Heart Failure With A Normal Ejection Fraction Research Articles

Clinical and echocardiographic study of patients in heart failure with a normal/near normal ejection fraction

Background: Heart failure affects more than twenty million people worldwide. Epidemiological studies have shown that approximately one-half of the patients who develop heart failure have a normal or near normal ejection fraction. The diagnosis of heart failure with a normal ejection fraction (HFNEF) is difficult as compared to those with reduced ejection fraction, and so is the treatment. It is caused by diastolic ventricular dysfunction demonstrated by complementary methods. It affects primarily the elderly individuals with co-morbidities such as hypertension, diabetes, obesity, renal dysfunction, atrial fibrillation etc. The aim of this research was to study the clinical and echocardiographic profile of patients in heart failure with a normal/near normal ejection fraction. Methods: This was a prospective, open-labeled, observational study conducted on 70 subjects. All patients with suspected heart failure, fulfilling the Framingham criteria were included in the study. Patients with a reduced ejection fraction ( 1.2 mg%. Mean creatinine was 1.35 ± 0.65 mg%. 63% patients in the study group were anemic with a mean hemoglobin level of 11.3 ± 2.27 g%. 57% of the cases had HbA1c ≥ 5.7% of which, 28% had HbA1c in the pre-diabetic range. 16 patients (22.85%) had a history of atrial fibrillation. 22.8% patients had left ventricular diastolic dysfunction (LVDD) grade 1, 54.3% patients had LVDD grade 2, 20% has LVDD grade 3 and 2.85% had LVDD grad 4. 16 cases had a prolonged deceleration time (DT), with a mean DT of 225 ms. In cases of mild diastolic dysfunction due to impaired relaxation, IVRT was prolonged. Mean IVRT values in the LVDD grade 1 was 119 ms. The echocardiographic indices of restrictive cardiomyopathy showed an E/A ratio of >2.4 (mean 2.76) and E/e’ >15 (mean 17.51). IVRT was markedly reduced in patients with restrictive cardiomyopathy (mean IVRT was 51.09 ms). Conclusion: In the current study, we have seen that heart failure with normal or near normal ejection fraction is more common in females and in the elderly. Hypertension, diabetes mellitus, renal dysfunction, thyroid disorders and atrial fibrillation are associated commonly with HFNEF. Abnormal relaxation, pseudonormal filling pattern and restrictive filling are the mechanisms responsible for diastolic dysfunction.

Soluble ST2 as a Biomarker for Detecting Stable Heart Failure With a Normal Ejection Fraction in Hypertensive Patients

BackgroundWe investigated the measurement of soluble ST2 (sST2) in stable heart failure (HF) with a normal ejection fraction (HFNEF) in hypertensive patients. Methods and ResultsEchocardiography and serum N-terminal pro–B-type natriuretic peptide (NT-proBNP) and sST2 concentrations were evaluated in 107 hypertensive patients (65 ± 12 years, 57 male) with ejection fraction (EF) >50%. Among them, 68 patients with stable HF in functional class II and III were the HFNEF group. We found that the area under the receiver operating characteristic curve (AUC) for sST2 was 0.80 (95% CI 0.70–0.89; P < .001), relatively better than that for NT-proBNP (AUC 0.70, 95% CI 0.58–0.79; P = .003) to detect HFNEF. However, the NT-proBNP concentration, rather than sST2, was higher in HFNEF patients with functional class III (562 ± 891 vs 185 ± 242 pg/mL in functional class II; P = .009), and correlated better with mitral E/e′ (annular early diastolic velocity) (r = 0.327; P = .008) than sST2 concentrations in HFNEF patients. Multivariate analysis showed that sST2 >13.5 ng/mL was independently associated with HFNEF in hypertensive patients (odds ratio 11.7, 95% CI = 2.9–47.4; P = .001). ConclusionssST2 measurement provides diagnostic aid of stable HFNEF for hypertensive patients. Addition of NT-proBNP to sST2 could give further information regarding HF functional class and diastolic abnormality.

Heart Failure With a Normal Ejection Fraction: Treatments for a Complex Syndrome?

Heart failure with a normal ejection fraction (HFNEF) now comprises more than 50% of all patients with heart failure. As the population ages, HFNEF will continue to be a growing public health problem. Recent studies highlight the heterogeneity of this syndrome with regards to underlying pathophysiologic mechanisms. It has been recognized that multiple physiologic domains of cardiovascular function are abnormal in afflicted patients resulting in a reduced reserve capacity, which contributes in an integrated fashion to produce the observed phenotype. Additionally, the realization that differing aspects of this syndrome (eg, exercise limitations, pulmonary edema, and labile blood pressure) likely each have distinct physiologic causes further adds to the complexity. As a result of the heterogeneous nature of the pathophysiologic processes and comorbid illnesses in this population, there is a wide range of clinical outcomes. Accordingly, appreciation of the global nature of HFNEF ideally will better inform optimal design for future diagnostic and therapeutic strategies. Completed clinical trials have not resulted in any evidence-based treatments available for improving survival. Given the disappointing results of these investigations, there has been renewed interest in developing interventions that target underlying comorbidities and peripheral mechanisms. Additionally, nonpharmacologic interventions such as diet and exercise have shown promise in early, small clinical investigations. Finally, methods to more rationally subgroup patients to identify cohorts that could respond to targeted intervention are essential. Recognizing the success achieved in the treatment of systolic heart failure, or heart failure with a reduced ejection fraction (HFREF) by addressing neurohormonal and renal mechanisms, new therapies for HFNEF may be achieved by a similar shift in attention away from the heart.

Leptin, leptin gene and leptin receptor gene polymorphism in heart failure with preserved ejection fraction

Heart failure with a normal ejection fraction (HFNEF) is common in obesity and coronary artery disease (CAD). Both ischemia and reperfusion induce leptin (LEP) and leptin receptor (LEPR) gene expression. We aimed to investigate the possible associations of serum leptin, leptin gene and leptin receptor gene polymorphism with HFNEF in patients with CAD. 100 Egyptian CAD patients with HFNEF and 100 healthy subjects (the control group) were genotyped for LEP and LEPR polymorphism. Leptin levels were measured. Serum leptin levels were significantly increased in patients compared to the control group. There was a significant increase in the leptin gene (AA genotype) and the leptin receptor gene (RR genotype) in HFNEF patients compared to the control group. Leptin levels, leptin gene (AA genotype) and LEPR (RR genotype) were more associated with NYHA III than with NYHA I and II. We thus concluded that HFNEF is associated with increased serum leptin levels, and the LEP AA genotype or LEPR RR genotype carries at least a threefold increased risk of developing HFNEF.

The Diagnosis and Treatment of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common hereditary disease of the heart. In this article, we summarize the current state of the diagnosis and treatment of HCM on the basis of a selective review of recent publications with relevance to clinical practice. Several hundred mutations in more than 27 genes, most of which encode sarcomeric structures, are associated with the HCM phenotype. Thus, HCM can be thought of as a sarcomeric disease, with myocardial fiber disarray as its histological hallmark. There are two types of HCM, a more common, obstructive type (HOCM, 70%) and a less common, non-obstructive type (HNCM; in all cases of HCM, testing should be performed to detect outflow obstruction at rest and/or on provocation, and to thereby determine whether HOCM or HNCM is present. The symptoms of HCM include dyspnea, angina pectoris, palpitations, dizziness, and occasionally syncope. Because sudden cardiac death is the most serious complication of HCM, particularly in young and asymptomatic patients, it follows that correct diagnosis, followed by risk stratification of patients with regard to the need for prophylactic implantation of an implantable cardiac defibrillator (ICD), can be of life-saving importance. The pharmacotherapy of symptomatic HNCM consists of the treatment of heart failure with a normal ejection fraction (HFNEF). In HOCM, the patient's symptoms and the obstructive gradient are the guide to treatment with beta-blockers or verapamil. For patients with drug-resistant disease, surgical myectomy and percutaneous septal ablation are now standard treatments. A near-normal life expectancy and a highly satisfactory quality of life are now realistic treatment goals for patients with HCM.

Reduced left atrial function on exercise in patients with heart failure and normal ejection fraction

AimsThe cardinal symptom of heart failure with a normal ejection fraction (HFNEF) is exertional dyspnoea. The authors hypothesised that failure of left atrial (LA) compensatory mechanism particularly on exercise contributes...

Diastolic Dysfunction

It has recently become firmly established that patients can experience chronic and acute heart failure with a normal ejection fraction (HFNEF).1–5 We now know this disorder is the dominant form of HF in the community, and that compared with HF with reduced ejection fraction (HFREF), it is increasing in prevalence and incidence,6 causes at least as many hospitalizations and healthcare expenditures,1,6,7 causes at least as severe chronic symptoms and reduced objectively measured exercise tolerance,4 and, once patients are hospitalized, has death rates that are similarly grim.1,6 Until recently, however, we have invested nearly all our resources into understanding the pathophysiology and treatment of HFREF. As a result, a physician managing a patient with HFREF can rely on practice guidelines that are solidly supported by dozens of large trials demonstrating substantial improvements in each of the meaningful HF outcomes: mortality, hospitalizations, exercise intolerance, and reduced quality of life. When the patient instead has HFNEF, there is relatively little information about pathophysiology or treatment to guide the physician. This fact is reflected in outcomes, which a recent study indicates are improving in patients with HFREF but worsening in those with HFNEF.6 This disconcerting imbalance is magnified by sex and age, as the large burden of HFNEF falls primarily on older women.1,2,6 Article p 2051 In the present issue of Circulation , Westermann and colleagues8 report a welcomed and important study aimed at addressing the dearth of information about the pathophysiology of HFNEF. They studied 70 very well-characterized patients with documented symptoms of HF, normal left ventricular (LV) EF, and no other detectable cause for their symptoms, including pulmonary and ischemic heart disease. The investigators used a conductance catheter to measure pressure–volume loops during supine rest, handgrip exercise, and atrial pacing to 120 bpm. They …

2007 Laennec Clinician/Educator Lecture—Unraveling the Mysteries of Diastology

Diastolic dysfunction plays a critical role in the pathophysiology of producing signs and symptoms of heart failure. Heart failure with a normal ejection fraction (HFnlEF) is one of the leading causes of hospital admissions today and is associated with significant morbidity and mortality. It is thus important to understand the pathophysiology of diastolic dysfunction, which itself is a complex series of multiple interrelated events, including relaxation, suction, ventricular interaction, ventricular arterial coupling, pericardial restraint, and myocardial viscoelastic forces. It was difficult for the clinician to understand “diastology” in the past. Initial studies were limited to complex equations derived from animal models and were difficult to apply to patient care. The development of radionuclide angiography and Doppler echocardiography allowed noninvasive rapid assessment of volumetric filling and flow velocity curves, which began to provide insight into the complex process of diastolic filling for the clinician. As our understanding of diastology evolved over the past 2 decades, it has become clear that we now need to pursue new areas to understand this fascinating subject and apply it to patient care. These areas include the underlying mechanism HFnlEF (ventricular-vascular coupling versus true myocardial stiffness), relationship of rest versus exercise hemodynamics, and the complex ventricular fiber “twisting and shortening” of both contraction and relaxation.

Left Heart Failure With a Normal Ejection Fraction: Identification of Different Pathophysiologic Mechanisms

Background Although heart failure with a normal ejection fraction (HFNEF) is a clinically heterogeneous syndrome, a single pathophysiologic mechanism, diastolic dysfunction, is often ascribed to explain this condition. In view of the clinical heterogeneity of these patients, we hypothesized that subgroups of HFNEF patients may have different underlying pathophysiologic mechanisms. Methods and Results Freehand 3-dimensional echocardiography was used to measure left ventricular end-systolic and end-diastolic volumes in 99 asymptomatic normal controls and 2 groups with chronic heart failure: 35 patients with normal ejection fraction with longstanding hypertension (hypertensive HFNEF) and 11 patients with hypertrophic cardiomyopathy without a history of hypertension (nonhypertensive HFNEF). These data, combined with cuff sphygmomanometry and Doppler estimates of LV end-diastolic pressure (EDP) yielded estimated pressure-volume loops and slope (E es,sb) of the end-systolic pressure-volume relationship, a load independent index of chamber contractility. Nonhypertensive HFNEF patients required high EDPs (21 ± 2 versus 15 ± 3 mm Hg in normals, P < .0001) to achieve normal EDVs (98 ± 25 versus 95 ± 21 mL in normals, P = NS). Although systolic function (E es,sb) did not differ from normal, systolic blood pressure was lower than normal in these patients (114 ± 10 versus 124 ± 14 mm Hg in normals, P < .05). Hypertensive HFNEF patients also had increased EDP (20 ± 2 mm Hg), but this was observed at higher than normal EDVs (118 ± 29 mL, P < .05). Among patients with hypertensive HFNEF, 2 subgroups emerged, 1 with a high E es,sb (4.23 ± 0.54 versus 2.1 ± 0.7 mm Hg/mL) and 1 with normal E es,sb (2.31 ± 0.51 mm Hg/mL). The former group was composed of elderly women with small body size (body surface area 1.7 ± 0.2 versus 1.9 ± 0.2 m 2, P = .02) who had concentrically remodeled ventricles and low stroke volumes. The latter group was more diverse in age, body size, and included patients of both genders with increases in ventricular volumes, stroke volume, and mass consistent with a volume overload state. Conclusion Although HFNEF is commonly thought of as being the result of a single hemodynamic mechanism, these data indicate that subgroups exist with distinctly different underlying pathophysiologies.

Hospitalization for heart failure in the presence of a normal left ventricular ejection fraction: Results of the New York heart failure registry

ObjectivesWe conducted a prospective multicenter registry in a large metropolitan area to define the clinical characteristics, hospital course, treatment, and factors precipitating decompensation in patients hospitalized for heart failure with a normal ejection fraction (HFNEF). BackgroundThe clinical profile of patients hospitalized for HFNEF has been characterized by retrospective analyses of hospital records and state data banks, with few prospective single-center studies. MethodsPatients hospitalized for heart failure (HF) at 24 medical centers in the New York metropolitan area and found to have a left ventricular (LV) ejection fraction of ≥50% within seven days of admission were included in this registry. Patient demographics, signs and symptoms of HF, coexisting and exacerbating cardiovascular and medical conditions, treatment, laboratory tests, procedures, and hospital outcomes data were collected. Analysis by gender and race was prespecified. ResultsOf 619 patients, 73% were women, who were on average four years older than men (72.8 ± 14.1 years vs. 68.6 ± 13.8 years, p < 0.001). Black non-Hispanic patients comprised 30% of the study population. They were eight years younger than other patients (66.0 ± 14.2 years vs. 74 ± 13.5 years p < 0.001). Co-morbid conditions and their prevalence were: hypertension, 78%; increased LV mass, 82%; diabetes, 46%; and obesity, 46%. Before clinical decompensation that precipitated hospitalization, 86% of patients had chronic symptoms compatible with New York Heart Association functional classes II to IV. Factors precipitating clinical decompensation were identified in 53% of patients. In-hospital mortality was 4.2%. ConclusionsPatients hospitalized for HFNEF are most often chronically incapacitated elderly women with a history of hypertension and increased LV mass. Reasons for clinical decompensation are identified in only one-half of patients.