Reassessing the role of antitachycardia pacing in fast ventricular arrhythmias in primary prevention implantable cardioverter-defibrillator recipients: Results from MADIT-RIT

BACKGROUND: In Multicenter Automatic Defibrillator Implantation Trial - Reduce Inappropriate Therapy (MADIT-RIT), high-rate cutoff (arm B) and delayed therapy (arm C) reduced the risk of inappropriate implantable cardioverter-defibrillator (ICD) interventions when compared with conventional programming (arm A); however, appropriate but unnecessary therapies were not evaluated. OBJECTIVE: The purpose of this study was to assess the value of antitachycardia pacing (ATP) for fast ventricular arrhythmias (VAs) ≥ 200 beats/min in patients with primary prevention ICD. METHODS: We compared ATP only, ATP and shock, and shock only rates in patients in MADIT-RIT treated for VAs ≥ 200 beats/min. The only difference between these randomized groups was the time delay between ventricular tachycardia detection and therapy (3.4 seconds vs 4.9 seconds vs 14.4 seconds). RESULTS: In arm A, 11.5% patients had events, the initial therapy was ATP in 10.5% and shock in 1%, and the final therapy was ATP in 8% and shock in 3.5%. In arm B, 6.6% had events, 4.2% were initially treated with ATP and 2.4% with shock, and the final therapy was ATP in 2.8% and shock in 3.8%. In arm C, 4.7% had events, 2.5% were initially treated with ATP and 2.3% with shock, and the final therapy was ATP in 1.4% and shock in 3.3%. The final shock rate was similar in arm A vs arm B (3.5% vs 3.8%; P = .800) and in arm A vs arm C (3.5% vs 3.3%; P = .855) despite the marked discrepancy in initial ATP therapy utilization. CONCLUSION: In MADIT-RIT, there was a significant reduction in ATP interventions with therapy delays due to spontaneous termination, with no difference in shock therapies, suggesting that earlier interventions for VAs ≥ 200 beats/min are likely unnecessary, leading to an overestimation of the value of ATP in primary prevention ICD recipients

Primary prevention implantable cardioverter defibrillator in cardiac resynchronization therapy recipients with advanced chronic kidney disease

IntroductionThe implantable cardioverter defibrillator (ICD) is effective for the prevention of sudden cardiac death (SCD) in patients with heart failure and a reduced ejection fraction (HFrEF). The benefit of the ICD in patients with advanced CKD, remains elusive. Moreover, the benefit of the ICD in patients with advanced chronic kidney disease (CKD) and HFrEF who are cardiac resynchronization therapy (CRT) recipients may be attenuated.HypothesisWe hypothesized that patients with CKD who are CRT recipients may derive less benefit from the ICD due to the competing risk of dying prior to experiencing an arrhythmia.MethodsThe study population included 1,015 patients receiving CRT with defibrillator (CRT-D) device for primary prevention of SCD who were enrolled in either (Multicenter Automated Defibrillator Implantation Trial) MADIT-CRT trial or the Ranolazine in High-Risk Patients with Implanted Cardioverter Defibrillator (RAID) trial. The cohort was divided into two groups based on the stage of CKD: those with Stage 1 to 3a KD, labeled as (S1-S3a)KD. The second group included patients with Stage 3b to stage 5 kidney disease, labeled as (S3b-S5)KD. The primary endpoint was any ventricular tachycardia (VT) or ventricular fibrillation (VF) (Any VT/VF).ResultsThe cumulative incidence of Any VT/VF was 23.5% in patients with (S1-S3a)KD and 12.6% in those with (S3b-S5)KD (p < 0.001) The incidence of Death without Any VT/VF was 6.6% in patients with (S1-S3a)KD and 21.6% in patients with (S3b-S5)KD (p < 0.001). A Fine and Gray multivariate competing risk regression model showed that Patients with (S3b-S5)KD had a 43% less risk of experiencing Any VT/VF when compared to those with (S1-S3a)KD (HR = 0.56, 95% CI [0.33–0.94] p = 0.03. After two years of follow up, there was almost a 5-fold increased risk of Death without Any VT/VF among patients with (S3b-S5)KD when compared to those with (S1-S3a)KD [HR = 4.63, 95% CI (2.46–8.72), p for interaction with time = 0.012].ConclusionDue to their lower incidence of arrhythmias and higher risk of dying prior to experiencing an arrhythmia, the benefit of the ICD may be attenuated in CRT recipients with advanced CKD. Future prospective trials should evaluate whether CRT without a defibrillator may be more appropriate for these patients

Atrial Fibrillation in Long QT Syndrome by Genotype

BACKGROUND: Long QT syndrome (LQTS) is caused by the abnormal function of ion channels, which may also affect atrial electrophysiology and be associated with the risk of atrial fibrillation (AF). However, large-scale studies of AF risk among patients with LQTS and its relation to LQTS manifestations are lacking. We aimed to assess the risk of AF and its relationship to the LQTS genotype and the long-term prognosis in patients with LQTS. METHODS: Genotype-positive patients with LQTS (784 LQT1, 746 LQT2, and 233 LQT3) were compared with 2043 genotype-negative family members. Information on the occurrence of AF was based on physician-reported ECG-verified events. Multivariate Cox proportional hazards regression analyses were performed for ages 0 to 60 and after 60 years (reflecting an early and late-onset of AF) to assess the risk of incident AF by genotype and the relationship of AF to the risk of cardiac events defined as syncope, documented torsades de pointes, and aborted cardiac arrest or sudden cardiac death. RESULTS: In patients followed from birth to 60 years of age, patients with LQT3 had an increased risk of AF compared with genotype-negative family members (hazard ratio=6.62; 95% CI, 2.04-21.49; P<0.001), while neither LQT1 nor LQT2 demonstrated increased AF risk. After the age of 60 years, patients with LQT2 had significantly lower risk of AF compared with genotype-negative controls (hazard ratio=0.07; 95% CI, 0.01-0.53, P=0.011). AF was a significant predictor of cardiac events in patients with LQT3 through the age of 60 (hazard ratio=5.38; 95% CI, 1.17-24.82; P=0.031). CONCLUSIONS: Our data demonstrate an increased risk of early age AF in patients with LQT3 and also indicate a protective effect of the LQT2 genotype in it's association with a decreased risk of AF after the age of 60

Quantitative T-wave morphology assessment from surface ECG is linked with cardiac events risk in genotype-positive KCNH2 mutation carriers with normal QTc values

Introduction: Long QT syndrome (LQTS) mutation carriers have elevated the risk of cardiac events even in the absence of QTc prolongation; however, mutation penetrance in patients with normal QTc may be reflected in abnormal T-wave shape, particularly in KCNH2 mutation carriers. We aimed to assess whether the magnitude of a three-dimensional T-wave vector (TwVM) will identify KCNH2-mutation carriers with normal QTc at risk for cardiac events. Methods: Adult LQT2 patients with QTc < 460 ms in men and <470 ms in women (n = 113, age 42 ± 16 years, 43% male) were compared with genotype-negative family members (n = 1007). The TwVM was calculated using T-wave amplitudes in leads V6, II, and V2 as the square root of (TV62 + TII2 + (0.5*TV2)2). Cox regression analysis adjusted for gender and time-dependent beta-blocker use was performed to assess cardiac event (CE) risk, defined as syncope, aborted cardiac arrest, implantable cardioverter-defibrillator therapy, or sudden death. Results: Dichotomized by median of 0.30 mV, lower TwVM was associated with elevated CE risk compared to those with high TwVM (HR = 2.95, 95% CI, 1.25-6.98, P =.014) and also remained significant after including sex and time-dependent beta-blocker usage in the Cox regression analysis (HR = 2.64, 95% CI, 1.64-4.24, P <.001). However, these associations were found only in women but not in men who had low event rates. Conclusion: T-wave morphology quantified as repolarization vector magnitude using T-wave amplitudes retrieved from standard 12-lead electrocardiogram predicts cardiac events risk in LQT2 women and appears useful for risk stratification of KCNH2-mutation carriers without QTc prolongation

CHA 2 DS 2 -VASc Score and the Risk of Ventricular Tachyarrhythmic Events and Mortality in MADIT-CRT

Background We hypothesized that multiple cardiovascular comorbidities, incorporated in the CHA DS -VASc score, may be useful in the assessment of ventricular tachyarrhythmias (VTAs) and mortality risk in heart failure (HF) patients. Methods and Results We evaluated the association between the CHA DS -VASc score (dichotomized as high at the upper quartile [≥5] and further assessed as a continuous measure) and the risk of VTA and death among 1804 patients enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy). A high CHA DS -VASc score (n=464; 26%) was inversely associated with the risk of any VTA (hazard ratio [HR]: 0.64; =0.001), fast VTA >200 beats/min (HR; 0.51; <0.001), and appropriate implantable cardioverter-defibrillator shocks (HR: 0.60; <0.001). In contrast, a high score was directly correlated with mortality risk (HR: 1.92; <0.001) and the risk of HF or death (HR: 1.60; <0.001). Consistently, each 1-U increment in CHA DS -VASc was associated with a significant 13% ( =0.003) reduction in VTA risk but a corresponding 33% ( <0.001) increase in mortality risk. Patients with a high CHA DS -VASc score and left bundle-branch block derived a pronounced 53% ( <0.001) reduction in the risk of HF or death with cardiac resynchronization therapy with defibrillator versus implantable cardioverter-defibrillator-only therapy. Conclusions Our findings suggest that a high CHA DS -VASc score can be used to identify patients with mild HF who have low VTA risk and high morbidity or mortality risk and may derive a pronounced clinical benefit from cardiac resynchronization therapy without a defibrillator. These data suggest a possible role for the CHA DS -VASc score in device selection among candidates for biventricular pacing

Risk Stratification of Type 2 Long-QT Syndrome Mutation Carriers with Normal QTc Interval : The Value of Sex, T-Wave Morphology, and Mutation Type

Background: Long-QT (LQT) syndrome mutation carriers have higher risk of cardiac events than unaffected family members even in the absence of QTc prolongation. Changes in T-wave morphology may reflect penetrance of LQT syndrome mutations. We aimed to assess whether T-wave morphology may improve risk stratification of LQT2 mutation carriers with normal QTc interval. Methods: LQT2 mutation carriers with QTc <460 ms in men and <470 ms in women (n=154) were compared with unaffected family members (n=1007). Baseline ECGs recorded at age ≥18 years underwent blinded assessment. Flat, notched, or negative T waves in leads II or V5 were considered abnormal. Cox regression analysis was performed to assess the association between T-wave morphology, the presence of mutations in the pore region of KCNH2, and the risk of cardiac events defined as syncope, aborted cardiac arrest, defibrillator therapy, or sudden cardiac death. Sex-specific associations were estimated using interactions terms. Results: LQT2 female carriers with abnormal T-wave morphology had significantly higher risk of cardiac events compared with LQT2 female carriers with normal T waves (hazard ratio, 3.31; 95% confidence interval, 1.68-6.52; P=0.001), whereas this association was not significant in men. LQT2 men with pore location of mutations have significantly higher risk of cardiac events than those with nonpore mutations (hazard ratio, 6.01; 95% confidence interval, 1.50-24.08; P=0.011), whereas no such association was found in women. Conclusions: The risk of cardiac events in LQT2 carriers with normal QTc is associated with abnormal T-wave morphology in women and pore location of mutation in men. The findings further indicate sex-specific differences in phenotype and genotype relationship in LQT2 patients

The QT scale: a weight scale measuring the QTc interval

"This is the peer reviewed version of the following article: [Ann Noninvasive Electrocardiol 2017;22(1):e12378, DOI: 10.1111/anec.12378], which has been published in final form at [http://onlinelibrary.wiley.com/doi/10.1111/anec.12378/pdf]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."Despite the strong evidence of the clinical utility of QTc prolongation as a surrogate marker of cardiac risk, QTc measurement is not part of clinical routine either in hospital or in physician of fi ces. We evaluated a novel device ( “the QT scale”) to measure heart rate (HR) and QTc interval.Peer Reviewe

Initial Development of the Myasthenia Gravis-Health Index (MG-HI): Measuring the Most Prevalent and Impactful Symptoms Identified in Myasthenia Gravis (P10-11.013)

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