Substrate For Ventricular Arrhythmias Research Articles

Arrhythmic Risk Stratification by Cardiovascular Magnetic ResonanceImaging in Patients With Nonischemic Cardiomyopathy.

Myocardial fibrosis (MF) forms part of the arrhythmic substrate for ventricular arrhythmias (VAs). This study sought to determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmias in patients with nonischemic cardiomyopathy (NICM). Patients with NICM in a derivation cohort (n=866) and a validation cohort (n=848) underwent quantification of TF and GZF. The primary composite endpoint was sudden cardiac death or VAs (ventricular fibrillation or ventricular tachycardia). The primary endpoint was met by 52 of 866 (6.0%) patients in the derivation cohort (median follow-up: 7.5 years; Q1-Q3: 5.2-9.3 years). In competing-risks analyses, MF on visual assessment (MFVA) predicted the primary endpoint (HR: 5.83; 95%CI: 3.15-10.8). Quantified MF measures permitted categorization into 3 risk groups: a TF of >0g and≤10g was associated with an intermediate risk (HR: 4.03; 95%CI: 1.99-8.16), and a TF of >10g was associated with the highest risk (HR: 9.17; 95%CI: 4.64-18.1) compared to patients with no MFVA (lowest risk). Similar trends were observed in the validation cohort. Categorization into these 3 risk groups was achievable using TF or GZF in combination or in isolation. In contrast, LVEF of<35% was a poor predictor of the primary endpoint (validation cohort HR: 1.99; 95%CI: 0.99-4.01). MFVA is a strong predictor of sudden cardiac death and VAs in NICM. TF and GZF mass added incremental value to MFVA. In contrast, LVEF was a poor discriminator of arrhythmic risk.

Arrhythmic risk stratification in non-ischemic cardiomyopathy using cardiovascular magnetic resonance

Abstract Background Myocardial fibrosis (MF) is an essential component of the arrhythmic substrate for ventricular arrhythmias (VAs). Aims To determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than LVEF in predicting ventricular arrhythmias in patients with non-ischemic cardiomyopathy (NICM). Methods and results Patients with NICM in a derivation cohort (n=866) and a validation cohort (n=848) underwent quantification of TF and GZF. The primary composite endpoint was sudden cardiac death (SCD) or VAs (ventricular fibrillation or sustained ventricular tachycardia). The primary endpoint was met by 52/866 (6.0%) patients in the derivation cohort (follow-up of 7.5 years [interquartile range, IQR] 5.2-9.3). In competing risk analyses, MF on visual assessment (MFVA) predicted the primary endpoint (hazard ratio [HR] 5.83, 95% confidence intervals [CI] 3.15-10.8). Quantified MF measures permitted categorization into 3 risk groups: a TF &amp;gt;0 ≤ 10 g was associated with an intermediate risk (HR: 4.03 [95% CI 1.99-8.16]) and a TF &amp;gt; 10g with the highest risk (HR: 9.17 [95% CI 4.64-18.1]) compared to no MFVA (lowest risk) (Figure). Similar trends were observed in the validation cohort. Categorization into 3 risk groups was achievable using TF or GZF in combination or in isolation. In contrast, LVEF&amp;lt;35% was a poor predictor of the primary endpoint (validation cohort HR:1.99, 95% CI 0.99-0.41). Conclusions MFVA is a strong predictor of SCD and VAs in NICM. TF and GZF mass added incremental value to MFVA. In contrast, LVEF was not useful in arrhythmic risk stratification.

Right Ventricular Function in Arrhythmogenic Right Ventricular Cardiomyopathy: Potential Value of Strain Echocardiography

Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiomyopathy, characterized by abnormal cell adhesions, disrupted intercellular signaling, and fibrofatty replacement of the myocardium. These changes serve as a substrate for ventricular arrhythmias, placing patients at risk of sudden cardiac death, even in the early stages of the disease. Current echocardiographic criteria for diagnosing arrhythmogenic right ventricular cardiomyopathy lack sensitivity, but novel markers of cardiac deformation are not subject to the same technical limitations as current guideline-recommended measures. Measuring cardiac deformation using speckle tracking allows for meticulous quantification of global systolic function, regional function, and dyssynchronous contraction. Consequently, speckle tracking to quantify myocardial strain could potentially be useful in the diagnostic process for the determination of disease progression and to assist risk stratification for ventricular arrhythmias and sudden cardiac death. This narrative review provides an overview of the potential use of different myocardial right ventricular strain measures for characterizing right ventricular dysfunction in arrhythmogenic right ventricular cardiomyopathy and its utility in assessing the risk of ventricular arrhythmias.

Endomyocardial substrate of ventricular arrhythmias in patients with autoimmune rheumatic diseases.

Delayed enhancement-magnetic resonance imaging (DE-MRI) has demonstrated that nonischemic cardiomyopathy is mainly characterized by intramural or epicardial fibrosis whereas global endomyocardial fibrosis suggests cardiac involvement in autoimmune rheumatic diseases or amyloidosis. Conduction disorders and sudden cardiac death are important manifestations of autoimmune rheumatic diseases with cardiac involvement but the substrates of ventricular arrhythmias in autoimmune rheumatic diseases have not been fully elucidated. 20 patients with autoimmune rheumatic diseases presenting with ventricular tachycardia (VT) (n = 11) or frequent ventricular extrasystoles (n = 9) underwent DE-MRI and/or endocardial electroanatomical mapping of the left ventricle (LV). Ten patients with autoimmune rheumatic diseases underwent VT ablation. Global endomyocardial fibrosis without myocardial thickening and unrelated to coronary territories was detected by DE-MRI or electroanatomical voltage mapping in 9 of 20 patients with autoimmune rheumatic diseases. In the other patients with autoimmune rheumatic diseases, limited regions of predominantly epicardial (n = 4) and intramyocardial (n = 5) fibrosis or only minimal fibrosis (n = 2) were found using DE-MRI. Endocardial low-amplitude diastolic potentials and pre-systolic Purkinje or fascicular potentials, mostly within fibrotic areas, were identified as the targets of successful VT ablation in 7 of 10 patients with autoimmune rheumatic diseases. Global endomyocardial fibrosis can be a tool to diagnose severe cardiac involvement in autoimmune rheumatic diseases and may serve as the substrate of ventricular arrhythmias in a substantial part of patients.

Regressed Septal Cardiac Rhabdomyoma as a Substrate for Ventricular Arrhythmias

Regressed Septal Cardiac Rhabdomyoma as a Substrate for Ventricular Arrhythmias

Long-term follow-up of idiopathic ventricular fibrillation: A 30-year experience from our hospital

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Idiopathic ventricular fibrillation (IVF) is responsible for 5-7% of sudden cardiac arrests in the absence of substrate for ventricular arrhythmia, structural diseases, or primary arrhythmic syndromes. The characteristics, management, and prognosis of these patients are unclear. Purpose To investigate the clinical features, management, and prognosis of IVF in our hospital healthcare system Methods Mayo Database Explorer software was used to identify IVF patients from our hospital electronic medical records between 1990 to 2022 in 5 states. The medical records were manually reviewed. Results A total of 132 patients were initially diagnosed with IVF. During the 9.2±6.8 years mean follow-up, 36 [27.3%] patients were later diagnosed with structural diseases or primary arrhythmic syndromes (dilated cardiomyopathy [41.7%], Long QT syndrome [27.8%], catecholaminergic polymorphic ventricular tachycardia [8.3%], Brugada syndrome [5.6%], mitral valve-related arrhythmia [5.6%], and short QT syndrome [2.8%]). Among the rest of the 96 patients with true IVF (mean age 38.4±15.7 years, male 59.4%, Caucasian 80.2%, hypertension 28.1%, diabetes 8.3%), 91 (94.8%) patients presented with out-of-hospital cardiac arrest and 88 (91.7%) patients had a history of syncope. Early repolarization and fragmented QRS were noted in 32 (33.3%) and 28 (29.1%) patients, respectively. Defibrillators were implanted in 92 (95.8%) patients. Genetic testing was performed in 35 (36.5%) patients, and possible associated mutations were found in 13 (37.1%) patients. An Electrophysiology study was conducted in 55 (57.3%) patients, and ventricular fibrillation was induced in 17 (30.9%) patients. The medical management with antiarrhythmic drugs was selected in 60 (62.5%) patients, and the catheter ablation ± anti-arrhythmic drugs was selected in 36 (37.5%) patients. The recurrence of ventricular fibrillation during 9.2±6.8 years of mean follow-up was significantly higher in the ablation strategy group (p=0.0003) (Figure 1). Conclusions We reported the largest cohort of IVF patients from a single healthcare system. Early repolarization and fragmented QRS were common in IVF. The possible associated mutations were found in one-third of IVF who underwent genetic testing. The ventricular fibrillation recurrences were significantly higher in the catheter ablation strategy group.

Worldwide Experience With an Irrigated Needle Catheter for Ablation of Refractory Ventricular Arrhythmias: Final Report

BackgroundWe previously reported feasibility of irrigated needle ablation (INA) with a retractable 27-G end-hole needle catheter to treat nonendocardial ventricular arrhythmia substrate, an important cause of ablation failure. ObjectivesThe purpose of this study was to report outcomes and complications in our entire INA-treated population. MethodsPatients with recurrent sustained monomorphic ventricular tachycardia (VT) or high-density premature ventricular contractions (PVCs) despite radiofrequency ablation were prospectively enrolled at 4 centers. Endpoints included a 70% decrease in VT frequency or PVC burden decrease to <5,000/24 h at 6 months. ResultsINA was performed in 111 patients (median: 2 failed prior ablations, 71% nonischemic heart disease, and left ventricular ejection fraction 36% ± 14%). INA acutely abolished targeted PVCs in 33 of 37 patients (89%), and PVCs were reduced to <5,000/day in 29 patients (78%). During 6-month follow-up, freedom from hospitalization was observed in 50 of 72 patients with VT (69%), and improvement or abolition of VT occurred in 47%. All patients received multiple INA applications, with more in the VT group than in the PVC group (median: 12 [IQR: 7-19] vs 7 [5-15]; P < 0.01). After INA, additional endocardial standard radiofrequency ablation was required in 23% of patients. Adverse events included 4 pericardial effusions (3.5%), 3 cases of (anticipated) atrioventricular block (2.6%), and 3 heart failure exacerbations (2.6%). During 6-month follow-up, 5 deaths occurred; none were procedure-related. ConclusionsINA achieves improved arrhythmia control in 78% of patients with PVCs and avoids hospitalization in 69% of patients with VT refractory to standard ablation at 6-month follow-up. Procedural risks are acceptable. (Intramural Needle Ablation for Ablation of Recurrent Ventricular Tachycardia, NCT01791543; Intramural Needle Ablation for the Treatment of Refractory Ventricular Arrhythmias, NCT03204981)

PO-01-163 CHARACTERIZATION OF ATRIAL SUBSTRATE USING CLOSE-COUPLED PACED ELECTROGRAM FEATURE ANALYSIS (PEFA) IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION

Mapping strategies that lead to a better understanding and therapy for persistent atrial fibrillation (AF) are urged. Paced electrogram feature analysis (PEFA) exposes slow conduction zones as substrate for ventricular arrhythmias and previous studies support its efficacy for guiding ablation. PEFA has not been studied in the left atrium (LA). Our goal was to demonstrate that PEFA exposes slow conduction areas in the LA that may trigger and perpetuate AF. Prospective exploratory cohort study. The intervention group was formed by patients with paroxysmal AF undergoing catheter ablation (Group A), compared to a control group of patients without AF and structurally normal heart presenting for left-sided electrophysiological procedures (Group B). Antiarrhythmic drugs were discontinued at least five half-lives before the study and amiodarone, at least 3 months LA effective refractory period (AERP) was defined while pacing from the LA appendage (LAA). PEFA protocol consisted of a paced (S1) at 600 ms with an extra stimulus (S2) at a fixed coupling interval of AERP+30ms. EGM conduction time (time from pacing artifact to first deflection), EGM latency (conduction time from pacing artefact to local activation time of the S2 less same value for S1), EGM duration (first deflection to last deflection), EGM propagation time (latency + EGM duration), and last deflection (sum of CT + EGM duration) were defined (Figure 1). Group B data was used as the reference values, the percentage of abnormal EGM features in group A compared to group B were calculated. Twenty-four AF and 8 control patients were included. EGM features were evaluated in 13 different locations of the LA with a total of 12,291 EGMs to analyze (Table 1). Compared to non-AF controls, AF patients had a higher percentage of abnormal latency (10.43%, p<0.001), propagation time (12.04%, p<0.001), and last deflection (10.49%, p<0.001) for all locations evaluated together, however, the LA roof expressed more remarkable abnormal EGM properties than other areas (Table 1). There was no statistically significant difference in EGM duration between groups (p=0.83). PEFA exhibits abnormal conduction properties (latency, propagation time and last deflection) in certain areas of the LA. This may be used in the future to characterize AF substrate; objective assessment of these responses may inform ablation sites in patients with atrial fibrillation and warrants further study.Tabled 1Paced electrogram fractionation characteristics in patients with AF (Group A) and controls (Group B)EGM characteristicLatency (CT in S2 less CT in S1)Propagation (latency + EGM duration)Last deflection (sum of CT + EGM duration)Group A (N=9823)Time in ms (SD)Group B (N=2464)Time in ms (SD)% Abnormalp-valueGroup A (N=9823)Time in ms (SD)Group B (N=2464)Time in ms (SD)% Abnormalp-valueGroup A (N=9359)Time in ms (SD)Group B (N=2468)Time in ms (SD)% Abnormalp-valueAll54.7 (27.7)45.4 (21.9)10.43%<0.001*111.1 (35.9)101.6 (25.7)12.04%<0.001*172.0 (43.0)157.7 (31.5)10.49%<0.001*Anterior wall51.3 (28.4)45.1 (18.1)11.17%<0.001*113.2 (35.7)98.1 (22.3)19.39%<0.001*158.9 (34.7)154.5 (33.3)6.195%0.057Floor52.9 (27.2)36.6 (22.3)18.06%<0.001*109.2 (35.5)96.6 (28.3)10.31%<0.001*168.2 (44.7)149.8 (32.8)11.30%<0.001*LAA43.6 (40.5)32.7 (24.6)2.80%0.001*106.7 (48.2)100.4 (32.5)6.54%0.1192138.8 (48.2)131.0 (28.3)9.91%0.047*Left anterior wall55.0 (22.6)45.3 (18.0)14.34%<0.001*109.5 (29.5)104.4 (23.6)7.46%0.005*175.4 (38.4)153.6 (22.6)14.14%<0.001*LIPV33.8 (30.3)52.8 (14.4)6.94%<0.001*79.3 (36.7)96.9 (18.8)7.67%0.009*151.7 (34.5)161.0 (17.8)6.99%0.1470LSPV44.6 (34.7)54.4 (17.3)9.38%0.011*101.7 (44.3)102.7 (24.2)13.13%0.8265173.9 (33.8)169.0 (23.3)6.25%0.2189Mitral isthmus46.0 (26.0)43.6 (26.1)0.94%0.3334105.5 (35.0)101.3 (29.8)5.82%0.19137.5 (38.7)128.0 (29.2)7.36%0.006*Posterior wall53.9 (23.6)41.7 (16.7)19.26%<0.001*108.8 (33.2)92.5 (16.8)25.64%<0.001*178.6 (38.0)151.8 (21.4)27.61%<0.001*Right anterior wall62.1 (26.4)55.5 (15.8)17.47%<0.001*112.6 (33.7)109.3 (24.9)11.43%0.01191.6 (46.5)179.4 (24.7)14.08%<0.001*RIPV53.8 (13.1)60.3 (12.3)4.00%<0.001*97.1 (33.2)98.4 (18.1)6.4%0.01182.8 (32.8)184.5 (16.2)3.01%0.0682Roof57.1 (22.5)46.9 (17.3)26.63%<0.001*117.3 (30.3)100.2 (28.3)39.95%<0.001*175.5 (34.3)154.0 (49.5)36.96%<0.001*RSPV72.6 (27.0)63.5 (15.1)18.47%0.003*128.8 (46.3)113.4 (28.6)16.30%0.003*199.3 (29.5)200.4 (23.1)4.324%0.7597Septum61.7 (27.7)44.4 (28.0)10.64%<0.001*118.3 (37.7)106.4 (28.2)15.51%<0.001*184.6 (37.6)161.7 (30.2)12.61%<0.001**Statistically significant, CT: Conduction time, EGM: Electrogram, LAA: Left atrium appendage, LIPV: Left inferior pulmonary vein, LSPV: Left superior pulmonary vein, RIPV: Right inferior pulmonary vein, LIPV: Left inferior pulmonary vein. Open table in a new tab

Mitral Annular Substrate and Ventricular Arrhythmias in Arrhythmogenic Mitral Valve Prolapse With Mitral Annular Disjunction

BackgroundIn patients with bileaflet mitral valve prolapse (MVP), mitral annular disjunction (MAD) is associated with increased risk of sudden cardiac death via incompletely understood mechanisms. ObjectivesThis study assessed the substrate for ventricular arrhythmias in patients with bileaflet MVP and MAD as well as outcomes of catheter ablation with an emphasis on sustained, monomorphic ventricular tachycardia (VT). MethodsA total of 18 consecutive patients (11 women, mean age 54 ± 15 years) with bileaflet MVP and MAD underwent catheter ablation for VT, and/or premature ventricular complexes (PVCs). Eight patients had a prior cardiac arrest. ResultsPVCs were targeted for ablation in all 18 patients (symptomatic PVCs n = 15, PVC-induced ventricular fibrillation n = 3). Sustained monomorphic VT was targeted in 7 of 18 patients. Electroanatomic mapping showed low voltage in the area of the mitral annulus corresponding to VT target sites in 6 of 7 patients with sustained VT. Four of 7 patients had low voltage in the areas of MAD. Six of 7 patients with VT were rendered noninducible post-ablation. The PVC burden was reduced from 11.0% ± 10.4% to 4.0% ± 5.5% (P = 0.004). Over a mean follow-up of 33.9 ± 43.4 months, no VTs recurred. There were no major complications. No repeat ablations for VT occurred. Five of 18 patients required repeat ablation for PVCs. ConclusionsIn patients with bileaflet MVP and MAD undergoing catheter ablation, the mitral valve annulus often contains low-voltage areas harboring the substrate for monomorphic VT and PVCs. Ablation in these patients was safe and improved arrhythmia control.

Myocardial infarction-related ventricular arrhythmias

Ventricular arrhythmias are among the most serious complications of myocardial infarction that defi ne not only increased morbidity and mortality, but also signifi cantly impaired quality of life. The pathogenesis of ventricular arrhythmias that arise during and after myocardial infarction is a combination of various triggering and modulating factors. We present a summary of the main structural and functional changes that occur with myocardial ischemia and create substrate for ventricular arrhythmias. The electrophysiological mechanisms underlying infarction-related ventricular arrhythmias are reviewed, as well as the most common pharmacological and non-pharmacological treatment&amp;rsquo;s strategies.

Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise.

The health benefits of regular physical exercise are well known. Even so, there is increasing evidence that the exercise regimes of elite athletes can evoke cardiac arrhythmias including ventricular fibrillation and even sudden cardiac death (SCD). The mechanism of exercise-induced arrhythmia and SCD is poorly understood. Here, we show that chronic training in a canine model (12 sedentary and 12 trained dogs) that mimics the regime of elite athletes induces electrophysiological remodeling (measured by ECG, patch-clamp, and immunocytochemical techniques) resulting in increases of both the trigger and the substrate for ventricular arrhythmias. Thus, 4 months sustained training lengthened ventricular repolarization (QTc: 237.1±3.4 ms vs. 213.6±2.8 ms, n=12; APD90: 472.8±29.6 ms vs. 370.1±32.7 ms, n=29 vs. 25), decreased transient outward potassium current (6.4±0.5 pA/pF vs. 8.8±0.9 pA/pF at 50 mV, n=54 vs. 42), and increased the short-term variability of repolarization (29.5±3.8 ms vs. 17.5±4.0 ms, n=27 vs. 18). Left ventricular fibrosis and HCN4 protein expression were also enhanced. These changes were associated with enhanced ectopic activity (number of escape beats from 0/hr to 29.7±20.3/hr) in vivo and arrhythmia susceptibility (elicited ventricular fibrillation: 3 of 10 sedentary dogs vs. 6 of 10 trained dogs). Our findings provide in vivo, cellular electrophysiological and molecular biological evidence for the enhanced susceptibility to ventricular arrhythmia in an experimental large animal model of endurance training.

Frequency Domain Analysis of Endocardial Electrograms for Detection of Nontransmural Myocardial Fibrosis in Nonischemic Cardiomyopathy

BackgroundVoltage mapping in nonischemic cardiomyopathy can fail to identify midmyocardial substrate for ventricular arrhythmias, an important cause of ablation failure. ObjectivesThe aim of this study was to assess whether frequency domain analysis of endocardial left ventricular electrograms (EGMs) can better predict the presence of midmyocardial fibrosis (MMF) compared with voltage amplitude. MethodsNonischemic cardiomyopathy patients undergoing ventricular tachycardia ablation with registered preprocedural cardiac computed tomography and late iodine enhancement were included. Presence of fibrosis at each EGM site was assessed. Bipolar and unipolar EGMs were transformed to the frequency domain using multitaper spectral analysis. Singular value decomposition of the EGM frequency spectrum was used within a supervised machine learning process to select features to predict the presence of MMF and compare against predictions using voltage amplitude. ResultsThirteen patients were included (median age 57 years [IQR: 28-73 years], median ejection fraction 40% [IQR: 15%-57%]). A total of 6,015 EGM pairs were processed: 2,459 EGM pairs in MMF areas and 3,556 EGM pairs in non-MMF areas. Supervised classifiers were trained with stratified k-fold cross-validation within patients. The distribution of mean area under the curve metrics using frequency features, f, was significantly greater than voltage feature area under the curve metrics, v, (mean f = 0.841 [95% CI: 0.789-0.884] vs mean v = 0.591 [95% CI: 0.530-0.658]; P < 0.001), indicating that frequency-trained classifiers better predicted the presence of MMF. ConclusionsThese data indicate the promising discriminatory value of endocardial EGM frequency content in the assessment of concealed myocardial substrate. Further studies are needed to investigate the importance of the specific frequency features identified.

Incidence and prognostic significance of malignant arrhythmias during (repetitive) Holter electrocardiograms in patients with pulmonary hypertension.

In patients with pulmonary hypertension (PH), increased pulmonary vascular resistance (PVR) may lead to increased right ventricular afterload and cardiac remodelling, potentially providing the substrate for ventricular arrhythmias. Studies dealing with long term monitoring of patients with PH are rare. The present study evaluated the incidence and the types of arrhythmias retrospectively recorded by Holter ECG in patients with newly detected PH during a long-term Holter ECG follow-up. Moreover, their impact on patient survival was evaluated. Medical records were screened for demographic data, aetiology of PH, incidence of coronary heart disease, level of brain natriuretic peptide (BNP), results from Holter ECG monitoring, 6-minute walk test distance, echocardiographic data and hemodynamic data derived from right heart catheterization. Two subgroups were analyzed: 1. patients (n = 65) with PH (group 1 + 4) and derivation of at least 1 Holter ECG within 12 months from initial detection of PH and 2. patients (all PH etiologies, n = 59) with 3 follow-up Holter ECGs. The frequency and complexity of premature ventricular contractions (PVC) was classified into "lower" and "higher" (=non sustained ventricular tachycardia, nsVT) burden. Holter ECG revealed sinus rhythm (SR) in most of the patients (n = 60). Incidence of atrial fibrillation (AFib) was low (n = 4). Patients with premature atrial contractions (PAC) tend to have a shorter period of survival (p = 0.098), PVC were not correlated with significant survival differences. During follow-up PAC and PVC were common in all PH groups. Holter ECG revealed non sustained ventricular tachycardia in 19/59 patients [(32.2%); n = 6 during first Holter-ECG, n = 13 during second/third Holter-ECG]. In all patients suffering from nsVT during follow-up previous Holter ECG revealed multiform/repetitive PVC. PVC burden was not linked to differences in systolic pulmonary arterial pressure, right atrial pressure, brain natriuretic peptide and results of six-minute walk test. Patients with PAC tend to have a shortened survival. None of the evaluated parameters (BNP, TAPSE, sPAP) was correlated with the development of arrhythmias. Patients with multiform/repetitive PVC seem to be at risk for ventricular arrhythmias.

NT-proBNP is superior to novel plasma biomarkers for predicting adverse outcome in arrhythmogenic right ventricular cardiomyopathy

Abstract Background/Introduction Arrhythmogenic right ventricular cardiomyopathy is a heritable heart muscle disease characterized by progressive substitution of the myocardium with fibrous and fatty tissue, which is the substrate for ventricular arrhythmia, systolic dysfunction and heart failure. Determining the optimal time for heart transplantation is challenging and, therefore, finding risk factors for disease progression is needed. Purpose The purpose of the study was to evaluate the role of markers of myocardial fibrosis sST2, Gal-3, MMP-2 and MMP-9, as well as NT-proBNP and hsTnT, in predicting major adverse outcomes in ARVC. Moreover, we aimed to identify other risk factors for developing end-stage heart failure. Methods We included 91 patients with the definite diagnosis of ARVC according to the 2010 Task Force Criteria (59 males, mean age of 47±16 years). Patients were interviewed for their medical history, electrocardiography and echocardiography were performed and plasma levels of selected biomarkers were measured. Thereafter, subjects were followed for the occurrence of the composite endpoint of death or heart transplantation (HTx) and major arrhythmic events defined as ventricular fibrillation, sustained ventricular tachycardia or appropriate implantable cardioverter-defibrillator intervention. Results During the median follow-up of 36,4 months [29,8–41,2], 13 subjects (14%) reached the composite endpoint of death or HTx and 27 subjects (30%) experienced major arrhythmic event. Among the studied biomarkers, significantly higher levels of sST2, MMP-2, NT-proBNP and hsTnT were found in patients who achieved the composite endpoint. The remaining prognostic factors are shown in Table 1. In the multivariate analysis, three factors turned out to be significant: higher NT-proBNP levels (the cut-off point ≥890.3 pg/m), greater right ventricular end-diastolic area (the cut-off point ≥39.0 cm2) and history of atrial tachycardia. Kaplan-Meyer survival analysis depending on the number of predictors is presented in Figure 1. None of the biomarkers predicted major arrhythmic events. Conclusions NT-proBNP ≥890.3 pg/ml, RV area ≥39.0 cm2 and history of atrial tachycardia are independent risk factors for death or HTx in ARVC. Among the studied biomarkers, higher levels of sST2, MMP-2, NT-proBNP and hsTnT were observed in patients who reached the composite endpoint. Biomarkers had no value in predicting ventricular arrhythmias. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): National Institute of Cardiology, Warsaw, Poland

Ventricular tachycardia mechanisms and prevention in patients with severe heart failure and left ventricular assist device

Abstract Terminal Heart Failure with reduced Ejection Fraction (HFrEF) is associated with severe morbidity and mortality. Mechanical Left Ventricular Assist Devices (LVAD) are often used to provide these patients with a last resort therapy and as bridge to transplant. However, HFrEF patients with LVAD have significant myocardial substrate for ventricular arrhythmias and the LVAD itself might be regarded as pro-arrhythmogenic. Aim of the current study was to investigate the mechanism of ventricular arrhythmias in LVAD patients and to provide evidence for the hypothesis that ad-hoc ablation/substrate modification during surgical LVAD implantation might reduce the risk of VT. We retrospectively analyzed invasive ablation procedures in patients with VT±LVAD and determined the mechanism of arrhythmia during electrophysiological examination (using 3D electroanatomical and local activation time mapping; Carto; Biosense Webster) in LVAD (n=17) and non-LVAD (n=12) subgroups. Mean age of the predominantly male (97%) patients was 60±2 years. VTs were directly LVAD associated (i.e. focal, adjacent to LVAD insertion or macro-reentry, around LVAD) in almost half of the LVAD patients. Number of radiofrequency ablation (RF) lesions and RF time were not significantly different between LVAD associated VT and non-LVAD associated VT patients. Within the LVAD patient group, freedom from VT (mean follow-up 40±6 months) was 50% upon ablation in patients with VTs originating from the LVAD region and 70% if ablation was conducted in non-LVAD regions. None of the LVAD associated and 22% of non-LVAD associated VT patients died during follow-up of these critically ill patients. Moreover, to reduce LVAD related arrhythmias and based on additional ex-vivo/in-silico derived data, we propose a distinctive (i.e. “star” shaped, LVAD encirclement) epicardial substrate modification during surgical LVAD implantation. In summary, a significant percentage of patients with LVAD exhibit LVAD-associated focal/macro-reentry VT and recurrence rates are high. VT likelihood is reduced ex-vivo/in-silico upon substrate modification targeting myocardium adjacent to a possible LVAD implantation site. Epicardial RF ablation during surgical LVAD implantation might allow prevention of LVAD-associated focal/macro-reentry VT. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): DFG

Intracardiac echocardiography techniques to identify ventricular arrhythmia substrate.

Intracardiac echocardiography (ICE) is increasingly used to facilitate catheter ablation of ventricular arrhythmias (VA). It allows intraprocedural recognition of myocardial substrate, optimization of catheter-tissue contact, identification of anatomical barriers to ablation, and early recognition of complications. In the era where the 3-dimensionality of substrate for VA is increasingly recognized, ICE is invaluable in identifying scar topography in the endocardial, midmyocardial, and epicardial layers. ICE assists in identifying endocavitary structures that are a common source of VA in idiopathic and structural heart disease. Furthermore, as substrate imaging of the right ventricle has not been optimized with other imaging modalities, ICE offers a unique opportunity to visualize substrate in this chamber. Real-time substrate identification can be particularly useful where there are contraindications to use of other imaging modalities or the images are obscured by artefact in the presence of cardiac device leads. In this review we provide a step-by-step guide in the techniques used to image ventricular arrhythmia substrate with ICE. We also discuss the benefits and limitations of this technique in comparison to other imaging modalities.

Reproducibility of ventricular arrhythmias at exercise testing for prediction of non-ischaemic left ventricular scar in athletes.

The non-ischaemic left ventricular scar (NILVS) is an emerging substrate of ventricular arrhythmias (VA) in the athlete. We tested the diagnostic value of VA reproducibility at repeated exercise testing (ET). We included consecutive athletes who underwent cardiac magnetic resonance (CMR) for evaluation of VA and two consecutive ET off-therapy within 12 months. Those with a positive family history of premature sudden death/cardiomyopathy, syncope/pre-syncope, ECG or echocardiography abnormalities, or low-risk VA (exercise-suppressed infundibular or fascicular VA) were excluded. The NILVS was defined as subepicardial/midmyocardial stria of late gadolinium enhancement involving >5% of the LV mass. Reproducibility was defined as the occurrence of VA with the same pattern and behaviour during repeated ET. Of 325 athletes who underwent CMR for evaluation of VA, 75 were included, and 30 showed NILVS involving three [2-4] LV segments. At first ET, athletes with NILVS showed a higher prevalence of exercise-induced VA (93% vs. 53%, P < 0.001), while other VA characteristics did not differ between groups. At repeated ET, reproducibility was observed in 97% of athletes with vs. 13% without NILVS (P < 0.001). The remaining 87% of athletes with normal CMR either did not show any VA at repeated ET (59%) or showed arrhythmias with different patterns, mostly infundibular. Reproducibility yielded a positive predictive value for NILVS of 83% and a negative predictive value of 98%. VA reproducibility at repeated ET predicted an underlying NILVS in athletes with VA and otherwise normal clinical work-up. This finding may improve risk stratification and appropriate CMR referral of athletes with apparently idiopathic VA.

Multimodality Imaging of Sudden Cardiac Death and Acute Complications in Acute Coronary Syndrome.

Sudden cardiac death (SCD) is a potentially fatal event usually caused by a cardiac arrhythmia, which is often the result of coronary artery disease (CAD). Up to 80% of patients suffering from SCD have concomitant CAD. Arrhythmic complications may occur in patients with acute coronary syndrome (ACS) before admission, during revascularization procedures, and in hospital intensive care monitoring. In addition, about 20% of patients who survive cardiac arrest develop a transmural myocardial infarction (MI). Prevention of ACS can be evaluated in selected patients using cardiac computed tomography angiography (CCTA), while diagnosis can be depicted using electrocardiography (ECG), and complications can be evaluated with cardiac magnetic resonance (CMR) and echocardiography. CCTA can evaluate plaque, burden of disease, stenosis, and adverse plaque characteristics, in patients with chest pain. ECG and echocardiography are the first-line tests for ACS and are affordable and useful for diagnosis. CMR can evaluate function and the presence of complications after ACS, such as development of ventricular thrombus and presence of myocardial tissue characterization abnormalities that can be the substrate of ventricular arrhythmias.

Mitral Annulus Disjunction and Arrhythmic Mitral Valve Prolapse: Emerging Role of Cardiac Magnetic Resonance Imaging in the Workup.

Mitral valve prolapse is a commonly described entity with a highly variable and benign course. However, it is associated with ventricular arrhythmias and sudden cardiac death in a small subset of patients. Recent studies have yielded insight into myocardial mechanics and the causation of ventricular arrhythmias in these groups of patients. Mitral annular disjunction (MAD) characterized by detachment of mitral annulus from left ventricular myocardium is associated with morphological and functional remodeling of the left ventricular myocardium. Resultant fibrosis acts as a substrate of ventricular arrhythmia and sudden cardiac death. We present two such cases of arrhythmic mitral valve prolapse associated with MAD. Cardiac magnetic resonance imaging provides excellent morphological information and also helps in the assessment of fibrosis.

Assessment of myocardial lipomatous metaplasia using an optimized out-of-phase cine steady-state free-precession sequence: Validation and clinical implementation.

Myocardial lipomatous metaplasia, which can serve as substrate for ventricular arrhythmias, is usually composed of regions in which there is an admixture of fat and nonfat tissue. Although dedicated sequences for the detection of fat are available, it would be time-consuming and burdensome to routinely use these techniques to image the entire heart of all patients as part of a typical cardiac MRI exam. Conventional steady-state free-precession (SSFP) cine imaging is insensitive to detecting myocardial regions with partial fatty infiltration. We developed an optimization process for SSFP imaging to set fat signal consistently "out-of-phase" with water throughout the heart, so that intramyocardial regions with partial volume fat would be detected as paradoxically dark regions. The optimized SSFP sequence was evaluated using a fat phantom, through simulations, and in 50 consecutive patients undergoing clinical cardiac MRI. Findings were validated using standard Dixon gradient-recalled-echo (GRE) imaging as the reference. Phantom studies of test tubes with diverse fat concentrations demonstrated good agreement between measured signal intensity and simulated values calculated using Bloch equations. In patients, a line of signal cancellation at the interface between myocardium and epicardial fat was noted in all cases, confirming that SSFP images were consistently out-of-phase throughout the entire heart. Intramyocardial dark regions identified on out-of-phase SSFP images were entirely dark throughout in 33 patients (66%) and displayed an India-ink pattern in 17 (34%). In all cases, dark intramyocardial regions were also seen in the same locations on out-of-phase GRE and were absent on in-phase GRE, confirming that these regions represent areas with partial fat. In conclusion, if appropriately optimized, SSFP cine imaging allows for consistent detection of myocardial fatty metaplasia in patients undergoing routine clinical cardiac MRI without the need for additional image acquisitions using dedicated fat-specific sequences.