Characterization of Endocardial Electrophysiological Substrate in Patients With Nonischemic Cardiomyopathy and Monomorphic Ventricular Tachycardia

Hsia, Henry H.; Callans, David J.; Marchlinski, Francis E.

doi:10.1161/01.cir.0000083725.72693.ea

Cited by 337 publications

(128 citation statements)

References 31 publications

Supporting

Mentioning

120

Contrasting

Order By: Relevance

“…However, it is characteristic of patients demonstrating monomorphic VTs associated with nonischemic cardiomyopathies. 21,22 A similar distribution of fibrosis has recently been described with the use of late gadolinium enhancement MRI in patients with lamin A/C (LMNA) mutation cardiomyopathy. 23 This regional localization may be related to the effects of local mechanical stresses, which might have particularly important effects when part of the mechanosensor apparatus, like ILK, is deleted.…”

Section: Are There Specific Electrophysiological Features Of the Arrhmentioning

confidence: 64%

Loss of Cardiomyocyte Integrin-Linked Kinase Produces an Arrhythmogenic Cardiomyopathy in Mice

Quang

Maguy

et al. 2015

Circ: Arrhythmia and Electrophysiology

View full text Add to dashboard Cite

Background— Integrin-linked kinase (ILK), a serine/threonine protein kinase, has roles in cell signaling and molecular scaffolding. ILK mutation/deletion causes cardiomyopathic phenotypes, but the functional and electrophysiological features have not been characterized. This study investigated the structural, functional, ion channel, and electrophysiological changes associated with cardiomyocyte-directed ILK deletion in mice. Methods and Results— Adult mice with cardiomyocyte-directed ILK knockout were compared with littermate controls. Knockout mice showed markedly increased mortality, with sudden death beginning after 5 weeks and 100% mortality at 18 weeks. In 10-week-old knockout mice, spontaneous and inducible ventricular tachyarrhythmias were common, occurring in 60% and 86%, respectively, and absent in controls ( P <0.001, P <0.05 versus knockout mice). Ventricular refractoriness was prolonged, along with both QRS and QT interval. Action potentials were prolonged and displayed triggered activity. A wide range of ion currents were downregulated, including total, fast and slow components of transient outward K + current and inward rectifier K + current, along with corresponding ion channel subunit genes, providing a plausible explanation of action potential prolongation. At 5 weeks, only voltage-dependent K + currents were reduced, possibly related to direct ILK-Kv4.2 subunit interactions. Action potentials were prolonged, but no arrhythmias or cardiac dysfunction were noted. Structural remodeling was prominent at 10 weeks: connexin-43 was downregulated and redistributed to lateral cell margins, and left ventricular fibrosis occurred, with a strong regional distribution (predominating in the basal left ventricle). Conduction was slowed. High-throughput quantitative polymerase reaction gene-expression studies in 10-week-old ILK knockout showed upregulation of structural, remodeling and fibrosis-related genes, and downregulation of a wide range of ion channel and transporter subunits. Conclusions— Cardiomyocyte ILK deletion produces a lethal arrhythmogenic cardiomyopathy associated with important ion channel and structural remodeling.

show abstract

Section: Are There Specific Electrophysiological Features Of the Arrhmentioning

confidence: 64%

Loss of Cardiomyocyte Integrin-Linked Kinase Produces an Arrhythmogenic Cardiomyopathy in Mice

Quang

Maguy

et al. 2015

Circ: Arrhythmia and Electrophysiology

View full text Add to dashboard Cite

show abstract

“…With the exception of in ARVC and BrS, the arrhythmogenic substrates in NICM that could be identified using electroanatomic mapping are mostly located in the basal or perivalvular region of the LV, which is distinct from the ischemic substrates along the territories of the coronary arteries 52. Both endocardial or epicardial diseased substrates in NICM could exist and contain critical isthmuses for a successful ablation 53.…”

Section: Management Of Vt In Nicmmentioning

confidence: 99%

Ventricular arrhythmias in nonischemic cardiomyopathy

Chung

Lin

et al. 2018

Journal of Arrhythmia

View full text Add to dashboard Cite

Nonischemic cardiomyopathies (NICMs) are composed of variable disease entities, including primary and secondary cardiomyopathies. Determining the etiology of NICM provides pivotal roles of not only the understanding of the individual pathogenesis, but also the clinical management, such as risk stratification, pharmacological treatment, and intervention therapies. Despite the diverse causes of NICM, these cases mostly require clinical attention owing to progressive myocardial injury, resulting in ventricular dysfunction and heart failure. The interaction between the diseased ventricular substrates and systemic/neurophysiological factors contributes to the cornerstones responsible for ventricular arrhythmogenesis and sudden cardiac death (SCD). Prevention of SCD and diminishing ventricular tachyarrhythmias are the important mainstays for the management of NICM patients. Given the understanding of the abnormal ventricular substrates and advancement of navigation systems, radiofrequency catheter ablation (RFCA) has become an adjunctive or alternative strategy for NICM patients who experience drug‐refractory ventricular tachycardias (VTs). Successful ablation can frequently be achieved at the expense of an epicardial intervention. A recent study has proven the survival benefits for NICM patients who are free from recurrent VTs after a successful RFCA, regardless of the New York Heart Association (NYHA) functional class status or left ventricular ejection fraction. Additionally, recent evidence has highlighted the better delineation of a diseased myocardium through the incorporation of cardiovascular magnetic resonance imaging (CMRI) and 3D mapping systems, which can facilitate the identification of critical ventricular arrhythmogenic substrates in NICM patients.

show abstract

“…10 The reported difference in postablation outcomes between ischemic and nonischemic VTs may be related to certain peculiarities in underlying arrhythmia substrate in NIDCM, such as less late potentials, involvement of epimyocardial layers, and absence of dense scar. 8,[11][12][13] The aim of this study was to investigate the effect of VT noninducibility as an end point and proof for successful ablation on the rate of VT recurrence and survival in patients with NIDCM.…”

mentioning

confidence: 99%

Catheter Ablation of Ventricular Tachycardia and Mortality in Patients With Nonischemic Dilated Cardiomyopathy

Dinov

Arya

Schratter

et al. 2015

Circ: Arrhythmia and Electrophysiology

View full text Add to dashboard Cite

Background-Data on outcomes after catheter ablation of ventricular tachycardia (VT) in patients with nonischemic dilated cardiomyopathy (NIDCM) are insufficient. We aimed to investigate the effects of successful catheter ablation of VT on cardiac mortality in patients with NIDCM. Methods and Results-One hundred two patients with NIDCM (86 men; mean age, 58.8±15.2 years; mean ejection fraction, 33.3±11.9%) underwent VT ablation. After catheter ablation, a programmed ventricular stimulation to test for success was performed. Complete VT noninducibility was achieved in 62 (61%) patients and partial success or failure in 32 (31%) patients. During 2 years of follow-up, VT recurrence was observed in 33 patients (53%) without inducible VTs and in 24 patients (75%) with inducible VT inducible (P=0.041). VT inducibility was associated with higher VT recurrence (adjusted hazard ratio, 1.84; 95% confidence interval, 1.08-3.13; P=0.025). The primary end point of all-cause mortality was reached in 9 patients (15%) with noninducible VTs versus 11 patients (34%) with inducible sustained VTs (P=0.026). VT inducibility was associated with all-cause mortality (adjusted hazard ratio, 2.73; 95% confidence interval, 1.003-7.43; P=0.049). Conclusions-In patients with NIDCM and recurrent sustained VTs, a complete ablation of all inducible VTs may be achieved in 60% of the cases. The complete noninducibility may be a preferable end point of ablation because it was associated with better long-term success. Importantly, if possible to achieve through ablation, a complete VT noninducibility was associated with reduction of the likelihood for all-cause mortality in patients with NIDCM.

show abstract

Characterization of Endocardial Electrophysiological Substrate in Patients With Nonischemic Cardiomyopathy and Monomorphic Ventricular Tachycardia

Cited by 337 publications

References 31 publications

Loss of Cardiomyocyte Integrin-Linked Kinase Produces an Arrhythmogenic Cardiomyopathy in Mice

Loss of Cardiomyocyte Integrin-Linked Kinase Produces an Arrhythmogenic Cardiomyopathy in Mice

Ventricular arrhythmias in nonischemic cardiomyopathy

Catheter Ablation of Ventricular Tachycardia and Mortality in Patients With Nonischemic Dilated Cardiomyopathy

Contact Info

Product

Resources

About