Comparison of mean platelet volume values among different causes of pulmonary hypertension

Background: Pulmonary hypertension is caused by a heterogenous group of disorders with diverse pathophysiological mechanisms, with ultimate structural changes in the pulmonary vascular bed. Platelet activation plays an important role in the development of pulmonary arterial hypertension, while it is unknown whether it contributes to pathogenesis in other conditions. We aimed to investigate platelet activation in different causes of pulmonary hypertension by means of mean platelet volume measurement. Methods: A total of 67 patients with different causes of pulmonary hypertension, and 31 controls, were retrospectively reviewed. Patients with pulmonary hypertension were further grouped according to underlying disease, including pulmonary arterial hypertension, pulmonary hypertension due to left ventricular failure, and pulmonary hypertension due to chronic obstructive pulmonary disorder. All patients and controls&#8217; past medical data, admission echocardiograms and complete blood counts were reviewed. Results: Patients with pulmonary hypertension had higher mean platelet volume levels compared to healthy controls (8.77 &#177; 1.18 vs 7.89 &#177; 0.53; p < 0.001), and statistical significance was still present when pulmonary arterial hypertension patients were not included in the pulmonary hypertension group (8.59 &#177; 1.23 vs 7.89 &#177; 0.53; p < 0.001). Among patients with pulmonary hypertension, the pulmonary arterial hypertension group and the pulmonary hypertension due to left ventricular failure group had higher mean platelet volumes compared to healthy controls. Mean platelet volume did not correlate with pulmonary artery pressure. Conclusions: Our results indicate that mean platelet volume is not only elevated in pulmonary arterial hypertension, but also due to other causes of pulmonary hypertension. (Cardiol J 2012; 19, 2: 180&#8211;187

Journal of Cardiovascular Magnetic Resonance / Pulmonary artery to aorta ratio for the detection of pulmonary hypertension : cardiovascular magnetic resonance and invasive hemodynamics in heart failure with preserved ejection fraction

Background Previous work indicates that dilatation of the pulmonary artery (PA) itself or in relation to the ascending aorta (PA:Ao ratio) predicts pulmonary hypertension (PH). Whether these results also apply for heart failure with preserved ejection fraction (HFpEF) is unknown. In the present study we evaluated the diagnostic and prognostic power of PA diameter and PA:Ao ratio on top of right ventricular (RV) size, function, and septomarginal trabeculation (SMT) thickness by cardiovascular magnetic resonance (CMR) in HFpEF. Methods and Results 159 consecutive HFpEF patients were prospectively enrolled. Of these, 111 underwent CMR and invasive hemodynamic evaluation. By invasive assessment 64 % of patients suffered from moderate/severe PH (mean pulmonary artery pressure (mPAP) 30 mmHg). Significant differences between groups with and without moderate/severe PH were observed with respect to PA diameter (30.9 5.1 mm versus 26 5.1 mm, p < 0.001), PA:Ao ratio (0.93 0.16 versus 0.78 0.14, p < 0.001), and SMT diameter (4.6 1.5 mm versus 3.8 1.2 mm; p = 0.008). The strongest correlation with mPAP was found for PA:Ao ratio (r = 0.421, p < 0.001). By ROC analysis the best cut-off for the detection of moderate/severe PH was found for a PA:Ao ratio of 0.83. Patients were followed for 22.0 14.9 months. By Kaplan Meier analysis event-free survival was significantly worse in patients with a PA:Ao ratio 0.83 (log rank, p = 0.004). By multivariable Cox-regression analysis PA:Ao ratio was independently associated with event-free survival (p = 0.003). Conclusion PA:Ao ratio is an easily measureable noninvasive indicator for the presence and severity of PH in HFpEF, and it is related with outcome.(VLID)486713

Comparing the levels of CTLA-4-dependent biological defects in patients with LRBA deficiency and CTLA-4 insufficiency

Background Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency and cytotoxic T-lymphocyte protein-4 (CTLA-4) insufficiency are recently described disorders that present with susceptibility to infections, autoimmunity, and lymphoproliferation. Clinical and immunological comparisons of the diseases with long-term follow-up have not been previously reported. We sought to compare the clinical and laboratory manifestations of both diseases and investigate the role of flow cytometry in predicting the genetic defect in patients with LRBA deficiency and CTLA-4 insufficiency. Methods Patients were evaluated clinically with laboratory assessments for lymphocyte subsets, T follicular helper cells (T-FH), LRBA expression, and expression of CD25, FOXP3, and CTLA4 in regulatory T cells (Tregs) at baseline and 16 h post-stimulation. Results LRBA-deficient patients (n = 29) showed significantly early age of symptom onset, higher rates of pneumonia, autoimmunity, chronic diarrhea, and failure to thrive compared to CTLA-4 insufficiency (n = 12). In total, 29 patients received abatacept with favorable responses and the overall survival probability was not different between transplanted versus non-transplanted patients in LRBA deficiency. Meanwhile, higher probability of survival was observed in CTLA-4-insufficient patients (p = 0.04). The T-cell subsets showed more deviation to memory cells in CTLA-4-insufficiency, accompanied by low percentages of Treg and dysregulated cT(FH) cells response in both diseases. Cumulative numbers of autoimmunities positively correlated with cT(FH) frequencies. Baseline CTLA-4 expression was significantly diminished in LRBA deficiency and CTLA-4 insufficiency, but significant induction in CTLA-4 was observed after short-term T-cell stimulation in LRBA deficiency and controls, while this elevation was less in CTLA-4 insufficiency, allowing to differentiate this disease from LRBA deficiency with high sensitivity (87.5%) and specificity (90%). Conclusion This cohort provided detailed clinical and laboratory comparisons for LRBA deficiency and CTLA-4 insufficiency. The flow cytometric approach is useful in predicting the defective gene; thus, targeted sequencing can be conducted to provide rapid diagnosis and treatment for these diseases impacting the CTLA-4 pathway