A Common Variant in NID1 Gene Associated with the Prognosis of Heart Failure

Heart failure is a common condition responsible for at least 290 000 deaths each year in the United States alone.1 A small minority of heart failure cases are attributed to Mendelian or familial cardiomyopathies. The majority of systolic heart failure cases are not familial but represent the end result of 1 or many conditions that primarily injure the myocardium sufficiently to diminish cardiac output in the absence of compensatory mechanisms. Paradoxically, because they also injure the myocardium, it is the chronic actions of the compensatory mechanisms that in many instances contribute to the progression from simple cardiac injury to dilated cardiomyopathy and overt heart failure. Thus, the epidemiology of common heart failure appears to be just as sporadic as its major antecedent conditions (atherosclerosis, diabetes, hypertension, and viral myocarditis). Familial trends in preclinical cardiac remodeling2 and risk of developing heart failure3 reveal an important role for genetic modifiers in addition to clinical and environmental factors. Candidate gene studies performed over the past 10 years have identified a few polymorphic gene variants that modify risk or progression of common heart failure.4 Whole-genome sequencing will lead to the discovery of other genetic modifiers that were not candidates.5 The imminent availability of individual whole-genome sequences at a cost competitive with available genetic tests for familial cardiomyopathy will no doubt further expand the list of putative genetic heart failure modifiers. Heart failure risk alleles along with traditional clinical factors will need to be considered by clinical cardiologists in their design of optimal disease surveillance and prevention programs and in individually tailoring heart failure management. The use of individual genetic make-up is likely to have the earliest and greatest impact on managing patients with heart failure by tailoring available pharmacotherapeutics to optimize patient response and minimize adverse effects (ie, the …

Treatment of Diabetes in People with Heart Failure

Background:Reported studies have shown that expression levels of microRNAs (miRNAs) are related to survival time of patients with heart failure (HF). A systematic review and meta-analysis were conducted to study circulating miRNAs expression and patient outcome.Methods:Meta-analysis estimating expression levels of circulating miRNAs in HF patients from January 2010 until June 30, 2018, through conducting online searches in Pub Med, Cochrane Database of Systematic, EMBASE and Web of Science and reviewed by 2 independent researchers. Using pooled hazard ratio with a 95% confidence interval to assess the correlation between miRNAs expression levels and overall survival.Results:Four relevant articles assessing 19 circulating miRNAs in 867 patients were included. In conclusion, the meta-analysis results suggest that HF patients with low expression of serum miR-1, miR-423-5p, miR-126, miR-21, miR-23, miR-30d, miR-18a-5p, miR-16-5p, miR-18b-5p, miR-27a-3p, miR-26b-5p, miR-30e-5p, miR-106a-5p, miR-233-3P, miR-301a-3p, miR-423-3P, and miR-128 have significantly worse overall survival (P < .05). Among them, miR-18a-5p, miR-18b-5p, miR-30d, miR-30e-5p, and miR-423-5p are strong biomarkers of prognosis in HF.

Successes and failures of current treatment of heart failure

Heart failure

Why is depression bad for the failing heart? a review of the mechanistic relationship between depression and heart failure

Mitochondrial dysfunction plays a vital role in the pathophysiologic process of heart failure (HF). As a quality control system, mitochondrial fusion and fission are under control of mitochondrial fusion and fission-related proteins. The objective of this study was to investigate the effects of common variants in mitochondrial fusion and fission-related genes on the prognosis of HF. We performed whole exome sequencing (WES) with 1000 HF patients; the statistically significant variant was further genotyped in the replicated population with 2324 HF patients. A series of function analysis including western blot, cell proliferation assay, and in vitro OMA1 activity assay were conducted to illuminate the underlying mechanism. We identified a missense variant rs17117699 associated with the prognosis of HF in group without β-blocker use rather than with β-blocker use in two-stage population: adjusted P = 0.79, HR = 0.88 (0.36-2.13) in group with β-blocker use and adjusted P = 0.016, HR = 1.43 (1.07-1.91) in group without β-blocker in first-stage population; adjusted P = 0.42, HR = 0.85 (0.56-1.28) in group with β-blocker use and adjusted P = 0.015, HR = 1.39 (1.06-1.82) in group without β-blocker in replicated stage. Functional analysis indicated that rs17117699-G allele increased the activity of OMA1 assessed by the ratio of S-OPA1 to L-OPA1 and suppressed cells proliferation under ISO treatment when compared with rs17117699-T allele. Furthermore, OMA1 functioned downstream of β-adrenergic receptor signaling and ISO-induced OPA1 cleavage is dependent on OMA1. Our findings demonstrate that rs17117699T>G in OMA1 increases the risk of HF mortality via enhancing its OPA1 cleavage activity. It is a promising potential treatment target for HF. NCT03461107. https://www.clinicaltrials.gov/ct2/show/NCT03461107?term=03461107&cond=Heart+Failure&cntry=CN&rank=1.

Section 11: Evaluation and Management of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

Objective To investigate the relationship between the prognosis of patients with coronary heart disease in elderly heart failure between lipid levels. Methods 720 cases of coronary heart disease in elderly patients with heart failure, according to the survival of the follow-up period were divided into survival group and death group, comparing lipid levels in each group of patients, the use of multivariate Cox regression analysis to investigate the effects of lipids in elderly patients with heart failure, coronary artery disease prognosis. Results Age group of death, old myocardial infarction （OMI）, the probability of occurrence of atrial fibrillation, anemia was significantly higher than that of the survival group（ X2 = 5. 626,4. 597,5. 632,6. 461, all P 〈 0.05 ）, HDL-C, EF, ACEI/ARB and statins was significantly lower than those of the survival group（ t = 10. 725,9. 563,8. 457,9. 170 ,P 〈 0.05 or P 〈 0.01 ）. An- giotensin-converting enzyme inhibitors（ ACEI） /angiotensin Ⅱ receptor antagonists（ARB） would help to improve the prognosis（ r = 0. 678 ,P 〈 0. 01 ） , whereas low levels and low levels of HDL-C, NYHA Ⅲ-grade IV, age was a risk fae- tor（r =1.052,2.298,2.586,all P〈0. 01）. Conclusion There is a close contact between HDL-C and prognosis of heart failure in elderly patients with coronary heart disease,in order to improve the prognosis of patients,it ean be ap- propriately managed to elevate HDL-C levels. Key words: Coronary disease ; Heart failure, congestive ; Prognosis ; Lipoproteins ; Aged

Phosphoinositide 3‐kinase γ (PI3Kγ) is G‐protein‐coupled receptor‐activated lipid kinase with both kinase‐dependent and kinase‐independent activity. Plenty of evidence have demonstrated that PI3Kγ participated in TAC and I/R‐induced myocardial remodelling and heart failure (HF). In this study, we tested the hypothesis that common variants in the PI3Kγ gene (PIK3CG) were associated with the prognosis of HF in the Chinese Han population. Through re‐sequencing and genotyping, we finally identified a common variant in the 3′UTR of PIK3CG strongly associated with the prognosis of HF in two‐stage population: adjusted p = 0.007, hazard ratio = 0.56 (0.36–0.85) in the first cohort and adjusted p = 0.024, hazard ratio = 0.39 (0.17–0.88) in the replicated cohort. A series of functional assays revealed that rs10215499‐A allele suppressed PIK3CG translation by facilitating has‐miR‐133a‐3p binding, but not the G allele. Subjects carrying the GG genotype showed higher mRNA and protein level than those with AA and AG genotype. Furthermore, overexpression of PIK3CG could protect AC16 from hypoxia/reoxygenation (H/R)‐induced apoptosis, while the case was opposite for PIK3CG silencing. In conclusion, common variant rs10215499 in the 3′‐UTR of PIK3CG might affect the prognosis of HF by interfering with miR‐133a‐3p binding and PIK3CG is a promising target for HF treatment in the future.

Heart failure and its treatment from the perspective of sympathetic nerve activity

Receptor‐interacting protein kinase 3 (RIP3) is a key determinant of necroptosis and participates in ischaemia—and oxidative stress‐induced necroptosis, myocardial remodelling and heart failure (HF). In this study, we tested the hypothesis that common variants in RIP3 gene were associated with the risk and prognosis of HF in the Chinese Han population. By re‐sequencing and luciferase assays, we identified a common functional variant in the RIP3 promoter region. The rs3212247‐T allele suppressed RIP3 promoter activity by facilitating transcription factor SOX17 binding, but not the C allele. We further recruited 2961 control participants and 3194 HF patients who underwent a mean follow‐up of 19 months (6‐31 months) for this study. Rs3212247 and another missense variant rs3212254 were genotyped. Although rs3212247 did not significantly associate with increased risk of HF (odds ratio = 1.00, 95% CI = 0.92‐1.08, P = 0.91), it raised the risk for cardiovascular death and cardiac transplantation (hazard ratio = 1.47, 95% CI = 1.13‐1.91, P = 0.004). Moreover, participants carrying the rs3212247 CC genotype had higher plasma levels of RIP3 than those carrying the TT or TC genotype (p for trend = 0.02) in New York Heart Association class III HF group. No association was found between the RIP3 missense variant rs3212254 and risk or prognosis of HF after adjustment for traditional risk factors. In conclusion, genetic variant in RIP3 promoter region is associated with increased RIP3 transcription, thus contributed to the poor prognosis of HF patients. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT03461107?term=03461107&cond=Heart+Failure&cntry=CN&rank=1. Unique identifier: NCT03461107.

2003: The year in heart failure*1

Background Hyperuricaemia is associated with a poorer prognosis in heart failure (HF) patients. Benefits of hyperuricaemia treatment with allopurinol have not yet been confirmed in clinical practice. The aim of our work was to assess the benefit of allopurinol treatment in a large cohort of HF patients. Methods and results The prospective acute heart failure registry (AHEAD) was used to select 3,160 hospitalized patients with a known level of uric acid (UA) who were discharged in a stable condition. Hyperuricaemia was defined as UA ≥500μmol/l and/or allopurinol treatment at admission. The patients were classified into three groups: without hyperuricaemia, with treated hyperuricaemia and with untreated hyperuricaemia at discharge. Two- and five-year all-cause mortality were defined as endpoints. Patients without hyperuricaemia, unlike those with hyperuricaemia, had a higher left ventricular ejection fraction, a better renal function and higher haemoglobin levels, had less frequently diabetes mellitus and atrial fibrillation, and showed better tolerance to treatment with ACEIs/ARBs and/or beta-blockers. In a primary analysis, the patients without hyperuricaemia had the highest survival rate. After using the propensity score to set up comparable groups, the patients without hyperuricaemia had a similar five-year survival rate as those with untreated hyperuricaemia (42.0% vs 39.7%, p=0.362) whereas those with treated hyperuricaemia had a poorer prognosis (32.4% survival rate; p=0.006 vs non-hyperuricaemia group and p=0.073 vs untreated group). Conclusion Hyperuricaemia was associated with an unfavourable cardiovascular risk profile in HF patients. Treatment of hyperuricaemia with low doses of allopurinol did not improve the longterm prognosis of HF patients. Acknowledgement/Funding Ministry of Health CZ 65269705 and MUNI/A/1250/2017

ObjectivesThe purpose of this study was to assess the clinical characteristics, treatments, and prognosis of acute heart failure (AHF) in the emergency department.MethodsA prospective, cohort, multicentre, non-interventional registry study of...