Idiopathic ventricular fibrillation: the ongoing quest for diagnostic refinement

EP Europace ◽  
2020 ◽  
Author(s):  
Giulio Conte ◽  
John R Giudicessi ◽  
Michael J Ackerman
Keyword(s):  
Ventricular Fibrillation ◽  
Heart Diseases ◽  
Sudden Cardiac Arrest ◽  
Polymorphic Ventricular Tachycardia ◽  
Molecular Evidence ◽  
Idiopathic Ventricular Fibrillation ◽  
Diagnostic Approaches ◽  
Exercise Induced ◽  
Definition Of ◽  
Electrocardiogram Ecg

Abstract Prior to the recognition of distinct clinical entities, such as Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and long QT syndrome, all sudden cardiac arrest (SCA) survivors with ventricular fibrillation (VF) and apparently structurally normal hearts were labelled as idiopathic ventricular fibrillation (IVF). Over the last three decades, the definition of IVF has changed substantially, mostly as result of the identification of the spectrum of SCA-predisposing genetic heart diseases (GHDs), and the molecular evidence, by post-mortem genetic analysis (aka, the molecular autopsy), of cardiac channelopathies as the pathogenic basis for up to 35% of unexplained cases of sudden cardiac death (SCD) in the young. The evolution of the definition of IVF over time has led to a progressively greater awareness of the need for an extensive diagnostic assessment in unexplained SCA survivors. Nevertheless, GHDs are still underdiagnosed among SCA survivors, due to the underuse of pharmacological challenges (i.e. sodium channel blocker test), misrecognition of electrocardiogram (ECG) abnormalities/patterns (i.e. early repolarization pattern or exercise-induced ventricular bigeminy) or errors in the measurement of ECG parameters (e.g. the heart-rate corrected QT interval). In this review, we discuss the epidemiology, diagnostic approaches, and the controversies related to role of the genetic background in unexplained SCA survivors with a default diagnosis of IVF.

Abstract 17878: Calmodulin Mutation (CALM-F90L) Associated With Familial Idiopathic Ventricular Fibrillation Disrupts L-type Ca Channel Inactivation and Activates Sarcoplasmic Reticulum Ca Release in Ventricular Myocytes

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Dmytro Kryshtal ◽  
Hyun S Hwang ◽  
Christopher Johnson ◽  
Walter Chazin ◽  
Alfred L George ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Sarcoplasmic Reticulum ◽  
Binding Affinity ◽  
Ventricular Myocytes ◽  
Qt Prolongation ◽  
Polymorphic Ventricular Tachycardia ◽  
Ca Channel ◽  
Idiopathic Ventricular Fibrillation ◽  
Channel Inactivation ◽  
Exercise Induced

Introduction: The F90L mutation in calmodulin (CaM) has been associated with a familial form of autosomal-dominant idiopathic ventricular fibrillation (IVF) with features of exercise-induced QT prolongation, but the underlying arrhythmia mechanism is unknown. We previously found that CaM mutations that cause sudden death due to catecholaminergic polymorphic ventricular tachycardia (CPVT) activate ryanodine receptor (RyR2) Ca release channels; whereas CaM mutations associated with long QT syndrome (LQTS) have no effects on RyR2 channels but prolong the cardiac action potential by impairing L-type Ca current inactivation. Objective: To determine the effect of F90L mutant CaM on Ca binding affinity, L-type Ca currents and Ca handling and compare them to CaM mutants associated with CPVT (CPVT-CaM) and LQTS (LQTS-CaM). Methods and Results: We prepared recombinant wild-type (WT) and mutant CaM proteins associated with CPVT (N54I), LQTS (D96V, D130G, F142L) and IVF (F90L). Similar to LQTS CaMs, the F90L IVF mutation drastically reduced Ca binding affinity of CaM C-lobe (7-fold reduction compared to WT-CaM), whereas CPVT N54I has no effect. In voltage-clamped mouse ventricular myocytes dialyzed either with WT or mutant CaM, IVF-CaM F90L significantly impaired L-type Ca channel inactivation, similar to the effect of LQTS-CaMs, whereas CPVT-CaM had no effect (Fig. A, **p<0.01 vs WT). Next, mutant CaMs effects on sarcoplasmic reticulum Ca release were tested in permeabilized ventricular myocytes. At physiological free CaM [100 nM] and Ca [120 nM], IVF-CaM F90L increased spontaneous Ca wave activity analogous to CPVT-CaM N54I, but of significantly smaller effect size (Fig. B). In contrast, LQTS-CaMs had either no effect or reduced Ca waves (Fig. B). Conclusion: The F90L CaM mutation shares characteristics with both CPVT and LQTS CaMs, which may help explain clinical features of modest exercise-induced QT prolongation and sudden arrhythmic death in patient carriers.

scholarly journals Classification of Cardiac Arrhythmia using improved Feature Selection methods and Ensemble Classifiers

2022 ◽  
Vol 2161 (1) ◽  
pp. 012003
Author(s):  
Rajat Jain ◽  
Pranam R Betrabet ◽  
B Ashwath Rao ◽  
N V Subba Reddy
Keyword(s):  
Feature Selection ◽  
Heart Diseases ◽  
Sudden Cardiac Arrest ◽  
Principal Component ◽  
Ensemble Classifier ◽  
Ensemble Classifiers ◽  
Life Threatening ◽  
Electrocardiogram Ecg ◽  
Feature Selection Techniques

Abstract Arrhythmia is one of the life-threatening heart diseases which is diagnosed and analyzed using electrocardiogram (ECG) recordings and other symptoms namely rapid heartbeat or chest-pounding, shortness of breath, near fainting spells, insufficient pumping of blood from the heart, etc along with sudden cardiac arrest. Arrhythmia records a hasty and aberrant ECG. In this implementation, the arrhythmia dataset is collected from the UCI machine learning repository and then classified the records into sixteen stated classes using multiclass classification. The large feature set of the dataset is reduced using improved feature selection techniques such as t-Distributed Stochastic Neighbor Embedding (TSNE), Principal Component Analysis (PCA), Uniform Manifold Approximation, and Projection (UMAP) and then an Ensemble Classifier is built to analyse the classification accuracy on arrhythmia dataset to conclude when and which approach gives optimal results.

scholarly journals Identification of Loss-of-function RyR2 Mutations Associated with Idiopathic Ventricular Fibrillation and Sudden Death

2021 ◽  
Author(s):  
Xiaowei Zhong ◽  
Wenting Guo ◽  
Jinhong Wei ◽  
Yijun Tang ◽  
Yingjie Liu ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Sudden Death ◽  
Negative Impact ◽  
Deficiency Syndrome ◽  
Dominant Negative ◽  
Exercise Stress ◽  
Hek293 Cells ◽  
Polymorphic Ventricular Tachycardia ◽  
Loss Of Function ◽  
Idiopathic Ventricular Fibrillation

Mutations in cardiac ryanodine receptor (RyR2) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT). Most CPVT RyR2 mutations characterized are gain-of-function (GOF), indicating enhanced RyR2 function as a major cause of CPVT. Loss-of-function (LOF) RyR2 mutations have also been identified and are linked to a distinct entity of cardiac arrhythmia termed RyR2 Ca2+ release deficiency syndrome (CRDS). Exercise stress testing (EST) is routinely used to diagnose CPVT, but it is ineffective for CRDS. There is currently no effective diagnostic tool for CRDS in humans. An alternative strategy to assess the risk for CRDS is to directly determine the functional impact of the associated RyR2 mutations. To this end, we have functionally screened 18 RyR2 mutations that are associated with idiopathic ventricular fibrillation (IVF) or sudden death. We found two additional RyR2 LOF mutations E4146K and G4935R. The E4146K mutation markedly suppressed caffeine activation of RyR2 and abolished store overload induced Ca2+ release in HEK293 cells. E4146K also severely reduced cytosolic Ca2+ activation and abolished luminal Ca2+ activation of single RyR2 channels. The G4935R mutation completely abolished caffeine activation of and [3H]ryanodine binding to RyR2. Co-expression studies showed that the G4935R mutation exerted dominant negative impact on the RyR2 wildtype channel. Interestingly, the RyR2-G4935R mutant carrier had a negative EST, and the E4146K carrier had a family history of sudden death during sleep, which are different from phenotypes of typical CPVT. Thus, our data further support the link between RyR2 LOF and a new entity of cardiac arrhythmias distinct from CPVT.

scholarly journals High haemoglobin A1c level is a possible risk factor for ventricular fibrillation in sudden cardiac arrest among non-diabetic individuals in the general population

EP Europace ◽  
2020 ◽  
Vol 22 (3) ◽  
pp. 394-400
Author(s):  
Laura H van Dongen ◽  
Marieke T Blom ◽  
Abdenasser Bardai ◽  
Paulien C M Homma ◽  
Joline W J Beulens ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Hba1c Level ◽  
Sudden Cardiac Arrest ◽  
Fold Increase ◽  
Glycated Haemoglobin ◽  
Haemoglobin A1c ◽  
Electrocardiogram Ecg ◽  
Control Study ◽  
Hba1c Levels

Abstract Aims This study aimed to establish whether higher levels of glycated haemoglobin (HbA1c) are associated with increased sudden cardiac arrest (SCA) risk in non-diabetic individuals. Methods and results Case–control study in non-diabetic individuals (HbA1c &lt; 6.5%) in the Netherlands. Cases were SCA patients with electrocardiogram (ECG)-documented ventricular fibrillation (VF, the predominant cause of SCA) and HbA1c measurements immediately after VF, prospectively included in September 2009–December 2012. Controls (up to 10 per case) were age/sex-matched non-SCA individuals, included in July 2006–November 2007. We studied 306 cases (56.4 ± 6.8 years, 79.1% male) and 1722 controls (54.0 ± 6.8 years, 64.8% male). HbA1c levels were higher in cases than in controls (5.8 ± 0.3% vs. 5.4 ± 0.3%, P &lt; 0.001). The proportion of increased HbA1c (≥5.7%) was 63.1% in cases and 19.3% in controls (P &lt; 0.001). Multivariate regression models indicated that increased HbA1c was associated with a &gt; six-fold increased VF risk [adjusted odds ratio (ORadj) 6.74 (5.00–9.09)] and that 0.1% increase in HbA1c level was associated with 1.4-fold increase in VF risk, independent of concomitant cardiovascular risk factors. Increased VF risk at higher HbA1c is associated with acute myocardial infarction (MI) as cause of VF [OR 1.14 (1.04–1.24)], but the association between HbA1c and VF was similar in non-MI patients [OR 1.32 (1.21–1.44)] and MI patients [OR 1.47 (1.37–1.58)]. Conclusion Among non-diabetic individuals, risk of VF increased with rising HbA1c levels, independent of concomitant cardiovascular disease. Future studies should establish whether HbA1c level may be used as biomarker to recognize individuals at risk for VF.

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