Age and Aspirin Dosing in Secondary Prevention of Atherosclerotic Cardiovascular Disease.

BACKGROUND: In patients with atherosclerotic cardiovascular disease, increasing age is concurrently associated with higher risks of ischemic and bleeding events. The objectives are to determine the impact of aspirin dose on clinical outcomes according to age in atherosclerotic cardiovascular disease. METHODS AND RESULTS: In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) trial, patients with atherosclerotic cardiovascular disease were randomized to daily aspirin doses of 81 mg or 325 mg. The primary effectiveness end point was death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety end point was hospitalization for bleeding requiring transfusion. A total of 15 076 participants were randomized to aspirin 81 mg (n=7540) or 325 mg (n=7536) daily (median follow-up: 26.2 months; interquartile range: 19.0-34.9 months). Median age was 67.6 years (interquartile range: 60.7-73.6 years). Among participants aged <65 years (n=5841 [38.7%]), a primary end point occurred in 226 (7.54%) in the 81 mg group, and in 191 (6.80%) in the 325 mg group (adjusted hazard ratio [HR], 1.23 [95% CI, 1.01-1.49]). Among participants aged ≥65 years (n=9235 [61.3%]), a primary end point occurred in 364 (7.12%) in the 81 mg group, and in 378 (7.96%) in the 325 mg group (adjusted HR, 0.95 [95% CI, 0.82-1.10]). The age-dose interaction was not significant (P=0.559). There was no significant interaction between age and the randomized aspirin dose for the secondary effectiveness and the primary safety bleeding end points (P>0.05 for all). CONCLUSIONS: Age does not modify the impact of aspirin dosing (81 mg or 325 mg daily) on clinical end points in secondary prevention of atherosclerotic cardiovascular disease.

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease and Diabetes Mellitus: A Subgroup Analysis of the ADAPTABLE Trial.

OBJECTIVE: Patients with diabetes mellitus (DM) and concomitant atherosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events. RESEARCH DESIGN AND METHODS: ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was assessed on the primary effectiveness outcome, a composite of all-cause death, hospitalization for myocardial infarction, or hospitalization for stroke, and the primary safety outcome of hospitalization for major bleeding. In this prespecified analysis, we used Cox proportional hazards models to compare aspirin dosing in patients with and without DM for the primary effectiveness and safety outcome. RESULTS: Of 15,076 patients, 5,676 (39%) had DM of whom 2,820 (49.7%) were assigned to 81 mg aspirin and 2,856 (50.3%) to 325 mg aspirin. Patients with versus without DM had higher rates of the composite cardiovascular outcome (9.6% vs. 5.9%; P < 0.001) and bleeding events (0.78% vs. 0.50%; P < 0.001). When comparing 81 mg vs. 325 mg of aspirin, patients with DM had no difference in the primary effectiveness outcome (9.3% vs. 10.0%; hazard ratio [HR] 0.98 [95% CI 0.83-1.16]; P = 0.265) or safety outcome (0.87% vs. 0.69%; subdistribution HR 1.25 [95% CI 0.72-2.16]; P = 0.772). CONCLUSIONS: This study confirms the inherently higher risk of patients with DM irrespective of aspirin dosing. Our findings suggest that a higher dose of aspirin yields no added clinical benefit, even in a more vulnerable population.

Effectiveness and Safety of Enteric-Coated vs Uncoated Aspirin in Patients With Cardiovascular Disease: A Secondary Analysis of the ADAPTABLE Randomized Clinical Trial.

Importance: Clinicians recommend enteric-coated aspirin to decrease gastrointestinal bleeding in secondary prevention of coronary artery disease even though studies suggest platelet inhibition is decreased with enteric-coated vs uncoated aspirin formulations. Objective: To assess whether receipt of enteric-coated vs uncoated aspirin is associated with effectiveness or safety outcomes. Design, Setting, and Participants: This is a post hoc secondary analysis of ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic study of 15 076 patients with atherosclerotic cardiovascular disease having data in the National Patient-Centered Clinical Research Network. Patients were enrolled from April 19, 2016, through June 30, 2020, and randomly assigned to receive high (325 mg) vs low (81 mg) doses of daily aspirin. The present analysis assessed the effectiveness and safety of enteric-coated vs uncoated aspirin among those participants who reported aspirin formulation at baseline. Data were analyzed from November 11, 2019, to July 3, 2023. Intervention: ADAPTABLE participants were regrouped according to aspirin formulation self-reported at baseline, with a median (IQR) follow-up of 26.2 (19.8-35.4) months. Main Outcomes and Measures: The primary effectiveness end point was the cumulative incidence of the composite of myocardial infarction, stroke, or death from any cause, and the primary safety end point was major bleeding events (hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage). Cumulative incidence at median follow-up for primary effectiveness and primary safety end points was compared between participants taking enteric-coated or uncoated aspirin using unadjusted and multivariable Cox proportional hazards models. All analyses were conducted for the intention-to-treat population. Results: Baseline aspirin formulation used in ADAPTABLE was self-reported for 10 678 participants (median [IQR] age, 68.0 [61.3-73.7] years; 7285 men [68.2%]), of whom 7366 (69.0%) took enteric-coated aspirin and 3312 (31.0%) took uncoated aspirin. No significant difference in effectiveness (adjusted hazard ratio [AHR], 0.94; 95% CI, 0.80-1.09; P = .40) or safety (AHR, 0.82; 95% CI, 0.49-1.37; P = .46) outcomes between the enteric-coated aspirin and uncoated aspirin cohorts was found. Within enteric-coated aspirin and uncoated aspirin, aspirin dose had no association with effectiveness (enteric-coated aspirin AHR, 1.13; 95% CI, 0.88-1.45 and uncoated aspirin AHR, 0.99; 95% CI, 0.83-1.18; interaction P = .41) or safety (enteric-coated aspirin AHR, 2.37; 95% CI, 1.02-5.50 and uncoated aspirin AHR, 0.89; 95% CI, 0.49-1.64; interaction P = .07). Conclusions and Relevance: In this post hoc secondary analysis of the ADAPTABLE randomized clinical trial, enteric-coated aspirin was not associated with significantly higher risk of myocardial infarction, stroke, or death or with lower bleeding risk compared with uncoated aspirin, regardless of dose, although a reduction in bleeding with enteric-coated aspirin cannot be excluded. More research is needed to confirm whether enteric-coated aspirin formulations or newer formulations will improve outcomes in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.

Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients Treated With P2Y12 Inhibitors.

Background The ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high- versus low-dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. Methods and Results Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22-1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91-2.22]). We found no interaction in the relative effectiveness and safety of high- versus low-dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high-dose compared with low-dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. Conclusions In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high- versus low-dose aspirin was not modified by baseline P2Y12 inhibitor use. Registration https://www.clinical.trials.gov. Unique identifier: NCT02697916.

Comparison of the effectiveness and safety of 2 aspirin doses in secondary prevention of cardiovascular outcomes in patients with chronic kidney disease: A subgroup analysis of ADAPTABLE.

BACKGROUND: Among patients with established cardiovascular disease, the ADAPTABLE trial found no significant differences in cardiovascular events and bleeding rates between 81 mg and 325 mg of aspirin (ASA) daily. In this secondary analysis from the ADAPTABLE trial, we studied the effectiveness and safety of ASA dosing in patients with a history of chronic kidney disease (CKD). METHODS: ADAPTABLE participants were stratified based on the presence or absence of CKD, defined using ICD-9/10-CM codes. Within the CKD group, we compared outcomes between patients taking ASA 81 mg and 325 mg. The primary effectiveness outcome was defined as a composite of all cause death, myocardial infarction, or stroke and the primary safety outcome was hospitalization for major bleeding. Adjusted Cox proportional hazard models were utilized to report differences between the groups. RESULTS: After excluding 414 (2.7%) patients due to missing medical history, a total of 14,662 patients were included from the ADAPTABLE cohort, of whom 2,648 (18%) patients had CKD. Patients with CKD were older (median age 69.4 vs 67.1 years; P < .0001) and less likely to be white (71.5% vs 81.7%; P < .0001) when compared to those without CKD. At a median follow-up of 26.2 months, CKD was associated with an increased risk of both the primary effectiveness outcome (adjusted HR 1.79 [1.57, 2.05] P < .001 and the primary safety outcome (adjusted HR 4.64 (2.98, 7.21), P < .001 and P < .05, respectively) regardless of ASA dose. There was no significant difference in effectiveness (adjusted HR 1.01 95% CI 0.82, 1.23; P = .95) or safety (adjusted HR 0.93; 95% CI 0.52, 1.64; P = .79) between ASA groups. CONCLUSIONS: Patients with CKD were more likely than those without CKD to have adverse cardiovascular events or death and were also more likely to have major bleeding requiring hospitalization. However, there was no association between ASA dose and study outcomes among these patients with CKD.

Surge of neurophysiological coupling and connectivity of gamma oscillations in the dying human brain.

The brain is assumed to be hypoactive during cardiac arrest. However, animal models of cardiac and respiratory arrest demonstrate a surge of gamma oscillations and functional connectivity. To investigate whether these preclinical findings translate to humans, we analyzed electroencephalogram and electrocardiogram signals in four comatose dying patients before and after the withdrawal of ventilatory support. Two of the four patients exhibited a rapid and marked surge of gamma power, surge of cross-frequency coupling of gamma waves with slower oscillations, and increased interhemispheric functional and directed connectivity in gamma bands. High-frequency oscillations paralleled the activation of beta/gamma cross-frequency coupling within the somatosensory cortices. Importantly, both patients displayed surges of functional and directed connectivity at multiple frequency bands within the posterior cortical "hot zone," a region postulated to be critical for conscious processing. This gamma activity was stimulated by global hypoxia and surged further as cardiac conditions deteriorated in the dying patients. These data demonstrate that the surge of gamma power and connectivity observed in animal models of cardiac arrest can be observed in select patients during the process of dying.

Oral hygiene and infective endocarditis: a case control study.

OBJECTIVE: To determine if oral hygiene is associated with infective endocarditis (IE) among those at moderate risk for IE. STUDY DESIGN: This is a case control study of oral hygiene among hospitalized patients with IE (cases) and outpatients with heart valve disease but without IE (controls). The primary outcome was the mean dental calculus index. Secondary outcomes included other measures of oral hygiene and periodontal disease (e.g., dental plaque, gingivitis) and categorization of blood culture bacterial species in case participants. RESULTS: The 62 case participants had 53% greater mean dental calculus index than the 119 control participants (0.84, 0.55, respectively; difference = 0.29, 95% CI: 0.11, 0.48; P = .002) and 26% greater mean dental plaque index (0.88, 0.70, respectively; difference = 0.18, 95% CI: 0.01.0.36; P = .043). Overall, cases reported fewer dentist and dental hygiene visits (P = .013) and fewer dental visits in the 12 weeks before enrollment than controls (P = .007). Common oral bacteria were identified from blood cultures in 27 of 62 cases (44%). CONCLUSIONS: These data provide evidence to support and strengthen current American Heart Association guidance that those at risk for IE can reduce potential sources of IE-related bacteremia by maintaining optimal oral health through regular professional dental care and oral hygiene procedures.

Importance of patient engagement in the conduct of pragmatic multicenter randomized controlled trials: The ADAPTABLE experience.

BACKGROUND/AIMS: Actively engaging patient partners in the conduct of trials is crucial to ensure the studies answer genuine, patient-centered, unmet clinical needs, and to facilitate participant recruitment and retention. The aim of this article is to demonstrate the feasibility of patient engagement within a large pragmatic multicenter randomized controlled trial, specifically for the purposes of dissemination of study information/updates and to favorize recruitment and retention. METHODS: In the patient-centric, pragmatic ADAPTABLE randomized trial, transparent and timely dissemination of information on the study updates to the trial participants was undertaken to create meaningful engagement and to facilitate retention. A national panel of patient partners, the Adaptors, were directly involved in this information dissemination strategy, and study participants were engaged both nationally and locally to design recruitment methods iteratively during the conduct of the trial. All Adaptors had a lived experience with cardiovascular disease. RESULTS: Adaptors attended bi-weekly meetings facilitated by the director of the study's patient-powered research network. They drafted and/or edited newsletters and ad hoc educational information written in a lay-friendly manner for study participants, which were regularly distributed to the ADAPTABLE community, in addition to online forums where participants could share their experience of their involvement in ADAPTABLE. To spur recruitment, a patient-driven initiative was to draft letters sharing their story, which were distributed by the local study teams. Patient partners thought that using patients' voice to provide their perspectives on why they believed this project was important would be more engaging for prospective participants than traditional approaches. CONCLUSIONS: ADAPTABLE's experience has demonstrated the feasibility of engaging patients as partners in the conduct of a large-scale, multi-center, pragmatic randomized controlled trial. Future trials should embrace and iteratively improve this model by engaging patient partners as early as study protocol development and funding applications, and quantify its impact on the effectiveness and value of the trial.

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

BACKGROUND: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).

Rationale and Design of the Aspirin Dosing-A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) Trial.

Importance: Determining the right dosage of aspirin for the secondary prevention treatment of atherosclerotic cardiovascular disease (ASCVD) remains an unanswered and critical question. Objective: To report the rationale and design for a randomized clinical trial to determine the optimal dosage of aspirin to be used for secondary prevention of ASCVD, using an innovative research method. Design, Setting, and Participants: This pragmatic, open-label, patient-centered, randomized clinical trial is being conducted in 15 000 patients within the National Patient-Centered Clinical Research Network (PCORnet), a distributed research network of partners including clinical research networks, health plan research networks, and patient-powered research networks across the United States. Patients with established ASCVD treated in routine clinical practice within the network are eligible. Patient recruitment began in April 2016. Enrollment was completed in June 2019. Final follow-up is expected to be completed by June 2020. Interventions: Participants are randomized on a web platform in a 1:1 fashion to either 81 mg or 325 mg of aspirin daily. Main Outcomes and Measures: The primary efficacy end point is the composite of all-cause mortality, hospitalization for nonfatal myocardial infarction, or hospitalization for a nonfatal stroke. The primary safety end point is hospitalization for major bleeding associated with a blood-product transfusion. End points are captured through regular queries of the health systems' common data model within the structure of PCORnet's distributed data environment. Conclusions and Relevance: As a pragmatic study and the first interventional trial conducted within the PCORnet electronic data infrastructure, this trial is testing several unique and innovative operational approaches that have the potential to disrupt and transform the conduct of future patient-centered randomized clinical trials by evaluating treatments integrated in clinical practice while at the same time determining the optimal dosage of aspirin for secondary prevention of ASCVD. Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.

Electrocardiomatrix Facilitates Accurate Detection of Atrial Fibrillation in Stroke Patients.

Background and Purpose- Cardiac telemetry is a routine part of inpatient ischemic stroke/transient ischemic attack evaluation to assess for atrial fibrillation (AF). Yet, tools to assist stroke clinicians in the evaluation of the large quantities of telemetry data are limited. The investigators developed a new method to evaluate electrocardiographic signals, electrocardiomatrix, that was applied to stroke unit telemetry data to determine its feasibility, validity, and usefulness. Electrocardiomatrix displays telemetry data in a 3-dimensional matrix that allows for more accurate and less time consuming P-wave analysis. Methods- In this single-center, prospective, observational study conducted in a stroke unit, all telemetry data from ischemic stroke and transient ischemic attack patients were collected (April 2017-January 2018) for examination facilitated by electrocardiomatrix. AF>30 seconds was identified through review of electrocardiomatrix-generated matrices by a nonphysician researcher. Electrocardiomatrix results were compared with the clinical team's medical record documentation of AF identified through telemetry. A study cardiologist reviewed the standard telemetry associated with all AF episodes identified by electrocardiomatrix and each case of disagreement. Results- Telemetry data (median 46 hours [interquartile range: 22-90]) were analyzed among 265 unique subjects (88% ischemic stroke). Electrocardiomatrix was successfully applied in 260 (98%) of cases. The positive predictive value of electrocardiomatrix compared with the clinical documentation was 86% overall and 100% among the subset with no prior history of AF. For the 5 false-positive and 5 false-negative cases, expert overview disagreed with the clinical documentation and confirmed the electrocardiomatrix-based diagnosis. Conclusions- The application of electrocardiomatrix to stroke unit-acquired telemetry data is feasible and appears to have superior accuracy compared with traditional monitor analysis by noncardiologists.

Surge of corticocardiac coupling in SHRSP rats exposed to forebrain cerebral ischemia.

Sudden death is an important but underrecognized consequence of stroke. Acute stroke can disturb central control of autonomic function and result in cardiac dysfunction and sudden death. Previous study showed that bilateral common carotid artery ligation (BCCAL) in the spontaneously hypertensive stroke-prone rat strain (SHRSP) is a well-established model for forebrain ischemic sudden death. This study aims to investigate the temporal dynamic changes in electrical activities of the brain and heart and functional interactions between the two vital organs following forebrain ischemia. EEG and ECG signals were simultaneously collected from nine SHRSP and eight Wistar-Kyoto (WKY) rats. RR interval was analyzed to investigate the cardiac response to brain ischemia. EEG power and coherence (CCoh) analysis were conducted to study the cortical response. Corticocardiac coherence (CCCoh) and directional connectivity (CCCon) were analyzed to determine brain-heart connection. Heart rate variability (HRV) was analyzed to evaluate autonomic functionality. BCCAL resulted in 100% mortality in SHRSP within 14 h, whereas no mortality was observed in WKY rats. The functionality of both the brain and the heart were significantly altered in SHRSP compared with WKY rats after BCCAL. SHRSP, but not WKY rats, exhibited intermittent surge of CCCoh, which paralleled the elevated CCCon and reduced HRV, following the onset of ischemia until sudden death. Elevated brain-heart coupling invariably associated with the disruption of the autonomic nervous system and the risk of sudden death. This study may improve our understanding of the mechanism of forebrain ischemia-induced sudden death. NEW & NOTEWORTHY This study demonstrates a marked surge of corticocardiac coupling in rats dying from focal cerebral ischemia, consistent with our earlier data in rats exposed to fatal asphyxia. Since the bidirectional electrical signal coupling (corticocardiac coherence) and communication (corticocardiac connectivity) between the brain and the heart are only identified in dying animals, they could be used as potential biomarkers to predict the risk of sudden death.

Reported obstructive sleep apnea does not diminish the cardiometabolic health benefits from a comprehensive lifestyle intervention program.

Obstructive sleep apnea (OSA) commonly coexists with the metabolic syndrome, a condition for which behavioral changes are often prescribed. Whether OSA diminishes the cardiometabolic health benefits from lifestyle interventions remains unclear. We evaluated 278 consecutive metabolic syndrome participants enrolled in a 12-week comprehensive lifestyle intervention program. The changes in blood pressure (BP), along with other metabolic health parameters, from baseline to follow-up were compared between those with and without OSA. Mean age was 52.4 ± 10.9 years and 37% were male. At enrollment, mean body mass index (BMI) was 38.2 ± 7.7 kg/m2 . OSA was reported in 126 of 269 final participants (47%). At baseline, participants with reported OSA were more likely to be male, older, have a higher BMI, waist and neck size (all P < 0.05). At program completion, participants with (-5.8 ± 16.1/-3.0 ± 10.0 mm Hg) and without OSA (-4.7 ± 13.1/-3.3 ± 8.2 mm Hg) had significant reductions in systolic and diastolic BP as well as BMI, fasting glucose, and triglyceride levels. There were no significant differences in the absolute or percentage changes in BP or other metabolic parameters between groups. Our findings support that patients with the metabolic syndrome can derive substantial health benefits, including reductions in BP, by a lifestyle intervention program regardless of the presence of OSA.

Accurate detection of atrial fibrillation and atrial flutter using the electrocardiomatrix technique.

BACKGROUND: Atrial fibrillation (AFIB) and atrial flutter (AFL) are two common cardiac arrhythmias that predispose patients to serious medical conditions. There is a need to accurately detect these arrhythmias to prevent diseases and reduce mortality. Apart from accurately detecting these arrhythmias, it is also important to distinguish between AFIB and AFL due to differing clinical treatments. METHODS: In this study, we applied a new technology, the electrocardiomatrix (ECM) invented in our lab, in detecting AFIB and AFL in human patients. ECM converts 2D ECG signals into a 3D color matrix, which renders arrhythmia detection intuitive, fast, and accurate. Using ECM, we analyzed the ECG signals from the online MIT-BIH Atrial Fibrillation Database (PhysioNet), and compared our ECM-based results to manual annotations based on ECG by physicians. RESULTS: Results demonstrate that ECM and PhysioNet annotations of AFIB and AFL agree more than 99% of the time. The sensitivities of the ECM for AFIB and AFL detection were 99.2% and 98.0%, respectively, and the specificities of the ECM for AFIB and AFL were both at 99.8% and 99.8%. CONCLUSIONS: This study demonstrates that ECM is a reliable method for accurate identification of AFIB and AFL.

Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest.

Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients.

Efficacy of Sleep Tool Education During Hospitalization: A Randomized Controlled Trial.

BACKGROUND: Patients are commonly provided tools in the hospital to overcome poor sleep. Whether education on use of sleep tools can impact health outcomes from a patient perspective is not known. METHODS: We recruited 120 adults admitted to a nonintensive care unit cardiac-monitored floor. All patients received a set of sleep-enhancing tools (eye mask, ear plugs, and a white noise machine) and were randomized to receive direct education on use of and benefit of these sleep-enhancing tools (intervention), or an equal amount of time was spent discussing general benefits of sleep (control). Measurement of several symptom domains was assessed daily by health outcome survey responses, and change from baseline was assessed for differences between groups. Inpatient opioid use and length of stay were also measured. RESULTS: Participants randomized to receive the education intervention had a significantly greater decrease in fatigue scores over the 3 days, compared with controls (5.30 ± 6.93 vs 1.81 ± 6.96, t = 2.32, P = .028). There was a trend toward improvements in multiple other sleep-related domains, including sleep disturbance, sleep-related impairment, physical functioning, pain severity, or pain interference (all P >.140). There was no difference in length of stay between intervention and control groups (7.40 ± 7.29 vs 7.71 ± 6.06 days, P = .996). The change in number of opioid equivalents taken did not differ use between the groups (P = .688). CONCLUSION: In a randomized trial of education in the use of sleep-enhancing tools while hospitalized, patient fatigue was significantly improved, whereas several other patient-reported outcomes showed a trend toward improvements. Implementation of this very low-cost approach to improving sleep and well-being could substantially improve the patient care experience.

Occult obstructive sleep apnea and clinical outcomes of radiofrequency catheter ablation in patients with atrial fibrillation.

BACKGROUND: Recurrent atrial fibrillation (AF) after successful cardioversion can be predicted by obstructive sleep apnea (OSA) diagnosed by polysomnography. However, it is not known whether the validated STOP-BANG questionnaire can predict AF recurrence after radiofrequency ablation (RFA). Our objective is to determine the prevalence of unrecognized OSA in patients with AF and its relation to freedom from AF after RFA. METHODS: Validated surveys were administered to 247 consecutive AF patients following radiofrequency ablation from January to October 2011. OSA status was assessed at baseline RFA. Clinical follow up occurred at 3-6 month intervals. RESULTS: OSA had been previously diagnosed in 94/247 (38%). Among 153 patients without prior diagnosis of OSA, 121 (79%) had high risk STOP-BANG scores for OSA. Probability of maintaining sinus rhythm after RFA was similar among patients with known OSA (66/94, 70%) and high risk OSA scores (95/124, 77%) and higher than among patients with low risk OSA scores (29/32, 91%, P=0.03). Among patients without prior OSA, a high risk STOP-BANG score did predict recurrent AF (OR = 3.7, 95 % CI 1.4-11.4, P = 0.0005). Multivariate analysis showed a higher risk of atrial arrhythmia recurrence for non-paroxysmal AF patients (OR = 3.1, ± 95 % CI 1.4-7.1, P = 0.005). CONCLUSIONS: The majority of AF patients undergoing RFA have high risk OSA scores, suggesting that OSA is vastly underdiagnosed in this population. STOP-BANG independently predicted recurrent AF in patients without a prior diagnosis of OSA.