The adjunctive role of antiphospholipid antibodies in systemic lupus erythematosus cardiac involvement.

OBJECTIVE: To evaluate the prevalence of cardiac alterations by trans thoracic echocardiography (TTE) and the possible role of aPLs in determining heart damage in SLE patients. PATIENTS AND METHODS: We investigated 34 consecutive Caucasian SLE patients and 34 age and sex- matched controls. All patients underwent TTE. Lupus anticoagulant (LA) was assayed. IgG and IgM antiphospholipid antibodies against cardiolipin (aCL), phosphatidylinositol (aPI), phosphatidylserine (aPS), phosphatidic acid (aPA), and anti-Beta2-glycoprotein I antibodies (aBeta2GPI) were determined by ELISA. RESULTS: Nineteen (56%) SLE patients showed at least one cardiac abnormality (P < 0.0001 - RR 19; OR 41.8; 95% CI 5.1-342). The predominant valve dysfunctions were represented by mitral (21%) and tricuspidal (18%) regurgitation. Aortic regurgitation was observed in 12% of patients, pericardial effusion and left atrial enlargement were identified in 15% and 12% of cases, respectively. Mitral valvular strands were detected in one patient. The prevalence of cardiac abnormalities correlated with disease duration. Echocardiographic alterations were more common in aPLs positive than in aPLs negative patients (P = 0.02 - RR 2.5; OR 6.1; 95% CI 1.2-30.1). Patients with IgG-aPA, -aPI and -aPS had a higher prevalence of left atrial enlargement (P < 0.05); IgG-aPA and -aPI were significantly associated with increased interventricular septum thickness (P < 0.05). CONCLUSION: Our findings confirm that the heart is one of the main target in SLE patients. The association between aPLs and cardiac impairment suggests an adjunctive role of these autoantibodies in determining heart damage. SLE vasculopathy is a multifactorial process leading to accelerated atherosclerosis. Heart involvement over the course of disease requires a comprehensive screening and management of traditional and new cardiovascular risk factors to prevent cardiac damage, which represents the primary cause of morbidity and mortality in SLE patients.

[Effects of aldosterone receptor blocker therapy on cardiac remodeling]. / Effetto sul rimodellamento cardiovascolare della inibizione recettoriale dell'aldosterone.

Cardiac remodeling is a physiologic or pathologic condition that occurs after myocardial infarction, pressure overload, myocardial inflammatory diseases, idiopathic dilated cardiomyopathy or volume overload. In spite of different etiologies, molecular, biochemical and mechanical processes are the same. The change in left ventricular function brings about a complex neuro-hormonal disorder, and disease progression is due to the combined action of several biological factors with toxic effects on the heart and vessels. The renin-angiotensin-aldosterone system (RAAS) is very important in this process, through the effects on hydro-saline balance or through direct processes on myocardium. A direct effect of aldosterone in myocardial fibrosis after the detection of heart tissue aldosterone production has been demonstrated. In the past, the attention of physicians and researchers was focused on angiotensin II inhibition; and therefore, on angiotensin-converting enzyme (ACE) inhibitors, considering them sufficient to antagonize the effects of aldosterone. Nevertheless, this theory has been confuted in recent studies, with the evidence of elevated plasmatic aldosterone levels in patients treated with ACE-inhibitors and angiotensin receptor blockers. This phenomenon probably is due to the activation of secondary ACTH mediated pathways of trial aldosterone production. It has been demonstrated that aldosterone receptor inhibition is effective in reducing cardiac remodeling and mortality. AREA-IN CHF is the first multicentric, double blind, randomized, placebo control study to compare canrenone, an aldosterone receptor blocker, with placebo. The primary end point is the echocardiographic evaluation of left ventricular remodeling. Secondary end points are left ventricular end-systolic volume, ejection fraction, diastolic filling patterns, NYHA functional class, and mortality and hospitalizations of cardiac origin. In addition, bio-humoral effects of aldosterone receptor blocker therapy will be investigated. The study results will be available at the end of 2006.

Ectopic pregnancy on previous cesarean section scar. Case report.

This report concerns a very rare case of ectopic pregnancy on previous cesarean section scar, with its clinical therapeutic solutions. The increasing amount of cesarean sections could cause, in the next years, a greater probability to meet cases such this one. Here it follows a description of the diagnostic iter and the surgical therapy with laparotomic approach.

Vitamin D status in patients affected by Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS) is an inborn error of cholesterol biosynthesis characterized by developmental delay and multiple malformations. Some of the patients have skin photosensitivity and therefore tend to avoid direct exposure to sunlight.SLOS patients typically have low concentrations of cholesterol and abnormally high concentrations of its precursor 7-dehydrocholesterol (7-DHC) in biological fluids and tissues. 7-DHC is also a precursor in the cutaneous synthesis of vitamin D. Sunlight exposure plays a major role in this pathway and reactions transforming 7-DHC into vitamin D and then into 25-hydroxyvitamin D are known not to be specifically regulated. The aim of this study was to evaluate vitamin D status in SLOS patients. We measured 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations and markers of calcium metabolism in five SLOS patients. Despite abnormally high concentrations of 7-DHC, circulating concentrations of vitamin D metabolites were not significantly different from appropriate controls matched for sex, age and season of blood collection. The analysis of historical serum samples stored in our laboratory from the same cases plus 10 other SLOS patients further supported these findings. Our data suggest that SLOS patients have a peculiar vitamin D metabolism that protects them from vitamin D intoxication. This appears to be due in most cases to decreased transformation of 7-DHC into 25-hydroxyvitamin D, perhaps depending on reduced sunlight exposure as a consequence of photosensitivity. Possible alternative mechanisms are discussed.

Increased plasma levels of adrenomedullin, a vasoactive peptide, in patients with end-stage pulmonary disease.

AIM: To study adrenomedullin (AM) plasma levels in patients with severe lung disease and to analyze the relationship between AM and heart changes, hemodynamics and blood gases. METHODS: Case control study of 56 patients (36 men, 20 women) with severe lung disease and 9 control subjects (7 men, 2 women). Patients with end-stage pulmonary disease, including chronic obstructive pulmonary disease (COPD, n=11), cystic fibrosis (CF, 26), idiopatic pulmonary fibrosis (ILD, n=9), and idiopatic pulmonary arterial hypertension (PAH, n=10), who were evaluated for lung trasplantation between January 1997 and September 2000, and nine patients who underwent lung surgery for a solitary benign nodule. AM plasma levels in pulmonary artery (mixed venous blood, vein) and aorta or femoral artery (arterial, art), art and vein blood gases, pulmonary hemodynamics, systemic hemodynamics, two-dimensional transthoracic echocardiography and echo-Doppler study. RESULTS: Plasma AM (art and ven) levels were higher among patients' group compared to the controls (AMart p<0.02 and AMven p<0.04) for CF, ILD, PAH (AMart, pg ml(-1) Controls 13.7+/-3.6, COPD 22.8+/-6.2, CF 28.1+/-11.4, ILD 34.1+/-14.3, PAH 35.1+/-18.9; AMven, pg ml(-1) Controls 14.2+/-4.8, COPD 28.1+/-12.6, CF 31.7+/-14.1, ILD 38.7+/-16.5, PAH 40.1+/-4.4). We found with a trend towards higher concentration in ILD and PAH patients compared to COPD and CF but no statistical significant differences. Mixed-venous AM was higher than arterial AM in all groups resulting in AM uptake (AMPulmUp pg min(-1) Controls 4.8+/-22.6, COPD 21.1+/-44.9, CF 20.6+/-45.1, ILD 23.7+/-38.5, PAH 29.9+/-49.7). The univariate analysis showed a weak but significant correlation between AMart and mean systemic arterial pressure, heart rate, mean pulmonary arterial pressure and systemic vascular resistance. In the multivariate analysis, four variables emerged as independent factors of AMart including mean pulmonary arterial pressure, heart rate, mean systemic arterial pressure and left ventricular diastolic diameter (F=8.6, p<0.00001, r=0.60, r2=0.32). A similar weak correlation was apparent between AMven, systemic vascular resistance, and mean pulmonary arterial pressure. The results of multivariate analysis identify right atrial enlargement, mean right atrial pressure, heart rate and left ventricular dimensions as the only independent variables related to AMven (F=4.3, p<0.0004 r=0.56, r2=0.26). AM pulmonary uptake was significantly correlated with AMven (r=0.65), but not with hemodynamic, blood gas and echocardiographic variables. CONCLUSIONS: AM plasma levels are elevated in patients with severe lung disease in face of a preserved pulmonary uptake. These results suggest that the high AM plasma levels in patients with severe lung disease are not caused by a reduced pulmonary clearance, instead suggesting a systemic production.