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).

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.

Prophylactic implantable defibrillator in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation or sustained ventricular tachycardia.

BACKGROUND: The role of implantable cardioverter-defibrillator (ICD) in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation (VF) or sustained ventricular tachycardia is an unsolved issue. METHODS AND RESULTS: We studied 106 consecutive patients (62 men and 44 women; age, 35.6±18 years) with arrhythmogenic right ventricular cardiomyopathy/dysplasia who received an ICD based on 1 or more arrhythmic risk factors such as syncope, nonsustained ventricular tachycardia, familial sudden death, and inducibility at programmed ventricular stimulation. During follow-up of 58±35 months, 25 patients (24%) had appropriate ICD interventions and 17 (16%) had shocks for life-threatening VF or ventricular flutter. At 48 months, the actual survival rate was 100% compared with the VF/ventricular flutter-free survival rate of 77% (log-rank P=0.01). Syncope significantly predicted any appropriate ICD interventions (hazard ratio, 2.94; 95% confidence interval, 1.83 to 4.67; P=0.013) and shocks for VF/ventricular flutter (hazard ratio, 3.16; 95% confidence interval, 1.39 to 5.63; P=0.005). The positive predictive value of programmed ventricular stimulation was 35% for any appropriate ICD intervention and 20% for shocks for VF/ventricular flutter, with a negative predictive value of 70% and 74%. None of the 27 asymptomatic patients with isolated familial sudden death had appropriate ICD therapy. Twenty patients (19%) had inappropriate ICD interventions, and 18 (17%) had device-related complications. CONCLUSIONS: One fourth of patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior sustained ventricular tachycardia or VF had appropriate ICD interventions. Syncope was an important predictor of life-saving ICD intervention and is an indication for ICD. Prophylactic ICD may not be indicated in asymptomatic patients because of their low arrhythmic risk regardless of familial sudden death and programmed ventricular stimulation findings. Programmed ventricular stimulation had a low predictive accuracy for ICD therapy.

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.

Reader- and instrument-dependent variability in the electrocardiographic assessment of arrhythmogenic right ventricular dysplasia/cardiomyopathy.

INTRODUCTION: Despite the use of standardized definitions, widely varying prevalence estimates of electrocardiographic (ECG) features related to arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) have been reported in different cohorts. This study was aimed at examining the variability in the ECG interpretation resulting from the same reader, different readers, and using different ECG-resolutions. METHODS AND RESULTS: Blinded to other clinical data, 2 readers examined quantitative and qualitative ECG features of 20 (10 ARVD/C) randomly selected individuals. ECGs were recorded at standard-speed (SS) and double-speed-double-amplitude (DS) settings. The SS ECGs were scanned, magnified 4×, and evaluated using electronic calipers (EL). One reader repeated all measurements. For both readers, the intraclass correlation coefficient (ICC) for the measurement of QRS duration was good between conventional and electronic evaluation [DS vs EL: Reader 1--0.64 (0.52-0.73); Reader 2--0.67 (0.55-0.76)][SS vs EL: Reader 1--0.60 (0.47-0.70); Reader 2--0.60 (0.47-0.70)]. Using the same resolution, the intrareader ICC was good for SS [0.70 (0.59-0.78)], DS [0.85 (0.80-0.90)], and EL [0.70 (0.69-0.83)] resolutions, but deteriorated for interreader comparisons [0.50 (0.36-0.62), 0.75 (0.66-0.82), and 0.75 (0.66-0.82), respectively]. For qualitative parameters, the intra- and interreader agreement was inconsistent for all but 2 parameters. Both readers were in perfect agreement while interpreting right precordial T-wave inversion [κ= 1] and right bundle branch block morphology (RBBB) [κ= 0.83 (0.5-1.0)] even when using SS resolution. CONCLUSIONS: Right precordial t-wave inversion and RBBB are the only ECG parameters that can be detected consistently even using the conventionally used ECG-resolution. The substantial variability in evaluation of other parameters is not improved even with the use of higher resolutions.

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.

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.

Electrocardiographic features of arrhythmogenic right ventricular dysplasia.

BACKGROUND: The purpose of this study was to reevaluate the ECG features of arrhythmogenic right ventricular dysplasia (ARVD). The second objective was to evaluate the sensitivity and specificity of the standard and newly proposed diagnostic ECG markers in the presence of a right bundle-branch block (RBBB). METHODS AND RESULTS: One hundred patients with ARVD (57 men; aged 39+/-15 years) and 57 controls (21 men; aged 40+/-17 years) were included. Among the 100 patients with ARVD, a complete RBBB was present in 17 patients, and 15 patients had an incomplete RBBB. T-wave inversion through V(3) demonstrated optimal sensitivity and specificity in both ARVD patients without a complete RBBB or incomplete RBBB (71% [95% confidence interval, 58% to 81%] and 96% [95% confidence interval, 81% to 100%], respectively) and in ARVD patients with incomplete RBBB (73% [95% confidence interval, 45% to 92%] and 95% [95% confidence interval, 77% to 100%], respectively). Between ARVD patients and controls with a complete RBBB, the only 2 parameters that differed were the prevalence of T-wave inversion through V(4) (59% versus 12%, respectively; P<0.05) and an r'/s ratio in V(1) <1 (88% versus 14%, respectively; P<0.005). In ARVD patients with complete RBBB, the most sensitive and specific parameter was an r'/s ratio <1. CONCLUSIONS: We evaluated comprehensively the diagnostic value of ECG markers for ARVD. On the basis of the findings, we propose an algorithm, with examination of QRS morphology being the first step, for ECG evaluation of ARVD patients. Definite criteria are then applied on the basis of the presence of no RBBB, incomplete RBBB, and complete RBBB to obtain the best diagnostic utility of the ECG.

Diagnostic and prognostic utility of electrocardiography for left ventricular hypertrophy defined by magnetic resonance imaging in relationship to ethnicity: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Left ventricular mass is a strong predictor of cardiovascular disease (CVD), and magnetic resonance imaging (MRI) of the heart is a standard of reference for left ventricular mass measurement. Ethnicity is believed to affect electrocardiographic (ECG) performance. We evaluated the diagnostic and prognostic performance of ECG for left ventricular hypertrophy (LVH) as defined by MRI in relationship to ethnicity. METHODS: Data were analyzed from 4,967 participants (48% men, mean age 62 +/- 10 years; 39% white, 13% Chinese, 26% African American, 22% Hispanic) enrolled in the Multi-Ethic Study of Atherosclerosis (MESA) who were followed for a median of 4.8 years for incident CVD. RESULTS: Thirteen traditional ECG-LVH criteria were assessed, and showed overall and ethnicity-specific low sensitivity (10%-26%) and high specificity (88%-99%) in diagnosing MRI-defined LVH. Ten of 13 ECG-LVH criteria showed superior sensitivity and diagnostic performance in African Americans as compared with whites (P = .02-.001). The sum of amplitudes of S wave in V(1), S wave in V(2), and R wave in V(5) (a MESA-specific ECG-LVH criterion) offered higher sensitivity (40.4%) compared with prior ECG-LVH criteria while maintaining good specificity (90%) and diagnostic performance (receiver operating characteristic area = 0.65). In fully adjusted models, only the MESA-specific ECG-LVH criterion, Romhilt-Estes score, Framingham score, Cornell voltage, Cornell duration product, and Framingham-adjusted Cornell voltage predicted increased CVD risk (P < .05). CONCLUSIONS: Electrocardiography has low sensitivity but high specificity for detecting MRI-defined LVH. The performance of ECG for LVH detection varies by ethnicity, with African Americans showing higher sensitivity and overall performance compared with other ethnic groups.

A prospective study evaluating the role of obesity and obstructive sleep apnea for outcomes after catheter ablation of atrial fibrillation.

BACKGROUND: Obesity and obstructive sleep apnea (OSA) have a strong association with atrial fibrillation (AF). The purpose of this study was to prospectively determine the effects of obesity, assessed by the body mass index (BMI) and OSA on the efficacy of catheter ablation of AF. METHODS: The patient population consisted of 109 patients (mean age: 60 +/- 10 years, 79% male, 67% paroxysmal, mean BMI 28 +/- 5 kg/m(2)) who underwent catheter ablation of AF. Based on BMI, patients were classified as normal (<25 kg/m(2)), overweight (>or=25 and <30 kg/m(2)), or obese (>or=30 kg/m(2)). OSA was assessed by the Berlin questionnaire. Clinical success was defined as at least 90% reduction in AF burden after 3-month blanking period. Mean duration of follow-up was 11 +/- 4 months. RESULTS: Of the 75 patients with clinical success, 25 (33%) had normal BMI, 29 (39%) were overweight, and 21 (28%) were obese. Among the 34 patients with failed outcome, 5 (15%) had normal BMI, 14 (41%) were overweight, and 15 (44%) were obese (P = 0.04). Twenty-eight of the 48 patients with OSA (58%) had clinical success as opposed to 47 of the 61 patients (77%) without OSA (P = 0.036). On multivariate analysis, only BMI emerged as an independent predictor of procedural failure ((OR 1.11, CI: 1.00-1.21, P = 0.03). CONCLUSIONS: The results of this prospective study show that obesity, a modifiable risk factor, is an independent predictor of procedural failure after catheter ablation of AF. Whether treating obesity may improve the results of catheter ablation of AF warrants further investigation.

Outcomes in patients requiring cardioversion following catheter ablation of atrial fibrillation.

INTRODUCTION: Early recurrence of atrial tachyarrhythmias is commonly noted after catheter ablation of atrial fibrillation (AF). The long-term outcomes of patients who require cardioversion for persistent AF after AF ablation is not known. This study reports the outcomes of patients who underwent cardioversion for persistent AF or atrial flutter following an AF ablation procedure. METHODS: The patient population comprised 55 patients (mean age 58 +/- 10 years, 35% paroxysmal) who underwent catheter ablation of AF and subsequently required electrical cardioversion for persistent AF (45 patients) or atrial flutter (10 patients). Cardioversion was defined as early (within 90 days of the ablation procedure) or late (between 90 and 180 days following ablation). RESULTS: The mean follow-up duration was 15 +/- 8 months. Forty-six of the 55 patients (84%) patients experienced recurrence during follow-up. The average time to recurrence after cardioversion was 37 days. Of the 55 patients, 8 (15%) patients had a complete success, 11 (20%) patients had a partial success and 36 patients (65%) had a failed outcome. Seven of the 43 patients (16%) who underwent early cardioversion had a complete success as opposed to one of 12 patients (8%) who underwent late cardioversion (P = 0.49). CONCLUSIONS: This study shows that >80% of patients who undergo cardioversion for persistent AF or atrial flutter after AF ablation have recurrence. The timing of cardioversion did not affect the outcome. These findings allow clinicians to provide realistic expectations to patients regarding the long-term outcome and/or requirement for a second ablation procedure.

Transoesophageal echocardiography predictors of periprocedural cerebrovascular accident in patients undergoing catheter ablation of atrial fibrillation.

AIMS: To assess the utility of transoesophageal echocardiography (TEE) parameters such as spontaneous echo contrast (SEC), left atrial (LA) appendage velocities, and aortic plaque in predicting periprocedural cerebrovascular accidents (CVAs) in patients undergoing catheter ablation of atrial fibrillation (AF). METHODS AND RESULTS: Five hundred and seventy-nine consecutive patients underwent catheter ablation of AF with pre-procedural TEE, 94% of whom also received pre-procedural warfarin and enoxaparin bridging. Of the 579 patients, 10 patients (cases) who developed periprocedural CVA (1.7%) and 40 randomly selected patients who did not develop CVA (controls) were included (50 study patients, age 58 ± 11 years, 82% male, 54% persistent AF). Periprocedural CVA was defined as a new neurological deficit that occurred anytime between the start of the procedure and 30 days after AF ablation. Demographic, clinical, and TEE variables of cases and controls were compared using standard statistical analyses. Patients with CVA more often had coronary artery disease [odds ratio (OR) 6.0, P = 0.03], previous history of CVA (OR 8.2, P = 0.02), and CHADS(2) score ≥ 2 (OR 5.4, P = 0.03) than patients without CVA. There was no difference in any of the TEE parameters (SEC, LA appendage velocity and area, patent foramen ovale, atrial septal aneurysm, valve abnormality, and aortic plaque). When these TEE parameters were adjusted for coronary artery disease, prior CVA and CHADS(2) ≥ 2, none emerged as an independent predictor of CVA. CONCLUSION: Transoesophageal echocardiographic variables (other than LA thrombus) were not associated with the occurrence of periprocedural CVA in our patients undergoing catheter ablation of AF who generally received pre-procedural anticoagulation. Despite serving as markers of a thrombogenic milieu, the presence of SEC, low LA appendage velocities, and aortic plaque may not increase the risk of periprocedural CVA after AF ablation.

Failure in short-term prediction of ventricular tachycardia and ventricular fibrillation from continuous electrocardiogram in intensive care unit patients.

BACKGROUND: Patients in the intensive care unit (ICU) setting are prone to malignant ventricular arrhythmias. We sought to test whether electrocardiographic (ECG) markers of autonomic tone, ventricular irritability, and repolarization lability could be used in short-term prediction of ventricular arrhythmias in this patient population. METHODS: We studied 38 patients with sustained (>30 seconds) monomorphic ventricular tachycardia, polymorphic ventricular tachycardia, or ventricular fibrillation while monitored in the ICU and 30 patients without arrhythmia in the ICU who served as controls. All patients had at least 12 hours of continuously recorded multilead ECG before arrhythmic event. Mean heart rate and measures of heart rate variability, QT variability, and ventricular ectopy were quantified in 1-hour epochs for the 12 hours before the arrhythmic event and in 5-minute epochs for the last hour preevent (and using a random termination time point in controls). RESULTS: A modest downward trend in QT variability and a rise in heart rate were observed hours before polymorphic ventricular tachycardia and ventricular fibrillation events, although no significant changes heralded monomorphic ventricular tachycardia and no changes in any parameter predicted imminent ventricular arrhythmia of any type. There were no significant differences in ECG parameters between arrhythmia patients and controls. CONCLUSIONS: In ICU patients, sustained ventricular arrhythmias are not preceded by change in ECG measures of autonomic tone, repolarization variability, and ventricular ectopy. Short-term arrhythmia prediction may be difficult or impossible in this patient population based on ECG measures alone.

Efficacy of multidisciplinary outpatient management (MOM) program in long term heart failure care.

BACKGROUND: Heart failure (HF) management programs worldwide have reported conflicting outcomes in the past. OBJECTIVES: We sought to determine retrospectively whether the multidisciplinary outpatient management (MOM) program [heart failure clinic (HFC)], decreased readmission rates (RR), duration of hospital stay, and/or mortality in HF patients. METHODS: Records of 138 HF patients who had their first encounter either as admission for HF at St. Agnes Hospital or visit to HFC during the period June 2005 through June 2006 were evaluated for outcomes through September 2007. Twenty-seven patients were followed in the HFC and 111 were in the non-HFC group. During follow up, 39 of the non-HFC group patients crossed over to the HFC group. All baseline parameters, except age (P = 0.006), were similar in both groups. RESULTS: In the HFC group 4 patients had a total of 5 readmissions, whereas 85 patients had a total of 187 readmissions (P < 0.001) in the non-HFC group. Average lengths of hospitalization were 5.2 +/- 4.8 days and 4.2 +/- 3.2 days (P = 0.18) and the number of readmissions/patient/year was 0.3 and 1.45 (P < 0.001) in the HFC and non-HFC groups, respectively. In the subgroup analysis of cross overs (n = 39), there was a 60% reduction in the readmission rate after crossing over to the HFC group. The significance of decreased mortality in the HFC group could not be assessed due to the small sample size. CONCLUSION: The study suggests that the MOM program can significantly reduce RR secondary to HF.

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.

Correlation of left atrial diameter by echocardiography and left atrial volume by computed tomography.

INTRODUCTION: For patients undergoing catheter ablation of atrial fibrillation (AF), left atrial size is a predictor of recurrence of AF during follow-up. For this reason, major clinical trials have used a left atrial diameter (LAD) of more than 5.0 or 5.5 cm, assessed by echocardiography, as an exclusion criterion for patients deemed candidates for ablation of AF. However, whether LAD accurately reflects true left atrial size has not been systematically investigated. Therefore, the purpose of this study was to test the hypothesis that LAD, measured by echocardiography, accurately correlates to left atrial volume measured by computed tomography (CT). METHODS AND RESULTS: We included 50 patients (mean age 56 +/- 12 years, five female) with symptomatic AF (40% paroxysmal, 60% persistent), referred for catheter ablation. In each patient, transthoracic echocardiography was performed. Additionally, all patients underwent CT using a 64-slice CT scanner. Left atrial volume was calculated by manually tracing left atrial area on each CT cross-sectional image. Patients had a mean LAD measured by echocardiography of 4.5 +/- 0.7 cm, ranging from 2.9 to 5.7 cm. Left atrial volume measured by CT ranged from 67 mL to 270 mL with a mean value of 146 +/- 49 mL. A poor correlation was noted between LAD and left atrial volume, r = 0.49 (P < 0.001). CONCLUSION: LAD measured by echocardiography correlates poorly with left atrial volume measured by CT in patients with AF. As a result, selecting patients with AF for treatment with catheter ablation should not be based on an echocardiographic-derived LAD alone.

Ibutilide-induced changes in the temporal lability of ventricular repolarization in patients with and without structural heart disease.

INTRODUCTION: Ibutilide has been shown to prolong repolarization times and increase the risk of ventricular tachyarrhythmias particularly in patients with structural heart disease. The mechanisms underlying its proarrhythmic effects remain incompletely understood. We sought to define the effects of ibutilide on the temporal lability of ventricular repolarization in patients with and without structural heart disease. METHODS: Twenty-four patients referred for electrophysiology study underwent monophasic action potential (MAP) recordings in the right ventricle during sinus rhythm and random interval right atrial pacing (RIAP). Ibutilide was subsequently administered and the recordings repeated both in sinus rhythm and with RIAP. Digitized recordings were analyzed offline for calculation of the QT variability index (QTVI) based on surface ECG, and the MAP duration variability index (MAPDVI) based on the intracardiac MAP signal. RESULTS: Of 24 patients enrolled, analyses were performed in 21 patients (mean age 59 +/- 15 years, 38% women). In three patients, the data were not analyzed due to frequent premature ventricular complexes. Ibutilide resulted in significant changes in heart rate (mean difference: -7.4 +/- 0.91 bpm, P < 0.0001) and the surface QT interval (mean difference: 59.6 +/- 12.2 ms, P = 0.0001) during sinus rhythm. After ibutilide, QTVI remained unchanged from baseline during sinus rhythm but was significantly different in the setting of RIAP (mean difference: 0.345 +/- 0.098, P = 0.0022). With subgroup analyses, these differences remained significant regardless of the presence or absence of heart disease. CONCLUSION: Ibutilide results in overall prolongation of ventricular repolarization and reductions in baseline sinus rates. Ibutilide increases temporal lability of repolarization only with enriched fluctuations in heart rate.

Incidence and predictors of left atrial thrombus prior to catheter ablation of atrial fibrillation.

BACKGROUND: Transesophageal echocardiography (TEE) is commonly used prior to catheter ablation of atrial fibrillation (AF) in order to exclude left atrial (LA) thrombus. However, the incidence and predictors of LA thrombus detected with TEE have not been systematically examined in this setting. METHODS: This study included 732 cases (mean age 57 +/- 11 years; 23% female; 353 persistent AF) in 585 consecutive patients referred for catheter ablation of AF. Patients were anticoagulated for at least 4 weeks prior to the procedure and then bridged with enoxaparin. TEE was performed in all cases within 24 hours prior to ablation. RESULTS: Preprocedural TEE revealed LA thrombus in 12 of 732 cases (1.6%), all located in the LA appendage. Among these 12 patients, 9 had persistent AF and 3 had paroxysmal AF. All patients with thrombus had an LA size >or= 4.5 cm. LA thrombus was present in 0.3%, 1.4%, and 5.3% of patients with CHADS(2) scores of 0, 1, and >or= 2, respectively. In multivariate analysis, a CHADS(2) score >or= 2 and larger LA diameter remained significant predictors of LA thrombus. CONCLUSIONS: Despite oral anticoagulation treatment, there is a small but significant incidence of LA thrombus by TEE prior to AF ablation. A CHADS(2) score >or= 2 and larger LA diameter are independent predictors of LA thrombus in this patient population, while type of AF or rhythm at the time of TEE is not. The risk of LA thrombus is low in patients with a CHADS(2) score of 0 and in patients with an LA diameter < 4.5 cm.