Device Therapies Among Patients Receiving Primary Prevention Implantable Cardioverter-Defibrillators in the Cardiovascular Research Network

BACKGROUND: Primary prevention implantable cardioverter-defibrillators (ICDs) reduce mortality in selected patients with left ventricular systolic dysfunction by delivering therapies (antitachycardia pacing or shocks) to terminate potentially lethal arrhythmias; inappropriate therapies also occur. We assessed device therapies among adults receiving primary prevention ICDs in 7 healthcare systems. METHODS AND RESULTS: We linked medical record data, adjudicated device therapies, and the National Cardiovascular Data Registry ICD Registry. Survival analysis evaluated therapy probability and predictors after ICD implant from 2006 to 2009, with attention to Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups: left ventricular ejection fraction, 31% to 35%; nonischemic cardiomyopathy \u3c9 \u3emonths\u27 duration; and New York Heart Association class IV heart failure with cardiac resynchronization therapy defibrillator. Among 2540 patients, 35% wereold, 26% were women, and 59% were white. During 27 (median) months, 738 (29%) received ≥1 therapy. Three-year therapy risk was 36% (appropriate, 24%; inappropriate, 12%). Appropriate therapy was more common in men (adjusted hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.43-2.35). Inappropriate therapy was more common in patients with atrial fibrillation (adjusted HR, 2.20; 95% CI, 1.68-2.87), but less common among patients ≥65 years old versus younger (adjusted HR, 0.72; 95% CI, 0.54-0.95) and in recent implants (eg, in 2009 versus 2006; adjusted HR, 0.66; 95% CI, 0.46-0.95). In Centers for Medicare and Medicaid Services Coverage With Evidence Development analysis, inappropriate therapy was less common with cardiac resynchronization therapy defibrillator versus single chamber (adjusted HR, 0.55; 95% CI, 0.36-0.84); therapy risk did not otherwise differ for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups. CONCLUSIONS: In this community cohort of primary prevention patients receiving ICD, therapy delivery varied across demographic and clinical characteristics, but did not differ meaningfully for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups

Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results from the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators

Background In US clinical practice, many patients who undergo placement of an implantable cardioverter‐defibrillator (ICD) for primary prevention of sudden cardiac death receive dual‐chamber devices. The superiority of dual‐chamber over single‐chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single‐ and dual‐chamber ICDs for primary prevention. Methods and Results We identified patients receiving a single‐ or dual‐chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter‐Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all‐cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital‐level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single‐chamber device and 46.0% (n=479) received a dual‐chamber device. In a propensity‐weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59–1.38 [P=0.65]), all‐cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87–1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72–1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93–1.53 [P=0.17]). Conclusions Among patients who received an ICD for primary prevention without indications for pacing, dual‐chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single‐chamber devices. This study does not justify the use of dual‐chamber devices to minimize inappropriate shocks

The conundrum of increased burden of end-stage renal disease in Asians

The conundrum of increased burden of end-stage renal disease in Asians.BackgroundFew cohort studies have examined the risk of end-stage renal disease (ESRD) among Asians compared with whites and blacks.MethodsTo compare the incidence of ESRD in Asians, whites, and blacks in Northern California, we examined sociodemographic and clinical data on 299,168 adults who underwent a screening health checkup at Kaiser Permanente between 1964 and 1985. Incident cases of ESRD were ascertained by matching patient identifiers with the nationally comprehensive United States Renal Data System ESRD registry.ResultsOverall, 1346 cases of ESRD occurred during 7,837,310 person-years of follow-up. The age-adjusted rate of ESRD (per 100,000 person-years) was 14.0 [95% confidence interval (CI) 10.5-18.5] among Asians, 7.9 (95% CI 6.5-9.5) among whites, and 43.4 (95% CI 36.6-51.4)] among blacks. Controlling for age, gender, educational attainment, diabetes, prior myocardial infarction, serum creatinine, systolic and diastolic blood pressure, proteinuria, hematuria, cigarette smoking, serum total cholesterol, and body mass index increased the risk of ESRD in Asians relative to whites from 1.69 to 2.08 (95% CI 1.61-2.67). By contrast, adjustment for the same covariates decreased the risk of ESRD in blacks relative to whites from 5.30 to 3.28 (95% CI 2.91-3.69).ConclusionFactors contributing to the excess ESRD risk in Asians relative to whites extend beyond usually considered sociodemographic and comorbidity disparities. Strategies aimed at examining novel risk factors for kidney disease and efforts to increase awareness of kidney disease among Asians may reduce ESRD incidence in this high-risk group

Effect of Diabetes and Glycemic Control on Ischemic Stroke Risk in AF Patients ATRIA Study

BackgroundDiagnosed diabetes mellitus (DM) is a consistently documented risk factor for ischemic stroke in patients with atrial fibrillation (AF).ObjectivesThe purpose of this study was to assess the association between duration of diabetes and elevated hemoglobin A1c (HbA1c) with risk of stroke among diabetic patients with AF.MethodsWe assessed this association in the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) California community-based cohort of AF patients (study years 1996 to 2003) where all events were clinician adjudicated. We used Cox proportional hazards regression to estimate the rate of ischemic stroke in diabetic patients according to time-varying measures of estimated duration of diabetes (≥3 years compared with <3 years) and HbA1c values (≥9.0% and 7.0% to 8.9% compared with <7.0%), focusing on periods where patients were not anticoagulated.ResultsThere were 2,101 diabetic patients included in the duration analysis: 40% with duration <3 years and 60% with duration ≥3 years at baseline. Among 1,933 diabetic patients included in the HbA1c analysis, 46% had HbA1c <7.0%, 36% between 7.0% and 8.9%, and 19% ≥9.0% at baseline. Duration of diabetes ≥3 years was associated with an increased rate of ischemic stroke compared with duration <3 years (adjusted hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.10 to 2.76). The increased stroke rate was observed in older (age ≥75 years) and younger (age <75 years) individuals. Neither poor glycemic control (HbA1c ≥9.0%, adjusted HR: 1.04, 95% CI: 0.57 to 1.92) nor moderately increased HbA1c (7.0% to 8.9%, adjusted HR: 1.21, 95% CI: 0.77 to 1.91) were significantly associated with an increased rate of ischemic stroke compared with patients who had HbA1c <7.0%.ConclusionsDuration of diabetes is a more important predictor of ischemic stroke than glycemic control in patients who have diabetes and AF

Incident frailty and cognitive impairment by heart failure status in older patients with atrial fibrillation: the SAGE-AF study

Background: Atrial fibrillation (AF) and heart failure (HF) frequently co-occur in older individuals. Among patients with AF, HF increases risks for stroke and death, but the associations between HF and incident cognition and physical impairment remain unknown. We aimed to examine the cross-sectional and prospective associations between HF, cognition, and frailty among older patients with AF. Methods: The SAGE-AF (Systematic Assessment of Geriatric Elements in AF) study enrolled 1244 patients with AF (mean age 76 years, 48% women) from five practices in Massachusetts and Georgia. HF at baseline was identified from electronic health records using ICD-9/10 codes. At baseline and 1-year, frailty was assessed by Cardiovascular Health Survey score and cognition was assessed by the Montreal Cognitive Assessment. Results: Patients with prevalent HF (n = 463, 37.2%) were older, less likely to be non-Hispanic white, had less education, and had greater cardiovascular comorbidity burden and higher CHA2DS2VASC and HAS-BLED scores than patients without HF (all P\u27s \u3c 0.01). In multivariable adjusted regression models, HF (present vs. absent) was associated with both prevalent frailty (adjusted odds ratio [aOR]: 2.38, 95% confidence interval [CI]: 1.64-3.46) and incident frailty at 1 year (aOR: 2.48, 95% CI: 1.37-4.51). HF was also independently associated with baseline cognitive impairment (aOR: 1.60, 95% CI: 1.22-2.11), but not with developing cognitive impairment at 1 year (aOR 1.04, 95%CI: 0.64-1.70). Conclusions: Among ambulatory older patients with AF, the co-existence of HF identifies individuals with physical and cognitive impairments who are at higher short-term risk for becoming frail. Preventive strategies to this vulnerable subgroup merit consideration

Patterns of Complex Comorbidity in Older Patients with Heart Failure

Background Heart failure (HF) carries a high burden of comorbidity with approximately one half of patients with HF having at least one additional comorbid condition present. Rates of comorbidity in patients with HF have steadily increased over the past 2 decades. Objective To examine patterns of comorbidity among older patients with HF in the Cardiovascular Research Network PRESERVE cohort. Methods PRESERVE Cohort Data are from the CVRN PRESERVE cohort which is a multicenter cohort of 37,054 patients [mean age = 74 years (SD = 12.4 yrs); 46% female] with HF diagnosed between 2005 and 2008 currently being conducted at 4 CVRN sites: KPNC, KPCO, KPNW, and FCHP. The primary data source for the PRESERVE cohort was the HMO Research Network Virtual Data Warehouse. Identification of Coexisting Diseases Coexisiting illnesses at the time of HF diagnosis were based on diagnoses and procedures mapped to relevant International Classification of Diseases, Ninth Edition (ICD-9) codes. For the purposes of characterizing clusters of comorbidities, we focused on coexisting conditions with a prevalence rate of ≥3%. Statistical Analysis We used the Agglomerative Clustering technique to characterize patterns of comorbidity. Over multiple iterations, each condition is clustered with the condition with which it has the highest squared correlation. This process is repeated to determine whether assigning a condition to a different cluster increases the amount of explained variance [ranging from 1.0 (all variance explained) to 0.0 (no variance explained)]. The conditions in each cluster are as correlated as possible among themselves and as uncorrelated as possible with conditions in other clusters. Results Burden of Comorbidity There was a high degree of comorbidity and multi-morbidity among patients with HF. (Table 1) Hypertension and arrhythmias were the comorbidities of HF that occurred most often in the absence of other chronic conditions (4.8% and 4.7%, respectively). The average number of comorbid conditions varied from 3.5 to 5.2. Patients with HF and unstable angina or other thromboembolic disorders had the highest multi-morbidity (mean = 5.2 conditions), whereas those with HF and hypertension had the lowest (mean = 3.5). Clustering of Comorbiditites A five-cluster structure was derived. Cluster 1: Dyslipidemia, Hypertension, Diabetes Mellitus, Visual Impairment Cluster 2: Acute Myocardial Infarction, Unstable Angina, Thromboembolic Disorder, Dementia Cluster 3: Aortic Valvular Disease, Cancer, Hearing Impairment, Arrthythmia Cluster 4: Peripheral Arterial Disease, Stroke Cluster 5: Lung Disease, Liver Disease, Depression Discussion and Conclusions Cluster analysis is an innovative approach to examining the co-occurrence of diseases and allows for identification of broad patterns of multi-morbidity beyond the pairings of diseases or disease counts. Patients with HF have a high rate of multi-morbidity, with an average of 4 co-occurring conditions. Intuitive and unintuitive patterns of clustering were identified. Randomized clinical trials in HF will need to include more diverse patient populations in order to adapt to the increasingly complex patient population. A cluster analysis approach to characterizing patterns of comorbidity may help indentify important patient subgroups

Interleukin-6 Is a Risk Factor for Atrial Fibrillation in Chronic Kidney Disease: Findings from the CRIC Study.

Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with chronic kidney disease (CKD). In this study, we examined the association between inflammation and AF in 3,762 adults with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. AF was determined at baseline by self-report and electrocardiogram (ECG). Plasma concentrations of interleukin(IL)-1, IL-1 Receptor antagonist, IL-6, tumor necrosis factor (TNF)-α, transforming growth factor-β, high sensitivity C-Reactive protein, and fibrinogen, measured at baseline. At baseline, 642 subjects had history of AF, but only 44 had AF in ECG recording. During a mean follow-up of 3.7 years, 108 subjects developed new-onset AF. There was no significant association between inflammatory biomarkers and past history of AF. After adjustment for demographic characteristics, comorbid conditions, laboratory values, echocardiographic variables, and medication use, plasma IL-6 level was significantly associated with presence of AF at baseline (Odds ratio [OR], 1.61; 95% confidence interval [CI], 1.21 to 2.14; P = 0.001) and new-onset AF (OR, 1.25; 95% CI, 1.02 to 1.53; P = 0.03). To summarize, plasma IL-6 level is an independent and consistent predictor of AF in patients with CKD