Drugs For Treatment Of Heart Failure Research Articles

Drug Treatment of Heart Failure in Children: Focus on Recent Recommendations from the ISHLT Guidelines for the Management of Pediatric Heart Failure.

The International Society of Heart and Lung Transplantation (ISHLT) recently updated consensus pediatric heart failure guidelines from those published in 2004 with an aim to provide a practical evidence-based resource whilst recognizing the influence of adult heart failure practice. The new guidelines were formed from published evidence for heart failure management and used parallels with adult literature where pediatric evidence was lacking. This is a summary of the pharmacological therapies discussed in the new 2014 guidelines, emphasizing changes from the previous recommendations with regards to treatment of chronic heart failure with reduced ejection fraction, chronic heart failure with preserved ejection fraction, and acute decompensated heart failure. Each recommendation is classified according to strength and level of evidence. We also discuss future perspectives in the pharmacological treatment of heart failure. The 2014 ISHLT guidelines have evolved considerably from those published in 2004 with extensive information surrounding the underlying pathophysiology, investigations and recommended treatment. The new guidelines contain a modest amount of new pediatric data on pharmacological therapies and extrapolate adult data when appropriate. It is likely that most new recommendations for pediatric heart failure will continue to be based on therapies of proven benefit in adult heart failure studies.

New Targets in the Drug Treatment of Heart Failure.

Heart failure is a complex syndrome that has been a major contributor to readmissions into hospitals in the USA. Currently, a large number of medications are being used to treat the symptoms of the disease-digoxin, diuretics, renin-angiotensin-aldosterone system inhibitors, β-blockers, and vasodilators. There is no doubt that the given pharmaceutical therapy has been effective in lowering hospital readmission rates and prolonging life in individual chronic heart failure patients. Despite this, admission rates following heart failure hospitalization remain high, resulting in a substantial financial strain on healthcare institutions. Clearly, there is much room for improvement in heart failure therapy and management in reducing readmission rates. In this review, we address the unmet needs in the current drug treatment of chronic heart failure and describe novel drug targets that are currently under investigation.

Heart Rate–Dependent Left Ventricular Diastolic Function in Patients With and Without Heart Failure

BackgroundChronic heart rate (HR) reduction in the treatment of heart failure (HF) with systolic dysfunction is beneficial, but the immediate mechanical advantages or disadvantages of altering HR are incompletely understood. We examined the effects of increasing HR on early and late diastole in humans with and without HF. Methods and ResultsWe studied force-interval relationships of the left ventricle (LV) in 11 HF patients and 14 control subjects. HR was controlled by right atrial pacing, and LV pressure was recorded by a micromanometer-tipped catheter. The time constant of isovolumic relaxation (tau) was calculated, and simultaneous sonographic images were analyzed for LV volumes. The end-diastolic pressure-volume relationship (EDPVR) was analyzed with the use of a single-beat method. Tau was shortened in response to increasing HR in both groups; the slope of this relationship was steeper in HF than in control subjects. The predicted volume at a theoretic pressure of 0 mm Hg (V30) increased at higher HRs compared with baseline, shifting the predicted EDPVR compliance curve to the right in HF patients but not in control subjects. ConclusionsIn HF, changes in HR affect early relaxation and diastolic compliance to a greater extent than in control subjects. Our study reinforces current recommendations for HR-lowering drug treatment in HF.

Relation of the Severity of Obstructive Sleep Apnea in Response to Anti-Arrhythmic Drugs in Patients With Atrial Fibrillation or Atrial Flutter

Atrial fibrillation (AF) is more common in those with obstructive sleep apnea (OSA) than in unaffected subjects and recurs more frequently in the presence of severe OSA after electrical cardioversion and AF ablation. However, it is unknown whether the severity of OSA influences the efficacy of antiarrhythmic drug (AAD) therapy in patients with OSA and AF. The aim of this study was to examine the impact of OSA severity on the treatment of patients with symptomatic AF using AADs. Sixty-one patients (mean age 62 ± 15 years, 21 women) treated with AADs for symptomatic AF who underwent overnight polysomnography were studied. Rhythm control was prospectively defined as successful if a patient remained on the same AAD therapy for ≥6 months with ≥75% reduction in symptomatic AF burden. Twenty-four patients (40%) had severe OSA. Thirty patients (49%) were rhythm controlled with AADs. Nonresponders to AADs were more likely to have severe OSA than milder disease (52% vs 23%, p <0.05); those with severe OSA were less likely to respond to AADs than participants with nonsevere OSA (39% vs 70%, p = 0.02). Nonresponders had higher apnea-hypopnea indexes than responders (34 ± 25 vs 22 ± 18 events/hour, p = 0.05), but there were no differences between these groups in minimum oxygen saturation or percentage of time spent in rapid eye movement sleep. In conclusion, patients with severe OSA are less likely to respond to AAD therapy for AF than those with milder forms of OSA.

Efeito favorável da terapia farmacológica otimizada da insuficiência cardíaca sobre as arritmias ventriculares

Ventricular arrhythmic events have a strong impact on the mortality of patients with heart failure. The benefits of the optimized drug treatment of heart failure in reducing ventricular arrhythmia have not been well documented yet. To analyze the effects of the optimized drug treatment of heart failure on ventricular arrhythmia. This is a clinical study with a non-randomized design of 85 consecutive (open cohort) non-selected patients, with a mean age of 63.8+/-12.2 years; 42 were males and 43 were females. All patients had a diagnosis of heart failure (HF), NYHA Functional Class II to IV, EF <or=0.40 and, after treatment optimization, they were followed from January 2002 to May 2004, regarding the ventricular arrhythmia behavior, at admission and at the end of the study. At the start of the study, 60% of patients presented more than 1,000 ventricular extrasystoles in 24 hours, 100% pairs and 100% nonsustained ventricular tachycardia (NSVT). During a follow-up period of 8 to 27 months (20.0 + 4.8 months) a significant decrease in the total number of ventricular extrasystoles/24 hrs, number of pairs and number of NSVT episodes was observed (p<0.05). The improvement in functional class and performance at the six-minute walk test was also observed. A decrease in hospital admissions was also observed in relation to the period prior to the study inclusion (4.8 hospital admissions/patient/year and at the end of the study, 2.7 hospital admissions/patient/year) (p<0.005). The optimized treatment of HF decreased the incidence of ventricular arrhythmias. The improvement in the functional class, physical performance and the decreased number of hospitalizations can be attributed to the optimized treatment of HF.

Multiple Neurohumoral Modulating Agents in Systolic Dysfunction Heart Failure: Are We Lowering Blood Pressure Too Much?

Background Disease-modifying drug treatment in heart failure (HF) reduces blood pressure. Titration of these agents is guided by clinic blood pressure readings; however, the impact of such treatment on blood pressure is unknown because diurnal blood pressure patterns remain poorly described. The aim of this study was to examine the impact of additional neurohumoral modulating agents on ambulatory blood pressure monitoring (ABPM) control in patients with systolic HF and examine the relationship between the burden of hypotension and clinical outcomes. Methods and Results In a prospective analysis on 45 patients undergoing initiation and optimization of additional medications (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or β-blockers), mean daytime systolic ( P = .035) and mean daytime and nocturnal diastolic hypotensive episodes (both P < .001) increased significantly posttitration. There was no change in clinic blood pressure before and after titration. In a cross-sectional analysis on 144 patients, those with the most diastolic hypotensive episodes had higher rates of HF readmissions ( P = .01) and the composite end point of all-cause mortality and all-cause readmissions ( P = .03). Conclusions Additional neurohumoral modulating agents could produce significant increases in 24-hour hypotension burden despite reassuring clinic blood pressure readings. The burden of diastolic hypotension is independently predictive of HF readmissions and the composite end point of all-cause mortality and emergency readmissions.

A device is not a drug

A device is not a drug

Improving clinical outcomes with drug treatment in heart failure: what have trials taught?

Pharmacologic clinical trials in heart failure (HF) have provided substantial advances in effective treatment of this condition, moving us from our focus on short-term symptom relief to an expectation of substantial improvement in long-term clinical outcomes for our patients. Based on an appreciation of the importance of neurohormonal activation in the pathophysiology of HF, clinical trials have demonstrated the value of angiotensin-converting enzyme (ACE) inhibitors and β-blockers in impeding the progression of HF and in reducing morbidity and mortality for patients with this condition. Clinical trials have further demonstrated the benefits of digoxin in improving symptoms and reducing hospitalization frequency, as well as in aldosterone blockade, at least in patients with severe symptoms. Given the ethical imperative to treat with ACE inhibitors, the angiotensin receptor antagonists have been difficult to study; nevertheless, their value is becoming increasingly clear, particularly for patients intolerant of ACE inhibitors. Trials with several classes of newer agents—cytokine antagonists, endothelin receptor blockers, and vasopeptidase inhibitors—have recently yielded disappointing results. Early results with vasopressin receptor antagonists provide some promise of long-term benefit. Clinical trials have provided significant treatment advances; ongoing and future trials will demonstrate the degree to which we can improve on what we have achieved to date with pharmacologic treatments.

Brain natriuretic peptide-guided therapy for heart failure

The drug treatment of heart failure, once simple, has become complex. Apart from a loop diuretic and digoxin, most patients should now be receiving an angiotensin-converting enzyme inhibitor (or angiotensin II receptor blocker), a beta-blocker and spironolactone. Newer drugs, such as endothelin-receptor antagonists and combined blockers of converting-enzyme and neutral endopeptidase, might soon become available. When to introduce these drugs and what dose is optimal for any individual, are questions that currently vex clinicians. We proposed that plasma levels of the cardiac hormone brain natriuretic peptide (BNP, or better, its 1-76 amino-acid N-terminal fragment, N-BNP), would provide an objective index for guiding drug treatment in patients with established, stable cardiac failure. In a pilot study, 69 patients were randomized to drug treatment based on clinical criteria, or based on plasma levels of N-BNP. After a median follow-up of 9.6 months, those in the N-BNP group had fewer clinical end-points than those in the group managed by clinical criteria alone (19 vs 54; P= 0.02). These preliminary data encourage the concept that the increasingly complex pharmacotherapy for heart failure, both chronic (as in this trial) and acute, might best be guided by an objective measure such as plasma levels of BNP or N-BNP.

Gender and drug treatment as determinants of mortality in a cohort of heart failure patients.

We assessed gender differences in the risk of mortality in heart failure (HF) patients and evaluated the association between HF drug treatment and mortality. We identified a cohort of 820 patients with newly diagnosed HF in 1996 in UK general practices. The diagnosis of HF was confirmed by the general practitioner. Fifty per cent were females and 27% were less than 70 years old. During a mean follow-up of 2 years, 172 patients died. We used computerized records to assess risk factors and drugs prescribed as treatment. The information on severity was assessed through a questionnaire. We performed a nested case-control analysis, and observed that men had twice the risk of dying than females, however the effect of age on mortality was stronger in females than males. We found a similar interaction between HF severity and sex. Data on use of some cardiovascular drugs such as diuretics, beta-blockers ACE-inhibitors and calcium channel blockers were suggestive of a reduced mortality risk. Current use of nitrates and glycosides carried an increased risk. Older age, male sex and severity of HF were the main predictors of mortality among HF patients. Long-term use of beta-blockers was associated with a significantly reduced risk of mortality.

Dilemmas in the drug treatment of heart failure

The clinical outcomes for patients in chronic heart failure can be improved by optimising drug and

Drug treatment of heart failure - Do nursing-home residents deserve better?

Objective - To describe and assess drug treatment of heart failure (HF) in nursing-home residents. Design - Descriptive cross-sectional study. Individual patient information was obtained from the medical records and drug-dispensing cards. Setting - Nursing homes in Bergen, Norway. Main outcome measures - Demographic data, diagnostic data (main diagnoses, diagnostic indications for the drugs used), medications (drugs, dosage and duration of use). Results - Data were gathered from 23 of 27 obtainable institutions representing 1552 residents (86% of the Bergen nursing-home population); 469 (30%) of the residents used drugs for HF, the majority of whom (293 patients) were treated with furosemide only. Supplementary angiotensin-converting enzyme (ACE) in-hibitors (predominantly in sub-target doses) were provided to 17% of the HF patients. About one out of four used drug combinations which we considered to be potentially harmful for HF patients. Conclusions ? ACE inhibitors are probably under-utilised for HF in nursing-home residents. Potentially harmful drug combinations commonly occur. Both diagnosis and drug treatment for HF should be challenged in the nursing-home setting.

Etiology and response to drug treatment in heart failure

Clinical trials in heart failure (HF) tend to randomize patients according to demographic characteristics and severity of left ventricular dysfunction, without taking account of the precise diagnosis. This article reviews results from recent trials suggesting that the etiology of HF, and particularly whether it is ischemic or nonischemic, may influence the long-term prognosis and the response to treatment. Some studies, but not all, suggest that nonischemic HF has a better prognosis than ischemic HF. The data on the benefits of angiotensin-converting enzyme inhibitors in ischemic versus nonischemic HF are conflicting. Carvedilol, and recently, bisoprolol have been shown to reduce mortality in ischemic and non-ischemic HF, whereas metoprolol has, to date, improved prognosis only in dilated cardiomyopathy. Better responses to digoxin, amlodipine and amiodarone have been reported in non-ischemic HF. There is at present no clear explanation for the apparent therapeutic differences between ischemic and nonischemic HF. Absence of a rigorous definition of “nonischemic HF” in many studies makes interpretation of the results difficult. Further studies to clarify the effects of etiology of HF on the response to treatment could be particularly important for preventing progression to more advanced stages, in which any type of drug therapy may have limited value in prolonging survival. An individualized therapeutic approach, based on etiology of HF and possibly other factors such as plasma drug levels or the levels of neurohormones, could result in major progress in treating HF patients.

Cardiac troponin T isoform expression correlates with pathophysiological descriptors in patients who underwent corrective surgery for congenital heart disease.

This study examined cardiac troponin T (cTnT) isoform expression in patients who had undergone surgery at Duke University Medical Center (Durham, NC) between December 1, 1993, and January 31, 1995, to correct congenital heart defects. The human heart expresses four cTnT isoforms (cTnT1 through cTnT4) whose sequence differences result from combinatorial alternative splicing of two exons. We have previously shown that cTnT4 is expressed at higher levels in severely failing hearts from transplant patients. In this study, we tested the hypothesis that congenital heart defects that have a more negative effect on myocardial function increase cTnT4 expression. We used the presence or absence of drug treatment for heart failure or congested circulation before surgery and the duration of inotropic support after corrective surgery as indicators of the pathophysiological state of the heart just before surgery. Right atrial appendage tissue was collected from 34 patients, 6 days to 35 years old (median age, 3.4 months). The amounts of the cTnT1 through cTnT4 isoforms, measured as a percentage of total cTnT, were determined from Western blots probed with MAb13-11, a cTnT-specific monoclonal antibody. We found that cTnT4 expression correlated positively with the duration of inotropic support and was higher in patients who received drug treatment before surgery than in those who did not. Furthermore, we found that the percent of cTnT4 was significantly higher in hearts with congenital defects that caused congestive failure than in hearts with tetralogy of Fallot. These findings suggest that in patients with congenital cardiac defects, cTnT4 expression is modulated by heart failure and is increased in hearts that are more hemodynamically stressed.

P1-200 - Effects of OPC-18790 in combination with drugs for heart failure treatment in anesthetized dogs

P1-200 - Effects of OPC-18790 in combination with drugs for heart failure treatment in anesthetized dogs

The management of heart failure: A matter of definition?

The term heart failure has become a label for more than one clinical entity. For many years heart failure has been used to denote patients with various heart diseases who have begun to suffer from fluid retention, pulmonary venous hypertension, or systemic venous hypertension, either alone or in combination. More recently, the term heart failure has been applied to the combination of effort intolerance and reduced left ventricular contractility due to ischemic heart disease or other myocardial disease. Comparison of the results of epidemiological studies and therapeutic trials is complicated by variation in the composition of the patient populations selected for study. Drug treatment of heart failure remains fairly empirical. Distinction should be made between immediate or prognostic benefits related to the etiological diagnosis, and benefits related specifically to prevention and relief of, for example, fluid retention, rhythm disturbances, or ventricular hypertrophy. The response of individual patients to several forms of drug treatment, including digoxin, ACE inhibitors, and beta-blockade, is unpredictable. Prospective identification of patients liable to respond well to these drugs is not yet possible, but would greatly assist the choice of treatment. At present, trial of therapy is required in each patient to establish benefit and to avoid long-term treatment of nonresponders.

Drug treatment of heart failure

In my early years in Lancaster I remember my senior colleague Dr W J Hay asking whether or not digoxin and diuretics remained routine treatment for congestive cardiac failure; in fact there had been little change, in that digoxin was being used less often. Recently there have been three important alterations in management. These are:-( 1) improved diagnostic capabilities,(2) the introduction of new drugs, particularly ACE inhibitors, and(3) the reappraisal of older drugs including hydralazine, nitrates and digitalis. Finally we have seen the establishment of cardiac transplantation, various attempts at mechanical cardiac assistance and cardiomyoplasty which are out ide the scope of this article but which need to be borne in mind when drugs fail.

Physiological changes due to age. Implications for drug therapy of congestive heart failure.

The segment of the population considered to be 'elderly' is consistently growing. At the same time, the number of patients with congestive heart failure continues to grow. Therefore, it is important to consider whether older patients with congestive heart failure have characteristics that identify an aging effect in addition to the obvious abnormalities produced by heart failure. Furthermore, it is important to determine the relevance of these abnormalities to the use of pharmacological therapy. Within a population of 128 consecutive heart failure patients, age-related increases of systemic vascular resistance, changes in baroreceptor responses, and increases of plasma noradrenaline (norepinephrine) levels were identified. In addition, an age-related reduction of renal function was clearly evident in patients > 65 years of age. These changes affect the use of digoxin, diuretics and angiotensin converting enzyme (ACE) inhibitors. Most notably, marked reduction of renal function in such patients must be considered in the drug treatment of heart failure.

Effect of Enalapril on Plasma Atrial Natriuretic Peptide in Late Recovery Phase of Acute Myocardial Infarction

A 12 week randomised, double blind, placebo controlled study on the effect of enalapril (5-20 mg daily) on the concentration of plasma atrial natriuretic peptide level and activity of the sympathetic nervous system and renin angiotensin system was done on 27 patients who had suffered an uncomplicated acute myocardial infarction two to six months earlier. None of our patients needed drug treatment for heart failure, but their exercise capacity was markedly limited. Plasma neurohormone concentrations at baseline and after 12 weeks of treatment were also compared with those of healthy controls. Concentrations of plasma atrial natriuretic peptide concentrations remained high throughout the study in those patients on beta-blockers. Enalapril treatment had no definite effect on the concentrations of plasma atrial natriuretic peptide or other neurohormone.

Drug Treatment of Heart Failure

Drug Treatment of Heart Failure