Outcomes In Chronic Heart Failure Research Articles

Evaluation and Management of Chronic Heart Failure in Children and Adolescents With Congenital Heart Disease: A Scientific Statement From the American Heart Association.

With continued medical and surgical advancements, most children and adolescents with congenital heart disease are expected to survive to adulthood. Chronic heart failure is increasingly being recognized as a major contributor to ongoing morbidity and mortality in this population as it ages, and treatment strategies to prevent and treat heart failure in the pediatric population are needed. In addition to primary myocardial dysfunction, anatomical and pathophysiological abnormalities specific to various congenital heart disease lesions contribute to the development of heart failure and affect potential strategies commonly used to treat adult patients with heart failure. This scientific statement highlights the significant knowledge gaps in understanding the epidemiology, pathophysiology, staging, and outcomes of chronic heart failure in children and adolescents with congenital heart disease not amenable to catheter-based or surgical interventions. Efforts to harmonize the definitions, staging, follow-up, and approach to heart failure in children with congenital heart disease are critical to enable the conduct of rigorous scientific studies to advance our understanding of the actual burden of heart failure in this population and to allow the development of evidence-based heart failure therapies that can improve outcomes for this high-risk cohort.

Prognostic Impact of Repeated NT-proBNP Measurements in Patients With Heart Failure With Reduced Ejection Fraction

BackgroundAlthough clinical studies have demonstrated the association between a single N-terminal pro–B-type natriuretic peptide (NT-proBNP) measurement and clinical outcomes in chronic heart failure, the biomarker is frequently measured serially in clinical practice. ObjectivesThe aim of this study was to determine the added prognostic value of repeated NT-proBNP measurements compared with single measurements alone for chronic heart failure patients. MethodsIn the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study, 894 study participants with chronic heart failure with reduced ejection fraction were enrolled at 45 outpatient sites in the United States and Canada. Repeated NT-proBNP levels were measured over a 2-year study period. Associations between repeated NT-proBNP measurements and trial endpoints were assessed using a joint longitudinal and survival model. ResultsAfter adjustment for baseline covariates, each doubling of the baseline NT-proBNP level was associated with a HR of 1.17 (95% CI: 1.08-1.28; P = 0.0003) for the primary trial endpoint of cardiovascular death or heart failure hospitalization. Serial measurements increased the adjusted HR for the primary trial endpoint to 1.66 (95% CI: 1.50-1.84; P < 0.0001), and a similar increased risk was observed across secondary trial endpoints. In joint modeling, an increase in NT-proBNP occurred weeks before the onset of adjudicated events. ConclusionsRepeated NT-proBNP measurements are a strong predictor of outcomes in heart failure with reduced ejection fraction with an increase in concentration occurring well before event onset. These results may support routine NT-proBNP monitoring to assist in clinical decision making. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840)

From heart failure and kidney dysfunction to cardiorenal syndrome: TMAO may be a bridge

The study of trimethylamine oxide (TMAO), a metabolite of gut microbiota, and heart failure and chronic kidney disease has made preliminary achievements and been summarized by many researchers, but its research in the field of cardiorenal syndrome is just beginning. TMAO is derived from the trimethylamine (TMA) that is produced by the gut microbiota after consumption of carnitine and choline and is then transformed by flavin-containing monooxygenase (FMO) in the liver. Numerous research results have shown that TMAO not only participates in the pathophysiological progression of heart and renal diseases but also significantly affects outcomes in chronic heart failure (CHF) and chronic kidney disease (CKD), besides influencing the general health of populations. Elevated circulating TMAO levels are associated with adverse cardiovascular events such as HF, myocardial infarction, and stroke, patients with CKD have a poor prognosis as well. However, no study has confirmed an association between TMAO and cardiorenal syndrome (CRS). As a syndrome in which heart and kidney diseases intersect, CRS is often overlooked by clinicians. Here, we summarize the research on TMAO in HF and kidney disease and review the existing biomarkers of CRS. At the same time, we introduced the relationship between exercise and gut microbiota, and appropriately explored the possible mechanisms by which exercise affects gut microbiota. Finally, we discuss whether TMAO can serve as a biomarker of CRS, with the aim of providing new strategies for the detection, prognostic, and treatment evaluation of CRS.

Right Ventricular Dysfunction and Exercise Impairment in Patients with Heart Failure, Insulin Resistance, and Diabetes Mellitus: Insights from the T.O.S.CA. Registry (Cardiovascular Diabetology 2022).

Insulin resistance (IR) and type 2 diabetes mellitus (T2D) are known to affect the progression of chronic heart failure (CHF), but little evidence exists about the impact of IR and T2D on right ventricular dysfunction and exercise tolerance. Insights from the T.O.S.C.A. Registry: Echocardiographic hallmarks and cardiopulmonary exercise test (CPET) results were evaluated at baseline and after an average time of 36 months. T2D patients exhibited a greater intraventricular septum (IVS) thickness (11 ± 2 mm, 10 ± 2 mm, 10 ± 2 mm, in T2D, IR, and EU, respectively; p<.05) and LV wall thickness (0.34 ± 0.1, 0.32 ± 0.1, and 0.32 ± 0.1, in T2D, IR, and EU, respectively; p<.05). Moreover, T2D patients exhibited worse LV filling dynamics with larger left atrial volume index compared to IR and EU. Right ventricle dysfunction, expressed as a lower TAPSE/PASP ratio, was found in T2D [0.52(0.32-0.72)] than in EU and IR [0.60(0.30-0.90); p<.05]. T2D patients showed a significantly lower VO2 max peak when compared to IR and EU patients (15.8 ± 3.8 vs. 16.5 ± 4.3 vs. 18.4 ± 4.3 ml/Kg/min; p<.003), with an inverse relationship between the HOMAIR classes and VO2 max. Right ventricle structure and function deteriorated more rapidly in T2D, as suggested by more relevant deterioration in TAPSE/PASP ratio (-10% in EU patients, -14% in IR patients, -21% in T2D; p<.05). The study findings suggest that the right ventricle structure, function, and cardiopulmonary performance deteriorate with IR and, more evidently, due to chronic exposure to hyperglycemia in T2D. Impaired exercise tolerance, poor cardiorespiratory fitness, diastolic dysfunction, and left atrial enlargement predispose patients to poor quality of life, suboptimal adherence to physical activity, and an overall increase in the risk of all-cause and cardiovascular mortality. In addition, chronic hyperglycemia accelerates the progression of these alterations, especially in patients with poor glycemic control over time. Highly selective and even more non-selective sodium glucose transporter type 2 inhibitors and glucagon-like peptide 1 receptor agonists should be considered as the first-line therapy for improving CV outcomes in T2D and CHF. Further studies are needed to understand the role of these molecules in treating pre-clinical conditions, such as IR and metabolic syndrome.

Regional Handling and Prognostic Performance of Circulating Insulin-Like Growth Factor Binding Protein-7 in Heart Failure

BackgroundRegional handling and the prognostic performance of insulin-like growth factor binding protein (IGFBP)-7, in contrast or in combination with other candidate biomarkers, in chronic heart failure (CHF) remain uncertain. ObjectivesThe authors investigated the regional handling of plasma IGFBP-7 and its association with long-term outcomes in CHF in comparison with selected circulating biomarkers. MethodsPlasma concentrations of IGFBP-7, N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin-T, growth differentiation factor-15, and high-sensitivity C-reactive protein were measured prospectively in a cohort with CHF (n = 863). The primary outcome was the composite of heart failure (HF) hospitalization or all-cause mortality. In a separate non-HF cohort (n = 66) undergoing cardiac catheterization, transorgan gradients of plasma IGFBP-7 concentrations were evaluated. ResultsAmong 863 patients (age 69 ± 14 years, 30% female, 36% HF with preserved ejection fraction), IGFBP-7 (median: 121 [IQR: 99-156] ng/mL) related inversely to left ventricular volumes but directly to diastolic function. Above the optimal cutoff, IGFBP-7 ≥110 ng/mL was independently associated with 32% increased hazard of the primary outcome: 1.32 (95% CI: 1.06-1.64). Among the 5 markers, IGFBP-7 had the highest hazard for a proportional increment in plasma concentrations independent of HF phenotype in single- and double-biomarker models, and provided incremental prognostic value beyond clinical predictors plus NT-proBNP, high-sensitivity troponin-T, and high-sensitivity C-reactive protein (P < 0.05). Assessment of regional concentrations indicated renal secretion of IGFBP-7 in contrast to renal extraction of NT-proBNP, possible cardiac extraction of IGFBP-7 in contrast to secretion of NT-proBNP, and common hepatic extraction of both peptides. ConclusionsTransorgan regulation of IGFBP-7 is distinct from NT-proBNP. Circulating IGFBP-7 independently predicts adverse outcomes in CHF with a strong prognostic performance when compared with other well-recognized cardiac-specific or noncardiac prognostic markers.

Растворимый супрессор туморогенности 2 (sST2) как предиктор неблагоприятного течения хронической сердечной недостаточности

Растворимый супрессор туморогенности 2 (sST2) как предиктор неблагоприятного течения хронической сердечной недостаточности

Cardiovascular-renal protective effect and molecular mechanism of finerenone in type 2 diabetic mellitus.

Chronic kidney diseases (CKD) and cardiovascular diseases (CVD) are the main complications in type 2 diabetic mellitus (T2DM), increasing the risk of cardiovascular and all-cause mortality. Current therapeutic strategies that delay the progression of CKD and the development of CVD include angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), sodium-glucose co-transporter 2 inhibitors (SGLT-2i) and GLP-1 receptor agonists (GLP-1RA). In the progression of CKD and CVD, mineralocorticoid receptor (MR) overactivation leads to inflammation and fibrosis in the heart, kidney and vascular system, making mineralocorticoid receptor antagonists (MRAs) as a promising therapeutic option in T2DM with CKD and CVD. Finerenone is the third generation highly selective non-steroidal MRAs. It significantly reduces the risk of cardiovascular and renal complications. Finerenone also improves the cardiovascular-renal outcomes in T2DM patients with CKD and/or chronic heart failure (CHF). It is safer and more effective than the first- and second-generation MRAs due to its higher selectivity and specificity, resulting in a lower incidence of adverse effects including hyperkalemia, renal insufficiency and androgen-like effects. Finerenone shows potent effect on improving the outcomes of CHF, refractory hypertension, and diabetic nephropathy. Recently studies have shown that finerenone may have potential therapeutic effect on diabetic retinopathy, primary aldosteronism, atrial fibrillation, pulmonary hypertension and so on. In this review, we discuss the characteristics of finerenone, the new third-generation MRA, and compared with the first- and second-generation steroidal MRAs and other nonsteroidal MRAs. We also focus on its safety and efficacy of clinical application on CKD with T2DM patients. We hope to provide new insights for the clinical application and therapeutic prospect.

Early repolarization pattern on ECG predicts worse outcomes in patients hospitalized due to chronic heart failure decompensation

BackgroundTo improve the outcomes of patients with chronic heart failure (CHF), it is important to identify reliable prognostic tools. Early repolarization pattern (ER) on 12‑lead electrocardiogram (ECG) is a predictor of worse outcomes, which has been widely researched in the general population but not in the CHF population. ObjectiveTo evaluate the incidence and prognostic value of ER and compare its prognostic significance with other non-invasive diagnostic methods for CHF outcomes and hospital readmissions. MethodsThe study included 301 patients (166 men and 135 women) hospitalized for CHF decompensation. CHF diagnosis was confirmed according to the current guidelines. The patients underwent standard tests and impedance cardiography (ICG) at enrollment and on the day of discharge. ResultsThirty-one confirmed ER cases (10.3%) were enrolled. During a median follow-up period of 18 months, 128 cardiac-related deaths were observed (42.5%), with 23 (74.2%) and 105 (38.9%) patients in the ER and non-ER groups, respectively (p < 0.001). The ER group had more readmissions than the non-ER group did at 6-months (2 [1, 2] vs. 1 [1, 2]; p=0.04) and 12-months (3 [2–4] vs. 2 [1–3]; p<0.001). ER on ECG (hazard ratio [HR] 2.59; 95% confidence interval [CI] 1.64–4.07; p<0.001), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels ≥425.5 pmoL/L (HR 5.1; 95% CI 3.33–7.83; p < 0.001), thoracic fluid content (TFC) ≥36.9 1/kΩ (HR 4.6; 95% CI 2.7–7.85, p < 0.001), and left ventricular ejection fraction (LVEF) ≤40% (HR 4.94; 95% CI 2.83–8.65; p < 0.001) were independently and significantly associated with cardiac death. ConclusionsThe combination of ER, LVEF ≤40%, NT-proBNP, or TFC provides an incremental prognostic value for cardiac-related death in patients with CHF.

Differences in red blood cell mass profiles impact intravascular volume and outcome risk in chronic heart failure.

To identify different red blood cell mass (RBCM) profiles, separate from haemoglobin concentrations, and their impact on blood volume expansion and clinical outcomes in chronic heart failure. RBCM was measured at hospital discharge using standardized nuclear medicine indicator-dilution methodology in patients following diuretic treatment for clinical congestion. Individual RBCM phenotypes were prospectively identified and analysed for heart failure-related mortality or first rehospitalization over 1year. Of 132 patients, 42 (32%) demonstrated normal RBCM, 36 (27%) RBCM deficit (true anaemia), and 54 (41%) RBCM excess (erythrocythemia). Dilutional 'anaemia' defined by haemoglobin <12g/dL with normal or an excess in RBCM with plasma volume expansion was identified in 37 (28%) patients. There were 61 composite outcome events, which included 38 deaths (29% of cohort) occurring over the 1year follow-up period [14/36 (39%) in RBCM deficit, 12/42 (29%) in normal RBCM, and 12/54 (22%) in RBCM excess subgroups]. By Kaplan-Meier and multivariate analyses, RBCM excess was independently associated with the best event-free survival while RBCM deficit (true anaemia) the poorest outcomes; both compared with normal RBCM (P<0.001). Dilutional 'anaemia' demonstrated a lower risk compared with true anaemia (P=0.03). Markedly different RBCM profiles are identifiable among comparably compensated heart failure patients, and this variability carries significant implications for post-hospital outcomes. Novel to this analysis and in contrast to RBCM deficit is the independent association of RBCM excess with better event-free survival compared with normal RBCM. The distinction of RBCM profiles to guide risk stratification and individualized patient management strategies warrants further study.

Clinical and Immunological Parameters in the Diagnostics of Asthenic Syndrome in Patients with Chronic Heart Failure

Background: the significance of the asthenic syndrome as one of the most distressing symptoms affecting the clinical outcome of chronic heart failure (CHF), and insufficient understanding of the pathophysiological aspects of asthenia determines the need to study the clinical and biological features of this syndrome in cardiac pathology. Objective: to determine of a number of inflammatory and autoimmune blood parameters in patients with CHF associated with asthenic disorders in comparison with hypertensive disease in relation to clinical and gender-age characteristics of patients. Patients and methods: 62 patients with CHF (study group; 64.4 ± 9.7 years) and 50 patients with hypertensive disease (HD) (comparison group; 55 ± 9.7 years) were examined. Somatic examination included consultation with a cardiologist. Psychometric assessment was performed using the MFI-20 scale and the MLHFQ questionnaire. In patients' blood, leukocyte elastase (LE) activity, α1-proteinase inhibitor (α1-PI), leukocyte inhibitory index (LII), concentration of CRP, IL-6, and levels of antibodies to S-100B and myelin basic protein were determined. Results: patients with CHF characterized by more pronounced manifestations of all dimensional asthenic disorders compared to patients with HD. The deterioration of CHF patients' quality of life was accompanied by the aggravation of asthenic symptoms on all subscales of the MFI-20 scale. In patients with CHF and HD, multidirectional changes in the leukocyte inhibitory index and significant quantitative differences in other immune parameters compared with the normative values were detected. CHF associated with asthenia was characterized by decreased activity of the blood proteolytic system (decrease in LII), a significant increase in the concentration of IL-6, CRP and antibodies to S-100B in the blood of patients compared to comparison group. Negative correlations between LE activity and several dimensions of the MFI-20 scale, and positive correlations between the severity of general asthenia, patient age, and IL-6 and CRP concentrations indicate the involvement of inflammation in the pathophysiology of asthenic disorders in the cardiac pathology discussed. Conclusion: low activity of blood proteolytic system and high level of inflammation are unfavorable factors in the development of asthenia in chronic heart failure. Qualitative and quantitative features of the spectrum of immunological parameters in patients with CHF are correlated with clinical and genderage characteristics and reflect the severity of both cardiological changes and asthenic symptoms.

Circulating Angiokines Are Associated With Reverse Remodeling and Outcomes in Chronic Heart Failure

We sought to determine whether circulating modifiers of endothelial function are associated with cardiac structure and clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). We measured 25 proteins related to endothelial function in 99 patients from the GUIDE-IT study. Protein levels were evaluated for association with echocardiographic parameters and the incidence of all-cause death and hospitalization for heart failure (HHF). Higher concentrations of angiopoietin 2 (ANGPT2), vascular endothelial growth factor receptor 1 (VEGFR1) and hepatocyte growth factor (HGF) were significantly associated with worse function and larger ventricular volumes. Over time, decreases in ANGPT2 and, to a lesser extent, VEGFR1 and HGF, were associated with improvements in cardiac size and function. Individuals with higher concentrations of ANGPT2, VEGFR1 or HGF had increased risks for a composite of death and HHF in the following year (HR 2.76 (95% CI 1.73-4.40) per 2-fold change in ANGPT2; HR 1.76 (95% CI 1.11-2.79) for VEGFR1; and HR 4.04 (95% CI 2.19-7.44) for HGF). Proteins related to endothelial function associate with cardiac size, cardiac function and clinical outcomes in patients with HFrEF. These results support the concept that endothelial function may be an important contributor to the progression to and the recovery from HFrEF.

CARDIAC CACHEXIA AND CLINICAL OUTCOME OF CHRONIC HEART FAILURE DUE TO RHEUMATIC HEART DISEASE

Background: Rheumatic Heart Disease (RHD) is still a significant cause of cardiovascular morbidity and death in developing countries like Indonesia. However, despite being one of the most preventable chronic diseases, RHD still receives less attention, especially in Southeast Asia. PJR that is not treated immediately can develop into chronic heart failure. When heart failure has entered the stage of congestive heart failure, there is activation of a complex network of metabolic, immune, and characteristic neurohormonal factors that can result in cachexia. Cachexia can be an indicator of decreased survival in patients with chronic heart failure due to RHD. Objective: To determine the relationship between cachexia and clinical outcomes of chronic heart failure due to RHD at RSUD Dr. Soetomo. Methods: This study was an analytic observational study using a retrospective cohort design. Data were collected by taking secondary data in the form of patient medical records. There were 106 patients who were taken by non-probability sampling technique. Correlation was determined using Mann-Whitney test and Chi-square test. Result: A total of 106 patients consisted of 53 people with cachexia and 53 people without cachexia, represented both groups dominated by female (57.6%), with largest age range was late adulthood (36-45 years) in both groups (32.1%). Education level data mostly came from secondary schools with a total of 71 people (66.9%) in both groups. The most common type of valve lesion in both groups was mitral stenosis (53.7%). The frequency of hospitalization in patients with cachexia was more frequent with an average of 1.25 times compared to patients without cachexia with an average of 1.02 times. Mortality was higher in patients with cachexia as many as 7 per 53 people (0.13%) compared to patients without cachexia as many as 3 per 53 people (0.06%). With Mann-Whitney and chi-square tests, it was found that cachexia had no effect on the hospitalization frequency (p=0.453) and mortality (p=0.319). Conclusion: Clinical outcomes in chronic heart failure patients due to RHD with cachexia are found to be higher in hospitalization frequency and mortality compared to patients with no cachexia.

Identification of predictive factors interacting with heart rate reduction for potential beneficial clinical outcomes in chronic heart failure: A systematic literature review and meta-analysis.

There is an absence of clinical evidence on what factors modify the effect of heart rate (HR)-reducing treatment on mortality and morbidity in symptomatic heart failure patients with reduced ejection fraction (HFrEF). We performed a Bayesian meta-analysis and meta-regression to identify predictive factors that interact with HR-reducing therapy. A systematic review was performed to identify randomized placebo-controlled trials that enrolled symptomatic HFrEF patients. The primary objective was to evaluate how different predictive factors modify the efficacy of HR-reducing therapy on clinical outcomes. Secondary objectives included the evaluation of subgroups stratified by a HR reduction threshold of 10bpm. Data from 20 studies were synthesized and HR-reducing therapy was responsible for 16.7%, 16.4%, and 21.1% risk reductions in all-cause mortality, cardiovascular (CV)-related mortality, and rehospitalization due to worsening HF (WHF), respectively. Empirical Bayes meta-regression showed that type 2 diabetes mellitus (T2DM) significantly modified the efficacy of HR-reducing therapy on all-cause mortality (slope=0.012 in log risk ratio (RR) per 1%-unit [95% credible interval (CrI) 0.004, 0.021]) and CV-related mortality (0.01 in log RR per 1%-unit [95% CrI 0.0003, 0.0200]). There were insufficient studies to perform a meta-regression when stratifying by a HR reduction threshold of 10bpm; however, when including all studies, we observed a significant effect modification for rehospitalization due to WHF (p=0.004). This meta-analysis focused on the central tenet of HR-reducing therapy and revealed that T2DM is a predictor of HR-reducing treatment effect on all-cause mortality and CV-related mortality in HFrEF patients.

Blood volume and chronic kidney disease in heart failure - Can volume expansion help balance the Cardio-Renal Axis for better clinical outcomes?

Intravascular volume is largely regulated by the kidneys but how differences in intravascular volume profiles interact with chronic kidney disease (CKD) to influence outcomes in chronic heart failure (HF) has not been explored. Our hypothesis was that a greater degree of volume expansion (VE) would moderate the impact of CKD on HF-related clinical outcomes. Quantitative blood volume (BV) data were available in 137 patients at the time of hospital discharge using a nuclear medicine radiolabeled albumin indicator-dilution technique. The study patients were stratified by the cohort median glomerular filtration rate (GFR, 44 ml/min/1.73 m2 ). An a priori cut-point of ≥+25% above normal BV was then used to further stratify the two GFR subgroups and prospectively analyzed for 1-year HF-related mortality or 1st re-hospitalization. Persistent BV expansions ≥+25% were present in 51% of the cohort. In the subgroup with GFR above the median (N=68) greater or lesser BV expansion from +25% did not differentiate outcomes. However, in the subgroup with GFR below the median (N=69), BV expansion-stratified risk (log-rank p=0.022) with <+25% VE associated with poorer outcomes, while VE ≥ + 25% was associated with lower risk and comparable to GFR above the median. In patients with chronic HF, significant intravascular VE and CKD are common co-existing conditions. The presence of larger VE, however, appears to be a factor mitigating the impact of declining renal function on clinical outcomes, and as an element of volume pathophysiology warrants further study.

Echocardiographic characteristics of patients with ischemic and non-ischemic chronic heart failure with reduced ejection fraction

T The data indicate differences in the adverse outcomes of chronic heart failure (CHF) in both ischemic (ICMP) and non-ischemic origins. The knowledge of the structural and functional myocardial state, especially of the left ventricle (LV), is insufficient for accurate risk stratification of unfavorable events in different etiopathogenetic forms of CHF. Aim . To make a comparative analysis of echocardiographic characteristics of CHF patients with reduced LV ejection fraction (EF) ≤35% depending on the origin of CHF. Material and methods. 498 patients of CHF 3-4 functional class of NYHA (New-York Heart Association) with EF ≤35% taking optimal drug therapy were included in the study. Based on the etiology of CHF, two groups of patients with CHF of ischemic genesis (n=254) and dilated cardiomyopathy (DCMP, n=244) were formed. Two-dimensional echocardiography techniques in Band M-mode, color Doppler, and tissue Doppler imaging were carried out. Results. Patients with ICMP and DCMP had the same pattern of LV remodeling (mainly on the type of eccentric hypertrophy), but they reliably differed in the basic parameters of LV architectonics: endsystolic and end-diastolic dimensions, LV volume, LV myocardial mass and values of these indicators, indexed by body surface area. DCMP patients had a higher value of medial-lateral dimension and volume of left atrial, pathological mitral and tricuspid regurgitation was registered more often. Conclusion. It was found that left heart dimensions and volumes of DCMP patients exceed similar parameters in patients with ICMP. The possible association of the results with future adverse outcomes of CHF demands further research.

Sustained-Release Ivabradine Hemisulfate in Patients With Systolic Heart Failure

BackgroundIvabradine has potent actions in reducing heart rate and improving clinical outcomes of chronic heart failure with reduced ejection fraction (HFrEF). At present, only the short-acting formulation of ivabradine is available that needs to be administered twice daily. ObjectivesThis study sought to evaluate the role of ivabradine hemisulfate sustained release (SR), a novel long-acting formulation of ivabradine dosed once daily, in stable patients with HFrEF. MethodsPatients with stabilized HFrEF in New York Heart Association functional class II-IV were enrolled and randomized to receive placebo or ivabradine SR in addition to standard medications. The primary endpoint was the change of left ventricular (LV) end-systolic volume index from baseline to week 32. ResultsWe randomly assigned 181 patients to placebo and 179 patients to ivabradine SR. After 32 weeks, a significant improvement of LV end-systolic volume index from baseline was observed in both arms with a greater effect in the ivabradine SR arm. Ivabradine SR therapy also exhibited superiority in improving LV end-diastolic volume index, LV ejection fraction, resting heart rate, the Kansas City Cardiomyopathy Questionnaire score, and hospital admission for heart failure worsening and cardiovascular disease in comparison to placebo. Overall adverse events showed no difference between the treatment arms. There were fewer occurrences of worsening heart failure in the ivabradine SR arm. ConclusionsThe present study demonstrates that ivabradine SR once daily in addition to optimum standard therapy improved heart function in patients with HFrEF. (Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets [FIRST]; NCT02188082)

Association of Repetitive Dosing of Levosimendan with Reduction of NYHA Class and NT-proBNP Levels in Decompensated Heart Failure: A Retrospective Cohort Study.

BackgroundThere is evidence that repetitive administration of levosimendan can improve outcome in chronic heart failure patients.ObjectiveThe aim of this retrospective study was to investigate the effect of therapy with levosimendan (LEV) additional to standard medical care in patients with symptomatic heart failure (HFrEF = heart failure with reduced ejection fraction) on NYHA class, NT-proBNP values, ejection fraction (EF) and body weight.Patients and Methods178 participating patients (125 male, 53 female; mean age of 73 ± 13 years) were grouped according to whether LEV was given once (group 1) or repetitively (group 2). In group 2 data were analysed for first treatment with LEV (group 2a) and for the following repetitive LEV treatments (group 2b). The differentiation was required to see if there were different results for the particular groups.ResultsRepetitive dosing was given between two and 11 times, leading to 47 repetitive applications of LEV and a total of 225 (178 once + 47 repetitive) applications. The mean time between the repetitive dosing was 133 days or 4.3 months. LEV in addition to standard medical treatment was associated with reduction of NT-proBNP levels from 9138 to 7051 pg/mL (p < 0.05). The corresponding values in group 2a and group 2b were 8790–4717 pg/mL (p < 0.05) as well as 13,681–7581 pg/mL (p < 0.05). The ejection fraction measured by echocardiography improved from 30 to 38% in group 1, from 31 to 45% in group 2a and from 30 to 35% in group 2b (p < 0.05). Addition of LEV was associated with significant reduction of NYHA class and bodyweight in all groups. No adverse side effects (e.g., rhythm disorder, hypotension, electrolyte disorder) were seen.ConclusionLEV may be useful as an additive to standard care of treatment for patients with acute de novo decompensation due to acute heart failure as well as to prevent further deterioration in patients with chronic heart failure disease at high risk for hospitalisation. Intraindividual changes in NT-proBNP levels may be useful in decision-making about the need for additional treatment options in patients with worsening heart failure.

Assessment of Trimetazidine Treatment in Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention.

Aims Trimetazidine (TMZ) is effective at improving clinical outcomes in chronic heart failure and stable coronary artery disease patients. However, no single study has comprehensively evaluated the efficacy of TMZ in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI). Methods We enrolled 401 Chinese patients. All patients received the same drug prescription except for TMZ. In blinded fashion, patients were randomized to either a control or an experimental group in which 60 mg TMZ was provided at admission and then at 20 mg three times a day thereafter. At 2 and/or 6 days, we evaluated creatine kinase (CK and CK-MB), cardiac troponin I (cTnI), C-reaction protein (CRP), serum tumor necrosis factor (TNF-α), serum creatinine (Cr), serum urea, glucose, glutamic pyruvic transaminase (ALT), and glutamic oxaloacetic transaminase (AST). Additionally, by echocardiography, we assessed left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), and cardiac output (CO). Results CK and CKMB, which were recorded on the second day in the hospital (each p=0.022), and cTNI, which was recorded on the sixth day in the hospital (p=0.003), were reduced with TMZ treatment compared to control. In addition, ALT and AST (p=0.001, p=0.000, respectively) and glucose after 6 days (p=0.011) were significantly lower in the study group than in the control group. Furthermore, LVEF after 10–14 days and 6 months after discharge (p=0.039 and p=0.047, respectively) was increased with TMZ treatment. The effects of TMZ on CRP, TNF-α, Cr, urea, LVEDD, and CO were not significant (all p > 0.05). Conclusions For AMI patients undergoing PCI, TMZ reduced circulating biomarkers of myocardial infarction, reduced values of ALT, AST, and glucose, and improved cardiac function compared with the control group.

Complementary Role of Combined Indirect and Direct Cardiac Sympathetic (Hyper)Activity Assessment in Patients with Heart Failure by Spectral Analysis of Heart Rate Variability and Nuclear Imaging: Possible Application in the Evaluation of Exercise Training Effects.

In chronic heart failure (CHF), abnormalities in cardiac autonomic control, characterized by sympathetic overactivity, contribute to the progression of the disease and are associated with an unfavorable prognosis. Assessing cardiac autonomic status is clinically important in the management of patients with CHF. To this aim, heart rate variability (HRV) analysis has been extensively used as a non-invasive tool for assessing cardiac autonomic regulation, and has been shown to predict the clinical outcome in patients with CHF. Adrenergic nerve activity has also been estimated using iodine-123 (I-123) metaiodobenzylguanidine (MIBG), a noradrenaline analogue. MIBG is an analogue of norepinephrine sharing the same cellular mechanism of uptake, storage, and release in presynaptic sympathetic neurons. As an innervation tracer, 123I-MIBG allows for the evaluation of cardiac sympathetic neuronal function. Cardiac MIBG imaging has also been reported to predict a poor clinical outcome in CHF. MIBG provides direct information on the function of the presynaptic sympathetic nerve endings, whereas HRV, which depends on postsynaptic signal transduction, reflects the end-organ response of the sinus node. The aim of this brief review is to provide the reader with some basic concepts regarding the spectral analysis of HRV and MIBG, highlighting what is known about their respective roles in detecting cardiac sympathetic hyperactivity in CHF and, in perspective, their possible combined use in assessing non-pharmacological treatments in patients with CHF and reduced ejection fraction, with a particular focus on the effects of exercise training.

Prognostic value of the combination of uric acid and NT-proBNP in patients with chronic heart failure

ObjectiveHyperuricemia is associated with poor outcomes in chronic heart failure (HF). We aimed to evaluate whether uric acid (UA) alone or in combination with N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a good predictor of all-cause mortality, HF hospitalization, and the composite endpoint of HF hospitalization or all-cause mortality in chronic HF. MethodsUA and NT-proBNP levels were evaluated retrospectively in 861 chronic HF patients with a left ventricular ejection fraction of ≤50%. The patients were compared by dividing them into 4 groups according to the cut-off values of UA and NT-proBNP. ResultsSerum UA concentrations were ≥ 7.0 mg/dL in 46.5% of the subjects. With a median follow-up of 30 months, 201 (23.3%) patients died and 308 (35.8%) patients were hospitalized during the study. The all-cause mortality rate was higher in the hyperuricemic group than that of the normouricemic group (p < 0.001). A multivariate Cox regression model revealed that UA and NT-proBNP were independent predictors of all-cause mortality (HR: 1.105, 95% CI: 1.019-1.198, p = 0.016 and HR: 3.743, CI: 2.647-5.292, p < 0.001, respectively). Patients were divided into 4 groups based on UA (≥ 7 and < 7 mg/dL) and NT-proBNP (≥ 2279 and < 2279 ng/L) levels. All-cause mortality, HF hospitalization, and the composite endpoint of HF hospitalization or all-cause mortality rates were higher in the group with high UA and NT-proBNP levels (p < 0.001, p < 0.001, p < 0.001, respectively). ConclusionHyperuricemia alone is an independent predictor of all-cause mortality in chronic HF. However, the combination of UA and NT-proBNP appears to be a stronger predictor of poor outcomes.