IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertension.

AV-101 (imatinib) powder for inhalation, an investigational dry powder inhaled formulation of imatinib designed to target the underlying pathobiology of pulmonary arterial hypertension, was generally well tolerated in healthy adults in a phase 1 single and multiple ascending dose study. Inhaled Imatinib Pulmonary Arterial Hypertension Clinical Trial (IMPAHCT; NCT05036135) is a phase 2b/3, randomized, double-blind, placebo-controlled, dose-ranging, and confirmatory study. IMPAHCT is designed to identify an optimal AV-101 dose (phase 2b primary endpoint: pulmonary vascular resistance) and assess the efficacy (phase 3 primary endpoint: 6-min walk distance), safety, and tolerability of AV-101 dose levels in subjects with pulmonary arterial hypertension using background therapies. The study has an operationally seamless, adaptive design allowing for continuous recruitment. It includes three parts; subjects enrolled in Part 1 (phase 2b dose-response portion) or Part 2 (phase 3 intermediate portion) will be randomized 1:1:1:1 to 10, 35, 70 mg AV-101, or placebo (twice daily), respectively. Subjects enrolled in Part 3 (phase 3 optimal dose portion) will be randomized 1:1 to the optimal dose of AV-101 and placebo (twice daily), respectively. All study parts include a screening period, a 24-week treatment period, and a 30-day safety follow-up period; the total duration is ∼32 weeks. Participation is possible in only one study part. IMPAHCT has the potential to advance therapies for patients with pulmonary arterial hypertension by assessing the efficacy and safety of a novel investigational drug-device combination (AV-101) using an improved study design that has the potential to save 6-12 months of development time. ClinicalTrials.gov Identifier: NCT05036135.

AV-101, a novel inhaled dry-powder formulation of imatinib, in healthy adult participants: a phase 1 single and multiple ascending dose study.

Background: Oral imatinib has been shown to be effective, but poorly tolerated, in patients with advanced pulmonary arterial hypertension (PAH). To maintain efficacy while improving tolerability, AV-101, a dry powder inhaled formulation of imatinib, was developed to deliver imatinib directly to the lungs. Methods: This phase 1, placebo-controlled, randomised single ascending dose (SAD) and multiple ascending dose (MAD) study evaluated the safety/tolerability and pharmacokinetics of AV-101 in healthy adults. The SAD study included five AV-101 cohorts (1 mg, 3 mg, 10 mg, 30 mg, 90 mg) and placebo, and a single-dose oral imatinib 400-mg cohort. The MAD study included three AV-101 cohorts (10 mg, 30 mg, 90 mg) and placebo; dosing occurred twice daily for 7 days. Results: 82 participants (SAD n=48, MAD n=34) were enrolled. For the SAD study, peak plasma concentrations of imatinib occurred within 3 h of dosing with lower systemic exposure compared to oral imatinib (p<0.001). For the MAD study, systemic exposure of imatinib was higher after multiple doses of AV-101 compared to a single dose, but steady-state plasma concentrations were lower for the highest AV-101 cohort (90 mg) compared to simulated steady-state oral imatinib at day 7 (p=0.0002). Across AV-101 MAD dose cohorts, the most common treatment-emergent adverse events were cough (n=7, 27%) and headache (n=4, 15%). Conclusions: AV-101 was well tolerated in healthy adults, and targeted doses of AV-101 significantly reduced the systemic exposure of imatinib compared with oral imatinib. An ongoing phase 2b/phase 3 study (IMPAHCT; clinicaltrials.gov identifier NCT05036135) will evaluate the safety/tolerability and clinical benefit of AV-101 for PAH.

INSPIRE: Safety and tolerability of inhaled Yutrepia (treprostinil) in pulmonary arterial hypertension (PAH).

The INSPIRE trial was a Phase 3, open-label, multicenter trial (LTI-301) that enrolled patients with pulmonary arterial hypertension (PAH) ≥ 18 years of age who transitioned to Yutrepia from nebulized treprostinil (Transition) or added Yutrepia to prostacyclin naïve patients on ≤2 nonprostacyclin oral therapies. The objectives of the trial were to evaluate the safety and tolerability of Yutrepia (dry-powder formulation of treprostinil) in patients with PAH. The primary safety measures were the incidence of adverse events (AEs) and serious AEs. Exploratory efficacy measures were also assessed during the trial. Transition patients initiated Yutrepia at a dose comparable to their nebulized treprostinil dose while prostacyclin naïve patients received 26.5-mcg QID; up-titration in 26.5-mcg increments was permitted for both groups. A total of 121 patients were enrolled, of which 29 patients discontinued from the trial, with the most common reason being AEs. Eighty percent of the Transition group and 96% of the prostacyclin naïve group titrated to a dose ≥79.5 mcg QID at Day 360, respectively, with one patient achieving a dose of 212-mcg QID. The most common AEs were cough, headache, upper respiratory tract infection, dyspnea, dizziness, throat irritation, diarrhea, chest discomfort, fatigue, and nasopharyngitis. Most of these events were considered treatment-related though mild to moderate in severity and expected for prostacyclin therapy administered by inhalation. In an evaluation of exploratory efficacy measures, patients remained stable or improved over the 1 year of treatment. Yutrepia was found to be a convenient, safe, and well-tolerated inhaled prostacyclin treatment option for PAH patients.

Erratum: Health disparities and treatment approaches in portopulmonary hypertension and idiopathic pulmonary arterial hypertension: An analysis of the Pulmonary Hypertension Association Registry.

[This corrects the article DOI: 10.1177/20458940211020913.].

Comparison of shock reversal with high or low dose hydrocortisone in intensive care unit patients with septic shock: A retrospective cohort study.

PURPOSE: This study aims to describe differences in shock reversal between hydrocortisone 200 mg and 300 mg per day dosing regimens in patients with septic shock. METHODS: This is a multi-center retrospective study including patients admitted to intensive care units with septic shock receiving vasopressors and hydrocortisone between 2013 and 2018. We compared patients who received low dose hydrocortisone (50 mg every 6 h) versus high dose hydrocortisone (100 mg every 8 h) on the primary outcome of shock reversal. RESULTS: 319 patients (low dose group, n = 134 and high dose group, n = 185) were included. In the multivariate regression model, high-dose steroids were associated with shock reversal [OR (95% CI) = 2.278 (1.063-4.880), p = 0.034]. This was not confirmed in the propensity score matched analysis [OR (95% CI) =2.202 (0.892-5.437), p = 0.087]. High dose steroids were associated with a lower need for additional vasopressor therapy (22% vs. 34%, p = 0.012) and lower shock recurrence (6.7% vs. 16%, p = 0.013), which was confirmed with propensity score matching. CONCLUSIONS: Low and high dose hydrocortisone have similar rates of shock reversal in septic shock patients. Hydrocortisone 100 mg every 8 h may reduce rates of recurrence of shock and reduce the need for additional vasopressors.

Implantable system for treprostinil and lung transplantation: case series from delivery for pulmonary arterial hypertension study.

The implanted system for treprostinil has been described in previous publications. There is no information published about how to handle this system around lung or heart-lung transplantation. We present the experience from the DelIVery for Pulmonary Arterial Hypertension study. Seven subjects from five pulmonary arterial hypertension centers were included in this retrospective chart review. All subjects were participating in the previously described DelIVery for pulmonary arterial hypertension study. Seven subjects with implanted pumps have been listed for lung or heart-lung transplant. Six subjects underwent lung or heart-lung transplantation and one remains on the transplant list. Three different methods of patient management for transplant were used. In three subjects, the implanted system was filled with saline prior to transplantation and treprostinil was infused via an external system. Three subjects had their drug-filled implanted pump and catheter system explanted at the time of transplant. One patient had the drug-filled implanted system removed prior to being listed for transplantation. Four subjects were hospitalized while waiting for transplantation. In conclusion, the implanted system for treprostinil is an important advance in the care of pulmonary arterial hypertension subjects. The experience described here provides three effective strategies for managing the implanted system around lung or heart-lung transplantation. The optimal strategy will depend on patient characteristics and lung transplant program preferences and wait list times.

Health disparities and treatment approaches in portopulmonary hypertension and idiopathic pulmonary arterial hypertension: an analysis of the Pulmonary Hypertension Association Registry.

Compared to idiopathic pulmonary arterial hypertension (IPAH), patients with portopulmonary hypertension (POPH) have worse survival. Health disparities may contribute to these differences but have not been studied. We sought to compare socioeconomic factors in patients with POPH and IPAH and to determine whether socioeconomic status and/or POPH diagnosis were associated with treatment and health-care utilization. We performed a cross-sectional study of adults enrolled in the Pulmonary Hypertension Association Registry. Patients with IPAH (n = 344) and POPH (n = 57) were compared. Compared with IPAH, patients with POPH were less likely to be college graduates (19.6% vs. 34.9%, p = 0.02) and more likely to be unemployed (54.7% vs. 30.5%, p < 0.001) and have an annual household income below poverty level (45.7% vs. 19.0%, p < 0.001). Patients with POPH had similar functional class, quality of life, 6-min walk distance, and mean pulmonary arterial pressure with a higher cardiac index. Compared with IPAH, patients with POPH were less likely to receive combination therapy (46.4% vs. 62.2%, p = 0.03) and endothelin receptor antagonists (28.6% vs. 55.1%, p < 0.001) at enrollment with similar treatment at follow-up. Patients with POPH had more emergency department visits (1.7 ± 2.1 vs. 0.9 ± 1.2, p = 0.009) and hospitalizations in the six months preceding enrollment (1.5 ± 2.1 vs. 0.8 ± 1.1, p = 0.02). Both POPH diagnosis and lower education level were independently associated with a higher number of emergency department visits. Compared to IPAH, patients with POPH have lower socioeconomic status, are less likely to receive initial combination therapy and endothelin receptor antagonists but have similar treatment at follow-up, and have increased health-care utilization.

Long-term results of the DelIVery for Pulmonary Arterial Hypertension trial.

BACKGROUND: The DelIVery for Pulmonary Arterial Hypertension clinical trial was a multi-center, prospective, single arm, Investigational Device Exemption study utilizing a fully implantable, programmable intravascular delivery system consisting of a pump and a catheter for intravenous treprostinil. The study met its primary endpoint and demonstrated that the intravascular delivery system significantly reduced catheter related complications at 22,000 subject-days of follow-up compared with a predefined objective performance criterion. Here we summarize the results obtained during a 6.4-year follow-up period. METHODS: Throughout study follow-up, participants had clinic visits and medication refills at least every 12 weeks (dependent on the subjects' dose). All adverse events and intravascular delivery system complications were evaluated and recorded. RESULTS: Sixty pulmonary arterial hypertension subjects were followed post device implantation for approximately 282 patient-years (range 87 days to 6.4 years). Of the 60 subjects, 14 died (1 related to intravascular delivery system pump failure), 2 withdrew after lung transplants, and 2 withdrew due to pump pocket infection. No catheter-related bloodstream infections, catheter thrombosis or occlusions, or catheter kinks occurred through 282 patient-years. Two participants had adverse events of abdominal pain, rash, due to subcutaneous treprostinil "leaks" after one catheter puncture and one catheter laceration during pump refill and replacement, respectively. Eight pump failure events occurred: seven pump motor stalls and one early replacement (faulty battery). CONCLUSION: Delivery of treprostinil with an intravascular delivery system is a safe alternative to an external delivery system, while providing enhanced life experiences. To preserve the risk-benefit ratio, treatment at specialized pulmonary arterial hypertension centers is recommended until training is disseminated at other sites.

Nebulized milrinone use in a pulmonary hypertensive crisis.

Significant advances have been achieved over the past few decades regarding comprehension of the pathogenesis of pulmonary arterial hypertension (PAH). The development of new agents and use of existing drug therapies have targeted the underlying abnormalities and pathways leading to progression of PAH. Milrinone, a phosphodiesterase inhibitor, remains a therapeutic option. Unfortunately, intravenous administration of the drug in patients with PAH may be limited by systemic hypotension, especially in those already receiving prostanoid treatment. We describe a 42-year-old woman with acute decompensated idiopathic PAH who was given nebulized milrinone as a novel adjunctive therapy. She was acutely treated with intravenous treprostinil 2 ng/kg/minute and inhaled nitric oxide 20 ppm. However, increasing the treprostinil infusion rate or adding other therapies such as intravenous milrinone for acute symptomatic relief was limited by her hemodynamic instability, which required treatment with dobutamine, vasopressin, and epinephrine. Nebulized milrinone was added as salvage therapy for her acute PAH crisis. After 8 days of therapy, the patient's PAH symptoms improved without compromising her mean arterial pressure and heart rate. Nebulized milrinone in addition to inhaled nitric oxide and low-dose intravenous treprostinil may have played a major role in the acute management of her PAH crisis. Further studies are needed to assess the role of nebulized milrinone in patients with PAH.

Blue after splenectomy.

INTRODUCTION: We present a 51 year old, African American, female who presented with persistent hypoxemia. She had been taking dapsone for many years for prophylaxis against Pneumocystic Jiroveci with no symptoms but eventually developed methemoglobinemia only after a splenectomy. From our literature review there are no documented cases that have demonstrated this relationship between dapsone, splenic function and methemoglobin and we hope to share our perplexing case and shed light on the interaction. DESCRIPTION: Our patient has type 1 diabetes and underwent multiple pancreas transplants and an initial kidney transplant during her disease course. One year prior to her presentation she underwent a distal pancreatectomy and an incidental splenectomy during the same procedure. She had been taking dapsone for approximately 17 years due to her allergy to sulfamethoxazole/trimethoprim and her immunosuppressive regimen included tacrolimus, sirolimus, and low dose prednisone. She had presented for a routine, post-surgery follow up visit when she was diagnosed with hypoxemia. After an extensive but unsuccessful work up for persistent hypoxemia, she presented to our clinic for a second opinion. Repeat testing of the arterial blood gas in clinic showed a significant methemoglobin (MHb) level of 16.6 mg/dl. DISCUSSION: Although methemoglobinemia is a well-known risk of dapsone exposure, we report a case that suggests that splenectomy can interact with dapsone to further increase the risk of methemobloginemia. We believe that our patient did not develop methemoglobinemia initially, despite being on dapsone for many years because her spleen was able to remove older more susceptible erythrocytes from the circulation leaving the more robust younger erythrocytes. With the splenectomy, the number of older erythrocytes in the peripheral circulation increased and resulted in an accumulation of MHb leading to the low oxygen saturations. Her dapsone was immediately stopped and she was started on vitamin C with a 3 day follow up revealing resolution of her methemoglobinemia and normal oxygen saturation on room air.

Transition from parenteral to oral treprostinil in pulmonary arterial hypertension.

BACKGROUND: Parenteral prostanoids are effective treatment for pulmonary arterial hypertension, but long-term pump infusion systems have significant delivery-related safety and convenience limitations. METHODS: Subjects with a favorable risk profile transitioned from parenteral to oral treprostinil using a protocol-driven titration during 5 days of inpatient observation. Baseline and Week 24 assessments included 6-minute walk distance, echocardiogram, right heart catheterization, pharmacokinetics, treatment satisfaction and quality of life. Thirty-three subjects (76% female, mean age 50 years) enrolled; 85% were using subcutaneous treprostinil with a median dose of 57 (range 25 to 111) ng/kg/min. Participants were using background, approved non-prostanoid therapy, including 9 on 2 oral therapies; baseline right atrial pressure and cardiac output were in the normal range. All 33 subjects transitioned to oral treprostinil therapy within 4 weeks, but 2 transitioned back to parenteral drug before Week 24. At Week 24, subjects were taking a median total daily dose of 44 (15 to 75) mg, with 25 of 31 using a 3-times-daily regimen at 7- to 9-hour intervals. RESULTS: The 6-minute walk distance was preserved (median +17 m [-98 to 95 m]) at its baseline of 446 m. Hemodynamic variables, including pulmonary vascular resistance, were similar at Week 24 except for mixed venous saturation, which dropped from a median of 71% to 68% (p < 0.001). Overall quality of life and treatment satisfaction measures did not change; however, mood-related symptom and treatment convenience subscores improved. Common adverse effects included headache, nausea, flushing and diarrhea. CONCLUSIONS: Lower risk patients managed on parenteral treprostinil may be candidates for transition to a more convenient, oral form of the drug.

Recommendations for the use of oral treprostinil in clinical practice: a Delphi consensus project pulmonary circulation.

Oral treprostinil was recently labeled for treatment of pulmonary arterial hypertension. Similar to the period immediately after parenteral treprostinil was approved, there is a significant knowledge gap for practicing physicians who might prescribe oral treprostinil. Despite its oral route of delivery, use of the drug is challenging because of the requirement for careful titration and management of drug-related adverse effects. We aimed to create a consensus document combining available evidence with expert opinion to provide guidance for use of oral treprostinil. Following a methodology commonly used in business and social sciences (the 'Delphi Process'), two investigators from the oral treprostinil (Freedom) studies created a series of statements based on available evidence and the package insert. The set of 'best practice' statements was circulated to nine other Freedom trial investigators. Their comments were incorporated into the document as new line items for further vote and comment. The subsequent document was put to vote line by line (scale of -5 to +5) and a final statement was drafted. Consensus recommendations include initial therapy with 0.125 mg for treatment naÿ patients, three times daily dosing, aggressive use of antidiarrheal medication, and a strong preference for use of the drug in combination with other approved PAH therapies. This process was particularly valuable in providing guidance for the management of adverse events (where essentially no data is available). The Delphi process was useful to codify investigator experience and subsequently develop investigator consensus about practical issues for physicians who may wish to prescribe oral treprostinil.

Totally Implantable IV Treprostinil Therapy in Pulmonary Hypertension Assessment of the Implantation Procedure.

BACKGROUND: Prostacyclins improve symptoms and survival in pulmonary arterial hypertension (PAH). In response to risks associated with external delivery systems, an implantable IV infusion system was developed. A multicenter, prospective, single-arm, clinical trial (DelIVery for PAH) was conducted to evaluate this system for treprostinil in PAH. This analysis describes the findings related to the implant procedure. METHODS: Patients (N = 64) with PAH (World Health Organization group 1) receiving stable IV treprostinil were enrolled. Patients were transitioned to a temporary peripheral IV infusion catheter prior to the procedure. System implantation was performed at 10 centers under general anesthesia or deep IV sedation by clinicians from various specialties. Central venous access was via the cephalic, subclavian, jugular, or axillary vein. Using an introducer and fluoroscopic guidance, the distal tip of the infusion catheter was placed at the superior caval-atrial junction. The catheter was tunneled from the venous access site to an abdominal subcutaneous pocket, where the pump was placed. RESULTS: Of the 64 patients enrolled, four exited prior to implantation. All 60 implant procedures were successful. At baseline, all patients were receiving treprostinil via an external pump at a mean dose of 71.4 ± 27.8 ng/kg/min (range: 22-142 ng/kg/min). The implant averaged 102 ± 32 min (range: 47-184 min). Clinically significant implant procedure-related complications included one pneumothorax, two infections, and one episode of atrial fibrillation. There were three postimplantation catheter dislocations in two patients. Common implant-related events that were not complications included implant site pain (83%) and bruising (17%). CONCLUSIONS: The procedure for inserting a fully implantable system for treprostinil was successfully performed, with few complications. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01321073; URL: www.clinicaltrials.gov.

Treprostinil Administered to Treat Pulmonary Arterial Hypertension Using a Fully Implantable Programmable Intravascular Delivery System: Results of the DelIVery for PAH Trial.

BACKGROUND: The use of systemic prostanoids in severe pulmonary arterial hypertension (PAH) is often limited by patient/physician dissatisfaction with the delivery methods. Complications associated with external pump-delivered continuous therapy include IV catheter-related bloodstream infections and subcutaneous infusion site pain. We therefore investigated a fully implantable intravascular delivery system for treprostinil infusion. METHODS: A multicenter, prospective, single-arm, clinical trial (DelIVery for Pulmonary Arterial Hypertension) was conducted by using an implantable intravascular delivery system. The implanted pumps were refilled percutaneously at least every 12 weeks. The primary end point was the rate of catheter-related complications using the new model 10642 catheter compared with a predefined objective performance criterion of 2.5 per 1,000 patient-days based on the literature. RESULTS: Patients (n = 60) with severe PAH (World Health Organization group 1) receiving a stable dose of IV treprostinil for at least 4 weeks received an implant device and were followed up for 12.1 ± 4.4 months. Six catheter-related complications occurred, corresponding to a complication rate of 0.27 per 1,000 patient-days. The 97.5% upper one-sided confidence bound of 0.59 was less than the predefined criterion of 2.5 per 1,000 patient-days (P < .0001). Plasma treprostinil levels at 1 week postimplantation were highly correlated with baseline levels (r = 0.91; P < .0001). The delivery system management time as reported by the patients was 2.5 ± 1.7 hours per week preimplantation, and this time decreased to 0.6 ± 0.8 hour per week at 6 months' postimplantation (P < .0001). All patients rated overall satisfaction with the implantable system as good, very good, or excellent at 6 weeks and 6 months. There were no catheter-related bloodstream infections or catheter occlusions. CONCLUSIONS: The implantable intravascular delivery system delivered treprostinil to patients with PAH with a low rate of catheter-related complications and a high rate of patient satisfaction. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01321073; URL: www.clinicaltrials.gov.

Pharmacokinetic evaluation of ambrisentan.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a life-threatening and progressive disease characterized by increasing pulmonary vascular resistance leading to right ventricular failure and premature death. Current therapies target three major pathways involving endothelin, prostacyclin and NO. Ambrisentan is an oral, once daily, selective endothelin receptor antagonist. AREAS COVERED: This review focuses on, and critically appraises, the clinical efficacy and safety of ambrisentan as well as its pharmacokinetic and pharmacodynamic properties. The article also gives an expert perspective on the role of ambrisentan in the management of PAH. EXPERT OPINION: Ambrisentan is an effective and safe treatment which is, in the authors' opinion, a valuable addition to the armamentarium against PAH. Ambrisentan offers a relative lack of drug interactions, once daily dosing and reassuring liver safety, offering safety and convenience advantages over bosentan. Presently, there is a lack of comparative studies between PDE5 inhibitors and endothelin receptor antagonists and a lack of data comparing bosentan with ambrisentan. This is hindering data-based conclusions regarding relative efficacy and further studies are needed to define the role of ambrisentan in the management of PAH.

Inhaled epoprostenol for the treatment of pulmonary arterial hypertension in critically ill adults.

Pulmonary arterial hypertension (PAH) is a progressive disease without a cure. The primary treatment goal for patients with this disease is improving pulmonary blood flow through vasodilation of the pulmonary arteries. Several drugs are available that ameliorate walk distance and hemodynamics, but their maximum tolerated doses are limited in critically ill patients with PAH because of systemic vasodilation resulting in hypotension. The ideal vasodilator would be cost-effective, safe, and selective to the pulmonary vasculature; no such agent currently exists. Inhaled nitric oxide selectively reduces pulmonary pressures without systemic hypotension. However, it is expensive, potentially toxic, and requires complex technology for monitoring and administration. Inhaled epoprostenol may be an alternative therapy to minimize systemic hypotension, which often accompanies rapid intravenous titration. To evaluate the safety and efficacy of inhaled epoprostenol in critically ill patients with PAH, we conducted a literature search by using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases (1966-August 2009) for relevant studies. Case reports and in vitro studies were excluded. Overall, 11 studies met the inclusion criteria. The PAH population included patients requiring cardiac surgery, lung or heart transplantation, or nonspecific intensive care. All trials showed that inhaled epoprostenol significantly decreased pulmonary pressures without lowering systemic blood pressure. The duration of therapy in most studies was 10-15 minutes, with one study evaluating its effects up to an average of 45.6 hours. Pulmonary pressures returned to baseline soon after drug discontinuation. Minimal adverse events were reported. Thus, inhaled epoprostenol in various subgroups of critically ill patients was effective in reducing pulmonary pressures. However, the significance of these effects on improving clinical outcomes remains unknown. Further studies are needed to determine the role of inhaled epoprostenol in critically ill patients with PAH.

Phosphodiesterase-5 inhibitors in management of pulmonary hypertension: safety, tolerability, and efficacy.

Pulmonary arterial hypertension (PAH) is a progressive disease that causes severe disability and has no cure. Over the past 20 years, a variety of treatment options have evolved for the management of PAH. With an expanded therapeutic armamentarium come more complex decisions regarding treatment options. Agent selection depends upon several factors including efficacy, side effect profile, and cost, as well as convenience of administration. We have undertaken a review of phosphodiesterase-5 (PDE-5) inhibitors in PAH with a focus on efficacy and safety. A literature search was conducted using the Medline and Cochrane Central Register of Controlled Trials databases (1966-February 2010) for relevant randomized clinical studies. Overall, 10 studies met our inclusion criteria. Sildenafil was the most commonly studied agent, followed by tadalafil and vardenafil. Most trials found that the PDE-5 inhibitors significantly improved exercise capacity and lowered pulmonary pressures. However, there were conflicting results regarding these agents' impact on improving cardiac function and functional class. Overall, these medications were effective and well tolerated with a relatively benign side effect profile. The PDE-5 inhibitors are an important option in treating PAH. While most of the published clinical data involved sildenafil, the other PDE-5 inhibitors show promise as well. Further studies are needed to determine the optimal doses of this therapeutic drug class, as well as its effects as adjunctive therapy with other agents in PAH.

Angiojet catheter-based thrombectomy in a neonate with postoperative pulmonary embolism.

A 2-day-old male with pulmonary atresia and an intact ventricular septum underwent central aortopulmonary shunt placement and right ventricular outflow tract reconstruction. Postoperatively, the patient had difficulty weaning from mechanical ventilation and was found to have a large thrombus occluding the entire right lower pulmonary artery. The patient underwent successful percutaneous catheter-based thrombectomy in the early postoperative period with the Possis AngioJet catheter. The patient had immediate improvement in gas exchange and was able to be weaned from the ventilator shortly thereafter. This represents the first published use of mechanical thrombectomy in a postoperative neonate.