Virgílio da Rocha Olsen

Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival

Circulating levels of matrix metalloproteinase-2 (MMP-2) predict mortality and hospital admission in heart failure (HF) patients. However, the role of MMP-2 gene polymorphisms in the susceptibility and prognosis of HF remains elusive. In this study, 308 HF outpatients (216 Caucasian- and 92 African-Brazilians) and 333 healthy subjects (256 Caucasian- and 77 African-Brazilians) were genotyped for the -1575G>A (rs243866), -1059G>A (rs17859821), and -790G>T (rs243864) polymorphisms in the MMP-2 gene. Polymorphisms were analyzed individually and in combination (haplotype), and positive associations were adjusted for clinical covariates. Although allele frequencies were similar in HF patients and controls in both ethnic groups, homozygotes for the minor alleles were not found among African-Brazilian patients. After a median follow-up of 5.3 years, 124 patients (40.3%) died (54.8% of them for HF). In Caucasian-Brazilians, the TT genotype of the -790G>T polymorphism was associated with a decreased risk of HF-related death as compared with GT genotype (hazard ratio [HR] = 0.512, 95% confidence interval [CI] 0.285–0.920). However, this association was lost after adjusting for clinical covariates (HR = 0.703, 95% CI 0.365–1.353). Haplotype analysis revealed similar findings, as patients homozygous for the -1575G/-1059G/-790T haplotype had a lower rate of HF-related death than those with any other haplotype combination (12.9% versus 28.5%, respectively; P = 0.010). Again, this association did not remain after adjusting for clinical covariates (HR = 0.521, 95% CI 0.248–1.093). Our study does not exclude the possibility that polymorphisms in MMP-2 gene, particularly the -790G>T polymorphism, might be related to HF prognosis. However, due to the limitations of the study, our findings need to be confirmed in further larger studies.

QRS Widening Rates and Genetic Polymorphisms of Matrix Metalloproteinases in a Cohort of Patients With Chronic Heart Failure

BACKGROUND QRS duration is considered to be an indicator of adverse outcome in patients with heart failure (HF), and genetic polymorphisms may be involved in this conductivity impairment. We studied the prognostic impact of the QRS widening rate (QRS-WR) on patients with HF and the influence of the matrix metalloproteinases gene polymorphisms on the QRS-WR. METHODS This prospective cohort study included 184 patients with left ventricular (LV) systolic dysfunction (LV ejection fraction [LVEF] < 45%). The QRS-WR was calculated as the difference between 2 electrocardiogram assessments (in ms) divided by the time elapsed between each evaluation (months). The MMP-1 -1607 1G/2G, MMP-2 -790G/T and -1575G/A, MMP-3 -1171 5A/6A, MMP-9 -1562 C/T and R279Q, and MMP-12 -82A/G polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism. RESULTS Patients were predominantly white (68%) men (67%) in New York Heart Association functional classes I and II (77%). Patients with HF with a QRS-WR ≥ 0.5 ms/month had more HF-related deaths and more combined clinical events than those with a QRS-WR < 0.5 ms/month (P = 0.03 and P = 0.01, respectively). After adjusting for other covariates, the QRS-WR remained an independent predictor of combined clinical events (hazard ratio, 1.6; 95% confidence interval, 1.1-2.5; P = 0.02). The MMP-1 2G2G genotype was associated with nearly a 2-fold increase in QRS-WR (P = 0.03). Conversely, patients with the MMP-3 5A5A genotype and a nonischemic cause of HF were protected against QRS enlargement (P = 0.03). CONCLUSIONS QRS-WR retains prognostic value in patients with chronic HF receiving guideline-based pharmacologic treatment. MMP gene polymorphisms can influence the rate of QRS enlargement over time.

Causes and Predictors of In-Hospital Mortality in Patients Admitted with or for Heart Failure at a Tertiary Hospital in Brazil

Background Although heart failure (HF) has high morbidity and mortality, studies in Latin America on causes and predictors of in-hospital mortality are scarce. We also do not know the evolution of patients with compensated HF hospitalized for other reasons. Objective To identify causes and predictors of in-hospital mortality in patients hospitalized for acute decompensated HF (ADHF), compared to those with HF and admitted to the hospital for non-HF related causes (NDHF). Methods Historical cohort of patients hospitalized in a public tertiary hospital in Brazil with a diagnosis of HF identified by the Charlson Comorbidity Index (CCI). Results A total of 2056 patients hospitalized between January 2009 and December 2010 (51% men, median age of 71 years, length of stay of 15 days) were evaluated. There were 17.6% of deaths during hospitalization, of which 58.4% were non-cardiovascular (63.6% NDHF vs 47.4% ADHF, p = 0.004). Infectious causes were responsible for most of the deaths and only 21.6% of the deaths were attributed to HF. The independent predictors of in-hospital mortality were similar between the groups and included: age, length of stay, elevated potassium, clinical comorbidities, and CCI. Renal insufficiency was the most relevant predictor in both groups. Conclusion Patients hospitalized with HF have high in-hospital mortality, regardless of the primary reason for hospitalization. Few deaths are directly attributed to HF; Age, renal function and levels of serum potassium, length of stay, comorbid burden and CCI were independent predictors of in-hospital death in a Brazilian tertiary hospital.

Encapsulated mononuclear stem cells: paracrine action for the treatment of acute myocardial infarction

Cell therapy is considered as a treatment option for acute myocardial infarction (AMI). Released molecules by cells paracrine action may promote tissue regeneration. Therefore we used bone-marrow mononuclear cells (BMMNCs) from GFP+ Wistar rats encapsulated in sodium alginate for AMI treatment. Animals were randomly allocated into groups – empty (EC); BMMNC capsules; or sham. AMI was induced by occlusion of left anterior artery and capsules were delivered intrathoracically. Troponin I was measured 24h after AMI and echocardiography was performed at 48h and 7d after AMI. On day 7 animals were euthanized and their hearts were harvested. Tissue levels of TNF-α, IL-6, IL-10, cleaved caspase-3, and catalase were measured. Technical procedures were performed by blinded operators. There was no difference in either heart morphofunctional parameters or biochemical analysis between AMI groups. We conclude that the paracrine effects of BMMNCs lacks efficacy to modulate events associated with AMI in the rat.