Comparison of Low and Full Dose Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Renal Dysfunction (from a National Registry).

The use of direct oral anticoagulants for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) is robust. However, the efficacy and safety of different dosage in patients with renal dysfunction is still a clinical challenge. We aimed to evaluate the clinical characteristics and outcomes of patients treated with apixaban in its different doses. A multicenter prospective cohort study, where consecutive eligible apixaban or warfarin treated patients with NVAF and renal impairment, were registered. Patients were followed-up for clinical events over a mean period of 1 year. Analyses were performed according to the dose of apixaban given, with consideration to the standard indications for dose reduction. Primary outcome was a composite of 1-year mortality, stroke or systemic embolism, major bleeding and myocardial infarction, while secondary outcomes included those components separated. Among the study population (n = 2,140), risk of composite outcome was significantly lower in the high dose apixaban group (10%, n = 491) than the low dose group (18%, n = 673) and the warfarin group (18%, n = 976) p <0.001. Results of 1-year mortality were similar. Apixaban dosing analysis revealed 65% of patients were appropriately dosed, while 31% were under-dosed and 4% were over-dosed. Furthermore, 53% of patients treated with low dose apixaban were under-dosed. Propensity score analysis revealed that patients who were appropriately treated with low-dose apixaban had a trend towards better composite outcome and mortality than 1:1 matched warfarin treated patients (18% vs 24%, p = 0.09 and 16% vs 23%, p = 0.06, respectively). Overall, appropriately dosed apixaban treated patients at any dose had significantly better outcomes than matched warfarin treated patients (composite outcome probability of 13.1% vs 18.6%, p = 0.007). In conclusion, apixaban at any dose is a reasonable alternative to warfarin in patients with renal impairment, possibly associated with improved outcomes.

Effect of supplemented intake of omega-3 fatty acids on arrhythmias in patients with ICD: fish oil therapy may reduce ventricular arrhythmia.

PURPOSE: The aim of this study was to evaluate the effects of fish oils, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on ventricular tachyarrhythmic episodes (VTEs) in implantable cardioverter defibrillator (ICD) recipients with ischemic cardiomyopathy. METHODS: One hundred five ICD recipients with ischemic cardiomyopathy received 3.6 g of EPA and DHA and placebo for 6 months, each at a random order, with a 4-month washout period between treatments. Eighty-seven patients completed the 16-month study protocol. The primary end point was any VTE (including sustained and non-sustained ventricular tachycardias at a rate of >150 bpm) as recorded by the ICDs. Secondary end points included device therapy (anti-tachycardia pacing (ATP) or shocks). RESULTS: During treatment with fish oils, there was a significant increase in EPA and DHA concentrations in red blood cells (RBCs) and subcutaneous fat tissue. Among 87 patients who completed the study protocol, the mean number of VTEs was significantly lower during treatment with fish oil (1.7) vs. placebo (5.6; p = 0.035). Appropriate device therapy for VTE occurred in 18 (21%) patients. Fish oil therapy was associated with a trend toward fewer VTEs terminated with ATP (2.8 ± 13.7 vs. 0.5 ± 2.1, respectively; p = 0.077). VTE terminated by ICD shocks, however, was rare, and rates were similar between both groups (0.11 ± 0.6 vs. 0.10 ± 0.4, p = not significant, respectively). CONCLUSIONS: Our data suggest that fish oil therapy may be associated with a reduction in the frequency of VTE in ICD recipients with ischemic cardiomyopathy.

Cryotherapy ablation of parahisian accessory pathways in children.

BACKGROUND: Because of its safety profile, cryoablation has become an alternative therapy for septal arrhythmias, including parahisian accessory pathways (APs). Data regarding its efficacy, safety, and late outcome for parahisian APs in children are limited. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of cryoablation of parahisian APs in children. METHODS: Fifty-nine cryoablations of parahisian APs were performed in 50 patients [76% males; median age 16.5 years (range 5.3-20 years)]. Thirty-three had manifest APs and 17 had concealed APs. The time to effect was defined as the duration of time from reaching -30°C to the disappearance of AP during the cryomapping phase. The acute success rate for the first ablation was 94% (47/50). RESULTS: Mean fluoroscopy time and number of cryoablations were 28.5 ± 23.3 minutes and 2.6 ± 1.2 seconds, respectively. The time to effect was 8.5 ± 7.1 seconds. The overall recurrence rate was 14.9%, decreasing from 40% in the first 10 cases to 8.1% in the next 37 (P <.02). Multivariate analysis showed that the only independent predictor for recurrence rate was time to effect <10 seconds (P <.001). A high recurrence rate was also associated with concealed APs and ablation during supraventricular tachycardia (P <.03 and P <.05, respectively). The patients who had recurrence underwent a second successful cryoablation. During median follow-up of 59.7 months (range 6-102 months), a long-term success rate of 94% was achieved. No permanent ablation-related complications occurred. CONCLUSION: Cryoablation of parahisian APs has excellent short- and long-term efficacy and safety profile. Increased physician experience is associated with a reduced recurrence rate.

Congenital long QT syndromes: prevalence, pathophysiology and management.

Long QT syndrome is a genetic disorder associated with life threatening ventricular arrhythmias and sudden death. This inherited arrhythmic disorder exhibits genetic heterogeneity, incomplete penetrance, and variable expressivity. During the past two decades there have been major advancements in understanding the genotype-phenotype correlations in LQTS. This genotype-phenotype relationship can lead to improved management of LQTS. However, development of genotype-specific or mutation-specific management strategies is very challenging. This review describes the pathophysiology of LQTS, genotype-phenotype correlations, and focuses on the management of LQTS. In general, the treatment of LQTS consists of lifestyle modifications, medical therapy with beta-blockers, device and surgical therapy. We further summarize current data on the efficacy of pharmacological treatment options for the three most prevalent LQTS variants including beta-blockers in LQT1, LQT2 and LQT3, sodium channel blockers and ranolazine for LQT3, potassium supplementation and spironolactone for LQT2, and possibly sex hormone-based therapy for LQT2.

Temporal trends in the use of high-dose potent statins following acute coronary syndrome in Israel.

OBJECTIVES: This study aimed to evaluate factors associated with the prescription of high-dose potent statin (HDPS) therapy following hospitalization for acute coronary events. STUDY DESIGN: Sub-analysis was made using the data of 3,525 patients enrolled in the 2008 and 2010 Acute Coronary Syndrome Israeli Surveys (ACSIS). METHODS: Analyses were carried out to identify demographic and clinical factors associated with the prescription of HDPS therapy (atorvastatin 40-80 mg/day or rosuvastatin 20-40 mg/day) at discharge compared with the prescription of lower-dose statins. RESULTS: Among the study patients, 1,387 (39%) were discharged on HDPS, 1,860 (53%) with lower-dose statin regimens and 278 (8%) with no recommendation for statin therapy. Multivariate logistic regression analysis showed that pre-admission usage of HDPS and participation in the more recent (2010) ACSIS survey were independently associated with a higher likelihood of HDPS prescription at discharge from the index event (odds ratio, OR, 21.07, p < 0.001, and 5.61, p < 0.001, respectively), whereas factors independently associated with a lack of HDPS prescription included age >75 years (OR 0.76, p = 0.03), low-density lipoprotein-cholesterol levels <100 mg/dl on admission (OR 0.67, p < 0.001) and a history of heart failure prior to the index hospitalization (OR 0.54, p = 0.0018). The 30-day compliance with the HDPS regimen was 98%. CONCLUSIONS: The findings show increased use of HDPS therapy in acute coronary syndrome (ACS) patients, although this mode of medical therapy is still underutilized in the important subset of high-risk ACS patients.

Genotype-specific risk stratification and management of patients with long QT syndrome.

Long QT syndrome (LQTS) is an inherited disorder associated with life-threatening ventricular arrhythmias. An understanding of the relationship between the genotype and phenotype characteristics of LQTS can lead to improved risk stratification and management of this hereditary arrhythmogenic disorder. Risk stratification in LQTS relies on combined assessment of clinical, electrocardiographic, and mutations-specific factors. Studies have shown that there are genotype-specific risk factors for arrhythmic events including age, gender, resting heart rate, QT corrected for heart rate, prior syncope, the postpartum period, menopause, mutation location, type of mutation, the biophysical function of the mutation, and response to beta-blockers. Importantly, genotype-specific therapeutic options have been suggested. Lifestyle changes are recommended according to the prevalent trigger for cardiac events. Beta-blockers confer greater benefit among patients with LQT1 with the greatest benefit among those with cytoplasmic loops mutations; specific beta-blocker agents may provide greater protection than other agents in specific LQTS genotypes. Potassium supplementation and sex hormone-based therapy may protect patients with LQT2. Sodium channel blockers such as mexiletine, flecainide, and ranolazine could be treatment options in LQT3.

In silico cardiac risk assessment in patients with long QT syndrome: type 1: clinical predictability of cardiac models.

OBJECTIVES: The study was designed to assess the ability of computer-simulated electrocardiography parameters to predict clinical outcomes and to risk-stratify patients with long QT syndrome type 1 (LQT1). BACKGROUND: Although attempts have been made to correlate mutation-specific ion channel dysfunction with patient phenotype in long QT syndrome, these have been largely unsuccessful. Systems-level computational models can be used to predict consequences of complex changes in channel function to the overall heart rhythm. METHODS: A total of 633 LQT1-genotyped subjects with 34 mutations from multinational long QT syndrome registries were studied. Cellular electrophysiology function was determined for the mutations and introduced in a 1-dimensional transmural electrocardiography computer model. The mutation effect on transmural repolarization was determined for each mutation and related to the risk for cardiac events (syncope, aborted cardiac arrest, and sudden cardiac death) among patients. RESULTS: Multivariate analysis showed that mutation-specific transmural repolarization prolongation (TRP) was associated with an increased risk for cardiac events (35% per 10-ms increment [p < 0.0001]; ≥upper quartile hazard ratio: 2.80 [p < 0.0001]) and life-threatening events (aborted cardiac arrest/sudden cardiac death: 27% per 10-ms increment [p = 0.03]; ≥upper quartile hazard ratio: 2.24 [p = 0.002]) independently of patients' individual QT interval corrected for heart rate (QTc). Subgroup analysis showed that among patients with mild to moderate QTc duration (<500 ms), the risk associated with TRP was maintained (36% per 10 ms [p < 0.0001]), whereas the patient's individual QTc was not associated with a significant risk increase after adjustment for TRP. CONCLUSIONS: These findings suggest that simulated repolarization can be used to predict clinical outcomes and to improve risk stratification in patients with LQT1, with a more pronounced effect among patients with a lower-range QTc, in whom a patient's individual QTc may provide less incremental prognostic information.

Atrial burst pacing with biphasic and monophasic waveforms for atrial fibrillation.

BACKGROUND: Biphasic pacing is a novel mode of pacing that was suggested to increase cardiac conduction velocity as compared with cathodal monophasic pacing. We aimed to evaluate the safety and efficacy of rapid atrial pacing to convert atrial fibrillation (AF) to normal sinus rhythm. METHODS: Multiple biphasic (anodal/cathodal), reverse biphasic (cathodal/anodal), and monophasic (cathodal) atrial pacing therapies were performed among 12 patients undergoing left atrial catheter ablation for AF. The efficacy end point was successful conversion of AF to sinus rhythm, and safety end point no induction of ventricular arrhythmias. Patients were paced at three cycle lengths (100, 200, and 333 msec) for 60 seconds at three locations (right and left atrial appendages and coronary sinus). RESULTS: Among the 66 biphasic (anodal/cathodal) pacing procedures one procedure in a patient with chronic AF, which involved pacing at the left atrial appendage with a cycle length of 200 msec, led to conversion of AF to sinus rhythm. None of the 66 monophasic pacing procedures or the 66 reverse biphasic (cathodal/anodal) pacing procedures was associated with AF termination. None of the biphasic pacing procedures was associated with induction of ventricular arrhythmias. CONCLUSIONS: Rapid atrial pacing using a variety of waveforms at the cycle length and output used in the current study was found to be safe. There was a single success in converting a chronic AF to sinus rhythm.