Heart rate turbulence assessment in systemic sclerosis: the role for the detection of cardiac autonomic nervous system dysfunction.

OBJECTIVE: To assess the heart rate turbulence (HRT) in patients with SSc as a method of assessment for cardiac autonomic nervous function. METHODS: We prospectively studied 68 consecutive patients with SSc before inclusion in the study. After a detailed clinical evaluation, including echocardiography, 45 subjects [aged 54.6 (14.7) years; 40 women] underwent 24-h Holter monitoring for HRT and time- and frequency-domain heart rate variability (HRV) assessment. Results were compared with those in 30 age- and sex-matched healthy controls. RESULTS: As compared with controls, HRT was impaired in SSc patients: the median turbulence onset (TO) was higher (P = 0.0001) and the median turbulence slope (TS) was lower (P = 0.0003). Abnormal HRT (TO > or =0.0% and/or TS < or =2.5 ms/RR) was found in 42% of SSc patients. Moreover, SSc duration correlated negatively with values of TS (r = -0.3; P = 0.045). HRT did not differ between diffuse and limited SSc groups. All estimated time- and the majority of frequency-domain values of HRV parameters in SSc were significantly lower than in controls. Significant correlations were also demonstrated between HRT and HRV parameters. CONCLUSIONS: HRT, like HRV assessment, indicates a frequent impairment of the cardiac autonomic nervous system in SSc patients, irrespective of the SSc type.

Heart rate turbulence impairment and ventricular arrhythmias in patients with systemic sclerosis.

BACKGROUND: Arrhythmias, conduction disturbances, and cardiac autonomic nervous system dysfunction are the most frequent cardiovascular complications in systemic sclerosis (scleroderma). The aim of the study was to assess heart rate turbulence (HRT) in systemic sclerosis patients and to identify the relationship between HRT and occurrence of arrhythmias. METHODS: Forty-five patients with scleroderma (aged 54.6 +/- 14.7 years) and 30 healthy sex- and age-matched subjects were examined. In addition to routine studies, 24-hour Holter monitoring with assessment of HRT was performed. RESULTS: As compared to controls, HRT was significantly impaired in systemic sclerosis patients. Abnormal HRT defined as turbulence onset (TO) > or =0.0% and/or turbulence slope (TS) < or =2.5 ms/RR (ms/RR interval) was found in 19 (42%) scleroderma patients and in no members of the control group. Serious ventricular arrhythmias Lown class IV (VA-LownIV), for example, couplets and/or nonsustained ventricular tachycardias, were observed in 16 (36%) scleroderma patients. The median value of TS was significantly lower in systemic sclerosis patients with VA-LownIV than in patients without VA-LownIV (3.68 vs 7.00 ms/RR, P = 0.02). The area under curve of ROC analysis for prediction of VA-LownIV was 0.72 (95% confidence interval [CI] 0.56-0.87) and revealed that TS <9.0 ms/RR was associated with VA-Lown IV occurrence, with sensitivity of 93.7% and specificity of 44.8%. Univariate and multivariate analyses confirmed that lower values of TS were associated with VA-LownIV occurrence (odds ratio 1.52, 95% CI 1.09-2.12, P = 0.01). CONCLUSIONS: Patients with systemic sclerosis are characterized by significant HRT impairment. Assessment of HRT and especially TS is useful in the identification of patients at risk for ventricular arrhythmias.

Non-invasive diagnostic and functional evaluation of cardiac involvement in patients with systemic sclerosis.

Elevated serum brain natriuretic peptide (BNP) released from myocytes of ventricles upon stretch have been found in patients with isolated right ventricular (RV) pressure overload. However, limited data suggest that serum BNP may be elevated in systemic sclerosis (SSc) patients, especially with RV dysfunction. We assessed serum N-terminal proBNP (NT-proBNP) in SSc and evaluated whether it reflects the severity of RV overload. We prospectively studied 51 consecutive patients (47F, mean age 53.3 +/- 15.2 years) with SSc (mean disease duration 9 +/- 12.4 years). The control group formed 31 healthy subjects (27F, mean age 52.6 +/- 12.1 years). NT-proBNP level, 6-minute walking test (6MWT), and transthoracic echocardiography (TTE) for the assessment of RV overload were performed. Serum NT-proBNP exceeded the reference value of 125 pg/mL in 31 (61%) SSc patients. The mean serum log NT-proBNP concentration in SSc was higher than in controls (2.138 +/- 0.527 vs. 1.634 +/- 0.420 pg/mL, p < 0.001). 13 (25%) SSc patients have tricuspid regurgitation peak gradient (TRPG) exceeding 31 mmHg reflecting pulmonary arterial hypertension (PAH). The SSc presented other echocardiographic signs of RV overload. Mean 6MWT distance was shorter in SSc than in controls (528 +/- 100 vs. 617 +/- 80 m, p < 0.001). NT-proBNP level correlated positively with TRPG, RV diameter, RV Tei index and negatively with 6MWT distance. ROC analysis identified >115 pg/ml as the best NT-proBNP threshold predicting PAH for SSc patients (sensitivity 92%, specificity 44%). Results of our study suggest that NT-proBNP measurement is a useful screening method for PAH in SSc patients. Since elevated plasma NT-proBNP level reflects the degree of right ventricular overload and limitation of exercise capacity, abnormal NT-proBNP levels should imply further evaluation including echocardiography.

Assessment of left and right ventricular diastolic function in patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease characterised by vascular changes and immunologically induced fibrosis of the skin and internal organs. Systemic sclerosis may be associated with both right (RV) and left ventricular (LV) diastolic dysfunction. AIM: To analyse RV and LV myocardial diastolic function in patients with SSc and its relation to exercise capacity. METHODS: We prospectively studied 51 consecutive patients (47 females, 4 males, age 53.3+/-15.2 years) with SSc (mean disease duration 9+/-12.4 years) and a group of 31 age-matched healthy subjects (28 females, 3 males, age 52.68+/-12.1 years). In addition to conventional investigation, transthoracic echocardiography (TTE) for assessment of RV and LV myocardial diastolic function and 6-minute walking test (6MWT) were performed. RESULTS: Abnormal LV filling, as expressed by an inverted mitral E/A ratio (Mit E/A <1), was detected in 28 (55%) SSc patients and in 8 (25%) controls (p <0.001). The mean value of Mit E/A in the SSc group was lower than in controls (1.0+/-0.3 vs. 1.2+/-0.3, p=0.04). There were no differences in pulmonary venous flow between SSc patients and controls. The mean value of Tei index for the LV was higher in SSc than in controls (0.44+/-0.08 vs. 0.38+/-0.05, p <0.001). Abnormal RV filling, as expressed by an inverted tricuspid E/A ratio (TR E/A <1), was detected in 16 (31%) SSc patients and in 5 (16%) controls (p <0.001). Patients with SSc were found to have an inverted Tr E/A ratio (Tr E/A <1), indicating abnormal RV filling. The mean value of Tr E/A in SSc was lower than in controls (1.0+/-0.2 vs. 1.2+/-0.3, p=0.04). The mean value of Tei index for the RV was higher in SSc patients than in controls (0.35+/-0.07 vs. 0.29+/-0.03, p <0.001). In multiple regression analysis Tr E/A ratio was independently correlated with Mit E/A ratio (r=0.65, p=0.01). The mean 6MWT distance was shorter in the SSc group than in controls (528+/-100.6 vs. 617.7+/-80 m, p <0.001) and the mean saturation of capillary blood after the 6-MWT was lower in SSc patients (92.7+/-4.9 vs. 97.2+/-1.2%, p <0.001). Mean desaturation after test and D sat was significantly more pronounced in the SSc group than in controls (3.4+/-3.1 vs. 0.7+/-0.9, p <0.001). The Tr E/A ratio and Mit E/A ratio correlated positively with 6MWT distance (r=0,49, p=0.01 and r=0.48, p=0.02). CONCLUSIONS: Impaired RV and LV relaxation is observed in a significant percentage of SSc patients and is associated with decreased exercise capacity.

Usefulness of echocardiography in the identification of an excessive increase in pulmonary arterial pressure in patients with systemic sclerosis.

BACKGROUND: In systemic sclerosis (SSc), changes in the lungs and pulmonary hypertension (PH) are complications most adversely affecting the prognosis. Given the availability of specific treatment, early diagnosis of PH is very important. Exercise echocardiography, by increasing the patient's cardiac output, makes it possible to identify patients with elevated pulmonary artery pressure (PAP) during exercise. The diagnostic role of exercise echocardiography is still unclear, mainly because of the lack of prospective studies. AIM: To identify SSc patients with abnormally elevated PAP at rest or with a significant increase PAP during exercise, subsequently verified by right heart catheterisation (RHC). METHODS: A total of 71 consecutive patients (67 females and 4 males, mean age 56.9 ± 17.1 years) with SSc diagnosed according to the American College of Rheumatology criteria were enrolled in this prospective study. The patients underwent transthoracic echocardiography (Philips iE33) with the measurement of tricuspid regurgitation peak gradient (TRPG) and an exercise test involving the standard treadmill exercise according to the Bruce protocol with the evaluation of TRPG at 1 min following the completion of exercise. The PH was suspected when TRPG at rest was 〉 31 mm Hg (V(max) 〉 2.8 m/s) or increased by at least 20 mm Hg from baseline following exercise. Patients with suspected PH were referred for resting and exercise RHC. RESULTS: The exercise testing was performed in 67 patients revealing normal left ventricular (LV) systolic function in all of them. The mean LV ejection fraction was 66.1% ± 3.9%. The TRPG at rest could be recorded in 65 (97%) patients with the mean value of 26.9 ± ± 7.6 mm Hg (range 17-57 mm Hg). A resting TRPG of 〉 31 mm Hg, suggestive of possible PH, was demonstrated in 14 (21%) patients. During exercise test 56 (84%) patients achieved the maximum heart rate. A Doppler spectrum enabling the measurement of TRPG following the exercise was obtained in 66 (98.5%) patients. The gradient following the exercise could not be measured in one patient with a resting TRPG of 30 mm Hg. The mean post-exercise TRPG was 40.3 ± 4.1 mm Hg (range 17-70) and the mean post-exercise increase in TRPG was 12.9 ± 8.5 mm Hg (range 2-38). A TRPG increase of 〉 20 mm Hg was found in 11 (16%) patients (including 4 patients with resting values exceeding 31 mm Hg and 7 patients with normal resting values). Twenty-one (31%) patients with echocardiographic suspicion of PH (TRPG 〉 31 mm Hg at rest and/or a post-exercise increase in TRPG of more than 20 mm Hg) were referred for RHC with 16 patients actually undergoing the procedure. Four out of these 16 patients were qualified because of the "positive" exercise echocardiography in the presence of normal TRPG values. During catheterisation arterial PH was found in 2 patients, and an excessive precapillary PAP elevation in 2 further patients. Resting venous PH was found in 1 patient and an excessive postcapillary PAP elevation at rest was demonstrated in 11 patients. CONCLUSIONS: Exercise echocardiography is a safe and useful screening tool for PH diagnosis in patients with SSc. It enables to identify patients with normal systolic PAP at rest but a significant increase during exercise. The final confirmation of PH and differentiation between precapillary arterial and postcapillary venous PH requires RHC.

Pulmonary hypertension in systemic sclerosis determines cardiac autonomic dysfunction assessed by heart rate turbulence.

There is limited data on heart rate turbulence (HRT) in systemic sclerosis (SSc) patients, potentially threatened with cardiac autonomic dysfunction. We performed 24-hour Holter monitoring for HRT assessment in 45 patients with SSc and 30 healthy controls. Abnormal HRT defined as turbulence onset (TO) >or=0.0% and/or turbulence slope (TS)

Penicillin-induced anti-p200 pemphigoid: an unusual morphology.

We report here a case of a 52-year-old woman with erythema gyratum repens-like lesions appearing during anti-p200 pemphigoid, probably induced by oral penicillin. The diagnosis of anti-p200 pemphigoid was made by the presence of in vivo bound and circulating IgG anti-basement membrane zone auto-antibody reactive with the dermal side of salt-split skin and with 200 kDa protein in dermal extract on Western immunoblot. Laser scanning confocal microscopic study disclosed the localization of IgG at the lamina lucida-lamina densa border. Skin lesions responded poorly to high dose of prednisone and the combination of prednisone and dapsone. When methotrexate was added, skin lesions healed within 3 weeks. To our knowledge, erythema gyratum repens-like lesions have not been described previously in this disorder. Thus, we have expanded the clinical morphological spectrum of patients with anti-p200 pemphigoid and first described a patient whose disorder was probably drug-induced.