Objectively Measured, but Not Self-Reported, Medication Adherence Independently Predicts Event-Free Survival in Patients With Heart Failure
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Heart failure is a clinical syndrome associated with poor quality of life, substantial healthcare resource utilization, and premature mortality, in large part related to high rates of hospitalizations. The clinical manifestations of heart failure are similar regardless of the ejection fraction. Unlike heart failure with reduced ejection fraction, there are few therapeutic options for treating heart failure with preserved ejection fraction. Molecular therapies that have shown reduced mortality and morbidity in heart failure with reduced ejection have not been proven to be effective for patients with heart failure and preserved ejection fraction. The study of pathophysiological processes involved in the production of heart failure with preserved ejection fraction is the basis for identifying new therapeutic means. In this narrative review, we intend to synthesize the existing therapeutic means, but also those under research (metabolic and microRNA therapy) for the treatment of heart failure with preserved ejection fraction.
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To study the characteristics and prognostic implications of type 2 diabetes in different heart failure entities from a nationwide perspective.This observational study comprised 30,696 heart failure patients prospectively included in the Swedish Heart Failure Registry (SwedeHF) 2003-2011 from specialist care, with mortality information available until December 2014. Patients were categorized into three heart failure entities by their left ventricular ejection fraction (heart failure with preserved ejection fraction: ⩾50%, heart failure with mid-range ejection fraction: 40%-49% and heart failure with reduced ejection fraction: <40%). All-cause mortality stratified by type 2 diabetes and heart failure entity was studied by Cox regression.Among the patients, 22% had heart failure with preserved ejection fraction, 21% had heart failure with mid-range ejection fraction and 57% had heart failure with reduced ejection fraction. The proportion of type 2 diabetes was similar, ≈25% in each heart failure entity. Patients with type 2 diabetes and heart failure with preserved ejection fraction were older, more often female and burdened with hypertension and renal impairment compared with heart failure with mid-range ejection fraction and heart failure with reduced ejection fraction patients among whom ischaemic heart disease was more common. Type 2 diabetes remained an independent mortality predictor across all heart failure entities after multivariable adjustment, somewhat stronger in heart failure with left ventricular ejection fraction below 50% (hazard ratio, 95% confidence interval; heart failure with preserved ejection fraction: 1.32 [1.22-1.43], heart failure with mid-range ejection fraction: 1.51 [1.39-1.65], heart failure with reduced ejection fraction: 1.46 [1.39-1.54]; p-value for interaction, p = 0.0049).Type 2 diabetes is an independent mortality predictor across all heart failure entities increasing mortality risk by 30%-50%. In type 2 diabetes, the heart failure with mid-range ejection fraction entity resembles heart failure with reduced ejection fraction in clinical characteristics, risk factor pattern and prognosis.
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The findings of randomized trials of neurohormonal modulation have been neutral in heart failure with preserved ejection fraction and consistently positive in heart failure with reduced ejection. Left ventricular remodeling promotes the development and progression of heart failure with preserved and reduced ejection fraction. However, different stimuli mediate left ventricular remodeling that is commonly concentric in heart failure with preserved ejection fraction and eccentric in heart failure with reduced ejection. The stimuli that promote concentric left ventricular remodeling may account for the neutral findings of neuhormonal modulation in heart failure with preserved ejection fraction. Low-grade systemic inflammation-induced microvascular endothelial dysfunction is currently the leading hypothesis behind the development and progression of heart failure with preserved ejection fraction. The hypothesis provided the rationale for several randomized controlled trials that have led to neutral findings. The trials and their limitations are reviewed.
Ventricular remodeling
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Diastolic heart failure
Concomitant
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Elderly patients are underrepresented in clinical trials but comprise the majority of heart failure patients. Data on age-specific use of heart failure therapy are limited. The European Society of Cardiology heart failure guidelines provide no age-specific treatment recommendations. We investigated practice-based heart failure management in a large registry at heart failure outpatient clinics.We studied 8351 heart failure with reduced ejection fraction patients at 34 Dutch outpatient clinics between 2013 and 2016. The mean age was 72.3 ± 11.8 years and we divided age into three categories: less than 60 years (13.9%); 60-74 years (36.0%); and 75 years and over (50.2%).Elderly heart failure with reduced ejection fraction patients (≥75 years) received significantly fewer beta-blockers (77.8% vs. 84.2%), renin-angiotensin system inhibitors (75.2% vs. 89.7%), mineralocorticoid receptor antagonists (50.6% vs. 59.6%) and ivabradine (2.9% vs. 9.3%), but significantly more diuretics (88.1% vs. 72.6%) compared to patients aged less than 60 years (Pfor all trends < 0.01). Moreover, the prescribed target dosages were significantly lower in elderly patients. Also, implantable cardioverter defibrillator (18.9% vs. 44.1%) and cardiac resynchronisation therapy device (14.6% vs. 16.7%) implantation rates were significantly lower in elderly patients. A similar trend in drug prescription was observed in patients with heart failure with mid-range ejection fraction as in heart failure with reduced ejection fraction.With increasing age, heart failure with reduced ejection fraction patients less often received guideline-recommended medication prescriptions and also in a lower dosage. In addition, a lower percentage of implantable cardioverter defibrillator and cardiac resynchronisation therapy device implantation in elderly patients was observed.
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ABSTRACT: Left ventricular ejection fraction was measured by gated wall motion in 62 patients, 75 years old or older, admitted to a Geriatric Acute Assessment Ward. From this group, 42 patients not taking digitalis or other cardioactive medication were selected for analysis. Thirty of them had clinically identifiable heart disease, whereas 12 did not. Resting left ventricular ejection fractions in the 12 patients without clinically identifiable heart disease averaged 0.60 ± 0.09. None had an ejection fraction below 0.50. In the 30 patients with clinically identifiable heart disease, mean ejection fraction was 0.49 ± 0.15 (range 0.17‐0.84), P < 0.01. In the patients with heart disease, reduction of ejection fraction was correlated with either cardiac enlargement or congestive heart failure. Neither age nor electrocardiographic abnormalities added to the strength of this correlation. Fifty‐eight per cent of patients with congestive heart failure had ejection fractions 3=0.40, suggesting that congestive heart failure in this age group is frequently related to diastolic left ventricular dysfunction unaccompanied by major systolic dysfunction. The prognosis of patients with congestive heart failure and ejection fractions above 0.35 was significantly better than of patients with congestive heart failure and ejection fractions below 0.35. From these data and other data available in the literature, it is proposed that the lower limit for ejection fraction be 0.50 for patients 75 years old or older. Congestive heart failure in patients 75 years old or older appears to be associated with relatively higher ejection fractions or even with ejection fractions within the normal range. In these patients, digitalis may not be indicated, and short term‐prognosis is relatively favorable.
Hypertensive heart disease
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To describe the impact of ejection fraction on the prognosis during 2 years after coronary artery bypass grafting (CABG).All patients in western Sweden who underwent CABG without concomitant valve surgery between June 1988 and June 1991.In all, 2121 patients were operated upon and information on ejection fraction was available for 1961 patients (92%). Of these patients, 178 (9%) had an ejection fraction < 40%, 517 (26%) an ejection fraction of 40-59% and 1266 (65%) an ejection fraction > or = 60%. In these groups the mortalities during the first 30 days after CABG were 5.1, 4.3 and 2.2%, respectively (P < 0.01). The corresponding values for mortalities between 30 days and 2 years were 7.7, 4.3 and 3.3%, respectively (P < 0.01). Patients with a lower ejection fraction were more frequently men and more frequently had a history of cardiovascular disease. In multivariate analysis the preoperative ejection fraction was an independent predictor for total 2-year mortality. Patients with a low ejection fraction died more frequently in association with ventricular fibrillation. Morbidity was, with the exception of that for rehospitalization due to heart failure and infection, not associated significantly with the preoperative ejection fraction.During the 2 years after CABG a low preoperative ejection fraction was associated with a higher mortality, but the association with morbidity was more complex.
Concomitant
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• Chronic heart failure with preserved ejection fraction is as common as chronic heart failure with reduced ejection fraction.• After hospitalization for heart failure with preserved ejection fraction, prognosis and rehospitalization rates are comparable to heart failure with reduced ejection fraction.• Systolic function of the cardiac muscle is impaired in heart failure with preserved ejection fraction.• According to a recent consensus statement of the Heart Failure Association of the European Society of Cardiology, the diagnosis of heart failure with preserved ejection fraction remains challenging, but the use of serum brain natriuretic peptide (BNP) and tissue Doppler imaging (TDI) has increased accuracy.• Treatment of heart failure with preserved ejection fraction should be empiric, and phenotype-oriented as well as symptom-oriented.
Brain natriuretic peptide
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Last two decade, heart failure with preserved ejection fraction was deprived from being considered as a part of spectrum of heart failure. May be heart failure with preserved ejection fraction was common but not recognized by cardiology fraternity. Heart failure with reduced ejection fraction and heart failure with preserved ejection fraction each make up about half of the overall heart failure burden. But the paradox is: morbidity and mortality in heart failure with preserved ejection fraction despite being similar to patients with heart failure with reduced ejection fraction, today’s cardiology community has not much to offer in terms of mortality reducing treatment. The term diastolic heart failure has been well replaced by heart failure with preserved ejection fraction because multiple non-diastolic abnormalities in cardiovascular function also contribute to heart failure with preserved ejection fraction and diastolic dysfunction always accompanied heart failure with reduced ejection fraction. Diagnosis of heart failure with preserved ejection fraction is an uphill task since it relies upon careful clinical evaluation, doppler (pulse wave and tissue) echocardiography, and invasive hemodynamic assessment after exclusion of potential noncardiac causes of symptoms suggestive of heart failure. Patients with heart failure with preserved ejection fraction are usually older women with a history of hypertension. Obesity, coronary artery disease, diabetes mellitus, and atrial fibrillation are also highly prevalent in heart failure with preserved ejection fraction. Cornerstone of treatment of this entity revolves around treatment of underlying cause and symptom guided therapy. Nepalese Heart Journal | Volume 10 | No.1 | November 2013| Pages 46-56 DOI: http://dx.doi.org/10.3126/njh.v10i1.9747
Diastolic heart failure
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