[Show abstract][Hide abstract] ABSTRACT: Among patients with implantable pacemakers and defibrillators, sub-clinical atrial fibrillation (SCAF) is associated with an increased risk of stroke; however, there is limited understanding of their temporal relationship.
The ASSERT trial enrolled 2580 pacemaker and defibrillator patients ≥ 65 years old, with a history of hypertension, but without a history of atrial fibrillation. Pacemakers and ICDs precisely logged the time and duration of all episodes of SCAF and recorded electrograms which were adjudicated by experts. We examined the temporal relationship between SCAF > 6 minutes in duration and stroke or systemic embolism. Of 51 patients who experienced stroke or systemic embolism during follow-up; 26 (51%) had SCAF. In 18 patients (35%) SCAF was detected prior to stroke or systemic embolism. However, only 4 patients (8%) had SCAF detected within 30 days prior and only one of these 4 patients was experiencing SCAF at the time of their stroke. In the 14 patients with SCAF detected more than 30 days prior to stroke or systemic embolism, the most recent episode occurred at a median interval of 339 days (P25-P75: 211-619) earlier. Eight patients (16%) had SCAF detected only after their stroke, despite continuous monitoring for median duration of 228 (P25-P75: 202-719) days prior to their event.
Although SCAF is associated with an increased risk of stroke and embolism, very few patients had SCAF in the month prior to their event.
http://www.clinicaltrials.gov. Identifier: NCT00256152.
[Show abstract][Hide abstract] ABSTRACT: Ethnic Difference in Atrial Fibrillation Incidence. Introduction: Atrial fibrillation (AF) is suggested to be less common among black and Asian individuals, which could reflect bias in symptom reporting and access to care. In the Asymptomatic AF and Stroke Evaluation in Pacemaker Patients and the AF Reduction Atrial Pacing Trial (ASSERT), patients with hypertension but no history of AF had AF recorded via an implanted pacemaker or defibrillator, thus allowing both symptomatic and asymptomatic AF incidence to be determined without ascertainment bias. Methods and Results: The ASSERT enrolled 2,580 patients in 23 countries in North America, Europe, and Asia. AF was defined as device-recorded AF episodes >190/min, lasting either for >6 minutes or >6 hours in duration. All ethnic groups with >50 patients were enrolled. Ethnic groups studied include Europeans (n = 1900), black Africans (n = 73), Chinese (n = 89), and Japanese (n = 105) patients. Compared to Europeans, black Africans had more risk factors for AF such as heart failure (27.8 vs 14.6%) and diabetes (41.7 vs 26.3%). At 2.5 years follow-up, all 3 non-European races had a lower incidence of AF (8.3%, 10.1%, and 9.5% vs 18.0%, respectively, for AF>6 minutes, P < 0.006). When adjusted for baseline difference, Chinese had a lower incidence of AF > 6 minutes (P < 0.007), and Japanese and black Africans had a lower incidence of AF > 6 hours (P < 0.04 and P = 0.057, respectively). Conclusions: Black Africans, Chinese, and Japanese had lower incidence of AF compared to Europeans. In the case of black Africans, this is despite an increased prevalence of AF risk factors. (J Cardiovasc Electrophysiol, Vol. pp. 1-7).
Journal of Cardiovascular Electrophysiology 01/2013; · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pacing algorithms to prevent atrial fibrillation (AF) have been tested in studies of modest size and duration with inconclusive results.
To prospectively evaluate the relationship between subclinical AF and stroke in patients 65 years of age or older with no previous AF receiving a first pacemaker or an implantable cardioverter-defibrillator for standard indications. Three months following device implantation, pacemaker patients were randomized to have continuous atrial overdrive pacing (CAOP) algorithm turned "ON" or "OFF." The primary study outcome was development of electrocardiogram-documented AF >6 minutes.
A total of 2343 patients were randomized and followed for a mean of 2.5 years. The primary outcome occurred in 60 patients in the CAOP ON group (1.96% per year) and in 45 in the CAOP OFF group (1.44% per year; relative risk 1.38; 95% confidence interval 0.94-2.03; P = .10). Major clinical events (stroke, myocardial infarct, cardiovascular death, systemic embolism, heart failure hospitalization) occurred at similar frequencies in the 2 groups. In the CAOP ON group, 133 of the 1164 patients (11.4%) crossed over to CAOP OFF compared with 12 of the 1179 (1.0%) who crossed over from OFF to ON (P <.0001). False-positive device detections of AF were more common among patients assigned to CAOP ON (23%) than among patients assigned to CAOP OFF (7.7%; relative risk 2.99; 95% confidence interval 2.40-3.74; P <.001). Pacemaker generator replacement for battery depletion occurred in 4.4% of the subjects randomized to CAOP ON and in 2.5% of the patients assigned to CAOP OFF (relative risk 1.70; 95% confidence interval 1.08-2.67; P = .02).
CAOP does not prevent new-onset AF, is poorly tolerated, and accelerates pulse generator battery depletion.
Heart rhythm: the official journal of the Heart Rhythm Society 06/2012; 9(10):1667-73. · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In animal models of atrial fibrillation (AF), changes in atrial electrophysiological properties are associated with the development of AF. Their relevance to human AF is unclear.
The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial enrolled 2580 patients receiving a dual-chamber pacemaker, who were older than the age of 65 and had a history of hypertension, but no history of AF. Serial noninvasive electrophysiological testing was performed over 2 years in a subgroup of 485 patients. There were no differences in the clinical characteristics between patients with and those without device-detected atrial tachyarrhythmias during the first year. Patients with atrial tachyarrhythmias had longer paced (153±29 versus 145±28 ms; P=0.046) and sensed (128±46 versus 118±25 ms; P=0.06) P-wave durations and were more likely to have AF induced during electrophysiological testing (23.5% versus 13.6%; P=0.03). They had similar corrected sinus node recovery times at 90 bpm (388±554 versus 376 ± 466 ms; P=0.86), atrial effective refractory periods at 90 bpm (250±32 versus 248±36 ms; P=0.70), and rate-adaptive shortening of the atrial effective refractory periods (14±13 versus 12±14 ms; P=0.11). There were no significant differences in the change in electrophysiological properties over 2 years between patients with and those without atrial tachyarrhythmias.
Prolonged P-wave duration, but not differences in atrial effective refractory periods, was associated with the development of atrial tachyarrhythmias in pacemaker patients.
Circulation Arrhythmia and Electrophysiology 06/2012; 5(4):626-31. · 5.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: One quarter of strokes are of unknown cause, and subclinical atrial fibrillation may be a common etiologic factor. Pacemakers can detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented atrial fibrillation. We evaluated whether subclinical episodes of rapid atrial rate detected by implanted devices were associated with an increased risk of ischemic stroke in patients who did not have other evidence of atrial fibrillation.
We enrolled 2580 patients, 65 years of age or older, with hypertension and no history of atrial fibrillation, in whom a pacemaker or defibrillator had recently been implanted. We monitored the patients for 3 months to detect subclinical atrial tachyarrhythmias (episodes of atrial rate >190 beats per minute for more than 6 minutes) and followed them for a mean of 2.5 years for the primary outcome of ischemic stroke or systemic embolism. Patients with pacemakers were randomly assigned to receive or not to receive continuous atrial overdrive pacing.
By 3 months, subclinical atrial tachyarrhythmias detected by implanted devices had occurred in 261 patients (10.1%). Subclinical atrial tachyarrhythmias were associated with an increased risk of clinical atrial fibrillation (hazard ratio, 5.56; 95% confidence interval [CI], 3.78 to 8.17; P<0.001) and of ischemic stroke or systemic embolism (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P=0.007). Of 51 patients who had a primary outcome event, 11 had had subclinical atrial tachyarrhythmias detected by 3 months, and none had had clinical atrial fibrillation by 3 months. The population attributable risk of stroke or systemic embolism associated with subclinical atrial tachyarrhythmias was 13%. Subclinical atrial tachyarrhythmias remained predictive of the primary outcome after adjustment for predictors of stroke (hazard ratio, 2.50; 95% CI, 1.28 to 4.89; P=0.008). Continuous atrial overdrive pacing did not prevent atrial fibrillation.
Subclinical atrial tachyarrhythmias, without clinical atrial fibrillation, occurred frequently in patients with pacemakers and were associated with a significantly increased risk of ischemic stroke or systemic embolism. (Funded by St. Jude Medical; ASSERT ClinicalTrials.gov number, NCT00256152.).
New England Journal of Medicine 01/2012; 366(2):120-9. · 54.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sudden cardiac arrest (SCA) is the most common cause of death in the United States. Despite national guidelines, patients at risk for SCA often fail to receive evidence-based therapies. Racial and ethnic minorities and women are at particularly high risk for undertreatment. To address the persistent challenges in improving the quality of care for SCA, the Duke Center for the Prevention of Sudden Cardiac Death at the Duke Clinical Research Institute (Durham, NC) reconvened the Sudden Cardiac Arrest Thought Leadership Alliance. Experts from clinical cardiology, cardiac electrophysiology, health policy and economics, the US Food and Drug Administration, the Centers for Medicare and Medicaid Services, the Agency for Health Care Research and Quality, and device and pharmaceutical manufacturers discussed the development of SCA educational tools for patients and providers, mechanisms of implementing successful tools to help providers identify patients in their practice at risk for SCA, disparities in SCA prevention, and performance measures related to SCA care. This article summarizes the discussions held at this meeting.
American heart journal 08/2011; 162(2):222-31. · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sudden cardiac arrest (SCA) is the most common cause of death in the Unites States. Despite its major impact on public health, significant challenges exist at the patient, provider, public, and policy levels with respect to raising more widespread awareness and understanding of SCA risks, identifying patients at risk for SCA, addressing barriers to SCA care, and eliminating disparities in SCA care and outcomes. To address many of these challenges, the Duke Center for the Prevention of Sudden Cardiac Death at the Duke Clinical Research Institute (Durham, NC) held a think tank meeting on December 7, 2009, convening experts on this issue from clinical cardiology, cardiac electrophysiology, health policy and economics, the US Food and Drug Administration, the Centers for Medicare and Medicaid Services, the Agency for Health Care Research and Quality, and device and pharmaceutical manufacturers. The specific goals of the meeting were to examine existing educational tools on SCA for patients, health care providers, and the public and explore ways to enhance and disseminate these tools; to propose a framework for improved identification of patients at risk of SCA; and to review the latest data on disparities in SCA care and explore ways to reduce these disparities. This article summarizes the discussions that occurred at the meeting.
American heart journal 10/2010; 160(4):605-18. · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter-defibrillator (ICD) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction < or =35% on optimal medical therapy. Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown.
SCD-HeFT randomized 2521 subjects to placebo, amiodarone, or shock-only, single-lead ICD therapy. Over a median follow-up of 45.5 months, a total of 666 deaths occurred, which were reviewed by an Events Committee and initially categorized as cardiac or noncardiac. Cardiac deaths were further adjudicated as resulting from sudden death presumed to be ventricular tachyarrhythmic, bradyarrhythmia, heart failure, or other cardiac causes. ICD therapy significantly reduced cardiac mortality compared with placebo (adjusted hazard ratio, 0.76; 95% confidence interval, 0.60 to 0.95) and tachyarrhythmia mortality (adjusted hazard ratio, 0.40; 95% confidence interval, 0.27 to 0.59) and had no impact on mortality resulting from heart failure or noncardiac causes. The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure. The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease. Compared with placebo, amiodarone had no significant effect on any mode of death.
ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality. Amiodarone had no effect on all-cause mortality or its cause-specific components, except an increase in non-cardiac mortality in class III patients. [corrected]
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000609.
[Show abstract][Hide abstract] ABSTRACT: Because the burden of sudden cardiac death (SCD) is substantial, it is important to use all guideline-driven therapies to prevent SCD. Among those therapies is the implantable cardioverter defibrillator (ICD). When indicated, ICD use is beneficial and cost-effective. Unfortunately, studies suggest that most patients who have indications for this therapy for primary or secondary prevention of SCD are not receiving it. To explore potential reasons for this underuse and to propose potential facilitators for ICD dissemination, the Duke Center for the Prevention of SCD at the Duke Clinical Research Institute (Durham, NC) organized a think tank meeting of experts on this issue. The meeting took place on December 12 and 13, 2007, and it included representatives of clinical cardiology, cardiac electrophysiology, general internal medicine, economics, health policy, the US Food and Drug Administration, the Centers for Medicare and Medicaid Services, the Agency for Health care Research and Quality, and the device and pharmaceutical industry. Although the meeting was funded by industry participants, this article summarizing the presentations and discussions that occurred at the meeting presents the expert opinion of the authors.
American heart journal 11/2008; 156(4):613-22. · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular Reflexes and Electrophysiology. The autonomic nervous system mediates control of the heart and circulation for several sensors located throughout the cardiovascular system. Afferent signals originate from mechanoreceptors located in the carotid sinus, aorta, chambers of the heart, and great veins near the heart, and from chemoreceptors in the aortic arch and carotid sinus. Efferent signals are transmitted through the vagus and sympathetic nerves to the heart and vascular tree. Hemodynamic and electrophysiologic homeostasis is maintained by beat-to-beat regulation via these reflexes. Several cardiovascular diseases are often accompanied by abnormal function of these reflexes; moreover, abnormalities of reflex control of the circulation often contribute to the pathophysiology of many cardiovascular diseases.
[Show abstract][Hide abstract] ABSTRACT: Mortality events in studies of cardiovascular disease are currently adjudicated using different methodologies depending on the investigators' preferences. Traditionally, deaths have been categorized by a single term, such as sudden, ischemic, or pump failure, a method that can be referred to as "categorical". In contrast, deaths may be categorized using several specific pieces of information about the event, a method that can be referred to as "multiparameter descriptive." Herein, we describe an adaptation of this descriptive method in a trial of patients with heart failure and arrhythmias.
Case examples were selected from two clinical trials of an investigational implantable cardioverter-defibrillator (ICD)-biventricular pacing system in patients with symptomatic heart failure and a class I indication for ICD implantation, and the complete results for one of the trials are given. Deaths were classified according to the new descriptive method, and also according to published categorical methods for heart failure and arrhythmia trials. The descriptive method preserved traditional arrhythmia and heart failure trial single category classifications of death. Furthermore, there was agreement between the arrhythmia and heart failure category classifications in 126 of the 148 of the mortality events adjudicated (85%).
A descriptive method for the classification of death retains more data and allows for comparison among trials using different classification schemes. This may allow greater mechanistic insight into study populations that have diverse and frequently multiple etiologies of death.
[Show abstract][Hide abstract] ABSTRACT: Although current evidence supporting a more precise strategy for identifying patients at highest risk for sudden cardiac death (SCD) is sparse, strategies for translating existing and future evidence into clinical practice and policy are needed today. A great many unanswered questions exist. Examples include the following: At what level of risk for SCD should we pursue further testing or therapy? How should clinical strategies ethically and economically balance alternative outcomes? How can we best translate optimal strategies into clinical practice so as to prevent tomorrow's SCDs? On July 20 and 21, 2006, a group of individuals with expertise in clinical cardiovascular medicine, biostatistics, economics, and health policy was joined by government (Food and Drug Administration; Centers for Medicare and Medicaid Services; National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality), professional societies (Heart Rhythm Society), and industry to discuss strategies for risk assessment and prevention of SCD. The meeting was organized by the Duke Center for the Prevention of Sudden Cardiac Death and the Duke Clinical Research Institute. This article, the second of 2 documents, summarizes the policy discussions of that meeting, discusses an analytic framework for evaluating the risks and benefits associated with SCD prevention and risk stratification, and addresses the translation of SCD risk assessment strategies into practice and policy.
American heart journal 07/2007; 153(6):951-9. · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Atrial overdrive pacing algorithms may be effective in preventing or suppressing atrial fibrillation (AF). However, the maintenance of a heart rate incessantly faster than spontaneous could induce left ventricular (LV) dysfunction and promote heart failure (HF) on the long term.
This post hoc analysis examined the effects of a new overdrive algorithm on the incidence of HF-related adverse events in 411 patients enrolled in the ADOPT-A trial.
The AF Suppression algorithm was randomly programmed ON in 209 patients (treatment group) versus OFF in 202 patients (control group). The incidence of HF-related adverse events and HF-related deaths over a 6-month follow-up was compared between the two groups. Patients with versus without HF-related clinical events were also compared to each other within each group.
There were eight HF-related adverse clinical events (3.8%) in the treatment group and 11 (5.4%) in the control group, including four HF-related deaths (1.9 vs. 2.0%) in each group during follow-up. Baseline NYHA functional class in patients with versus without HF-related adverse events was 1.4 +/- 0.5 versus 1.5 +/- 0.7 in the control, and 1.5 +/- 0.8 versus 1.5 +/- 0.6 in the treatment group. LV ejection fraction (EF) was 49 +/- 7% in patients with, versus 57 +/- 12% in patients without HF-related adverse events, in the control group, and 43 +/- 14% in patients with, versus 56 +/- 13% in patients without HF-related adverse events, in the treatment group. LVEF was lowest and similar in both groups among patients who died from HF (35 +/- 10% in the control and 38 +/- 27% in the treatment group).
In ADOPT-A, HF-related clinical events and deaths were related to LV dysfunction and not to atrial pacing overdriven by the AF suppression algorithm.
[Show abstract][Hide abstract] ABSTRACT: Accurate and timely prediction of sudden cardiac death (SCD) is a necessary prerequisite for effective prevention and therapy. Although the largest number of SCD events occurs in patients without overt heart disease, there are currently no tests that are of proven predictive value in this population. Efforts in risk stratification for SCD have focused primarily on predicting SCD in patients with known structural heart disease. Despite the ubiquity of tests that have been purported to predict SCD vulnerability in such patients, there is little consensus on which test, in addition to the left ventricular ejection fraction, should be used to determine which patients will benefit from an implantable cardioverter defibrillator. On July 20 and 21, 2006, a group of experts representing clinical cardiology, cardiac electrophysiology, biostatistics, economics, and health policy were joined by representatives of the US Food and Drug administration, Centers for Medicare Services, Agency for Health Research and Quality, the Heart Rhythm Society, and the device and pharmaceutical industry for a round table meeting to review current data on strategies of risk stratification for SCD, to explore methods to translate these strategies into practice and policy, and to identify areas that need to be addressed by future research studies. The meeting was organized by the Duke Center for the Prevention of SCD at the Duke Clinical Research Institute and was funded by industry participants. This article summarizes the presentations and discussions that occurred at that meeting.
American heart journal 07/2007; 153(6):941-50. · 4.56 Impact Factor