Dexmedetomidine Sedation for Paroxysmal Supraventricular Tachycardia Ablation Is Not Associated With Alteration of Arrhythmia Inducibility.

BACKGROUND: Dexmedetomidine (Dex) is an attractive agent for procedural sedation due to its unique pharmacodynamic profile, specifically affording predictable sedation without concurrent respiratory depression. However, Dex has previously been reported to prevent or terminate arrhythmias. The purpose of this study was to investigate paroxysmal supraventricular tachycardia (PSVT) inducibility and homeostatic stability during electrophysiology studies (EPSs) and ablation when a standardized Dex protocol was used as the primary sedation agent. METHODS: We performed a retrospective review of 163 consecutive procedures for PSVT ablation that received Dex as the primary sedative with adjunct fentanyl and midazolam boluses (DEX-FENT-MIDAZ). This cohort was compared to 163 consecutive control procedures wherein strictly fentanyl and midazolam were used for sedation. The primary outcome reviewed was PSVT inducibility assessed before ablation. Reviewed secondary outcomes included level of sedation and intraprocedure hemodynamics and oxygenation. RESULTS: The arrhythmia profiles of the DEX-FENT-MIDAZ and control cohorts were very similar. The overall incidence of a "negative" EPSs in which arrhythmia was not induced was 24% in the DEX-FENT-MIDAZ group and 26% in the control group (P = .7). Unintended deep sedation was significantly less with DEX-FENT-MIDAZ (4.3% vs 27%; P ≤ .0001). However, DEX-FENT-MIDAZ use was associated with a higher incidence of intraprocedure hypotension. CONCLUSIONS: Dex sedation during EPSs is not associated with a reduction in PSVT inducibility. The therapeutic utility of Dex during EPS arises from the predictable sedation Dex affords but is associated with an increased incidence of intraprocedure hypotension.

Health-Related Quality of Life in the Spironolactone to Reduce ICD Therapy (SPIRIT) Trial.

To describe health related quality of life (HRQOL) and symptoms in the SPIRIT trial and determine effects of implantable cardioverter defibrillator (ICD) shocks on HRQOL over 24 months. Ninety participants aged 66 ± 10 years, 96% men, 75% with NYHA class II, with an ICD were randomized to spironolactone 25 mg (N = 44) or placebo (N = 46). HRQOL was measured every 6 months for 24 months using: Patient Concerns Assessment (PCA), Short Form Health Survey-Veterans Version (SF-36V), and Kansas City Cardiomyopathy Questionnaire (KCCQ). Linear mixed modeling compared changes in HRQOL over-time and ANCOVA compared HRQOL between those getting an ICD shock or not. Over 24-months, there were no differences in HRQOL between the spironolactone versus placebo groups. Those with at least one ICD shock reported significantly lower HRQOL and more symptoms at 6- and 24-months. Patients receiving one or more ICD shocks reported significant reductions in HRQOL and higher symptoms.

Adaptive Cardiac Resynchronization Therapy Effect on Electrical Dyssynchrony (aCRT-ELSYNC): A randomized controlled trial.

BACKGROUND: Adaptive cardiac resynchronization therapy (aCRT) is known to have clinical benefits over conventional CRT, but the mechanisms are unclear. OBJECTIVE: Compare effects of aCRT and conventional CRT on electrical dyssynchrony. METHODS: A prospective, double-blind, 1:1 parallel-group assignment randomized controlled trial in patients receiving CRT for routine clinical indications. Participants underwent cardiac computed tomography and 128-electrode body surface mapping. The primary outcome was change in electrical dyssynchrony measured on the epicardial surface using noninvasive electrocardiographic imaging before and 6 months post-CRT. Ventricular electrical uncoupling (VEU) was calculated as the difference between the mean left ventricular (LV) and right ventricular (RV) activation times. An electrical dyssynchrony index (EDI) was computed as the standard deviation of local epicardial activation times. RESULTS: We randomized 27 participants (aged 64 ± 12 years; 34% female; 53% ischemic cardiomyopathy; LV ejection fraction 28% ± 8%; QRS duration 155 ± 21 ms; typical left bundle branch block [LBBB] in 13%) to conventional CRT (n = 15) vs aCRT (n = 12). In atypical LBBB (n = 11; 41%) with S waves in V5-V6, conduction block occurred in the anterior RV, as opposed to the interventricular groove in strict LBBB. As compared to baseline, VEU reduced post-CRT in the aCRT (median reduction 18.9 [interquartile range 4.3-29.2 ms; P = .034]), but not in the conventional CRT (21.4 [-30.0 to 49.9 ms; P = .525]) group. There were no differences in the degree of change in VEU and EDI indices between treatment groups. CONCLUSION: The effect of aCRT and conventional CRT on electrical dyssynchrony is largely similar, but only aCRT harmoniously reduced interventricular dyssynchrony by reducing RV uncoupling.

Syncope, seizure, or both? An unusual case of complete heart block.

Syncope and epileptic seizures have common presenting features that make it difficult to determine if a patient's collapse is primarily cardiac or neurologic. The distinction is blurred further if epileptic neural activity provokes cardiac arrhythmias known to cause syncope. We present a case of convulsive movements, progressive atrioventricular block, and syncope in a patient known to have epilepsy. The history, serial electrocardiographic tracings, and other diagnostic tests strongly suggest the ictal bradycardia syndrome. The case illustrates interesting aspects of central autonomic function and the diagnostic and therapeutic dilemmas of evaluating and treating patients who present with this problem.

Outcomes of Telemedicine Video-Conferencing Clinic Versus In-Person Clinic Follow-Up for Implantable Cardioverter-Defibrillator Recipients.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) recipients require close follow-up that can be difficult for patients who have to travel long distances for clinic follow-up. We aimed to compare clinical outcomes between ICD patients followed-up in a telemedicine video-conferencing clinic (TMVC) and a conventional in-person clinic (CIC). We hypothesized that outcomes of patients followed in the TMVC are noninferior to the CIC. METHODS AND RESULTS: This retrospective study compares time to first appropriate ICD therapy, time to first inappropriate ICD therapy, time to first shock, and overall survival in patients followed in TMVC compared with CIC between 2001 and 2016. Two hundred and eighty-seven patients were followed in the TMVC group and 236 patients in the CIC. The average age of the TMVC and CIC groups was 64.13±9.38 and 65.23±8.57 years, respectively (P=0.164). There was no difference in the modified Seattle heart failure model score between the 2 groups (-0.12±1.0 versus -0.21±0.99; P=0.287). The Charlson comorbidity index score was higher in the CIC group compared with the TMVC group (7.0 versus 6.0; P=0.01). Mean duration of follow-up was 4.8 years. Adjusted and unadjusted tests of noninferiority found TMVC was not inferior to in-person follow-up for the prespecified outcomes. CONCLUSIONS: Video-conferencing ICD follow-up for patients in areas where electrophysiology subspecialty care is not available leads to outcomes that are noninferior to CIC follow-up.

Successful Ablation of Epicardial Premature Ventricular Complexes Near the Great Cardiac Vein from the Left Ventricular Endocardium Despite Predictors of Failure.

Mapping and ablating premature ventricular complexes (PVCs) that originate near the great cardiac vein (GCV) and anterior interventricular vein (AIV) can pose several challenges related to the advancement and positioning of catheters within these veins, the delivery of effective lesions, and the risk of collateral injury to the left coronary arteries and left phrenic nerve. When ablation of these PVCs from inside the GCV/AIV is not possible, a systematic assessment of nearby vantage points, such as the left coronary cusp (LCC) and left ventricular (LV) endocardial breakout site, should be considered, in addition to the performance of a more invasive epicardial ablation procedure via a percutaneous pericardial puncture or thoracotomy. Several electrocardiographic, anatomic, and electrogram timing features have been shown to predict the likelihood of successful ablation from a non-epicardial site, such as the LCC or LV endocardium, but none of these spots is considered to be a perfect location. The case described here in this report is a demonstration of a safe and successful ablation of GCV PVCs from the LV endocardial breakout site using adequate power and lesion duration, even when the site was 17 mm away from the putative origin, and some previously described electrocardiographic and electrogram-based predictors of success suggested the outcome would not be positive.

Oral anticoagulation in elderly adults with atrial fibrillation: integrating new options with old concepts.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and the second most common cardiovascular condition in adults in the United States. It is prevalent in the elderly population and is an important risk factor for stroke. Oral anticoagulation offers significant protection against AF-related thromboembolic events, but several complex issues that contribute to its underuse in elderly adults surround it. To aid clinicians in their approach to these problems, a comprehensive PubMed-based search of the literature published in English from 1990 through July 2012 was conducted using the following terms or combination of terms: atrial fibrillation, elderly, antiplatelet, anticoagulation, stroke, bleeding, hemorrhage, and falls. Additional references were identified in a manual search of bibliographies in retrieved articles. The data were then synthesized to address the most relevant questions regarding anticoagulation in elderly adults, including fall risk, responsiveness to warfarin, physician perception of risks, and other barriers to the prescription of anticoagulants. Recently proposed risk-stratification schemes for stroke and hemorrhage that could refine the selection of antithrombotic therapy for AF are highlighted. Finally, available data on the use of antiplatelet therapy, warfarin, and new oral anticoagulants (direct thrombin inhibitor and factor Xa inhibitors) in AF are summarized.

The effect of spironolactone on ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators.

BACKGROUND: Previous studies have suggested that aldosterone blockade can reduce the incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients with heart failure. The SPIronolactone to Reduce ICD Therapy (SPIRIT) trial was designed to test the hypothesis that spironolactone reduces the incidence of VT/VF in patients with implantable cardioverter-defibrillators (ICDs) who are at moderately high risk for recurrent VT/VF. METHODS AND RESULTS: Ninety patients who had ICDs who were at moderately high risk for recurrent VT/VF and who were not candidates for spironolactone by current heart failure guidelines were randomized to receive spironolactone 25 mg daily or placebo in a double-blind fashion. All patients had previously received ICD therapy (shock or antitachycardia pacing) for VT/VF within 2 years of randomization or an ICD for secondary prevention of VT/VF within 6 months of randomization. The primary end point was time to first recurrence of VT/VF requiring ICD therapy. After a median follow-up of 35 months, the Kaplan-Meier probability estimates for VT/VF requiring ICD therapy were 68.7% in the placebo group and 84.7% in the spironolactone group. Compared with placebo, spironolactone was associated with a similar risk of VT/VF (hazard ratio, 1.01; 95% CI, 0.64-1.83; P=0.71). There was no significant difference between the median times to first VT/VF recurrence requiring ICD therapy in the 2 groups. CONCLUSIONS: In patients with ICDs who were at moderately high risk for recurrent VT/VF on account of a recent VT/VF event that was either sustained or treated by the ICD and who were not candidates for spironolactone by current heart failure guidelines, spironolactone did not delay the first recurrence of VT/VF or reduce the risk of recurrent VT/VF.

Nonsense-mediated mRNA decay caused by a frameshift mutation in a large kindred of type 2 long QT syndrome.

BACKGROUND: Nonsense and frameshift mutations are common in congenital long QT syndrome type 2 (LQT2). We previously demonstrated that hERG nonsense mutations cause degradation of mutant mRNA by nonsense-mediated mRNA decay (NMD) and are associated with mild clinical phenotypes. The impact of NMD on the expression of hERG frameshift mutations and their phenotypic severity is not clear. OBJECTIVE: The purpose of this study was to examine the role of NMD in the pathogenesis of a hERG frameshift mutation, P926AfsX14, identified in a large LQT2 kindred and characterize genotype-phenotype correlations. METHODS: Genetic screening was performed among family members. Phenotyping was performed by assessment of ECGs and LQTS-related cardiac events. The functional effect of P926AfsX14 was studied using hERG cDNA and minigene constructs expressed in HEK293 cells. RESULTS: Significant cardiac events occurred in carriers of the P926AfsX14 mutation. When expressed from cDNA, the P926AfsX14 mutant channel was only mildly defective. However, when expressed from a minigene, the P926AfsX14 mutation caused a significant reduction in mutant mRNA, protein, and hERG current. Inhibition of NMD by RNA interference knockdown of up-frameshift protein 1 partially restored expression of mutant mRNA and protein and led to a significant increase in hERG current in the mutant cells. These results suggest that NMD is involved in the pathogenic mechanism of the P926AfsX14 mutation. CONCLUSION: Our findings suggest that the hERG frameshift mutation P926AfsX14 primarily results in degradation of mutant mRNA by the NMD pathway rather than production of truncated proteins. When combined with environmental triggers and genetic modifiers, LQT2 frameshift mutations associated with NMD can manifest with a severe clinical phenotype.

Coxibs and heart disease: what we have learned and what else we need to know.

Since their approval in 1998, the popularity of selective cyclooxygenase-2 (COX2) inhibitors has swung from a domination of drug sales to serious disputes about their cardiovascular safety. Despite the numerous studies on COX2 inhibitors that have emerged, drawing conclusions about their cardiovascular safety has been complicated by conflicting results, underpowered clinical trials, and the lack of a placebo group and use of post hoc analyses in many trials. Nonetheless, certain conclusions can be made with reasonable accuracy. This review addresses the controversy in 3 segments. It begins with a discussion of the several mechanisms proposed to explain how selective COX2 inhibition impacts the cardiovascular system. This is followed by a recount of the several clinical studies that delved into the cardiovascular outcomes associated with COX2 inhibitors. Finally, answers to key questions are provided to assist the clinician in devising a systematic approach to the risk-benefit analysis of COX2 inhibitors in actual practice.

Sudden death prophylaxis in heart failure.

Sudden cardiac death (SCD) is the leading cause of mortality in heart failure (HF). Today the implantable cardioverter-defibrillator (ICD) has become a commonplace therapy around the world for patients with both ischemic and non-ischemic cardiomyopathy and an ejection fraction (EF) < or = 35%. However, EF alone does not discriminate between the modes of death from HF (sudden arrhythmic death vs. non-sudden death). Other risk statifiers, such as electrophysiologic study and microvolt T-wave alternans testing, should therefore be used in the appropriate settings to minimize the number of unnecessary device implants. In addition, left ventricular mechanical dyssynchrony has now become recognized as an additional major marker of cardiac mortality. Its assessment should entail echocardiography rather than measurement of the QRS duration. This will allow us to better integrate the ability of cardiac resynchronization therapy (CRT) in enhancing cardiac function with the ability of an ICD in preventing SCD. This review aims to: 1) give a synthesis of the published evidence regarding the value of implantable ICDs and CRT in the primary prophylaxis of SCD in HF; 2) discuss controversial clinical issues in this area; and 3) recommend practical device-based management strategies.