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Biomedical subjects

Gregg C Fonarow

Publications and source records attributed to Gregg C Fonarow.

At least 37 records · Page 2Linked to original sources

Total cholesterol levels and mortality risk in nonischemic systolic heart failure.

BACKGROUND: Prior studies have demonstrated that low serum total cholesterol (TC) is associated with increased mortality in heart failure (HF); however, this association has not been consistently observed in HF of nonischemic etiology. METHODS: We analyzed a cohort of 614 patients with nonischemic systolic HF (left ventricular ejection fraction [LVEF] <40%). Fasting lipid panels were drawn at time of referral. Patients were stratified into quartiles of TC (Q1 <133, Q2 134-168, Q3 169-209, and Q4 >210 mg/dL). RESULTS: The cohort was 68% male, mean age was 48 +/- 13 years, and LVEF was 23% +/- 7%. Patients with lower serum TC had worse hemodynamic profiles, lower LVEF, and higher New York Heart Association class. Low TC was associated with increased risk of 1-year death and urgent transplant (UT) (49%, 29%, 18%, 14% for Q1-Q4 respectively, P < .0001) as well as all-cause mortality (P < .0001). On multivariate analysis, adjusting for multiple HF prognostic factors, low TC proved to be an independent predictor of worse outcomes, with hazard ratios for death and UT of 3.4, 1.8, and 1.6 for Q1 to Q3, respectively, compared with Q4. Based on receiver operating characteristic curve analysis, the best cutoff for prediction of death and UT for TC was 161 mg/dL. CONCLUSIONS: Low TC is strongly associated with increased mortality in patients with nonischemic, systolic HF. Further research is necessary to determine the nature of this relationship, optimal lipid levels, and the therapeutic role, if any, of statins in patients with established HF.

Adult↗

Are registry hospitals different? A comparison of patients admitted to hospitals of a commercial heart failure registry with those from national and community cohorts.

BACKGROUND: Clinical registries have been created to address questions that are difficult to answer with clinical trials. However, the applicability of registry findings to the general population has been questioned because of concerns over potential bias in the selection of participating hospitals. The purpose of this study was to determine if patients admitted to hospitals participating in a heart failure registry (ADHERE) are comparable with patients admitted to other hospitals, including those admitted to Framingham area hospitals. METHODS: We used a 20% random sample of all Medicare patients discharged during 1984 to 2001 to determine rates of hospitalization, procedure use, and survival after a first admission for heart failure (none in the prior 3 years). Hospitals were classified as participating in the ADHERE registry (n = 189), located within or near Framingham, MA (n = 9), or other (n = 5541). RESULTS: A total of 725,702 first admissions were identified, including 80,338 to ADHERE hospitals and 1716 to Framingham area hospitals. Minimal differences in patient characteristics were noted between patients admitted to ADHERE and non-ADHERE hospitals, although patients admitted to Framingham area hospitals were more likely to be white (95%) than were patients admitted to ADHERE (84%) or other hospitals (87%, P < .0001). Mortality at 1 year was 35.8% for ADHERE, 36.2% for other hospitalized patients, and 32.9% for Framingham patients (P < .0001). Rehospitalization for heart failure at 90 days was 13.0% for following admission to ADHERE, 13.0% to other hospitals, and 16.4% to Framingham hospitals (P = .0004). After adjustment for patient characteristics, differences in outcome between ADHERE and non-ADHERE hospitals remained minimal. CONCLUSION: Patients admitted with heart failure to ADHERE registry hospitals had similar baseline characteristics and outcomes to other patients.

Aged↗

The confounding issue of comorbid renal insufficiency.

The United States is currently beleaguered by twin epidemics, heart failure (HF) and renal insufficiency (RI). HF and RI frequently coexist in the same patient, and this conjunction, often called the "cardiorenal syndrome," has important therapeutic and prognostic implications. Approximately 60% to 80% of patients hospitalized for HF have at least stage III renal dysfunction as defined by the National Kidney Foundation (NKF), and this comorbid RI is associated with significantly increased morbidity and mortality risk. Numerous studies have demonstrated that in patients with HF, indices of renal function are the most powerful independent mortality risk predictors. Comorbid RI can result from both intrinsic renal disease and inadequate renal perfusion. Atherosclerosis, renal vascular disease, diabetes mellitus, and hypertension are significant precursors of both HF and RI. Moreover, diminished renal perfusion is frequently a consequence of the hemodynamic changes associated with HF and its treatment. Both HF and RI stimulate neurohormonal activation, increasing both preload and afterload and reducing cardiac output. Inotropic agents augment this neurohormonal activation. In addition, diuretics can produce hypovolemia and intravenous vasodilators can cause hypotension, further diminishing renal perfusion. Management of these patients requires successfully negotiating the delicate balance between adequate volume reduction and worsening renal function. Despite this, few evidence-based data are available to guide management decisions, indicating a compelling need for additional studies in this patient population.

Acute Disease↗

Gender differences in in-hospital management and outcomes in patients with decompensated heart failure: analysis from the Acute Decompensated Heart Failure National Registry (ADHERE).

BACKGROUND: The impact of gender differences has not been well described in patients hospitalized with acute decompensated heart failure (ADHF). METHODS AND RESULTS: Through review of medical records, data on characteristics, treatments, and outcomes were analyzed on 105,388 patient records according to gender. Women accounted for 52% of these admissions and were older than men (74.5 versus 70.1 years,) and more commonly had preserved left ventricular function (51% versus 28%). Based on history, women were less likely to have coronary artery disease (51% versus 64%) and its risk factors, but more commonly had hypertension (76% versus 70%). Both genders received similar intravenous diuretic regimens, but fewer women received vasoactive therapy (24% vs 31%). Evidence-based oral therapies were underused in both genders. Women consistently received less procedure-oriented therapy. Mean length of stay (women 5.9, men 5.8 days) and the risk-adjusted in-hospital mortality (adjusted odds ratio 0.974 [0.910-1.042], P = .4390) were similar in both genders. CONCLUSION: More women than men are hospitalized with ADHF. Heart failure with preserved left ventricular function predominates in women. Though women are treated less aggressively, treatment gaps exists in both sexes. Despite these differences, length of stay and in-hospital mortality rates are similar.

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Diabetic cardiomyopathy.

This article focuses on advances in the understanding of the pathogenesis and treatment of diabetic cardiomyopathy. Patients with diabetes are at an elevated risk for heart failure, and comorbid heart failure confers an increased risk of morbidity and mortality. Diabetic cardiomyopathy and to apply proven lifesaving therapies in all heart failure patients, including those with diabetes, in the absence of contraindications or intolerance.

Cardiomyopathies↗

Epidemiology of dialysis patients and heart failure patients.

The epidemiology of maintenance dialysis patients and heart failure patients has striking similarities. Both groups have a high prevalence of comorbid conditions, a high hospitalization rate, a low self-reported quality of life, and an excessively high mortality risk, mostly because of cardiovascular causes. Observational studies in both dialysis and heart failure patients have indicated the lack of a significant association between the traditional cardiovascular risk factors and mortality, or the existence of a paradoxic or reverse association, in that obesity, hypercholesterolemia, and hypertension appear to confer survival advantages. The time discrepancy between the 2 sets of risk factors, that is, overnutrition (long-term killer) versus undernutrition (short-term killer) may explain the overwhelming role of malnutrition, inflammation, and cachexia in causing the reverse epidemiology, which may exist in more than 20 million Americans. We have reviewed the opposing views about the concept of reverse epidemiology in dialysis and heart failure patients, the recent Die Deutsche Diabetes Dialyze study findings, and the possible role of racial disparities. Contradictory findings on hyperhomocysteinemia in dialysis patients are reviewed in greater details as a possible example of publication bias. Additional findings related to intravenous iron and serum ferritin, calcium, and leptin levels in dialysis patients may enhance our understanding of the new paradigm. The association between obesity and increased death risk in kidney transplanted patients is reviewed as an example of the reversal of reverse epidemiology. Studying the epidemiology of dialysis patients as the archetypical population with such paradoxic associations may lead to the development of population-specific guidelines and treatment strategies beyond the current Framingham cardiovascular risk factor paradigm.

Dialysis↗

Profile of carvedilol controlled-release: a new once-daily formulation of carvedilol.

Carvedilol is a third-generation beta(1)- and beta(2)-blocker that also possesses alpha(1)-adrenergic-blocking properties. This compound has: i) shown superior efficacy to certain other beta-blockers in heart failure, ii) can improve myocardial function (e.g., in myocardial infarction) and iii) is the only beta-blocker shown to significantly reduce mortality and morbidity (such as reinfarction and development of heart failure) in postmyocardial infarction patients with left ventricular dysfunction (LVD). The currently available preparation of carvedilol needs to be taken twice daily; however, studies have shown that the need for twice-daily dosing may decrease adherence. A once-daily formulation of carvedilol (controlled release) is expected to become available in 2007. The pharmacokinetic and pharmacodynamic properties of the new formulation are equivalent to the twice-daily formulation. A number of investigations have demonstrated equivalence between the twice-daily and once-daily formulations; thus, carvedilol controlled-release is expected to provide not only the same life-prolonging benefits of twice-daily carvedilol, but also the convenience of once-daily dosing.

Carbazoles↗

Beta-blockers for the post-myocardial infarction patient: current clinical evidence and practical considerations.

Beta-blockers significantly decrease the risk of mortality in patients after myocardial infarction (MI). Furthermore, beta-blockers reduce the risk of reinfarction and mortality in both the immediate and long term after an MI. Guidelines recommend that post-MI patients should be started on beta-blocker therapy and continued indefinitely, unless absolutely contraindicated or not tolerated. Despite compelling evidence, many patients are not prescribed beta-blockers after a myocardial event. In addition, some patients are treated with agents whose long-term use has not been shown to be effective. This article discusses practical implementation of beta-blockers, provides the rationale for choosing specific beta-blockers, and presents protocols for initiating or switching to evidence-based therapies in the acute and chronic post-MI period.

Adrenergic beta-Antagonists↗

Congestion in acute heart failure syndromes: importance of early recognition and treatment.

The vast majority of acute heart failure syndrome (AHFS) hospitalizations are related to clinical congestion, rather than to a low cardiac output state. Patients develop hemodynamic congestion (high left ventricular filling pressure) several days to weeks before the onset of clinical symptoms and signs. Congestion is an important predictor of both mortality and morbidity in patients with AHFS. As a result, congestion is an essential evaluative and therapeutic target in AHFS patients. It is plausible that early identification of hemodynamic congestion, before the clinical manifestations are present, could reduce the need for hospital admission and readmission.

Acute Disease↗

How well are chronic heart failure patients being managed?

Heart failure (HF) remains a major public health problem, affecting 5 million patients in the United States. The personal burden of HF includes debilitating symptoms, activity limitations, frequent hospitalizations, arrhythmias, and increased mortality. Despite the compelling scientific evidence that angiotensin-converting enzyme inhibitors, beta-blockers, and aldosterone antagonists reduce hospitalizations and mortality in patients with HF, these life-prolonging therapies continue to be underutilized. Device therapy for HF, including implantable cardioverter defibrillators and cardiac resynchronization therapy, has recently been demonstrated to also result in substantial mortality reduction. Accurate evaluation of patients with HF is critical for the appropriate selection and monitoring of therapy to reduce symptoms as well as for the prevention of recurrent hospitalizations. A number of studies in a variety of clinical settings have documented that a significant proportion of patients with HF are not receiving treatment with guideline-recommended, evidence-based therapies. Treatment gaps have also been documented in providing other components of care for patients with HF, including assessment for congestion and patient education. Recent studies demonstrate that hospital-based systems can improve medical care and education of hospitalized HF patients and accelerate use of evidence-based, guideline-recommended therapies by administering them before hospital discharge. HF disease management programs have also been shown to improve HF treatment, resulting in substantial reduction in hospitalizations and mortality. Application of validated and reproducible noninvasive techniques to monitor patients with chronic HF is an important step in maximizing interventions to improve outcomes in this patient population. Further efforts are clearly needed to improve the monitoring of HF patients in the hospital and outpatient settings, as well as to ensure the implementation of effective strategies and systems that increase the use of evidence-based therapies, in order to reduce the substantial HF morbidity and mortality risk.

Adrenergic beta-Antagonists↗

Congestion is an important diagnostic and therapeutic target in heart failure.

Most hospitalizations for acute heart failure syndrome (AHFS) are related to clinical congestion as a result of high left ventricular diastolic pressure (LVDP) rather than to low cardiac output. Patients frequently develop "hemodynamic congestion" (high LVDP) several days to weeks before the onset of symptoms and signs of clinical congestion. By the time symptoms and signs are evident, patients generally require hospitalization. High LVDP increases left ventricular (LV) wall stress and possibly contributes to neurohormonal activation and LV remodeling, thereby contributing to progression of heart failure (HF). Congestion is a major predictor of both morbidity and mortality in HF. Some methods may aid in the evaluation of silent hemodynamic congestion, but these assessment tools are generally underused. Identification of hemodynamic congestion, before the clinical manifestations appear, may potentially prevent hospitalization and slow the progression of HF by allowing life-saving interventions to be implemented sooner.

Acute Disease↗

B-type natriuretic peptide levels in obese patients with advanced heart failure.

UNLABELLED: Although recent studies show that obesity, or elevated body mass index (BMI), is associated with lower levels of B-type natriuretic peptide (BNP), it is unknown whether BMI affects the prognostic value of BNP in heart failure (HF). This study confirms the relationship between high BMI and low BNP in patients with advanced systolic HF. Despite relatively lower levels of BNP in overweight and obesity, BNP predicts worse symptoms, impaired hemodynamics, and higher mortality in HF at all levels of BMI. OBJECTIVES: This study aimed to examine the influence of obesity on the predictive value of the B-type natriuretic peptide (BNP) assay in heart failure (HF). BACKGROUND: Recent studies show that obesity, or elevated body mass index (BMI), is associated with lower circulating levels of BNP both in the general population and in patients with HF. METHODS: We analyzed data from 316 systolic HF (left ventricular ejection fraction [LVEF] < or =40%) patients [age, 53 +/- 13 years; mean LVEF, 24 +/- 7%; 48% ischemic] followed up at a university HF center. Patients were divided into categories of BMI: lean (BMI <25 kg/m2), overweight (BMI = 25 to 29.9 kg/m2), and obese (BMI > or =30 kg/m2). RESULTS: The BNP levels were significantly lower in overweight and obese compared with lean patients (p = 0.0001); median BNP (interquartile range) for the lean (n = 131), overweight (n = 99), and obese (n = 86) groups was 747 (272 to 1,300), 380 (143 to 856), and 332 (118 to 617) pg/ml, respectively. In each BMI category, elevated BNP was significantly associated with worse symptoms and higher pulmonary capillary wedge pressure. Higher BNP was also a significant independent predictor of survival independent of BMI. Optimal BNP cutoff for prediction of death or urgent transplant in lean, overweight, and obese HF patients was 590, 471, and 342 pg/ml, respectively. CONCLUSIONS: Although BNP levels are relatively lower in overweight and obese HF patients, BNP predicts worse symptoms, impaired hemodynamics, and higher mortality at all levels of BMI.

Biomarkers↗

Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database.

UNLABELLED: Approximately 50% of patients hospitalized for heart failure have preserved systolic function. These patients are more likely to be older, women, and hypertensive. Their duration of hospitalization is similar to that of heart failure patients with systolic dysfunction, but their in-hospital mortality risk is lower. This mortality risk is increased in the setting of renal insufficiency, and the two most important risk predictors are elevated blood urea nitrogen and systolic blood pressure < or = 125 mm Hg. Medical treatment strategies for patients with preserved systolic function are inconsistent and reflect the need for efficacious evidence-based treatment regimens. OBJECTIVES: The aims of this analysis were to describe the clinical characteristics, management, and outcomes of patients hospitalized for acute decompensated heart failure (HF) with preserved systolic function (PSF). BACKGROUND: Clinically meaningful characteristics of these patients have not been fully studied in a large database. METHODS: Data from >100,000 hospitalizations from the Acute Decompensated Heart Failure National Registry (ADHERE) database were analyzed. RESULTS: Heart failure with PSF was present in 50.4% of patients with in-hospital assessment of left ventricular function. When compared with patients with systolic dysfunction, patients with PSF were more likely to be older, women, and hypertensive and less likely to have had a prior myocardial infarction or be receiving an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. In-hospital mortality was lower in patients with PSF compared with patients with systolic dysfunction (2.8% vs. 3.9%; adjusted odds ratio [OR]: 0.86; p = 0.005), but duration of intensive care unit stay and total hospital length of stay were similar. Serum creatinine >2 mg/dl was associated with increased in-hospital mortality in both systolic function groups (PSF: 4.8%; systolic dysfunction: 8.4%; p < 0.0001), and the most powerful predictors of in-hospital mortality in both groups were blood urea nitrogen >37 mg/dl (OR: 2.53; 95% confidence interval [CI]: 2.22 to 2.87) and systolic blood pressure < or =125 mm Hg (OR: 2.58; 95% CI: 2.33 to 2.86). CONCLUSIONS: Heart failure with PSF is common and is characterized by a unique patient profile. Event rates are worrisome and reflect a need for more effective management strategies.

Aged↗

High-density lipoprotein function recent advances.

Although high-density lipoproteins (HDL) possess many features that contribute to the association between elevated HDL cholesterol and protection from atherosclerosis, these lipoproteins may be modified in certain individuals and/or circumstances to become proinflammatory. The ability of HDL to inhibit or paradoxically to enhance vascular inflammation, lipid oxidation, plaque growth, and thrombosis reflects changes in specific enzyme and protein components. The anti-inflammatory and proinflammatory functional properties of HDL can now be assessed using cell-based and cell-free assays. Acute or chronic systemic inflammation and the metabolic syndrome appear to render HDL proinflammatory. In contrast, statins and experimental agents such as apolipoprotein A-1 mimetics render HDL more anti-inflammatory. Functional characterization of HDL is a promising method for enhanced assessment of cardiovascular risk and effectiveness of risk reduction.

Animals↗

Pathophysiologic targets in the early phase of acute heart failure syndromes.

An episode of acute heart failure syndromes (AHFS) can be defined as a rapid or gradual onset of signs and symptoms of heart failure (HF) in hospital admission and can arise from a variety of pathophysiologic mechanisms. This article reviews our current understanding of the pathophysiology of AHFS in order to identify potential therapeutic targets. Most patients with AHFS present with either normal systolic blood pressure or elevated blood pressure. Patients who present with elevated systolic blood pressure usually have pulmonary congestion and a relatively preserved left ventricular ejection fraction (LVEF), and have symptoms that typically develop abruptly, these patients often are elderly women. Patients with normal systolic blood pressure presenting with systemic congestion and reduced LVEF are usually younger, with a history of chronic HF, and have symptoms that develop gradually over days or weeks. Accordingly, most episodes of AHFS can be classified as either "vascular" failure or "cardiac" failure. In addition to the abnormal hemodynamics (increase in pulmonary capillary wedge pressure and/or decrease in cardiac output) that characterize patients with AHFS, myocardial injury--which may be related to a decrease in coronary perfusion and/or further activation of neurohormones and renal dysfunction (ie, the cardiorenal syndrome)--probably contributes to short-term and post-discharge cardiac events. Patients with AHFS also have significant cardiac and non-cardiac underlying conditions that contribute to the pathogenesis of AHFS, including coronary artery disease (ischemia, hibernating myocardium, and endothelial dysfunction), hypertension, atrial fibrillation, and type 2 diabetes mellitus. The goals of therapy for AHFS should be not only to improve symptoms and hemodynamics, but also to preserve or improve renal function and prevent myocardial damage.

Acute Disease↗

Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality.

We determined the effects of early statin treatment in acute myocardial infarction (AMI) on in-hospital morbidity and mortality. Experimental models of ischemia and reperfusion have shown that statins have early cardioprotective effects. However, the effect of statin use within the first 24 hours of admission on early morbidity and mortality in AMI has not been well studied. Data were collected on 300,823 patients who had AMI in the National Registry of Myocardial Infarction 4. In-hospital events were compared between patients who continued statin therapy received before the index AMI hospitalization (n = 17,118) or newly started statin therapy within the first 24 hours of hospitalization (n = 21,978) and patients who did not receive early statin treatment (n = 126,128) or whose statin therapy was discontinued (n = 9,411). New or continued treatment with a statin in the first 24 hours was associated with a decreased risk of mortality compared with no statin use (4.0% and 5.3% compared with 15.4% no statin). Discontinuation of statin treatment was associated with a slightly increased risk of mortality (16.5%). Early statin use was also associated with a lower incidence of cardiogenic shock, arrhythmias, cardiac arrest, rupture, but not recurrent myocardial infarction. Propensity analysis yielded mortality odds ratios of 0.46 for continued therapy, 0.42 for newly started therapy, and 1.25 for discontinued therapy for matched pairs versus no statin therapy (all p values <0.0001). In conclusion, the use of statin therapy within the first 24 hours of hospitalization for AMI is associated with a significantly lower rate of early complications and in-hospital mortality.

Aged↗