Characteristics of patients with atrial high rate episodes detected by implanted defibrillator and resynchronization devices.

AIMS: Atrial high rate episodes (AHREs) are associated with increased risks of thromboembolism and cardiovascular mortality. However, the clinical characteristics of patients developing AHRE of various durations are not well studied. METHODS AND RESULTS: This was an ancillary analysis of the multicentre, randomized IMPACT trial. In the present analysis, we classified patients according to the duration of AHRE ≤6 min, >6 min to ≤6 h, >6 to ≤24 h and >24 h, and investigated the association between clinical factors and the development of each duration of AHRE. Of 2718 patients included in the trial, 945 (34.8%) developed AHRE. The incidence rates of each AHRE duration category were 5.4/100, 12.0/100, 6.8/100, and 3.3/100 patient-years, respectively. The incidence rates of AHRE >6 h were significantly higher in patients at high risk of thromboembolism (CHADS2 score ≥3) compared to those at low risk (CHADS2 score 1 or 2). Using Cox regression analysis, age ≥65 years and history of atrial fibrillation (AF) and/or atrial flutter (AFL) were risk factors for AHRE >6 min. In addition, hypertension was associated with AHRE >24 h (hazard ratio 2.13, 95% confidence interval 1.24-3.65, P = 0.006). CONCLUSION: Atrial high rate episode >6 min to ≤6 h were most prevalent among all AHRE duration categories. Longer AHREs were more common in patients at risk of thromboembolism. Age and history of AF/AFL were risk factors for AHRE >6 min. Furthermore, hypertension showed a strong impact on the development of AHRE >24 h rather than age.

Determinants of Time in Therapeutic Range in Patients Receiving Oral Anticoagulants (A Substudy of IMPACT).

Implanted cardiac arrhythmia devices can detect atrial tachyarrhythmias (atrial high-rate episodes [AHREs]) that are considered to correlate with atrial fibrillation and risk of stroke. In the IMPACT trial, oral anticoagulation was initiated when AHREs were detected by implanted cardioverter-defibrillators and withdrawn when they abated, according to a protocol accounting both for AHRE duration as detected by remote device monitoring and stroke risk assessment. In this analysis, we ascertained determinants of time in therapeutic range (TTR) among protocol-determined vitamin K antagonist-treated patients during the trial. We enrolled 2,718 patients with at least 1 additional stroke risk factor (CHADS2 score ≥1) at 104 arrhythmia centers. The sex, age <60, medical history, treatments interacting with VKA, tobacco use (2 points) and race (2 points for non-Caucasian) (SAMe-TT2R2) score is a simple clinical-derived score designed to aid decision-making on whether a patient is likely to achieve good anticoagulation control on vitamin K antagonist (e.g., warfarin), which was calculated and related to TTR achieved using the Rosendaal method. We analyzed 229 patients (mean age 66.7 years; mean CHADS2 score 2.85 [SD 1.1]) with mean TTR of 0.536 (SD 0.23) overall. Univariate analysis identified 5 variables associated with differences in mean TTR. Mean TTR was lower in those who were women (p = 0.031), of black race (p = 0.005) and in New York Heart Association class IV (p = 0.014), whereas hemoglobin >13.5 g/dl (p = 0.010) and New York Heart Association class I (p = 0.037) were associated with higher mean TTR. There was a significant difference in mean TTR value between US and non-US sites (Canada and Germany) (mean TTR for US: 0.513 vs non-US: 0.686; p <0.0001). Mean TTR was significantly lower (Δ = 0.1382, 95% CI 0.0382 to 0.2382) for patients with SAMe-TT2R2 scores of 4 (p = 0.007) and higher (Δ = 0.0612, 95% CI 0.0005 to 0.1219) for patients with SAMe-TT2R2 scores of 1 (p = 0.048). Linear regression confirmed a significant association between lower SAMe-TT2R2 score and improved anticoagulation control (p = 0.0021) with a 1-unit decrease in SAMe-TT2R2 score associated with an increase in TTR of 0.0404 (95% CI 0.0149 to 0.0659). In conclusion, clinical, geographical, and demographic factors were associated with the quality of anticoagulation control as reflected by TTR. Although overall TTR in this population was poor, lower SAMe-TT2R2 scores were associated with better TTR.

Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices.

AIMS: Atrial tachyarrhythmias (ATs) detected by implanted devices are often atrial fibrillation or flutter (AF) associated with stroke. We hypothesized that introduction and termination of anticoagulation based upon AT monitoring would reduce both stroke and bleeding. METHODS AND RESULTS: We randomized 2718 patients with dual-chamber and biventricular defibrillators to start and stop anticoagulation based on remote rhythm monitoring vs. usual office-based follow-up with anticoagulation determined by standard clinical criteria. The primary analysis compared the composite endpoint of stroke, systemic embolism, and major bleeding with the two strategies. The trial was stopped after 2 years median follow-up based on futility of finding a difference in primary endpoints between groups. A total of 945 patients (34.8%) developed AT, 264 meeting study anticoagulation criteria. Adjudicated atrial electrograms confirmed AF in 91%; median time to initiate anticoagulation was 3 vs. 54 days in the intervention and control groups, respectively (P < 0.001). Primary events (2.4 vs. 2.3 per 100 patient-years) did not differ between groups (HR 1.06; 95% CI 0.75-1.51; P = 0.732). Major bleeding occurred at 1.6 vs. 1.2 per 100 patient-years (HR 1.39; 95% CI 0.89-2.17; P = 0.145). In patients with AT, thromboembolism rates were 1.0 vs. 1.6 per 100 patient-years (relative risk -35.3%; 95% CI -70.8 to 35.3%; P = 0.251). Although AT burden was associated with thromboembolism, there was no temporal relationship between AT and stroke. CONCLUSION: In patients with implanted defibrillators, the strategy of early initiation and interruption of anticoagulation based on remotely detected AT did not prevent thromboembolism and bleeding. CLINICAL TRIAL REGISTRATION: IMPACT ClinicalTrials.gov identifier: NCT00559988 ( http://clinicaltrials.gov/ct2/show/NCT00559988?term=NCT00559988&rank=1 ).

Multicenter randomized study of anticoagulation guided by remote rhythm monitoring in patients with implantable cardioverter-defibrillator and CRT-D devices: Rationale, design, and clinical characteristics of the initially enrolled cohort The IMPACT study.

Atrial fibrillation and atrial flutter are common cardiac arrhythmias associated with an increased risk of stroke in patients with additional risk factors. Anticoagulation ameliorates stroke risk, but because these arrhythmias may occur intermittently without symptoms, initiation of prophylactic therapy is often delayed until electrocardiographic documentation is obtained. The IMPACT study is a multicenter, randomized trial of remote surveillance technology in patients with implanted dual-chamber cardiac resynchronization therapy defibrillator (CRT-D) devices designed to test the hypothesis that initiation and withdrawal of oral anticoagulant therapy guided by continuous ambulatory monitoring of the atrial electrogram improve clinical outcomes by reducing the combined rate of stroke, systemic embolism, and major bleeding compared with conventional clinical management. For those in the intervention group, early detection of atrial high-rate episodes (AHRE) generates an automatic alert to initiate anticoagulation based on patient-specific stroke risk stratification. Subsequently, freedom from AHRE for predefined periods prompts withdrawal of anticoagulation to avoid bleeding. Patients in the control arm are managed conventionally, the anticoagulation decision prompted by incidental detection of atrial fibrillation or atrial flutter during routine clinical follow-up. The results will help define the clinical utility of wireless remote cardiac rhythm surveillance and help establish the critical threshold of AHRE burden warranting anticoagulant therapy in patients at risk of stroke. In this report, we describe the study design and baseline demographic and clinical features of the initial cohort (227 patients).

Reduced endothelium-dependent and -independent dilation of conductance arteries in African Americans.

OBJECTIVES: The goal of this study was to determine whether racial differences exist in the functional behavior of conduit vessels. BACKGROUND: Compared with Caucasians, African Americans have a higher prevalence of cardiovascular disease and its complications, which may be related to reduced nitric oxide (NO)-dependent and -independent vasodilation of the microvasculature. However, whether a similar impairment is also present at the level of the conductance arteries is unknown. METHODS: To this end, we studied endothelium-dependent (posthyperemia flow-mediated dilation) and -independent (nitroglycerin) vascular responses of the brachial artery by high-resolution ultrasound imaging. There were 46 black subjects (23 men and 23 women; age 37 +/- 8 years and 38 +/- 9 years, respectively) and 46 white subjects (23 men and 23 women; age 38 +/- 11 years and 36 +/- 9 years, respectively) in this study. RESULTS: Baseline diameter was similar in blacks and in whites (4.4 +/- 0.9 mm and 4.1 +/- 0.7 mm, respectively). Mean reactive hyperemia after cuff deflation was similar in the two groups (793 +/- 653% in black and 852 +/- 734% in white subjects, respectively; p = 0.5). Flow-mediated dilation was significantly lower in black compared with white individuals (4.79 +/- 3.5% vs. 8.87 +/- 4.5%, respectively; p < 0.0001). Nitroglycerin-mediated dilation was also significantly lower in black individuals compared with white individuals (10.99 +/- 4.6% vs. 14.98 +/- 5.4%, respectively; p = 0.0002). CONCLUSIONS: African Americans show reduced responsiveness of conductance vessels to both endogenous and exogenous NO compared with Caucasian Americans. These findings expand our understanding of racial differences in vascular function and suggest a mechanistic explanation for the increased incidence and severity of cardiovascular disease observed in African Americans.

Role of cyclooxygenase products in the regulation of vascular tone and in the endothelial vasodilator function of normal, hypertensive, and hypercholesterolemic humans.

A defective vascular activity of endothelial vasoactive substances is observed in essential hypertension and hypercholesterolemia, and is believed to participate in the vascular abnormalities characteristic of these conditions. The present study aimed to determine the role of cyclooxygenase (COX) products in the maintenance of vascular tone and in the endothelium-mediated vasodilation of healthy subjects, and to investigate their contribution to the endothelial dysfunction of essential hypertensive and hypercholesterolemic patients. The effects of intra-arterial aspirin (acetylsalicylic acid [ASA], 1, 3, and 10 mg/min) were assessed on basal forearm blood flow (strain gauge plethysmography) and on responses to acetylcholine (7.5, 15 and 30 microg/min) and sodium nitroprusside (0.8, 1.6 and 3.2 microg/min) in 24 normal, 23 hypertensive, and 24 hypercholesterolemic subjects. Basal forearm blood flow was not different among the 3 groups (p = 0.95). ASA resulted in a significant reduction of forearm blood flow from baseline in normal (p = 0.003), hypertensive (p = 0.001), and hypercholesterolemic subjects (p = 0.001), without any difference among the 3 groups (p = 0.90). ASA significantly improved the effect of acetylcholine in normal (p = 0.008), hypertensive (p = 0.008), and hypercholesterolemic subjects (p = 0.022), without significant difference among the 3 groups (p = 0.46). ASA did not significantly modify the vasodilator effect of sodium nitroprusside in any of the 3 groups. These findings suggest that in humans, vasodilator prostanoids actively contribute to the maintenance of basal vascular tone, whereas vasoconstrictor products of COX activity limit endothelium-dependent vasodilation. COX products do not appear to play a major role in the endothelial dysfunction of hypertensive or hypercholesterolemic patients.