Prevalence and Prognostic Impact of Pathogenic Variants in Patients With Dilated Cardiomyopathy Referred for Ventricular Tachycardia Ablation

Ebert, Micaela; Wijnmaalen, Adrianus P.; Riva, Marta; Trines, Serge A.; Androulakis, Afa; Glashan, Claire A.; Schalij, Martin J.; Tintelen, J. Peter van; Jongbloed, Jan D. H.; Zeppenfeld, Katja

doi:10.1016/j.jacep.2020.04.025

Cited by 19 publications

(24 citation statements)

References 32 publications

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“…Of importance, DCM is a term describing a phenotypic cardiomyopathy, with different predisposing genetic and acquired etiologies, contributing to the development of the heart disease, so that the patients with DCM are representing a heterogenous population. In a recent study, Ebert et al examined the incidence and relationship of pathological gene variants in patients with DCM referred for catheter ablation of ventricular tachycardia [ 17 ]. The authors reported an 38% incidence of pathogenic carriers associated with development of DCM, mainly LMNA, and showed a two-fold increase of VT recurrence after ablation procedure in those patients compared to patients without genetical predisposition.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Outcomes after Catheter Ablation of Ventricular Tachycardia in Dilated vs. Ischemic Cardiomyopathy

Chakarov

Müller

Ene

et al. 2022

JCM

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Ischemic (ICM) and dilated cardiomyopathy (DCM) represent the two main underlying heart diseases in patients referred for catheter ablation of ventricular tachycardia (VT). While VT ablation in ischemic cardiomyopathy is relatively well-studied, data in patients with DCM are still scarce. The study aimed to compare the acute and long-term outcomes in patients with ICM and DCM who underwent VT ablation at a high-volume center. Consecutive patients who underwent VT ablation from April 2018 to April 2021 were included retrospectively. Patients with ischemic cardiomyopathy were compared to those with dilated cardiomyopathy. The primary endpoint was rate of VT recurrences, the secondary endpoints included overall mortality, rehospitalization because of cardiac condition (VT, acute heart failure, acute myocardial infarction, heart transplantation or implantation of left ventricular assisting device), and major adverse cardiac events (MACE) at long-term follow-up. A total of 225 patients admitted for first VT ablation were included. A total of 156 patients (69%) revealed ICM and 69 (31%) DCM. After a mean follow-up of 22 months, the primary endpoint of VT recurrence occurred significantly more often in the patients with dilated cardiomyopathy (ICM n = 47; 37% vs. DCM n = 34; 64%; p = 0.001). In regard to the secondary endpoint of overall mortality, there was no difference between the two patient cohorts (DCM n = 9; 15% vs. ICM n = 22; 16%; p = 0.677); the patients with DCM showed significantly higher rehospitalization rates due to cardiac conditions (75% vs. 59%; p = 0.038) and more frequent MACE (68% vs. 52%; p= 0.036). In a Cox regression model, electrical storm at admission was shown to be a predictor for VT recurrence after successful catheter ablation (HR = 1.942: 95% CI 1.237–3.050; p = 0.004), while the ablation of every induced VT morphology during the procedure (HR = 0.522; 95% CI = 0.307–0.885; p = 0.016) contributed to a positive long-term outcome. DCM is associated with a higher risk of VT recurrence after catheter ablation compared to ICM. Furthermore, patients with DCM are more frequent re-hospitalized in the majority of cases due the VT recurrence. There is no difference in the long-term mortality between the two cohorts.

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Section: Discussionmentioning

confidence: 99%

Long-Term Outcomes after Catheter Ablation of Ventricular Tachycardia in Dilated vs. Ischemic Cardiomyopathy

Chakarov

Müller

Ene

et al. 2022

JCM

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“…In a study investigating the influence of pathogenic or likely pathogenic mutations on ablation outcomes in patients with dilated cardiomyopathy (DCM), among those with such mutations (38% DCM) 60% had a dominant basal anteroseptal scar, and 41% had a dominant inferolateral scar. 99 LMNA 98,108,111 appears to have a higher predilection for basal anteroseptal myocardium, with other mutations favoring the inferoseptal wall. Previous studies demonstrated worse catheter ablation outcomes for targeting anteroseptal compared to inferolateral scars, 110,111 possibly due to less fat over the inferolateral wall, epicardial accessibility, and challenging intramural substrate.…”

Section: Rhythm Controlmentioning

confidence: 93%

“…Recent data examining a cohort of patients with idiopathic cardiomyopathy undergoing VT ablation following monomorphic VT found that 49% of those with likely or known pathogenic variants had LVEF 35%. 98 In a large European registry cohort of 269 patients with LMNA ACM, NSVT, LVEF ,45%, male sex, and loss-offunction variants were associated with VAs, but only if 2 factors were present. 99 In a study of 28 families affected by FLNC truncating mutations, mean LVEF in those with SCD was 39.6% 6 12%.…”

Section: Risk Stratification For Scdmentioning

confidence: 98%

“…Pathogenic mutation-positive patients had a worse prognosis, with decreased 24-month VT-free survival (16% vs 54%; P 5 .001) and higher cardiac mortality in those with likely or confirmed pathogenic mutations. 98 Median time to transplantation, ventricular assist device, or death was found to be 18 months if high-burden VT was observed on ICD interrogation in patients with laminopathies; therefore, a high burden of VT should prompt referral to a heart failure specialist. 107…”

Section: Rhythm Controlmentioning

confidence: 99%

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Ventricular arrhythmia management in patients with genetic cardiomyopathies

Sharif

Lubitz

2021

Heart Rhythm O2

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Genetic cardiomyopathies are associated with increased risk for cardiac arrhythmias and sudden cardiac death. The management of ventricular arrhythmias (VAs) in patients with these conditions can be nuanced due to particular disease-based considerations, yet data specifically addressing management in these patients are limited. Here we describe the current evidence-based approach to the management of ventricular rhythm disorders in patients with genetic forms of cardiomyopathy, namely, hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, left ventricular noncompaction, and Brugada syndrome, including recommendations from consensus guideline statements when available.

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“…More than 90% of these VTs are due to scar-related reentry and fewer than 10% are due to bundle branch reentry involving the Purkinje system or a focal mechanism. 96 Ebert et al 24 performed genetic testing on 98 consecutive patients with DCM, referred for catheter ablation of sustained monomorphic VT in the LV, finding pathogenic mutations in 38%, dominated by variants in LMNA and TTN , but also including PLN (phospholamban), SCN5A, RBM20 (RNA-binding motif 20), and DSP. Genotype-positive patients had worse outcomes, with 81% having recurrent VT and 51% dying or requiring heart transplant during median follow-up of 28 months.…”

Section: Arrhythmia Mechanisms and Phenotypes In Genetic Cardiomyopathymentioning

confidence: 99%

Arrhythmias as Presentation of Genetic Cardiomyopathy

Laws

Lancaster

Shoemaker

et al. 2022

Circulation Research

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There is increasing evidence regarding the prevalence of genetic cardiomyopathies, for which arrhythmias may be the first presentation. Ventricular and atrial arrhythmias presenting in the absence of known myocardial disease are often labelled as idiopathic, or lone. While ventricular arrhythmias are well-recognized as presentation for arrhythmogenic cardiomyopathy in the right ventricle, the scope of arrhythmogenic cardiomyopathy has broadened to include those with dominant left ventricular involvement, usually with a phenotype of dilated cardiomyopathy. In addition, careful evaluation for genetic cardiomyopathy is also warranted for patients presenting with frequent premature ventricular contractions, conduction system disease, and early onset atrial fibrillation, in which most detected genes are in the cardiomyopathy panels. Sudden death can occur early in the course of these genetic cardiomyopathies, for which risk is not adequately tracked by left ventricular ejection fraction. Only a few of the cardiomyopathy genotypes implicated in early sudden death are recognized in current indications for implantable cardioverter defibrillators which otherwise rely upon a left ventricular ejection fraction ≤0.35 in dilated cardiomyopathy. The genetic diagnoses impact other aspects of clinical management such as exercise prescription and pharmacological therapy of arrhythmias, and new therapies are coming into clinical investigation for specific genetic cardiomyopathies. The expansion of available genetic information and implications raises new challenges for genetic counseling, particularly with the family member who has no evidence of a cardiomyopathy phenotype and may face a potentially negative impact of a genetic diagnosis. Discussions of risk for both probands and relatives need to be tailored to their numeric literacy during shared decision-making. For patients presenting with arrhythmias or cardiomyopathy, extension of genetic testing and its implications will enable cascade screening, intervention to change the trajectory for specific genotype-phenotype profiles, and enable further development and evaluation of emerging targeted therapies.

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Prevalence and Prognostic Impact of Pathogenic Variants in Patients With Dilated Cardiomyopathy Referred for Ventricular Tachycardia Ablation

Cited by 19 publications

References 32 publications

Long-Term Outcomes after Catheter Ablation of Ventricular Tachycardia in Dilated vs. Ischemic Cardiomyopathy

Long-Term Outcomes after Catheter Ablation of Ventricular Tachycardia in Dilated vs. Ischemic Cardiomyopathy

Ventricular arrhythmia management in patients with genetic cardiomyopathies

Arrhythmias as Presentation of Genetic Cardiomyopathy

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