Cardiac vascular calcification and QT interval in ESRD patients: is there a link?

We will present our experience and our preliminary data about the correlation between cardiac calcification and QT interval (and QT dispersion) in uraemia. We studied 32 haemodialysis (HD) patients (age 69 +/- 16 years, time on dialysis 32 +/- 27 months) and 12 chronic kidney disease stage 4 (CKD-4) patients (age 66 +/- 17 years, uraemia duration 38 +/- 16 months). The patients were characterized by a good mineral control, as shown by serum phosphate levels (3.6 +/- 1.3 mg/dl in CKD-4 and 4.3 +/- 1.6 mg/dl in HD patients) and Ca x P product (46 +/- 17 and 49 +/- 16 mg(2)/dl(2), respectively). The parathyroid hormone levels were higher in HD than CKD-4 patients (p < 0.0001). A TC score >400 was found to be highly prevalent in both groups. Significantly more HD patients (62.5%) showed cardiac calcification than CKD-4 patients (33%; p = 0.01). The patients were matched for TC scores higher or lower than 400. The two groups differed by gender (p < 0.05), age (p = 0.026), frequency of diabetes mellitus (p < 0.01), uraemia follow-up period (p < 0.001), low-density lipoprotein cholesterol level (p = 0.009), Ca x P product (p = 0.002), parathyroid hormone level (p < 0.0001), and corrected QT dispersion (p < 0.0001). The QT interval was higher in HD and CKD-4 patients with higher TC scores (approximately 11%), but QT interval dispersion was significantly higher in patients with TC scores >400. QT dispersion showed a linear correlation with TC scores in both groups (r = 0.899 and p < 0.0001 and r = 0.901 and p < 0.0001). Male gender, age, time (months) of uraemia, low-density lipoprotein cholesterol, albumin, calcium x phosphorus product, parathyroid hormone, and TC score are important determinants of QT dispersion. Our data show that it is possible to link dysrhythmias and cardiac calcification in uraemic patients.     

Mechanical limitation of pulmonary blood flow facilitates heart transplantation in older infants with hypoplastic left heart syndrome.

OBJECTIVES: Progression of pulmonary vascular disease limits heart transplantation for hypoplastic left heart syndrome (HLHS) to early infancy. Our objective was to assess the impact of bilateral pulmonary artery banding (PAB) on the operative courses of HLHS infants transplanted at ages older than 4 months. METHODS: Courses of all HLHS patients in our center who remained listed to age >or=120 days before heart transplantation were assessed. Patients undergoing transplantation after standard management (control group) were compared to patients having a prior pulmonary blood flow limiting procedure (PAB group). RESULTS: Of 16 identified patients, one crossed over to stage I Norwood on day 185 and died post-operatively. Fifteen patients were transplanted at age >or=120 days (control group n=9, PAB group n=6). Four PAB patients had open PA band placement. Two PAB patients underwent experimental percutaneous bilateral internal pulmonary artery flow limiting device insertion. The PAB group mean age at banding was 141+/-54 days, and mean interval from PAB to transplant was 35+/-31 days (range 1.5-68 days). No differences in age at transplant, weight at transplant, warm graft ischemia time or total graft ischemia time were detected between groups. Mean times of mechanical ventilation (control 143+/-69h vs. PAB 44+/-13h), inhaled nitric oxide (control 126+/-70h vs. PAB 37+/-9h), inotropic support (control 171+/-64h vs. PAB 87+/-17h), intensive care unit (ICU) stay (control 8.3+/-2.7 days vs. PAB 4.5+/-1.4 days), and hospital stay (control 10.4+/-3.9 days vs. PAB 7.0+/-1.1 days) were all lower in the PAB group (P<0.05 all comparisons). Two control patients died, three required extracorporeal membrane oxygenation (ECMO), and six did not tolerate primary chest closure. No PAB patient died or required ECMO. All PAB patients tolerated primary chest closure. All PAB patients had widely patent branch pulmonary arteries with no re-interventions to date. All hospital survivors remain alive (mean follow-up, control 50.2 months, PAB 11.5 months). CONCLUSIONS: Pre-transplant mechanical limitation of pulmonary blood flow simplified management and reduced morbidity for HLHS patients undergoing heart transplantation at ages >or=4 months. This strategy extends the permissible transplant waiting time in older infants with HLHS.     

SV-IV Peptide1–16 reduces coagulant power in normal Factor V and Factor V Leiden

Background

Alefacept (anti-CD2) biological therapy selectively targets effector memory T cells (Tem) in psoriasis vulgaris, a model Type 1 autoimmune disease.

Methods

Circulating leukocytes were phenotyped in patients receiving alefacept for moderate to severe psoriasis.

Results

In all patients, this treatment caused a preferential decrease in effector memory T cells (CCR7^- CD45RA^-) (mean 63% reduction) for both CD4⁺ and CD8⁺ Tem, while central memory T cells (Tcm) (CCR7⁺CD45RA^-) were less affected, and naïve T cells (CCR7⁺CD45RA⁺) were relatively spared. Circulating CD8⁺ effector T cells and Type 1 T cells (IFN-γ-producing) were also significantly reduced.

Conclusion

Alefacept causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis.     

Risk stratification and prognosis of patients with known or suspected coronary artery disease by use of supine bicycle exercise stress echocardiography.

BACKGROUND: The aim of this study was to assess the long-term predictive values of supine bicycle exercise stress echocardiography (ESE), and the ESE additional role compared to other traditional clinical and rest echocardiographic variables, in 607 patients with low, intermediate and high pretest risk of cardiac events. METHODS: Clinical status and long-term outcome were assessed for a mean period of 46 months (range 12-60 months). ESE was performed for the diagnosis of suspected coronary artery disease (CAD) in 267 patients (43.9%), and for risk stratification of known CAD in 340 patients (56.1%). At baseline, the mean value of wall motion score index (WMSI) was 1.22 +/- 0.36, and the mean left ventricular ejection fraction was 58.5 +/- 10.9%. RESULTS: ESE was positive for ischemia in 210 patients (34.9%), while ECG was suggestive for ischemia in 157 patients (25.8%). During the test only 97 patients (15.9%) experienced angina. At peak effort, the mean WMSI was 1.38 +/- 0.46. A low workload was achieved by 158 patients (26.1%). During the follow-up period there were 222 events, including 82 hard events (36.9%), 48 deaths (21.6%) and 34 acute non-fatal myocardial infarction (15.3%). At stepwise multivariate model, cigarette smoking (p < 0.01), peak WMSI (p < 0.001), ESE positive for ischemia (p < 0.001) and low workload (p < 0.01) were the only independent predictors of cardiac death, while positive ESE, peak WMSI, angina during the test and hypercholesterolemia were the only independent determinants of hard cardiac events. The cumulative 5-year mean survival rate according to ESE response was 95.9% in patients with negative ESE, and 83.7% in patients with positive ESE (log rank 13.6; p < 0.00001). CONCLUSIONS: ESE yields prognostic information in known or suspected CAD, especially in patients with intermediate pretest risk level. The combined evaluation of clinical variables and other ESE variables, such as peak WMSI and exercise capacity, may further select patients at greatest risk of cardiac death in the overall population.     

Effect of L-arginine on circulating endothelial progenitor cells and VEGF after moderate physical training in mice

Alteration of levels and functional activities of circulating endothelial progenitor cells (EPCs) induced by risk factors for coronary heart disease (CHD) profoundly influence their role in the regeneration of tissue ischemia and angiogenesis. Among antioxidant nutrients in the prevention of CHD, L-arginine is particularly effective in enhancing the protection afforded by moderate physical exercise. Here, we aimed to evaluate the effects of L-arginine on EPC levels in C57BL/6J mice subjected to moderate physical exercise. Results showed that supplementation with L-arginine potentiates the effects of moderate physical exercise by increasing significantly EPCs (P<0.001) and VEGF serum levels (P<0.001). Our report highlights the beneficial effect of l-arginine in the modulation of EPC levels and VEGF secretion.     

Regression of left ventricular hypertrophy and systolic function in hypertensive patients during long-term treatment with ketanserin

Summary It is now generally accepted that antihypertensive therapy can induce regression of left ventricular hypertrophy (LVH) in hypertensive subjects. However, the influence of LVH reversal on both the systolic and diastolic functions, and particularly the ability of the heart to meet sudden overloads caused by exercise and/or recurrence of hypertension, remain unanswered questions. The long-term effects of ketanserin, a selective serotonin S₂-receptor antagonist with additional alpha₁-adrenergic blocking properties, on LVH and systolic function were studied in 13 untreated subjects (age range 35–55 years) with mild-to-moderate essential hypertension, echocardiographic evidence of LVH, and normal ejection fraction. Blood pressure values and echocardiographic measurements of dimensions, wall thicknesses, and indices of LV mass were determined before and after 3, 6, and 12 months treatment; ejection fractions at rest and during exercise were evaluated by equilibrium multigated radionucleide angiocardiography at baseline and after 12 months of therapy. Mean arterial pressure was significantly reduced from the first month of treatment (p<0.001) and remained well controlled up to the end of the trial. Both posterior and septum wall thicknesses decreased after 3 months of therapy and remained stable throughout the whole study period. LV mass index decreased from a mean ± SD of 187.7±47.6 g/m² to a mean of 157.81±31.63 g/m² (p<0.01) at the third month, reaching greater decreases after 6 months (156.05±31.00 g/m²) and after 12 months (153.21±28.80 g/m²) of treatment. A significant correlation was found between LV mass and posterior wall thickness at the different observation times in the study. Finally, the regression of LVH at the end of therapy was not associated with impairment of systolic function, as assessed by measurements of ejection fraction at rest and during exercise.