Life-threatening Ventricular Arrhythmias In Patients Research Articles

Abstract 11956: Arumenamide-787 Suppresses Arrhythmogenesis Associated With the J Wave Syndrome as Well as Hypothermia

Background: The J-wave syndromes (JWS), comprised of Brugada (BrS) and early repolarization syndromes (ERS), increase the risk of life-threatening ventricular arrhythmias in patients resulting in sudden cardiac death. There are limited therapeutic strategies to treat these life-threatening conditions. Present management is via an implantable cardioverter defibrillator and/or medication, including quinidine. However, these treatments may have serious side-effects. Thus, novel therapies are needed to treat JWS. In this study, we investigate the effects of ARumenamide-787 (AR-787) in suppressing the electrocardiographic and arrhythmic manifestations of JWS and hypothermia. Methods: We studied the effects of AR-787 on sodium current (I Na ) and the delayed-rectifier potassium current (I Kr ) in HEK-293 cells stably expressing the α- and β1-subunits of the cardiac (Na V 1.5) sodium channel or the hERG channel. In addition, we studied its effect on the transient outward potassium current (I to ) and calcium current (I Ca ) from dissociated canine ventricular myocytes, along with action potentials and ECG from coronary-perfused right (RV) and left (LV) ventricular wedge preparations. The I to agonist, NS5806, I Ca blocker, verapamil, and sodium current (I Na ) blocker, ajmaline, to induce the electrocardiographic and arrhythmic manifestations of JWS (prominent J waves/ST segment elevation, phase 2 reentry, and polymorphic VT/VF) in right and left canine ventricular wedge preparations. Results: AR-787 exerted pleiotropic effects on the cardiac ion channels. The predominant effect was an inhibition of I to and enhancement of I Na , with subtle effects to inhibit the I Kr and augment I Ca . AR-787 diminished the electrocardiographic J wave and prevented and/or suppressed all arrhythmic activity in canine RV and LV experimental models of BrS, ERS and hypothermia. We observed no arrhythmogenic effects of AR-787 on I Kr . Conclusions: Our findings point to AR-787 as a promising candidate for the pharmacologic treatment of JWS and hypothermia. AR-787 suppresses the electrocardiographic and arrhythmic manifestations of JWS and hypothermia without significant prolongation of the QT interval, as with the classic BrS drug, quinidine.

PO-05-135 SIGNAL-AVERAGED ECG IN THE NORDIC ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY REGISTRY: ASSOCIATION WITH PREVALENT LIFE-THREATENING ARRHYTHMIAS AND ASCERTAINMENT OF CLINICAL DIAGNOSIS.

In arrhythmogenic right ventricular cardiomyopathy (ARVC), minor depolarization criteria by TFC2010 include ventricular late potentials (LP) assessed using signal-averaged ECG (SAECG) and terminal activation duration (TAD). TAD is measured from a standard V1 lead, which favors its use in clinical practice, however its ability to fully replace LP in ARVC workup is not clear. 1. To assess the association between TAD and LP and the prevalence of life-threatening ventricular arrhythmias in patients with ARVC. 2. To assess diagnostic impact of SAECG by characterizing the subgroup of patients, who would not have received definite ARVC diagnosis if LP were not considered. Patients with definite ARVC or genotype-positive family members who underwent SAECG were included (n=358, 47% women, age 41±16 years, 43% probands, 67% definite ARVC). LP and TAD were defined according to TFC2010 criteria. TFC score was calculated by assigning 2 points for major and 1 for minor criterium. Ventricular tachycardia (VT) was defined as sustained VT, aborted cardiac arrest or appropriate ICD shock. Logistic regression adjusted for clinical covariates was used to test association of TAD and LP with prevalent VT. In a subgroup of patients with TFC score 4, i.e. minimally required for diagnosis, patients who would be reclassified into borderline category if LP not considered (LP-dependent, n=38) were compared with those who had TFC score 4 regardless of LP (LP-independent, n=30) in terms of proband status, prevalence of imaging criteria and VT. LP were found in 209 patients (58%); TAD in 65 (18%); 90 patients had prevalent VT (25%). LP was associated with prevalent VT (OR=2.5 95%CI 1.2-5.3; Sensitivity 84%, Specificity 50%) while TAD was not (OR=1.6 95%CI 0.7-3.6; Sensitivity 32%, Specificity 87%). In the LP-dependent group, 9 of 14 (64 %) probands had prevalent VT, 7 (50%) survived cardiac arrest and 4 (29%) were genotype-positive. Clinical characteristics did not demonstrate significant differences between LP-dependent and LP-independent subgroups. LP is independently associated with VT and is more sensitive than TAD in identification of patients with prevalent VT. LP were critical for ascertainment of ARVC diagnosis required for initiation of family screening in 9% probands. Although the diagnostic impact of LP varies depending on SAECG availability, our data support its use as a sensitive non-invasive diagnostic tool.

Sildenafil affects the human Kir2.1 and Kir2.2 channels at clinically relevant concentrations: Inhibition potentiated by low Ba2.

Sildenafil (Viagra), the first approved and widely used oral drug for the treatment of erectile dysfunction, was occasionally associated with life-threatening ventricular arrhythmias in patients. Since inward rectifier potassium current (I K1) may considerably contribute to this arrhythmogenesis, we investigated the effect of sildenafil on the human Kir2.1 and Kir2.2, the prevailing subunits forming the ventricular I K1 channels. Experiments were performed by the whole-cell patch clamp technique at 37°C using Chinese hamster ovary cells transiently expressing the human Kir2.1 and Kir2.2 channels. Changes of both the inward and outward current components (at -110 and -50mV, respectively) were tested to be able to consider the physiological relevance of the sildenafil effect (changes at -110 and -50mV did not significantly differ, results at -50mV are listed below). A significant Kir2.1 inhibition was observed at all applied sildenafil concentrations (16.1% ± 3.7%, 20.0% ± 2.6%, and 15.0% ± 3.0% at 0.1, 1, and 10μM, respectively). The inhibitory effect of 0.1μM sildenafil was potentiated by the presence of a low concentration of Ba2+ (0.1μM) which induced only a slight Kir2.1 inhibition by 5.95% ± 0.75% alone (the combined effect was 35.5% ± 3.4%). The subtherapeutic and therapeutic sildenafil concentrations (0.1 and 1μM) caused a dual effect on Kir2.2 channels whereas a significant Kir2.2 activation was observed at the supratherapeutic sildenafil concentration (10μM: 34.1% ± 5.6%). All effects were fully reversible. This is the first study demonstrating that sildenafil at clinically relevant concentrations inhibits both the inward and outward current components of the main human ventricular I K1 subunit Kir2.1. This inhibitory effect was significantly potentiated by a low concentration of environmental contaminant Ba2+ in agreement with recently reported data on rat ventricular I K1 which additionally showed a significant repolarization delay. Considering the similar subunit composition of the human and rat ventricular I K1 channels, the observed effects might contribute to sildenafil-associated arrhythmogenesis in clinical practice.

Monitoring of Serum Potassium and Calcium Levels in End-Stage Renal Disease Patients by ECG Depolarization Morphology Analysis.

Objective: Non-invasive estimation of serum potassium, , and calcium, , can help to prevent life-threatening ventricular arrhythmias in patients with advanced renal disease, but current methods for estimation of electrolyte levels have limitations. We aimed to develop new markers based on the morphology of the QRS complex of the electrocardiogram (ECG). Methods: ECG recordings from 29 patients undergoing hemodialysis (HD) were processed. Mean warped QRS complexes were computed in two-minute windows at the start of an HD session, at the end of each HD hour and 48 h after it. We quantified QRS width, amplitude and the proposed QRS morphology-based markers that were computed by warping techniques. Reference and were determined from blood samples acquired at the time points where the markers were estimated. Linear regression models were used to estimate electrolyte levels from the QRS markers individually and in combination with T wave morphology markers. Leave-one-out cross-validation was used to assess the performance of the estimators. Results: All markers, except for QRS width, strongly correlated with (median Pearson correlation coefficients, r, ranging from 0.81 to 0.87) and with (r ranging from 0.61 to 0.76). QRS morphology markers showed very low sensitivity to heart rate (HR). Actual and estimated serum electrolyte levels differed, on average, by less than 0.035 mM (relative error of 0.018) for and 0.010 mM (relative error of 0.004) for when patient-specific multivariable estimators combining QRS and T wave markers were used. Conclusion: QRS morphological markers allow non-invasive estimation of and with low sensitivity to HR. The estimation performance is improved when multivariable models, including T wave markers, are considered. Significance: Markers based on the QRS complex of the ECG could contribute to non-invasive monitoring of serum electrolyte levels and arrhythmia risk prediction in patients with renal disease.

Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers: Anti-arrhythmic Drug for Arrhythmogenic Right Ventricular Cardiomyopathy.

Background: Current treatment guidelines for arrhythmogenic right ventricular cardiomyopathy (ARVC) mainly emphasize on prevention of ventricular arrhythmic events. Despite the progressive nature of ARVC, therapeutic options focusing on decelerating disease progression are scarce.Methods and Results: This retrospective observational cohort study included 311 patients [age, 39.1 ± 14.4 years; male, 233 (74.9%)] with a definite diagnosis of ARVC as determined by the 2010 Task Force Diagnostic Criteria. Among them, 113 patients (36.3%) received ACEI/ARB treatment. Disease progression was evaluated according to repeat transthoracic echocardiograms with a linear mixed model. Patients receiving ACEI/ARB treatment were associated with slower disease progression reflected by a gradual decrease in tricuspid annular plane systolic excursion than those not receiving ACEI/ARB treatment (0.37 vs. 0.61 mm per year decrease, P < 0.001) and slower dilation of right ventricular outflow tract (0.57 vs. 1.06 mm per year increased, P = 0.003). Cox proportional hazard regression models were used to evaluate the association between life-threatening ventricular tachycardia events and ACEI/ARB treatment. A reduced risk of life-threatening ventricular arrhythmia was associated with ACEI/ARB treatment compared to that without ACEI/ARB treatment (adjusted HR: 0.71, 95% CI: 0.52–0.96, P = 0.031).Conclusions: ACEI/ARB treatment is associated with slower disease progression and lower risk of life-threatening ventricular arrhythmia in patients with ARVC. Delaying disease progression may pave way for reducing life-threatening ventricular arrhythmia risk.

Impact of Myocardial Bridge on Life-Threatening Ventricular Arrhythmia in Patients With Implantable Cardioverter Defibrillator.

BackgroundMyocardial bridge (MB), common anatomic variant, is generally considered benign, while previous studies have shown associations between MB and various cardiovascular pathologies. This study aimed to investigate for the first time possible impact of MB on long‐term outcomes in patients with implantable cardioverter defibrillator, focusing on life‐threatening ventricular arrhythmia (LTVA).Methods and ResultsThis retrospective analysis included 140 patients with implantable cardioverter defibrillator implantation for primary (n=23) or secondary (n=117) prevention of sudden cardiac death. Angiographically apparent MB was identified on coronary angiography as systolic milking appearance with significant arterial compression. The primary end point was the first episode(s) of LTVA defined as appropriate implantable cardioverter defibrillator treatments (antitachyarrhythmia pacing and/or shock) or sudden cardiac death, assessed for a median of 4.5 (2.2–7.1) years. During the follow‐up period, LTVA occurred in 37.9% of patients. Angiographically apparent MB was present in 22.1% of patients; this group showed younger age, lower rates of coronary risk factors and ischemic cardiomyopathy, higher prevalence of vasospastic angina and greater left ventricular ejection fraction compared with those without. Despite its lower risk profiles above, Kaplan–Meier analysis revealed significantly lower event‐free rates in patients with versus without angiographically apparent MB. In multivariate analysis, presence of angiographically apparent MB was independently associated with LTVA (hazard ratio, 4.24; 95% CI, 2.39–7.55; P<0.0001).ConclusionsAngiographically apparent MB was the independent determinant of LTVA in patients with implantable cardioverter defibrillator. Although further studies will need to confirm our findings, assessment of MB appears to enhance identification of high‐risk patients who may benefit from closer follow‐up and targeted therapies.

Association Between Hyperaldosteronemia and Electrophysiological Myocardial Activity in Heart Failure with Preserved Ejection Fraction

Background. Sudden cardiac death, one of the most common types of cardiac death, is most often triggered by ventricular arrhythmia. Plasma aldosterone level has been shown to be an independent risk factor of life-threatening ventricular arrhythmia in patients with left ventricular systolic dysfunction following acute myocardial infarction. Whether either effect also occurs in patients with heart failure and preserved ejection fraction is currently unknown. Purpose. The study aims to investigate the relationship between plasma aldosterone level and ventricular arrhythmias in longterm heart failure with preserved ejection fraction. Methods. A cross-sectional study included 158 patients (58 men and 100 women, mean age 62.3±7.4 years) with heart failure with preserved ejection fraction (&gt; 50%). Patients had no history of primary aldosteronism and did not use the mineralocorticoid receptor antagonists during the last 6 weeks. Aldosterone plasma level was measured and 24-hour electrocardiographic monitoring was performed. Results. According to laboratory results 99 patients (62.7%, 95% confidence interval 55.0-70.0%) had normal (40-160 pg/ml) aldosterone plasma level (nAld) and 59 patients (37.3%, 95% CI 30.0-45.0%) had high (&gt; 160 pg/ml) aldosterone level (hAld). hAld patients more often had QTc prolongation (44.1% versus 18.2%) and ventricular arrhythmias (83.1% vs 61.6%) compared to nAld patients (all Ps &lt;0.001). The number of ventricular premature complexes in 24 hours were higher in hAld group (median 214, range 64-758) compared to nAld (median 52, range 16-198, P &lt; 0.003). hAld patients more often occurred bigemy, couple ventricular ectopy and nonsustained ventricular tachycardia (39.0% vs 19.0%, р=0.01). In Cox regression model’s high aldosterone plasma level was the independent risk factors of QTc prolongation (odds ratio 1.6, 95% confidence interval 1.1-5.7, p=0.034) and prognostically unfavorable ventricular arrhythmias (odds ratio 1.8, 95% confidence interval 1.2-6.8, p=0.024). Conclusion. In long-term HFpEF plasma aldosterone level is significantly related to QTc prolongation as well as ventricular arrhythmias.

P480Aldosterone plasma level as risk factor of ventricular arrhythmias in heart failure with preserved ejection fraction

Abstract Background. Sudden cardiac death, one of the most common types of cardiac death, is most often triggered by ventricular arrhythmia. Plasma aldosterone level has been shown to be an independent risk factor of life-threatening ventricular arrhythmia in patients with left ventricular systolic dysfunction following acute myocardial infarction. Whether either effect also occurs in patients with heart failure and preserved ejection fraction (HFpEF) is currently unknown. Purpose. The study aims to investigate the relationship between plasma aldosterone level and ventricular arrhythmias in long-term HFpEF. Methods. The study included 158 patients (58 men and 100 women, mean age 62.3 ± 7.4 years) with HFpEF (&amp;gt; 50%). All patients had a history of hospitalization due to HFpEF during the last 12 months, left ventricular diastolic dysfunction and / or elevated NT-proBNP level. Median confirmed HFpEF duration was 5 (range 4-8) years. Patients had no history of primary aldosteronism and did not use the mineralocorticoid receptor antagonists during the last 6 weeks. Aldosterone plasma level was measured and 24-hour electrocardiographic monitoring was performed. Results. According to laboratory results 99 patients (67.1%, 95% confidence interval (CI) 59.6-74.2%) had normal (40-160 pg/ml) aldosterone plasma level (nAld) and 59 patients (37.3%, 95% CI 30.0-45.0%) had high (&amp;gt; 160 pg/ml) aldosterone level (hAld). hAld patients more often had QTc prolongation (44.1% versus 18.2%) and ventricular arrhythmias (83.1% vs 61.6%) compared to nAld patients (all Ps &amp;lt; 0.001). The number of ventricular premature complexes in 24 hours was higher in hAld group (median 214, range 64-758) compared to nAld (median 52, range 16-198, P &amp;lt; 0.003). hAld patients more often occurred bigemy, couple ventricular ectopy and nonsustained ventricular tachycardia (39.0% vs 19.0%, P = 0.01). In Cox regression models high aldosterone plasma level was the independent risk factors of QTc prolongation (odds ratio (OR) 1.6, 95% CI 1.1-5.7, P = 0.034) and prognostically unfavorable ventricular arrhythmias (OR 1.8, 95% CI 1.2-6.8, P = 0.024). Conclusion. In long-term HFpEF plasma aldosterone level is significantly related to QTc prolongation as well as ventricular arrhythmias.

Long-Term Arrhythmic Risk Assessment in Biopsy-Proven Myocarditis.

This study sought to assess long-term arrhythmic risk in patients with myocarditis who received an implantable cardioverter-defibrillator (ICD). The arrhythmic risk of patients with myocarditis overtime remains poorly known. The study enrolled 56 patients with biopsy-proven myocarditis who received an ICD for either primary (57%) or secondary prevention (43%) according to current guidelines. Clinical characteristics, biopsy findings, electrophysiological data from endocardial 3-dimensional electroanatomic voltage mapping, and device interrogation data were analyzed to detect arrhythmic events overtime. Coronary angiography excluded significant coronary artery disease in all patients. At a mean follow-up of 74 ± 60months (median 65months), 25 (45%) patients had major ventricular arrhythmias treated by ICD intervention (76% being terminated by ICD shock and 24% by antitachyarrhythmia burst pacing). At multivariable analysis, the presence of sustained ventricular tachycardia on admission (hazard ratio: 13.0; 95% confidence interval: 2.0 to 35.0; p=0.032) and the extension of the areas of low potentials at the bipolar endocardial mapping (hazard ratio: 1.19; 95% confidence interval: 1.04 to 1.37; p=0.013) were the only independent predictors of appropriate ICD interventions. A cutoff value of 10% of abnormal bipolar area at electroanatomical ventricular mapping discriminated patients with appropriate ICD interventions with a sensitivity of 89% and a specificity of 85%. The study demonstrates that the prevalence of life-threatening ventricular arrhythmias in patients with myocarditis receiving an ICD according to current guidelines is high and the arrhythmic risk persists late overtime. Electroanatomical ventricular mapping may be a useful tool to identify patients at greater arrhythmic risk.

2397Lesion-specific risk for sudden cardiac death or life-threatening ventricular arrhythmias in adult congenital heart disease

Abstract Background Risk models for primary prevention strategies in adult congenital heart disease (ACHD) must incorporate the heterogeneous risk for sudden cardiac death (SCD) and life-threatening ventricular arrhythmias (LTVA) as stratified by underlying lesion. Objectives To determine lesion-specific risk for SCD and LTVA in ACHD. Methods We analyzed 3311 ACHD patients (50% males) prospectively followed-up for 37510 person/years. SCD cases were confirmed by means of the Spanish National Death Registry. In addition, we identified all cases of resuscitated cardiac arrest or ventricular tachycardia requiring cardioversion. According to the incidence rate of the composite end-point of SCD and LTVA, lesions were stratified into four groups of risk. Cumulative freedom from SCD or LTVA in patients at high, moderate, low and very low risk were compared by using Cox regression model with left truncation. The c-index of this lesion-specific risk stratification was calculated by using the β-coefficients. The discriminative ability of this lesion-specific risk stratification was also tested in an external cohort of 203 SCD-LTVA cases and 2287 controls from 20 different centers. Results 71 patients experienced an event (53 SCD, 18 LTVA). Patients at highest risk (incidence rate &gt;1%) were those with Rastelli procedure, severe coronary abnormalities, complex Fallot and cyanotic patients, either Eisenmenger or non-Eisenmenger; at moderate risk (incidence rate 0.25–1.0%) non-complex Fallot, Mustard/Senning repair, Fontan procedures and congenitally corrected transposition; at low risk (incidence rate 0.1–0.25%) Ebstein anomaly and left heart lesions; and at very low risk (incidence rate &lt;0.1%) left-to-right shunts and right ventricular outflow lesions. The discriminative ability in a multicenter external cohort was excellent (c-index ranged from 0.748 to 0.819 by center). Lesion-specific risk and C-index Conclusions A lesion-specific risk stratification based on the incidence rate of SCD and LTVA was performed and validated. This approach could result in a more individualized risk assessment. Acknowledgement/Funding Instituto de Salud Carlos III, Ministerio de Economía y Competividad, Spain (Exp PI14/02099 and PI17/01327) and co-financed by FEDER

5956Multimodality prediction of life-threatening ventricular arrhythmia in patients with arrhythmogenic cardiomyopathy; a prospective cohort study

5956Multimodality prediction of life-threatening ventricular arrhythmia in patients with arrhythmogenic cardiomyopathy; a prospective cohort study

Prediction of Life-Threatening Ventricular Arrhythmia in Patients With Arrhythmogenic Cardiomyopathy: A Primary Prevention Cohort Study

ObjectivesThis study aimed to identify clinical, electrocardiographic (ECG) and cardiac imaging predictors of first-time life-threatening ventricular arrhythmia in patients with arrhythmogenic cardiomyopathy (AC). BackgroundThe role of clinical, electrocardiographic, and cardiac imaging parameters in risk stratification of patients without ventricular arrhythmia is unclear. MethodsWe followed consecutive AC probands and mutation-positive family members with no documented ventricular arrhythmia from time of diagnosis to first event. We assessed clinical, electrocardiographic, and cardiac imaging parameters according to Task Force Criteria of 2010 in addition to left ventricular (LV) and strain parameters. High-intensity exercise was defined as >6 metabolic equivalents. ResultsWe included 117 patients (29% probands, 50% female, age 40 ± 17 years). During 4.2 (interquartile range [IQR]: 2.4 to 7.4) years of follow-up, 18 (15%) patients experienced life-threatening ventricular arrhythmias. The 1-, 2-, and 5-year incidence was 6%, 9%, and 22%, respectively. History of high-intensity exercise, T-wave inversions ≥V3, and greater LV mechanical dispersion were the strongest risk markers (adjusted hazard ratio [HR]: 4.7 [95% confidence interval (CI): 1.2 to 17.5]; p = 0.02, 4.7 [95% CI: 1.6 to 13.9]; p = 0.005), and 1.4 [95% CI: 1.2 to 1.6] by 10-ms increments; p < 0.001, respectively). Median arrhythmia-free survival in patients with all risk factors was 1.2 (95% CI: 0.4 to 1.9) years, compared with an estimated 12.0 (95% CI: 11.5 to 12.5) years in patients without any risk factors. ConclusionsHistory of high-intensity exercise, electrocardiographic T-wave inversions ≥V3, and greater LV mechanical dispersion were strong predictors of life-threatening ventricular arrhythmia. Patients without any of these risk factors had minimal risk, whereas ≥2 risk factors increased the risk dramatically. This may help to make decisions on primary preventive implantable cardioverter defibrillator (ICD) therapy.

Can chronotropic incompetence predict life-threatening ventricular arrhythmias in patients with stable ischemic heart disease?

Background:Chronotropic incompetence has prognostic value of all-cause and cardiovascular mortality in both patients with asymptomatic and symptomatic ischemic heart disease (IHD), regardless of traditional risk factors. The aim of this study was to investigate the relationship between chronotropic response during exercise test and the development of ventricular arrhythmias.Methods:153 patients with stable ischemic heart disease were screened and observed during the 24 months since October 2014 in a university hospital in Astana Kazakhstan. They underwent bedside electrocardiography, 24h heart rate Holter monitoring, echocardiography, exercise stress test (treadmill) for assessment of chronotropic index calculating at first contact. Holter- electrocardiography was repeated three times (at 3, 6, 12 months of follow-up period) to reveal life-threatening ventricular arrhythmias.Results:The quantity of the ventricular extrasystoles was higher in the group with low chronotropic index. Low chronotropic index increased the risk of high grade ventricular extrasystoles more than two times (P=0.015); episodes of non-sustained VT more than three times (p<0.001); and episodes of sustained VT more than nine times (p<0.001).Conclusions:Chronotropic index less than 35.6 increases the risk for life-threatening ventricular arrhythmias in patients with stable chronicle ischemic heart disease irrespectively of severe left ventricle systolic dysfunction.

Prevalence and Prognostic Significance of Nonsustained Ventricular Tachycardia in Patients With a Left Ventricular Ejection Fraction from 35% to 50%

The risk of life-threatening ventricular arrhythmias in patients with mild-to-moderately reduced left ventricular ejection fraction (LVEF) is unknown. This retrospective case-control study aims to identify the prevalence, risk factors, and outcomes associated with the development of nonsustained ventricular tachycardia (NSVT) as documented on permanent pacemakers or implantable loop recorders in tertiary care center patients with an LVEF of 35% to 50%. Data pertaining to patient demographics, previous medical history, heart failure functional class, echocardiographic parameters, and survival were compared between the groups. Of the 326 patients with an LVEF within the target range, 90 patients (27.6%) had NSVT recorded on their device and 236 patients (72.4%) did not. Compared with patients without NSVT, patients with NSVT had a higher body mass index (28.4 kg/m2 vs 26.8 kg/m2, p = 0.02), more ischemic heart disease (57.8% vs 32.8%, p < 0.0001), higher left atrial volume index (45.8 ml/m2 vs 42.0 ml/m2, p = 0.04), and lower use of antiarrhythmic medications (4.4% vs 11.9%, p = 0.04). The presence of NSVT and the duration of NSVT had no relation to survival, supporting the notion that NSVT is a benign finding in patients with an LVEF of 35% to 50%.

Phosphorylation of serine96 of histidine-rich calcium-binding protein by the Fam20C kinase functions to prevent cardiac arrhythmia

Precise Ca cycling through the sarcoplasmic reticulum (SR), a Ca storage organelle, is critical for proper cardiac muscle function. This cycling initially involves SR release of Ca via the ryanodine receptor, which is regulated by its interacting proteins junctin and triadin. The sarco/endoplasmic reticulum Ca ATPase (SERCA) pump then refills SR Ca stores. Histidine-rich Ca-binding protein (HRC) resides in the lumen of the SR, where it contributes to the regulation of Ca cycling by protecting stressed or failing hearts. The common Ser96Ala human genetic variant of HRC strongly correlates with life-threatening ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy. However, the underlying molecular pathways of this disease remain undefined. Here, we demonstrate that family with sequence similarity 20C (Fam20C), a recently characterized protein kinase in the secretory pathway, phosphorylates HRC on Ser96. HRC Ser96 phosphorylation was confirmed in cells and human hearts. Furthermore, a Ser96Asp HRC variant, which mimics constitutive phosphorylation of Ser96, diminished delayed aftercontractions in HRC null cardiac myocytes. This HRC phosphomimetic variant was also able to rescue the aftercontractions elicited by the Ser96Ala variant, demonstrating that phosphorylation of Ser96 is critical for the cardioprotective function of HRC. Phosphorylation of HRC on Ser96 regulated the interactions of HRC with both triadin and SERCA2a, suggesting a unique mechanism for regulation of SR Ca homeostasis. This demonstration of the role of Fam20C-dependent phosphorylation in heart disease will open new avenues for potential therapeutic approaches against arrhythmias.

Pre-cardiac transplant amiodarone use is not associated with postoperative mortality: An updated meta-analysis

BackgroundAmiodarone remains the preferred agent for the treatment and prevention of life-threatening ventricular arrhythmias in patients with end-stage heart failure. While several reports suggest that pre-operative amiodarone exposure worsens outcomes in heart transplant recipients, other studies have failed to validate this relationship. We sought to clarify this issue by performing a meta-analysis of the available literature surrounding this topic. MethodsWe searched Medline, SCOPUS and the Cochrane Central Register of Controlled Trials through December 15th 2016, as well as proceedings from related conferences over the prior 3years. Included studies evaluated patients undergoing cardiac transplantation who had received pre-transplant amiodarone and reported postoperative mortality. Outcomes were pooled using a Hartung-Knapp random-effects model producing odds ratios (OR) and 95% confidence intervals (CI). Statistical heterogeneity was evaluated using the Cochrane Q statistic p-value and I2 value. Publication bias was assessed by visual inspection of funnel plots and using Egger's weighted regression statistic. ResultsNine studies including 16,509 participants were included in the overall analysis. Use of pre-transplant amiodarone was not associated with an increase in postoperative mortality versus control (OR 1.38, 95% 0.8 to 2.36). Moderate statistical heterogeneity was present (I2=45.8%, p=0.06); visual inspection of funnel plot analysis did not suggest publication bias. No association was noted between a longer duration of follow-up and higher odds of mortality with amiodarone use (p=0.91). ConclusionMeta-analysis of the available evidence suggests that pre-operative amiodarone exposure does not increase mortality in cardiac transplant recipients.

A New Electrocardiographic Marker of Sudden Death in Brugada Syndrome: The S-Wave in Lead I

BackgroundRisk stratification in asymptomatic patients remains by far the most important yet unresolved clinical problem in the Brugada syndrome (BrS). ObjectivesThis study sought to analyze the usefulness of electrocardiographic parameters as markers of sudden cardiac death (SCD) in BrS. MethodsThis study analyzed data from 347 consecutive patients (78.4% male; mean age 45 ± 13.1 years) with spontaneous type 1 BrS by ECG parameters but with no history of cardiac arrest (including 91.1% asymptomatic at presentation, 5.2% with a history of atrial fibrillation [AF], and 4% with a history of arrhythmic syncope). Electrocardiographic characteristics at the first clinic visit were analyzed to predict ventricular fibrillation (VF)/SCD during follow-up. ResultsDuring the follow-up (48 ± 38 months), 276 (79.5%) patients remained asymptomatic, 39 (11.2%) developed syncope, and 32 (9.2%) developed VF/SCD. Patients who developed VF/SCD had a lower prevalence of SCN5A gene mutations (p = 0.009) and a higher prevalence of positive electrophysiological study results (p < 0.0001), a family history of SCD (p = 0.03), and AF (p < 0.0001). The most powerful marker for VF/SCD was a significant S-wave (≥0.1 mV and/or ≥40 ms) in lead I. In the multivariate analysis, the duration of S-wave in lead I ≥40 ms (hazard ratio: 39.1) and AF (hazard ratio: 3.7) were independent predictors of VF/SCD during follow-up. Electroanatomic mapping in 12 patients showed an endocardial activation time significantly longer in patients with an S-wave in lead I, mostly because of a significant delay in the anterolateral right ventricular outflow tract. ConclusionsThe presence of a wide and/or large S-wave in lead I was a powerful predictor of life-threatening ventricular arrhythmias in patients with BrS and no history of cardiac arrest at presentation. However, the prognostic value of a significant S-wave in lead I should be confirmed by larger studies and by an independent confirmation cohort of healthy subjects.

Phantom Shocks and Automated Implantable Cardioverter Defibrillators

An automatic implantable cardioverter defibrillator (AICD) is a life-saving device that has become the standard of care for primary and secondary prevention of life-threatening ventricular arrhythmias in patients predisposed to these conditions. As AICD placement has become more commonplace, the phenomenon of “phantom shocks (PSs)” (in which the patient perceives that they are being shocked by their AICDwithout any objective proof that the shock occurred) has similarly become more prevalent. Theories on the etiology of PSs reported in the literature have focused on their representation of a posttraumatic re-experience phenomenon. Here, we present the case of a woman with PSs so severe that they precipitated a suicide attempt.

Cardiac Sarcoidosis: Electrophysiological Outcomes on Long‐Term Follow‐Up and the Role of the Implantable Cardioverter‐Defibrillator

The objectives of this study were to identify the predictors of life-threatening ventricular arrhythmias in patients with cardiac sarcoidosis (CS) and to evaluate the role of the implantable cardioverter-defibrillator (ICD) in this patient population. ICD implantation is a class IIA recommendation for patients with CS. However, some indications for ICD implantation in CS patients are still unclear and not enough data are available to establish predictors of malignant ventricular tachyarrhythmias in this group of patients. We retrospectively identified all consecutive patients who were diagnosed with CS, during the period from March 2002 to April 2010. Cardiac rhythm devices were regularly interrogated and clinical data recorded during follow-up visits. Thirty-three patients (17 male) with CS were identified. The mean age was 53 ± 11. The mean left ventricular ejection fraction (LVEF) was 41 ± 18%. Thirty patients received an ICD. Twelve patients (36.3%) had sustained ventricular arrhythmias. Eleven patients received appropriate therapies and 9 patients received inappropriate shocks, representing 36.7% and 30.0% of the ICD population, respectively. Patients who received appropriate ICD therapies were younger with mean age 47.4 ± 7.8, and had a lower mean LVEF 33.0 ± 12.0 compared to those who did not receive ICD therapies (P = 0.0301 and 0.0341, respectively). There were no other demographic, clinical, electrocardiographic, electrophysiological, or imaging markers that predicted the future occurrence of appropriate ICD therapies in our cohort of patients. CS is strongly associated with malignant ventricular arrhythmias. No specific predictors of such tachyarrhythmias emerged, other than young age and low LVEF.

Early Repolarization and Sudden Cardiac Death Due to an Acute Coronary Event

Tikkanen et al1 propose a significant and independent association between inferior/lateral ECG early repolarization (ER) patterns and sudden cardiac death (SCD) during an acute coronary event—an observation mainly based on the inclusion of ER pattern in multivariate predictive models for the occurrence of SCD, even after adjustment for several variables with usual prognostic value. Recent/new investigation has claimed a role for ER in the pathogenesis of idiopathic ventricular fibrillation or cardiac death in the community-based general population2 and in patients with ischemic or nonischemic chronic heart failure.3 ER (in particular, notching in the inferior leads) has also been shown to increase the risk of life-threatening ventricular arrhythmias in patients with coronary artery disease, even …