Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders.

BACKGROUND: Few biomarkers are available for early identification of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) in systemic sclerosis (SS) and scleroderma spectrum disorders (SSD). AIMS: To evaluate Gas6, sAxl, and sMer as biomarkers for cardiopulmonary complications of SS and SSD. METHODS: In a cross-sectional observational study, we recruited 125 consecutive patients, affected by SS and SSD and referred to a tertiary-level pulmonary hypertension outpatient clinic. All patients underwent a comprehensive evaluation for identification of PAH and ILD. Gas6, sMer, and sAxl concentrations were measured with ELISA protocols, and concentrations were compared according to PAH or ILD. RESULTS: Nineteen subjects had pulmonary hypertension (PH) (14 PAH), and 39 had ILD (6 severe). Plasma sMer was increased in PAH (18.6 ng/ml IQR [11.7-20.3]) with respect to the absence (12.4 [8.0-15.8]) or other form of pulmonary hypertension (9.6 [7.4-12.5]; K-W variance p < 0.04). Conversely, Gas6 and sAxl levels were slightly increased in mild ILD (25.8 ng/ml [19.5-32.1] and 24.6 [20.1-32.5]) and reduced in severe ILD (16.6 [15.0-22.1] and 15.5 [14.9-22.4]) in comparison to no evidence of ILD (23.4 [18.8-28.1] and 21.6 [18.1-28.4]; K-W, p ≤ 0.05). Plasma sMer ≥ 19 ng/ml has 50% sensitivity and 92% specificity in PAH identification (area under the ROC curve (AUC) 0.697, p < 0.03). Values of Gas6 ≤ 24.5 ng/ml and of sAxl ≤ 15.5 ng/ml have 100% and 67% sensitivity and 47% and 86% specificity, respectively, in identifying severe ILD (Gas6 AUC 0.787, p < 0.001; sAxl AUC 0.705, p < 0.05). CONCLUSIONS: The assay of Gas6 sAxl and sMer may be useful to help in the identification of PAH and ILD in SS and SSD patients. The Gas6/TAM system seems to be relevant in cardiopulmonary complications of SS and SSD and merits further investigations.

Prevalence of undiagnosed chronic thromboembolic pulmonary hypertension after pulmonary embolism.

Chronic thromboembolic pulmonary hypertension is associated with adverse prognosis. Early diagnosis is important to better identify patients who would benefit from a well established therapeutic strategy. The purpose of our study was to evaluate long-term incidence of undiagnosed chronic thromboembolic pulmonary hypertension after acute pulmonary embolism and the utility of a long-term follow-up including an echocardiographic-based screening programme to early detect this disease. We evaluated retrospectively 282 patients discharged from the 'Maggiore della Carità' Hospital, Università del Piemonte Orientale, Novara, Italy, with diagnosis of acute pulmonary embolism between November 2006 and October 2009. One hundred and eleven patients underwent a clinical late echocardiographic screening programme after the acute event. Patients with suspected pulmonary hypertension based on echocardiographic evidence of systolic pulmonary artery pressure of at least 40  mmHg underwent complete work-up for chronic thromboembolic pulmonary hypertension assessment, including ventilation-perfusion lung scintigraphy and right heart catheterization. One hundred and eleven patients were included in the study. Pulmonary hypertension was suspected in 15 patients; five patients had chronic thromboembolic pulmonary hypertension confirmed by ventilation-perfusion lung scintigraphy, right heart catheterization and pulmonary angiography. Two patients with clinical class functionally advanced underwent surgical pulmonary endarterectomy and two asymptomatic patients underwent medical treatment. The prevalence of undiagnosed chronic thromboembolic pulmonary hypertension was 4.5%. Chronic thromboembolic pulmonary hypertension is a serious disease with a poor prognosis if not treated early. Surgical treatment is decisive. After surgery, the majority of patients have a substantial improvement in their functional status and in haemodynamic variables. Many patients are asymptomatic. Implementation of screening programmes may be helpful for an early diagnosis and early proper therapy.

Cardiac dyssynchrony quantitated by time-to-peak or temporal uniformity of strain at longitudinal, circumferential, and radial level: implications for resynchronization therapy.

BACKGROUND: The standard deviation of time to peak strain (TPS-SD) has been proposed as an index of left ventricular (LV) dyssynchrony in patients to be resynchronized. However, TPS-SD is sensitive to noise, and the influence of outliers on TPS-SD is also relevant. Alternatively, dyssynchrony can be indexed by temporal uniformity of strain (TUS), whereby a time plot of regional strains, arranged for LV location, is subjected to Fourier analysis. If segments shorten simultaneously (synchronously), the plot appears as a straight line, with power only in the zero-order Fourier term, whereas regionally clustered dyssynchrony generates an undulating plot with higher power in the first-order term. TUS index reflects zero-order relative to first-order plus zero-order power. METHODS: In this study, TUS and TPS-SD were computed in 68 patients (QRS duration >/= 120 ms; ejection fraction