Little is known about patients’ views surrounding the ethical and legal aspects of managing pacemakers (PMs) and implantable cardioverter-defibrillators (ICDs) near the end of life. Patients with hypertrophic cardiomyopathy (HC) are at heightened risk of sudden cardiac death and are common recipients of such devices. Patients with HC recruited from the membership of the Hypertrophic Cardiomyopathy Association were surveyed about their clinical histories, advance care planning, legal knowledge, and ethical beliefs relating to the withdrawal of PM and ICD therapy. The mean age of the 546 patients was 49.1 years, 47% were women, and 57% had ICDs. Only 46% of the respondents had completed an advance directive, only 51% had a healthcare proxy, and cardiac implantable electrical devices (CIEDs) were commonly not addressed in either (92% and 58%, respectively). Many patients characterized deactivating PMs or ICDs as euthanasia or physician-assisted suicide (29% for PMs and 17% for ICDs), and >50% expressed uncertainty regarding the legality of device deactivation. Patients viewed deactivation of ICDs and PMs as morally different from other life-sustaining therapies such as mechanical ventilation and dialysis, and these views varied substantially according to the CIED type (p <0.0001). The respondents expressed concerns regarding clinical conflicts related to religion, ethical and legal uncertainty, and informed consent. In conclusion, patients who have, or are eligible to receive, CIEDs might require improved advance care planning and education regarding the ethical and legal options for managing CIEDs at the end of life.

It is not well known whether systemic iron overload per se in hereditary hemochromatosis (HH) is associated with cardiac arrhythmias before other signs and symptoms of cardiovascular disease occur. In this study, we examined the incidence of cardiac arrhythmias in cardiac asymptomatic HH subjects (NYHA functional class I), and compared it to that in age/gender-matched normal volunteers. The 42 HH subjects and 19 normal volunteer control subjects recruited through the NHLBI-sponsored "Heart Study of Hemochromatosis" completed 48-hour Holter electrocardiography ambulatory monitoring at the baseline evaluation. The HH subjects were classified as newly diagnosed (Group A) and chronically treated subjects (Group B). All HH subjects had C282Y homozygosity, and the normal volunteers lacked any HFE gene mutations which are known to cause HH. Although statistically insignificant, the incidence of ventricular and supraventricular ectopy tended to be higher in the combined HH groups than the controls. Supraventricular ectopy was more frequently noted in Group B as compared to the controls (ectopy rate per hour; 11.1±29.9 vs. 1.5±3.5, P < 0.05 by Kurskal Wallis test). No examples of heart block, other than first degree atrioventricular node block, were seen in any of the subjects. The incidence of cardiac arrhythmias was not significantly reduced after 6 months of intensive iron removal therapy in Group A subjects. No life threatening arrhythmias were observed in our HH subjects. In conclusion, our data suggest that the incidence of cardiac arrhythmias is, at most, marginally increased in asymptomatic HH subjects. A larger clinical study is warranted to further clarify our observation.

Children with single ventricle (SV) physiology have increased ventricular work and are at risk for heart failure (HF). However, HF diagnosis is especially difficult because there are few objective measures of HF validated in this cohort. We previously showed that plasma B-type natriuretic peptide (BNP) levels were sensitive and specific for detecting HF in a small, heterogeneous SV cohort. The aim of this study was to define the impact of SV morphology and stage of palliation on the correlation between BNP and HF. We also examined the utility of N-terminal pro-BNP (NT-proBNP), a more stable product of pre-BNP processing, as a biomarker of HF in these patients. A cross-sectional observational study of SV children 1 month–7 years was conducted. The presence of HF was defined as a Ross score >2. The association of BNP or NT-proBNP with HF was assessed using logistic regression and ROC curves. Twenty-two of 71 included children (31%) had clinical HF. A doubling of BNP was associated with an odds ratio for HF of 2.20 (95%CI 1.36–3.55, p=0.001) with a c-statistic >75%, yielding a detection threshold of ≥45 pg/ml. This threshold was preserved when patients were stratified by right ventricular morphology or stage of surgical palliation. Similarly, a doubling of NT-proBNP was associated with an odds ratio for HF of 1.92 (95% CI 1.17–3.14, p=0.009). In contrast with BNP, the threshold value of NT-proBNP for predicting HF decreased with stage of palliation. In conclusion, plasma BNP and NT-proBNP are reliable tests for clinical HF in young children with SV physiology, specifically those with right ventricular morphology, regardless of stage of palliation.

The purpose of this study was to evaluate the prognostic value of stress echocardiography in patients with angiographically significant coronary artery disease (CAD). Two hundred sixty patients (mean age 63 ± 10 years, 58% men) who underwent stress echocardiography (41% treadmill, 59% dobutamine) and coronary angiography within 3 months and without intervening coronary revascularization were evaluated. All patients had significant CAD as defined by coronary stenosis ≥70% in major epicardial vessels or branches (45% had single-vessel disease, and 55% had multivessel disease). The left ventricle was divided into 16 segments and scored on a 5-point scale of wall motion. Patients with abnormal results on stress echocardiography were defined as those with stress-induced ischemia (increase in wall motion score of ≥1 grade). Follow-up (3.1 ± 1.2 years) for nonfatal myocardial infarction (n = 23) and cardiac death (n = 6) was obtained. In patients with angiographically significant CAD, stress echocardiography effectively risk stratified normal (no ischemia, n = 91) in contrast to abnormal (ischemia, n = 169) groups for cardiac events (event rate 1.0%/year vs 4.9%/year, p = 0.01). Multivariate logistic regression analysis identified multivessel CAD (hazard ratio 2.53, 95% confidence interval 1.16 to 5.51, p = 0.02) and number of segments in which ischemia was present (hazard ratio 4.31, 95% confidence interval 1.29 to 14.38, p = 0.01) as predictors of cardiac events. A Cox proportional-hazards model for cardiac events showed small, significant incremental value of stress echocardiography over coronary angiography (p = 0.02) and the highest global chi-square value for both (p = 0.004). In conclusion, in patients with angiographically significant CAD, (1) normal results on stress echocardiography conferred a benign prognosis (event rate 1.0%/year), and (2) stress echocardiographic results (no ischemia vs ischemia) added incremental prognostic value to coronary angiographic results, and (3) stress echocardiography and coronary angiography together provided additive prognostic value, with the highest global chi-square value.

Few data are available on factors associated with low adherence or early clopidogrel discontinuation following percutaneous coronary intervention (PCI). Patients (n=284) were evaluated prior to hospital discharge following PCI to identify factors associated with low adherence to clopidogrel 30 days later. Pre-PCI adherence to daily medications was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8) and categorized as low, medium, or high (scores <6, 6 to <8 and 8, respectively). Low adherence to clopidogrel was defined as a MMAS-8 score < 6 (n=21) or having discontinued clopidogrel (n=11), both ascertained during a 30-day post-PCI interview. At 30 days post-PCI, 11% of patients had low adherence to clopidogrel. The odds ratios (95% confidence interval) for low adherence to clopidogrel was 3.78 (1.09 – 13.1), 3.06 (1.36 – 6.87), 2.46 (0.97 – 6.27) and 3.36 (0.99 – 11.4) for patients who reported, prior to PCI, taking smaller doses of medication due to cost, had difficulty filling prescriptions, had difficulty reaching their primary physician and were not comfortable asking their doctor for instructions, respectively. The odds ratios (95% CI) for low clopidogrel adherence following PCI among patients with medium and low, versus high adherence, to daily medications prior to PCI was 6.13 (1.34 – 28.2) and 10.9 (2.46 – 48.7), respectively. The c-statistic associated with pre-PCI MMAS-8 scores for discriminating low clopidogrel adherence at 30 days post-PCI was 0.733 (95% CI: 0.650 – 0.852). Pre-PCI adherence to daily medications may be a useful indicator for identifying patients who will have low clopidogrel adherence following PCI.

Little is known about the familial aggregation of intermittent claudication (IC). Our objective was to examine whether parental IC increased adult offspring risk of IC independent of established cardiovascular risk factors. We evaluated Offspring cohort participants of the Framingham Heart Study (FHS) who were 30 years or older, cardiovascular disease (CVD) free, and had both parents enrolled in the FHS (n= 2970 unique participants, 53% women). Pooled proportional hazards regression was used to examine whether the 12 year risk for incident IC in offspring participants was associated with parental IC adjusting for age, sex, diabetes, smoking, systolic blood pressure, total cholesterol, high density lipoprotein (HDL) cholesterol, anti-hypertensive and lipid treatment. Among 909 person-exams in the parental IC history group and 5397 person-exams in the no parental IC history group there were 101 incident IC events (29 with parental IC history, 72 without parental IC history) during follow-up. Age and sex adjusted 12-year cumulative incidence rates per 1000 person-years were 5.08 (95% CI: 2.74; 7.33) and 2.34 (95% CI: 1.46; 3.19) in participants with and without parental IC history. Parental history of IC significantly increased the risk of incident IC in offspring (multivariable adjusted hazard ratio of 1.81, 95% CI 1.14, 2.88). The hazard ratio was unchanged with adjustment for occurrence of CVD (1.83, 95% CI 1.15, 2.91). In conclusion, IC in parents increases risk for IC in adult offspring independent of established risk factors. These data suggest a genetic component of peripheral artery disease and support future research into genetic causes.

Digital peripheral arterial tonometry (PAT) is an emerging, non-invasive method to assess vascular function. The physiology underlying this phenotype, however, remains unclear. Therefore, we evaluated the relationship between digital PAT and established brachial artery ultrasound measures of vascular function under basal conditions and following reactive hyperemia. Using a cross-sectional study design, digital PAT and brachial artery ultrasound with pulsed wave Doppler were simultaneously completed at baseline and following reactive hyperemia in both individuals with established coronary artery disease (n=99) and healthy volunteers at low cardiovascular disease risk (n=40). Under basal conditions, the digital pulse volume amplitude demonstrated a significant positive correlation with the brachial artery velocity-time integral, that was independent of arterial diameter, in both the healthy volunteer (rs=0.64, P<0.001) and coronary artery disease (rs=0.63, P<0.001) cohorts. Similar positive relationships were observed with baseline brachial artery blood flow velocity and blood flow. In contrast, no relationship between the reactive hyperemia-evoked digital PAT ratio and either brachial artery flow-mediated dilation or shear stress was observed in either cohort (P=NS). In conclusion, these findings demonstrate that digital PAT measures of vascular function more closely reflect basal blood flow in the brachial artery than reactive hyperemia-induced changes in arterial diameter or flow velocity, and the presence of vascular disease does not modify the physiology underlying the digital PAT phenotype.

Disease management programs that target patients with the highest risk of subsequent costs may help payers and providers control health care costs, but identifying these patients prospectively is challenging. We hypothesized that medical history and clinical data from a heart failure registry could be used to prospectively identify patients with heart failure most likely to incur high costs. We linked Medicare inpatient claims to clinical registry data for patients with heart failure and calculated total Medicare costs during the year after the index heart failure hospitalization. We defined patients as having high costs if they were in the upper 5% (> $76,500) of the distribution. We used logistic regression models to identify patient and clinical characteristics associated with high costs. Costs for the 40,317 patients in the study varied widely. Patients in the upper 5% of the cost distribution incurred mean costs of $117,193 ± $55,550 during 1 year of follow-up, compared with $17,086 ± $17,792 for the lower-cost group. Demographic and clinical characteristics associated with high costs included younger age and black race; history of anemia, chronic obstructive pulmonary disease, ischemic heart disease, diabetes mellitus, or peripheral vascular disease; serum creatinine level; and systolic blood pressure at admission. Mean 1-year Medicare costs for patients whom the model predicted would exceed the high-cost threshold were more than twice the costs for patients below the threshold. In conclusion, model based on variables from clinical registries can identify a group of patients with heart failure who, on average, will incur higher costs in the first year after hospitalization.

While opening an occluded infarct-related artery (IRA) > 24 hours post myocardial infarction in stable patients in the Occluded Artery Trial (OAT) did not reduce events over 7 years, there was a suggestion that effect of treatment may differ by patient age. Baseline characteristics and outcomes by treatment with percutaneous coronary intervention (PCI) vs. optimal medical therapy (MED) alone were compared by pre-specified stratification at age 65. P<0.01 was pre-specified as significant for OAT secondary analyses. The primary outcome was death, myocardial infarction or Class IV heart failure. Patients > 65 years of age (n=641) were more likely to be female, non-smokers, and to have hypertension, lower estimated glomerular filtration rate and multivessel disease compared to younger patients (age ≤ 65, n=1560), p<0.001. There was no significant observed interaction between treatment assignment and age for the primary outcome after adjustment (p=0.1) and there was no difference between PCI and MED observed in either age group. At 7 year follow-up, younger patients tended to have angina more often compared to the older group (H.R. 1.21, 99% CI: 1.00–1.46, p=0.01). The 7-year composite primary outcome was more common in older patients (p<0.001), and age remained significant after co-variate adjustment (H.R. 1.42, 99% CI: 1.09–1.84). The rate of early PCI complications was low in both age groups. The trend toward a differential effect of PCI in the young vs. the old for the primary outcome was likely driven by measured and unmeasured confounders, and by chance. PCI reduces angina to a similar degree in the young and old. There is no indication for routine PCI to open a persistently occluded IRA in stable patients post-MI regardless of age.

Warfarin is a complex but highly effective treatment for reducing thromboembolic risk in atrial fibrillation (AF). We examined contemporary warfarin treatment rates in AF prior to the expected introduction of newer anticoagulants and the extent of practice-level variation in warfarin use. Within the National Cardiovascular Data Registry PINNACLE program between July 2008 and December 2009, we identified 9113 outpatients with AF from 20 sites who were at moderate to high risk for stroke (CHADS2 score >1) and would be optimally treated with warfarin. Using hierarchical regression models, the extent of site-level variation was quantified with the median rate ratio, which can be interpreted as the likelihood that 2 random practices would differ in treating ‘identical’ patients with warfarin. The overall rate of warfarin treatment was only 55.1% (5018/9913). Both untreated patients and treated patients had mean CHADS2 scores of 2.5 (P=0.38) and similar rates of heart failure, hypertension, diabetes mellitus, and prior stroke, suggesting an almost ‘random’ pattern of treatment. At the practice level, however, there was substantial variation in treatment, ranging from 25% to 80% (interquartile range for practices: 50% to 65%), with a median rate ratio of 1.31 (1.22, 1.55), P<0.001. In conclusion, within the PINNACLE registry, we found that warfarin treatment in AF was suboptimal, with large variations in treatment observed across practices. Our findings suggest important opportunities for practice-level improvement in stroke prevention for outpatients with AF and define a benchmark treatment rate prior to the introduction of newer anticoagulant agents.

Potential upstream determinants of coronary heart disease (CHD) include life-course socioeconomic position (e.g., childhood socioeconomic circumstances, own education and occupation); however, several plausible biological mechanisms by which socioeconomic position (SEP) may influence CHD are poorly understood. Several CHD risk factors appear to be more strongly associated with SEP in women than in men; little is known as to whether any CHD risk factors may be more strongly associated with SEP in men. Objectives were to evaluate whether cumulative life-course SEP is associated with a measurement of subclinical atherosclerosis, the ankle–brachial index (ABI), in men and women. This study was a prospective analysis of 1,454 participants from the Framingham Heart Study Offspring Cohort (mean age 57 years, 53.8% women). Cumulative SEP was calculated by summing tertile scores for father’s education, own education, and own occupation. ABI was dichotomized as low (≤ 1.1) and normal (> 1.1 to 1.4). After adjustment for age and CHD risk factors cumulative life-course SEP was associated with low ABI in men (odds ratio [OR] 2.04, 95% confidence interval [CI] 1.22 to 3.42, for low vs high cumulative SEP score) but not in women (OR 0.86, 95% CI 0.56 to 1.33). Associations with low ABI in men were substantially driven by their own education (OR 4.13, 95% CI 1.86 to 9.16, for lower vs higher than high school education). In conclusion, cumulative life-course SEP was associated with low ABI in men but not in women.

Several studies have reported that inflammatory markers are associated with atrial fibrillation (AF). White blood cell (WBC) count is a widely available and broadly utilized marker of systemic inflammation. We sought to investigate the association between increased WBC count and incident AF, and whether this association is mediated by smoking, myocardial infarction and heart failure. We examined participants in the Framingham Heart Study Original Cohort. Cox proportional hazard regression analysis was used to examine the relation between WBC count and incident AF over 5-year follow-up period. We adjusted for standard AF risk factors, and smoking, previous myocardial infarction, as well as interim myocardial infarction and heart failure prior to incident AF. Our sample consisted of 936 participants, mean age was 76±6 years and 61% were women. Median WBC count was 6.4*109/L (25th-75th percentile 5.6*109/L- 7.8*109/L). During a median follow-up of 5 years, 82 participants (9%) developed new-onset AF. After adjusting for standard risk factors for AF, increased WBC count was significantly associated with incident AF, with a hazard ratio per standard deviation (0.26*109/L) increase of 2.22, (95% confidence interval, 1.10–4.48; P=0.03). We found no substantive differences adjusting for smoking, previous myocardial infarction, interim myocardial infarction and heart failure. In conclusion, in our community-based sample, increased WBC count was associated with incident AF during 5-years of follow-up. Our findings provide additional evidence for the relation between systemic inflammation and AF.

Subjects at risk for atherosclerosis may have dysfunctional high-density lipoprotein (HDL) despite normal cholesterol content in plasma. We considered whether efflux of excess cellular cholesterol to HDL from obese subjects is associated with impaired arterial endothelial function, a biomarker of cardiovascular risk. Fifty-four overweight (body mass index [BMI] 25 – 29.9 kg/m2) or obese women (BMI ≥ 30 kg/m2), age 46 ± 11 years, were enrolled in a worksite wellness program. HDL cholesterol averaged 57 ± 17 mg/dL and was inversely associated with BMI (r= −0.419, P= 0.002). Endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Cholesterol efflux from 3H-cholesterol-labeled BHK cells transfected with the ATP-binding cassette transporter 1 (ABCA1) showed 8.2 to 22.5% cholesterol efflux over 18 hours when incubated with 1% serum and was positively correlated with FMD (P <0.05), especially in the 34 subjects with BMI ≥ 30 kg/m2 (r= 0.482, P= 0.004). This relation was independent of age, HDL or low-density lipoprotein cholesterol (LDL) concentrations in plasma, blood pressure or insulin resistance by stepwise multiple regression analysis (β= 0.31, R2= 0.21, P= 0.007). Nitration of apoA-I tyrosine residues (by sandwich ELISA) was significantly higher in women with BMI ≥ 30 kg/m2 and the lowest cholesterol efflux than in women with BMI 25 – 29.9 kg/m2 and the highest cholesterol efflux (P= 0.01). We conclude that decreased cholesterol efflux via the ABCA1 transporter is associated with increased nitration of apoA-I in HDL and is an independent predictor of impaired endothelial function in women with BMI ≥ 30 kg/m2. This finding suggests that functional measures of HDL may be better markers for cardiovascular risk than HDL cholesterol levels in this population.

Despite reports of patients with resuscitated sudden cardiac arrest (rSCA) receiving acute cardiac catheterization, the efficacy of this strategy is largely unknown. We hypothesized that acute cardiac catheterization of patients with rSCA would improve survival to hospital discharge. A retrospective cohort of 240 patients with out-of-hospital rSCA due to ventricular tachycardia or fibrillation was identified from 11 institutions in Seattle, Washington, between 1999 and 2002. Patients were grouped into those receiving acute catheterization within 6 hours (≤ 6 hours group, n = 61) and into those with deferred catheterization at > 6 hours or no catheterization during the index hospitalization (>6 hours group, n = 179). We directed attention to survival to hospital discharge, neurologic status, extent of coronary artery disease presenting electrocardiographic (ECG) findings, and pre-arrest symptoms. Propensity score methods were used to adjust for the likelihood of receiving acute catheterization. Survival was greater in patients who underwent acute catheterization ≤ 6 hours group (72%) vs. >6 hours group (49%) (p=0.001). Percutaneous coronary intervention was performed in 38/61 (62%) of patients in ≤ 6 hours group, and 13/170 (7%) in > 6 hours group, p<0.0001. Neurologic status was similar for both groups. A significantly higher percentage of patients in the acute catheterization group had symptoms prior to cardiac arrest, and had ST-segment elevation on post-resuscitation ECG. Age, bystander cardiopulmonary resuscitation, daytime presentation, history of percutaneous coronary intervention or stroke, and acute ST elevation were all positively associated with receiving cardiac catheterization. In conclusion, in this series of patients who sustained out-of-hospital cardiac arrest, acute catheterization (within 6 hours of presentation) was associated with improved survival.

Primary care site may play an important role in cardiovascular disease prevalence; however, the distribution of risk factors and outcomes across care sites is not known. We conducted a cross-sectional analysis of 21,778 adult participants from the National Health and Nutrition Examination Survey (99-08) using multivariable logistic regression to assess the relationship between site of usual care and disease prevalence. We examine patients’ self-reported history of several chronic conditions (Hypertension, Diabetes, and Hypercholesterolemia), awareness of chronic conditions, and associated cardiovascular events (Angina, CHD, CVD, MI, and Stroke). After adjustment for demographic and healthcare utilization characteristics, there were no significant differences in the prevalence of diabetes or hypercholesterolemia between patients receiving usual care at private doctors’ offices, hospital outpatient clinics, community-based clinics, and emergency rooms(ER). However, participants without a usual source of care and those receiving usual care at an ER have significantly lower awareness of their chronic conditions than participants at other sites. The odds of having a history of each of the adverse cardiovascular events ranged between 2.21 and 4.18 times higher for people receiving usual care at ER’s relative to private doctors’ offices. In conclusion, participants who report utilizing ER’s as their usual site of care are disproportionately more likely to have a history of poor cardiovascular outcomes and are more likely to be unaware of having hypertension or hypercholesterolemia. As health care reform takes place and millions more begin seeking care, it is imperative to ensure access to longitudinal care sites designed for continuous disease management.

Few prospective studies have explored the association between renal function and risk of incident atrial fibrillation (AF) in apparently healthy populations. A total of 24,746 women participating in the Women’s Health Study who were free of cardiovascular disease (CVD), AF and provided a blood sample at baseline were prospectively followed for incident AF from 1993 to 2010. AF events were confirmed by medical chart review. Estimated glomerular filtration rate (eGFR) was calculated from baseline creatinine using the Chronic Kidney Disease – Epidemiology equation. Cox models were used to estimate hazard ratios (HR) and 95% CI for incident AF across eGFR categories controlling for AF risk factors. During 15.4 years (median) of follow-up, 786 incident AF events occurred. The multivariable-adjusted HR for incident AF across eGFR categories (<60, 60–74.9, 75–89, and ≥ 90 ml/min/1.73 m2) were:1.36 (1.00–1.84), 0.90 (0.71–1.14), 0.99 (0.84–1.18) and 1.00, respectively, without evidence of a linear association (P for trend, 0.48). Similarly, there was no significant curvilinear association (P quadratic, 0.10) in multivariable analysis across categories. As compared to women with an eGFR ≥ 60 ml/min/1.73 m2, the 1008 women with an eGFR < 60 ml/min/1.73 m2 had a multivariable adjusted HR for AF of 1.39 (1.04–1.86, p value 0.03). In conclusion, no significant linear or curvilinear relationship was observed between incident AF and less severe impairment of renal function in this large prospective cohort of women. However, a significant elevation in AF risk was observed at a threshold eGFR of < 60 ml/min/1.73 m2.

The aim of this study was to analyze using noninvasive cardiac examinations a series of young athletes discovered to have ventricular arrhythmias (VAs) during the preparticipation screening program for competitive sports. One hundred forty-five athletes (mean age 17 ± 5 years) were evaluated. The study protocol included electrocardiography (ECG), exercise testing, 2-dimensional and Doppler echocardiography, 24-hour Holter monitoring, signal-averaged ECG, and in selected cases contrast-enhanced cardiac magnetic resonance imaging. Results of ECG were normal in most athletes (85%). VAs were initially detected prevalently during exercise testing (85%) and in the remaining cases on ECG and Holter monitoring. Premature ventricular complexes disappeared during exercise in 56% of subjects. Premature ventricular complexes during Holter monitoring averaged 4,700 per day, predominantly monomorphic (88%), single, and/or in couplets (79%). The most important echocardiographic findings were mitral valve prolapse in 29 patients (20%), congenital heart disease in 4 (3%), and right ventricular regional kinetic abnormalities in 5 (3.5%). On cardiac magnetic resonance imaging, right ventricular regional kinetic abnormalities were detected in 9 of 30 athletes and were diagnostic of arrhythmogenic right ventricular cardiomyopathy in only 1 athlete. Overall, 30% of athletes were judged to have potentially dangerous VAs. In asymptomatic athletes with prevalently normal ECG, most VAs can be identified by adding an exercise test during preparticipation screening. In conclusion, cardiac screening with noninvasive examinations remains a fundamental tool for the identification of a possible pathologic substrate and for the characterization of electrical instability.

Anticoagulation has been shown to reduce ischemic stroke in atrial fibrillation (AF). However, concerns remain regarding their safety and efficacy in those ≥70 years of age who comprise most AF patients. Of the 4060 patients (mean age, 65 years; range, 49–80 years) in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 2248 (55% of 4060) were 70–80 years of age, 1901 of whom were receiving warfarin. Propensity score for warfarin use, estimated for each of the 2248 patients, were used to match 227 of the 347 no-warfarin patients (in 1:1, 1:2 or 1:3 sets) with 616 warfarin patients, who were balanced on 45 baseline characteristics. All-cause mortality occurred in 18% and 33% of matched patients receiving and not receiving warfarin, respectively, during up to six (mean, 3.4) years of follow-up (hazard ratio {HR} when warfarin use was compared with its non-use, 0.58; 95% confidence interval {CI}, 0.43–0.77; p<0.001). All-cause hospitalization occurred in 64% and 67% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use, 0.93; 95% CI, 0.77–1.12; p=0.423). Ischemic stroke occurred in 4% and 8% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use, 0.57; 95% CI, 0.31–1.04; p=0.068). Major bleeding occurred in 7% and 10% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use, 0.73; 95% CI, 0.44–1.22; p=0.229). In conclusion, warfarin use was associated with reduced mortality in septuagenarian AF patients but had no association with hospitalization or major bleeding.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by fibrofatty replacement of the myocardium and ventricular arrhythmias, associated with mutations in the desmosomal genes. Only a missense mutation in the DES gene coding for desmin, the intermediate filament protein expressed by cardiac and skeletal muscle cells, has been recently associated with ARVC. We screened 91 ARVC index cases (53 negative for mutations in desmosomal genes and an additional 38 carrying desmosomal gene mutations) for DES mutations. Two rare missense variants were identified. The heterozygous p.K241E substitution was detected in 1 patient affected with a severe form of ARVC who also carried the p.T816RfsX10 mutation in plakophilin-2 gene. This DES substitution, showing an allele frequency of <0.01 in the control population, is predicted to cause an intolerant amino acid change in a highly conserved protein domain. Thus, it can be considered a rare variant with a possible modifier effect on the phenotypic expression of the concomitant mutation. The previously known p.A213V substitution was identified in 1 patient with ARVC who was negative for mutations in the desmosomal genes. Because a greater prevalence of p.A213V has been reported in patients with heart dilation than in control subjects, the hypothesis that this rare variant could have an unfavorable effect on cardiac remodeling cannot be ruled out. In conclusion, our data help to establish that, in the absence of skeletal muscle involvement suggestive of a desminopathy, the probability of DES mutations in ARVC is very low. These findings have important implications in the mutation screening strategy for patients with ARVC.

Although moderate alcohol drinkers have lower rates of incident coronary artery disease (CAD) than abstainers, much less is known about the health effects of different patterns of alcohol use in women with established CAD. In the Determinants of Myocardial Infarction Onset Study, 1,253 women hospitalized for acute myocardial infarction (AMI) in 64 centers nationwide from 1989–1996 were followed for mortality through 12/31/2007. Of the women, 761 (61%) reported abstention in the year prior to their MI, 280 (22%) reported consumption of <1 serving/week, 75 (6%) reported consumption of 1–3 servings/week, and 137 (11%) reported consumption of 3 or more servings/week. Using Cox proportional hazards models, we investigated the associations between total weekly volume of consumption, drinking days/week, drinks/drinking day, and beverage type with 10-year mortality adjusting for clinical and socioeconomic potential confounders. Compared with abstention, adjusted hazard ratios and 95% confidence intervals were 0.66 (0.50, 0.86) for <1 serving/wk, 0.65 (0.38, 1.11) for 1–3 servings/wk, and 0.65 (0.38, 1.11) for 3 or more servings/wk (p-trend 0.008). We found no differences by beverage type and generally inverse associations of both drinking frequency and quantity with mortality. In conclusion, in women who survive MI, moderate drinking is associated with a decreased risk of mortality, with no clear differences on the basis of pattern or beverage type. Our results suggest that women who survive MI need not abstain from alcohol, but any derived benefit would appear to occur well below currently recommended limits in alcohol consumption.

Blood lipids and high sensitivity C-reactive protein (hsCRP) are altered by hormone therapy. The goal of the current study was to determine whether lipids and hsCRP have predictive value for hormone therapy benefit or risk for coronary heart disease (CHD) events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women’s Health Initiative hormone trials. Baseline lipids and hsCRP were obtained from 271 incident CHD cases and 707 controls. In a combined trial analysis, a favorable lipid status at baseline tended to predict better CHD outcomes when taking conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low density lipoprotein (LDL)/high density lipoprotein (HDL) ratio <2.5 had no increase in risk of CHD when taking CEE with or without MPA (OR 0.60, 95%CI=0.34–1.06), whereas women with an LDL/HDL ratio ≥2.5 had an increased risk of CHD (OR 1.73, 95%CI=1.18–2.53) (p-value for interaction = 0.02). Low hsCRP levels added marginally to the value of LDL/HDL<2.5 when predicting CHD benefit on hormone therapy. In conclusion, postmenopausal women with undesirable lipid levels had excess CHD risk when using CEE with or without MPA; however, women with favorable lipid levels, especially an LDL/HDL ratio < 2.5, did not have an elevated risk of CHD with CEE with or without MPA, irrespective of hsCRP levels.

Diabetes mellitus and obesity are increasing in prevalence and are associated with an elevated risk of atrial fibrillation (AF). Given the aging of the US population, AF is projected to concomitantly increase in prevalence in the upcoming decades. Both diabetes and obesity are associated with insulin resistance. Whether insulin resistance is an intermediate step for the development of AF is uncertain. We hypothesized that insulin resistance is associated with an increased risk of incident AF. We examined the association of insulin resistance with incident AF using multivariable Cox proportional hazards regression adjusting for established AF risk factors (age, sex, systolic blood pressure, hypertension treatment, PR interval, significant heart murmur, heart failure and body mass index). Of the 3,023 eligible participants (55% women; mean age 59 years) representing 4,583 persons-examinations (Framingham Offspring 5th and 7th examination cycles), 279 individuals developed AF (9.3%) up to 10 years of follow-up. With multivariable modeling, insulin resistance was not significantly associated with incident AF (hazard ratio comparing the top with the other three quartiles of homeostatic model assessment index (HOMA) 1.18, 95% confidence interval 0.84 to 1.65, p = 0.34). In a community-based cohort with up to 10 years follow-up, no significant association was observed between insulin resistance and incident AF.

Analogous to rapid ventricular pacing, frequent ventricular premature complexes (VPCs) may predispose over time to cardiomyopathy and subsequent heart failure (HF). We examined the association of frequent VPCs with HF incidence in a population-based cohort, free of HF and coronary heart disease (CHD) at baseline. At study baseline (1987-89), at least one VPC on a 2-minute rhythm ECG strip was seen in 5.5% (739/13486) of the middle aged (45-64 years old at baseline), white and African-American, men and women of the ARIC cohort. Incident HF was defined as the first appearance of ICD code ‘428.x’ in hospital discharge record or death certificate through 2005. Over an average follow up of 15.6 years, incident HF was seen in 10% subjects (19.4% in those with VPCs vs. 9.4% in those without). The age, race, and gender adjusted hazard ratio (HR) of HF for VPCs was 1.89 (95% CI = 1.59, 2.24). After multivariable adjustment for potential confounders, HR (95% CI) of HF for those with any VPC vs. no VPCs was 1.63 (1.36, 1.96). After additional adjustment for incident CHD as a time-varying covariate, the HR (95% CI) was 1.71 (1.42, 2.08). Presence of higher frequency of VPCs or complex VPCs had similar rates of HF as compared to single VPC and all were higher than no VPC group. In conclusion, in this large population based cohort, presence of VPCs is associated with incident HF independent of incident CHD.

Caregivers may represent an opportunity to improve cardiovascular disease (CVD) outcomes but prospective data are limited. We studied 3188 consecutive patients [41% minority, 39% female] admitted to a university hospital medical cardiovascular service to evaluate the association between having a caregiver and rehospitalization/death at 1 year. Clinical outcomes at 1 year were documented by a hospital-based clinical information system supplemented by standardized questionnaire. Comorbidities were documented by hospital electronic record review. At baseline, 13% (n=417) of patients had a paid caregiver and 25% (n=789) had only an informal caregiver. Having a caregiver was associated with rehospitalization or death at 1 year (OR=1.68; 95%CI=1.45–1.95), which varied by paid (OR=2.46; 95%CI=1.96–3.09) and informal (OR=1.40; 95%CI=1.18–1.65) caregiver status. Having a caregiver was significantly (p<.05) associated with age ≥65 years, racial/ethnic minority, lack of health insurance, past medical history of diabetes mellitus or hypertension, a Ghali comorbidity index >1, chronic obstructive pulmonary disease, or taking ≥ 9 prescriptions medications. The relation between caregiving and rehospitalization/death at 1 year was attenuated, but remained significant after adjustment (Paid OR=1.64; 95%CI=1.26–2.12 and Informal OR=1.20; 95%CI=1.00–1.44). In conclusion, risk of rehospitalization/death was significantly higher among cardiac patients with caregivers and was not fully explained by traditional comorbidities. Systematic determination of having a caregiver may be a simple method to identify patients at heightened risk of poor clinical outcomes.

Dysregulation of autonomic nervous system dynamics is important in the pathophysiology of cardiovascular risk in obstructive sleep apnea (OSA). Heart rate variability (HRV) and impedance cardiography measures can estimate autonomic activity but have not gained traction clinically. We hypothesized that, even in a cohort of mild, asymptomatic OSA patients without overt cardiovascular disease, daytime HRV metrics and impedance cardiography measurements of pre-ejection period (PEP) would demonstrate increased sympathetic and decreased parasympathetic modulation compared with matched controls. Obese individuals (BMI ≥30 kg/m2) without any known cardiovascular or inflammatory comorbidities were recruited from the community. Subjects underwent standard in-laboratory polysomnograms (PSG), followed by simultaneous electrocardiography (ECG) and impedance cardiography recordings while supine, supine with paced breathing, and after standing. 74 subjects were studied, and 59% had OSA (apnea-hypopnea index (AHI) ≥10episodes/hr) with a median AHI of 25.8/hr. OSA subjects had significantly decreased daytime time- and frequency-domain HRV indices, but not significantly different PEP, when compared to controls. AHI was a significant independent predictor of time-domain HRV measures in all awake conditions, after controlling for age, gender, blood pressure, fasting cholesterol levels and hemoglobin A1C. In conclusion, our results demonstrate reductions in cardiac vagal modulation, as measured by multiple daytime time-domain markers of HRV, among asymptomatic OSA patients versus controls. Further prospective outcomes-based studies are needed to evaluate the applicability of these metrics for noninvasive screening of obese asymptomatic OSA patients, prior to the onset of overt cardiovascular disease.