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Objectives: This study sought to determine whether left atrial (LA) dysfunction predicts heart failure (HF) hospitalization in subjects with preserved baseline ejection fraction (EF). Background: Among patients with preserved EF, factors leading to HF are not fully understood. Cross-sectional studies have demonstrated LA dysfunction at the time of HF, but longitudinal data on antecedent atrial function are lacking. Methods: We performed resting transthoracic echocardiography in 855 subjects with coronary heart disease and EF ≥50%. Left atrial functional index (LAFI) was calculated as ([LA emptying fraction × left ventricular outflow tract-velocity time integral] / [indexed LA end-systolic volume]), where LA emptying fraction was defined as (LA end-systolic volume − LA end-diastolic volume) / LA end-systolic volume. We used Cox models to evaluate the association between LAFI and HF hospitalization. Results: Over a median follow-up of 7.9 years, 106 participants (12.4%) were hospitalized for HF. Rates of HF hospitalization were inversely proportional to quartile (Q) of LAFI: Q1, 47 per 1,000 person-years; Q2, 18.3; Q3, 9.6; and Q4, 5.3 (p < 0.001). Each standard deviation decrease in LAFI was associated with a 2.6-fold increased hazard of adverse cardiovascular outcomes (unadjusted hazard ratio: 2.6, 95% confidence interval: 2.1 to 3.3, p < 0.001), and the association persisted even after adjustment for clinical risk factors, N-terminal pro–B-type natriuretic peptide, and a wide range of echocardiographic parameters (adjusted hazard ratio: 1.5, 95% confidence interval: 1.0 to 2.1, p = 0.05). Conclusions: Left atrial dysfunction independently predicts HF hospitalization in subjects with coronary heart disease and preserved baseline EF. The LAFI may be useful for HF risk stratification, and LA dysfunction may be a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Serum adiponectin protects against incident ischemic heart disease (IHD). However, in patients with existing IHD, higher adiponectin levels are paradoxically associated with worse outcomes. We investigated this paradox by evaluating the relationship between adiponectin and cardiovascular events in patients with existing IHD. Methods: We measured total serum adiponectin and cardiac disease severity by stress echocardiography in 981 outpatients with stable IHD who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent heart failure hospitalizations, myocardial infarction, and death were recorded. Results: During an average of 7.1 years of follow-up, patients with adiponectin levels in the highest quartile were more likely than those in the lowest quartile to be hospitalized for heart failure (23% vs. 13%; demographics-adjusted hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.04–2.56, p =0.03) or die (49% vs. 31%; HR 1.67, 95% CI 1.24–2.26, p <0.008), but not more likely to have a myocardial infarction (12% vs. 17%; HR 0.64, 95% CI 0.38–1.06, p =0.08). The combined outcome of myocardial infarction, heart failure, or death occurred in 56% (136/245) of participants in the highest quartile of adiponectin vs. 38% (94/246) of participants in the lowest quartile (HR 1.54, 95% CI 1.31–2.21, p <0.002). Adjustment for left ventricular ejection fraction, diastolic dysfunction, inducible ischemia, C-reactive protein, and NT-proBNP attenuated the association between higher adiponectin and increased risk of subsequent events (HR 1.43, 95% CI 0.98–2.09, p =0.06). Conclusions: Higher concentrations of adiponectin were associated with heart failure and mortality among patients with existing IHD. [Copyright &y& Elsevier]

Heart failure (HF) is a common public health problem, and many new cases are now recognized to occur in patients with preserved left ventricular ejection fraction. β Blockers improve the outcomes of patients with known left ventricular systolic dysfunction, but whether β blockers provide similar protection among patients with left ventricular diastolic dysfunction is unclear. We studied the association between use of β blockers and subsequent hospitalization for HF in patients with diastolic dysfunction and stable coronary heart disease. We evaluated medication use and performed echocardiography at baseline in a prospective cohort of 911 outpatients with known coronary heart disease from the Heart and Soul Study. Hospitalizations for HF were assessed by blinded review of the medical records during an average follow-up of 5.2 years. Of the 911 participants, 118 (13%) had diastolic dysfunction, of whom 2 were lost to follow-up. Of the 116 remaining patients, 19 (25%) of the 77 using β blockers were hospitalized for HF compared to 16 (41%) of the 39 not using β blockers (age-adjusted hazard ratio 0.51, 95% confidence interval 0.26 to 1.00; p = 0.05). This association remained after additional adjustment for gender, smoking, history of myocardial infarction, diabetes, and creatinine (hazard ratio 0.46, 95% confidence interval 0.23 to 0.93; p = 0.03). The results were similar after excluding 31 participants with a history of self-reported HF (hazard ratio 0.33, 95% confidence interval 0.13 to 0.86; p = 0.02) and 24 participants with concurrent systolic dysfunction (hazard ratio 0.36, 95% confidence interval 0.14 to 0.89; p = 0.03). In conclusion, the use of β blockers is associated with a decreased risk of hospitalization for HF in patients with diastolic dysfunction and stable coronary heart disease. [Copyright &y& Elsevier]

Obesity is an independent risk factor for recurrent events among patients with established coronary heart disease (CHD). The goal of the present study was to identify potential mechanisms underlying this association. We measured the waist-to-hip ratio and body mass index in 979 outpatients with stable CHD and followed them for a mean of 4.9 years. We used proportional hazards models to evaluate the extent to which the association of obesity with subsequent heart failure (HF) hospitalization or cardiovascular (CV) events (myocardial infarction, stroke, or CHD death) was explained by baseline co-morbidities, cardiac disease severity, inflammation, insulin resistance, neurohormones and adipokines. Of the 979 participants, 128 (13%) were hospitalized for HF and 152 (16%) developed a CV event. Each standard deviation (SD) increase in the waist-to-hip ratio was associated with a 30% increased risk of HF hospitalization (unadjusted hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.1 to 1.6). This association was not attenuated after adjustment for potential mediators (HR 1.6, 95% CI 1.2 to 2.1). Likewise, each SD increase in the waist-to-hip ratio was associated with a 20% greater risk of CV events (unadjusted HR 1.2, 95% CI 1.0 to 1.4), and this remained unchanged after adjustment for potential mediators (adjusted HR 1.3, 95% CI 1.0 to 1.5). The body mass index was not associated with the risk of HF or CV events. In conclusion, abdominal obesity is an independent predictor of HF hospitalization and recurrent CV events in patients with stable CHD. This association does not appear to be mediated by co-morbid conditions, cardiac disease severity, insulin resistance, inflammation, neurohormones, or adipokines. [Copyright &y& Elsevier]

Diastolic dysfunction is usually identified by the combination of characteristic mitral and pulmonary vein flow patterns. However, obtaining a complete set of echocardiographic parameters can be technically difficult and data may conflict. We hypothesized that as a stand-alone variable, (ventricular) diastolic dominant pulmonary vein flow would predict heart failure (HF) hospitalizations and cardiovascular death. Standard transthoracic echocardiograms were obtained in 906 subjects from the Heart and Soul Study, a prospective study of the effects of depression on coronary heart disease. Pulmonary vein flow pattern was determined using the dominant velocity–time integral. Cardiac events were determined by 2 independent adjudicators, and Cox proportional hazards models were used. Systolic dominant pulmonary vein flow was present in 89% of subjects, and diastolic dominant, in the remaining 11%. During an average 4.1 years of follow-up, subjects with diastolic dominant pulmonary vein flow had a 25% rate of HF hospitalization and 9% rate of cardiovascular death. After multivariate adjustment including left ventricular ejection fraction, diastolic pulmonary vein flow was associated with a 3-fold risk of HF hospitalization (p = 0.001) and a 2-fold risk of HF hospitalization or death (p = 0.004). In conclusion, diastolic dominant pulmonary vein flow pattern was a stand-alone predictor of adverse cardiac events, and its presence was associated with significantly higher rates of HF hospitalizations and cardiovascular death. [Copyright &y& Elsevier]

The predictive value of left atrial (LA) dilatation in ambulatory adults with coronary artery disease is not known. It was hypothesized that echocardiographic LA volume index (LAVI) predicts heart failure (HF) hospitalization and mortality with similar statistical power as left ventricular ejection fraction (LVEF) in ambulatory adults with coronary artery disease. We measured LAVI in 935 adults without atrial fibrillation, atrial flutter, or significant mitral valve disease in the Heart and Soul Study. LAVI was calculated using the biplane method of disks. Outcomes included HF hospitalization and mortality. Logistic regression odds ratios (ORs) were calculated and adjusted for age, demographics, medical history, left ventricular mass, diastolic function, and LVEF. Mean LAVI was 32 ± 11 ml/m2, and mean LVEF was 62 ± 10%. Sixty-six patients (7%) had LAVI >50 ml/m2. There were 108 HF hospitalizations and 180 deaths at 4.3 years of follow-up. C statistics calculated as the area under the receiver-operator characteristic curve were the same (0.60) for LAVI and LVEF in predicting mortality. The unadjusted OR for HF hospitalization was 4.4 for LAVI >50 ml/m2 and 5.3 for LVEF <45% (p <0.001). In those with normal LVEF, the ORs for LAVI >50 ml/m2 were 5.2 for HF hospitalization (p <0.0001) and 2.5 for mortality (p = 0.006). After multivariate adjustment, LAVI >50 ml/m2 was predictive of HF hospitalization (OR 2.4, p = 0.02), and LAVI >40 ml/m2 was predictive of mortality (OR 1.9, p = 0.005). In conclusion, LAVI had similar predictability as LVEF for HF hospitalization and mortality in ambulatory adults with coronary artery disease. [Copyright &y& Elsevier]

The association of asymptomatic left ventricular (LV) diastolic dysfunction with cardiovascular outcomes in ambulatory patients with coronary heart disease (CHD) and no history of heart failure (HF) was examined. LV diastolic HF predicts adverse cardiovascular outcomes. However, the prevalence and prognosis of asymptomatic LV diastolic dysfunction in patients with established CHD in the absence of clinical HF is unknown. Six hundred ninety-three patients with stable CHD, normal systolic function (LV ejection fraction ≥50%), and no history of HF were evaluated. Echocardiography was used to classify LV diastolic function, and Cox proportional hazards models were used to evaluate the association of LV diastolic dysfunction with cardiovascular outcomes during 3 years of follow-up. Of 693 subjects with normal systolic function and no history of HF, 455 (66%) had normal LV diastolic function, 166 (24%) had mild LV diastolic dysfunction, and 72 (10%) had moderate to severe LV diastolic dysfunction. After multivariable adjustment, the presence of moderate to severe LV diastolic dysfunction was strongly predictive of incident hospitalization for HF (hazard ratio 6.3, 95% confidence interval 2.4 to 16.1, p = 0.0003) and death from heart disease (HR 3.9, 95% confidence interval 1.0 to 14.8, p = 0.05). In conclusion, moderate to severe LV diastolic dysfunction was present in 10% of patients with stable CHD with normal ejection fraction and no history of HF and predicts subsequent hospitalization for HF and death from heart disease. Patients with asymptomatic LV diastolic dysfunction may benefit from more aggressive therapy to prevent or delay the development of HF. [Copyright &y& Elsevier]