Treatment patterns and deep molecular response in chronic phase - chronic myeloid leukemia patients treated with second-line nilotinib or dasatinib: a multi-country retrospective chart review study.

Achievement of MR4.5 (BCR-ABL1 ≤ 0.0032% on international scale) is an important goal of tyrosine kinase inhibitor (TKI) treatment for patients with chronic myeloid leukemia (CML). This study describes treatment patterns by region and assesses time to achieve MR4.5 in patients with CML - chronic phase (CP) treated with second-line nilotinib or dasatinib in 10 countries. A multivariate Cox proportional hazards model was used to assess time to MR4.5 for nilotinib versus dasatinib. The model accounted for the competing-risk event of TKI resistance, included random effects for country clustering, and was adjusted for baseline covariates. The study included 280 patients treated with either nilotinib (N = 135 [48%]) or dasatinib (N = 145 [52%]) as second-line TKI with median treatment durations of 19.1 and 18.7 months, respectively. Nilotinib was observed to be better in achieving MR4.5 than dasatinib (adjusted hazard ratio = 1.37, 95% CI [1.11, 1.69]) suggesting second-line nilotinib may perform better in achieving MR4.5 than dasatinib.

Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd.

The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose-optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re-escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2-75·1%) achieved major molecular response (BCR-ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re-escalation). The safety profile of nilotinib was consistent with prior studies. The most common non-haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188).

Clinical and serum-based markers are associated with death within 1 year of de novo implant in primary prevention ICD recipients.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) implantation is contraindicated in those with <1-year life expectancy. OBJECTIVES: The aim of this study was to develop a risk prediction score for 1-year mortality in patients with primary prevention ICDs and to determine the incremental improvement in discrimination when serum-based biomarkers are added to traditional clinical variables. METHODS: We analyzed data from the Prospective Observational Study of Implantable Cardioverter-Defibrillators, a large prospective observational study of patients undergoing primary prevention ICD implantation who were extensively phenotyped for clinical and serum-based biomarkers. We identified variables predicting 1-year mortality and synthesized them into a comprehensive risk scoring construct using backward selection. RESULTS: Of 1189 patients deemed by their treating physicians as having a reasonable 1-year life expectancy, 62 (5.2%) patients died within 1 year of ICD implantation. The risk score, composed of 6 clinical factors (age ≥75 years, New York Heart Association class III/IV, atrial fibrillation, estimated glomerular filtration rate <30 mL/min/1.73 m(2), diabetes, and use of diuretics), had good discrimination (area under the curve 0.77) for 1-year mortality. Addition of 3 biomarkers (tumor necrosis factor α receptor II, pro-brain natriuretic peptide, and cardiac troponin T) further improved model discrimination to 0.82. Patients with 0-1, 2-3, 4-6, or 7-9 risk factors had 1-year mortality rates of 0.8%, 2.7%, 16.1%, and 46.2%, respectively. CONCLUSION: Individuals with more comorbidities and elevation of specific serum biomarkers were at increased risk of all-cause mortality despite being deemed as having a reasonable 1-year life expectancy. A simple risk score composed of readily available clinical data and serum biomarkers may better identify patients at high risk of early mortality and improve patient selection and counseling for primary prevention ICD therapy.

Protein biomarkers identify patients unlikely to benefit from primary prevention implantable cardioverter defibrillators: findings from the Prospective Observational Study of Implantable Cardioverter Defibrillators (PROSE-ICD).

BACKGROUND: Primary prevention implantable cardioverter defibrillators (ICDs) reduce all-cause mortality, but the benefits are heterogeneous. Current risk stratification based on left ventricular ejection fraction has limited discrimination power. We hypothesize that biomarkers for inflammation, neurohumoral activation, and cardiac injury can predict appropriate shocks and all-cause mortality in patients with primary prevention ICDs. METHODS AND RESULTS: The Prospective Observational Study of Implantable Cardioverter Defibrillators (PROSe-ICD) enrolled 1189 patients with systolic heart failure who underwent ICD implantation for primary prevention of sudden cardiac death. The primary end point was an ICD shock for adjudicated ventricular tachyarrhythmia. The secondary end point was all-cause mortality. After a median follow-up of 4.0 years, 137 subjects experienced an appropriate ICD shock and 343 participants died (incidence rates of 3.2 and 5.8 per 100 person-years, respectively). In multivariable-adjusted models, higher interleukin-6 levels increased the risk of appropriate ICD shocks. In contrast, C-reactive protein, interleukin-6, tumor necrosis factor-α receptor II, pro-brain natriuretic peptide (pro-BNP), and cardiac troponin T showed significant linear trends for increased risk of all-cause mortality across quartiles. A score combining these 5 biomarkers identified patients who were much more likely to die than to receive an appropriate shock from the ICD. CONCLUSIONS: An increase in serum biomarkers of inflammation, neurohumoral activation, and myocardial injury increased the risk for death but poorly predicted the likelihood of an ICD shock. These findings highlight the potential importance of serum-based biomarkers in identifying patients who are unlikely to benefit from primary prevention ICDs. CLINICAL TRIAL REGISTRATION URL: clinicaltrials.gov; Unique Identifier: NCT00733590.

Prospective observational study of implantable cardioverter-defibrillators in primary prevention of sudden cardiac death: study design and cohort description.

BACKGROUND: Primary-prevention implantable cardioverter-defibrillators (ICDs) reduce total mortality in patients with severe left ventricular systolic function. However, only a minority of patients benefit from these devices. We designed the Prospective Observational Study of Implantable Cardioverter-Defibrillators (PROSE-ICD) to identify risk factors and enhance our understanding of the biological mechanisms that predispose to arrhythmic death in patients undergoing ICD implantation for primary prevention of sudden death. METHODS AND RESULTS: This is a multicenter prospective cohort study with a target enrollment of 1200 patients. The primary end point is ICD shocks for adjudicated ventricular tachyarrhythmias. The secondary end point is total mortality. All patients undergo a comprehensive evaluation including history and physical examination, signal-averaged electrocardiograms, and blood sampling for genomic, proteomic, and metabolomic analyses. Patients are evaluated every 6 months and after every known ICD shock for additional electrocardiographic and blood sampling. As of December 2011, a total of 1177 patients have been enrolled with more nonwhite and female patients compared to previous randomized trials. A total of 143 patients have reached the primary end point, whereas a total of 260 patients died over an average follow-up of 59 months. The PROSE-ICD study represents a real-world cohort of individuals with systolic heart failure receiving primary-prevention ICDs. CONCLUSIONS: Extensive electrophysiological and structural phenotyping as well as the availability of serial DNA and serum samples will be important resources for evaluating novel metrics for risk stratification and identifying patients at risk for arrhythmic sudden death. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/ Unique Identifier: NCT00733590.

Predictors of high defibrillation threshold in the modern era.

INTRODUCTION: High defibrillation threshold (DFT) is a clinical problem in 1-8% of implantable cardioverter-defibrillator implants. Some clinicians and investigators question whether the benefits of routine DFT testing outweigh the risks. Identification of the predictors of elevated DFT may allow selective application of DFT testing. However, the clinical characteristics of patients with high DFT in the modern era have not been well-defined. METHODS: All patients who underwent DFT testing in our institution during an 8-year period were reviewed for this retrospective study. High DFT was defined as less than a 10-J safety margin on initial testing. For each case, the two cases preceding and two cases following by the same implanter were selected as controls. RESULTS: Of the 2,138 patients who underwent DFT testing, 48 (2.2%) met criteria for high DFT. Compared to 192 control patients, patients with high DFT were more likely to be younger (P = 0.004), have nonischemic cardiomyopathy (P = 0.036), have a longer QRS interval (P = 0.026), and have a left ventricular ejection fraction (LVEF) ≤ 0.25 (P = 0.013). On multivariate analysis, only younger age (P = 0.016) and LVEF ≤ 0.25 (P = 0.010) remained statistically significant predictors of elevated DFT. CONCLUSIONS: High DFT was identified in 2.2% of ICD implants in our institution in recent years. Although younger age and depressed LVEF predicts this problem, elevated DFT occurred in patients of all ages and ejection fractions. Elimination of routine DFT testing appears to be premature given the prevalence and unpredictability of elevated DFT.

Treatment patterns and clinical outcomes in patients with metastatic colorectal cancer initially treated with FOLFOX-bevacizumab or FOLFIRI-bevacizumab: results from ARIES, a bevacizumab observational cohort study.

BACKGROUND: The Avastin Registry: Investigation of Effectiveness and Safety (ARIES) study is a prospective, community-based observational cohort study that evaluated the effectiveness and safety of first-line treatment patterns, assessing the impact of chemotherapy choice and treatment duration. METHODS: The ARIES study enrolled patients with metastatic colorectal cancer (mCRC) receiving first-line chemotherapy with bevacizumab and followed them longitudinally. The protocol did not specify treatment regimens or assessments. Analyses included all patients who initiated bevacizumab in combination with either first-line oxaliplatin with infusional 5-fluorouracil and leucovorin (FOLFOX) or irinotecan with infusional 5-fluorouracil and leucovorin (FOLFIRI). Progression-free survival (PFS) and overall survival (OS) times were estimated using Kaplan-Meier methods. Hazard ratios (HRs) were estimated with multivariate Cox regression analysis, adjusting for potential confounding factors. RESULTS: In total, 1,550 patients with first-line mCRC were enrolled (median follow-up, 21 months) and most received FOLFOX-bevacizumab (n = 968) or FOLFIRI-bevacizumab (n = 243) as first-line therapy. The baseline characteristics and median treatment duration were generally similar between subgroups. There were no significant differences in the median PFS (10.3 months vs. 10.2 months) or OS (23.7 months vs. 25.5 months) time between the FOLFOX-bevacizumab and FOLFIRI-bevacizumab subgroups, respectively, by unadjusted analyses. Multivariate analyses showed FOLFIRI-bevacizumab resulted in a similar PFS (HR, 1.03; 95% confidence interval [CI], 0.88-1.21) and OS (HR, 0.95; 95% CI, 0.78-1.16) outcome as with FOLFOX-bevacizumab. The incidence proportions of bevacizumab-associated adverse events were similar for FOLFOX- and FOLFIRI-based therapies. CONCLUSIONS: In first-line mCRC patients, the FOLFOX-bevacizumab and FOLFIRI-bevacizumab regimens were associated with similar treatment patterns and clinical outcomes.

Outcomes of catheter ablation of ventricular tachycardia in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

BACKGROUND: Prior studies evaluating the efficacy of catheter ablation of ventricular tachycardia (VT) among patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) have reported varied outcomes. More recently, studies have suggested that an epicardial ablation is necessary for improved outcomes after catheter ablation of VT. The overall objective of the present study was to assess the efficacy of radiofrequency catheter ablation (RFA) of VT in ARVD/C, with particular focus on newer ablation strategies, including epicardial catheter ablation. METHODS AND RESULTS: The study population included 87 patients with ARVD/C who underwent a total of 175 RFA procedures between 1992 and 2011 at 80 different electrophysiology centers. Recurrence of VT following RFA and effect of RFA on the burden of VT were assessed. The mean age of the cohort was 38±13 years. Over a mean follow-up of 88.3±66 months, the overall freedom from VT of the 175 procedures was 47%, 21%, and 15%, at 1, 5, and 10 years, respectively. The cumulative freedom from VT following epicardial RFA was 64% and 45% at 1 and 5 years, respectively, which was significantly longer than endocardial RFA (P=0.021). Survival free of VT among procedures with 3D electroanatomic mapping was significantly longer compared to those without (P=0.016). Burden of VT was reduced irrespective of the ablation strategy (P<0.001). CONCLUSIONS: Although VT recurrences are common, RFA results in a significant reduction in the burden of VT in patients with ARVD/C. Further, although the use of 3D electroanatomic mapping systems and epicardial ablation strategies are associated with longer survival free of VT, recurrence rates remain considerable.

Combined cardiac magnetic resonance imaging and C-reactive protein levels identify a cohort at low risk for defibrillator firings and death.

BACKGROUND: Annually, ≈80,000 Americans receive guideline-based primary prevention implantable cardioverter-defibrillators (ICDs), but appropriate firing rates are low. Current selection criteria for ICDs rely on left ventricular ejection fraction, which lacks sensitivity and specificity. Because scar-related myocardial tissue heterogeneity is a substrate for life-threatening arrhythmias, we hypothesized that cardiac magnetic resonance identification of myocardial heterogeneity improves risk stratification through (1) its association with adverse cardiac events independent of clinical factors and biomarker levels and (2) its ability to identify particularly high- and low-risk subgroups. METHODS AND RESULTS: In 235 patients with chronic ischemic and nonischemic cardiomyopathy with a left ventricular ejection fraction of ≤35% undergoing clinically indicated primary prevention ICD implantation, gadolinium-enhanced cardiac magnetic resonance was prospectively performed to quantify the amount of heterogeneous myocardial tissue (gray zone [GZ]) and dense core scar. Serum high-sensitivity C-reactive protein (hsCRP) and other biomarkers were assayed. The primary end point was appropriate ICD shock for ventricular tachycardia/fibrillation or cardiac death, which occurred in 45 (19%) patients at a 3.6-year median follow-up. On univariable analysis, only diuretics, hsCRP, GZ, and core scar were associated with outcome. After multivariable adjustment, GZ and hsCRP remained independently associated with outcome (P<0.001). Patients in the lowest tertile for both GZ and hsCRP (n=42) were at particularly low risk (0.7% per year event rate), whereas those in the highest tertile for both GZ and hsCRP (n=32) had an event rate of 16.1% per year, P<0.001. CONCLUSIONS: In a cohort of primary prevention ICD candidates, combining a myocardial heterogeneity index with an inflammatory biomarker identified a subgroup with a very low risk for adverse cardiac events, including ventricular arrhythmias. This novel approach warrants further investigation to confirm its value as a clinical risk stratification tool. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00181233.

Mild-to-moderate kidney dysfunction and the risk of sudden cardiac death in the setting of acute myocardial infarction.

BACKGROUND: Although end-stage renal disease is known to elevate the risk of sudden cardiac death (SCD), the role of less severe renal impairment in SCD is unclear. OBJECTIVE: The purpose of this study was to examine the association between mild-to-moderate renal impairment and first ischemic ventricular fibrillation (VF). METHODS: Renal function in patients included in the Arrhythmia Genetics in the NEtherlands Study (AGNES) were compared. Cases (n = 337, age 56 ± 1 year, 80% men) were defined as patients who had survived VF at the time of their first acute ST elevation myocardial infarction (STEMI), and controls (n = 339, age 58 ± 1 years, 80% men) were defined as those without VF during their first acute STEMI. Estimated glomerular filtration rate (eGFR) at the time of acute STEMI was computed using the 4-variable Modification of Diet in Renal Disease equation. RESULTS: At eGFR less than 105 mL/min, a decrease in eGFR was associated with elevated odds of developing VF during STEMI. The association was essentially flat at eGFR levels >105 mL/min. The lowest eGFR quintile was associated with a >6-fold increase in odds of developing VF compared to the fourth quintile. This association between eGFR and VF at the time of STEMI remained significant after adjusting for potential confounders including electrolyte levels. CONCLUSION: Mild-to-moderate kidney dysfunction is associated with a significantly elevated risk of VF in the setting of acute STEMI. Further studies are needed to investigate the precise mechanisms by which mild kidney function results in VF.

QT-interval duration and mortality rate: results from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Extreme prolongation or reduction of the QT interval predisposes patients to malignant ventricular arrhythmias and sudden cardiac death, but the association of variations in the QT interval within a reference range with mortality end points in the general population is unclear. METHODS: We included 7828 men and women from the Third National Health and Nutrition Examination Survey. Baseline QT interval was measured via standard 12-lead electrocardiographic readings. Mortality end points were assessed through December 31, 2006 (2291 deaths). RESULTS: After an average follow-up of 13.7 years, the association between QT interval and mortality end points was U-shaped. The multivariate-adjusted hazard ratios comparing participants at or above the 95th percentile of age-, sex-, race-, and R-R interval-corrected QT interval (≥439 milliseconds) with participants in the middle quintile (401 to <410 milliseconds) were 2.03 (95% confidence interval, 1.46-2.81) for total mortality, 2.55 (1.59-4.09) for mortality due to cardiovascular disease (CVD), 1.63 (0.96-2.75) for mortality due to coronary heart disease, and 1.65 (1.16-2.35) for non-CVD mortality. The corresponding hazard ratios comparing participants with a corrected QT interval below the fifth percentile (<377 milliseconds) with those in the middle quintile were 1.39 (95% confidence interval, 1.02-1.88) for total mortality, 1.35 (0.77-2.36) for CVD mortality, 1.02 (0.44-2.38) for coronary heart disease mortality, and 1.42 (0.97-2.08) for non-CVD mortality. Increased mortality also was observed with less extreme deviations of QT-interval duration. Similar, albeit weaker, associations also were observed with Bazett-corrected QT intervals. CONCLUSION: Shortened and prolonged QT-interval durations, even within a reference range, are associated with increased mortality risk in the general population.

Incidence and predictors of implantable cardioverter-defibrillator therapy in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy undergoing implantable cardioverter-defibrillator implantation for primary prevention.

OBJECTIVES: The purpose of this study was to define the incidence and predictors of implantable cardioverter-defibrillator (ICD) therapy in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) after placement of an ICD for primary prevention. BACKGROUND: Patients with a diagnosis of ARVD/C often receive an ICD for prevention of sudden cardiac death. METHODS: Patients (n = 84) from the Johns Hopkins registry with definite or probable ARVD/C who underwent ICD implantation for primary prevention were studied. Detailed phenotypic, genotype, and ICD event information was obtained and appropriate ICD therapies were adjudicated based on intracardiac electrograms. RESULTS: Over a mean follow-up of 4.7 ± 3.4 years, appropriate ICD therapy was seen in 40 patients (48%), of whom 16 (19%) received interventions for potentially fatal ventricular fibrillation/flutter episodes. Proband status (p < 0.001), inducibility at electrophysiologic study (p = 0.005), presence of nonsustained ventricular tachycardia (p < 0 .001), and Holter premature ventricular complex count >1,000/24 h (p = 0.024) were identified as significant predictors of appropriate ICD therapy. The 5-year survival free of appropriate ICD therapy for patients with 1, 2, 3, and 4 risk factors was 100%, 83%, 21%, and 15%, respectively. Inducibility at electrophysiologic study (hazard ratio: 4.5, 95% confidence interval: 1.4 to 15, p = 0.013) and nonsustained ventricular tachycardia (hazard ratio: 10.5, 95% confidence interval: 2.4 to 46.2, p = 0.002) remained as significant predictors on multivariable analysis. CONCLUSIONS: Nearly one-half of the ARVD/C patients with primary prevention ICD implantation experience appropriate ICD interventions. Inducibility at electrophysiologic study and nonsustained ventricular tachycardia are independent strong predictors of appropriate ICD therapy. An increase in ventricular ectopy burden was associated with progressively lower event-free (appropriate ICD interventions) survival. Incremental risk of ventricular arrhythmias and ICD therapy was observed with the presence of multiple risk factors.

Sex-steroid hormones and electrocardiographic QT-interval duration: findings from the third National Health and Nutrition Examination Survey and the Multi-Ethnic Study of Atherosclerosis.

The association between physiologic levels of sex hormones and QT-interval duration in humans was evaluated using data from 727 men enrolled in the Third National Health and Nutrition Examination Survey and 2,942 men and 1,885 postmenopausal women enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Testosterone, estradiol, and sex hormone-binding globulin levels were measured in serum and free testosterone was calculated from those values. QT interval was measured using a standard 12-lead electrocardiogram. In men from the Third National Health and Nutrition Survey, the multivariate adjusted differences in average QT-interval duration comparing the highest quartiles with the lowest quartiles of total testosterone and free testosterone were -8.5 ms (95% confidence interval (CI): -15.5, -1.4) and -8.0 ms (95% CI: -13.2, -2.8), respectively. The corresponding differences were -1.8 ms (95% CI: -3.8, -0.2), and -4.7 ms (95% CI: -6.7, -2.6), respectively, in men from MESA and -0.6 ms (95% CI: -3.0, 1.8) and 0.8 ms (95% CI: -1.6, 3.3), respectively, in postmenopausal women from MESA. Estradiol levels were not associated with QT-interval duration in men, but there was a marginally significant positive association in postmenopausal women. The findings suggest that testosterone levels may explain differences in QT-interval duration between men and women and could be a contributor to population variability in QT-interval duration among men.

Electrocardiographic QT interval and mortality: a meta-analysis.

BACKGROUND: Extremely abnormal prolongation of the electrocardiographic QT interval is associated with malignant ventricular arrhythmias and sudden cardiac death. However, the implications of variations in QT-interval length within normal limits for mortality in the general population are still unclear. METHODS: We performed a meta-analysis to investigate the relation of QT interval with mortality endpoints. Inverse-variance weighted random-effects models were used to summarize the relative risks across studies. Twenty-three observational studies were included. RESULTS: The pooled relative risk estimates comparing the highest with the lowest categories of QT-interval length were 1.35 (95% confidence interval = 1.24-1.46) for total mortality, 1.51 (1.29-1.78) for cardiovascular mortality, 1.71 (1.36-2.15) for coronary heart disease mortality, and 1.44 (1.01-2.04) for sudden cardiac death. A 50 milliseconds increase in QT interval was associated with a relative risk of 1.20 (1.15-1.26) for total mortality, 1.29 (1.15-1.46) for cardiovascular mortality, 1.49 (1.25-1.76) for coronary heart disease mortality, and 1.24 (0.97-1.60) for sudden cardiac death. CONCLUSIONS: We found consistent associations between prolonged QT interval and increased risk of total, cardiovascular, coronary, and sudden cardiac death. QT-interval length is a determinant of mortality in the general population.

Conventional pulmonary vein isolation compared with the "box isolation" method: a randomized clinical trial.

PURPOSE: Esophageal injury is a potential complication with radiofrequency ablation in the posterior wall of the left atrium (LA). The "box isolation" method isolates the posterior LA wall including the pulmonary veins without ablation on the posterior LA wall. This study compares the acute and long-term efficacy of the box isolation method with conventional circumferential pulmonary vein isolation (PVI) for catheter ablation of AF. METHODS: Twenty-nine patients (age 60 ± 9 years, 62% male, 79% paroxysmal) with drug refractory AF underwent catheter ablation. Sixteen of the 29 patients (55%) underwent box isolation. Recurrence of AF was detected by checking the daily recorded rhythm strip on a portable home ECG monitor, irrespective of the symptoms. Mean follow-up duration was 10 ± 2 months. RESULTS: Complete isolation of the posterior LA using box isolation lesions was achieved in three of 16 (19%) patients. The other 13 patients underwent creation of additional lesions until all PVs were isolated. Of the 16 patients who underwent box isolation, four patients (25%) had complete success, six patients (38%) had improvement, and the remaining six patients (37%) had failure. Of the 13 patients who underwent the standard PV isolation, two patients (15%) had complete success, eight patients (62%) had improvement, and the remaining three patients (23%) had failure (p = 0.44). CONCLUSION: In this pilot study, the efficacy of box isolation is similar to the circumferential PVI for catheter ablation of AF. Few patients achieved PVI with box method alone. Based on these results, we do not recommend the box isolation strategy.

Serum 25-hydroxyvitamin D, calcium, phosphorus, and electrocardiographic QT interval duration: findings from NHANES III and ARIC.

CONTEXT: Disturbances in 25-hydroxyvitamin D, calcium, and phosphorus concentrations have been associated with increased risks of total and cardiovascular mortality. It is possible that changes in electrocardiographic QT interval duration may mediate these effects, but the association of 25-hydroxyvitamin D, phosphorus, and calcium concentrations with QT interval duration has not been evaluated in general population samples. OBJECTIVE: The objective of the study was to evaluate the association of 25-hydroxyvitamin D, phosphorus, and calcium concentrations with QT interval duration in two large samples of the U.S. general population. DESIGN: This study included cross-sectional analyses the Third National Health and Nutrition Survey (NHANES III) and the Atherosclerosis Risk in Communities (ARIC) study. SETTING: The study was conducted in the general community. PATIENTS OR OTHER PARTICIPANTS: Patients included 7,312 men and women from NHANES III and 14,825 men and women from the ARIC study. INTERVENTIONS: Serum 25-hydroxyvitamin D, total and ionized calcium, and inorganic phosphorus were measured in NHANES III, and serum total calcium and inorganic phosphorus were measured in ARIC. MAIN OUTCOME MEASURE: QT interval duration was obtained from standard 12-lead electrocardiograms. RESULTS: In NHANES III, the multivariate adjusted differences in average QT interval duration comparing the highest vs. the lowest quartiles of serum total calcium, ionized calcium, and phosphorus were -3.6 msec (-5.8 to -1.3; P for trend = 0.005), -5.4 msec (-7.4 to -3.5; P for trend <0.001), and 3.9 msec (2.0-5.9; P for trend <0.001), respectively. The corresponding differences in ARIC were -3.1 msec (-4.3 to -2.0; P for trend <0.001), -2.9 msec (-3.8 to -1.9; P for trend <0.001), and 2.3 msec (1.3-3.3; P for trend <0.001). No association was found between 25-hydroxyvitamin D concentrations and QT interval duration. CONCLUSIONS: In two large samples of the general population, QT interval duration was inversely associated with the serum total and ionized calcium and positively associated with serum phosphorus.

Demographic profile of patients undergoing catheter ablation of atrial fibrillation.

BACKGROUND: Catheter ablation is a widely accepted treatment for drug refractory atrial fibrillation (AF). The purpose of our study was to examine secular trends in the demographic profile of patients undergoing AF ablation. METHODS AND RESULTS: Data for 792 patients who underwent catheter ablation for AF at Johns Hopkins Hospital between years 2001 and 2009 were systematically reviewed. There has been a steady increase in total number of procedures and repeat procedures. The majority of patients undergoing AF ablation at our institution are men (76.6%). Females accounted for 36.0% of patients in 2001 versus 19.6% in 2009. A total of 93.3% of patients undergoing AF ablation were Caucasian. The mean age of patients has increased over time (52 years in 2001 to 60 years in 2009, P = 0.015) and the number of antiarrhythmic drugs (AADs) used prior to first ablation has decreased (2.3 to 1.2, P = 0.009). In addition, the mean duration of AF prior to first referral has decreased (7.8 years in 2001 vs 4.2 years in 2009). CONCLUSION: There is a significant gender and racial disparity in patients undergoing AF ablation favoring Caucasian men that warrants further investigation. We also observed a significant increase in age of patients, decrease in number of AADs, and increase in number of repeat procedures. These results are important when interpreting outcomes of AF ablation and designing future trials.

Coffee, alcohol, smoking, physical activity and QT interval duration: results from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Abnormalities in the electrocardiographic QT interval duration have been associated with an increased risk of ventricular arrhythmias and sudden cardiac death. However, there is substantial uncertainty about the effect of modifiable factors such as coffee intake, cigarette smoking, alcohol consumption, and physical activity on QT interval duration. METHODS: We studied 7795 men and women from the Third National Health and Nutrition Survey (NHANES III, 1988-1994). Baseline QT interval was measured from the standard 12-lead electrocardiogram. Coffee and tea intake, alcohol consumption, leisure-time physical activities over the past month, and lifetime smoking habits were determined using validated questionnaires during the home interview. RESULTS: In the fully adjusted model, the average differences in QT interval comparing participants drinking ≥6 cups/day to those who did not drink any were -1.2 ms (95% CI -4.4 to 2.0) for coffee, and -2.0 ms (-11.2 to 7.3) for tea, respectively. The average differences in QT interval duration comparing current to never smokers was 1.2 ms (-0.6 to 2.9) while the average difference in QT interval duration comparing participants drinking ≥7 drinks/week to non-drinkers was 1.8 ms (-0.5 to 4.0). The age, race/ethnicity, and RR-interval adjusted differences in average QT interval duration comparing men with binge drinking episodes to non-drinkers or drinkers without binge drinking were 2.8 ms (0.4 to 5.3) and 4.0 ms (1.6 to 6.4), respectively. The corresponding differences in women were 1.1 (-2.9 to 5.2) and 1.7 ms (-2.3 to 5.7). Finally, the average differences in QT interval comparing the highest vs. the lowest categories of total physical activity was -0.8 ms (-3.0 to 1.4). CONCLUSION: Binge drinking was associated with longer QT interval in men but not in women. QT interval duration was not associated with other modifiable factors including coffee and tea intake, smoking, and physical activity.

A new electrocardiogram marker to identify patients at low risk for ventricular tachyarrhythmias: sum magnitude of the absolute QRST integral.

OBJECTIVE: We proposed and tested a novel electrocardiogram marker of risk of ventricular arrhythmias (VAs). METHODS: Digital orthogonal electrocardiograms were recorded at rest before implantable cardioverter-defibrillator (ICD) implantation in 508 participants of a primary prevention ICDs prospective cohort study (mean ± SD age, 60 ± 12 years; 377 male [74%]). The sum magnitude of the absolute QRST integral in 3 orthogonal leads (SAI QRST) was calculated. A derivation cohort of 128 patients was used to define a cutoff; a validation cohort (n = 380) was used to test a predictive value. RESULTS: During a mean follow-up of 18 months, 58 patients received appropriate ICD therapies. The SAI QRST was lower in patients with VA (105.2 ± 60.1 vs 138.4 ± 85.7 mV ms, P = .002). In the Cox proportional hazards analysis, patients with SAI QRST not exceeding 145 mV ms had about 4-fold higher risk of VA (hazard ratio, 3.6; 95% confidence interval, 1.96-6.71; P < .0001) and a 6-fold higher risk of monomorphic ventricular tachycardia (hazard ratio, 6.58; 95% confidence interval, 1.46-29.69; P = .014), whereas prediction of polymorphic ventricular tachycardia or ventricular fibrillation did not reach statistical significance. CONCLUSION: High SAI QRST is associated with low risk of sustained VA in patients with structural heart disease.