Jerome L Fleg

National Heart, Lung, and Blood Institute, 베서스다, Maryland, United States

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Publications (264)1907.08 Total impact

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    ABSTRACT: Whether a coronary artery calcium (CAC) scan provides added value to coronary computed tomographic angiography (CCTA) in emergency department patients with acute chest pain remains unsettled. We sought to determine the value of CAC scan in patients with acute chest pain undergoing CCTA. In the multicenter Rule Out Myocardial Infarction using Computer-Assisted Tomography (ROMICAT) II trial, we enrolled low-intermediate risk emergency department patients with symptoms suggesting acute coronary syndrome (ACS). In this prespecified subanalysis of 473 patients (54±8 years, 53% men) who underwent both CAC scanning and CCTA, the ACS rate was 8%. Overall, 53% of patients had CAC=0 of whom 2 (0.8%) developed ACS, whereas 7% had CAC>400 with 49% whom developed ACS. C-statistic of CAC>0 was 0.76, whereas that using the optimal cut point of CAC≥22 was 0.81. Continuous CAC score had lower discriminatory capacity than CCTA (c-statistic, 0.86 versus 0.92; P=0.03). Compared with CCTA alone, there was no benefit combining CAC score with CCTA (c-statistic, 0.93; P=0.88) or with selective CCTA strategies after initial CAC>0 or optimal cut point CAC≥22 (P≥0.09). Mean radiation dose from CAC acquisition was 1.4±0.7 mSv. Higher CAC scores resulted in more nondiagnostic CCTA studies although the majority remained interpretable. In emergency department patients with acute chest pain, CAC score does not provide incremental value beyond CCTA for ACS diagnosis. CAC=0 does not exclude ACS, nor a high CAC score preclude interpretation of CCTA in most patients. Thus, CAC results should not influence the decision to proceed with CCTA, and the decision to perform a CAC scan should be balanced with the additional radiation exposure required. Unique identifier: NCT01084239. © 2015 American Heart Association, Inc.
    Circulation Cardiovascular Imaging 03/2015; 8(3). DOI:10.1161/CIRCIMAGING.114.002225 · 5.80 Impact Factor
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    ABSTRACT: To the Editor:In our study showing no increase in the rate of falls with intensive blood pressure (BP) control in the ACCORD trial, Dr. Jolobe inquires whether the prevalence of orthostatic hypotension differed between the intensive and standard BP control groups. He further notes that orthostatic hypotension may not be accompanied by symptoms. The ACCORD BP trial did gather data on orthostatic BP change and dizziness on standing in a subgroup of participants. Of the 3,099 participants included in our analysis, orthostatic BP measurements and reports of dizziness or lightheadedness on standing during the measurement are available on 905 participants at baseline. We also have data on a subgroup of 607 participants who were assessed for health-related quality of life at baseline and 12 months. This included a question about dizziness on standing within the previous month.Seated and standing brachial artery BP was measured using an Omron model HEM-907 automatic sphygmomanometer. After 7 m ...
    Journal of General Internal Medicine 02/2015; DOI:10.1007/s11606-015-3191-z · 3.42 Impact Factor
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    ABSTRACT: -Previous studies have demonstrated the psychosocial impact of Heart Failure in patients with reduced ejection fraction (EF). However, the effects on patients with preserved EF have not yet been elucidated. The present study aimed to determine the baseline characteristics of participants with Heart Failure with preserved ejection fraction (HFpEF) as it relates to impaired quality of life (QOL) and depression, identify predictors of poor QOL and depression, and determine the correlation between QOL and depression. -Among patients enrolled in the TOPCAT trial, 3400 patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), 3395 patients completed EuroQOL 5D Visual Analog Scale (EQ-5D VAS), and 1431 patients in US and Canada completed the Patient Health Questionnaire-9. The mean summary score on the KCCQ was 54.8; and on EQ-5D VAS was 60.3; 27% of patients had moderate to severe depression. Factors associated with better KCCQ and EQ-5D VAS via multiple logistic regression analysis (MLRA) were American region, older age; no history of angina pectoris or asthma, no use of hypoglycemic agent; more activity level; and lower NYHA class. Factors associated with depression via MLRA included younger age, female gender, comorbid angina, COPD, use of a hypoglycemic agent, lower activity level, higher NYHA class, and SSRI use. There were significant correlations between each of the QOL scores and depression. -Patients with HFpEF who were younger, had higher NYHA class or comorbid angina pectoris, had lower activity levels, lived in Eastern Europe or were taking hypoglycemic agents, were more likely to have impaired QOL and depression. Clinical Trial Registration-URL: Unique identifier: NCT00094302.
    Circulation Heart Failure 02/2015; 8(2). DOI:10.1161/CIRCHEARTFAILURE.114.001838 · 6.68 Impact Factor
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    Circulation Heart Failure 01/2015; 8(1):209-20. DOI:10.1161/CIRCHEARTFAILURE.113.001420 · 6.68 Impact Factor
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    ABSTRACT: -Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) patients with heart failure and preserved left ventricular ejection fraction assigned to spironolactone did not achieve a significant reduction in the primary composite outcome (time to cardiovascular death, aborted cardiac arrest, or hospitalization for management of heart failure) compared with patients receiving placebo. In a post hoc analysis, an ≈4-fold difference was identified in this composite event rate between the 1678 patients randomized from Russia and Georgia compared with the 1767 enrolled from the United States, Canada, Brazil, and Argentina (the Americas). -To better understand this regional difference in clinical outcomes, demographic characteristics of these populations and their responses to spironolactone were explored. Patients from Russia/Georgia were younger, had less atrial fibrillation and diabetes mellitus, but were more likely to have had prior myocardial infarction or a hospitalization for heart failure. Russia/Georgia patients also had lower left ventricular ejection fraction and creatinine but higher diastolic blood pressure (all P<0.001). Hyperkalemia and doubling of creatinine were more likely and hypokalemia was less likely in patients receiving spironolactone in the Americas with no significant treatment effects in Russia/Georgia. All clinical event rates were markedly lower in Russia/Georgia, and there was no detectable impact of spironolactone on any outcomes. In contrast, in the Americas, the rates of the primary outcome, cardiovascular death, and hospitalization for heart failure were significantly reduced by spironolactone. -This post hoc analysis demonstrated greater potassium and creatinine changes and possible clinical benefits with spironolactone in patients with heart failure and preserved ejection fraction from the Americas. Clinical Trial Registration-URL: Unique identifier: NCT00094302.
    Circulation 11/2014; 131(1). DOI:10.1161/CIRCULATIONAHA.114.013255 · 14.95 Impact Factor
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    ABSTRACT: Purpose To determine the association between nonalcoholic fatty liver disease ( NAFLD nonalcoholic fatty liver disease ) and the presence of high-risk coronary atherosclerotic plaque as assessed with coronary computed tomographic (CT) angiography. Materials and Methods This study was approved by the local ethics committees; informed consent was obtained. Patients randomized to the coronary CT angiography arm of the Rule Out Myocardial Infarction using Computer Assisted Tomography, or ROMICAT Rule Out Myocardial Infarction using Computer Assisted Tomography , II trial who underwent both nonenhanced CT to assess calcium score and contrast material-enhanced coronary CT angiography were included. Readers assessed coronary CT angiography images for the presence of coronary plaque, significant stenosis (≥50%), and high-risk plaque features (positive remodeling, CT attenuation < 30 HU, napkin-ring sign, spotty calcium). NAFLD nonalcoholic fatty liver disease was defined as hepatic steatosis at nonenhanced CT (liver minus spleen CT attenuation < 1 HU) without evidence of clinical liver disease, liver cirrhosis, or alcohol abuse. To determine the association between high-risk plaque and NAFLD nonalcoholic fatty liver disease , univariable and multivariable logistic regression analyses were performed, with high-risk plaque as a dependent variable and NAFLD nonalcoholic fatty liver disease , traditional risk factors, and extent of coronary atherosclerosis as independent variables. Results Overall, 182 (40.9%) of 445 patients had CT evidence of NAFLD nonalcoholic fatty liver disease . High-risk plaque was more frequent in patients with NAFLD nonalcoholic fatty liver disease than in patients without NAFLD nonalcoholic fatty liver disease (59.3% vs 19.0%, respectively; P < .001). The association between NAFLD nonalcoholic fatty liver disease and high-risk plaque (odds ratio, 2.13; 95% confidence interval: 1.18, 3.85) persisted after adjusting for the extent and severity of coronary atherosclerosis and traditional risk factors. Conclusion NAFLD nonalcoholic fatty liver disease is associated with advanced high-risk coronary plaque, independent of traditional cardiovascular risk factors and the extent and severity of coronary artery disease. © RSNA, 2014.
    Radiology 11/2014; DOI:10.1148/radiol.14140933 · 6.21 Impact Factor
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    ABSTRACT: We sought to determine if outcomes with exercise training in heart failure (HF) vary according to ventricular pacing type. Heart Failure: A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) randomized 2331 outpatients with HF and LVEF ≤35% to usual care plus exercise training or usual care alone. We examined the relation between outcomes and randomized treatment by ventricular pacing status using Cox proportional hazards modeling. In HF-ACTION 1118 patients (48%) had an implanted cardiac rhythm device; 683 with right ventricular and 435 with biventricular pacemakers. Patients with pacing devices were older, more frequently white, and had lower peak VO2 (p<.001 for all). Peak VO2 improved similarly with training in groups with and without pacing devices. The primary composite endpoint, all-cause death or hospitalization, was reduced only in patients randomized to exercise training without a device (HR 0.79 [95% CI 0.67-.93], p=0.004; RV pacing HR 1.04 [95% CI 0.84-1.28], p=0.74; BiV pacing HR 1.05 [95% CI 0.82-1.34], p=0.72; interaction p=0.058). Exercise training may improve exercise capacity in patients with implanted cardiac devices. However, the apparent beneficial effects of exercise on hospitalization or death may be attenuated in patients with implanted cardiac devices and requires further study. Copyright © 2014 Elsevier Inc. All rights reserved.
    Journal of Cardiac Failure 10/2014; DOI:10.1016/j.cardfail.2014.10.004 · 3.07 Impact Factor
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    ABSTRACT: This study sought to determine the multicenter reproducibility of magnetic resonance imaging (MRI) and the compatibility of different scanner platforms in assessing carotid plaque morphology and composition. A standardized multi-contrast MRI protocol was implemented at 16 imaging sites (GE: 8; Philips: 8). Sixty-eight subjects (61 ± 8 years; 52 males) were dispersedly recruited and scanned twice within 2 weeks on the same magnet. Images were reviewed centrally using a streamlined semiautomatic approach. Quantitative volumetric measurements on plaque morphology (lumen, wall, and outer wall) and plaque tissue composition [lipid-rich necrotic core (LRNC), calcification, and fibrous tissue] were obtained. Inter-scan reproducibility was summarized using the within-subject standard deviation, coefficient of variation (CV) and intraclass correlation coefficient (ICC). Good to excellent reproducibility was observed for both morphological (ICC range 0.98-0.99) and compositional (ICC range 0.88-0.96) measurements. Measurement precision was related to the size of structures (CV range 2.5-4.9 % for morphology, 36-44 % for LRNC and calcification). Comparable measurement variability was found between the two platforms on both plaque morphology and tissue composition. In conclusion, good to excellent inter-scan reproducibility of carotid MRI can be achieved in multicenter settings with comparable measurement precision between platforms, which may facilitate future multicenter endeavors that use serial MRI to monitor atherosclerotic plaque progression.
    The International Journal of Cardiovascular Imaging 09/2014; 31(1). DOI:10.1007/s10554-014-0532-7 · 2.32 Impact Factor
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    ABSTRACT: Background It is not known whether high-risk plaque, as detected by coronary computed tomography angiography (CTA), permits improved early diagnosis of acute coronary syndromes (ACS) independently to the presence of significant coronary artery disease (CAD) in patients with acute chest pain. Objectives The primary aim of this study was to determine whether high-risk plaque features, as detected by CTA in the emergency department (ED), may improve diagnostic certainty of ACS independently and incrementally to the presence of significant CAD and clinical risk assessment in patients with acute chest pain but without objective evidence of myocardial ischemia or myocardial infarction (MI). Methods We included patients randomized to the coronary CTA arm of the ROMICAT-II (Rule Out Myocardial Infarction/Ischemia Using Computer-Assisted Tomography II) trial. Readers assessed coronary CTA qualitatively for the presence of nonobstructive CAD (1% to 49% stenosis), significant CAD (≥50% or ≥70% stenosis), and the presence of at least 1 of the high-risk plaque features (positive remodeling, low <30 Hounsfield units plaque, napkin-ring sign, spotty calcium). In logistic regression analysis, we determined the association of high-risk plaque with ACS (MI or unstable angina pectoris) during the index hospitalization and whether this was independent of significant CAD and clinical risk assessment. Results Overall, 37 of 472 patients who underwent coronary CTA with diagnostic image quality (mean age 53.9 ± 8.0 years; 52.8% men) had ACS (7.8%; MI n = 5; unstable angina pectoris n = 32). CAD was present in 262 patients (55.5%; nonobstructive CAD in 217 patients [46.0%] and significant CAD with ≥50% stenosis in 45 patients [9.5%]). High-risk plaques were more frequent in patients with ACS and remained a significant predictor of ACS (odds ratio [OR]: 8.9; 95% CI: 1.8 to 43.3; p = 0.006) after adjustment for ≥50% stenosis (OR: 38.6; 95% CI: 14.2 to 104.7; p < 0.001) and clinical risk assessment (age, sex, number of cardiovascular risk factors). Similar results were observed after adjustment for ≥70% stenosis. Conclusions In patients presenting to the ED with acute chest pain but negative initial electrocardiogram and troponin, presence of high-risk plaques on coronary CTA increased the likelihood of ACS independent of significant CAD and clinical risk assessment (age, sex, and number of cardiovascular risk factors). (Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239)
    Journal of the American College of Cardiology 08/2014; 64(7):684–692. DOI:10.1016/j.jacc.2014.05.039 · 15.34 Impact Factor
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    ABSTRACT: To the Editor: The results of the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial were published in the Journal in 2011.(1) This study showed no incremental clinical benefit from the addition of high-dose extended-release niacin (Niaspan, AbbVie) to statin therapy during a 36-month mean follow-up period in 3414 patients who had stable atherosclerotic disease, low baseline levels of high-density lipoprotein (HDL) cholesterol, and elevated triglyceride levels. In that article, we provided data on adverse events resulting in a reduction in the dose or discontinuation of the study drug. These results were . . .
    New England Journal of Medicine 07/2014; 371(3):288-90. DOI:10.1056/NEJMc1311039 · 54.42 Impact Factor
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    ABSTRACT: In order to identify patients at increased risk of cardiovascular outcomes, apparent treatment resistant hypertension (aTRH) is defined as having a blood pressure above goal despite the use of three or more antihypertensive therapies of different classes at maximally tolerated doses, ideally including a diuretic. In light of growing scientific interest in the treatment of this group, a multi-stakeholder think-tank was convened to discuss the current state of knowledge, improve the care of these patients, and identify appropriate study populations for future observational and randomized trials in the field. Although recent epidemiologic studies in selected populations estimate the prevalence of aTRH is 10-15%, further large-scale observational studies will be needed to better elucidate risk factors. In order to spur the development of therapies for aTRH, the development of an “aTRH” label for pharmacologic and device therapies with a developmental pathway including treatment added to the use of existing therapies is favored. Although demonstration of adequate blood pressure lower should be sufficient to gain FDA approval for therapies targeting aTRH, assessment of improvement in quality of life and cardiovascular outcomes are also desirable and considered in CMS coverage decisions. Device trials under the aTRH label will need uniform and consistent processes for defining appropriate patient populations and post-approval registries assessing both long-term safety and duration of responses. Finally, patients with aTRH are likely to benefit from evaluation by a hypertension team in order to assure proper patient identification, diagnostic work-up and therapeutic management prior to consideration of advanced or novel therapies to lower BP.
    American Heart Journal 06/2014; 167(6). DOI:10.1016/j.ahj.2014.02.008 · 4.56 Impact Factor
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    ABSTRACT: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis. In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT number, NCT00094302.).
    New England Journal of Medicine 04/2014; 370(15):1383-92. DOI:10.1056/NEJMoa1313731 · 54.42 Impact Factor
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    ABSTRACT: Although exercise-induced supraventricular arrhythmias (EISVA) increase with advancing age, it is unclear whether age-associated changes in cardiac structure or function play a major role in this increase. To address this question, we examined the relationship between M-mode echocardiographic variables and EISVA occurring during maximal treadmill exercise in 366 healthy volunteers aged 20 to 90 years from the Baltimore Longitudinal Study of Aging. Simple (i.e., isolated) EISVA were detected in 69 subjects (19%), and complex EISVA (i.e., comprising > 10% of beats in any minute or occurring in runs) in another 29 subjects (8%). Univariate predictors of any EISVA, whether simple or complex, were older age (p < 0.0001), male gender (p < 0.05), greater left atrial size (p < 0.01), left ventricular mass index (p < 0.0001), interventricular septal thickness (p < 0.001), isovolumic relaxation time (p < 0.01), atrial filling fraction (p < 0.01), reduced mitral E-F closure slope (p < 0.001), peak E velocity (p < 0.02), and peak E/A ratio (p < 0.0001). Lesser exercise duration (p < 0.01), lower maximal heart rate (p < 0.0001), and higher peak systolic and diastolic blood pressures (p < 0.001) were also associated with EISVA. However, by multiple logistic regression analysis, age (p < 0.0001) was the only independent predictor of any EISVA. Univariate predictors of complex EISVA were greater age (p < 0.0001), and atrial filling fraction (p < 0.001), diastolic blood pressure (p < 0.05), lesser mitral E-F slope (p < 0.004), exercise duration (p < 0.005) and maximal heart rate (p < 0.01). However, only age (p < 0.0001) independently predicted complex EISVA. Thus, in healthy volunteers undergoing maximal treadmill exercise. EISVA are associated with greater left ventricular wall thickness, reduced early diastolic performance, diminished exercise capacity and elevated exercise blood pressure. However, none of these variables are independent predictors of EISVA over and above the powerful effect of age.
    Aging (Milan, Italy) 02/2014; 9(1-2):120-6. DOI:10.1007/BF03340137 · 1.14 Impact Factor
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    ABSTRACT: Background In the main Digitalis Investigation Group (DIG) trial, digoxin reduced the risk of 30-day all-cause hospitalization in older systolic heart failure patients. However, this effect has not been studied in older diastolic heart failure patients. Methods In the ancillary DIG trial, of the 988 patients with chronic heart failure and preserved (> 45%) ejection fraction, 631 were age ≥ 65 years (mean age 73 years, 45% women, 12% non-whites), of whom 311 received digoxin. Results All-cause hospitalization 30-day post randomization occurred in 4% of patients in the placebo group and 9% each among those in the digoxin group receiving 0.125 mg and ≥ 0.25 mg a day dosage (P = .026). Hazard ratios (HR) and 95% confidence intervals (CI) for digoxin use overall for 30-day, 3-month, and 12-month all-cause hospitalizations were 2.46 (1.25-4.83), 1.45 (0.96-2.20) and 1.14 (0.89-1.46), respectively. There was one 30-day death in the placebo group. Digoxin-associated HRs (95% CIs) for 30-day hospitalizations due to cardiovascular, heart failure, and unstable angina causes were 2.82 (1.18-6.69), 0.51 (0.09-2.79), and 6.21 (0.75-51.62), respectively. Digoxin had no significant association with 30-day all-cause hospitalization among younger patients (6% vs 7% for placebo; HR 0.80; 95% CI, 0.36-1.79). Conclusions In older patients with chronic diastolic heart failure, digoxin increased the risk of 30-day all-cause hospital admission, but not during longer follow-up. Although chance finding due to small sample size is possible, these data suggest that unlike in systolic heart failure, digoxin may not reduce 30-day all-cause hospitalization in older diastolic heart failure patients.
    The American Journal of Medicine 02/2014; 127(2):132–139. · 5.30 Impact Factor
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    ABSTRACT: Repeated failure in the Army Physical Fitness Test (APFT) is associated with lower fitness level, premature discharge, and significant career disruption, at high economic and health costs to the individual soldier and the U.S. Army. We used cost-effectiveness analysis to estimate the health and economic implications of two exercise interventions for Army National Guard (ARNG) soldiers who had failed the APFT, a traditional remediation program and a new pedometer-based program called Fitness for Life, involving individual counseling and follow-up telephone calls. Effectiveness of the interventions was analyzed in terms of APFT pass rates and calculated 10-year coronary heart disease risk. Costs were calculated based on tracking of resources used in the programs. APFT pass rates were 54.3% and 47.9%, respectively, for traditional and Fitness for Life programs, p = not significant. Neither program affected 10-year coronary heart disease risk. For assumed APFT pass rates up to 40% without any formal remediation, both the traditional remediation program and the ARNG Fitness for Life intervention had cost savings without significant group differences. Depending on the ARNG unit and personnel preference, although the Fitness for Life Program was more expensive and thus less cost-effective, either program could be cost-effective and of benefit to the military.
    12/2013; 178(12):1353-7. DOI:10.7205/MILMED-D-13-00118
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    ABSTRACT: Heart failure is the leading cause for hospital readmission, the reduction of which is a priority under the Affordable Care Act. Digoxin reduces 30-day all-cause hospital admission in chronic systolic heart failure. Whether digoxin is effective in reducing readmission after hospitalization for acute decompensation remains unknown. Of the 5153 Medicare beneficiaries hospitalized for acute heart failure and not receiving digoxin, 1054 (20%) received new discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 5153 patients, were used to assemble a matched cohort of 1842 (921 pairs) patients (mean age, 76 years; 56% women; 25% African American) receiving and not receiving digoxin, who were balanced on 55 baseline characteristics. Thirty-day all-cause readmission occurred in 17% and 22% of matched patients receiving and not receiving digoxin, respectively (hazard ratio [HR] for digoxin, 0.77; 95% confidence interval [CI], 0.63-0.95). This beneficial association was observed only in those with ejection fraction <45% (HR 0.63; 95% CI, 0.47-0.83), but not in those with ejection fraction ≥45% (HR 0.91; 95% CI, 0.60-1.37; P for interaction, .145), a difference that persisted throughout the first 12 months postdischarge (P for interaction, .019). HRs (95% CIs) for 12-month heart failure readmission and all-cause mortality were 0.72 (0.61-0.86) and 0.83 (0.70-0.98), respectively. In Medicare beneficiaries with systolic heart failure, a discharge prescription of digoxin was associated with lower 30-day all-cause hospital readmission, which was maintained at 12 months, and was not at the expense of higher mortality. Future randomized controlled trials are needed to confirm these findings.
    The American journal of medicine 11/2013; DOI:10.1016/j.amjmed.2013.08.027 · 5.30 Impact Factor
  • Circulation 10/2013; 128(22). DOI:10.1161/01.cir.0000436752.99896.22 · 14.95 Impact Factor
  • Daniel E Forman, Ali Ahmed, Jerome L Fleg
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    ABSTRACT: Heart failure (HF) increases significantly in relation to advancing age, yet management for HF in very old adults remains ambiguous. With aging, not only do age-related, morphological and physiological cardiovascular changes predispose to HF, there is also increased prevalence of comorbid conditions that compound cardiac limitations (e.g., renal insufficiency and chronic obstructive lung disease) and others that tend to overwhelm limited cardiovascular reserves (e.g., infections and ischemia). Standard HF pharmacological and device therapies do little to moderate the wide spectrum of insidious age-related processes that are elemental to HF pathophysiology among older patients. Moreover, the utility of standard HF therapy is usually premised on its efficacy for life prolongation, whereas quality of life, increased physical and cognitive function, and preserved independence may be regarded as higher (or even highest) priority. In this review we study age-related susceptibility to HF, as well as the utility and limitations of standard HF strategies. Both HF with reduced ejection fraction and HF with preserved ejection fraction are considered.
    Current Heart Failure Reports 10/2013; DOI:10.1007/s11897-013-0163-7
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    ABSTRACT: The strength of race as an independent predictor of long-term outcomes in a contemporary chronic heart failure (HF) population and its association with exercise training response have not been well established. We aimed to investigate the association between race and outcomes and to explore interactions with exercise training in patients with ambulatory HF. We performed an analysis of HF-ACTION, which randomized 2331 patients with HF having an ejection fraction ≤35% to usual care with or without exercise training. We examined characteristics and outcomes (mortality/hospitalization, mortality, and cardiovascular mortality/HF hospitalization) by race using adjusted Cox models and explored an interaction with exercise training. There were 749 self-identified black patients (33%). Blacks were younger with significantly more hypertension and diabetes, less ischemic etiology, and lower socioeconomic status versus whites. Blacks had shorter 6-minute walk distance and lower peak VO2 at baseline. Over a median follow-up of 2.5 years, black race was associated with increased risk for all outcomes except mortality. After multivariable adjustment, black race was associated with increased mortality/hospitalization (hazard ratio [HR] 1.16, 95% CI 1.01-1.33) and cardiovascular mortality/HF hospitalization (HR 1.46, 95% CI 1.20-1.77). The hazard associated with black race was largely caused by increased HF hospitalization (HR 1.58, 95% CI 1.27-1.96), given similar cardiovascular mortality. There was no interaction between race and exercise training on outcomes (P > .5). Black race in patients with chronic HF was associated with increased prevalence of modifiable risk factors, lower exercise performance, and increased HF hospitalization, but not increased mortality or a differential response to exercise training.
    American heart journal 09/2013; 166(3):488-495.e1. DOI:10.1016/j.ahj.2013.06.002 · 4.56 Impact Factor
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    ABSTRACT: Background Anemia is associated with decreased functional capacity, reduced quality of life, and worsened outcomes among patients with heart failure (HF) due to reduced left ventricular ejection fraction (HFREF). We sought to evaluate the independent effect of anemia on clinical outcomes among those with HFREF. HypothesisAnemia is associated with cardiovascular events in patients with heart failure. Methods The HF-ACTION trial was a prospective, randomized trial of exercise therapy vs usual care in 2331 patients with HFREF. Patients with New York Heart Association class II to IV HF and left ventricular ejection fractions of ≤35% were recruited. Hemoglobin (Hb) was measured up to 1 year prior to entry and was stratified by quintile. Anemia was defined as baseline Hb <13 g/dL and <12 g/dL in men and women, respectively. Hemoglobin was assessed in 2 models: a global prediction model that had been previously developed, and a modified model including variables associated with anemia and the studied outcomes. ResultsHemoglobin was available at baseline in 1763 subjects (76% of total study population); their median age was 59.0 years, 73% were male, and 62% were Caucasian. The prevalence of anemia was 515/1763 (29%). Older age, female sex, African American race, diabetes, hypertension, and lower estimated glomerular filtration rates were all more frequent in lower Hb quintiles. Over a median follow-up of 30 months, the primary outcome of all-cause mortality or all-cause hospitalization occurred in 78% of those with anemia and 64% in those without (P < 0.001). The secondary outcomes of all-cause mortality alone,cardiovascular (CV) mortality or CV hospitalization, and CV mortality or HF hospitalization occurred in 23% vs 15%, 67% vs 54%, and 44 vs 29%, respectively (P < 0.001). Heart failure hospitalizations occurred in 36% vs 22%, and urgent outpatient visits for HF exacerbations occurred in 67% and 55%, respectively (P < 0.001). For the global model, there was an association observed for anemia and all-cause mortality or hospitalization (adjusted hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.01-1.32, P = 0.04), but other outcomes were not significant at P < 0.05. In the modified model, the adjusted HR for anemia and the primary outcome of all-cause mortality or all-cause hospitalization was 1.25 (95% CI: 1.10-1.42, P < 0.001). There were independent associations between anemia and all-cause death (HR: 1.11, 95% CI: 0.87-1.42, P = 0.38), CV death or CV hospitalization (HR: 1.16, 95% CI: 1.01-1.33, P = 0.035), and CV death and HF hospitalization (HR: 1.27, 95% CI: 1.06-1.51, P = 0.008). Conclusions Anemia modestly is associated with increased rates of death, hospitalization, and HF exacerbation in patients with chronic HFREF. After adjusting for other important covariates, anemia is independently associated with an excess hazard for all-cause mortality and all-cause hospitalization. Anemia is also associated with combinations of CV death and CV/HF hospitalizations as composite endpoints.
    Clinical Cardiology 08/2013; 36(10). DOI:10.1002/clc.22181 · 2.23 Impact Factor

Publication Stats

11k Citations
1,907.08 Total Impact Points


  • 2005–2015
    • National Heart, Lung, and Blood Institute
      • Division of Cardiovascular Sciences (DCVS)
      베서스다, Maryland, United States
    • Tufts University
      • Jean Mayer USDA Human Nutrition Research Center on Aging
      Georgia, United States
  • 1982–2014
    • National Institute on Aging
      • • Laboratory of Cardiovascular Science (LCS)
      • • Laboratory of Clinical Investigation (LCI)
      • • Human Cardiovascular Studies Unit
      Baltimore, MD, United States
  • 2013
    • Durham University
      Durham, England, United Kingdom
    • Brigham and Women's Hospital
      • Division of Cardiovascular Medicine
      Boston, Massachusetts, United States
  • 2001–2013
    • Duke University
      Durham, North Carolina, United States
    • INRCA Istituto Nazionale di Ricovero e Cura per Anziani
      Ancona, The Marches, Italy
  • 2011
    • American College of Cardiology
      Washington, Washington, D.C., United States
  • 2009–2011
    • University of North Carolina at Charlotte
      • School of Nursing
      Charlotte, NC, United States
  • 2010
    • Henry Ford Hospital
      Detroit, Michigan, United States
  • 2008
    • National Institutes of Health
      Maryland, United States
  • 2006
    • Cornell University
      Итак, New York, United States
  • 1990–2004
    • Johns Hopkins University
      • • Division of Cardiology
      • • School of Nursing
      • • Department of Medicine
      Baltimore, MD, United States
  • 1999–2003
    • University of Maryland, College Park
      • Department of Kinesiology
      College Park, MD, United States
  • 1986–2003
    • Johns Hopkins Medicine
      • • Department of Medicine
      • • Division of Cardiology
      Baltimore, MD, United States
  • 2000
    • Baylor Health Care System
      Dallas, Texas, United States
  • 1998
    • Greater Baltimore Medical Center
      Baltimore, Maryland, United States
  • 1982–1997
    • University of Maryland, Baltimore
      • Department of Medicine
      Baltimore, MD, United States
  • 1990–1996
    • National Institute of Aerospace
      Hampton, Virginia, United States