Lessons learned in developing a chronic thromboembolic pulmonary hypertension program.

PURPOSE OF REVIEW: Chronic thromboembolic pulmonary hypertension (CTEPH) is a deadly underdiagnosed form of pulmonary hypertension, traditionally treated with surgical extraction of thrombo-fibrotic lesions via pulmonary thrombendarterectomy (PTE) surgery. More recently, treatment options have expanded to pulmonary vasodilator medical therapy and balloon pulmonary angioplasty (BPA). This has led to increased awareness and detection of CTEPH, as well as growing interest in performing PTE and BPA. This review will describe the steps required to build a successful CTEPH team in the context of the rapidly evolving treatment of CTEPH. RECENT FINDINGS: CTEPH care requires a multidisciplinary team, including a Pulmonologist or Cardiologist expert in Pulmonary Hypertension, a PTE surgeon, a BPA interventionalist, a dedicated radiologist, cardiothoracic anesthesia and Vascular Medicine or Hematology. Careful assessment of precise imaging and hemodynamic data is needed for operability assessment in the context of the experience of the CTEPH team and surgeon. Medical therapy and BPA are indicated for inoperable CTEPH and residual CTEPH after PTE. Increasingly, multimodality approaches, including surgery, BPA and medical therapy are utilized for best outcomes. SUMMARY: An expert CTEPH center requires a multidisciplinary team with dedicated specialists, and time to develop the experience and expertise to achieve high volumes and good outcomes.

Inpatient Initiation of Oral Treprostinil in an Academic Medical System.

PURPOSE: Clinicians may transition patients on parenteral or inhaled prostacyclins to oral treprostinil for ease of use or to avoid adverse effects related to parenteral therapy. However, few data are available to guide these transitions in inpatients. The purpose of this analysis is to describe the inpatient initiation of oral treprostinil at an academic medical system. METHODS: This is a retrospective cohort analysis of patients newly initiated on oral treprostinil at Cleveland Clinic Heath System from 2015 to 2017. Demographic information regarding pulmonary arterial hypertension (PAH) history and previous PAH therapies were recorded. Outcomes evaluated included doses of oral treprostinil utilized, adverse effects related to therapy, and measures of clinical and functional status before and after the initiation of oral treprostinil. RESULTS: Overall, 29 patients were prescribed oral treprostinil, of which 15 patients were included in the analysis. Common reasons for initiation of oral treprostinil included disease progression (6, 40%) and patient desire (4, 25%). The median duration of transition/initiation of oral treprostinil was 4 days (range, 3-11 days). Median daily dose of oral treprostinil on day 1 of initiation was 2 mg (0.25-4 mg). By day 7, median daily dose was 15 mg (0.75-27.75 mg). Common adverse effects related to therapy were gastrointestinal (7, 47%) and headache (4, 27%). No patients required discontinuation of oral treprostinil due to adverse effects within 90 days of initiation. CONCLUSION: Inpatient initiation/transition to oral treprostinil was relatively well tolerated. Future studies should evaluate clinical outcomes surrounding the transitioning to oral treprostinil.

Subcutaneous to intravenous prostacyclin analog transition in pulmonary hypertension.

INTRODUCTION: Prostacyclin analogs are Food and Drug Administration-approved therapies for the treatment of pulmonary arterial hypertension and can be administered by inhalational, intravenous (IV), or subcutaneous (SQ) routes. Because there are limited data to guide the transition between SQ to IV prostacyclin analogs, we describe our experience. METHODS: We performed a retrospective review of patients with pulmonary hypertension diagnosed by right heart catheterization, who underwent transition from SQ to IV prostacyclin analogs. RESULTS: We included 7 patients with pulmonary arterial hypertension and 2 with chronic thromboembolic pulmonary hypertension in this retrospective study. Median (interquartile range) age was 54 (39-63) years, and 67% were women. The reasons for the SQ to IV switch were site pain (n = 6, 67%), major surgery (n = 2, 22%), and septic shock (n = 1, 11%). SQ treprostinil was converted to IV treprostinil (n = 5, 56%) or IV epoprostenol (n = 4, 44%). When SQ treprostinil was converted to IV treprostinil, the initial mean (range) dose decreased from 84.9 (36.5-167) to 70.8 (24-114) ng·kg⁻¹·min⁻¹. When SQ treprostinil was converted to IV epoprostenol, the dose decreased from 24.5 (17.5-30) to 13.3 (9-20) ng·kg⁻¹·min⁻¹. The patient transitioned from SQ to IV treprostinil in the context of septic shock died a month after hospitalization. No deteriorations were observed in the remaining patients during the first year. CONCLUSIONS: Under careful monitoring, SQ treprostinil was transitioned to IV treprostinil or epoprostenol without complications. Dosing downadjustment was needed in some patients who were switched over from SQ to IV prostacyclin analogs.

Causes and circumstances of death in pulmonary arterial hypertension.

RATIONALE: The causes and circumstances surrounding death are understudied in patients with pulmonary arterial hypertension (PAH). OBJECTIVES: We sought to determine the specific reasons and characteristics surrounding the death of patients with PAH. METHODS: All deaths of patients with pulmonary hypertension (PH) followed in the Cleveland Clinic Pulmonary Vascular Program were prospectively reviewed by the PH team. A total of 84 patients with PAH (age 58 ± 14 yr; 73% females) who died between June 2008 and May 2012 were included. MEASUREMENTS AND MAIN RESULTS: PH was determined to be the direct cause of death (right heart failure or sudden death) in 37 (44%) patients; PH contributed to but did not directly cause death in 37 (44%) patients; and the death was not related to PH in the remaining cases (n = 7; 8.3%). In three (3.6%) patients the final cause of death could not be adequately assessed. Most patients died in a healthcare environment and most received PH-specific therapies. In our cohort, 50% of all patients with PAH and 75.7% of those who died of right heart failure received parenteral prostanoid therapy. Less than half of patients had advanced healthcare directives. CONCLUSIONS: Most patients with PAH in our cohort died of their disease; however, right ventricular failure or sudden death was the sole cause of death in less than half of patients.

Sleep quality, depression, and quality of life in patients with pulmonary hypertension.

Pulmonary hypertension is a disabling disease characterized by progressive functional worsening, right heart failure, and death. Although pulmonary hypertension has been associated with poor quality of life, sleep quality has not been investigated in pulmonary hypertension patients. This was a cross-sectional study in which patients (N = 40) were asked to complete standardized questionnaires to assess sleep quality [using Pittsburgh Sleep Quality Index (PSQI)], insomnia, sleepiness, dyspnea, depression, restless leg syndrome, and quality of life [using Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)] during routine office visits. Baseline hemodynamics, pulmonary function tests, exercise capacity, and transthoracic echocardiogram were analyzed. Pulmonary hypertension functional class was World Health Organization class II [20 (50%)], III [18 (45%)], and IV [2 (5%)], and 29 (72.5%) had poor sleep quality. PSQI score was associated with CAMPHOR symptoms score (R = 0.61, P < 0.001), CAMPHOR activities score (R = 0.38, P = 0.016), CAMPHOR quality-of-life score (R = 0.45, P = 0.004), depression (R = 0.42, P = 0.007), and dyspnea (R = 0.36, P = 0.02). Sleep quality was not associated with age, gender, other comorbidities, pulmonary hypertension etiology, baseline hemodynamics, pulmonary function testing, echocardiographic parameters, or exercise capacity. Poor sleep quality is common in patients with pulmonary hypertension and correlates with depression, dyspnea, and poor quality of life. Improving sleep quality in patients with pulmonary hypertension may improve quality of life.

Subdural hematomas in pulmonary arterial hypertension patients treated with prostacyclin analogs [corrected].

Prostacyclin analogs therapy has been associated with development of thrombocytopenia. Little is known whether this treatment increases the risk of intracranial hemorrhage in pulmonary artery hypertension (PAH) patients. We queried the Cleveland Clinic billing database to identify cases of nontraumatic sudural hematoma (SDH) in patients with PAH. We identified those individuals who were receiving prostacyclin analogs therapy at the time of the neurological event and assessed whether these patients were also taking antiplatelet or anticoagulation therapies. We identified three cases of nontraumatic SDH in 856-patient-year of prostacylin analog treatment. All patients were women, had low normal platelet counts or thrombocytopenia, and were concomitantly receiving anticoagulation therapy in the appropriate therapeutic anticoagulation range. All three patients were managed conservatively and had no neurologic sequelae. Nontraumatic acute subdural hematoma is a rare event in patients with PAH treated with prostacyclin analogs. All affected patients were concomitantly receiving anticoagulation therapy.

Prevalence and characteristics of restless legs syndrome in patients with pulmonary hypertension.

BACKGROUND: Patients with pulmonary hypertension (PH) have an increased prevalence of risk factors for restless legs syndrome (RLS). We performed a cross-sectional study to determine the prevalence and characteristics of RLS in this population. METHODS: Patients filled out two questionnaires during a visit: (1) a diagnostic tool for RLS, based on the core clinical features; and (2) a 10-question rating scale used to assess severity. Data were obtained by medical record review with regard to demographics, characteristics of PH and known RLS risk factors. RESULTS: Restless legs syndrome was found in 43.6% (24 of 55) (mean age +/- SD: 49 +/- 14 years; 41 women, 14 men) of patients and 54% of these had moderate or severe RLS. Patients with RLS were younger but gender differences were not appreciated. Presence of RLS did not correlate with measures of PH severity; however, patients with RLS were more likely to have a better 6-minute walk distance (p = 0.015) and lower BNP level (p = 0.07) and less likely to be WHO Class IV or require oxygen during the 6-minute walk test. Patients with a history of hypothyroidism (67%; p = 0.04) and those on opioids for relief of leg pain (69%) were more likely to have RLS. CONCLUSIONS: Patients with PH had a very high prevalence of RLS and most had moderate or severe symptoms. RLS was more common in more active patients and those who were hypothyroid or on opioids for relief of leg pain. Patients with PH should be screened for RLS because good treatment options are available.