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ABSTRACT: Endomyocardial biopsy is the gold-standard procedure to diagnose acute cellular rejection after heart transplantation. This study assessed whether the blood levels of cytokines involved in inflammation and immune activation are useful to detect the presence of acute cellular rejection.
Blood specimens collected before 275 endomyocardial biopsies in 66 patients were assayed for levels of TNFalpha, IL6, IL1beta, and IL2 receptor. The biopsies were grouped according to the presence (n = 41) or absence (n = 234) of acute cellular rejection grade > or = 3A of the International Society for Heart and Lung Transplantation. We compared the levels of cytokines in the two groups.
Circulating IL6 levels were significantly higher when there was a low grade (0-2) cellular rejection in the biopsy versus the group of biopsies grade > or = 3A (19.8 +/- 27 versus 12.9 +/- 10 pg/mL; P = .001). An IL6 level higher than 30 pg/mL showed a negative predictive value of 95% for the presence of acute rejection grade > or = 3A.
In heart transplant patients, high levels of serum IL6 were associated with low grade cellular rejection. Determination of IL6 levels may be useful to reduce the number of endomyocardial biopsies during follow-up in these patients.
Transplantation Proceedings 11/2006; 38(9):3012-5. · 1.00 Impact Factor
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ABSTRACT: Daclizumab is a monoclonal antibody that binds to the interleukin-2 receptor. It has been used as induction therapy in heart transplantation with two to five repeated administrations over several weeks. The objective of our study was to estimate the efficacy and safety of induction therapy with only one dose of daclizumab in a consecutive series of patients undergoing heart transplantation.
Thirty-two consecutive heart transplants performed since July 2002, who received single-dose daclizumab as induction therapy, were compared with the 30 patients transplanted previously, who received OKT3. In both groups, maintenance immunosuppression included cyclosporine or tacrolimus, mycophenolate mofetil, and corticosteroids. Follow-up time was 1 year.
There were no baseline differences between the two groups regarding age, gender, or etiology. In the group treated with daclizumab there were more diabetics (43% versus 10%, P = .01) and the ischemia time was longer (192 versus 156 minutes, P = .03). During the first posttransplant year, 76% of patients treated with OKT3 and 55% of those treated with daclizumab presented acute rejection > or =3A; 20% and 25%, respectively, presented infections; and 5 (17%) patients in the OKT3 group and 2 (6%) in the group treated with daclizumab died. None of these differences was statistically significant.
Our experience suggests that induction therapy with a single-dose regimen of daclizumab seems to have an efficacy and safety profile similar to OKT3, and it is easier to administer and has a lower cost than other induction regimens.
Transplantation Proceedings 11/2005; 37(9):4036-8. · 1.00 Impact Factor
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ABSTRACT: Increased levels of circulating cytokines have been previously reported in patients with congestive heart failure; however, whether they have prognostic implications is still unknown. The aim of this study was to assess the prognostic implications of elevated serum cytokines in patients with heart failure and to identify the predictors of cytokine activation.
We assessed neurohormonal determinations, circulating cytokines, ejection fraction (EF) and end-diastolic and end-systolic left ventricular lengths in 87 patients (aged 57 +/- 9 years) with left ventricular dysfunction (EF 24% +/- 6%). In 48 patients, we also assessed cytokine receptors. During follow-up (mean, 14 +/- 9 months), 8 patients died and 12 had new heart failure episodes that required hospital admission, 5 of whom underwent heart transplantation. The univariate predictors of these events were serum interleukin-6 (IL-6) (p = 0.00001), New York Heart Association (NYHA) functional class (p = 0.0004), tumor necrosis factor-soluble receptor I (p = 0. 001), atrial natriuretic peptide (p = 0.002), tumor necrosis factor-soluble receptor II (p = 0.004), angiotensin II (p = 0.006), serum interleukin-1 beta (p = 0.01), and plasma renin activity (p = 0.02). Increased serum interleukin-6 (>10 pg/ml) was a significant predictor of death or new heart failure episodes according to the Kaplan-Meier survival method by log-rank test (p = 0.004). By Cox regression analysis, serum IL-6 (p = 0.0005) and the NYHA functional class (p = 0.005) were identified as independent predictors of prognosis.
In patients with congestive heart failure, increased serum IL-6 was identified as a powerful independent predictor of the combined end point: death, new heart failure episodes, and need for heart transplantation.
The Journal of Heart and Lung Transplantation 05/2000; 19(5):419-25. · 4.33 Impact Factor
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ABSTRACT: The aim of the study was to assess the incidence and clinical implications of increased plasma angiotensin II despite chronic ACE inhibitor therapy in patients with heart failure.
The studied population consisted of 70 patients (mean age 59+/-9 years). Plasma renin activity and plasma concentration of aldosterone, norepinephrine, atrial natriuretic peptide, angiotensin II, tumour necrosis factor, interleukin-6 and interleukin-1B were assessed at 6 months of ACE inhibitor therapy. Mean left ventricular ejection fraction was 24+/-5% and the end-systolic and end-diastolic diameters were 59+/-9 and 71+/-8 mm, respectively. Despite chronic enalapril or captopril therapy, 35 patients (50%) had increased plasma angiotensin II (median 33 pg. ml(-1), range 17-84), while it was in the normal range in the remaining 35 patients (median 10 pg. ml(-1), range 5-15). Plasma renin activity (P=0.005), interleukin-6 (P=0.004), New York Heart Association functional class III-IV (P=0. 006), furosemide dose (P=0.01), lack of beta-blocker therapy (P=0. 04) and norepinephrine (P=0.04) were univariately associated with increased angiotensin II. Multivariate regression analysis identified the plasma renin activity (0.0004), norepinephrine (0.02) and interleukin-6 (0.03) as independent predictors of plasma angiotensin II. During follow-up (35+/-29 months), nine (12.8%) patients died and 13 had new heart failure episodes. Increased plasma angiotensin II, despite ACE inhibitor therapy, was a significant predictor of death or heart failure according to the Kaplan-Meier survival method by log rank test (P=0.002).
Fifty per cent of patients with heart failure, ha increased plasma angiotension II despite chronic ACE inhibitor therapy. These patients had higher neurohormonal activation and poor prognosis.
European Heart Journal 01/2000; 21(1):53-7. · 10.48 Impact Factor
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ABSTRACT: Increased serum interleukin-6 (IL-6) was associated with a higher incidence of New York Heart Association functional classes III to IV and worse left ventricular function during follow-up. Patients with elevated serum IL-6 had poor prognosis. These results reinforce the concept that increased serum IL-6 may also play an important role in disease progression.
The American Journal of Cardiology 10/1998; 82(5):688-90, A8. · 3.37 Impact Factor
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ABSTRACT: The accumulation of fluid in the pericardium in an amount sufficient to cause severe obstruction to blood inflow to the ventricles results in cardiac tamponade. In this condition, relief of intrapericardial pressure by pericardiocentesis usually dramatically improves cardiac output, and can be lifesaving. We report a case of a patient with malignant cardiac tamponade in which cardiogenic shock developed after pericardiocentesis due to severe right ventricular dysfunction.
International Journal of Cardiology 05/1997; 59(2):212-4. · 7.08 Impact Factor
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ABSTRACT: The clinical outcomes of patients with fulminant acute myocarditis (FAM) range from death to complete recovery. We sought to identify clinical, biological, and echocardiographic characteristics of prognostic value for this population.
We prospectively included 185 patients with the diagnosis of acute myocarditis who were admitted to our institution between 2000 and 2007, selecting 15 who displayed FAM, namely, severe congestive heart failure or cardiogenic shock, requiring inotropic and/or mechanical circulatory support. Their mean age was 27.9 +/- 12.4 years (range, 12-52) and mean left ventricular ejection fraction (LVEF) was 22 +/- 8.4% (range, 10-35). Seven subjects had poor outcomes, defined as death (n = 4), urgent transplantation (x = 2), or persistent left ventricular dysfunction (n = 3). The other 6 individuals experienced complete recovery of ventricular function. Troponin-I values below 1 ng/mL on admission were significantly associated with greater in-hospital (P = .05) and mid-term poor outcomes (P = .001). Additionally, patients with poor outcomes showed significantly lower LVEF (17.6 +/- 6.2% vs 28.8 +/- 6.9%; P = .006).
Among patients with FAM, normal or minimal elevation of troponin-I and low LVEF on admission were associated with worse in-hospital and mid-term prognosis.
Transplantation Proceedings 41(6):2234-6. · 1.00 Impact Factor
