Bajwa, Abubakr A.

AbstractInhaled treprostinil is an approved therapy for pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease in the United States. Studies have confirmed the robust benefits and safety of nebulized inhaled treprostinil, but it requires a time investment for nebulizer preparation, maintenance, and treatment. A small, portable treprostinil dry powder inhaler has been developed for the treatment of PAH. The primary objective of this study was to evaluate the safety and tolerability of treprostinil inhalation powder (TreT) in patients currently treated with treprostinil inhalation solution. Fifty‐one patients on a stable dose of treprostinil inhalation solution enrolled and transitioned to TreT at a corresponding dose. Six‐minute walk distance (6MWD), device preference and satisfaction (Preference Questionnaire for Inhaled Treprostinil Devices [PQ‐ITD]), PAH Symptoms and Impact (PAH‐SYMPACT®) questionnaire, and systemic exposure and pharmacokinetics for up to 5 h were assessed at baseline for treprostinil inhalation solution and at Week 3 for TreT. Adverse events (AEs) were consistent with studies of inhaled treprostinil in patients with PAH, and there were no study drug‐related serious AEs. Statistically significant improvements occurred in 6MWD, PQ‐ITD, and PAH‐SYMPACT. Forty‐nine patients completed the 3‐week treatment phase and all elected to participate in an optional extension phase. These results demonstrate that, in patients with PAH, transition from treprostinil inhalation solution to TreT is safe, well‐tolerated, and accompanied by statistically significant improvements in key clinical assessments and patient‐reported outcomes with comparable systemic exposure between the two formulations at evaluated doses (trial registration: clinicaltrials.gov identifier: NCT03950739).

AbstractBackgroundTransthoracic echocardiography (TTE) and computerized axial tomography (CT) are complementary imaging techniques. It is possible that a combination of the two may offer a better way of identifying pulmonary hypertension (PH) than either one alone.ObjectivesTo determine the diagnostic accuracy of TTE combined with chest CT in pulmonary hypertension.MethodsWe performed a retrospective review of consecutive patients who had undergone TTE, CT and right heart catheterization (RHC) between 7/1/2008 and 6/30/2012. PH was defined as systolic pulmonary artery pressure >40 mm Hg or tricuspid regurgitant (TR) jet velocity >2.8m/s on TTE, ratio of diameter of pulmonary artery to ascending aorta (rPA) >1 or diameter of PA (dPA) >30 mm on CT, and mean PAP (mPAP) >25 mm Hg on RHC.ResultsThere was a total of 87 patients. The mean ± SD age was 54.3 ± 15.9 years and 69 (79%) were female. The prevalence of PH was 75%. The mean ± SD mPAP was 35.8 ± 14.2 mm Hg. The majority of the patients belonged to World Health Organization group I PH. Fifty per cent of the CT scans were done with intravenous contrast dye. The combination of TR jet velocity and rPA provided the best combination of sensitivity (98%) and specificity (70%) with an ROC area under the curve of 0.84.ConclusionThe combination of TTE and chest CT is better than either imaging technique alone in identifying patients with PH in a heterogeneous population and may exclude PH

The primary aim was to explore the safety and tolerability of inhaled treprostinil when used in patients with pulmonary hypertension (PH) with concomitant chronic obstructive pulmonary disease (COPD). Patients with a diagnosis of pre‐capillary PH (defined as pulmonary artery mean pressure of ≥ 25 mmHg and pulmonary artery wedge pressure or left ventricular end diastolic pressure of ≤ 15 mmHg) who were being initiated on inhaled treprostinil and had concomitant COPD (defined as FEV1/FVC ratio ≤ 70% with FEV1 ≥ 40% predicted) were considered for inclusion in this pilot study. Assessments included adverse events, physical exam, World Health Organization (WHO) functional class, 6‐minute walk test (6MWT), modified Borg dyspnea score, and concomitant medication. At baseline and week 16 St. George’s Respiratory Questionnaire (SGRQ), arterial blood gas (ABG), and pulmonary function test (PFT) were assessed. The median age was 65 years (age range, 56–80 years) and five patients (56%) were men. Among the nine patients, a majority had an increase in 6MWT from baseline to week 16 (median change, 19 m). Only three of the nine patients (33%) had an increase in A‐a gradient at week 16 (median change, –7). There was no difference in any of the following: arterial blood gases, WHO functional class, 6MWT results, or SGRQ scores from baseline to week 16. There was a statistically significant decline in several of the PFT measures, including FEV1 (median change, –0.18 L; P = 0.004; median change, –7% of predicted; P = 0.016), FVC (median change, –0.23 L; P = 0.027), and diffusion capacity for carbon monoxide (DLCO) (median change, –5% of predicted; P = 0.023). The small number of patients limits firm conclusions; however, inhaled treprostinil did not seem to adversely impact oxygenation in the majority of the study patients with pre‐capillary PH and COPD. While there may have an adverse impact on some pulmonary function parameters, the clinical significance is unclear.

The objective of this retrospective cohort study was to describe the incidence of paroxysmal atrial fibrillation and to determine its risk factors and effect on outcome in critically ill patients with sepsis. The study included 81 patients with sepsis admitted to an intensive care unit. In all, 25 patients (31%) developed paroxysmal atrial fibrillation. Advanced age, history of paroxysmal atrial fibrillation, higher severity of illness at intensive care unit admission, and lower left ventricular ejection fraction were risk factors for paroxysmal atrial fibrillation. Multiple logistic regression analysis showed that paroxysmal atrial fibrillation was independently associated with 28-day mortality (odds ratio = 3.284; 95% confidence interval, 1.126-9.574). The incidence of paroxysmal atrial fibrillation is high in critically ill patients with sepsis. It occurs more frequently in patients with advanced age, history of paroxysmal atrial fibrillation, high severity of illness, and lower left ventricular ejection fraction and is associated with increased mortality.