Mostafa Ahmed

Non-invasive screening for pulmonary hypertension in idiopathic pulmonary fibrosis

BACKGROUND Pulmonary hypertension (PH) is a common complication of idiopathic pulmonary fibrosis (IPF) that is associated with poor prognosis. Noninvasive screening for PH in IPF patients is challenging and a combination of several noninvasive determinations can improve discrimination. METHODS We included 235 IPF patients who underwent right heart catheterization (RHC) as part of the lung transplant evaluation. We measured electrocardiographic (ECG) and echocardiographic variables as well as the pulmonary artery (PA) and ascending aorta (AA) diameters on chest CT. We recorded results of arterial blood gases (ABG), pulmonary function (PFT) and 6-min walk tests (6MWT). RESULTS Several variables were predictors of PH in IPF patients in univariable models including a lower arterial oxygenation and 6MWT distance; worse right ventricular (RV) function, rightward deviation of the QRS axis and a higher FVC/DLCOc ratio, PA/AA diameter ratio, and estimated RV systolic pressure. In multivariable analysis, a worse RV function and higher PA/AA ratio remained predictors of PH (c-index 0.75 (0.65-0.84)). Similarly, a worse RV function, a higher PA/AA ratio and a rightward QRS axis deviation were independent predictors of precapillary PH (c-index 0.86 (0.76-0.92)). A combination of PA/AA diameter ratio <1.1, a QRS axis <90° and normal RV function showed a negative predictive value of 85% for precapillary PH. CONCLUSIONS There are significant differences in ECG, echocardiographic, chest CT, PFT and ABG parameters between IPF patients with and without PH. However, these noninvasive tests alone or combination have limited discrimination ability for PH screening in IPF.

Peripheral pulmonary artery stenosis as a cause of pulmonary hypertension in adults

Peripheral pulmonary artery stenosis (PPAS) is an underrecognized condition in the adult population. PPAS can lead to pulmonary hypertension but is likely misdiagnosed as either idiopathic pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. We retrospectively identified adult patients with PPAS either in its isolated form or related to other congenital defects from January 1998 to September 2012. We reviewed the patients’ clinical data by using our hospital electronic medical records and/or their paper charts. We identified 6 adult patients with PPAS with an age range of 16–56 years (1 woman and the rest men). Presenting signs and symptoms were thoracic murmurs, progressive dyspnea, and syncope. Three patients had Williams-Beuren syndrome. Pulmonary angiography showed that PPAS was predominantly located in main branches or lobar pulmonary arteries in 5 patients, while in 1 patient the arterial narrowing was at the level of the segmental pulmonary arteries. Right heart catheterization showed a mean pulmonary artery pressure (PAP) ranging from 35 to 60 mmHg. Balloon dilation was performed in all patients, predominantly in the lobar arteries, and it caused a decrease in mean PAP that ranged from 16% to 46% in 5 patients. In 1 patient the mean PAP did not decrease. All but 1 patient had follow-up echocardiograms at 1 year that showed stable echocardiographic findings. Pulmonary hypertension due to PPAS continues to presents a diagnostic challenge. Therefore, a high index of suspicion during the initial evaluation of pulmonary hypertension is essential for its prompt diagnosis and adequate treatment.

Treprostinil Iontophoresis in Idiopathic Pulmonary Arterial Hypertension.

Idiopathic pulmonary arterial hypertension (PAH) is a progressive disease without identifiable etiology and is characterized by elevated pulmonary vascular resistance that can lead to right heart failure and death (1). Initial studies characterized idiopathic PAH (IPAH) as a disease of the pulmonary circulation; however, recent data from us (2, 3) and other investigators (4–6) showed evidence of extrapulmonary vascular involvement. The extrapulmonary microcirculation can be studied in vivo, using cutaneous laser Doppler flowmetry (7), a methodology that can measure changes in skin flow in response to vasoactive stimuli. One stimulus is the cutaneous administration of prostacyclin (PGI2), using iontophoresis. Patients with IPAH have a marked reduction in PGI2 synthase (8) and expression of prostaglandin I2 receptors (9) in the lungs. More important, PGI2 analogs are potent medications to treat IPAH. Treprostinil is a PGI2 analog that increases cutaneous blood flow when administered by cathodal iontophoresis to healthy volunteers (10) and patients with systemic sclerosis (11). We hypothesize that patients with IPAH have systemic abnormalities in the PGI2 pathway that can be tested in vivo by cutaneous treprostinil iontophoresis. The research protocol was approved by the Cleveland Clinic Institutional Review Board, and all subjects provided written informed consent. We conducted this cross-sectional study between February 2013 and February 2015.We included consecutive patients who met hemodynamic criteria for PAH (12) and had the idiopathic or heritable (HPAH) forms of the disease. In addition, we studied ageand sex-matched control subjects without clinical evidence of pulmonary hypertension. We used the PeriFlux system 5000 (Perimed, Järfälla, Sweden) to test the effects of treprostinil iontophoresis and local thermal hyperemia. Treprostinil iontophoresis in patients was performed within 1 hour after right heart catheterization. Treprostinil (Remodulin 1 mg/ml) and its placebo (only treprostinil buffer) were iontophoresed for 30 minutes at 20 mA with a negative polarity. Measures were expressed as arbitrary perfusion units (PUs) (Figure 1). A detailed description of the methods is presented in the online supplement. Safety of the methodology was ascertained by recording local and/or systemic adverse effects in all subjects and by measuring treprostinil levels in plasma (at 20 minutes of iontophoresis) in a subset of individuals (n = 5). Patients (n = 24; IPAH = 22, HPAH = 2) and controls (n = 25) were ageand sex-matched. We also matched conditions known to be associated with systemic microvascular dysfunction. Patients were in New York Heart Association functional class I (n = 4, 17%), II (n = 7, 29%), III (n = 12, 50%), and IV (n = 1, 4%). Three quarters of patients were receiving PAHspecific therapies at the time of iontophoresis. Five (21%) and 7 (29%) received inhaled or parenteral PGI2 analogs, respectively. Patients had a mean pulmonary artery pressure of 44.56 14 mm Hg, cardiac index (thermodilution) of 2.86 0.79 L/min/m, and pulmonary vascular resistance of 7.56 4.3 Wood units. A total of 17 patients underwent inhaled nitric oxide challenge. With treprostinil iontophoresis, peak PUs, percentage change in PUs, and the percentage of peak PUs relative to the maximum value obtained by local hyperthermia were significantly reduced in patients compared with matched controls (Table 1). These relationships persisted after adjusting for skin resistance. The treprostinil buffer only minimally increased these determinations (n = 6), supporting the idea that the vasoactive effects are mostly a result of treprostinil. The receiver operating characteristic curve that tested the ability of the percentage change in PUs with treprostinil iontophoresis to discriminate between patients and controls showed an area under the curve of 0.75 (95% confidence interval [CI], 0.60–0.86; P = 0.0007). Patients treated with PGI2 analogs had higher baseline PUs (median [interquartile range], 7 [4–10] vs. 3 [2–6]; P = 0.04) and higher cardiac indexes (3.2 [2.8–3.6] vs. 2.4 [1.8–3.1] L/min/m; P = 0.01) than those not receiving this treatment. In addition, those receiving PGI2 analogs had a higher percentage change in PUs (517 [202–672] vs. 225 [86–274]%; P = 0.004) during treprostinil iontophoresis compared with individuals not receiving this treatment. In patients with IPAH not receiving PGI2 analogs (n = 12), the receiver operating characteristic curve of percentage change in PUs for discriminating patients versus controls showed an area under the curve of 0.87 (95% CI, 0.72–0.96; P , 0.0001). In this analysis, a cutoff of <300% had sensitivity of 83% and specificity of 87% to identify patients with IPAH from controls. The peak PUs during treprostinil iontophoresis was associated with New York Heart Association functional class (R =20.35; P = 0.01) and the number of PAH-specific therapies (R = 0.48; P = 0.02). We also noted a significant association between peak PU and cardiac index (R = 0.57; P = 0.004). We did not find an association between pulmonary vascular resistance, pulmonary vascular response to inhaled NO during right heart Supported by Clinical and Translational Science Collaborative KL2 (grant TR000440 to A.R.T.) from the National Center for Research Resources, a component of the National Institutes of Health, National Institutes of Health Roadmap for Medical Research. M.K.A. is supported by the Egyptian Cultural and Educational Research Scholar Program.

What is the best approach to a high systolic pulmonary artery pressure on echocardiography

This is a common incidental finding. What to do depends on clinical presentation, comorbidities, and results of other tests.

Synthesis of some heterocyclic compounds derived from indole as antimicrobial agents

ABSTRACT Recently, indoles are considered interesting heterocyclic compounds due to their wide range of biological activities such as antimicrobial activity. Herein, some new indole derivatives containing heterocyclic moieties were synthesized using 3-chloro-1H-Indole-2-carbaldehyde (1) as a starting material, then allowed to react with compounds containing active methylene under Knoevenagel condensation and afforded the corresponding compounds (2, 3, 9). Also, the compound (1) when allowed to react with hydrazine derivatives gave the corresponding thiosemiccarbazone, semicarbazone, and hydrazone derivatives (4, 5, 6). Reaction of thiosemicarbazone derivatives with α-halognated carbonyl compounds gave the thiazolyl indole derivatives (10, 12a–b). Cyclic chalcones (11a–c) were obtained when compound (10) reacted with different aromatic aldehydes. The structures of all new synthesized compounds were confirmed on the basis of spectral analysis, IR, 1H NMR, 13C NMR, and MS spectroscopy. All synthesized compounds were evaluated for their antimicrobial activity. Compounds (2, 5, 7, 8, 11a, 12a) showed high antibacterial activity and compounds (3, 6, 9, 10, 11a, 12a) showed high antifungal activity. GRAPHICAL ABSTRACT

Are transcutaneous oxygen and carbon dioxide determinations of value in pulmonary arterial hypertension

We hypothesized that transcutaneous gas determinations of O2 and CO2 (TcPO2 and TcPCO2) are associated with the severity of PAH.