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Biomedical subjects

Gregg C Fonarow

Publications and source records attributed to Gregg C Fonarow.

At least 19 recordsLinked to original sources

Association between performance measures and clinical outcomes for patients hospitalized with heart failure.

CONTEXT: Assessment of quality of care in heart failure has focused on the development and use of process-based performance measures, with the presumption that these processes are associated with improved clinical outcomes. However, this link remains largely untested. OBJECTIVE: To examine the relationship between current American College of Cardiology/American Heart Association (ACC/AHA) performance measures for patients hospitalized with heart failure and relevant clinical outcomes. DESIGN, SETTING, AND PATIENTS: The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure, a registry and performance improvement program for patients hospitalized with heart failure. Sixty- to ninety-day postdischarge follow-up data were prospectively collected from 5791 patients at 91 US hospitals in a prespecified 10% sample between March 2003 and December 2004. Mean patient age was 72.0 years, 51% were male, 78% were white, and 42% had ischemic etiology. Multivariable and propensity-adjusted analyses were performed to assess the process-outcome relationship for each performance measure in eligible patients. Additionally, we evaluated the process-outcome link of a potential performance measure for beta-blockade at discharge among eligible patients hospitalized with heart failure. MAIN OUTCOME MEASURES: Sixty- to ninety-day mortality and combined mortality/rehospitalization rates. RESULTS: Mortality during follow-up was 8.6% and mortality/rehospitalization was 36.2%. None of the 5 ACC/AHA heart failure performance measures was significantly associated with reduced early mortality risk, and only angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use at discharge was associated with 60- to 90-day postdischarge mortality or rehospitalization. Beta-blockade at the time of hospital discharge, currently not a heart failure performance measure, was strongly associated with reduced risk of mortality (hazard ratio, 0.48; 95% confidence interval, 0.30-0.79; P = .004) and mortality/rehospitalization during follow-up. CONCLUSIONS: Current heart failure performance measures, aside from prescription of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at discharge, have little relationship to patient mortality and combined mortality/rehospitalization in the first 60 to 90 days after discharge. Additional measures and better methods for identifying and validating heart failure performance measures may be needed to accurately assess and improve care of patients with heart failure.

Adrenergic beta-Antagonists↗

Modifying the anti-inflammatory effects of high-density lipoprotein.

The anti-inflammatory effects of high-density lipoproteins (HDL) are well documented and include inhibition of low-density lipoprotein (LDL) oxidation, reduction of inflammatory cytokines and vascular leukocyte adhesion molecules, and participation in innate immunity. However, certain conditions, including coronary disease, diabetes mellitus, systemic inflammation, and a diet high in saturated fat, are associated with modification of HDL such that it paradoxically enhances LDL oxidation and/or vascular inflammation. Treatment with statins and/or apolipoprotein A1 mimetic peptides improves HDL's anti-inflammatory functions, and these as well as other medications may represent a novel pathway through which to target atherosclerosis.

Humans↗

An obesity paradox in acute heart failure: analysis of body mass index and inhospital mortality for 108,927 patients in the Acute Decompensated Heart Failure National Registry.

BACKGROUND: Prior studies on chronic systolic heart failure (HF) have demonstrated that body mass index (BMI) is inversely associated with mortality, the so-called obesity paradox. The aim of this study was to determine whether BMI influences the mortality risk in acute decompensated HF, a subject not previously studied. METHODS: The Acute Decompensated Heart Failure National Registry was analyzed for acute HF hospitalizations in 263 hospitals in the United States from October 2001 through December 2004. Patients with documented height and weight were divided into BMI (measured in kilograms per square meter) quartiles. Inhospital mortality by BMI quartile for all the patients and for those with reduced (n = 43,255) and preserved (n = 37,901) systolic function was assessed. RESULTS: Body mass index quartiles in the 108,927 hospitalizations were QI (16.0-23.6 kg/m2), QII (23.7-27.7 kg/m2), QIII (27.8-33.3 kg/m2), and QIV (33.4-60.0 kg/m2). Patients in the higher BMI quartiles were younger, had more diabetes, and had a higher left ventricular ejection fraction. Inhospital mortality rates decreased in a near-linear fashion across successively higher BMI quartiles. After adjustments for age, sex, blood urea nitrogen, blood pressure, creatinine, sodium, heart rate, and dyspnea at rest, BMI quartile still predicted mortality risk. For every 5-U increase in BMI, the odds of risk-adjusted mortality was 10% lower (95% CI 0.88-0.93, P < .0001). CONCLUSIONS: In this cohort of hospitalized patients with HF, higher BMI was associated with lower inhospital mortality risk. The relationship between BMI and adverse outcomes in HF appears to be complex and deserving of further study.

Aged↗

Carvedilol use at discharge in patients hospitalized for heart failure is associated with improved survival: an analysis from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF).

BACKGROUND: The IMPACT-HF trial demonstrated that carvedilol use at the time of heart failure (HF) hospital discharge significantly increased 90-day postdischarge treatment rates. Whether there is an early survival benefit associated with this therapeutic approach in patients hospitalized for HF is unknown. We examined the early effects on mortality and rehospitalization of carvedilol use at discharge in patients hospitalized for HF and left ventricular systolic dysfunction (LVSD) compared with outcomes in patients who are eligible for, but do not receive, beta blockers before discharge. METHODS: The OPTIMIZE-HF program enrolled 5791 patients admitted with HF in a web-based registry at 91 hospitals participating with prespecified 60- to 90-day follow-up from March 2003 to December 2004. Outcomes data were prospectively collected on patients eligible for beta-blocker therapy and analyzed according to predischarge beta-blocker use. RESULTS: The mean age was 69.7 years; 63% were male, etiology was ischemic in 52%, and mean left ventricular ejection fraction was 24.3%. A total of 2720 patients had LVSD, among whom 2373 (87.2%) were eligible to receive a beta blocker at discharge and carvedilol was prescribed in 1162 (49.0%). Discharge use of carvedilol was associated with a significant reduction in mortality risk at 60 to 90 days (hazard ratio 0.46, P = .0006) and mortality or rehospitalization (odds ratio 0.71, P = .0175) compared to no predischarge beta blocker. Predischarge use of carvedilol was well tolerated with high rates of continued therapy at 60 to 90 days follow-up. Similar findings were observed for other evidence-based beta blockers. CONCLUSIONS: Carvedilol use at the time of HF hospital discharge is well tolerated, improves treatment rates, and is associated with an early survival benefit. These findings provide further support for guideline recommendations that carvedilol or other evidence-based beta blocker should be initiated before hospital discharge in stable patients with HF and LVSD.

Adrenergic beta-Antagonists↗

Usefulness of preimplantation B-type natriuretic peptide level for predicting response to cardiac resynchronization therapy.

Nearly 1/3 of patients with heart failure (HF) fail to respond to cardiac resynchronization therapy (CRT). The purpose of this study was to evaluate the value of preimplantation brain natriuretic peptide (BNP) in predicting the clinical response to CRT. We retrospectively analyzed 164 patients who underwent CRT. Patients with New York Heart Association functional class III or IV HF symptoms despite maximal medical therapy, who were not on inotropic medications, had left ventricular ejection fraction < or =35%, and QRS duration >130 ms were included in the study. CRT response in patients who survived at 6-month follow-up was defined as no HF hospitalization and improvement of > or =1 grades in the New York Heart Association classification. BNP assays were performed before implantation and at 6-month follow-up. Patients had ischemic (47%) or nonischemic (53%) cardiopathy. Responders (n = 107) and nonresponders (n = 57) had similar baseline characteristics. Cardiac death and hospitalization for HF occurred in 5 (4.7%) and 18 (31.6%) patients, respectively. CRT responders compared with nonresponders exhibited higher preimplantation BNP levels (800 +/- 823 vs 335 +/- 348 pg/ml, p = 0.0002) and a significant reduction in the QRS duration after implantation (-6 +/- 34 vs +7 +/- 32 ms, p = 0.048). The preimplantation BNP was the only independent predictor of the CRT response (p = 0.001). A BNP value > or =447 pg/ml demonstrated a sensitivity of 62% and specificity of 79% in identifying CRT response. In a subgroup of 41 patients who underwent Doppler tissue imaging analysis, the preimplantation BNP was higher in patients presenting with intraventricular dyssynchrony (845 +/- 779 vs 248 +/- 290 pg/ml, p = 0.04). In conclusion, the preimplantation BNP value independently predicts CRT response and was superior to QRS duration reduction in identifying CRT responders.

Biomarkers↗

Systolic blood pressure at admission, clinical characteristics, and outcomes in patients hospitalized with acute heart failure.

CONTEXT: The association between systolic blood pressure (SBP) at admission, clinical characteristics, and outcomes in patients hospitalized for heart failure who have reduced or relatively preserved systolic function has not been well studied. OBJECTIVE: To evaluate the relationship between SBP at admission, clinical profile, and outcomes in patients hospitalized for acute heart failure. DESIGN, SETTING, AND PATIENTS: Cohort study using data from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry and performance-improvement program for patients hospitalized with heart failure at 259 US hospitals between March 2003 and December 2004. Patients were divided into quartiles by SBP at hospital admission (<120, 120-139, 140-161, and >161 mm Hg). In-hospital outcomes were based on 48,612 patients aged 18 years or older with heart failure. Of the 41,267 patients with left ventricular function assessed, 21,149 (51%) had preserved left ventricular function. Postdischarge outcomes were based on a prespecified subgroup (n = 5791, 10% of patients) with follow-up data assessed between 60 and 90 days. MAIN OUTCOME MEASURES: In-hospital and postdischarge mortality. RESULTS: Patients with higher SBP were more likely to be female and black and to have preserved systolic function. Fifty percent of the patients had SBP higher than 140 mm Hg at admission. Patients with lower SBP at admission had higher in-hospital and postdischarge mortality rates. Higher SBP at admission was associated with lower in-hospital mortality rates: 7.2% (<120 mm Hg), 3.6% (120-139 mm Hg), 2.5% (140-161 mm Hg), and 1.7% (>161 mm Hg) (P<.001 for overall difference). Postdischarge mortality rates in the follow-up cohort by SBP at admission were 14.0%, 8.4%, 6.0%, and 5.4%, respectively (P<.001 for overall difference). CONCLUSIONS: Systolic hypertension is common in patients hospitalized for heart failure. Systolic blood pressure is an independent predictor of morbidity and mortality in patients with heart failure with either reduced or relatively preserved systolic function. Low SBP (<120 mm Hg) at hospital admission identifies patients who have a poor prognosis despite medical therapy. These findings may have important therapeutic implications because characteristics and outcomes differ greatly among patients with heart failure with varying SBP.

Acute Disease↗

Impact of early initiation of intravenous therapy for acute decompensated heart failure on outcomes in ADHERE.

BACKGROUND: Since most acute decompensated heart failure (ADHF) patients present for hospital care via the emergency department (ED), we sought to determine the impact of early ED initiation of ADHF-specific therapy, as indicated by nesiritide use, on subsequent outcomes. METHODS: We queried the Acute Decompensated Heart Failure National Registry (ADHERE) to identify patients with initial systolic blood pressure >90 mm Hg and negative cardiac biomarkers, hospitalized after presentation to the ED, who received nesiritide but no other intravenous vasoactive drugs. Intensive care unit use and total hospital length of stay were compared based on the hospital unit where nesiritide therapy was initiated after multivariate adjustment for baseline differences in study populations. RESULTS: Nesiritide was started in the ED in 1,613 patients (EDN group) and after admission to an inpatient unit in 2,687 patients (INN group). EDN patients had higher baseline systolic and diastolic blood pressure (both p < 0.001); while INN patients were more likely to be male and have baseline renal dysfunction (both p < 0.001). Nesiritide was initiated a median of 2.8 and 15.5 h after presentation in EDN and INN patients, respectively (p < 0.001). Compared to INN, EDN patients had a shorter adjusted mean total hospital length of stay (5.4 vs. 6.9 days; p < 0.001), were less likely to require transfer to the intensive care unit from another inpatient unit (odds ratio [OR]: 0.301; 95% confidence interval [CI]: 0.206-0.440), and were more likely to be discharged home (OR: 1.154; 95% CI: 1.005-1.325). CONCLUSIONS: Initiation of ADHF-specific therapy early, while the patient is in the ED, is associated with improved clinical outcomes.

Aged↗

Relation of loop diuretic dose to mortality in advanced heart failure.

Although loop diuretics are widely used in heart failure (HF), their effect on outcomes has not been evaluated in large clinical trials. This study sought to determine the dose-dependent relation between loop diuretic use and HF prognosis. A cohort of 1,354 patients with advanced systolic HF referred to a single center was studied. Patients were divided into quartiles of equivalent total daily loop diuretic dose: 0 to 40, 41 to 80, 81 to 160, and >160 mg. The cohort was 76% male, with a mean age of 53+/-13 years and a mean ejection fraction of 24+/-7%. The mean diuretic dose equivalence was 107+/-87 mg. The diuretic quartile groups were similar in terms of gender, body mass index, ischemic cause of HF, history of hypertension, and spironolactone use, but the highest quartile was associated with a smaller ejection fraction and lower serum sodium and hemoglobin levels but higher serum blood urea nitrogen and creatinine levels. There was a decrease in survival with increasing diuretic dose (83%, 81%, 68%, and 53% for quartiles 1, 2, 3, and 4, respectively). Even after extensive co-variate adjustment (age, gender, ischemic cause of HF, the ejection fraction, body mass index, pulmonary capillary wedge pressure, peak oxygen consumption, beta-blocker use, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, digoxin use, statin use, serum sodium, blood urea nitrogen, creatinine, hemoglobin, cholesterol, systolic blood pressure, and smoking history), diuretic quartile remained an independent predictor of mortality (quartile 4 vs quartile 1 hazard ratio 4.0, 95% confidence interval 1.9 to 8.4). In conclusion, in this cohort of patients with advanced HF, there was an independent, dose-dependent association between loop diuretic use and impaired survival. Higher loop diuretic dosages identify patients with HF at particularly high risk for mortality.

Adolescent↗

Improving outcomes in post-acute myocardial infarction heart failure: incorporation of aldosterone blockade into combination therapy to optimize neurohormonal blockade.

Although angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and beta-blockers have been proved to reduce mortality in patients with heart failure post-acute myocardial infarction (AMI), studies show that these agents are consistently underused in this population. Further, morbidity and mortality remain high even when standard-of-care therapies are applied. Thus, new strategies have been sought to better counteract the maladaptive effects of neurohormonal stimulation in post-AMI heart failure. The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) demonstrated that the selective aldosterone blocker eplerenone, when used in addition to standard therapy, results in significant incremental improvements in survival and morbidity and is safe and well tolerated in this setting. Based on this, major therapeutic guidelines in the United States and Europe now strongly recommend that all eligible patients with concomitant heart failure post-AMI be treated with an aldosterone blocker in addition to an ACE inhibitor (or an ARB) and a beta-blocker. To achieve needed improvements in outcomes in this population, early and consistent initiation of these evidence-based, guideline-recommended therapies in all eligible patients is crucial.

Adrenergic beta-Antagonists↗

Impact of obesity on quality of life and depression in patients with heart failure.

BACKGROUND: The effect of obesity on health related quality of life (HRQOL) and depression in a number of disease states is well documented, but its impact in heart failure (HF) patients remains speculative. We therefore examined the relationship between obesity, HRQOL, and depression in 358 patients with HF. METHODS AND RESULTS: Comparative analyses were conducted to determine if body mass index (BMI) was associated with HRQOL and depression in three groups of patients with HF-normal weight (BMI 18.5-24.9 kg/m2, n = 100), overweight (BMI 25-29.9 kg/m2, n = 141), and obese (BMI > or = 30 kg/m2, n = 117). Obese patients were younger than normal and overweight participants; all other demographic and clinical characteristics were similar. HRQOL and depression scores were significantly higher (worse) for obese patients. Body mass index was significantly correlated with all 3 scales of HRQOL (overall, r2 = .160; physical, r2 = .162; and mental, r2 = .217) as well as with depression (r2 = .166). CONCLUSION: Obese patients with HF are more likely to have poorer HRQOL, physical health, emotional well-being and depressive symptoms. Poorer HRQOL is predictive of worse outcomes in patients with HF; however, given the apparent obesity paradox in HF, further investigation of the impact of obesity in HF is urgently required.

Body Mass Index↗

Usefulness of a home-based exercise program for overweight and obese patients with advanced heart failure.

Exercise is an important behavior for long-term weight control in overweight and obese patients. However, little evidence exists confirming such findings in patients with advanced heart failure (HF). Using a prospective, experimental design, the effects of 24 weeks of a low-level, home-based walking program on weight loss were studied in overweight and obese (body mass index > or =27 kg/m(2)) patients with advanced HF who were randomized to exercise (n = 48) and control (n = 51) groups. Weight changes between the 2 groups at baseline and 6 months were compared using repeated-measures analysis of variance. Patients were on average aged 53.3 +/- 10.1 years and predominantly male (75%), Caucasian (57%), and married (55%). Most patients were in New York Heart Association class III or IV (67%), with a mean ejection fraction of 25%. Patients in the exercise group showed significant weight reduction from baseline to 6 months compared with those in the control group (-6.37 +/- 11.7 vs -0.33 +/- 9.3 kg, p = 0.002). No significant differences were noted between the 2 groups in 6-minute walk distance or depression, although the changes were in the anticipated direction. Modest weight losses of >5% were associated with cardiopulmonary exercise test-documented workload levels at 6 months (r = 0.331, p = 0.006), as well as decreased depression (r = -0.315, p = 0.01) and hostility (r = -0.355, p = 0.005). The number of hospital admissions was significantly smaller for patients in the exercise group compared with those in the control group (0.63 +/- 0.94 vs 1.07 +/- 0.95, p <0.05). In conclusion, the findings demonstrate the beneficial effects of a low-level, home-based walking program on weight loss in overweight and obese patients with advanced HF.

Adolescent↗

Hospital protocols and evidence-based therapies: the importance of integrating aldosterone blockade into the management of patients with post-acute myocardial infarction heart failure.

Left ventricular systolic dysfunction (LVSD) and clinical heart failure are common complications of acute myocardial infarction (AMI) and result in substantially increased mortality and morbidity. Evidence-based cardiovascular protective therapies, including angiotensin-converting enzyme inhibitors, beta blockers, antiplatelet agents, and lipid-lowering medications, improve outcomes for these patients. However, this population is significantly undertreated with these guideline-recommended agents. Critical pathways have been demonstrated to improve the quality and consistency of treatment; as such, the new American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of patients with ST-elevation myocardial infarction (STEMI) recommend that critical pathways be implemented for the management of these patients. The recent Eplerenone Post-acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) demonstrates that eplerenone, a selective aldosterone blocker, has incremental benefit in decreasing mortality and morbidity when used with standard care therapies in patients post AMI with heart failure and LVSD. The clinical trial evidence coupled with the national guidelines provides a strong rationale for routine incorporation of aldosterone blockade into new or already established critical pathways for AMI complicated by LVSD and heart failure.

Adrenergic beta-Antagonists↗

High-density lipoprotein: is it always atheroprotective?

High-density lipoproteins (HDLs) are appropriately recognized for their many atheroprotective functions, including reverse cholesterol transport, as well as antioxidant, anti-inflammatory, and antithrombotic effects. Furthermore, the inverse relationship between HDL cholesterol and atherosclerosis is well documented in many populations. However, there is an increasing body of evidence that there are circumstances in which HDL may not be protective, and may in fact paradoxically promote vascular inflammation and oxidation of low-density lipoproteins. Recent studies have provided insight as to specific chemical modifications and structural changes within HDL associated with this phenotype. The presence of proinflammatory HDL coincides with conditions associated with chronic systemic inflammation, including atherosclerosis.

Anticholesteremic Agents↗

An unexpected inverse relationship between HbA1c levels and mortality in patients with diabetes and advanced systolic heart failure.

BACKGROUND: In diabetes, poor glycemic control, as indexed by hemoglobin A1c (HbA1c), is associated with increased risk of cardiovascular events and new-onset heart failure (HF). However, in patients with diabetes and HF, the relationship between glucose control and survival has not been investigated. Our study aimed to evaluate the relationship between HbA1c levels and mortality in patients with diabetes and advanced systolic HF. METHODS: We studied a cohort of 123 patients with diabetes and advanced systolic HF referred to a single center with HbA1c values measured at presentation. The patients were grouped based on HbA1c: HbA1c < or = 7.0 (n = 49) and HbA1c > 7.0 (n = 74). RESULTS: The cohort was 70% men, ejection fraction of 25% +/- 7, 59% ischemic etiology, HbA1c 7.9 +/- 1.8, and diabetes duration of 8.6 +/- 9.0 years. The HbA1c groups were similar in age; sex; New York Heart Association class; body mass index; diabetes duration; and insulin, metformin, and glitazone use. HbA1c > 7.0 was associated with higher ejection fraction, increased beta-blocker, and sulfonlyurea use. Patients with HbA1c < or = 7.0 had significantly increased all-cause mortality, compared with those with HbA1c > 7.0 (35% vs 20%, hazard ratio 2.6, 95% CI 1.3-5.2, P < .01). In multivariate analysis, HbA1c < or = 7.0 remained associated with increased mortality (hazard ratio 2.3, 95% CI 1.0-5.2). CONCLUSIONS: Paradoxically, elevated HbA1c levels were associated with improved survival in this cohort of patients with diabetes and advanced HF. Further investigation is necessary to determine the nature of this relationship and optimal HbA1c in patients with diabetes and HF.

Adult↗

Reduced treatment success in lipid management among women with coronary heart disease or risk equivalents: results of a national survey.

BACKGROUND: This survey assessed and compared National Cholesterol Education Program (NCEP) Third Adult Treatment Panel lipid treatment goal achievement for men versus women undergoing treatment of dyslipidemia. METHODS: Patients receiving treatment for dyslipidemia from physicians (N = 376) in the United States who were high prescribers of lipid medications were enrolled in the NCEP Evaluation Project Utilizing Novel E-Technology (NEPTUNE) II. Data from a single office visit were collected and entered into the NEPTUNE software on a personal digital assistant and uploaded to a central database via the Internet. RESULTS: Of the 4885 patients evaluated, 2103 (43%) were women. NCEP Third Adult Treatment Panel low-density lipoprotein cholesterol (LDL-C) goal achievement was similar between women and men with 0 or 1 risk factor (89% and 88%, respectively) and 2 or more risk factors (75% and 76%, respectively). However, fewer women than men achieved goal in the coronary heart disease and risk equivalents (CHD + CHD RE) category (50% vs 60%, respectively; P < .001). Logistic regression analyses examining the association between sex and LDL-C treatment goal achievement, and evaluating potential confounding by other predictors of treatment success, indicated an age-adjusted odds ratio of 0.66 (95% confidence interval, 0.56-0.77; P < .001) and a multivariate odds ratio of 0.76 (95% confidence interval, 0.62-0.93; P = .009) for women compared with men in the CHD + CHD RE category. CONCLUSIONS: Female sex was associated with lower likelihood of LDL-C goal achievement among patients with CHD + CHD RE. This relationship remained significant after adjustment for other significant predictors of treatment success.

Anticholesteremic Agents↗