Sergio Morelli

Plasma endothelin-1 levels, pulmonary hypertension, and lung fibrosis in patients with systemic sclerosis

PURPOSE To investigate the behavior of circulating endothelin (ET)-1 concentrations in patients affected by systemic sclerosis, and to elucidate the possible relationships existing in this disease among plasma peptide levels, pulmonary hypertension, and lung fibrosis. PATIENTS AND METHODS Circulating ET-1 levels were determined by reverse-phase, high-pressure liquid chromatography followed by sensitive radioimmunoassay in 20 patients affected by systemic sclerosis (18 women and 2 men, mean age 48.1 +/- 13.7 years) with or without pulmonary hypertension as evaluated by Doppler echocardiography, or lung fibrosis as measured by a score method based on lung examination by high-resolution computed tomography (HRCT). A group of 18 normal volunteers served as controls (15 women and 3 men, mean age 45.0 +/- 10.1 years). RESULTS Plasma ET-1 levels were significantly higher (P < 0.001) in patients with systemic sclerosis (1.72 +/- 0.28 pg/mL) than in control subjects (0.63 +/- 0.06 pg/mL). Pulmonary artery systolic hypertension was detected in 10 patients (50%) with systemic sclerosis (56.2 +/- 18.0 mm Hg, range 37 to 97) versus none of the control subjects (30.2 +/- 2.2 mm Hg, P < 0.0001). Lung fibrosis was present in 12 patients (60%), with an HRCT overall score of 9.0 +/- 4.6. There were no significant differences in plasma ET-1 levels between patients with pulmonary hypertension (1.58 +/- 0.20 pg/mL) or without it (1.76 +/- 0.39 pg/mL, P = 0.188, not significant [NS]); or between patients with lung fibrosis (1.65 +/- 0.14 pg/mL) or without fibrosis (1.78 +/- 0.37 pg/mL, P = 0.290, NS). In particular, 6 patients had neither pulmonary hypertension nor lung fibrosis. In these patients, plasma ET-1 levels were similar compared with the others (1.85 +/- 0.49 versus 1.66 +/- 0.13, respectively; P = 0.180, NS). No correlations were observed between ET-1 levels and either pulmonary pressure levels or HRCT overall scores. CONCLUSIONS The use of a sensitive assay, highly selective for ET-1, showed higher levels of circulating peptide in patients affected by systemic sclerosis than in control subjects. Neither pulmonary hypertension nor lung fibrosis was accompanied by a further rise in plasma ET-1 concentrations.

CARDIAC INVOLVEMENT IN BEHCET'S DISEASE

To assess the prevalence and the extent of cardiac involvement in patients with Behçets disease and to investigate the possible causes that may predispose to this involvement, 30 patients affected by Behçets disease and 30 normal control subjects were submitted to M-mode, two-dimensional, and Doppler echocardiographic evaluation. Moreover, antinuclear and anticardiolipin autoantibodies were determined in the sera of both patients and control subjects. Finally, HLA-B51 positivity was assessed in the patients and in a historical control group. Mitral valve prolapse was observed in 50% and proximal aorta dilatation in 30% of the patients. There was a significant difference in the rate of these abnormalities in comparison with the control group. Left ventricular function parameters were similar between the two groups. The positivity rate of antinuclear and anticardiolipin autoantibodies was very low (7%), without differences between the groups. HLA-B51 was detected in 82.7% of the patients versus 21.7% in the control group (p < 0.00001). In conclusion, this study demonstrates a high rate of cardiac abnormalities in patients with Behçets disease.

Long term treatment of pulmonary arterial hypertension with beraprost, an oral prostacyclin analogue

OBJECTIVE To evaluate the effects of one years treatment with beraprost, an orally active prostacyclin analogue, in patients with severe pulmonary hypertension. PATIENTS 13 patients with severe pulmonary hypertension. This was primary in nine, thromboembolic in three, and caused by Eisenmenger syndrome in one. METHODS All patients underwent right heart catheterisation. Mean (SD) right atrial pressure was 5 (3) mm Hg, mean pulmonary artery pressure was 48 (12) mm Hg, cardiac index was 2.6 (0.8) l/min/m2, and mixed venous oxygen saturation was 68 (7)%. Beraprost was started at the dose of 20 μg three to four times a day (1 μg/kg/day), increasing after one month to 40 μg three to four times a day (2 μg/kg/day), with further increases of 20 μg three to four times a day in case of clinical deterioration. MAIN OUTCOME MEASURES New York Heart Association (NYHA) functional class, exercise capacity measured by distance walked in six minutes, and systolic pulmonary pressure (by echocardiography) were evaluated at baseline, after one months treatment, and then every three months for a year. RESULTS After the first month of treatment, NYHA class decreased from 3.4 (0.7) to 2.9 (0.7) (p < 0.05), the six minute walking distance increased from 213 (64) to 276 (101) m (p < 0.05), and systolic pulmonary artery pressure decreased from 93 (15) to 85 (18) mm Hg (NS). One patient died after 40 days from refractory right heart failure, and another was lost for follow up at six months. The 11 remaining patients had persistent improvements in functional class and exercise capacity and a significant decrease in systolic pulmonary artery pressure in the period from 1–12 months. Side effects were minor. CONCLUSIONS Oral administration of beraprost may result in long lasting clinical and haemodynamic improvements in patients with severe pulmonary hypertension.

Spondylodiscitis and infective endocarditis: case studies and review of the literature.

Study Design. This study evaluated the association between infective endocarditis and infective spondylodiscitis and its clinical features. Objectives. To report case studies of patients with spondylodiscitis complicating infective endocarditis. Summary of Background Data. Early diagnosis of infective endocarditis as the source of the spondylodiscitis is often difficult because clinical and radiologic patterns are similar to those present in spondylodiscitis alone. Methods. The case records of the patients with infective endocarditis admitted to our Department from 1991–1998 were reviewed. The diagnosis of spondylodiscitis was made on the basis of clinical features and of typical radiologic signs. Results. Among 30 patients affected by infective endocarditis, three also were affected by spondylodiscitis. All patients fully recovered after appropriate antibiotic therapy. Conclusions. In all patients with spondylodiscitis, infective endocarditis should be excluded, particularly in patients with a history of heart valve disease.

Pulmonary Arterial Hypertension Responsive to Immunosuppressive Therapy in Systemic Lupus Erythematosus

Two female patients with recent diagnosis of systemic lupus erythematosus (SLE) are reported. Pulmonary arterial hypertension was diagnosed by Doppler echocardiography. Immunosuppressive therapy was started at the time of diagnosis of SLE. After 2 months of therapy, Doppler echocardiography was repeated and the estimated pulmonary artery systolic pressure was substantially decreased from 78 to 42 mmHg and from 67 to 42 mmHg, respectively, along with significant improvement of the clinical conditions.

Pulmonary hypertension is associated with impaired exercise performance in patients with systemic sclerosis.

OBJECTIVE The aim of this study was to evaluate the exercise tolerance by expired gas analysis during stress test in patients with Systemic Sclerosis (SSc). METHODS Eighteen women (mean age 48.56+/-12.48 years) affected by SSc were studied. A complete echocardiographic examination including pulmonary artery systolic pressure estimation, pulmonary function tests, diffusion lung capacity for carbon monoxide (DLCO), and exercise test were performed. During exercise, breath-by-breath expired gas analysis was performed. RESULTS Seven patients (39%) had baseline pulmonary systolic hypertension (group A) and 11 patients (61%) did not (group B). Six patients had reduced DLCO values. Both maximal oxygen consumption (VO2max) and anaerobic threshold (VO2AT) values were markedly decreased compared to the predicted values. Seven of 18 patients were unable to complete a maximal exercise (5 of whom affected by pulmonary systolic hypertension). Group A patients showed reduced VO2max, VO2AT, and O2 pulse compared with patients with group B patients (p=0.004, 0.017, and 0.013, respectively); VO2max, VO2AT and O2 pulse were significantly correlated to baseline pulmonary artery systolic pressure. CONCLUSIONS An exercise intolerance in patients affected by SSc is present. Impairment of exercise performance is associated with pulmonary hypertension.Objective: The aim of this study was to evaluate the exercise tolerance by expired gas analysis during stress test in patients with Systemic Sclerosis (SSc). Methods

Left-sided heart valve abnormalities and risk of ischemic cerebrovascular accidents in patients with systemic lupus erythematosus

The aim of the study was to assess the relationship between ischemic cerebrovascular accidents (ICVAs), that is, transient ischemic attack (TIA) or stroke, and left-sided heart valve abnormalities (LHVAs) in patients with systemic lupus erythematosus (SLE). In total, 71 consecutive SLE patients were studied.At baseline, history, clinical and laboratoryevaluations, as well as trans-thoracic echocardiography (TTE) were performed. From the original population, so patients were followed up for a mean time of 5.80 + 1.53 years. After a mean period of 5.39 + 1.42 years; 40 patients underwent a repeat TTE. Previous ICVA history was present at baseline in 16 patients (22.5%). Of these, 13 (81.2%) had evidence of LHVAs on TTE. Previous ICVAs were significantly associated to diagnosis of secondary anti-phospholipid syndrome (SAPS), positivity for anti-cardiolipin antibodies (aCl), and LHVAs. Multivariate analysis confirmed the correlation between previous ICVAs and LHVAs. LHVAs were not more commonly observed in patients with SAPS compared to patients without SAPS. At the end of follow-up, irrespective of any differences in antithrombotic treatment, ICVAs had occurred in 13 patients.During follow-up, ICVAs had recurredin seven patients, while a first eventTIA occurredin one patient. Multivariate analysis confirmed the relationship between ICVAs and LHVAs, and a trend towards a positive correlation of the former with SAPS. This study demonstratesthat LHVAs represent a compelling risk factor for the development of ICVAs in SLE patients. Conversely, SAPS and aCl positivity, although associated with ICVAs, did not clearly correlate with LHVAs in our study. These results provide insight on the pathogenesis of ICVAs and may give clues on the potential efficacy of preventive/therapeutic strategies in different SLE subpopulations.

Early hepatitis during intravenous amiodarone administration

Two patients with acute changes suggesting acute hepatitis after parenteral amiodarone administration are described. No other explanation for liver damage was found in these patients. Normalization of liver function in spite of continuation of drug infusion was observed.

Parathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidism, as evaluated by exercise test

OBJECTIVE To investigate whether parathyroidectomy (PTx) reverses risk factors for arrhythmias related to the QT dynamic changes evaluated during bicycle ergometry exercise test (ET). METHODS Twenty-four postmenopausal women with primary hyperparathyroidism (PHPT) (mean age 60.08.4 years) and 30 sex- and age-matched controls underwent ET, echocardiography, and biochemical evaluation. The following stages were considered during ET: rest, peak exercise, and recovery. The patients were randomized to two groups: 12 underwent PTx (group A) and 12 were followed-up conservatively (group B). After 6 months, the patients were studied again. RESULTS Groups A and B showed no differences in mean baseline biochemical values, echocardiographic parameters, and QTC interval. PHPT patients showed an increased occurrence of ventricular premature beats (VPBS) during ET compared with controls (37.0 vs 6.6%, P=0.03). Serum calcium level was a predictor of VPBS (P=0.05). Mean value of QTC was in the normal range at baseline (Group A: 401±16.9; group B: 402.25±13.5 ms) but significantly lower than controls (417.8±25.1 ms, P<0.01). A negative correlation was found between QTc and calcium values (P=0.03). Physiological reduction of QTc interval from rest to peak exercise was not observed in PHPT patients before surgery. After PTx, group A had a significant reduction in VPBs compared with baseline (at baseline, 5 of 12 vs none of 12 patients after PTx, P=0.03) and a restored normal QT adaptation during ET. Group B showed no significant changes after a 6-month period. CONCLUSIONS PTx reduces the occurrence of VPBs and restored the QTc adaptation during ET.

Left Ventricular Mass in Dippers and Nondippers with Newly Diagnosed Hypertension

Hypertensive subjects can be subdivided into 2 groups, dippers and nondippers, according to the presence or the lack of a nocturnal fall of blood pressure of more than 10%. Several studies have investigated cardiac organ damage in the 2 groups with discordant results, but they included subjects with different onset, severity, and treatment of hypertension. The authors selected 23 dippers and 17 nondippers affected by newly (< 1 year) diagnosed grades 1 and 2 hypertension, never treated, who underwent 24-hour ambulatory blood pressure monitoring and M-mode echocardiography. They did not find significant differences between the 2 groups as regards the echocardiographic left ventricular and atrial dimensions or regarding the left ventricular mass, left ventricular mass index, or relative wall thickness. Also no significant differences were found in the rate of either left ventricular remodeling or left ventricular hyper trophy. These data suggest that nondipping status is not associated with a higher level of cardiac involvement in the early phases of hypertension compared to dipping status.