Patients with chronic heart failure (CHF) express enhanced catabolic metabolism finally resulting in overall weight loss, whereas adipokines might play a crucial role in signaling among tissues. The aim of this study was to investigate the possible associations of defined variability in leptin (dbSNP ID rs7799039), proopiomelanocortin (dbSNP ID rs3754860 and dbSNP ID rs1009388), and leptin receptor gene (dbSNP rs1137101) with CHF and evaluate their potential as the CHF susceptibility genes. The case-control study comprised a total of 372 patients of Caucasian origin with chronic heart failure (New York Heart Association [NYHA] functional classes II-IV, ejection fraction (EF) <40%) and 407 healthy controls. They were genotyped for the leptin (LEP) -2548 G/A, leptin receptor (LEPR) Gln223Arg, and proopiomelanocortin (POMC) RsaI (5'-untranslated region) and C1032G variants (intron 1) using PCR-based methodology. No case-control differences in genotype as well as allele frequencies were observed between CHF patients and controls. We constructed POMC RsaI/C1032G haplotypes, having found no significant association with body mass index (BMI), left ventricle ejection fraction (LVEF), left ventricle hypertrophy (LVH) and diabetes mellitus (DM). Multivariate regression analyses revealed an approximately 2-fold risk for NYHA class IV associated with the LEPR Gln223Arg (P = 0.0000001, odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.56-2.84); it also displayed an independent prediction role for LVEF in heart failure cases of all etiologies (P = 0.002, OR = 4.05, 95% CI = 1.36-10.06). In subanalyses according to CHF etiology the LEPR Gln223Arg showed an independent prediction role for NYHA IV in IHD patients (P = 0.0001, OR = 2.50, 95% CI = 1.69-3.82) and both for NYHA IV(P = 0.007, OR = 2.04, 95% CI = 1.20-3.84) and LVEF (P = 0.004, OR = 11.87, 95% CI = 2.08-55.6) in DCMP patients. The role of the polymorphic variants in the genes encoding for adipokines as potential CHF susceptibility genes is unclear. Based on our findings, the LEPR Gln223Arg polymorphism could be considered a disease susceptibility modulating factor both in ischemic heart disease or dilated cardiomyopathy patients.
Remodelling of extracellular matrix by activated matrix metalloproteinases is considered to contribute to progression of ventricle remodelling during chronic heart failure. The aim of this study was to associate two promoter polymorphisms, -790T/G and -735C/T, in the gene for matrix metalloproteinase (MMP)-2 (gelatinase A) with chronic heart failure (CHF). For this purpose, 164 patients (124 men, 40 women, median age 56 years, range 21-91 years) with CHF (functional class NYHA II-IV, ejection fraction median 25%, cardiothoracic index more than 50%) were compared with 196 control subjects without clinical signs of cardiovascular disease (131 men and 65 women, median age 56 years, range 27-84 years) in -790T/G and -735C/T MMP-2 genotype distributions and allelic frequencies. The genotypes were determined by polymerase chain reaction (PCR) with restriction analyses. A significant increase of the T allele of the -790T/G MMP-2 polymorphism (p = 0.04), as well as of the C allele of the -735C/T MMP-2 gene polymorphism, in patients with CHF was proven (p = 0.04). The heterozygote CT of the -735C/T MMP-2 polymorphism exhibits a 7 times higher odds ratio (OR) for the CHF patients with lower levels of total cholesterol (less than 5 mmol/l), especially for non-hypertensive CHF men (OR = 7.28, 95% confidence interval 1.51-35.03, p = 0.006). Determination of MMP polymorphisms in the regulatory area of the gene could help us to comprehend individual susceptibility of patients with CHF to MMP inhibitors based on known risks of MMP genotypes.
Aims: Heart transplantation (HTx) is the most effective therapy in patients with end-stage heart failure. Diabetesrelated complications are relative contraindications for heart transplantation. The aim of our study was to analyse the impact of DM (diabetes mellitus) at the time of heart transplantation and new-onset post-transplantation DM on long-term survival.Methods: A retrospective database analysis was performed on all patients who had undergone HTx at our institution between 4/1997 and 9/2007. Patients were divided into three groups: Group A -patients without DM; Group B -patients with new onset of DM after HTx; Group C -patients with DM prior to HTx.Results: Patients with DM before the surgery were more obese, their BMI was 27.7 ± 2.90, compared to groups A and B with BMI of 24.7 ± 3.37 and 25.3 ± 3.64 respectively (p = 0.0003). Patients in group B had statistically significantly higher risk of developing acute rejection (G 1B and more according to International Society of Heart and Lung Transplantation -ISHLT -classification) (p = 0.0350). The incidence of infections between individual groups showed no statistically significant differences (p = 0.5839). Five-year survival in group A was 82%, 10-year survival was 73%. Corresponding numbers for group B were 86% and 78%, for group C 86% and 83%. Differences between groups were not statistically significant (p = 0.2560).Conclusions: DM in patients after heart transplantation in our study had no effect on long-term survival of patients. Post-transplantation DM increases risk of acute rejections. Pre-transplantation DM was associated with excessive bodyweight or obesity.
The pharmacological treatment of dilated cardiomyopathy overlaps with the treatment of heart failure. The primary objective of this treatment is to slow the progression of disease and improve quality and length of life. All patients, including those with asymptomatic dysfunction of the left ventricle, ought to receive angiotensin converting enzyme inhibitors, (in the case of intolerance, angiotensin receptor blockers), and beta blockers. The results of studies involving aliskiren have been, so far, disappointing. In symptomatic heart failure NYHA II-IV diuretics and mineralcorticoid receptor antagonists should be added to treatment. Digoxin is recommended in the event of atrial fibrillation, and otherwise only in the event of NYHA III and IV. Ivabradine is recommended for patients with sinus rhythm and pulse rate of > 70/min. In decompensation of heart failure, dobutamine, phosphodiesterase inhibitors or levosimendan are administered over the short-term. Of the recent treatment options, the vasopressin blocker and adenosine A1 receptor antagonist (rolofylline) were disappointing. One treatment with potential for the future is omecamtiv mecarbil, a heart myosin activator.
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