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To further define the age-related distribution of diastolic function as defined by E/A ratio, in healthy male adults. The age-sensitive ratio of mitral inflow E-wave to A-wave (E/A) velocity is often considered in the evaluation of diastolic function. To appropriately direct a comprehensive evaluation of diastolic function, we sought to improve the characterization of the influence of age on E/A ratio. We analyzed echocardiographic data from the Mind Your heart Study, a cohort of outpatients recruited from two San Francisco Veterans centers to examine the effect of mental health on cardiovascular outcomes. Individuals with a history of heart disease or hypertension were excluded, leaving 313 veterans for analysis. We examined E/A by 5-year increments and performed linear and logistic regression analysis to predict trends in E/A and E dominance. Within the age ranges of population (54.9 ± 11.5), there is a steady gradual decline in absolute E/A ratio (beta coefficient/year- 0.018, P < .001) and the odds of E dominance similarly declines with age (odds ratio/year = 0.89, P < .001). Despite this decline, 90% of individuals below the age of 50 years maintain E dominance. Beyond age 50, 55% maintain E dominance, and beyond age 70, only 28% have E dominance. In this adequately healthy population, age-related progression of delayed relaxation appears to be a state of normality rather than diastolic dysfunction. Careful attention to specific cutoff points in age and E/A ratio could avoid misinterpretation or inappropriate management., (© 2019 Wiley Periodicals, Inc.)

Background: Prior studies suggested an association between bisphosphonates and atrial fibrillation/flutter (AF) in women. This relationship in men, including those with sleep-disordered breathing (SDB), remains unclear. This study evaluated the relationship between bisphosphonate use and prevalent (nocturnal) and incident (clinically relevant) AF in a population of community-dwelling older men., Methods: A total of 2,911 male participants (mean age, 76 years) of the prospective observational Osteoporotic Fractures in Men Study sleep cohort with overnight in-home polysomnography (PSG) constituted the analytic cohort. Nocturnal AF from ECGs during PSG and incident AF events were centrally adjudicated. The association of bisphosphonate use and AF was examined using multivariable-adjusted logistic regression for prevalent AF and Cox proportional hazards regression for incident AF., Results: A total of 123 (4.2%) men were current bisphosphonate users. Prevalent nocturnal AF was present in 138 participants (4.6%). After multivariable adjustment, there was a significant association between current bisphosphonate use and prevalent AF (OR, 2.33; 95% CI, 1.13-4.79). In the subset of men with moderate to severe SDB, this association was even more pronounced (OR, 3.22; 95% CI, 1.29-8.03). However, the multivariable-adjusted relationship between bisphosphonate use and incident AF did not reach statistical significance (adjusted hazard ratio, 1.53; 95% CI, 0.96-2.45)., Conclusions: These results support an association between bisphosphonate use and prevalent nocturnal AF in community-dwelling older men. The data further suggest that those with moderate to severe SDB may be a particularly vulnerable group susceptible to bisphosphonate-related AF. Similar associations were not seen for bisphosphonate use and clinically relevant incident AF., (Copyright © 2016 American College of Chest Physicians. All rights reserved.)

Background: Stroke distance of the left ventricular outflow tract (LVOT) or pulmonary artery (PA) is readily measurable by Doppler echocardiography. Stroke distance, calculated by the velocity time integral, expresses the average linear distance traveled by red blood cells during systole. We hypothesized that reduced stroke distance predicts heart failure (HF) hospitalization or mortality among ambulatory adults with stable coronary artery disease., Methods: We compared stroke distances by lowest quartile among 990 participants in the Heart and Soul Study. We calculated hazard ratios (HRs) for events adjusted for clinical and echocardiographic parameters., Results: At 5.9 ± 1.9-year follow-up, there were 154 HF hospitalizations and 271 all-cause deaths. Among 254 participants with LVOT stroke distance in the lowest quartile (≤ 18 cm), 24% developed HF hospitalization, compared with 10% of those with higher stroke distance (HR 2.7; CI, 2.0-3.8; P < .0001). This association remained after adjustment for multiple variables including medical history, heart rate, blood pressure, and left ventricular ejection fraction (HR 1.8; CI, 1.1-3.0; P = .02). Both LVOT stroke distance ≤ 18 cm and PA stroke distance ≤ 17 cm were independently associated with the combined end point of HF hospitalization and mortality (HR 1.4; CI, 1.1-1.9; P = .02)., Conclusion: Reduced stroke distance predicts HF hospitalization and mortality independent of clinical and other echocardiographic parameters among ambulatory adults with coronary artery disease., (Copyright © 2011 American Society of Echocardiography. All rights reserved.)

Background: the tissue spanning the mitral and aortic valves, the mitral-aortic intervalvular fibrosa (MAIVF), may be the site of pseudoaneurysm formation in the setting of infective endocarditis or congenital heart disease, or after valve surgery. Because of potential complications of MAIVF pseudoaneurysms, patients with such lesions are often referred for surgical repair., Methods: we identified 3 individuals with MAIVF pseudoaneurysms who were followed without surgical intervention after diagnosis of the MAIVF pseudoaneurysm. The courses of these patients are presented below., Results: the MAIVF pseudoaneurysms were measured to be stable in size over several years among 3 patients. Dimensions were 5.3 × 2.3, 7.6 × 4.9, and 4.8 × 2.5 cm. Surgical repair was considered too high a risk in 2 of the individuals, and the third individual refused a third surgical intervention. Of the 3 patients, 2 remain asymptomatic. The third patient was 87 years old when her MAIVF pseudoaneurysm was diagnosed, and she died of noncardiac causes at age 92 years., Conclusions: clinical surveillance and serial imaging of MIAVF pseudoaneurysms may be considered an alternative to surgical management in select individuals.

Purpose of Review: Accurate noninvasive evaluation of right heart hemodynamics is an essential component of the comprehensive cardiac examination. We aim to highlight recent advances in echocardiography allowing integration of measurements to obtain diagnostic accuracy., Recent Findings: Reports have advocated different imaging methods to describe right ventricular function and pulmonary artery pressure. Recent review articles provide comprehensive resources for the physician or technologist, and other articles compare echocardiography techniques, including strain imaging and three-dimensional echocardiography. We discuss the descriptions of the accuracy of Doppler echocardiography in comparison with cardiac catheterization., Summary: Several measurements should be taken together for an accurate interpretation of right heart hemodynamics. We advocate the measurement of the tricuspid regurgitation gradient, pulmonary regurgitation gradient, pulmonary artery stroke distance (velocity time integral; VTI), evaluation of right ventricular function, and right atrial pressure.

Background: Echocardiographic measurements of left ventricular (LV) mass, left atrial (LA) volume, and LV end-systolic volume (ESV) predict heart failure (HF) hospitalization and mortality. Indexing measurements by body size is thought to establish limits of normality among individuals varying in body habitus. The American Society of Echocardiography recommends dividing measurements by body surface area (BSA), but others have advocated alternative indexing methods., Methods: Echocardiographic measurements were collected in 1024 ambulatory adults with coronary artery disease. LV mass, LA volume, and LV ESV were calculated using truncated ellipse method and biplane method of disk formulae. Comparison between raw measurements and measurements divided by indexing parameters was made by hazard ratios per standard deviation increase in variable and c-statistics for BSA, BSA(0.43), BSA(1.5), height, height(0.25), height(2), height(2.7), body weight (BW), BW(0.26), body mass index (BMI), and BMI(0.27)., Results: Mean LV mass was 192 +/- 57 g, mean LA volume was 65 +/- 24 mL, and mean LV ESV was 41 +/- 26 mL. Average height was 171 +/- 9 cm, average BSA was 1.94 +/- 0.22 m(2), and average BMI was 28.4 +/- 5.3 kg/m(2). At an average follow-up of 5.6 +/- 1.8 years, there were 148 HF hospitalizations, 71 cardiovascular (CV) deaths, and 269 all-cause deaths. There was excellent correlation between raw measurements and those indexed by height (r = 0.98-0.99), and moderate correlation between raw measurements and those indexed by BW (r = 0.73-0.94). C-statistics and hazard ratios per standard deviation increase in indexed variables were similar for HF hospitalization, CV mortality, and all-cause mortality. There were no significant differences among indexing methods in ability to predict outcomes., Conclusion: The choice of indexing method by parameters of BSA, height, BW, and BMI does not affect the clinical usefulness of LV mass, LA volume, and LV ESV in predicting HF hospitalization, CV mortality, or all-cause mortality among ambulatory adults with coronary artery disease. Continued use of BSA to index measurements of LV mass, LA volume, and LV ESV is acceptable., (Copyright 2010 American Society of Echocardiography. All rights reserved.)

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.

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.

Background: Young severely obese patients with advanced heart failure may not be suitable candidates for cardiac transplantation because of surgical morbidity and availability of adequately sized donor hearts., Methods and Results: We report 2 patients with severe systolic dysfunction and Class IV heart failure despite maximal medical therapy who were considered for cardiac transplantation. Because of their severe obesity, transplantation was not considered an optimal therapy, and both were referred for bariatric surgery. The individuals had nonischemic cardiomyopathy. Both underwent laparoscopic vertical gastrectomy, minimizing surgical risk while providing definitive reduction in gastric volume. They experienced substantial weight loss and resolution of dyspnea. Inotrope infusion was discontinued in 1 dobutamine-dependent individual. They achieved weight reduction of 46 to 52 kg after the surgery. End-systolic volume index improved from 64 to 49 mL/m(2) and from 66 to 39 mL/m(2). Left ventricular ejection fraction improved from 20% to 45% and from 25% to 39%. They remain symptom-free and are no longer listed for transplant at 2 years' follow-up., Conclusions: Bariatric surgery may lead to improvement in left ventricular systolic dysfunction in young morbidly obese individuals with nonischemic cardiomyopathy. Potential explanations for the improvement in left ventricular function include reduced direct toxic effects of adiposity on cardiomyocytes and improved hemodynamics after weight loss. The potential for bariatric surgery to provide an alternative to heart transplantation in extreme obesity merits further study.

Background: Whether increased severity of heart failure in African Americans is a result of differences in cardiac physiology is uncertain. The end-diastolic pulmonary regurgitation (EDPR) gradient is associated with abnormal cardiac physiology. We hypothesized that African American race is associated with an elevated EDPR gradient that may partially predispose African Americans to heart failure., Methods: The Heart and Soul Study prospectively assessed the EDPR gradient in 480 patients with coronary disease. We used multivariable linear regression to investigate the independent association of African American race with EDPR gradient., Results: Compared with 393 non-African Americans, the 87 African Americans had similar indices of left ventricular systolic and diastolic function, left ventricular mass index, mitral regurgitation, peak tricuspid regurgitation gradient, and pulmonary velocity time integral. However, the EDPR gradient was significantly higher in African Americans (4.2 +/- 3.3 mm Hg) than in Caucasians (3.1 +/- 2.5 mm Hg) or other racial groups (3.5 +/- 2.7 mm Hg) (P = .008). In a multivariable model, African American race was a significant predictor of elevated EDPR gradient (beta coefficient 0.75, P = .03)., Conclusion: African American race is independently associated with an elevated EDPR gradient in patients with coronary artery disease.

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>or=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.

We describe a 45-year-old woman receiving infliximab therapy for rheumatoid arthritis who developed an overwhelming Plasmodium falciparum infection with cerebral malaria. Physicians should be aware that patients receiving tumor necrosis factor inhibitors, such as infliximab, may be at increased risk of life-threatening malarial infections.

Aortic sclerosis is associated with cardiovascular events in patients without coronary heart disease (CHD), but it is unclear whether this association exists in patients with established CHD or is independent of baseline cardiac disease severity. It is also unclear whether statins modify this association. In a prospective cohort study of 814 outpatients with established CHD and no evidence of aortic stenosis, the association of aortic sclerosis with subsequent cardiovascular events was examined using a multivariable Cox proportional hazards model. Of 814 participants, 324 (40%) had aortic sclerosis. During 4 years of follow-up, 10% with aortic sclerosis experienced a myocardial infarction (MI) compared with 5% of those without aortic sclerosis (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.1 to 3.1, p = 0.02). This association was unchanged after adjustment for potential confounders and mediators (HR 2.4, 95% CI 1.3 to 4.8, p = 0.009). However, the association between aortic sclerosis and MI appeared to differ by statin use (p = 0.15 for interaction). Aortic sclerosis predicted subsequent MI in subjects not administered statins (adjusted HR 4.1, 95% CI 1.1 to 15.7, p = 0.04), but not in those administered statins (adjusted HR 1.7, 95% CI 0.8 to 3.9, p = 0.18). In conclusion, aortic sclerosis was present in 40% of patients with CHD and is independently associated with a 2.4-fold increased rate of subsequent MI. Statins may attenuate the increased risk of future MI in patients with aortic sclerosis.

Objectives: We compared the predictive ability of tricuspid regurgitation (TR) and end-diastolic pulmonary regurgitation (EDPR) gradients in outpatients with coronary artery disease., Background: The TR and EDPR gradients, in conjunction with right atrial pressure, provide Doppler estimates of pulmonary artery systolic and diastolic pressures. We hypothesized that increases in TR or EDPR gradients in stable coronary artery disease would predict heart failure (HF) hospitalization or cardiovascular (CV) death., Methods: We measured TR and EDPR gradients in 717 adults with completed outcome adjudications who were recruited for the Heart and Soul Study. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for HF hospitalization, CV death, all-cause death, and the combined end point. Multivariate adjustments were made for age, gender, race, history of CV or pulmonary disease, functional class, and left ventricular ejection fraction., Results: There were 63 HF hospitalizations, 19 CV deaths, and 86 all-cause deaths at the 3-year follow-up. There were 466 measurable EDPR gradients and 573 measurable TR gradients. Age-adjusted ORs for EDPR >5 mm Hg predicted HF hospitalization (2.7, 95% CI 1.3 to 5.5, p = 0.006), all-cause death (2.5, 95% CI 1.4 to 4.4, p = 0.002), and HF hospitalization or CV death (2.7, 95% CI 1.4 to 5.2, p = 0.004). Age-adjusted OR for TR >30 mm Hg predicted HF hospitalization (3.4, 95% CI 1.9 to 6.2, p < 0.0001) and HF hospitalization or CV death (3.0, 95% CI 1.7 to 5.3, p = 0.0001). Multivariate adjusted OR per 5-mm Hg incremental increases in EDPR predicted HF hospitalization or CV death (1.9, 95% CI 1.01 to 3.6, p = 0.046) and all-cause death (1.7, 95% CI 1.05 to 2.8, p = 0.03). Multivariate adjusted OR per 10-mm Hg incremental increases in TR predicted HF hospitalization or CV death (1.6, 95% CI 1.1 to 2.4, p = 0.008)., Conclusions: Increases in EDPR or TR gradients predict HF hospitalization or CV death among ambulatory adults with coronary artery disease.

Background: Echocardiograms routinely sample pulmonary regurgitation signals from which it is possible to measure end diastolic gradients; these correlate with pulmonary artery diastolic pressures., Methods: We performed echocardiograms in 741 ambulatory adults with coronary artery disease who were recruited for the Heart and Soul Study. We compared indicators of cardiac status among individuals with normal (0-5.0 mm Hg) and elevated (> 5.0 mm Hg) end diastolic pulmonary regurgitation (EDPR) gradients., Results: Of the 481 participants with measurable EDPR gradients, 21% had elevated EDPR gradients (> 5.0 mm Hg). EDPR gradients > 5.0 mm Hg were associated with higher New York Heart Association functional class (P = .002), higher brain natriuretic peptide (P = .002), fewer metabolic equivalents achieved on treadmill testing (P < 0.001), and higher left ventricular mass (P < 0.001). The EDPR gradient > 5.0 mm Hg had a sensitivity of 25% (95% confidence interval 20-30%) and a specificity of 86% (80-91%) for detecting at least one of the following: systolic dysfunction, diastolic dysfunction, or abnormal wall motion score. The EDPR gradient > 5.0 mm HG was statistically equivalent to the tricuspid regurgitation (TR) gradient > 30 mm Hg in terms of diagnostic value (area under the receiver operating characteristic curve equaled 0.58 for each test). The EDPR gradient increased the yield of pulmonary artery pressures from 61% (TR gradient alone) to 84% (P < .0001)., Conclusion: The EDPR gradient provides valuable information independent of the TR gradient in evaluating pulmonary artery pressures and cardiac dysfunction.