Dirceu R. Almeida

Incremental shuttle and six-minute walking tests in the assessment of functional capacity in chronic heart failure

BACKGROUND The incremental shuttle test presents some theoretical advantages over the six-minute walk test in chronic heart failure (CHF), including better standardization and less dependency on collaboration. OBJECTIVES The present study evaluated test-retest repeatability, test accuracy in predicting a peak oxygen consumption (VO(2)) of 14 mL/kg/min or less, as well as the prognostic value of both walking tests in stable CHF patients. METHODS Sixty-three patients (44 men; New York Heart Association functional class II to IV) underwent an incremental treadmill exercise test and, on another day, the walk test in duplicate. RESULTS Patients showed well-preserved functional capacity according to the distance walked in both tests (six-minute walk test 491+/-94 m versus incremental shuttle walk test 422+/-119 m; P<0.001). Interestingly, the six-minute and incremental shuttle walk test differences in distance walked were higher in more disabled patients. The mean bias +/-95% CI of the within-test differences were similar (7+/-40 m and 8+/-45 m, respectively). Peak VO(2), but not distance walked in either test, was associated with survival (P<0.05). CONCLUSIONS The incremental shuttle walk test showed similar repeatability and accuracy in estimating peak VO(2) compared with the six-minute walk test in CHF patients. Direct measurement of peak VO(2), however, remains superior to either walking test in predicting survival--at least in patients with well-preserved functional capacity.

Intragraft activation of genes encoding cytotoxic T lymphocyte effector molecules precedes the histological evidence of rejection in human cardiac transplantation

BACKGROUND The purpose of the present study was to investigate transcripts of perforin, granzyme B, and Fas ligand (FasL) in heart transplants undergoing rejection. METHODS Quantitative reverse transcriptase-polymerase chain reaction was applied for mRNA detection in 29 endomyocardial biopsy specimens from 11 cardiac allograft recipients. RESULTS The mRNA levels of granzyme B, perforin, and FasL were higher (P<0.05) in biopsy specimens with rejection than in biopsy specimens without rejection (granzyme B, 0.53 vs. 0.09; perforin, 0.34 vs. 0; FasL, 0.57 vs. 0.36). In prerejection biopsy specimens, granzyme B and FasL levels were significantly higher than in biopsy specimens without rejection. Any two of the three transcripts were increased in 100% of prerejection, in 92% of rejection, and in 36% of no rejection biopsy specimens (P<0.04). CONCLUSIONS The assessment of intragraft levels of cytotoxic T lymphocyte effector molecule mRNA represents a valuable tool in the monitoring of cardiac allograft rejection, especially considering the predictive value for warning of impending acute rejection.

Monitoring of intragraft and peripheral blood TIRC7 expression as a diagnostic tool for acute cardiac rejection in humans

T-cell immune response cDNA 7 (TIRC7) is a recently described T-cell costimulatory molecule that exhibits a central role in T-cell activation in vitro and in vivo. The present study was undertaken to investigate association between intragraft and peripheral blood mononuclear cell (PBMC) TIRC7 mRNA levels and cardiac allograft rejection in humans. TIRC7 gene expression levels were determined by a quantitative-competitive reverse transcriptase-polymerase chain reaction (QC-RT-PCR) in endomyocardial biopsies and in PBMC from cardiac transplant recipients. Biopsies collected during rejection or up to 15 days before rejection showed heightened TIRC7 mRNA expression in comparison with biopsies without rejection. All prerejection and rejection biopsies showed TIRC7 mRNA upregulation, while this was present in only 30% of the biopsies without rejection. Regarding TIRC7 mRNA in PBMC, transplant recipients showed lower levels than healthy individuals and, in contrast to the results obtained in biopsies, the levels were lower during rejection than in rejection-free periods. In summary, TIRC7 mRNA expression levels increase in biopsies and decrease in peripheral blood during acute cardiac rejection. We conclude that intragraft detection of TIRC7 transcripts is a useful tool not only for the diagnosis but also for the prediction of acute heart allograft rejection episodes.

Vasoplegic syndrome after off-pump coronary artery bypass surgery

OBJECTIVE The vasoplegic syndrome (VS) has been implicated in life-threatening complications after open heart surgery, where the whole-body inflammatory reaction is attributed to the cardiopulmonary bypass (CPB). Off-pump coronary artery bypass grafting (OPCAB) has been recently achieving growing enthusiasm mainly due avoiding the side effects of CPB. However herein the occurrence of VS in OPCAB is reported. METHODS The vasoplegic syndrome usual findings occurring in the early postoperative period include severe hypotension, tachycardia, normal or elevated cardiac output and low systemic vascular resistance. Four patients underwent to OPCAB presented all the signs of VS intraoperatively or within the first 6 postoperative h. RESULTS The patients needed aggressive vasoactive drug support for hemodynamic stabilization and all of them developed complications. These patients also had tendency to require administration of blood and blood derivatives due to diffuse and oozing type bleeding. Mean intensive care unit stay of surviving patients was 70 h and mean period of postoperative hospitalization was 9 days. Tumor necrosis factor-alpha blood levels in one patient were elevated postoperatively though no signs of infection were observed. One patient died. CONCLUSIONS Although vasoplegic syndrome can complicate OPCAB surgery, the rationale for avoiding CPB remains valid considering the benefits provided by OPCAB.

Effects of home-based exercise training for patients with chronic heart failure and sleep apnoea: a randomized comparison of two different programmes

Objective: To evaluate the effects of home-based exercise for patients with chronic heart failure and sleep apnoea and to compare two different training programmes. Design: A randomized, prospective controlled trial. Setting: Department of Cardiology, University Hospital, Brazil. Subjects: Fifty chronic heart failure patients with sleep apnoea were randomized in three groups: Group 1 (aerobic training, n = 18), Group 2 (aerobic with strength training, n = 18), and Group 3 (untrained, n = 14). Interventions: The training programme for Groups 1 and 2 began with three supervised exercise sessions, after they underwent three months of home-based exercise. Patients were followed by weekly telephone call and were reviewed monthly. Group 3 had the status of physical activity evaluated weekly by interview to make sure they remained untrained. Main outcome measures: At baseline and after three months: cardiopulmonary exercise testing, isokinetic strength and endurance, Minnesota living with heart failure questionnaire and polysomnography. Adherence was evaluated weekly. Results: Of the 50 patients enrolled in the study, 45 completed the programme. Clinical events: Group 1 (one death), Group 2 (one myocardial infarction), Group 3 (one death and two strokes). None were training related. Training groups showed improvement in all outcomes evaluated and the adherence was an important factor (Group 1 = 98.5% and Group 2 = 100.2%, P = 0.743). Untrained Group 3 demonstrated significant decrease or no change on measurements after three months without training. Conclusion: Home-based exercise training is an important therapeutic strategy in chronic heart failure patients with sleep apnoea, and strength training resulted in a higher increase in muscle strength and endurance.

Interleukin-2 gene polymorphism is associated with renal but not cardiac transplant outcome

It was recently shown that IL-2 gene single nucleotide polymorphism (SNP) at position -330 (G-->T) is related to in vitro cytokine production levels, with the T/T and T/G genotypes being associated with low production and the G/G genotype associated with high production. The objective of this study was to investigate a possible influence of this polymorphism on renal and cardiac allograft outcomes. IL-2 SNP G-T (-330) was determined by PCR-RFLP in 67 recipients of heart allografts and in 63 recipients of renal grafts from HLA-haplo-identical, related donors. A higher frequency of the T/T genotype was observed in renal transplant patients who experienced at least one acute rejection episode during the first 3 months after transplantation than in those without rejection during this period (80% vs 49%, respectively, P <.05). Accordingly, the same genotype tended to be more frequent in renal recipients with a 6-month serum creatinine level above 1.5 mg/dL (median value for the whole group of kidney recipients) than in patients with lower creatinine levels (79% vs 45%, P <.08). Regarding cardiac transplant recipients, no associations were observed concerning acute rejection or graft survival. The finding of the association of T/T but not T/G genotype with acute kidney rejection was unexpected considering that both genotypes were shown to be associated with equal (low) IL-2 in vitro production. Further studies are necessary not only to dissect the nature of IL-2 T/T genotype association with kidney rejection, but also to explain why this genotype does not apparently influence cardiac allograft outcome.

Correlação entre qualidade de vida e capacidade funcional na insuficiência cardíaca

BACKGROUND: Patients with cardiac failure (CF) present progressive incapacity and decreased quality of life, both related to dyspnea and fatigue. Thus, there is the increasing interest in measring the quality of life (QL), by generic instrument, such as the 36-item Short-Form Health Survey (SF-36), by specific instrument, such as Minnesota Living with Heart Failure (MLHFQ). OBJECTIVE: This study has the objective to correlate the QL surveys, SF-36 and MLHFQ, with the functional capacity of patients with CF, expressed by the cardiopulmonary test and the TC6M. METHODS: Using the SF-36 and MLHFQ surveys for QL evaluation, for the evaluation of the functional capacity, it was used the cardiopulmonary test, being executed using a tredmill with Weber protocol, as well sa the distance covered in the walk test of six minutes (TC6M). RESULTS: Forty-six patients were selected with CF diagnosis (22 men, average age of 52 years old), classes II and III of New York Heart Association. It was observed that the mild correlation between the physical and emotional domains of SF-36 and VE/VCO2.peak (r=-0.3; p<0.05) and the distance covered in TC6M (r=0.4; p<0.05), respectively. It was also observed the mild to moderate correlations of MLHFQ total score with VO2.peak (r=-0.5; p<0.05), the aerobic threshold (r=-0.4; p<0.05) and the distance covered in TC6M (r=-0.5; p<0.05). CONCLUSION: The data suggest that the application of both evaluation instruments of QL, generic (SF-36) and specific (MLHFQ) in patients with CF, showed mild and moderate correlation with the variable of the cardiopulmonary test with the variables of the cardiopulmonary test and the distance covered in TC6M.

Molecular basis for the improvement in muscle metaboreflex and mechanoreflex control in exercise-trained humans with chronic heart failure

Previous studies have demonstrated that muscle mechanoreflex and metaboreflex controls are altered in heart failure (HF), which seems to be due to changes in cyclooxygenase (COX) pathway and changes in receptors on afferent neurons, including transient receptor potential vanilloid type-1 (TRPV1) and cannabinoid receptor type-1 (CB1). The purpose of the present study was to test the hypotheses: 1) exercise training (ET) alters the muscle metaboreflex and mechanoreflex control of muscle sympathetic nerve activity (MSNA) in HF patients. 2) The alteration in metaboreflex control is accompanied by increased expression of TRPV1 and CB1 receptors in skeletal muscle. 3) The alteration in mechanoreflex control is accompanied by COX-2 pathway in skeletal muscle. Thirty-four consecutive HF patients with ejection fractions <40% were randomized to untrained (n = 17; 54 ± 2 yr) or exercise-trained (n = 17; 56 ± 2 yr) groups. MSNA was recorded by microneurography. Mechanoreceptors were activated by passive exercise and metaboreceptors by postexercise circulatory arrest (PECA). COX-2 pathway, TRPV1, and CB1 receptors were measured in muscle biopsies. Following ET, resting MSNA was decreased compared with untrained group. During PECA (metaboreflex), MSNA responses were increased, which was accompanied by the expression of TRPV1 and CB1 receptors. During passive exercise (mechanoreflex), MSNA responses were decreased, which was accompanied by decreased expression of COX-2, prostaglandin-E2 receptor-4, and thromboxane-A2 receptor and by decreased in muscle inflammation, as indicated by increased miRNA-146 levels and the stable NF-κB/IκB-α ratio. In conclusion, ET alters muscle metaboreflex and mechanoreflex control of MSNA in HF patients. This alteration with ET is accompanied by alteration in TRPV1 and CB1 expression and COX-2 pathway and inflammation in skeletal muscle.

I Brazilian Registry of Heart Failure - Clinical Aspects, Care Quality and Hospitalization Outcomes.

Background Heart failure (HF) is one of the leading causes of hospitalization in adults in Brazil. However, most of the available data is limited to unicenter registries. The BREATHE registry is the first to include a large sample of hospitalized patients with decompensated HF from different regions in Brazil. Objective Describe the clinical characteristics, treatment and prognosis of hospitalized patients admitted with acute HF. Methods Observational registry study with longitudinal follow-up. The eligibility criteria included patients older than 18 years with a definitive diagnosis of HF, admitted to public or private hospitals. Assessed outcomes included the causes of decompensation, use of medications, care quality indicators, hemodynamic profile and intrahospital events. Results A total of 1,263 patients (64±16 years, 60% women) were included from 51 centers from different regions in Brazil. The most common comorbidities were hypertension (70.8%), dyslipidemia (36.7%) and diabetes (34%). Around 40% of the patients had normal left ventricular systolic function and most were admitted with a wet-warm clinical-hemodynamic profile. Vasodilators and intravenous inotropes were used in less than 15% of the studied cohort. Care quality indicators based on hospital discharge recommendations were reached in less than 65% of the patients. Intrahospital mortality affected 12.6% of all patients included. Conclusion The BREATHE study demonstrated the high intrahospital mortality of patients admitted with acute HF in Brazil, in addition to the low rate of prescription of drugs based on evidence.

Expression of CD40 ligand, interferon-gamma and Fas ligand genes in endomyocardial biopsies of human cardiac allografts: correlation with acute rejection

The purpose of the present study was to investigate the expression (mRNA) of CD40 ligand (CD40L), interferon-gamma (IFN-gamma) and Fas ligand (FasL) genes in human cardiac allografts in relation to the occurrence of acute cardiac allograft rejection as well as its possible value in predicting acute rejection. The mRNA levels were determined by a semiquantitative reverse transcriptase-polymerase chain reaction method in 39 samples of endomyocardial biopsies obtained from 10 adult cardiac transplant recipients within the first six months after transplantation. Biopsies with ongoing acute rejection showed significantly higher CD40L, IFN-gamma and FasL mRNA expression than biopsies without rejection. The median values of mRNA expression in biopsies with and without rejection were 0.116 and zero for CD40L (P<0.003), 0.080 and zero for IFN-gamma (P<0.0009), and 0.156 and zero for FasL (P<0.002), respectively. In addition, the levels of IFN-gamma mRNA were significantly increased 7 to 15 days before the appearance of histological evidence of rejection (median of 0.086 in pre-rejection biopsies), i.e., they presented a predictive value. This study provides further evidence of heightened expression of immune activation genes during rejection and shows that some of these markers may present predictive value for the occurrence of acute rejection.