Clinical Characteristics And Related Genes Of Heart Failure With Normal Ejection Fraction

Part one: Clinical Characteristics and Related Risk Factors of Heart Failure withNormal Ejection FractionBackground: Heart failure is one of the most important cardiovascular diseaseswhich are harmful to human health in the21st century. It is the end stage of mostcardiovascular diseases. Attention has focused mainly on those patients with heartfailure with reduced ejection fraction (HFREF). However, based on the previous studies,patients with heart failure with normal ejection fraction (HFNEF) have an increasedmorbidity. But the mortality in patients with HFNEF has remained unchanged becausemuch less is known about the pathophysiology and treatment of this disease. Sonowadays, HFNEF has become a research hotspot.Objective: To analyze the clinical characteristics and related risk factors of heartfailure with normal ejection fraction.Methods:960inpatients (≥40years old), admitted to our hospital from January2010to May2013, were divided into HFNEF group (n=245), HFREF group (n=473)and normal group (n=242). Their laboratory data, basic diseases, medical therapy andechocardiography parameters were analyzed.Results: The age of patients with HFNEF was older, the number of female patientswith HFNEF was higher, the serum sodium levels were higher, and the incidence ofhypertension, atrial fibrillation and cerebral infarction was significantly higher inHFNEF group than in HFREF group. Compared with HFREF, the use of angiotensin IIreceptor blockers and calcium channel blocker was much greater in HFNEF group(P<0.05). HFNEF group more often had normal left ventricular diameters and volumes,and concentric left ventricular hypertrophy. Compared with the normal group, HFNEFgroup had higher level of N-terminal pro-brain natriuretic peptide (NT-proBNP)(P<0.01). Besides, HFNEF group had a higher left ventricular mass index and larger left atrial than the normal group (P<0.01). Female and atrial fibrillation were theindependent risk factors for HFNEF in inpatients (P<0.05).Part two: Related Genes of Heart Failure with Normal Ejection FractionBackground: In recent years, HFNEF has become a hot topic in the field ofcardiovascular diseases. Although researchers have made some progress in thepathogenesis, there are still many problems to be studied, especially in terms ofHFNEF-related genes and polymorphisms. With the rapid development of the secondgeneration sequencing technology, some new ideas have been provided in terms ofpathogenesis, prevention, diagnosis and the treatment of HFNEF. Based on the basis ofwhole genome sequencing, genome-wide association studies (GWAS) and linkageanalysis, a large number of candidate genes, candidate regions or candidate locusassociated with important traits are located on chromosome. Target region capturesequencing which is used to study the interested genomic regions can meet the researchneeds. It is comparatively smaller than the whole exome, and can spend less and getmore information for the region of interest. In addition, target region sequencing isextremely suitable for case/control studies with large sample sizes. Target region capturesequencing can be used to not only find single nucleotide polymorphisms (SNPs) ofinterested genomic regions but also confirm them.Objective: We aimed to screen the susceptibility locus of HFNEF preliminarily.Methods:180inpatients (≥40years old) were divided into HFNEF group (n=60),HFREF group (n=60) and normal group (n=60). The gender and age of three groups arematched. Their clinical information and blood preparation (genomic DNA samples) arecollected. Target region capture sequencing and next-generation sequencing technologywere used to identify associated SNPs of HFNEF. It is the enrichment of specificregions or specific genes by microarray hybridization using NimbleGen SequenceCapture array based on designed probes which are designed according to the basesequence of genomic regions of interest. Then the high throughput sequencing andbioinformatics analysis were completed.Results: After removal of samples of substandard quality, a total of167samples finally underwent target region capture sequencing, including57in HFNEF group,54inHFREF group and56in control group. Using the human genome (hg19) as thereference genome, we found11SNPs that were significantly different in HFNEF groupafter bioinformatics analysis (P<0.001), which were located in the protein codingregions, non-coding regions,5’ untranslated regions (UTR5’) and3’ untranslatedregions (UTR3’) etc.Conclusion: HFNEF is a heterogeneous syndrome and about one third of theinpatients with heart failure have HFNEF. Female and atrial fibrillation were itsimportant risk factors in this crowd. The SNPs which were found to be significantlydifferent in HFNEF are very likely to affect the function of the genes, and furthermoreaffect the expression of the proteins, resulting in differences in phenotype.