (-15.8 [-17.1 - -14.5]%, P < 0.001), and so was RAGLS (22.8 [21.4 - 27.4]% vs. 31.5 [25.1 - 39.6]%, respectively, P < 0.001). In Cox regression, RVGLS (HR 1.36, P < 0.001) and RAGLS (HR 0.92, P = 0.002) were associated with higher risk of adverse events. In multivariable Cox regression models, RVGLS and RAGLS remained independent of and were incremental to age, gender, and conventional RV parameters, and model fit was improved when RVGLS and RAGLS were applied together rather than alone. RVGLS and RAGLS are more impaired in patients with adverse events and associated with adverse events independent of age, gender, and conventional RV parameters. When RVGLS and RAGLS are applied together, prediction models are improved suggesting that right heart strain may form part of the echocardiographic routine protocol in patients with ARVC.