Drug Therapy For Heart Failure Research Articles

Predictors of Unfavorable Prognosis in Patients with Heart Failure After Cardioverter-Defibrillator Implantation According to the Prospective Part of the Kuzbass Registry.

Identification of clinical and instrumental predictors for non-arrhythmic death in patients with heart failure (HF) and implantable cardioverter-defibrillator (ICD). Through a telephone survey and examination of medical records from hospital and polyclinic databases, data were obtained on the alive/dead status and causes of death for 260 patients with heart failure (HF) and ICD included in the Kuzbass Registry of Patients with ICD. The follow-up period was 1.5 years. Clinical and instrumental parameters entered into the registry before the ICD implantation were included in a univariate and multivariate step-by-step analysis using the logistic (for qualitative variables) and linear (for quantitative variables) regression with calculation of regression coefficients and construction of a prognostic regression model. The quality of the created model was assessed using a ROC analysis. During the observation period, 54 (20.8%) patients died. In 21 (38.8%) patients, death occurred in the hospital and was caused by acute decompensated heart failure in 15 (71.4%) patients, myocardial infarction in 3 (14.3%) patients, stroke in 1 (4.7%) patient, and pneumonia in 2 (9.5%) patients. 33 (61.2%) patients died outside the hospital; the cause of death was stated as the underlying disease associated with acute decompensated heart failure: in 9 (27.2%) patients, dilated cardiomyopathy; in 1 (3.0%) patient, rheumatic mitral disease; and in 23 (69.7%) patients, ischemic cardiomyopathy. According to the univariate regression model, the risk of death in the long-term period was increased by the QT interval prolongation (U 2.41, p = 0.0161); elevated pulmonary artery systolic pressure (U 4.30, p=0.0000) and increased left atrial size according to echocardiography (U 2.98, p=0.0029); stage IIB HF (OR 2.41; 95% CI: 1.26-4.6), NYHA III-IV (OR 3.03; 95% CI: 1.58-5.81); chronic obstructive pulmonary disease (OR 5.24; 95% CI: 2.04-13.45); and lack of optimal drug therapy (ODT) for HF before ICD implantation (OR 2.41; 95% CI: 1.29-4.49). The multivariate analysis identified the most significant factors included in the prognostic regression model: pulmonary artery systolic pressure above 45 mm Hg, social status, chronic obstructive pulmonary disease, and lack of ODT for HF. To ensure a maximum benefit from ICD, the factors that increase the likelihood of non-arrhythmic death should be considered before making a decision on ICD implantation. Particular attention should be paid to mandatory ODT for HF as the main modifiable risk factor for unfavorable prognosis.

Optimisation of conservative treatment of patients with severe heart failure by using hemosorption

Background. Heart failure (HF) is a complex cardiac pathology that is the main cause of hospitalisation among adults and is characterised by a high mortality. Dilated cardiomyopathy (DCM) is the most common cause of HF, and it can be fatal within a few years after the first symptoms appear. Many patients with HF remain refractory to medical therapy, despite its constant development and improvement. The study aims to compare the effectiveness of conservative treatment of patients with severe HF that occurred on the background of DCM using drug therapy and its combination with a course of hemosorption (HS). Materials and methods. We analysed treatment outcomes in 30 patients with severe HF against DCM (New York Heart Association class III–V, left ventricular ejection fraction (LV EF) < 30 %). Patients in group 1 (n = 13; N-terminal fragment of brain natriuretic peptide precursor (NT-pro BNP) 4,546.23 ± ± 3,265.01 pg/ml; LV EF 16.77 ± 2.92 %; LV end-diastolic volume (EDV) 261.31 ± 60.60 ml, LV end-systolic volume (ESV) 214.85 ± 49.44 ml) received drug therapy according to local protocols. In group 2 (n = 17; NT-pro BNP 3,974.49 ± 3,550.17 pg/ml; LV EF 18.18 ± 4.36 %; LV EDV 261.12 ± 79.96 ml, LV ESV 212.06 ± 71.67 ml), medical treatment was supplemented with a course of 3 HS procedures using granular deligandizing hemosorbent. Results. Patients in both study groups noted an improvement in well-being and a decrease in the severity of symptoms. The level of NT-pro BNP decreased to 2,609.92 ± 1,465.14 pg/ml (p < 0.01) in group 1 and to 975.35 ± 511.55 pg/ml (p < 0.05) in group 2. LV EF increased to 22.77 ± 4.69 % and 26.76 ± 5.02 %, respectively, in the groups (p < 0.01). In patients of group 1, LV EDV and LV ESV changed to 262.22 ± 40.92 ml and 211.33 ± 35.22 ml, respectively. In group 2, there was a significant decrease in LV EDV to 228.94 ± 73.16 ml and LV ESV to 170.88 ± 60.28 ml (p < 0.01). Conclusions. The use of HS in combination with drug therapy for severe HF on the background of DCM improves the clinical status of patients and LV systolic function.

X-linked Emery-Dreifuss muscular dystrophy is associated with a high risk of malignant ventricular arrhythmia

Abstract Background Emery-Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (X-linked) and LMNA (autosomal dominant). LMNA variants are known to cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA) [1], but the risk of cardiac complications in EMD variant-carriers is unknown. Purpose To determine the incidence of MVA and ESHF in EMD variant-carriers. Methods Consecutively referred individuals carrying EMD variants were recruited from 12 cardiomyopathy units in Europe and the USA. The incidence of MVA and ESHF in male and female EMD variant-carriers was determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDcardiac) were compared to consecutively recruited male LMNA variant-carriers with a cardiac phenotype (LMNAcardiac). Results Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers (mean (SD) ages 33.4 (13.3) and 43.3 (16.8) years, respectively; Table 1). Nine (23.6%) males developed MVA and five (13.2%) developed ESHF during a median follow-up time of 65.0 [24.3, 109.5] months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a mild cardiac phenotype at a median [IQR] age of 58.6 [53.2, 60.4] years. Incidence rates for MVA were similar for EMDcardiac and LMNAcardiac (4.8 versus 6.6 per hundred person-years, respectively; log-rank test p = 0.49; Figure 1). Incidence rates for ESHF were 2.4 per hundred person-years for EMDcardiac and 5.9 per hundred person-years for LMNAcardiac (log-rank test p = 0.09; Figure 1). Conclusions Male EMD variant-carriers have a high risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. These data suggest that early ICD implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease.Table 1Figure 1

Emery-Dreifuss muscular dystrophy Type 1 is associated with a high risk of malignant ventricular arrhythmias and end-stage heart failure.

Emery-Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (EDMD1) and LMNA (EDMD2). Cardiac conduction defects and atrial arrhythmia are common to both, but LMNA variants also cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA). This study aimed to better characterize the cardiac complications of EMD variants. Consecutively referred EMD variant-carriers were retrospectively recruited from 12 international cardiomyopathy units. MVA and ESHF incidences in male and female variant-carriers were determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDCARDIAC) were compared with consecutively recruited male LMNA variant-carriers with a cardiac phenotype at baseline (LMNACARDIAC). Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers [mean (SD) ages 33.4 (13.3) and 43.3 (16.8) years, respectively]. Nine (23.7%) males developed MVA and five (13.2%) developed ESHF during a median (inter-quartile range) follow-up of 65.0 (24.3-109.5) months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a cardiac phenotype at a median (inter-quartile range) age of 58.6 (53.2-60.4) years. Incidence rates for MVA were similar for EMDCARDIAC and LMNACARDIAC (4.8 and 6.6 per 100 person-years, respectively; log-rank P = .49). Incidence rates for ESHF were 2.4 and 5.9 per 100 person-years for EMDCARDIAC and LMNACARDIAC, respectively (log-rank P = .09). Male EMD variant-carriers have a risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. Early implantable cardioverter defibrillator implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease.

Analysis of methods for heart failure

Heart Failure (HF) is one of the major causes of death from various heart diseases and is a common complex clinical syndrome. HF has a high incidence and its 5-year survival rate is similar to that of patients with malignant tumors, which has a serious impact on the quality of life of patients and has become a major public health problem of worldwide concern. At this stage, the clinical treatment of HF is still mainly based on drug therapy. As clinical research progresses, more and more new HF therapeutic drugs are being introduced one after another, new uses of drugs are being discovered and clinical options for drug use are becoming more and more diverse. The drug therapy for HF is also changing from monotherapy to multi-target and multi-mechanism combined mode of action. Innovative mechanical therapy products are also bringing new strategies to the treatment of HF. This article reviews the medication treatment and device implantation strategies for the clinical treatment of HF.

Cardiomyopathy as cause of death in Duchenne muscular dystrophy: a longitudinal observational study.

Cardiomyopathy has become an important life-limiting factor since survival in Duchenne muscular dystrophy (DMD) has greatly increased with long-term ventilation and cough assistance. The aim of this study was to investigate the association between impaired left ventricular ejection fraction (LVEF) and survival. In a >20-year observational study in patients with DMD (age ≥16 years) with at least three echocardiograms, the association between LVEF and survival and time to cardiac or non-cardiac death was investigated using Kaplan-Meier survival analysis and Cox regression (for LVEF). In 67 DMD patients (430 echocardiograms), the decrease in LVEF over a mean±sd follow-up period of 9.1±5.1 years was -10.0±13.9% absolute, but LVEF progression varied widely. 84% were receiving an angiotensin-converting enzyme inhibitor and 54% a β-blocker at last follow-up with an LVEF of 37.5±12.4% at that time-point. Median (interquartile range) survival was 33 (25-40) years. 28 out of 67 (42%) of the cohort had died and LVEF was a significant negative predictor of survival (hazard ratio 0.95 (95% CI 0.91-0.99); p<0.007). Those who died of cardiac death (53% of known causes of death) had significantly lower LVEF at the time of death (LVEF -11.0% (95% CI -21.1- -0.9%); p=0.035) compared with non-cardiac death and tended to die at a younger age. Cardiomyopathy with systolic heart failure is the leading cause of death and lower LVEF is an independent predictor of mortality at younger ages in patients with DMD. Patients with DMD appear to be undertreated with respect to heart failure drug therapy.

Cardiac Resynchronization Therapy: current guidelines and recent advances beyond drug treatment.

Cardiac resynchronization therapy (CRT) is the therapy of choice for patients with symptomatic systolic heart failure (HF) and left bundle branch block (LBBB), despite optimal medical therapy (OMT). The recently published 2021 European Society of Cardiology (ESC) Guidelines on cardiac pacing and cardiac resynchronization therapy highlight the importance of CRT on top of OMT in HF patients with left ventricular ejection fraction (LVEF) ≤ 35%, sinus rhythm and typical LBBB with QRS duration ≥150ms. In the presence of medically intractable or recurrent after catheter ablation atrial fibrillation (AF), AV nodal ablation as an adjuvant therapy becomes more relevant in patients qualifying for the implantation of a biventricular system. Furthermore, CRT may be considered in cases when increased pacing of the right ventricle is not desirable. However, alternative pacing sites and strategies are currently available, if the CRT is not feasible and effective in patients. However, strategies targeting "multi-sides" or using "multi-leads" have shown superiority over classic CRT. On the other hand, conduction system pacing seems to be a promising technique. Although early results are positive, consistency during the long term is pending. The indication for additional defibrillation therapy (ICD) may occasionally be unnecessary and has to be considered individually. Due to the great development and success of heart failure drug therapy, its positive effect on LV function can lead to enormous improvement. Physicians must await these effects and findings, which hopefully could lead to a relevant LV improvement resulting in a definitive decision against an ICD.

Changes in the gut microbiota structure and function in rats with doxorubicin-induced heart failure.

The rat model of heart failure (HF) induced by doxorubicin (DOX), a broad spectrum and highly effective chemotherapeutic anthracycline with high-affinity to myocardial tissue that causes severe dose-dependent irreversible cardiotoxicity has been widely recognized and applied in HF pathogenesis and drug therapy studies. The gut microbiota (GM) has attracted significant attention due to its potential role in HF, and research in this area may provide beneficial therapeutic strategies for HF. Considering the differences in the route, mode, and total cumulative dose of DOX administration used to establish HF models, the optimal scheme for studying the correlation between GM and HF pathogenesis remains to be determined. Therefore, focusing on establishing the optimal scheme, we evaluated the correlation between GM composition/function and DOX-induced cardiotoxicity (DIC). Three schemes were investigated: DOX (at total cumulative doses of 12, 15 or 18 mg/kg using a fixed or alternating dose via a tail vein or intraperitoneal injection) was administered to Sprague Dawley (SD) for six consecutive weeks. The M-mode echocardiograms performed cardiac function evaluation. Pathological changes in the intestine were observed by H&E staining and in the heart by Masson staining. The serum levels of N-terminal pre-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) were measured by ELISA. The GM was analysed by 16S rRNA gene sequencing. Strikingly, based on the severity of cardiac dysfunction, there were marked differences in the abundance and grouping of GM under different schemes. The HF model established by tail vein injection of DOX (18 mg/kg, alternating doses) was more stable; moreover, the degree of myocardial injury and microbial composition were more consistent with the clinical manifestations of HF. The model of HF established by tail vein injection of doxorubicin, administered at 4mg/kg body weight (2mL/kg) at weeks 1, 3 and 5, and at 2mg/kg body weight (1mL/kg) at weeks 2, 4 and 6, with a cumulative total dose of 18mg/kg, is a better protocol to study the correlation between HF and GM.

Modern approaches to interpretation of clinical trial results to evaluate the effectiveness of heart failure therapy. Analysis of the results of randomized trials PARADIGM-HF, DAPA-HF, EMPEROR-Reduced and VICTORIA

The article discusses the results of modern studies evaluating the effectiveness of drug therapy for heart failure with reduced ejection fraction (HFrEF). Modern approaches to a comprehensive evaluation of data obtained in various randomized clinical trials (RCTs) are presented. The role of methods for presenting the RCT results is considered, as well as the difference between hazard ratio and relative risk is clarified. Expert opinions are discussed about the limitations of simplified approaches to comparing the results of large RCTs, which are based only on comparisons of hazard ratio without taking consideration of patient characteristics, study duration, and the absolute number of adverse outcomes that developed. Information is provided on the role of accounting for multiple comparisons in assessing clinical outcomes in RCTs. The article compares the VICTORIA results on the study of vericiguat in patients with a recent episode of HFrEF decompensation with RCTs on the evaluation of the effects of drugs that are part of standard therapy.

Challenges and Opportunities in Titrating Disease-Modifying Therapies in Heart Failure with Reduced Ejection Fraction and Chronic Kidney Disease.

Chronic kidney disease (CKD) is highly prevalent in patients with heart failure and reduced ejection fraction (HFrEF), representing a major factor of adverse outcomes. In clinical practice, it is one of the main reasons for not initiating, not titrating, and even withdrawing efficient heart failure drug therapies in patients. Despite limited data, studies show that HFrEF therapies maintain their benefits on cardiovascular outcomes in patients with CKD. Most HF drugs cause acute renal haemodynamic changes, but with stabilisation or even improvement after the acute phase, thus with no long-term worsening of the renal function. In this expert opinion-based paper, we challenge the pathophysiology misunderstandings that impede HF disease-modifying therapy implementation in this setting and propose a strategy for HF drug titration in patients with moderate, severe, and end-stage chronic kidney disease.

Effect of home non-invasive ventilation on left ventricular function and quality of life in patients with heart failure and central sleep apnea syndrome

Central Sleep Apnea Syndrome (CSAS) and Cheyne-Stokes breathing are prevalent in patients with heart failure with reduced ejection fraction (HFrEF). Positive respiratory pressure therapy (PAP) associated with drug therapy for heart failure can improve quality of life, although tolerance to PAP therapy can be difficult to achieve. Materials and method: Patients for this prospective, mono-center, cohort study were selected from patients with chronic heart failure who present at the Sleep Laboratory of the Medical Clinic of Pneumology, Oradea who underwent polysomnography. 38 HFrEF and CSAS patients were included between January 2019 to December 2021 in the study, with an apnea-hypopnea index (AHI) &gt;=15/hour of sleep. Echocardiographic hemodynamic parameters (left ventricular ejection fraction-LVEF, mitral regurgitation score), PAP compliance, and quality of life using the severe respiratory failure questionnaire (SRI) at the initiation of PAP and after 3 months were included. Results: After 3 months of PAP therapy LVEF increased significantly (from 31.4% ±12.2to 38.0%±10.9, p=0.0181), AHI decreased (from 40.1±18.7 to 6.8±6.1 events/h, p&lt;0.0001) and all the categories of SRI showed improvement with significant general score increase (from 57.0±15.1 to 66.6±16.9, p&lt;0.0001). Conclusion: The association of PAP therapy with drug therapy in patients with HFrEF and CSAS improves hemodynamic parameters and quality of life. Keywords: Chronic heart failure, positive airway pressure therapy, central sleep apnea syndrome

Efficacy of Xinbao pill on chronic heart failure: Study protocol of a multicenter, randomized, double-blind, placebo-controlled trial.

Introduction: Chronic heart failure (CHF) is a common cardiovascular disease. In China, Xinbao pill (XBP) is widely used as an adjuvant therapy for CHF. However, there is still a lack of high-quality clinical evidence. We designed this multicenter, randomized, double-blind, placebo-controlled trial to critically evaluate the efficacy and safety of XBP as an adjuvant treatment for patients with CHF. Methods and analysis: We will recruit 284 patients with a clinical diagnosis of "heart-kidney yang deficiency syndrome" CHF receiving treatment in six hospitals in China. Patients will be randomly assigned, in a 1:1 ratio, to the treatment or control group using a central randomization system. All patients will receive conventional drug therapy for heart failure combined XBP (Guangdong Xinbao Pharmaceutical Co., Ltd., Guangdong, China) or a placebo. Study physicians, subjects, outcome assessors, and statisticians will be blinded to the group assignment. The primary outcome will be the change in the proportion of patients who show a decrease in serum NT-proBNP of more than 30% after treatment. Secondary outcomes are NYHA class, 6-minute walk distance test, Minnesota Quality of Life Scale score, endpoint events, serum NT-proBNP, echocardiographic parameters, and traditional Chinese medicine (TCM) symptom score. Adverse events will be monitored throughout the trial. Data will be analyzed according to a predetermined statistical analysis plan. Discussion: The results of this study will provide solid evidence of the safety and efficacy of XBP as an alternative and complementary treatment measure for patients with CHF. Clinical Trial Registration: Chinese Clinical Trial Registration Center (ChiCTR2000038492).

Prognosis of low-flow low-gradient aortic valve stenosis with atrial fibrillation

Abstract Background Patients with Low-flow low-gradient (LFLG) aortic valve stenosis (AS) have possibly poor prognosis. Recently, it was reported that the LFLG AS patients have similar outcomes compared to high-gradient (HG) patients but worse outcomes compared to the normal-flow low-gradient [NFLG: SVi≥35 ml/m2, mPG &amp;lt;40mmHg] subgroup. The main determinant of LF state in severe AS patients with preserved LVEF are male gender, heart rate, LV volume and atrial fibrillation (AF). However, the relationship between the comorbidity with AF in LFLG AS and the risk of heart failure (HF) remains unclear. Purpose We elucidated about the prognosis of LFLG AS with AF. Methods We included 225 consecutive patients with severe AS (SAS, iAVA&amp;lt;0.6 cm2/m2) from 2013 to 2020. Among these patients, high-gradient SAS [HG-SAS; mean pressure gradient (mPG) ≥40 mmHg, n=88] and LFLG AS [stroke volume index (SVi) ≤35 ml/m2, mPG &amp;lt;40 mmHg, n=82] patients was extracted and the baseline characteristics including the presence or absence of AF were evaluated. The primary endpoint was worsening HF that required unplanned hospitalization or readjustment of HF drug therapy. Results Among patients with HG SAS and LFLG AS, worsening HF was observed in 65 patients. LFLG AS patients exhibited a higher oral rate of renin-angiotensin-system inhibitors (p=0.02). In addition, SVi and E/e' was lower in LFLG AS patients compared with HG SAS [SVi; 29.4 (24.4–34.0) versus 37.7 (28.2–45.3), p&amp;lt;0.0001, E/E'; 16.0 (13.1–21.5) vs 20.9 (16.0–27.4), p=0.002]. There is no differences between 2 groups in AF prevalence. Furthermore, 2 groups were subdivided as follow; HG SAS with AF (n=25), HG SAS without AF (n=63), LFLG AS with AF (n=24), LFLG AS without AF (n=58). The Kaplan Meier curves demonstrated LFLG SAS with AF experienced higher rate of worsening HF compared with HG SAS without AF and equivalent rate of worsening HF compared with HG SAS with AF (log rank, p&amp;lt;0.001). In the Cox hazard analysis among the LFLG AS patients, LFLG AS with paroxysmal AF (pAF, n=12) instead of chronic AF (cAF, n=12) showed a higher risk for worsening HF compared with those without AF (HR 5.0; 95% CI, 1.8–14; p=0.0028, HR 1.9; 95% CI, 0.62–5.8; p=0.26, respectively). Conclusion LFLG AS with AF exhibited a poor prognosis for HF compared with HG SAS without AF and equivalent rate of worsening HF compared with HG SAS with AF. Furthermore, the presence of pAf was associated with an increased risk of HF in patients with LFLF AS. Thus, intervention including drugs and catheter ablation for pAF in LFLG AS patients could lead to prevent worsening clinical outcomes. Funding Acknowledgement Type of funding sources: None.

Optimal Pharmacologic Treatment of Heart Failure With Preserved and Mildly Reduced Ejection Fraction

In recent years, significant progress has been made in the pharmacologic treatment of heart failure (HF) with reduced ejection fraction (HFrEF), but there is still insufficient evidence for drug therapy for HF with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF). To compare the outcomes associated with different drug combinations for the treatment of HFpEF and HFmrEF. A search of the PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was conducted for studies published from inception to October 9, 2021. Randomized clinical trials on the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs), β-blockers, and sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with HFpEF or HFmrEF. Data extraction and bias assessment were independently performed by 2 reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. All data for 3 outcomes were pooled with a fixed-effect model. The main outcomes were first hospitalization for HF, all-cause mortality, and cardiovascular mortality. Hazard ratios (HRs) and 95% credible intervals (CrIs) were evaluated using a bayesian network meta-analysis model. In this analysis, 19 randomized clinical trials, including 20 633 patients with HF and an ejection fraction of 40% or more, without a remarkable risk of bias were included. Compared with placebo, no treatments were associated with a significant reduction in the risk of all-cause death or cardiovascular death. SGLT2 inhibitors, ARNIs, and MRAs were associated with a significant decrease in the risk of HF hospitalization compared with placebo (SGLT2 inhibitors: HR, 0.71 [95% CrI, 0.60-0.83]; ARNIs: HR, 0.76 [95% CrI, 0.61-0.95]; MRAs: HR, 0.83 [95% CrI, 0.69-0.99]), and SGLT2 inhibitors were the optimal drug class in terms of reducing the risk for HF admission. Sensitivity analysis results demonstrated a progressive decrease in the risk of HF admission and an advance in mean rank associated with the increasing use of drug classes. The findings of this study suggest that SGLT2 inhibitors were the optimal drug class for HFpEF and HFmrEF, consistent with the most recent guideline recommendation. The incremental use of combinations of SGLT2 inhibitors, ACE inhibitors or ARBs, and β-blockers may be associated with accumulative benefits in HF hospitalization rather than all-cause death among patients with HFpEF and HFmrEF.

From Snake Venoms to Therapeutics: A Focus on Natriuretic Peptides

Snake venom is a cocktail of multifunctional biomolecules that has evolved with the purpose of capturing prey and for defense. These biomolecules are classified into different classes based on their functions. They include three-finger toxins, natriuretic peptides, phospholipases and metalloproteinases. The focus for this review is on the natriuretic peptide (NP), which is an active component that can be isolated from the venoms of vipers and mambas. In these venoms, NPs contribute to the lowering of blood pressure, causing a rapid loss of consciousness in the prey such that its mobility is reduced, paralyzing the prey, and often death follows. Over the past 30 years since the discovery of the first NP in the venom of the green mamba, venom NPs have shown potential in the development of drug therapy for heart failure. Venom NPs have long half-lives, different pharmacological profiles, and may also possess different functions in comparison to the mammalian NPs. Understanding their mechanisms of action provides the strategies needed to develop new NPs for treatment of heart failure. This review summarizes the venom NPs that have been identified over the years and how they can be useful in drug development.

Application of recommended therapies among patients with heart failure during the Syrian conflict: reality and barriers.

Lower socio-economic status may delay and even prevent the application of guideline-directed heart failure (HF) therapy for most patients. This study aims to evaluate the feasibility and possible difficulties facing the application of this treatment during the current Syrian conflict. A questionnaire on HF management and feasibility of recommended HF therapy was addressed to physicians practising cardiology in Syria. The questionnaire consisted of 30 questions and focused on the quality of HF management and awareness of recommended drug and device therapy for HF among physicians practising cardiology in Syria. A total of 228 physicians participated in the survey. Awareness of recommended medical and device therapy of HF was very high among participants (98% and 95%, respectively). The majority of participants (>75%) believe that more than half of HF patients do not receive optimal medical HF therapy. Ninety per cent of participants believe that <10% of patients with an appropriate indication for device therapy receive it. More than 75% of participants believe that the cost of medications, alone or in combination with other medical causes, represents the major problem facing the application of optimal HF medical therapy. More than 95% of participants reported that cost alone, or in combination with unavailability, is the primary reason why patients with appropriate indications are not offered device therapy. Despite the high level of awareness of recommended HF therapies among Syrian cardiologists, the majority of HF patients are still undertreated. Financial difficulties and lack of resources are the main causes of this problem.

Medicare Coverage and Out-of-Pocket Costs of Quadruple Drug Therapy for Heart Failure

BackgroundBeta-blockers, angiotensin receptor-neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors (SGLT2i), known as quadruple therapy, are recommended for patients with heart failure with reduced ejection fraction (HFrEF). ObjectivesThis study sought to determine Medicare coverage and out-of-pocket (OOP) costs of quadruple therapy and regimens excluding ARNI or SGLT2i. MethodsThis study assessed cost sharing, prior authorization, and step therapy in all 4,068 Medicare prescription drug plans in 2020. OOP costs were determined during the standard coverage period and annually based on the Medicare Part D standard benefit, inclusive of deductible, standard coverage, coverage gap, and catastrophic coverage. ResultsTier ≥3 cost sharing was required by 99.1% of plans for ARNI and 98.5% for at least 1 SGLT2i. Only ARNI required prior authorization (24.3% of plans), and step therapy was required only for SGLT2is (5.4%) and eplerenone (0.8%). The median 30-day standard coverage OOP cost of quadruple therapy was $94 (IQR: $84-$100), including $47 (IQR: $40-$47) for ARNI and $45 (IQR: $40-$47) for SGLT2i. The median annual OOP cost of quadruple therapy was $2,217 (IQR: $1,956-$2,579) compared with $1,319 (IQR: $1,067-$1,675) when excluding SGLT2i and $1,322 (IQR: $1,025-$1,588) when including SGLT2i and substituting an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for ARNI. The median 30-day OOP cost of generic regimens was $3 (IQR: $0-$9). ConclusionsMedicare drug plans restrict coverage of quadruple therapy through cost sharing, with OOP costs that are substantially higher than generic regimens. Quadruple therapy may be unaffordable for many Medicare patients with HFrEF unless medication prices and cost sharing are reduced.

Development and implementation of a heart failure telemonitoring system: the single centre experience

Aim To evaluate the efficacy of remote monitoring by the compliance with body weight control and drug therapy in patients with CHF, using a specially developed software module for chronic heart failure (CHF) monitoring.Material and methods During 2018-2020, 79 patients with dilated cardiomyopathy (mean age, 36.1 [34.2; 38.4] years) and NYHA II-IV functional class CHF were included in the outpatient telemonitoring (TM) program.Results The duration of monitoring was 965 [768; 1065] days. During the monitoring time, the compliance with outpatient body weight control significantly improved: 73.3 [70; 80] % at baseline vs. 86.7 [76.7; 86.7] % at the end of the 31st month (p&lt;0.001). The proportion of patients measuring their body weight at least 6 times a week significantly increased: 8.9 % at baseline vs. 58.1 % by the end of the monitoring (p&lt;0.001). There was no significant association between the time-related changes in the compliance with body weight control and drug therapy and the patient's gender. In addition, during long-term TM, a small but statistically significant increase in left ventricular ejection fraction was noted (36.3 [35.5; 37.2] % at baseline vs. 37.2 [35.8; 38.3] % at the end of monitoring; p=0.0008). The involvement of staff physicians in the remote correction of therapy for CHF decreased during the study: the number of system notifications that required a physician's response reduced over two years from 26.6 to 13 % (p=0.011).Conclusion Participation of patients with dilated cardiomyopathy and CHF in the structured TM program was associated with a significant increase in the compliance with regular self-control of body weight and drug therapy for heart failure.

P315 A CASE OF TAKOTSUBO CARDIOMYOPATHY IN A PATIENT WITH TAKAYASU’S ARTERITIS: THE CORONARY VASOSPASM AS A MISSING LINK BETWEEN THE IMMUNE SYSTEM AND ACUTE PSYCHOLOGICAL STRESS

Abstract Background Takayasu’s arteritis (TA) is a systemic inflammatory disease that affects aorta and its major branches. There are several cardiac manifestations of TA and, recently, an association with Takotsubo syndrome (TTS) was reported Case Presentation A 58–year–old Caucasian female, with history of severe asymptomatic aortic regurgitation (AR) with a recently documented normal LV systolic function and TA in remission under corticosteroids, was admitted in the emergency department with chest pain following an acute intense stressful event. ECG showed sinus tachycardia, T wave inversion in left precordial and lateral leads, and a QTc of 487 ms (Figure 1). Laboratorial evaluation presented high–sensitivity troponin I of 3494 ng/L and B–type natriuretic peptide of 4759 pg/mL. The transthoracic echocardiogram revealed severe dilation of LV with moderate systolic dysfunction, due to apical and midventricular akinesia (“apical ballooning” pattern), and severe AR (Figure 2). The coronary angiography showed normal coronary arteries. An acetylcholine provocative test showed spasm of both the left anterior descending and circumflex arteries, accompanied by chest pain and ST depression in ECG, reverted after intracoronary nitrates administration (Figure 3). The patient was switched to diltiazem and heart failure drug therapy was started. A cardiac magnetic resonance revealed severe dilation of the LV, apical hypokinesia, ejection fraction to 53%, signs of myocardial edema and increased extracellular volume in apical and mid–ventricular anterior and anterolateral walls, and absence of myocardial late gadolinium enhancement, compatible with TTS. Patient was discharged clinically stable, without signs of HF, with progressive reduction of troponin and BNP. A final diagnosis of myocardial infarction with nonobstructive coronary arteries (MINOCA) due to TTS and coronary vasospasm in a patient with TA was done Discussion TA is a rare disease and there are reports of its association both with TTS and coronary vasospasm. Besides that, coronary vasospasm may also be involved in the pathophysiology of TTS. Moreover, in this patient we could not exclude the role coronary diastolic hypoperfusion due to AR in the elicitation of coronary vasospasm. Therefore, although the mechanisms behind these pathologies are not yet fully studied, this case supports their relationship Conclusion We presented a case of a patient with TA admitted with MINOCA due to TTS and coronary vasospasm

Medical Treatment of Heart Failure with Reduced Ejection Fraction in the Elderly.

The aging population, higher burden of predisposing conditions and comorbidities along with improvements in therapy all contribute to the growing prevalence of heart failure (HF). Although the majority of trials have not demonstrated age-dependent heterogeneity in the efficacy or safety of medical treatment for HF, the latest trials demonstrate that older participants are less likely to receive established drug therapies for HF with reduced ejection fraction. There remains reluctance in real-world clinical practice to prescribe and up-titrate these medications in older people, possibly because of (mis)understanding about lower tolerance and greater propensity for developing adverse drug reactions. This is compounded by difficulties in the management of multiple medications, patient preferences and other non-medical considerations. Future research should provide a more granular analysis on how to approach medical and device therapies in elderly patients, with consideration of biological differences, difficulties in care delivery and issues relevant to patients’ values and perspectives. A variety of approaches are needed, with the central principle being to ‘add years to life – and life to years’. These include broader representation of elderly HF patients in clinical trials, improved education of healthcare professionals, wider provision of specialised centres for multidisciplinary HF management and stronger implementation of HF medical treatment in vulnerable patient groups.