Maria G. Karas

The impact of height on the risk of atrial fibrillation: the Cardiovascular Health Study.

AIMS Atrial fibrillation (AF) is the most common sustained arrhythmia. Increased body size has been associated with AF, but the relationship is not well understood. In this study, we examined the effect of increased height on the risk of AF and explore potential mediators and implications for clinical practice. METHODS AND RESULTS We examined data from 5860 individuals taking part in the Cardiovascular Health Study, a cohort study of older US adults followed for a median of 13.6 (women) and 10.3 years (men). Multivariate linear models and age-stratified Cox proportional hazards and risk models were used, with focus on the effect of height on both prevalent and incident AF. Among 684 (22.6%) and 568 (27.1%) incident cases in women and men, respectively, greater height was significantly associated with AF risk [hazard ratio (HR)(women) per 10 cm 1.32, confidence interval (CI) 1.16-1.50, P < 0.0001; HR(men) per 10 cm 1.26, CI 1.11-1.44, P < 0.0001]. The association was such that the incremental risk from sex was completely attenuated by the inclusion of height (for men, HR 1.48, CI 1.32-1.65, without height, and HR 0.94, CI 0.85-1.20, with height included). Inclusion of height in the Framingham model for incident AF improved discrimination. In sequential models, however, we found minimal attenuation of the risk estimates for AF with adjustment for left ventricular (LV) mass and left atrial (LA) dimension. The associations of LA and LV size measurements with AF risk were weakened when indexed to height. CONCLUSION Independent from sex, increased height is significantly associated with the risk of AF.

Characteristics of Hospitalizations for Heart Failure with Preserved Ejection Fraction

BACKGROUND Hospitalizations for heart failure with preserved ejection fraction (HFpEF) are increasing. There are limited data examining national trends in patients hospitalized with HFpEF. METHODS Using the Nationwide Inpatient Sample, we examined 5,046,879 hospitalizations with a diagnosis of acute heart failure in 2003-2012, stratifying hospitalizations by HFpEF and heart failure with reduced ejection fraction (HFrEF). Patient and hospital characteristics, in-hospital mortality, and length of stay were examined. RESULTS Compared with HFrEF, those with HFpEF were older, more commonly female, and more likely to have hypertension, atrial fibrillation, chronic lung disease, chronic renal failure, and anemia. Over time, HFpEF comprised increasing proportions of men and patients aged ≥75 years. In-hospital mortality rate for HFpEF decreased by 13%, largely due to improved survival in those aged ≥65 years. Multivariable regression analyses showed that pulmonary circulation disorders, liver disease, and chronic renal failure were independent predictors of in-hospital mortality, whereas treatable diseases including hypertension, coronary artery disease, and diabetes were inversely associated. CONCLUSIONS This study represents the largest cohort of patients hospitalized with HFpEF to date, yielding the following observations: number of hospitalizations for HFpEF was comparable with that of HFrEF; patients with HFpEF were most often women and elderly, with a high burden of comorbidities; outcomes appeared improved among a subset of patients; pulmonary hypertension, liver disease, and chronic renal failure were strongly associated with poor outcomes.

Relations of plasma total and high-molecular-weight adiponectin to new-onset heart failure in adults ≥65 years of age (from the Cardiovascular Health Study)

Adiponectin exhibits cardioprotective properties in experimental studies, but elevated levels have been linked to increased mortality in older adults and patients with chronic heart failure (HF). The adipokines association with new-onset HF remains less well defined. The aim of this study was to investigate the associations of total and high-molecular weight (HMW) adiponectin with incident HF (n = 780) and, in a subset, echocardiographic parameters in a community-based cohort of adults aged ≥65 years. Total and HMW adiponectin were measured in 3,228 subjects without prevalent HF, atrial fibrillation or CVD. The relations of total and HMW adiponectin with HF were nonlinear, with significant associations observed only for concentrations greater than the median (12.4 and 6.2 mg/L, respectively). After adjustment for potential confounders, the hazard ratios per SD increment in total adiponectin were 0.93 (95% confidence interval 0.72 to 1.21) for concentrations less than the median and 1.25 (95% confidence interval 1.14 to 1.38) higher than the median. There was a suggestion of effect modification by body mass index, whereby the association appeared strongest in participants with lower body mass indexes. Consistent with the HF findings, higher adiponectin tended to be associated with left ventricular systolic dysfunction and left atrial enlargement. Results were similar for HMW adiponectin. In conclusion, total and HMW adiponectin showed comparable relations with incident HF in this older cohort, with a threshold effect of increasing risk occurring at their median concentrations. High levels of adiponectin may mark or mediate age-related processes that lead to HF in older adults.

Stroke Risk and Mortality in Patients With Ventricular Assist Devices

Background and Purpose— Ventricular assist devices (VADs) have advanced the management of end-stage heart failure. However, these devices are associated with hemorrhagic and thrombotic complications, including stroke. We assessed the incidence, risk factors, and outcomes of ischemic and hemorrhagic stroke after VAD placement. Methods— Using administrative claims data from acute care hospitals in California, Florida, and New York from 2005 to 2013, we identified patients who underwent VAD placement, defined by the International Classification of Diseases, Ninth Revision, Clinical Modification code 37.66. Ischemic and hemorrhagic strokes were identified by previously validated coding algorithms. We used survival statistics to determine the incidence rates and Cox proportional hazard analyses to examine the associations. Results— Among 1813 patients, we identified 201 ischemic strokes and 116 hemorrhagic strokes during 3.4 (±2.0) years of follow-up after implantation of a VAD. The incidence of stroke was 8.7% per year (95% confidence interval [CI], 7.7–9.7). The annual incidence of ischemic stroke (5.5%; 95% CI, 4.8–6.4) was nearly double that of hemorrhagic stroke (3.1%; 95% CI, 2.6–3.8). Women faced a higher hazard of stroke than men (hazard ratio, 1.6; 95% CI, 1.2–2.1), particularly hemorrhagic stroke (hazard ratio, 2.2; 95% CI, 1.4–3.4). Stroke was strongly associated with subsequent in-hospital mortality (hazard ratio, 6.1; 95% CI, 4.6–7.9). Conclusions— The incidence of stroke after VAD implantation was 8.7% per year, and incident stroke was strongly associated with subsequent in-hospital mortality. Notably, ischemic stroke occurred at nearly twice the rate of hemorrhagic stroke. Women seemed to face a higher risk for hemorrhagic stroke than men.

Echocardiographic assessment of the right ventricle and associated hemodynamics

Echocardiographic imaging of the right ventricle has inherent challenges stemming from the chambers complex shape. More focus has been placed on right ventricular function recently because it is an independent prognostic indicator of morbidity and mortality in heart failure and pulmonary hypertension. Echocardiography is a widely available, inexpensive, and well-validated tool that allows for comprehensive evaluation of the right ventricles size and function. With improvements in ultrasound techniques and methods, there are many qualitative and quantitative indices that, when used in conjunction with noninvasive pulmonary hemodynamics, provide important diagnostic and prognostic information to the clinician. As echocardiographic modalities - particularly three-dimensional imaging - improve, enhanced assessment of the right ventricle will lead to a better understanding of the pathophysiology of right heart failure and enhanced ability to follow responses to therapy.

Measures of Body Size and Composition and Risk of Incident Atrial Fibrillation in Older People: The Cardiovascular Health Study.

Various anthropometric measures, including height, have been associated with atrial fibrillation (AF). This raises questions about the appropriateness of using ratio measures such as body mass index (BMI), which contains height squared in its denominator, in the evaluation of AF risk. Among older adults, the optimal anthropometric approach to risk stratification of AF remains uncertain. Anthropometric and bioelectrical impedance measures were obtained from 4,276 participants (mean age = 72.4 years) free of cardiovascular disease in the Cardiovascular Health Study. During follow-up (1989-2008), 1,050 cases of AF occurred. BMI showed a U-shaped association, whereas height, weight, waist circumference, hip circumference, fat mass, and fat-free mass were linearly related to incident AF. The strongest adjusted association occurred for height (per each 1-standard-deviation increment, hazard ratio = 1.38, 95% confidence interval: 1.25, 1.51), which exceeded all other measures, including weight (hazard ratio = 1.21, 95% confidence interval: 1.13, 1.29). Combined assessment of log-transformed weight and height showed regression coefficients that departed from the 1 to -2 ratio inherent in BMI, indicating a loss of predictive information. Risk estimates for AF tended to be stronger for hip circumference than for waist circumference and for fat-free mass than for fat mass, which was explained largely by height. These findings highlight the prominent role of body size and the inadequacy of BMI as determinants of AF in older adults.

Incremental Value of Biochemical and Echocardiographic Measures in Prediction of Ischemic Stroke The Strong Heart Study

Background and Purpose— American Indians have high rates of stroke. Improved risk stratification could enhance prevention, but the ability of biochemical and echocardiographic markers of preclinical disease to improve stroke prediction is not well-defined. Methods— We evaluated such markers as predictors of ischemic stroke in a community-based cohort of American Indians without prevalent cardiovascular or renal disease. Laboratory markers included C-reactive protein, fibrinogen, urine albumin-to-creatinine ratio, and glycohemoglobin (HbA1c), whereas echocardiographic parameters comprised left atrial diameter, left ventricular mass, mitral annular calcification, and the ratio of early to late mitral diastolic velocities. Predictive performance was judged by indices of discrimination, reclassification, and calibration. Results— After adjustment for standard risk factors, only HbA1c, albuminuria, and left atrial diameter were significantly associated with first ischemic stroke. Addition of HbA1c, although not urine albumin-to-creatinine ratio, to a basic clinical model significantly improved the C-statistic (0.714 versus 0.695; P=0.044), whereas left atrial diameter modestly enhanced integrated discrimination improvement (0.90%; P=0.004), but not the C-statistic (0.701; P=0.528). When combined with HbA1c, left atrial diameter further increased integrated discrimination improvement (1.81%; P<0.001) but not the C-statistic (0.716). No marker achieved significant net reclassification improvement. Conclusions— In this cohort at high cardiometabolic risk, HbA1c emerged as the foremost predictor of ischemic stroke when added to traditional risk factors, affording substantially improved discrimination, with a more modest contribution for left atrial diameter. These findings bolster the role of HbA1c in cardiovascular risk assessment among persons with glycometabolic disorders and provide impetus for further study of the incremental value of echocardiography in high-risk populations.

Sex‐ and Race‐Related Differences in Characteristics and Outcomes of Hospitalizations for Heart Failure With Preserved Ejection Fraction

Background Sex and race have emerged as important contributors to the phenotypic heterogeneity of heart failure with preserved ejection fraction (HFpEF). However, there remains a need to identify important sex‐ and race‐related differences in characteristics and outcomes using a nationally representative cohort. Methods and Results Data were obtained from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project—Nationwide Inpatient Sample files between 2008 and 2012. Hospitalizations with a diagnosis of HFpEF were included for analysis. Demographics, hospital characteristics, and age‐adjusted comorbidity prevalence rates were compared between men and women and whites and blacks. In‐hospital mortality was determined and compared for each subgroup. Multivariable regression analyses were used to identify and compare correlates of in‐hospital mortality for each subgroup. A sample of 1 889 608 hospitalizations was analyzed. Men with HFpEF were slightly younger than women with HFpEF and had a higher Elixhauser comorbidity score. Men experienced higher in‐hospital mortality compared with women, a finding that was attenuated after adjusting for comorbidity. Blacks with HFpEF were younger than whites with HFpEF, with lower rates of most comorbidities. Hypertension, diabetes, anemia, and chronic renal failure were more common among blacks. Blacks experienced lower in‐hospital mortality compared with whites, even after adjusting for age and comorbidity. Important correlates of mortality among all 4 subgroups included pulmonary circulation disorders, liver disease, and chronic renal failure. Atrial fibrillation was an important correlate of mortality only among women and blacks. Conclusions Differences in patient characteristics and outcomes reinforce the notion that sex and race contribute to the phenotypic heterogeneity of HFpEF.

Pulmonary tumour thrombotic microangiopathy as a cause of new-onset pulmonary hypertension in a patient with metastatic low-grade serous ovarian cancer

A 78-year-old woman with metastatic low-grade serous ovarian cancer presented with rapidly progressive exertional dyspnoea and hypoxia, and was found to have new-onset severe pulmonary hypertension (PH) by right heart catheterisation. A diagnosis of pulmonary tumour thrombotic microangiopathy (PTTM) was made at autopsy. PTTM is a rare complication of advanced cancer that often presents as rapidly progressive PH or acute hypoxic respiratory failure. Widespread tumour cell emboli in the pulmonary arteries and arterioles are hypothesised to induce fibrocellular subintimal proliferation and microthrombi, leading to increased pulmonary vascular resistance and PH. PTTM arising from serous ovarian cancer is exceedingly rare, with only two previously reported cases. A discussion of the pathophysiology, diagnosis and management of PTTM is presented.

CHARACTERIZATION AND IMPACT OF COMORBIDITY AMONG GENDER AND RACIAL SUBGROUPS HOSPITALIZED WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION

Heart failure with preserved ejection fraction (HFpEF) is challenging to treat in part due to its phenotypic heterogeneity. There are limited data on differences in characteristics and outcomes of gender and race subgroups. Using the Nationwide Inpatient Sample, we examined 2,102,780