cardiovascular-agents and Heart-Failure--Diastolic

Topics: Aged; Cardiovascular Agents; Combined Modality Therapy; Diagnosis, Differential; Drug Therapy, Combination; Heart Failure, Diastolic; Humans; Stroke Volume

Topics: Acetanilides; Adrenergic beta-Antagonists; Angina Pectoris; Atrial Fibrillation; Benzazepines; Calcium; Calcium Channel Blockers; Cardiovascular Agents; Coronary Artery Disease; Electrocardiography; Endothelium, Vascular; Heart Failure, Diastolic; Humans; Hypercalcemia; Ivabradine; Myocardial Ischemia; Nitrates; Piperazines; Ranolazine; Sodium; Sodium Channels; Sodium-Calcium Exchanger

The late Na current is of pathophysiological importance for the heart. Ranolazine is an innovative anti-ischemic and antianginal agent that inhibits the late Na current, thereby reducing the Na-dependent Ca-overload, which improves diastolic tone and oxygen handling during myocardial ischemia. In addition, ranolazine seems to exert beneficial effects on diastolic cardiac function. Moreover, there are experimental and clinical data about its antiarrhythmic properties. A beneficial atrial selectivity of ranolazine has been suggested that may be helpful for the treatment of atrial fibrillation. The purpose of this review article is to discuss possible future clinical indications based on novel experimental and preclinical results and the significance of the available data.

Topics: Acetanilides; Action Potentials; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Calcium; Cardiovascular Agents; Cations; Diastole; Enzyme Inhibitors; Heart Failure; Heart Failure, Diastolic; Humans; Myocardial Contraction; NAV1.5 Voltage-Gated Sodium Channel; Piperazines; Ranolazine; Sodium; Sodium-Calcium Exchanger

Diastolic heart failure, which is also called as heart failure with preserved ejection fraction, is a clinical syndrome in which patients have signs and symptoms of heart failure, normal or near normal left ventricular ejection fraction (≥ 50%) and evidence of diastolic dysfunction. Recent epidemiological studies have demonstrated that more than half of all heart failure patients have diastolic heart failure. The syndrome is more common in women than in men and the prevalence increases with age. Patients with diastolic heart failure form a fairly heterogeneous group with complex pathophysiologic mechanisms. The disease is often in association with other comorbidities, such as hypertension, diabetes mellitus or obesity. The diagnosis of diastolic heart failure is best achieved by two-dimensional and Doppler echocardiography, which can detect abnormal myocardial relaxation, decreased compliance and increased filling pressure in the setting of normal left ventricular dimensions and preserved ejection fraction. Unlike heart failure with reduced ejection fraction, there is no such an evidence-based treatment for heart failure with preserved ejection fraction, which would improve clinical outcomes. Thus, pharmacological therapy of diastolic heart failure is based mainly on empiric data, and aims to the normalization of blood pressure, reduction of left ventricular dimensions and increased heart rate, maintenance of normal atrial contraction and treatment of symptoms caused by congestion. Beneficial effects of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers may be utilized in patients with diastolic dysfunction, especially in those with hypertension. Beta-blockers appear to be useful in lowering heart rate and thereby prolonging left ventricular diastolic filling time, while diuretic therapy is the mainstay of treatment for preventing pulmonary congestion. Nonetheless, treatment of the underlying disease is also an important therapeutic approach. This review summarizes the state of current knowledge with regard to diastolic heart failure.

Topics: Age Factors; Cardiovascular Agents; Clinical Trials as Topic; Diagnosis, Differential; Female; Heart Failure, Diastolic; Hemodynamics; Humans; Male; Sex Factors; Stroke Volume

Diastolic heart failure, also termed as heart failure with normal or preserved ejection fraction has a high prevalence and mortality world wide. The clinical manifestation comprises typical symptoms and signs of heart failure along with normal or discretely reduced left ventricular ejection fraction. Though the etiology of diastolic heart failure is incompletely understood, functional and structural abnormalities of cardiomyocytes, the extracellular matrix, and the peripheral vasculature are assumed to contribute to the etiology of diastolic heart failure. The diagnosis requires typical symptoms and signs of heart failure, evidence of elevated natriuretic peptides and an impaired diastolic ventricular function, meanwhile left ventricular systolic function is normal or just slightly impaired. Catheter and MRI exams help to ensure the diagnosis. So far, no therapy has convincingly demonstrated a reduction of morbiditiy and mortality. Therefore, current guidelines emphasize the importance of an adequate treatment of risk factors and myocardial ischemia.

Topics: Algorithms; Blood Pressure; Cardiovascular Agents; Combined Modality Therapy; Echocardiography; Heart Failure, Diastolic; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume; Survival Rate; Ventricular Dysfunction, Left

Heart failure (HF) is a complex syndrome characterized by the inability of the heart to maintain a normal cardiac output without elevated intracardiac filling pressures, resulting in signs of pulmonary and peripheral edema and symptoms of dyspnea and fatigue. Central to the management of HF is a multifaceted pharmacological intervention to abate the harmful counter-regulatory effects of neurohormonal activation and avid salt and water retention. Whereas up to 40 years ago HF was managed with diuretics and leaf of digitalis, the cornerstones of therapy for HF patients with systolic dysfunction now include ACE inhibitors or angiotensin II type 1 receptor antagonists (angiotensin receptor blockers), β-adrenoceptor antagonists (β-blockers), and aldosterone antagonists, which have significantly improved survival. However, with the increasing number of beneficial therapies, there are challenges to implementing all of them. Specific cardiomyopathies also merit specific considerations with respect to treatment, and - unfortunately - there is no therapy for HF with preserved left ventricular ejection fraction that has been shown to improve survival. Although mortality has improved in HF, the biggest challenge to treatment lies in addressing the morbidity of this disease, which is now the most common reason for hospital admission in our aged population. As such, there are many therapies that may serve to improve the quality of life of HF patients. Future HF treatment regimens may include direct cellular therapy via hormone and cytokine signaling or cardiac regeneration through growth factors or cell therapy.

Topics: Animals; Cardiovascular Agents; Chronic Disease; Heart Failure, Diastolic; Heart Failure, Systolic; Hospitalization; Humans

Half of heart failure patients have diastolic heart failure, which has no effective treatments. Several studies indicate a role for ω-3 polyunsaturated fatty acids (PUFAs) in heart failure. Recent studies suggest that ω-3 PUFAs inhibit cardiac fibrosis and attenuate diastolic dysfunction. This opens up possible new avenues for treatment of diastolic heart failure. In this review, we focus on the antifibrotic effects of ω-3 PUFAs in heart and the underlying cellular and molecular mechanisms.

Topics: Animals; Cardiovascular Agents; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Diastole; Fatty Acids, Omega-3; Fibroblasts; Fibrosis; Heart Failure, Diastolic; Humans; Myocardium; Nitric Oxide; Signal Transduction; Transforming Growth Factor beta1

Diastolic heart failure (HF) is also referred to as HF with preserved left ventricular systolic function. The distinction between systolic and diastolic HFs is a pathophysiological one and isolated forms of left ventricular dysfunction are rarely observed. In diastolic HF left ventricular systolic function is normal or only slightly impaired, and the typical manifestations of HF result from increased filling pressure caused by impaired relaxation and compliance of the left ventricle. The predisposing factors for diastolic dysfunction include elderly age, female sex, obesity, coronary artery disease, hypertension and diabetes mellitus. Treatment of diastolic HF is aimed to stop the progression of the disease, relieve its symptoms, eliminate exacerbations and reduce the mortality. The management should include antihypertensive treatment, maintenance of the sinus rhythm, prevention of tachycardia, venous pressure reduction, prevention of myocardial ischemia and prevention of diabetes mellitus. The European Society of Cardiology specifies the type of therapy in diastolic HF based on: angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, non-dihydropyridine calcium channel blockers, diuretics. In order to improve the currently poor prognosis in this group of patients the treatment of diastolic HF must be optimised.

Topics: Cardiovascular Agents; Diastole; Drug Therapy, Combination; Heart Failure, Diastolic; Humans; Practice Guidelines as Topic; Stroke Volume; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

A considerable number of patients who undergo cardiac surgery have a variety of comorbid conditions that includes diastolic dysfunction. Abnormalities of diastolic function may lead to diastolic heart failure that can complicate their postoperative course. This form of failure occurs more commonly in patients with hypertensive or valvular heart disease, diabetes mellitus, myocardial ischaemia, as well as in hypertrophic or restrictive cardiomyopathy, and is more prevalent in the elderly. In spite of it being a common cause of heart failure it remains underreported in the postoperative heart. We reviewed relevant literature analysing the different therapeutic approaches and formulated a management plan for diastolic heart failure in the postoperative heart in the intensive care environment based on the most current understanding of this form of cardiac failure.

Topics: Cardiac Surgical Procedures; Cardiovascular Agents; Heart Failure, Diastolic; Humans; Perioperative Care; Terminology as Topic

Topics: Aged; Cardiovascular Agents; Diagnosis, Differential; Disease Management; Exercise; Female; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Prognosis

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.. 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.. 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).. 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.

Topics: Aged; Aged, 80 and over; Canada; Cardiotonic Agents; Cardiovascular Agents; Chronic Disease; Digoxin; Double-Blind Method; Female; Follow-Up Studies; Heart Failure, Diastolic; Humans; Kaplan-Meier Estimate; Male; Odds Ratio; Patient Admission; Patient Readmission; Proportional Hazards Models; Sample Size; Treatment Outcome; United States

Topics: Cardiovascular Agents; Double-Blind Method; Echocardiography, Doppler; Exercise Test; Exercise Tolerance; Heart Failure, Diastolic; Humans; Magnetic Resonance Imaging; Oxygen Consumption; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Recovery of Function; Research Design; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Time Factors; Treatment Outcome; Ventricular Function, Left

Heart failure with preserved ejection fraction (HFpEF), formerly referred to as diastolic heart failure (DHF), accounts for >50% of all HF patients. So far, there has been no specific treatment for impaired left ventricular (LV) relaxation. Data from in vitro and animal studies indicate that ranolazine improves diastolic function by inhibiting the late sodium current.. RAnoLazIne for the Treatment of Diastolic Heart Failure (RALI-DHF) is a prospective, single-center, randomized, double-blind, placebo-controlled proof-of-concept study to determine if ranolazine compared with placebo will be more effective in improving diastolic function in patients with HFpEF.. Twenty patients with HFpEF (EF ≥ 50% and ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity [E/E'] >15 or N-terminal pro-type brain natriuretic peptide >220 pg/mL) will be randomized to receive ranolazine or placebo in a 1.5:1 ratio during their catheterization if the LV end-diastolic pressure is ≥18 mm Hg and the time constant of relaxation (τ) is ≥50 ms. Treatment will consist of intravenous infusion of study drug (or placebo) for 24 hours, followed by oral treatment for a total of 14 days.. The study will include the following exploratory endpoints: (1) change from baseline to 30 minutes from initiation of intravenous study drug administration during cardiac catheterization hemodynamic parameters at both resting and paced (120 beats per minute) conditions: τ, LV end-diastolic pressure, and dP/dt(min) .; and (2) change from baseline to day 14 in E/E', maximal oxygen consumption, and N-terminal pro-type brain natriuretic peptide.. The RALI-DHF study is designed as a translational study to bridge the gap between basic science and therapeutics and to determine if ranolazine, compared with placebo, will be more effective in improving diastolic function in patients with HFpEF.

Topics: Acetanilides; Administration, Oral; Biomarkers; Cardiac Catheterization; Cardiovascular Agents; Double-Blind Method; Echocardiography, Doppler; Germany; Heart Failure, Diastolic; Humans; Infusions, Intravenous; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Piperazines; Placebo Effect; Prospective Studies; Ranolazine; Recovery of Function; Research Design; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Pressure

To assess the effect of Shenmai Injection (SMI) on left ventricular diastolic function (LVDF) in patients with chronic heart failure (CHF) by tissue Doppler imaging (TDI).. Sixty-four CHF patients were randomly assigned to two groups, the observation group and the control group. Basic treatment including polarized liquid therapy was given to all the patients. In addition, SMI was given to patients of the observation group. The treatment duration was 14 days. TDI was performed in all the patients 3 days prior to the initiation of the treatment and one week after the medication to measure the average movement velocity of the mitral ring of the left ventricle at the early systolic stage and late diastolic stage (Ea and Aa); the outcomes were compared with the corresponding parameters obtained from blood flow Doppler echocardiography, namely, the velocity of the E-wave (E) and A-wave (A).. After treatment, Ea and Ea/Aa increased and Aa decreased significantly in the observation group (P<0.05). In the control group, although some improvement was seen, there was no statistically significant change (P>0.05). No statistical significance was shown between groups in these parameters after treatment.. TDI assessment shows that SMI could effectively improve the LVDF in CHF patients.

Topics: Adult; Aged; Cardiovascular Agents; Chronic Disease; Diastole; Drug Combinations; Drugs, Chinese Herbal; Echocardiography, Doppler; Female; Heart Failure, Diastolic; Humans; Injections; Male; Middle Aged; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function

Topics: Aged; Atrial Fibrillation; Cardiovascular Agents; Contraindications; Digoxin; Drug Substitution; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Female; Heart Failure, Diastolic; Humans; Hypertension; Renal Insufficiency, Chronic; Treatment Outcome; Withholding Treatment

Topics: Biomarkers; Cardiovascular Agents; Heart Failure, Diastolic; Humans; Mineralocorticoid Receptor Antagonists; Spironolactone; Stroke Volume; Treatment Outcome; Ventricular Remodeling

Despite the increasing prevalence of heart failure with preserved left ventricular function, there are no specific treatments, partially because the mechanism of impaired relaxation is incompletely understood. Evidence indicates that cardiac relaxation may depend on nitric oxide (NO), generated by NO synthase (NOS) requiring the co-factor tetrahydrobiopterin (BH(4)). Recently, we reported that hypertension-induced diastolic dysfunction was accompanied by cardiac BH(4) depletion, NOS uncoupling, a depression in myofilament cross-bridge kinetics, and S-glutathionylation of myosin binding protein C (MyBP-C). We hypothesized that the mechanism by which BH(4) ameliorates diastolic dysfunction is by preventing glutathionylation of MyBP-C and thus reversing changes of myofilament properties that occur during diastolic dysfunction. We used the deoxycorticosterone acetate (DOCA)-salt mouse model, which demonstrates mild hypertension, myocardial oxidative stress, and diastolic dysfunction. Mice were divided into two groups that received control diet and two groups that received BH(4) supplement for 7days after developing diastolic dysfunction at post-operative day 11. Mice were assessed by echocardiography. Left ventricular papillary detergent-extracted fiber bundles were isolated for simultaneous determination of force and ATPase activity. Sarcomeric protein glutathionylation was assessed by immunoblotting. DOCA-salt mice exhibited diastolic dysfunction that was reversed after BH(4) treatment. Diastolic sarcomere length (DOCA-salt 1.70±0.01 vs. DOCA-salt+BH(4) 1.77±0.01μm, P<0.001) and relengthening (relaxation constant, τ, DOCA-salt 0.28±0.02 vs. DOCA-salt+BH(4) 0.08±0.01, P<0.001) were also restored to control by BH(4) treatment. pCa(50) for tension increased in DOCA-salt compared to sham but reverted to sham levels after BH(4) treatment. Maximum ATPase rate and tension cost (ΔATPase/ΔTension) decreased in DOCA-salt compared to sham, but increased after BH(4) treatment. Cardiac MyBP-C glutathionylation increased in DOCA-salt compared to sham, but decreased with BH(4) treatment. MyBP-C glutathionylation correlated with the presence of diastolic dysfunction. Our results suggest that by depressing S-glutathionylation of MyBP-C, BH(4) ameliorates diastolic dysfunction by reversing a decrease in cross-bridge turnover kinetics. These data provide evidence for modulation of cardiac relaxation by post-translational modification of myofilament proteins.

Topics: Adenosine Triphosphatases; Administration, Oral; Animals; Biopterins; Cardiovascular Agents; Carrier Proteins; Cells, Cultured; Desoxycorticosterone; Diastole; Dietary Supplements; Glutathione; Heart Failure, Diastolic; Mice; Myofibrils; Oxidative Stress; Protein Processing, Post-Translational; Stroke Volume; Ultrasonography

Diastolic heart failure (DHF) remains unexplained in some patients with recurrent admissions after full investigation. A study was directed for screening SLE and systemic autoimmune connective tissue disorders in recurrent unexplained DHF patients admitted at a short-stay and intermediate care unit. It was found that systemic autoimmune conditions explained 11% from all of cases. Therapy also prevented new readmissions. Autoimmunity should be investigated in DHF.

Topics: Abortion, Habitual; Aged; Aged, 80 and over; Autoimmune Diseases; Cardiovascular Agents; Connective Tissue Diseases; Critical Care; Delayed Diagnosis; Female; Heart Failure, Diastolic; Humans; Lupus Erythematosus, Systemic; Male; Mass Screening; Middle Aged; Mitral Valve Insufficiency; Pregnancy; Prospective Studies; Recurrence; Spain

Brain natriuretic peptide (BNP) and N-Terminal pro natriuretic peptide (NT-proBNP) are widely accepted to diagnose congestive heart failure (CHF) in the emergency room. The aim of this study was to evaluate the value of BNP and NT-proBNP to diagnose CHF in primary care.. Clinical and Doppler-echocardiographic assessment of patients referred by their general practitioner (GP) with the diagnosis of CHF. Receiver operating curves were used to evaluate the accuracy of BNP and NT-proBNP for echocardiographically confirmed systolic and/or diastolic heart failure.. Three hundred and eighty four patients (mean age of 65) were included. One hundred and ninety three (50%) patients had systolic heart failure and 31 (8%) had isolated diastolic heart failure. Using currently recommended cut-off values of BNP (less than 100 pg/ml) and NT-proBNP (less than 125 pg/ml) for exclusion of CHF, BNP was false negative in 25% and NT-proBNP in 10% of the patients. The area under the curve was better for NT-proBNP than for BNP (0.742 vs. 0.691).. In this population with a high prevalence of CHF, BNP and NT-proBNP failed to adequately rule out CHF. GP's should be cautious when using BNP and NT-proBNP in primary care. An echocardiography remains compulsory in unexplained dyspnea.

Topics: Aged; Biomarkers; Cardiovascular Agents; Chronic Disease; Dyspnea; Echocardiography, Doppler; Female; Heart Failure, Diastolic; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Primary Health Care; Prospective Studies; Referral and Consultation; ROC Curve; Switzerland; Treatment Outcome