Pharmacotherapy Of Chronic Heart Failure Research Articles

A Review of Contemporary and Future Pharmacotherapy for Chronic Heart Failure in Children.

This review delves into the most recent therapeutic approaches for pediatric chronic heart failure (HF) as proposed by the International Society for Heart and Lung Transplantation (ISHLT), which are not yet publicly available. The guideline proposes an exhaustive overview of the evolving pharmacological strategies that are transforming the management of HF in the pediatric population. The ISHLT guidelines recognize the scarcity of randomized clinical trials in children, leading to a predominance of consensus-based recommendations, designated as Level C evidence. This review article aims to shed light on the significant paradigm shifts in the proposed 2024 ISHLT guidelines for pediatric HF and their clinical ramifications for pediatric cardiology practitioners. Noteworthy advancements in the updated proposed guidelines include the endorsement of angiotensin receptor-neprilysin inhibitors (ARNIs), sodium-glucose cotransporter 2 inhibitors (SGLT2is), and soluble guanylate cyclase (sGC) stimulators for treating chronic HF with reduced ejection fraction (HFrEF) in children. These cutting-edge treatments show potential for enhancing outcomes in pediatric HFrEF. Nonetheless, the challenge persists in validating the efficacy of therapies proven in adult HFrEF for the pediatric cohort. Furthermore, the proposed ISHLT guidelines address the pharmacological management of chronic HF with preserved ejection fraction (HFpEF) in children, marking a significant step forward in pediatric HF care. This review also discusses the future HF drugs in the pipeline, their mechanism of actions, potential uses, and side effects.

The Impact of Pharmacotherapy for Heart Failure on Oxidative Stress-Role of New Drugs, Flozins.

Heart failure (HF) is a multifactorial clinical syndrome involving many complex processes. The causes may be related to abnormal heart structure and/or function. Changes in the renin-angiotensin-aldosterone system, the sympathetic nervous system, and the natriuretic peptide system are important in the pathophysiology of HF. Dysregulation or overexpression of these processes leads to changes in cardiac preload and afterload, changes in the vascular system, peripheral vascular dysfunction and remodeling, and endothelial dysfunction. One of the important factors responsible for the development of heart failure at the cellular level is oxidative stress. This condition leads to deleterious cellular effects as increased levels of free radicals gradually disrupt the state of equilibrium, and, as a consequence, the internal antioxidant defense system is damaged. This review focuses on pharmacotherapy for chronic heart failure with regard to oxidation-reduction metabolism, with special attention paid to the latest group of drugs, SGLT2 inhibitors-an integral part of HF treatment. These drugs have been shown to have beneficial effects by protecting the antioxidant system at the cellular level.

Dosing of basic pharmacotherapy and its effect on the prognosis of patients hospitalized for heart failure.

We analyzed the prescription and dosage of essential pharmacotherapy in chronic heart failure (HF) at the time of discharge from the hospitalization for cardiac decompensation and how it may have influenced the prognosis of the patients. We followed 4097 patients [mean age 70.7, 60.2% males] hospitalized for HF between 2010 and 2020. The vital status we ascertained from the population registry, other circumstances from the hospital information system. The prescription of beta-blockers (BB) was 77.5% (or only 60.8% of BB with evidence in HF), 79% of renin-angiotensin system (RAS) blockers, and 45.3% of mineralocorticoid receptor antagonists (MRA). Almost 87% of patients were treated with furosemide at the time of discharge, while only ≈53% of patients with ischemic etiology of HF took a statin. The highesttarget dose of BB was recommended in ≈11% of patients, RAS blockers in ≈ 24%, and MRA in ≈ 12% of patients. In patients with concomitant renal insufficiency, the prescription of BB and MRA was generally less frequent and on a significantly lower dosage. In contrast, the opposite was true for the RAS blocker (however statistically insignificant). In patients with EF ≤ 40%, the prescription of BB and RAS blockers were more frequent but in a significantly lower dosage. On the contrary, MRAs were recommended in these patients more often and in higher doses. In terms of mortality risk, patients treated only with a reduced dose of RAS blockers showed a 77% higher risk of death within one year (or 42% within five years). A significant relationship was also found between mortality and the recommended dose of furosemide. The prescription and dosage of essential pharmacotherapy are far from optimal, and in the case of RAS blockers, this affected the patient's prognosis as well.

Combined Neuro-Humoral Modulation and Outcomes in Patients with Chronic Heart Failure and Mildly Reduced or Preserved Ejection Fraction.

Pharmacotherapy of chronic heart failure with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF) remains challenging. We aimed to assess whether combined neuro-humoral modulation (NHM) (renin-angiotensin system inhibitors, betablockers, mineralocorticoid receptor antagonists) was differentially associated with outcome according to phenotype and age groups. Between 1999 and 2018 we recruited in a nationwide cardiology registry 4707 patients (HFmrEF n = 2298, HFpEF n = 2409) from three age groups: <65, 65-79 and 80+ years old. We analyzed clinical characteristics and 1 year all-cause mortality/cardiovascular hospitalization according to none/single, any double, or triple NHM. Prescription rates of no/single and triple NHM were 25.1% and 26.7% for HFmrEF; 36.5% and 17.9% for HFpEF patients, respectively. Older age was associated with higher prescription of no/single NHM in HFmrEF (ptrend = 0.001); the reverse was observed among HFpEF (ptrend = 0.005). Triple NHM increased over time in both phenotypes (all p for trend < 0.0001). Compared to no/single NHM, triple, but not double, NHM was associated with better outcomes in both HFmrEF (HR 0.700, 95%CI 0.505-0.969, p = 0.032) and HFpEF (HR 0.700, 95%CI 0.499-0.983, p = 0.039), with no interaction between NHM treatment and age groups (p = 0.58, p = 0.80, respectively). In a cardiology setting, among HF outpatients with EF > 40%, triple NHM treatment increased over time and was associated with better patient outcomes.

Peculiarities of pharmacotherapy of chronic heart failure with retained left ventricular efficiency and associated atrial fibrilation depending on the method of heart rhythm control

Introduction. Only small studies in selected centers have examined the effect of rhythm control strategy, including catheter ablation, on major cardiovascular events, mortality in patients with long-term atrial fibrillation and concomitant chronic heart failure with preserved left ventricular ejection fraction and features of pharmacotherapy. The aim. To study the peculiarities of pharmacotherapy in patients with heart failure with preserved left ventricular ejection fraction and concomitant atrial fibrillation over a long period of observation, depending on the implementation of a rhythm control strategy: radiofrequency ablation or pharmacotherapy and their impact on endpoints. Materials and Methods. The study included 194 patients with a mean age of 59.3 ± 8.5 years with atrial fibrillation and concomitant heart failure with preserved left ventricular ejection fraction I–III of the NYHA functional class. Patients were divided into 2 groups: 136 patients who underwent radiofrequency ablation, and 58 patients in the control group who did not undergo intervention and continued antiarrhythmic pharmacotherapy. The patients were compared according to the main clinical and demographic indicators. An assessment was made of the characteristics of pharmacotherapy and different stages of observation by group and its impact on endpoints. Results. In the control group, the use of antiarrhythmic drugs other than amiodarone and oral anticoagulants at the baseline of the study was associated with the primary endpoint. The chance of its occurrence was 3.9 times higher among patients taking other antiarrhythmic drugs (odds ratio–3.949, 95 % confidence interval 1.198–13.013) and 1.8 times lower among patients taking anticoagulants (odds ratio - 0.556, 95 % confidence interval 0.399–0.965). In the ablation group, the chance of a primary endpoint event occurring was 3.1 times higher among patients taking diuretics at 2-year follow-up (odds ratio –3.130, 95 % confidence interval 1.111–8.824), and beta-blockers were associated with 3.4 times lower chance of these events (odds ratio – 0.296, 95 % confidence interval 0.128–0.688). In the ablation group, there was a statistically significant decrease in the percentage of patients requiring diuretics 2 years after inclusion in the study compared with the 3-month stage (p < 0.001) and the inclusion stage (p < 0.001). Conclusions. Long-term use of beta-blockers after intervention is associated with a reduced risk of primary endpoint events in the ablation group. Taking diuretics, beta-adrenergic receptors, and renin-angiotensin-aldosterone system inhibitors during the first 3 months after the intervention reduces the risk of atrial fibrillation recurrence in the long-term follow-up period in the ablation group.

Chronic Heart Failure Pharmacotherapy is Still Developing

Chronic Heart Failure Pharmacotherapy is Still Developing

The contribution of individual mental health and socioeconomic status to the evolution of elderly patients with chronic heart failure.

The purpose of this article is to assess the impact of comorbid depression on the outcome of elderly patients diagnosed with chronic heart failure (CHF). We conducted a prospective analysis of the outcomes of 251 patients, hospitalized throughout 2019 for an exacerbation of CHF. The sample was divided into two groups: group A - 153 patients with major depressive disorder (MDD); group B - 98 patients without clinical depression. We analyzed the associations between socioeconomic status (SES) and the severity of depressive symptoms, pharmacotherapy, readmission, and mortality rates within 30 days and at one year. We classified patients' SES according to residence, income, education level, and family support. Quality of Life (QL) total scores were also assessed. The severity of mental health complaints was evaluated using the Montgomery-Asberg Depression Ratings (MADRS) scale; individual somatic evaluation included the analysis of the alteration of the left ventricular ejection fraction (LVEF), as well as details regarding pharmacotherapy with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers (BB). The patient sample appeared uniform in terms of SES and CHF pharmacotherapy. The main differences were the presence of comorbid MDD, with 60.91% of patients having clinical depression. These patients also reported a lower QL, reduced LVEF, more frequent, and extended hospitalizations with an overall higher one-year mortality than patients without MDD. Although depression is considered a risk factor for adverse outcomes in older adults with CHF, in our research, its impact was significantly associated with a reduced QL, but the association with a lower SES was inconclusive. MDD is a frequent comorbidity in patients with CHF, and is associated with a reduced LVEF and QL. Our results showed that, despite a similar therapeutic regimen, patients with comorbid MDD required more frequent, prolonged admissions and higher one-year mortality rates than those without MDD.

Catechin for the pharmacotherapy of chronic heart failure

Heart failure is an end stage of the process of cardiovascular diseases.It is a condition of the heavy preload and afterload of heart, where it was associated with a progressive dysfunction of cardiac ejection.It can cause the systemic (pulmonary) congestion and the perfusion deficiency.For chronic heart failure in children, it could be resulted from some congenital and obtained heart diseases.The clinical pharmacotherapy strategy is mainly focused on the symptoms, yet which could not improve the prognosis and quality of life.Current studies have demonstrated catechins with a variety of physiological functions that may be responsible for clinically beneficial effects.It has been identified as a protective role in cardiovascular diseases with an unclear mechanism.Hence, this paper reviewed the mechanism of catechins in chronic heart failure in children. Key words: Children; Chronic heart failure; Catechin; Mechanism

Новые возможности фармакотерапии у пациентов, страдающих хронической сердечной недостаточностью

In this article we have described clinical pharmacology and data of clinical studies of an innovational drug valsartan + sacubitril in patients with chronic heart failure (CHF). The use of supramolecular complex valsartan + sacubitril allows to elevate quality of life and improve prognosis of patients with CHF. High efficacy of valsartan+sacubitril relative to impact on composite primary end-point (cardiovascular death + hospitalization due to CHF) was demonstrated in the clinical trial PARADIGM-HF in which it was compared with angiotensin converting enzyme inhibitor enalapril. Advantages of the use of valsartan + sacubitril for the budget were demonstrated in pharmacoeconomic studies. These advantages are maximally realized at long-term administration. Cost-efficacy of the use of valsartan+sacubitril in pharmacotherapy of CHF is comparable with that of statins in the treatment of ischemic heart disease or implantation of a cardioverter-defibrillator in prevention of sudden cardiac death. Thus, introduction of the drug into practice can be expected to reduce budget expenditures.

Особенности фармакотерапии пациентов с хронической сердечной недостаточностью и сохраненной фракцией выброса левого желудочка

The review is devoted to pharmacotherapy of chronic heart failure (CHF) with preserved left ventricular ejection fraction. In this review we discuss data of meta-analyzes of randomized clinical trials and observational studies, as well as the indications for use of inhibitors of the renin-angiotensin-aldosterone system, β-blockers, and antagonists of mineralocorticoid receptors in these patients in current clinical guidelines. New approaches to therapy of CHF from the perspective of influence on myocardial fibrosis are considered in this review.

The role of galectin-3 in the diagnosis and control of the effectiveness of pharmacotherapy of chronic heart failure

Relevance. At present, it is urgent to develop new biomarkers that can serve as a tool for early diagnosis of the disease in order to select pharmacotherapy and further monitor its effectiveness. The goal is to evaluate the clinical value of the definition of galectin-3 in patients with chronic heart failure (CHF). Materials and methods. The study included 53 patients (31 women, 22 men) with CHF II-III functional class (FC) of the New York Heart Association (NYHA). The mean age of the patients was 71 years (95% confidence interval 68.99-74.37). A group of patients with NYHA FCh II CHF made up 14 people, a group of patients with NYHA-39 CHF III FC. The median of the initial level of the N-terminal brain natriuretic peptide (NT-proBNP) was 65.7 pmol/L, the median of the initial level of galectin-3 - 8.37 pmol/l. Results. The relationship of increased level of galectin-3 with reduced ejection fraction,% (r=-0.26, p=0.04), increased creatinine level (r=0.26, p=0.04) and increased level of NT-proBNP plasma (r=0.3, p=0.02). With other clinical indicators, such as systolic and diastolic blood pressure, heart rate, body mass index, 6-minute walk test, left ventricular mass index, glucose level, total cholesterol, glomerular filtration rate, no statistically significant association was found. A moderate correlation was obtained between the levels of NT-proBNP and galectin-3 plasma (r=0.3, p=0.02). Reduction in the level of galectin-3 after the treatment was detected in 84.3% of patients. The conclusion. Galectin-3 can serve as an additional diagnostic biomarker of CHF.

Роль антагонистов минералокортикоидных рецепторов в фармакотерапии хронической сердечной недостаточности

Роль антагонистов минералокортикоидных рецепторов в фармакотерапии хронической сердечной недостаточности

Роль галектина-3 в диагностике и контроле эффективности фармакотерапии хронической сердечной недостаточности

Роль галектина-3 в диагностике и контроле эффективности фармакотерапии хронической сердечной недостаточности

Pharmacology of heart failure: From basic science to novel therapies.

Chronic heart failure is one of the leading causes for hospitalization in the United States and Europe, and is accompanied by high mortality. Current pharmacological therapy of chronic heart failure with reduced ejection fraction is largely based on compounds that inhibit the detrimental action of the adrenergic and the renin-angiotensin-aldosterone systems on the heart. More than one decade after spironolactone, two novel therapeutic principles have been added to the very recently released guidelines on heart failure therapy: the HCN-channel inhibitor ivabradine and the combined angiotensin and neprilysin inhibitor valsartan/sacubitril. New compounds that are in phase II or III clinical evaluation include novel non-steroidal mineralocorticoid receptor antagonists, guanylate cyclase activators or myosine activators. A variety of novel candidate targets have been identified and the availability of gene transfer has just begun to accelerate translation from basic science to clinical application. This review provides an overview of current pharmacology and pharmacotherapy in chronic heart failure at three stages: the updated clinical guidelines of the American Heart Association and the European Society of Cardiology, new drugs which are in clinical development, and finally innovative drug targets and their mechanisms in heart failure which are emerging from preclinical studies will be discussed.

Development and optimization of pharmacotherapy for chronic heart failure with regards to kidney functional state

Development and optimization of pharmacotherapy for chronic heart failure with regards to kidney functional state

Development and optimization of pharmacotherapy for chronic heart failure with regards to kidney functional state

Development and optimization of pharmacotherapy for chronic heart failure with regards to kidney functional state

General practitioners' adherence to chronic heart failure guidelines regarding medication: the GP-HF study.

The adherence to the guidelines for pharmacotherapy of chronic heart failure (HF)-patients improves prognosis. Although general practitioners (GPs) treat the majority of HF-patients, information about GPs' current guideline adherence and their typical prescription rationales is sparse. A three-stage study design was employed. In Stage I, 206 patient records from 15 randomly chosen GP practices were analysed; 76% of patients were prescribed ACE-inhibitors or angiotensin receptor blockers (ACEIs/ARBs), 73% beta blocker (BBs), but only 18% mineralocorticoid receptor antagonists (MRAs). ACEI doses were at 62% of the guideline recommended target doses, BBs at 46%, while MRAs were sufficiently highly dosed. The guideline adherence indicator (GAI-3) was only 22%. In Stage II, GPs in all 15 practices were interviewed, and health record documentation deficits and patients' contraindications were taken into account. This increased the percentage of patients correctly prescribed ACEIs/ARBs to 87%, BBs to 84% and GAI-3 to 56%. MRAs exhibited the most frequent contraindications, but remained underprescribed. Many GPs seemed not to be aware of the therapeutic value of MRAs or the need to reach target doses of the indicated drug classes. Patients-interviewed in Stage III-reported good tolerability of HF-drugs and generally good compliance, although 11% discontinued HF-medication on their own. Guideline adherence of GPs was higher than expected from literature and might be further improved by highlighting MRAs as the third prognostically relevant drug class beside ACEIs/ARBs and BBs and stronger emphasis on target doses.

Plasma Neprilysin Concentrations: A New Prognostic Marker in Heart Failure?

Neprilysin, also known as neutral endopeptidase (NEP), endopeptidase 24.11, CD10, enkephalinase, and common acute lymphoblastic leukemia antigen (CALLA), is a membrane-bound metalloendopeptidase (EC 3.4.24.11) that has recently sprung to renewed prominence as a target in cardiovascular therapeutics. Numbered among the many substrates to NEP are multiple vasoactive peptides, including the cardiac natriuretic peptides, with important roles in regulating pressure and volume status in health and disease. In the 1990s, NEP inhibitors were combined with angiotensin converting enzyme inhibitor (ACEI) therapy with the hope of adding the expected multifaceted benefits of enhanced plasma and tissue natriuretic peptide levels to the proven benefits of ACEI-related suppression of adverse renin-angiotensin-aldosterone system activation. After initial promise from trials in hypertension and heart failure, drug development was halted due to an unacceptable incidence of angioneurotic edema. The current renewed interest in NEP reflects the recent success of a new combination, that of inhibition of NEP plus angiotensin II type 1 receptor blockade. The PARADIGM trial tested the NEP inhibitor sacubitril combined with the angiotensin receptor blocker valsartan (LCZ696) in chronic heart failure with reduced ejection fraction. The new treatment was significantly beneficial with respect to all important clinical endpoints and was associated with no excess of important adverse effects and in fact caused less renal failure and hyperkalemia than established evidence-based treatment with the ACEI enalapril. The results point to this strategy being the greatest advance in the pharmacotherapy of chronic heart failure in the last 20 years. In addition to its widespread tissue-based, membrane-bound form, NEP exists in a circulating nonbound form that retains catalytic activity. In the article published in Revista Espanola de Cardiologia, Bayes-Genis et al build on previous work to confirm their original finding that plasma NEP concentrations have

Pathogenetic treatment of chronic heart failure: the role of torasemide

The article discusses the torasemide pharmacokinetic characteristics which are favourably different from furosemide characteristics. We paid attention to the fact that torasemide had anti-aldosteronic and antifibrotic effects; all these characteristics were alien to other diuretics nature. The results of clinical studies showed torasemide ability to prevent the development and reverse myocardial fibrosis. Taking into account modern representations concerning the pathogenesis of chronic heart failure, in particular the role of diastolic dysfunction in developing haemodynamic compromise, we substantiated torasemide application as a part of complex pharmacotherapy of chronic heart failure in patients with elevated left ventricular filling pressure before the appearance of clinical manifestations of stagnation.

Патогенетическая терапия хронической сердечной недостаточности: позиция торасемида

The article discusses the torasemide pharmacokinetic characteristics which are favourably different from furosemide characteristics. We paid attention to the fact that torasemide had anti-aldosteronic and antifibrotic effects; all these characteristics were alien to other diuretics nature. The results of clinical studies showed torasemide ability to prevent the development and reverse myocardial fibrosis. Taking into account modern representations concerning the pathogenesis of chronic heart failure, in particular the role of diastolic dysfunction in developing haemodynamic compromise, we substantiated torasemide application as a part of complex pharmacotherapy of chronic heart failure in patients with elevated left ventricular filling pressure before the appearance of clinical manifestations of stagnation.