Does the calcineurin inhibitor have influence on cytomegalovirus infection in heart transplantation?

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in heart transplant (HTx). Our aim was to analyze the rate of CMV infection in HTx patients receiving treatment with cyclosporine (CsA) or tacrolimus (Tac). Ninety-five patients were randomized to receive either CsA (53.7%) or Tac (46.3%). We performed prophylaxis with valganciclovir in patients with the highest risk of CMV infection. We considered CMV infection as an increased viral load or the presence of CMV in histological samples. We analyzed baseline characteristics, CMV infection, and other complications. Event-free rates were calculated using the Kaplan-Meier method. There were no significant differences in baseline characteristics between both groups. CMV infection was detected in 31.6% of patients (in 66.7% due to asymptomatic replication). The group treated with Tac had a lower rate of CMV infection (15.9% vs. 45.1%, p = 0.002) and longer CMV infection-free survival time (1440 vs. 899 d, p = 0.001). No differences were observed in the complications analyzed in both groups. The independent risk factors for infection identified in the multivariate analysis were treatment with CsA and bacterial infections. This was the first study to demonstrate a lower rate of CMV infection in patients treated with Tac vs. those treated with CsA after HTx.

Impact of basal heart rate on long-term prognosis of heart transplant patients.

Previous studies in patients with heart failure have shown that an elevated basal heart rate (HR) is associated with a poor outcome. Our aim with this study was to investigate if this relationship is also present in heart transplantation (HTx) recipients. From 2003 until 2010, 256 HTx performed in our center were recruited. Patients who required pacemaker, heart-lung transplants, pediatrics, retransplants, and those patients with a survival of less than 1 year were excluded. The final number included in the analysis was 191. Using the HR obtained by EKG during elective admission at 1 year post-HTx and the survival rate, an ROC-curve was performed. The best point under the curve was achieved with 101 beats per minute (bpm), so patients were divided in two groups according to their HR. A comparison between survival curves of both groups was performed (Kaplan-Meier). Subsequently, a multivariate analysis considering HR and other variables with influence on survival according to the literature was carried out. A total of 136 patients were included in the group with HR ≤100 bpm, and 55 in the one with HR >100 bpm. There were no basal differences in both groups except for primary graft failure, which was more frequent in the >100 bpm group (30.9 vs. 17%, P = 0.033). Patients with ≤100 bpm had a better long prognosis (P < 0.001). The multivariate analysis proved that high HR was an independent predictor of mortality. Our study shows that HR should be considered as a prognosis factor in HTx patients.

Serum markers of apoptosis in the early period of heart transplantation.

CONTEXT AND OBJECTIVE: To assess the relationship between levels of serum markers of apoptosis and rejection grades in heart transplant (HTx). MATERIALS AND METHODS: A prospective study was conducted in 91 HTx. We correlated apoptosis markers and biopsy samples. The apoptosis markers were: TRAIL, TRAIL-R1, TRAIL-R2, TRAIL-R3, TRAIL-R4, sFas, sTNF-R1 and sTNF-R2. RESULTS: The only significant correlation with rejection grade was sFas (r=0.329; p=0.005). Cyclosporine showed a proapoptotic effect (sTNF-R1 0.02 and sTNF-R2 0.02) and everolimus an antiapoptotic effect (sTNF-R1 r= -0.523; p=0.0001 and sTNF-R2 r= -0.405; p=0.0001). CONCLUSIONS: The utility of specific apoptosis markers in peripheral blood for diagnosis of acute cellular rejection is low. Everolimus may have an anti-apoptotic effect.

Prevention of myocardial dysfunction by Eplerenon in experimental tachycardiomyopathy.

BACKGROUND: High-rate short-duration ventricular pacing induces myocardial hypokinesis that persists once the hemodynamic conditions have been recovered. The aim was to study the factors that determine the persistence of myocardial dysfunction when ventricular tachycardia has ceased and hemodynamic conditions have been restored. MATERIAL/METHODS: An in vivo experimental pig model was used consisting of a ventricular pacing series (n=10), a ventricular pacing and aldosterone blockade (eplerenon) series (n=6), and a control series without ventricular pacing (n=6). Electrical stimulation was performed from the epicardial base of the left ventricle at a frequency 60% above the basal rate for 2 hours followed by a recovery period of 60 minutes. Cardiac and myocardial function parameters were studied. Plasma levels of aldosterone, renin activity, and glutathione were measured. RESULTS: Electrically induced tachycardia produced hemodynamic and myocardial changes that persisted after stimulation had ceased, accompanied by an increase in aldosterone and a coronary flow decrease. These changes were not seen when aldosterone activity was blocked by eplerenon. There was a non-significant elevation in glutathione levels. CONCLUSIONS: These data show that although participation of other neurohormones cannot be ruled out, aldosterone blockade (eplerenon) ameliorates myocardial dysfunction persisting after ventricular tachycardia by preventing coronary endothelial dysfunction.

Mitochondrial changes induced by trimetazidine in the myocardium.

BACKGROUND: The aim was to assess the effect of trimetazidine (TMZ) on mitochondrial alterations induced in a canine model of brief, repeated episodes of ischemia. MATERIAL/METHODS: Twelve crossbred dogs were analyzed, after double-blind randomization, to a 7-day treatment with either TMZ or placebo. Twenty brief, complete occlusions of the left anterior descending coronary artery were performed. Mitochondrial analysis entailed a qualitative (percentage of mitochondrial damage, merging, pairing, vacuoles, and lipofucsin granules) and a quantitative size analysis (major and minor axes, perimeter, and area) of the mitochondria in the ischemic and control zones. RESULTS: Comparative study of the control zones revealed an increase in lipofucsin granules in the TMZ series and a greater percentage of damaged mitochondria and vacuoles. The control-zone mitochondria treated with TMZ presented a significant increase in the perimeter and major axis and a decrease in the minor axis (p<0.005). No significant differences were found between the series in the qualitative analysis of mitochondrial damage in the ischemic zone. The mitochondria in the TMZ series presented a greater major axis and perimeter than those in the placebo series (p<0.05), which presented a smaller minor axis. CONCLUSIONS: TMZ made the mitochondria adopt an elongated, "rod-like" morphology in both the control and ischemic zones. This is interpreted as an increase in the membrane surface. In the non-ischemic zone, TMZ produced an increase in mitochondrial turnover. There were no differences in the myocardium subjected to ischemia in both series in terms of observable mitochondrial damage.