Episodes Of Ventricular Tachyarrhythmias Research Articles

Loss of protein phosphatase 2A regulatory subunit PPP2R5A is associated with increased incidence of stress-induced proarrhythmia.

Protein phosphatase 2A (PP2A) is a serine/threonine-selective holoenzyme that controls Ca2+ homeostasis and contractility of the heart via dephosphorylation of regulatory proteins. In some genetically modified mouse models with increased arrhythmogenicity, a reduced expression of the regulatory subunit B56α of PP2A was found as a concomitant effect. Whether there is a general correlation between the abundance of B56α and the promotion of cardiac arrhythmogenesis remains unclear. The aim of this study was therefore to investigate the role of PP2A-B56α in the propensity for arrhythmic activity in the heart. The experimental analysis of this question has been addressed by using a mouse model with deletion of the PP2A-B56α gene, PPP2R5A (KO), in comparison to wild-type animals (WT). Evidence for arrhythmogenicity was investigated in whole animal, isolated heart and cardiomyocytes by ECG, recording of monophasic action potential (MAP) induced by programmed electrical stimulation (PES), measurement of Ca2+ transients under increased pacing frequencies and determination of total K+ channel currents (I K). ECG measurements showed a prolongation of QT time in KO vs. WT. KO mice exhibited a higher rate of premature ventricular contractions in the ECG. MAP measurements in Langendorff-perfused KO hearts showed increased episodes of ventricular tachyarrhythmia induced by PES. However, the KO hearts showed values for MAP duration that were similar to those in WT hearts. In contrast, KO showed more myocardial cells with spontaneous arrhythmogenic Ca2+ transient events compared to WT. The whole-cell patch-clamp technique applied to ventricular cardiomyocytes revealed comparable peak potassium channel current densities between KO and WT. These findings support the assumption that a decrease or even the loss of PP2A-B56α leads to an increased propensity of triggered arrhythmias. This could be based on the increased spontaneous Ca2+ tansients observed.

Whether to implant a defibrillator or not? The Possibility of Using the MADIT-ICD Benefit Score Calculator in Real Practice

To study the predictive capabilities of the MADIT-ICD Benefit Score calculator in assessing the benefit of implantable cardioverter defibrillator (ICD) placement for the primary prevention of sudden cardiac death (SCD). This study included 388 patients with NYHA II-IV functional class chronic heart failure (CHF) with a left ventricular ejection fraction (LVEF) ≤35 % who underwent ICD placement for the primary prevention of SCD. Patients were followed up for two years to record the endpoints of first-time paroxysmal sustained ventricular tachyarrhythmia (VT) or non-arrhythmic death. According to the results of calculation with the MADIT-ICD Benefit Score calculator, 276 (71 %) patients had a high risk of VT (score ≥7) and 150 (39 %) had a high risk of non-arrhythmic death (score ≥3). 336 (94%) patients would benefit from an ICD: 148 (38 %) with a high level of probability and 218 (56 %) with a medium level of probability. According to the incidence of endpoints, VT episodes predominated in the low-ICD benefit group (36%), while the high-ICD benefit group had a relatively high incidence of non-arrhythmic death (12%). The results obtained for a cohort of Russian patients with CHF and reduced LVEF indicated that the use of the MADIT-ICD Benefit Score in routine clinical practice does not improve the stratification of SCD risk compared to the traditional approach to selecting patients with CHF for ICD based on the LVEF value.

A pilot study for risk stratification of ventricular tachyarrhythmia in hypertrophic cardiomyopathy with routine echocardiography parameters

Ventricular tachyarrhythmia (VTA) are frequent arrhythmias in patients with hypertrophic cardiomyopathy (HCM). Representing a major risk factor for sudden cardiac death, Holter ECG at first clinical presentation appears insufficient. This study aims to investigate the ability of routinely obtained parameters associated with myocardial remodeling in stratifying for VTA in HCM. In this monocentric analysis, patients with HCM underwent 12-channel electrocardiography and echocardiography, including tissue doppler imaging. The study’s primary endpoint was the documentation of non-sustained and sustained ventricular tachycardia—summarized as ventricular tachyarrhythmias (VTA) on Holter ECG or active devices. The occurrence of VTA was exploratory. Based on our collective, we developed a risk model regarding VTA. Of 140 HCM patients, 38 (27.1%) had an episode of VTA. Patients with VTA were likelier to have a history of atrial fibrillation (p < 0.001), a thicker interventricular septum (p < 0.001) and lower peak systolic mitral annular velocity (p < 0.001). The parameters were independently associated with endpoint in univariate and multivariate logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.80 (sensitivity, 63%; specificity, 88%). Our risk model including these widely available parameters is able to distinguish low and high-risk of VTA in patients with HCM.

Importance of blood biomarker determination in the selection of patients with heart failure for cardioverterdefibrillator implantation

Aim. To conduct a comparative analysis of blood biomarker concentrations, to study their prognostic role in the occurrence of sustained ventricular tachyarrhythmia (VT) or VT episodes requiring electrotherapy in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) ≤35% without prior syncope or sustained ventricular arrhythmias.Material and methods. This single-center prospective clinical study included 319 patients (men, 83%) aged 57 (51-63) years with LVEF of 29 (24-33)% receiving optimal therapy for HF, hospitalized for cardioverterdefibrillator implantation for the purpose of primary prevention of sudden cardiac death. Before the procedure, the concentration of blood biomarkers (blood electrolytes, C-reactive protein, creatinine, Soluble suppression of tumorigenicity 2 (sST2), N-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3) was determined. Based on blood creatinine concentration, glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Patients underwent a two-year prospective follow-up to record the end point of newly occurring clinically significant VT episodes detected by an implantable cardioverter-defibrillator.Results. The studied arrhythmic endpoint occurred in 84 (26,3%) patients. The multivariate analysis revealed three blood biomarkers, the concentration of which was associated with the first manifestation of VT. With sST-2 &gt;35 ng/ml, this risk increased by ~3 times (odds ratio (OR)=2,86; 95% confidence interval (CI): 1,23-6,64 (p=0,013)). Galectin-3 level &gt;12 ng/ml had a comparable prognostic value (OR=2,64; 95% CI: 1,06-6,53 (p=0,032)). In case of an increase in NT-proBNP &gt;2000 pg/ml, the risk of the same outcome was 2,2 times lower (OR=0,46; 95% CI: 0,22-0,95 (p=0,034)).Conclusion. Pre-implantation laboratory screening of NT-proBNP, sST-2 and galectin-3 concentrations can help in personalized assessment of arrhythmic risk in patients with HF and LVEF ≤35% referred for interventional primary prevention of sudden cardiac death.

Etiologies, Mechanisms, Management, and Outcomes of Electrical Storm.

Electrical storm (ES) is characterized by three or more discrete sustained ventricular tachyarrhythmia episodes occurring within a limited time frame (generally ≤ 24 h) or an incessant ventricular tachyarrhythmia lasting > 12 h. In patients with an implantable cardioverterdefibrillator (ICD), ES is defined as three or more appropriate device therapies, separated from each other by at least 5 min, which occur within a 24-h period. ES may constitute a medical emergency, depending on the number arrhythmic episodes, their duration, the type, and the cycle length of the ventricular arrhythmias, as well as the underlying ventricular function. This narrative review was facilitated by a search of MEDLINE to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other clinically relevant studies. The search was limited to English-language reports published between 1999 and 2023. ES was searched using the terms mechanisms, genetics, channelopathies, management, pharmacological therapy, sedation, neuraxial modulation, cardiac sympathetic denervation, ICDs, and structural heart disease. Google and Google scholar as well as bibliographies of identified articles were reviewed for additional references. This manuscript examines the current strategies available to treat ES and compares pharmacological and invasive treatment strategies to diminish ES recurrence, morbidity, and mortality.

Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs

Ischemic heart disease, which is often associated with irreversibly damaged heart muscle, is a major global health burden. Here, we report the potential of stem cell-derived committed cardiac progenitors (CCPs) have in regenerative cardiology. Human pluripotent embryonic stem cells were differentiated to CCPs on a laminin 521 + 221 matrix, characterized with bulk and single-cell RNA sequencing, and transplanted into infarcted pig hearts. CCPs differentiated for eleven days expressed a set of genes showing higher expression than cells differentiated for seven days. Functional heart studies revealed significant improvement in left ventricular ejection fraction at four and twelve weeks following transplantation. We also observed significant improvements in ventricular wall thickness and a reduction in infarction size after CCP transplantation (p-value < 0.05). Immunohistology analyses revealed in vivo maturation of the CCPs into cardiomyocytes (CM). We observed temporary episodes of ventricular tachyarrhythmia (VT) in four pigs and persistent VT in one pig, but the remaining five pigs exhibited normal sinus rhythm. Importantly, all pigs survived without the formation of any tumors or VT-related abnormalities. We conclude that pluripotent stem cell-derived CCPs constitute a promising possibility for myocardial infarction treatment and that they may positively impact regenerative cardiology.

PO-04-226 RISK OF VENTRICULAR RECURRENT TACHYARRHYTHMIA IN PATIENTS RECEIVING PRIMARY PREVENTION IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS

Implantable cardioverter-defibrillators (ICDs) have demonstrated efficacy in reducing mortality attributable to sustained ventricular tachyarrhythmia (VTA) and have been used for primary prevention of sudden death. However, patients with primary prevention ICDs remain at risk for first and recurrent VTA, which are associated with increased morbidity and mortality. Currently, there are limited data on factors associated with recurrent VTA after the occurrence of a first episode in this population. Improved risk stratification may help tailor advanced therapies, such as catheter ablation or antiarrhythmic medications, to patients at a high risk for recurrence. The objective of this study was to quantify the risk for recurrent VTA after the occurrence of a first VTA episode among patients with a primary prevention ICD. The population comprised patients enrolled in five landmark ICD trials (MADIT-II, MADIT-Risk, MADIT-CRT, MADIT-RIT, RAID) who experienced a first episode of VTA (defined as ventricular tachycardia [VT] ≥170 bpm or ventricular fibrillation [VF]) after ICD implantation (N=789). The primary endpoint was recurrent VTA after a first episode. All-cause mortality associated with recurrent VTA was a secondary endpoint. Among 789 study patients who experienced a first VTA after ICD implantation, mean age was 63 ± 11 years, 17% were women, 64% had ischemic cardiomyopathy, and mean left ventricular ejection fraction (EF) was 24 ± 7%. Kaplan Meier analysis showed the risk of recurrent VTA after a first episode was very high (60% at 3 years [Figure - A]). Findings were consistent regardless of baseline risk factors, including age, sex, NYHA Class, EF. Furthermore, the burden of multiple VTA episodes after a first episode was also high (average of 3.6 episodes per patient at 3 years [Figure B]). Recurrent VTA was associated with a significant two-fold increased risk of subsequent death (HR=2.15, 95% CI 1.40-3.32, p=0.001 [Figure - C]). Among primary prevention ICD recipients who experience a first VTA, the burden of recurrent VTA and subsequent mortality increase is very high regardless of baseline risk factors. Intensification of therapies, including early catheter ablation, should be considered in primary prevention ICD recipients who experience a first VTA.

PO-02-087 NOVEL DEVICE-BASED DISCRIMINATORS IMPROVE DIFFERENTIATION OF POLYMORPHIC VT AND VF FROM MONOMORPHIC VT IN IMPLANTABLE CARDIAC DEFIBRILLATORS

ICDs rely upon programmable rate cutoffs to direct therapy delivery. Studies showing reduced mortality when high voltage therapy (HVT) is avoided have led to programming that promotes longer detection times and higher detection rates. However, such programming can also result in delayed therapy for hemodynamically compromising polymorphic VT (PVT) or ventricular fibrillation (VF). We aim to characterize ventricular tachyarrhythmia (VTA) features and develop an algorithm to improve discriminating power for PVT/VF versus MVT to enable tailored HVT. Dataset of de-identified episodes of VTA from Abbott’s Merlin.net database were adjudicated as PVT/VF or MVT by three blinded Electrophysiologists independently. Cohen’s Kappa score measured inter-observer agreement. Four discriminators from near-field ventricular channel during VTA were evaluated. 1) Mean cycle length (CL), 2) Rate-adjusted interval instability (RAII), defined as range of RR intervals divided by mean CL, 3) Mean peak amplitude, and 4) Mean peak amplitude instability, defined as mean difference of consecutive peak amplitudes. Receiver operating characteristic (ROC) curves and area under curve (AUC) scores were computed for each discriminator. The predictive performance of discriminators was assessed via multiple linear regression. Eighty VTA episodes (34 PVT/VF and 46 MVT) were adjudicated with excellent inter-observer agreement (kappa ≥ 0.9). All four discriminators showed significant difference between groups and each had good predictive ability to classify PVT/VF (Table 1). Multiple linear regression showed all discriminators reliably predicted PVT/VF (each p<0.001). The combination of all 4 discriminators best predicted PVT/VF (sum of squared errors =3.7 vs 12.0 for Mean CL alone). An algorithm for PVT/VF vs MVT discrimination incorporating all 4 individual discriminators achieved diagnostic sensitivity of 94% and specificity of 96%. Tachycardia rate cutoff sub-optimally differentiates PVT/VF from MVT. Discriminators based on variability and magnitude of intervals and peak amplitudes accurately identifies PVT/VF. Incorporating these discriminators in a device-based algorithm could tailor therapy ensuring prompt treatment in the highest risk arrhythmias while safely extending time to therapy to reduce unnecessary HVT.Tabled 1Table 1 - Characteristics of discriminators in PVT/VF and MVT groupsDiscriminatorPVT/VFMVTp-valueROC-AUCMean cycle length (ms)314±43423±83<0.0010.87Rate-adjusted interval instability (ms/ms)0.52±0.380.08±0.08<0.0010.90Mean peak amplitude (mV)3.1±1.85.8±1.3<0.0010.89Mean peak amplitude instability (mV)0.63±0.460.16±0.34<0.0010.87 Open table in a new tab

Association between metabolic dysfunction-associated fatty liver disease and supraventricular and ventricular tachyarrhythmias in patients with type 2 diabetes

BackgroundCurrently, it remains uncertain whether metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with increased risk of supraventricular and ventricular tachyarrhythmias in people with type 2 diabetes mellitus (T2DM). MethodsWe retrospectively examined the data of 367 ambulatory patients with T2DM who underwent 24-hour Holter monitoring between 2015 and 2022 for clinical indications, and who did not have pre-existing permanent atrial fibrillation (AF), kidney failure or known liver diseases. Paroxysmal supraventricular tachycardia (PSVT), paroxysmal AF and episodes of ventricular tachyarrhythmias (i.e., presence of ventricular tachycardia, >30 premature ventricular complexes per hour, or both) were recorded. The presence and severity of MAFLD was diagnosed by ultrasonography and fibrosis-4 (FIB-4) index. ResultsPatients with T2DM who had MAFLD (n = 238) had a significantly greater prevalence of PSVT (51.7% vs. 38.8%), paroxysmal AF (6.3% vs. 1.3%) and combined ventricular tachyarrhythmias (31.9% vs. 20.2%) compared to their counterparts without MAFLD (n = 129). MAFLD was significantly associated with a greater than two-fold risk of having PSVT (adjusted-odds ratio [OR] 2.04, 95% confidence interval 1.04–4.00) or ventricular tachyarrhythmias (adjusted-OR 2.44, 95%CI 1.16–5.11), after adjusting for age, sex, smoking, alcohol intake, diabetes-related factors, comorbidities, medication use and left ventricular ejection fraction on echocardiography. The risk of supraventricular and ventricular tachyarrhythmias was even greater amongst patients with MAFLD and FIB-4 ≥ 1.3. ConclusionsIn ambulatory patients with T2DM, the presence and severity of MAFLD was strongly associated with an increased risk of supraventricular and ventricular arrhythmias on 24-hour Holter monitoring.

Reduction in Ventricular Tachyarrhythmia Burden in Patients Enrolled in the RAIDTrial.

The RAID (Ranolazine Implantable Cardioverter-Defibrillator) randomized placebo-controlled trial showed that ranolazine treatment was associated with reduction in recurrent ventricular tachycardia (VT) requiring appropriate implantable cardioverter-defibrillator (ICD) therapy. This study aimed to identify groups of patients in whom ranolazine treatment would result in the highest reduction of ventricular tachyarrhythmia (VTA) burden. Andersen-Gill analyses were performed to identify variables associated with risk for VTA burden among 1,012 patients enrolled in RAID. The primary endpoint was VTA burden defined as VTA episodes requiring appropriate treatment. Multivariate analysis identified 7 factors associated with increased VTA burden: history of VTA, age≥65 years, New York Heart Association functional class≥III, QRS complex (≥130ms), low ejection fraction (<30%), atrial fibrillation (AF), and concomitant antiarrhythmic drug (AAD) therapy. The effect of ranolazine on VTA burden was seen among patients without concomitant AAD therapy (HR [HR]: 0.68; 95%CI: 0.55-0.84; P< 0.001), whereas no effect was seen among those who are concomitantly treated with other AADs (HR: 1.33; 95%CI: 0.90-1.96; P = 0.16); P = 0.003 for interaction. In patients with cardiac resynchronization therapy (CRT) ICDs, ranolazine treatment was associated with a 36% risk reduction for VTA recurrence (HR: 0.64; 95%CI: 0.47-0.86; P< 0.001), whereas among patients with ICDs without CRT no significant effect was noted (HR: 0.94; 95%CI: 0.74-1.18; P = 0.57); P = 0.047 for interaction. In patients with high risk for VTA, ranolazine is effective in reducing VTA burden, with significantly greater effect in CRT-treated patients, those without AF, and those not treated with concomitant AADs. In patients already on AADs or those with AF, the addition of ranolazine did not affect VTA burden. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253).

P384 SUDDEN CARDIAC ARREST: LET’S LOOK BEYOND CORONAROPATHY

Abstract Introduction Sudden cardiac arrest (SCA) is a high mortality event. Up to 70% of SCAs are caused by an acute coronary syndrome; nevertheless, it is essential to consider also non–ischemic causes while evaluating a post–SCA patient. Clinical Case A 68–year–old male patient with history of hypertension and dyslipidemia, presenting to the emergency room (ER) for syncope. While waiting in the ER, another sincopal episode happened and ventricular fibrillation was detected, therefore he was treated with a DC shock. At the ECG record after SCA, any acute alteration was seen. At the blood tests, an early rise of myocardial injury markers was found. At bedside echocardiography, a slight apical hypokinesia with hypertrabeculation was reported. Hence, coronarography was performed and a multivasal ateromasic coronaropathy was treated with angioplasty and drug–eluting stenting of left main artery, left anterior descending artery and left circumflex artery. In the following days, other ventricular tachyarrhythmias episodes happened and were treated with DC shocks. Due to ventricular arrhythmias relapses and echocardiographic findings, a cardiac MRI was performed, showing subepicardial fatty infiltration in the mid–apical lateral wall with parietal bulging suggesting left ventricle arrhythmogenic cardiomyopathy. So, a cardiac defibrillator was implanted in secondary prevention. Genetic analysis was run and reported a VUS mutation on RYR2 gene, still under evaluation as a possible cause for the clinical events. Conclusions The present clinical case shows that many causes may lead to SCA. Our patient experienced syncopal episodes related to ventricular arrhythmias and an arrhythmic storm which were most likely caused by an ischemic event on the base of an undiagnosed left ventricle arrhythmogenic cardiomyopathy.

Effect of Mineralocorticoid Receptor Antagonists on the Prognosis of Patients with Ventricular Tachyarrhythmias

Introduction: The study sought to assess the effect of treatment with mineralocorticoid receptor antagonists (MRAs) on long-term prognosis of patients with systolic heart failure (HF) surviving index episodes of ventricular tachyarrhythmias. Methods: A large retrospective registry was used including consecutive HF patients with left ventricular ejection fraction <45% and index episodes of ventricular tachyarrhythmias from 2002 to 2015. The primary endpoint was all-cause mortality at 3 years and secondary endpoints were rehospitalization, as well as the composite endpoint consisting of recurrent ventricular tachyarrhythmias, sudden cardiac death and appropriate implantabe cardioverter defibrillator (ICD) therapies at 3 years. Results: 748 patients were included, 20% treated with MRA and 80% without. At 3 years, treatment with MRA was not associated with improved all-cause mortality (22% vs. 24%, log-rank p = 0.968; hazard ratio (HR) = 1.008; 95% CI 0.690–1.472; p = 0.968). Accordingly, risk of the composite endpoint (28% vs. 27%; HR = 1.131; 95% CI 0.806–1.589; p = 0.476) and first cardiac rehospitalization (24% vs. 22%; HR = 1.139; 95% CI 0.788–1.648; p = 0.489) were not affected by treatment with MRA. Conclusion: In patients with ventricular tachyarrhythmias, treatment with MRA was not associated with improved all-cause mortality at 3 years. The therapeutic effect of MRA treatment in patients with ventricular tachyarrhythmias needs to be reinvestigated within further randomized controlled trials.

Incidence, Predictors and Clinical Impact of Ventricular Electrical Storm in Arrhythmogenic Cardiomyopathy Patients with an Implantable Cardioverter-Defibrillator: A Single-Center Report with Medium-Term Follow-Up.

BackgroundImplantable cardioverter–defibrillator (ICD) is the most effective strategy for prevention of ventricular tachyarrhythmia in patients with arrhythmogenic cardiomyopathy (ACM). However, some patients receive ventricular electrical storm (VES), characterized by multiple episodes of sustained ventricular tachyarrhythmia. The purpose of this study was to determine the incidence, predictors and prognostic implications of VES in ACM patients with an ICD.MethodsA total of 88 patients with definite ACM who received an ICD and followed up continuously were included in this study. VES was defined as the occurrence of ≥3 separate episodes of sustained ventricular arrhythmias within a 24-hour period.ResultsDuring a median follow-up time of 4.0 years (range 1.6–6.9), VES occurred in 19/88 patients (21.6%). The interval between the ICD implantation and the first VES ranged from 1 month to 128 months. The median number of ventricular tachyarrhythmia events per VES was 7.5 (range 3–32). Multivariate analysis showed that VES was associated with a high body mass index (BMI) [adjusted hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.00–1.45, P=0.048)] and extensive T-wave inversion (TWI) (HR 23.39, 95% CI 1.74–314.58, P=0.017). Kaplan–Meier method showed that patients with VES did not have a worse cardiac mortality compared to those without such an event.ConclusionThere is a relatively high incidence of VES in ACM patients. The presence of high BMI and extensive TWI were strong predictors of VES occurrence in ACM patients with ICD. VES does not independently confer increased cardiac mortality.

Genetic risk factors for dilated cardiomyopathy

Aim. To study the diagnostic significance of genetic testing in patients with dilated cardiomyopathy (DCM), identify predictors of life-threatening ventricular tachyarrhythmias (VTAs) and assess adverse clinical outcomes in different genetic groups.Material and methods. The study included 126 unrelated patients with verified DCM as follows: 70 (55,6%) probands with criteria for familial DCM and 56 (44,4%) individuals with a probable hereditary component. All patients (age, 43,1±11,3 years; men, 92 (73%); left ventricular ejection fraction, 30,6±8,43%; left ventricular enddiastolic diameter, 68,3±8,36 mm; follow-up period — median, 49 months) receive a complex of diagnostic investigations, including genetic screening using nextgeneration sequencing, followed by verification of variants by the Sanger method.Results. Pathogenic and likely pathogenic genetic variants were found in 61 (48,4%) of 126 patients with DCM. The dominant mutations were titin-truncating variants (TTNtvs), identified in 16 individuals (12,7%), and variants of lamin A/C (LMNA), identified in 13 probands (10,3%). Mutations in the other 19 genes were found in 32 (25,4%) patients. The following primary endpoints were assessed: sudden cardiac death (SCD), episodes of VTA (sustained ventricular tachycardia/ventricular fibrillation) and appropriate shocks of implanted cardiac resynchronization therapy (CRT)/cardioverter defibrillators (CVD) devices. As a result of ROC analysis, the following independent risk factors for SCD were identified: mutations in the LMNA gene (AUC, 0,760; p=0,0001) and non-sustained ventricular tachycardia (cut-off heart rate ≥161 bpm: AUC, 0,788; p=0,0001). When comparing the phenotypes and genotypes of DCM, TTNtv genotype was associated with a lower prevalence of complete left bundle branch block (χ2=7,46; p=0,024), a lower need for CRT/CVD implantation (χ2=5,70; p=0,017) and more rare episodes of sustained ventricular tachycardia/ventricular fibrillation (χ2=30,1; p=0,0001) compared with LMNA carriers. Kaplan-Meier analysis showed the worst prognosis in carriers of LMNA mutations both in relation to life-threatening VTA (log rang χ2=88,5; p=0,0001) and in achieving all unfavorable outcomes (χ2=27,8; p=0,0001) compared with groups of genenegative individuals, carriers of TTNtv and other genotypes.Conclusion. The phenotypes of DCM with TTNtv did not significantly differ in the incidence of VTAs and adverse outcomes compared with the gene-negative group and other genotypes (with the exception of LMNA). The contribution of the associations of LMNA mutations with VTAs on prognosis was confirmed, which shows the important role of LMNA genotype diagnosis for SCD risk stratification in patients with DCM.

Novel ventricular tachyarrhythmia detection enhancement detects undertreated life-threatening arrhythmias.

BackgroundVentricular tachyarrhythmias (VTA) with low and varying signal amplitudes and morphologies may not be successfully identified utilizing traditional implantable cardioverter-defibrillator algorithms.ObjectiveDevelop and validate a novel algorithm (VF Therapy Assurance, VFTA) to improve detection and timely delivery of high-voltage therapy (HVT) for these arrhythmias.MethodsArrhythmia detection was simulated on recorded VTA electrograms (EGMs) utilizing Abbott’s Merlin.net database. EGMs where an HVT occurred only when VFTA was enabled, or where VFTA provided an HVT >30 seconds earlier than without VFTA, were readjudicated with physician review. As VFTA never prevents detection or therapy, EGMs where VFTA did not activate or alter HVT were not adjudicated.ResultsAmong 564,353 recorded VTA EGMs from 20,000 devices, VFTA altered HVT in 105 EGMs from 67 devices. Physician adjudication determined that 81.9% (86/105) of these EGMs were true undertreated VTA episodes and would have received appropriate HVT with VFTA enabled. Furthermore, 65% of the episodes (56/86) were ventricular fibrillation, were polymorphic, did not self-terminate during the recording window, or were not amenable antitachycardia pacing. Of those, 87.5% (49/56) would not have elicited HVT without VFTA. Overall, VFTA provided new or earlier appropriate HVT in 0.27% (53/20,000) of devices with an increase in inappropriate HVT in 0.07% (14/20,000) devices.ConclusionThe VFTA algorithm successfully identifies VTA missed by traditional detection algorithms, owing to undersensed ventricular signals resulting in the rate falling below the programmed detection rate. The use of VFTA increases the likelihood of delivering life-saving HVT.

Biventricular Pacing Versus RightVentricular Pacing in Patients Supported With LVAD.

This study sought to evaluate the effects of right ventricular (RV) pacing versus biventricular (BiV) pacing on quality of life, functional status, and arrhythmias in LVAD patients. Cardiac resynchronization therapy (CRT) and left ventricular assist devices (LVADs) independently improve outcomes in heart failure patients, but the effects of combining these therapies remains unknown. We present the first prospective randomized study evaluating the effects of RV versus BiV pacing on quality of life, functional status, and arrhythmias in LVAD patients. In this prospective randomized crossover study, LVAD patients with prior CRT devices were alternated on RV and BiV pacing for planned 7-14-day periods. Ambulatory step count, 6-minute walk test distance, Kansas City Cardiomyopathy Questionnaire scores, arrhythmia burden, CRT lead function, and echocardiographic data were collected with each pacing mode. Thirty patients were enrolled, with a median age of 65 years, 67% male, and mean duration of LVAD support of 309days. Compared with BiV pacing, RV-only pacing resulted in 29% higher mean daily step count, 11% higher 6-minute walk test distance, and 7% improved KCCQ-12 score (all p<0.03). LV end-diastolic volume was significantly lower with RV pacing (220 vs. 250mL; p=0.03). Fewer patients had ventricular tachyarrhythmia episodes during RV pacing (p=0.03). RV lead impedance was lower with RV pacing (p=0.047), but no significant differences were observed in impedance across other CRT leads. In the first prospective randomized study comparing variable pacing in LVAD patients, RV pacing was associated with significantly improved functional status, quality of life, fewer ventricular tachyarrhythmias, and stable lead impedance compared with BiV pacing. This study supports turning off LV lead pacing in LVAD patients with CRT.

Role of stimulating growth factor 2 and galectin-3 in predicting the ventricular tachyarrhythmias in patients with ischemic cardiomyopathy

Aim. To assess the role of stimulating growth factor 2 (ST-2) and galectin-3 in predicting the ventricular tachyarrhythmias (VTA) in patients with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) &lt;35%.Material and methods. The study included 40 patients (men, 36 (90,0%); median age, 64,5 [57,5; 68,5] years) with CAD, NYHA class IIIII heart failure, LVEF &lt;35%, indications for implantable cardioverter defibrillator (ICD) (primary prevention of sudden cardiac death). Prior to ICD implantation, patients were measured for serum ST-2 and galectin-3 levels. For 18 months, patients were assessed for arrhythmic events recorded in the ICD memory.Results. The 1st group consisted of 10 (25,0%) patients who had VTA episodes, arrested by antitachycardia pacing or shock during 18-month follow-up. The 2nd group consisted of 30 (75,0%) patients without VTA episodes. It was found that ST-2 concentration &gt;22,48 ng/ml (p=0,02) and galectin-3 &gt;10,95 ng/ml (p=0,009) corresponded to appropriate ICD discharge. Multivariate ROC analysis demonstrated that the only independent predictor of VTA was ST-2 elevation (odds ratio, 1,11; 95% CI, 1,01-1,21; p=0,023).Conclusion. An increase in the concentration of both ST-2 &gt;22,48 ng/ml and galectin-3 &gt;10,95 ng/ml had a high predictive value in assessing the VTA risk in patients with ischemic cardiomyopathy. In multivariate analysis, an increase in ST-2 &gt;22,48 ng/ml was an independent predictor of VTA.

Voltage/Calcium Uncoupling Underlies Sustained Torsade de Pointes Ventricular Tachyarrhythmia in an Experimental Model of Long QT Syndrome.

BackgroundClinical experience showed that the majority of Torsade de Pointes (TdP) ventricular tachyarrhythmia (VT) in patients with long QT syndrome (LQTS) are self-terminating (ST), but the few that are non-self-terminating (NST) are potentially fatal. A paramount issue in clinical arrhythmology is to understand the electrophysiological mechanism of ST vs. NST TdP VT.MethodsWe investigated the electrophysiological mechanism of ST vs. NST TdP VT in the guinea pig Anthopleurin-A experimental model of LQTS, a close surrogate model of congenital LQT3. We utilized simultaneous optical recordings of membrane voltage (Vm) and intracellular calcium (Cai) and a robust analytical method based on spatiotemporal entropy difference (Ed) to investigate the hypothesis that early Vm/Cai uncoupling during TdP VT can play a primary role in perpetuation of VT episodes.ResultsWe analyzed a total of 35 episodes of TdP VT from 14 guinea pig surrogate models of LQTS, including 23 ST and 12 NST VTs. Ed values for NST VT were significantly higher than Ed values for ST VT. Analysis of wave front topology during the early phase of ST VT showed the Cai wave front following closely Vm wave front consistent with a lower degree of Ed. In contrast, NST VT was associated with uncoupling of Vm/Cai wave fronts during the first 2 or 3 cycles of VT associated with early wave break propagation pattern.ConclusionsUtilizing a robust analytical method we showed that, in comparison to ST TdP VT, NST VT was consistently predated by early uncoupling of Vm/Cai that destabilized wave front propagation and can explain a sustained complex reentrant excitation pattern.

Cardiac resynchronization therapy and ventricular tachyarrhythmia burden

Cardiac resynchronization therapy-defibrillator (CRT-D) may reduce the incidence of first ventricular tachyarrhythmia (VTA) in patients with heart failure (HF) and left bundle branch block (LBBB). The purpose of this study was to assess the effect of CRT-D on VTA burden in LBBB patients. We included 1281 patients with LBBB from MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy). VTA was defined as any treated or monitored sustained ventricular tachycardia (VT ≥180 bpm) or ventricular fibrillation (VF). Life-threatening VTA was defined as VT ≥200 bpm or VF. VTA recurrence was assessed using the Andersen-Gill model. During a mean follow-up of 2.5 years, 964 VTA episodes occurred in 264 patients (21%). The VTA rate per 100 person-years was significantly lower in the CRT-D group compared with the implantable cardioverter-defibrillator (ICD) group (20 vs 34; P<.01). Multivariate analysis demonstrated that CRT-D treatment was associated with a 32% risk reduction for VTA recurrence (hazard ratio 0.68; 95% confidence interval 0.57-0.82; P <.001), 57% risk reduction for recurrent life-threatening VTA, 54% risk reduction for recurrent appropriate ICD shocks, and 25% risk reduction for the combined endpoint of VTA and death. The effect of CRT-D on VTA burden was consistent among all tested subgroups but was more pronounced among patients in New York Heart Association functional class I. Landmark analysis showed that at 2 years, the cumulative probability of death subsequent to year one was highest (16%) among patients who had ≥2 VTA events during their first year. In patients with LBBB and HF, early intervention with CRT-D reduces mortality, VTA burden, and frequency of multiple appropriate ICD shocks. VTA burden is a powerful predictor of subsequent mortality.

No impact of mineralocorticoid receptor antagonists on long-term recurrences of ventricular tachyarrhythmias.

The study sought to assess the prognostic impact of treatment with mineralocorticoid receptor antagonists (MRA) on recurrences of ventricular tachyarrhythmias in implantable cardioverter-defibrillator (ICD) recipients with systolic heart failure (HF). Data regarding the outcome of patients with ventricular tachyarrhythmias treated with MRA is limited. A large retrospective registry was used including consecutive ICD recipients with systolic HF (i.e., left ventricular ejection fraction<45%) and index episodes of ventricular tachyarrhythmias from 2002 to 2016. Patients treated with MRA were compared to patients without (non-MRA). Kaplan-Meier and multivariable Cox regression analyses were applied for the evaluation of the primary endpoint defined as first recurrence of ventricular tachyarrhythmias at five years. Secondary endpoints were appropriate ICD therapies, first cardiac rehospitalization, and all-cause mortality. 366 ICD recipients with systolic HF were included, 20% treated with MRA (spironolactone: 65%; eplerenone: 35%) and 80% without. At five years, treatment with MRA was not associated with the primary endpoint of first recurrence of ventricular tachyarrhythmias [47%vs. 48%, log-rank p=0.732; hazard ratio (HR)=1.067; 95% confidence interval (CI) 0.736-1.546; p=0.732]. Accordingly, risk of first appropriate ICD therapies, first cardiac rehospitalization, and all-cause mortality were not affected by the presence of MRA therapy. Finally, patients with spironolactone and eplerenone had comparable risk of first recurrences of ventricular tachyarrhythmias (50%vs. 45%; p=0.255; HR=2.263; 95% CI 0.495-10.341; p=0.292). Treatment with MRA was not associated with recurrences of ventricular tachyarrhythmias and ICD therapies at five years.