Novel High-Throughput Quantitation of Potent hERG Blocker Dofetilide in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry: Application in a Phase 1 ECG Biomarker Validation Study

Abstract The authors developed a novel, sensitive high-throughput ultra-performance liquid chromatography-tandem mass spectrometric method for the determination of dofetilide in human plasma. To compensate for the matrix effect, a deuterated internal standard was used. The method employed a very low sample volume (50 μL) of plasma for sample processing by using simple protein precipitation extraction in a 96-well plate. The extracted samples were chromatographed on an Acquity BEH C18 column (2.1 × 100 mm, 1.7 μm) and eluted in a gradient manner at a flow rate of 0.5 mL/min for 2 min using 5 mM ammonium formate (0.1% formic acid) and methanol. The calibration curve was linear from 25 to 2,500 pg/mL with a correlation coefficient (r2) ≥ 0.99 (0.9969–0.9980; n = 3). The developed method was validated as per the current United States Food and Drug Administration’s guidance for industry on ‘Bioanalytical Method Validation’. The multiple reaction–monitoring mode was employed for quantitation of dofetilide with m/z 442.2/198.2 and dofetilide d4 with m/z 446.2/198.2. The validated method was used for evaluation of dofetilide concentration in the Comprehensive in vitro Proarrhythmia Assay phase 1 electrocardiogramic biomarker validation study.</jats:p

Prevalence of manual Strauss LBBB criteria in patients diagnosed with the automated Glasgow LBBB criteria.

About one-third of patients undergoing cardiac resynchronization therapy because of left bundle branch block (LBBB) and heart failure do not improve. Strauss et al. have developed strict criteria to more accurately define complete LBBB in this patient group. The aim of this study was to investigate the prevalence of the manual application of the Strauss criteria for LBBB (QRS≥140ms in men, ≥130ms in women, along with mid-QRS notching/slurring) in consecutive patients who have been diagnosed with LBBB by the automated Glasgow criteria (QRS≥120ms)

Abstract 18117: Trends in the Utilization and Outcomes of Medicare Beneficiaries Undergoing Catheter Ablation for Ventricular Tachycardia

Background: Sustained ventricular tachycardia (VT) is a significant cause of sudden death, progressive ventricular dysfunction, and heart failure hospitalizations. Radiofrequency catheter ablation is used to control incessant VT and prevent or reduce the frequency of VT episodes. However, data regarding mortality and complication rates with VT ablation are limited. Objective: To measure the incidence of procedural complications, repeat ablations, hospitalization for heart failure and ventricular tachycardia, and short and long term mortality in patients undergoing VT ablation. Methods: We conducted a population-based, retrospective cohort study of all fee-for-service Medicare beneficiaries who underwent catheter ablation for VT between 2000 and 2012. The main outcome measures were major complications within 30 days and 1-year rates of death, repeat ablation and heart failure and VT hospitalization. Results: There were 21,073 patients that received a VT ablation during the study period (mean age 70 years; 77% were men; 90% were white). The ablation frequency increased from 647 in 2000 to 2,760 in 2012. The 30-day incidence of pericardial complications was 2.3%, vascular complications 6.8%, stroke or transient ischemic attack 1.5%, need for mechanical circulatory support 2.3%, and death 4.2%. The 1-year incidence per 1,000 person-years for repeat ablation was 81, death 176, and hospitalization for heart failure and VT 156 and 272, respectively (Figure). Conclusions: Utilization of catheter ablation for VT has increased over the past 12 years. Major complications after VT ablation are relatively infrequent, but not trivial. These findings should inform discussion of potential procedural complications and long term prognosis and may have considerable implications when discussing treatment options for patients with VT. </jats:p

Right-Ventricular Enlargement in Arrhythmogenic Right-Ventricular Cardiomyopathy Is Associated with Decreased QRS Amplitudes and T-Wave Negativity

Background Arrhythmogenic right-ventricular cardiomyopathy (ARVC) can lead to RV dilatation. We hypothesized that electrocardiographic characteristics including QRS amplitudes in the extremity- and precordial leads, the S amplitude in lead V-1, and extent of T-wave negativity over the precordial leads are related to RV dilatation in this condition. MethodsIn 42 ARVC patients and 42 controls, we correlated total QRS amplitude in the extremity leads (Sigma QRS(ext)), precordial leads (Sigma QRS(prec)) and in all leads (Sigma QRS(tot) : summation of Sigma QRS(ext) and Sigma QRS(prec)), S amplitude in lead V-1 and the extent of T-wave inversion in the precordial leads (V-1 vs. beyond V-1) with RV end diastolic diameter (RVEDD) by echocardiography. ResultsIn the ARVC group, the mean age was 46 14 years, 31 patients were male, 28 had an implantable cardioverter defibrillator (ICD), and 7 had a LV ejection fraction (EF) <55%. The control group was age- and gender matched to the ARVC cohort. In contrast to controls, the Sigma QRS(ext) (regression coefficient (RC), -0.29; P = 0.020), Sigma QRS(prec) (RC, -0.20; P = 0.015), and Sigma QRS(tot) (RC, -0.14; P = 0.009) were lower with RV dilatation in ARVC. S amplitude in lead V-1 was not related to RV diameter (RC, -0.98; P = 0.088). Precordial T-wave inversion beyond lead V-1 (V-2-V-6) was associated with a larger RV diameter (RC, 8.58; P = 0.012). ConclusionsSummed QRS amplitudes in the extremity and precordial leads, and T-wave inversion beyond lead V-1 are associated with RV dilatation in patients with ARVC