Dilated Cardiomyopathy Ventricular Tachycardia Research Articles

Pleomorphic ventricular tachycardia in dilated cardiomyopathy is a strong predictor of VT recurrence after ablation independent of cardiac function: Comparison with ischemic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Background Compared to ICM patients, subgroups of DCM patients show higher VT recurrence rates after catheter ablation (CA), despite similar percentages of acute non-inducibility. Pleomorphic VTs (PL-VT) have been reported in ICM patients with fibrotic remodeling and progressive heart failure. Diffuse fibrosis is the dominant scar pattern in DCM. In these patients PL-VT may occur independent of cardiac function. Aim To investigate the prevalence, relation with cardiac function, and impact of PL-VT on long-term ablation outcome in patients with ICM and DCM. Methods Consecutive patients with ICM or DCM undergoing VT ablation (ICM 2009-2016; DCM 2008-2018) were included. PL-VT was defined as ≥1 spontaneous change of the 12-lead VT morphology lasting for ≥6 consecutive beats during the same induced VT episode. Complete procedural success was defined as non-inducibility of any VT at the end of the procedure. Patients were followed for VT recurrence and mortality. Results A total of 247 patients (86% men, age 63 ± 13 years) underwent CA for monomorphic VT, 152 with ICM (62%), and 95 with DCM (38%). Complete procedural success was achieved in 39% in ICM vs. 37% in DCM, respectively. PL-VT was observed in 22 and 29 patients with ICM and DCM, respectively (14% vs. 31%, P = 0.003). Among ICM patients, PL-VT was associated with a lower LVEF (PL-VT+ 28 ± 9% vs. PL-VT- 34 ± 12%, P = 0.02) and only occurred if LVEF was <40%. In contrast, in DCM patients, PL-VT was not related to cardiac function and occurred in 27% of patients with an EF >40%. After propensity score matching to account for baseline differences (age, gender, LVEF, prior VT ablation, VT storm, and amiodarone use), between ICM vs. DCM patients, the PLVT incidence was 4 times higher in DCM patients (7% [4/60] vs. 28% [17/60], P = 0.003). During a median follow-up of 30 months, 79 (32%) patients died (ICM 48 [32%), DCM 31 [33%], P = 0.88) and 120 (49%) patients had VT recurrence (ICM 59 [39%], DCM 61 [64%], P < 0.001). In Kaplan-Meier analyses, inducibility of PL-VT was associated with mortality only in ICM but not in DCM patients. In contrast, PL-VT was associated with poorer VT-free survival in both ICM and DCM patients (figure). In multivariate analyses, PL-VT remained a significant predictor of VT recurrence in DCM (HR 3.00, 95% CI 1.75-5.11, P < 0.001), independent of LVEF, (likely) pathogenic genetic mutation, amiodarone, endocardial low bipolar/unipolar voltage areas, dominant anteroseptal substrate, and non-complete acute procedural success, but not in ICM. Conclusions PL-VT was associated with poor systolic function and mortality in ICM, whereas it was independent of LVEF and the most decisive parameter for VT recurrence in DCM. This data suggests that PL-VT in DCM is a marker of a complex arrhythmic substrate challenging to control by CA. Abstract Figure. Kaplan-Meier analyses

Patients with coronary heart disease, dilated cardiomyopathy and idiopathic ventricular tachycardia share overlapping patterns of pathogenic variation in cardiac risk genes

BackgroundVentricular tachycardia (VT) is a major cause of sudden cardiac death (SCD). Clinical investigations can sometimes fail to identify the underlying cause of VT and the event is classified as idiopathic (iVT). VT contributes significantly to the morbidity and mortality in patients with coronary artery disease (CAD) and dilated cardiomyopathy (DCM). Since mutations in arrhythmia-associated genes frequently determine arrhythmia susceptibility screening for disease-predisposing variants could improve VT diagnostics and prevent SCD in patients.MethodsNinety-two patients diagnosed with coronary heart disease (CHD), DCM, or iVT were included in our study. We evaluated genetic profiles and variants in known cardiac risk genes by targeted next generation sequencing (NGS) using a newly designed custom panel of 96 genes. We hypothesized that shared morphological and phenotypical features among these subgroups may have an overlapping molecular base. To our knowledge, this was the first study of the deep sequencing of 96 targeted cardiac genes in Kazakhstan. The clinical significance of the sequence variants was interpreted according to the guidelines developed by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015. The ClinVar and Varsome databases were used to determine the variant classifications.ResultsTargeted sequencing and stepwise filtering of the annotated variants identified a total of 307 unique variants in 74 genes, totally 456 variants in the overall study group. We found 168 mutations listed in the Human Genome Mutation Database (HGMD) and another 256 rare/unique variants with elevated pathogenic potential. There was a predominance of high- to intermediate pathogenicity variants in LAMA2, MYBPC3, MYH6, KCNQ1, GAA, and DSG2 in CHD VT patients. Similar frequencies were observed in DCM VT, and iVT patients, pointing to a common molecular disease association. TTN, GAA, LAMA2, and MYBPC3 contained the most variants in the three subgroups which confirm the impact of these genes in the complex pathogenesis of cardiomyopathies and VT. The classification of 307 variants according to ACMG guidelines showed that nine (2.9%) variants could be classified as pathogenic, nine (2.9%) were likely pathogenic, 98 (31.9%) were of uncertain significance, 73 (23.8%) were likely benign, and 118 (38.4%) were benign. CHD VT patients carry rare genetic variants with increased pathogenic potential at a comparable frequency to DCM VT and iVT patients in genes related to sarcomere function, nuclear function, ion flux, and metabolism.ConclusionsIn this study we showed that in patients with VT secondary to coronary artery disease, DCM, or idiopathic etiology multiple rare mutations and clinically significant sequence variants in classic cardiac risk genes associated with cardiac channelopathies and cardiomyopathies were found in a similar pattern and at a comparable frequency.

Nonsustained ventricular tachycardia in dilated cardiomyopathy

In patients with structural heart disease, ventricular arrhythmias are associated with an increased risk of overall mortality and sudden cardiac death (SCD). Nonsustained ventricular tachycardia (NSVT) is common in patients with dilated cardiomyopathy of both ischemic and nonischemic origin. Recent studies suggest that NSVT may be a marker, but not a significant predictor, of mortality and SCD in that suppression of NSVT in these patients using antiarrhythmic drugs is of questionable benefit. Additionally, indications for implantable cardioverter defibrillator implantation do not include NSVT. This article focuses on the prognostic significance and treatment of patients with NSVT and ischemic or nonischemic dilated cardiomyopathy.

Endocardial and epicardial radiofrequency ablation of ventricular tachycardia associated with dilated cardiomyopathy: The importance of low-voltage scars

ObjectivesThe purpose of this study was to evaluate the occurrence, locations, and relationship of ventricular tachycardia (VT) to low-voltage areas in dilated cardiomyopathy (DCM). BackgroundThe substrate causing monomorphic VT after infarction is characterized by regions of low-voltage (<1.5 mV) scar on electroanatomic maps. The substrate causing VT associated with DCM is less well defined. MethodsA total of 28 patients were studied with endocardial (26 patients) and epicardial (8 patients) electroanatomic mapping. The VT circuits were defined by entrainment or pace mapping. ResultsVentricular tachycardia was due to focal VT in 5, bundle-branch re-entry in 2, and myocardial re-entry in 22 patients (both focal and re-entry VTs in 1 patient). All patients with myocardial re-entry had endocardial (20 of 20 patients) and/or epicardial (7 of 7 patients mapped) scar. Most (63%) endocardial scars were adjacent to a valve annulus. Of the 19 VT circuit isthmuses identified, 12 were associated with an endocardial scar and 7 with an epicardial scar. All myocardial re-entrant VTs were abolished in 12 of 22 patients, and inducible VT was modified in 4 patients. During follow-up of 334 ± 280 days, 54% of patients with myocardial re-entry were free of VT despite frequent episodes before ablation. ConclusionsThe VTs in DCM are most commonly the result of myocardial re-entry associated with scar. Scars are often adjacent to a valve annulus, deep in the endocardium, and can be greater in extent on the epicardium than on the endocardium. The use of epicardial mapping and radiofrequency is likely to improve success.

155 Predictive role for total and sudden death of non sustained ventricular tachycardia in dilated cardiomyopathy

155 Predictive role for total and sudden death of non sustained ventricular tachycardia in dilated cardiomyopathy

Suppressive effect of the Gly389 allele of the beta1-adrenergic receptor gene on the occurrence of ventricular tachycardia in dilated cardiomyopathy.

Beta-1-adrenergic receptor (beta1-AR) blockers reduce both the incidence of sudden death and the ventricular volume in heart failure. In vitro, the Gly389 variant of beta1-AR mediates less adenylyl cyclase activities than the Arg389 variant, so Arg389Gly polymorphism was investigated with regard to the genesis, progression, or arrhythmogenesis of dilated cardiomyopathy (DCM). Allele and genotype frequencies of the Arg389Gly polymorphism were determined in 163 DCM patients and 157 age- and sex-matched controls. There were no differences in genotype and allele frequencies between patients and controls. Echocardiograms, left ventriculograms and 24h-Holter electrocardiograms were evaluated in the DCM patients and none of the clinical indices, other than ventricular tachycardia (VT), differed among the 3 genotypes. The Gly389 allele was more frequent in the VT(-) group than in the VT(+) group (0.46 vs 0.24, p=0.001). In univariate analysis, the odds ratio for VT in patients carrying 1 or 2 copies of the Gly389 allele was 0.29 ([95% confidence interval, 0.13-0.64], p=0.002), when compared with the Arg389 homozygotes. The Gly389 variant supressed the occurrence of VT in DCM, suggesting that this allele confers a decreased risk of sudden death.

Relationship between the QT indices and the microvolt-level T wave alternans in cardiomyopathy.

The relationship between the QT indices and microvolt-level T wave alternans (TWA) is unknown in cardiomyopathy, so the present study examined 86 patients with cardiomyopathy who experienced TWA during exercise testing (EXT). The QT interval (QT), duration from the Q wave to the peak of the T wave (QTp), duration from the peak to the end of the T wave and the dispersion of these parameters were measured by 12-lead electrocardiogram at rest and during EXT. In dilated cardiomyopathy (DCM), TWA was positive (TWA+) in 19 patients and negative (TWA-) in 17. No significant difference was observed between the TWA+ and TWA- groups in any parameter. In hypertrophic cardiomyopathy (HCM), TWA was positive in 24 patients and negative in 12. Max QTc, max QTpc and mean QTpc during EXT in the TWA+ group were significantly longer than those in the TWA- group. The sensitivity of TWA for ventricular tachycardia (VT) was high in DCM and HCM, and that of max QTc >500 ms during EXT for VT was high in HCM (93%). TWA is a useful predictor for VT in DCM and HCM, and prolonged max QTc during exercise has a prognostic value in HCM. Repolarization abnormality during exercise plays an important role in the genesis of VT in cardiomyopathy.

Intractable recurrent ventricular tachycardia in dilated cardiomyopathy controlled by a vasodilating beta blocker.

Intractable recurrent ventricular tachycardia in dilated cardiomyopathy controlled by a vasodilating beta blocker.

Evaluation and treatment of nonsustained ventricular tachycardia.

The clinical significance of nonsustained ventricular tachycardia continues to undergo reevaluation as clinicians attempt to optimize screening strategies for identifying high-risk patients and to evaluate the efficacy of therapeutic interventions. The utility of ambulatory monitoring and programmed stimulation as screening tools in the patient who has suffered an infarction remains unsettled; ongoing clinical trials may help resolve these issues. New data suggest that the survival benefit associated with angiotensin-converting enzyme inhibition is unrelated to effects on spontaneous arrhythmias, similar to results previously reported for beta-blockers. Randomized clinical trials of prophylactic amiodarone in patients with congestive heart failure and nonsustained ventricular tachycardia have produced conflicting results. A strong relationship between polymorphic nonsustained ventricular tachycardia and sudden death in patients without structural heart disease or QT prolongation has been reported. The significance of nonsustained ventricular tachycardia in dilated cardiomyopathy and hypertrophic cardiomyopathy has also been reassessed.

QT interval dispersion: a non-invasive marker of susceptibility to arrhythmia in patients with sustained ventricular arrhythmias?

To assess QT interval dispersion on the surface electrocardiogram in patients with sustained ventricular arrhythmias. A retrospective and prospective blinded controlled study of patients referred for investigation of ventricular arrhythmias at a tertiary cardiac centre. 89 consecutive patients with sustained ventricular arrhythmias due to chronic ischaemic heart disease, cardiomyopathy, or ventricular tachycardia (VT) in a normal heart. 32 patients did not meet the inclusion criteria; therefore 57 patients were compared with a control group of 40 patients with myocardial disease but no history of arrhythmias and 12 normal controls with no myocardial disease. Standard 12 lead electrocardiograms were enlarged, the QT intervals for each lead measured, and QT dispersion calculated. There was a significantly greater mean QT dispersion (77 ms) in patients with sustained ventricular arrhythmias compared with the control group (38 ms, p < 0.01). This held for all groups; after myocardial infarction VT (82 (22) ms v control 38 (10) ms; p < 0.01), dilated cardiomyopathy VT (76 (18) ms v control 40 (11) ms, p < 0.01), and normal heart VT (65 (7) ms v control 32 (8), p < 0.05). There was also a greater QT dispersion in patients with impaired left ventricular function and VT, with a correlation between left ventricular function and QT dispersion in patients with VT (r = 0.56, p < 0.01). QT interval dispersion may be a further non-invasive marker of susceptibility to ventricular arrhythmias.

The effects of amiodarone on refractory ventricular tachycardia in dilated cardiomyopathy

The effects of amiodarone on refractory ventricular tachycardia in dilated cardiomyopathy

Value of the signal-averaged electrocardiogram as a predictor of sudden death in myocardial infarction and dilated cardiomyopathy.

To clarify the prognostic significance of signal averaged electrocardiogram (SAE), 100 patients with old myocardial infarction (OMI) and 54 patients with dilated cardiomyopathy (DCM) were studied. Late potentials (LPs) were detected in 31 patients with OMI and in 21 patients with DCM. During a mean follow up of 18 months (3 to 60) in OMI and 28 months (3 to 71) in DCM, 29 patients died. Fifteen patients died suddenly (8 in OMI, 7 in DCM). In OMI, the sensitivity (Se), specificity (Sp), predictive accuracy (PA) of LPs for sudden death were 75%, 72%, and 73%, respectively. The presence of either LPs or prolonged filtered QRS (f-QRS) predicted sudden death with a high Se, and the presence of both LPs and prolonged f-QRS predicted with high Sp and PA. In DCM, Se, Sp, and PA of LPs were lower than those in OMI (Se; 71%, Sp; 66%, PA; 67%). A life table analysis showed that the probability of remaining free from sudden death was significantly lower in patients with LPs than those without them in OMI, but no significant difference was observed between those with and without LPs in DCM. Patients with either LPs or prolonged f-QRS, however, had a significantly higher probability of sudden death in both diseases and no patient with normal SAE died suddenly. SAE was also useful in separating high risk patients in either normal or low cardiac index group in both diseases. Ventricular tachycardia (VT) and % fractional shortening in OMI and only VT in DCM were also useful predictors among other parameters. In conclusion, SAE provides useful information in a noninvasive method to identify patients at risk of sudden death, and patients with normal SAE have a low risk of sudden death in OMI and DCM.