Rapid Inpatient Titration of Intravenous Treprostinil for Pulmonary Arterial Hypertension: Safe and Tolerable.

There is no standard protocol for intravenous treprostinil dose escalation. In most cases, slow up-titration is performed in the outpatient setting. However, rapid up-titration in an inpatient setting is an alternative that provides opportunity for aggressive treatment of common side effects experienced during dose escalation. In this study, we describe our experience with inpatient rapid up-titration of intravenous treprostinil. This was a single-center, retrospective study in which we reviewed the data of subjects with pulmonary arterial hypertension treated at our center who underwent inpatient rapid up-titration of intravenous treprostinil. Our treprostinil dose escalation protocol included initiation at 2 ng·kg·min with subsequent up-titration by 1 ng·kg·min every 6 to 8 hours as tolerated by side effects. A total of 16 subjects were identified. Thirteen subjects were treprostinil naive (naive group), and 3 subjects were receiving subcutaneous treprostinil but were hospitalized for further intravenous up-titration of treprostinil dose (nonnaive group). In the naive group, the median maximum dose achieved was 20 ng·kg·min with an interquartile range (IQR) of 20-23 ng·kg·min. The median up-titration interval was 6 days (IQR: 4-9). In the nonnaive group, the median maximum dose achieved was 20 ng·kg·min (range: 17-30). The median up-titration interval was 8.5 days (range: 1.5-11). Overall, the median maximum dose achieved was 20 ng·kg·min (IQR: 20-23.5), and the median up-titration interval was 6 days (IQR: 4.6-9.25), with no reported significant adverse hemodynamic events. In patients with pulmonary arterial hypertension, rapid inpatient titration of intravenous treprostinil is safe and tolerable.

Pulmonary Hypertension and Atrial Septal Defect: Management Dilemma.

The decision making in patients with an atrial septal defect (ASD) in setting of pulmonary hypertension is complex. In the era of pulmonary arterial vasodilator therapy, every patient should undergo evaluation by pulmonary hypertension experts especially if defect closure is being considered. Defect closure in the inappropriate group can lead to poor outcomes.

Pulmonary arterial hypertension in the setting of pregnancy: a case series and standard treatment approach.

Pregnancy in patients with pulmonary arterial hypertension (PAH) is associated with a maternal mortality of 30-50% despite modern treatment modalities. The majority of maternal deaths in PAH patients occur either during labor and delivery or within 1 month postpartum. Cardiovascular collapse is attributed to a mismatch between the physiologic limitations of PAH and the changes that occur with pregnancy and delivery. In the Unites States, there is no consensus on the management of PAH in pregnancy. Several case reports have been published describing improved maternal-fetal outcomes, likely due to new advanced PH therapies, earlier diagnosis of PAH, and an adoption of a multidisciplinary treatment approach. We present five cases of gravid PAH patients successfully managed at our institution with a description of our standardized multidisciplinary treatment approach.

Pulmonary vasodilators: beyond the bounds of pulmonary arterial hypertension therapy in COVID-19.

Pulmonary arterial hypertension (PAH) and novel coronavirus (SARS-CoV-2) disease COVID-19 are characterized by extensive endothelial dysfunction and inflammation leading to vascular remodeling and severe microthrombi and microvascular obliterative disease. It is hypothesized that those patients with underlying lung disease, like PAH, represent a high-risk cohort in this pandemic. However, reports of COVID-19 in this cohort of patient have been scaring and an observational survey showed that the disease was relatively well tolerated. We postulate that specific PAH vasodilator may offer some protection and/or advantage in the case of concomitant COVID-19. Here we review the literature describing mechanisms of action for each of the broad categories of PAH therapy, and offer potential hypothesis about why this therapy may impact outcomes in COVID-19.

A 34-Year-Old Woman With Hoarseness of Voice and an Abnormal Echocardiogram.

CASE PRESENTATION: A 34-year-old woman presented for evaluation of several months of a hoarse voice and dyspnea on exertion that progressed over the last 3 years. She had a clinical diagnosis of asthma that had been treated with bronchodilators and inhaled corticosteroids for a few years. She continued to use her inhalers but with minimal symptomatic improvement. The patient was a lifelong nonsmoker with no history of drug abuse. She worked as a college professor and denied any significant environmental exposures or recent travel.

Partial anomalous pulmonary venous return: A case series with management approach.

Partial anomalous pulmonary venous return (PAPVR) is a rare congenital anomaly that results in a left-to-right shunt. Based on the shunt fraction, PAPVR has a wide spectrum of presentations. If a significant left-to-right shunt is left unrepaired, pulmonary vascular remodeling can occur resulting in the development of pulmonary arterial hypertension (PAH). Furthermore, if the condition is associated with an atrial septal defect (ASD), the patient can develop shunt reversal and Eisenmenger's syndrome in setting of severe PAH. Management plans include close observation, surgical repair, and treatment with pulmonary artery vasodilator therapies. Here, we present multiple cases of PAPVR to highlight the wide spectrum of presentations and the individualized treatment for each case.

Smoking-related interstitial fibrosis (SRIF) and pulmonary hypertension.

Smoking-related interstitial fibrosis (SRIF) is a relatively new term used to describe chronic interstitial fibrosis that can develop in smokers. The association of SRIF with pulmonary hypertension has not been described. We present a 55-year-old man with an extensive smoking history who presented for evaluation of insidious onset of dyspnoea on exertion and hypoxaemic respiratory failure. Physical examination was unremarkable. Pulmonary function testing demonstrated a marked reduction of the diffusion capacity with no obstruction or restriction. Ventilation perfusion scan showed no evidence of thromboembolic disease. High-resolution chest CT revealed minimal biapical pleural parenchymal scarring and subtle dependent atelectasis. Serological markers for connective tissue diseases were negative. Open lung biopsy was consistent with SRIF. Vascular intimal proliferation consistent with pulmonary hypertension was also noted. Right heart catheterisation yielded mild pulmonary hypertension and treatment was initiated with tadalafil and bosentan.

Pulmonary hypertension and idiopathic pulmonary fibrosis: a dastardly duo.

Pulmonary hypertension (PH) is a well-recognized complication of interstitial lung disease, including idiopathic pulmonary fibrosis (IPF). The underlying pathogenesis was initially hypothesized to be inflammatory but now is characterized as an over exuberant fibroproliferative process. The prevalence of PH in the setting of IPF has not been well described in the literature, with a reported occurrence from 32% to 85%. Diagnostically, recognizing underlying PH in the setting of IPF remains challenging because of nonspecific clinical symptoms and unrevealing ancillary testing. A high degree of clinical suspicion is paramount. The only reliable diagnostic tool for PH is right heart catheterization. The treatment of PH, in patients with IPF, is based on multiple factors, including disease severity, functional status and degree of hypoxemia. Medications currently approved to treat PH have been administered for PH in the setting of IPF, such as phosphodiesterase-5 inhibitors, nonselective endothelin receptor antagonists and prostacyclin analogues. The treatment of PH in the setting of IPF may also be difficult due to worsening ventilation-perfusion mismatch induced by selective pulmonary artery vasodilator therapy. Lung transplantation should be considered with patients refractory to pharmacological treatment. Identification of PH in IPF patients is crucial, as functional status and prognosis are greatly reduced. Given the high mortality rate and propensity for acute decompensation, IPF and PH patients should be evaluated for transplant early in their disease course.

Pulmonary artery stenosis secondary to fibrosing mediastinitis: management with cutting balloon angioplasty and endovascular stenting.

Cutting balloon angioplasty is a common treatment modality in the pediatric population for pulmonary artery stenosis. We present an adult with histoplasmosis induced fibrosing mediastinitis resulting in pulmonary artery stenosis that was successfully treated with cutting balloon angioplasty and subsequent stent deployment. Percutaneous endovascular stent placement has be shown to effectively alleviate pulmonary artery stenosis, however in-stent restenosis does limit durability. Pharmacologic therapy is indicated with either mediastinal adenitis or mediastinal granuloma with anti-fungal agents such as amphotericin B and itraconazole. Surgical intervention for histoplasmosis induced fibrosing mediastinitis is rarely indicated and may result in fatal complications that stem from mediastinal fibrosis due to resultant destruction of surgical planes. To our knowledge, this is the first reported case of utilizing cutting balloon angioplasty and stent insertion for the treatment of histoplasmosis induced fibrosing mediastinitis complicated by pulmonary artery stenosis.