Martha Kingman

Changes in Right Ventricular Structure and Function Assessed Using Cardiac Magnetic Resonance Imaging in Bosentan-Treated Patients With Pulmonary Arterial Hypertension

Patients with pulmonary arterial hypertension (PAH) usually show improvements in symptoms, exercise capacity, and hemodynamics after treatment with approved medical therapies. This study sought to determine whether improvement in right-sided cardiac function measured using cardiac magnetic resonance imaging would also be seen and whether these changes would correlate with improvement in exercise capacity. Sixteen patients with PAH underwent evaluation at baseline and after 12 months of treatment with bosentan. After treatment, cardiac index, pulmonary vascular resistance, and 6-minute walk distance improved, and there was a trend toward improvement in right ventricular (RV) stroke volume (70 +/- 27 to 81 +/- 30 ml; p = 0.08), but no change in RV ejection fraction (RVEF) or RV end-diastolic volume. Six-minute walk distance improved by 59 m (p <0.05) in the overall cohort and improved more in patients in whom RVEF increased compared with those with stable or decreased RVEF (+98 vs -37 m, respectively; p = 0.01). Three patients died during follow-up, and these patients had significantly lower RVEF and left ventricular end-diastolic volume indexes than surviving patients. In conclusion, these results suggest that cardiac magnetic resonance imaging may have value in determining response to therapy and prognosis in patients with PAH.

Prostacyclin administration errors in pulmonary arterial hypertension patients admitted to hospitals in the United States: A national survey

BACKGROUND Epoprostenol and treprostinil are intravenous prostacyclin medications used to treat pulmonary arterial hypertension (PAH). This survey explored hospital policies regarding prostacyclin infusions, and investigated the type and frequency of errors that occurred in the inpatient setting. METHODS Information on prostacyclin infusion policies and inpatient errors was obtained through detailed interviews with 18 PAH nurses, and through an electronic survey completed by 97 PAH clinicians. RESULTS The electronic survey respondents reported wide variability in prostacyclin infusion policies, including variability in the use of home vs hospital infusion pumps, and variability in the use and storage of back-up epoprostenol and treprostinil. Serious or potentially serious errors in medication administration were reported by 68% of survey respondents. The most common error types (reported by >or=25%), included: incorrect cassette placed in the pump; inaccurate pump programming; errant drug dosing; and inadvertent cessation of the pump. Nine errors, all at different centers, were believed to have contributed to patient death. In the separate interviews with the PAH nurses, 94% reported serious errors. These errors prompted many of the centers to implement policy changes in an attempt to reduce future errors, improve safety and optimize patient outcomes. CONCLUSIONS These findings suggest that prostacyclin infusion therapy is problematic and that an opportunity exists to improve safety. The development of standardized treatment guidelines should be considered.

Ambrisentan, an endothelin receptor type A-selective endothelin receptor antagonist, for the treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature characterized by vasoconstriction and vascular proliferation, which leads to right heart failure and death. Prostacyclin, NO and endothelin are felt to be key mediators in the development of PAH. We present the available published and presented data about ambrisentan, an ETA-selective endothelin receptor antagonist (ERA) and newest ERA agent to be approved by the FDA for the treatment of PAH in patients with WHO functional class II and III symptoms. Randomized, placebo-controlled trials have demonstrated a significant improvement in exercise capacity and decrease in time to clinical worsening, along with evidence to support an improvement in WHO functional class and quality of life for patients receiving ambrisentan. Long-term data have shown a 1-year survival of 95%; of the survivors, 94% remained on ambrisentan monotherapy. Endothelin receptor antagonists as a drug class have previously been associated with peripheral edema, aminotransferases abnormalities and a teratogenic risk to a developing fetus. Peripheral edema was observed in patients receiving ambrisentan; however, a greater percentage was experienced in patients aged > 65 years. In contrast, significant aminotransferase abnormalities were not observed with ambrisentan treatment in the placebo-controlled trials, and in all clinical trials combined the 1-year risk seems to be low (< 3%). Despite these data, the FDA requires monthly liver function tests monitoring. As with other ERAs, monthly pregnancy testing is required in all women of child bearing potential.

Living with pulmonary hypertension: unique insights from an international ethnographic study

Objectives To better understand the patients perspective of pulmonary hypertension (PH), including the impact of living with PH, disease management and treatment. Design This qualitative ethnographic study collected observational video footage, supplemented by field notes and patient diaries to assess the impact of PH on the patients life. Setting Patients were observed and filmed in their home for up to 6 h, capturing the environment, interactions and activities of everyday life. Participants Patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic PH who were receiving PAH-specific medication were recruited through healthcare professionals (HCPs) and patient associations in seven countries across four continents. Sampling was purposive and subgroup analysis was not intended. Results Overall, 39 patients with PH were enrolled. Many patients had a poor understanding of PH and found their ‘invisible’ disease difficult to explain to others. An important finding was the secrecy surrounding PH. Feelings of insecurity and isolation were regularly reported, and many patients admitted to hiding their symptoms. The marked improvement in symptoms after therapy initiation made assessment of disease progression more difficult as patients compared their quality of life (QoL) against pretreatment levels. Extensive planning and adherence to daily routines were required in patients’ everyday life. Conclusions Ethnography was used for the first time, in several countries, to evaluate the patients perception of living with PH. This approach revealed key findings that would not typically be uncovered using other qualitative techniques, including the secrecy surrounding PH, the difficulties in describing the disease and the challenges in assessing disease progression. A more tailored dissemination of information from HCPs and development of a simple and understandable PH definition may be beneficial in alleviating the secrecy reported by patients. A greater appreciation of how patients perceive their disease and QoL has the potential to improve PH management.

Long-term therapy with oral treprostinil in pulmonary arterial hypertension failed to lead to improvement in important physiologic measures: results from a single center

Sustained-release oral treprostinil, an oral prostacyclin, led to significant improvement in 6-minute walk distance (6MWD) versus placebo in treatment-naive patients with pulmonary arterial hypertension (PAH) but failed to lead to significant improvement in two 16-week trials in patients receiving background PAH therapies (FREEDOM studies). Long-term studies are lacking. Our objective was to evaluate 6MWD, functional class, hemodynamics, and other long-term outcomes during oral treprostinil administration in PAH. Patients receiving oral treprostinil through the FREEDOM studies at our institution were included and were followed for up to 7 years. The primary end point was change in pulmonary vascular resistance (PVR) at first follow-up catheterization. Other end points included 6MWD, functional class, and other hemodynamic results. Thirty-seven patients received oral treprostinil for a median of 948 days, with 81%, 61%, and 47% continuing therapy at 1, 2, and 3 years, respectively. Mean treprostinil dose at 3, 12, and 24 months was 4.3 ± 2.3, 8.6 ± 3.2, and 11.7 ± 5.8 mg/24 h, respectively. Compared with pretreatment values, there was no significant change in 6MWD at 3 or 12 months, no improvement in functional class at 12 months, and no significant change in hemodynamics at the first follow-up catheterization (N = 34). Oral treprostinil dose was inversely associated with change in PVR (r = −0.42, P < 0.05), and change in PVR was numerically better among patients in the highest dosing quartile. No significant improvement in 6MWD, functional class, or hemodynamics versus pretreatment values was seen with long-term oral treprostinil therapy, potentially because of inability to achieve a clinically effective dose.

Inhaled treprostinil for the treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension is a progressive disease characterized by vascular proliferation and vasoconstriction of the small pulmonary arteries that eventually leads to right-sided heart failure and death. Patients often initially have symptoms such as shortness of breath, fatigue, and edema; later in the disease, presyncope and syncope are common. Patients with progressive pulmonary arterial hypertension despite oral therapy and/or with severe disease typically require treatment with a prostanoid. Inhaled treprostinil (Tyvaso) is a prostacyclin analog indicated for the treatment of pulmonary arterial hypertension to increase walk distance in patients with symptoms classified as New York Heart Association functional class III. Inhaled treprostinil was approved by the Food and Drug Administration in July 2009. This article provides a brief overview of the pathophysiology of pulmonary arterial hypertension and reviews the mechanism of action, key clinical data, and the practical management of inhaled treprostinil in patients with pulmonary arterial hypertension.

Safety Recommendations for Administering Intravenous Prostacyclins in the Hospital

Prostacyclins are a high-risk category of continuous intravenous infusions increasingly used in hospitals to treat advanced pulmonary arterial hypertension, a rare condition characterized by vasoconstriction and vascular proliferation of the pulmonary arteries. Prostacyclins are given in doses of nanograms per kilogram per minute and have a narrow therapeutic dosing range for each patient. Sudden increases or decreases in dose can be life threatening. Previous studies revealed errors in the administration of these high-risk infusions, which in some instances led to serious adverse events, including death. The literature was reviewed for safety measures in administration of high-risk intravenous medications and input was obtained from leading experts in pulmonary arterial hypertension to create a set of safety recommendations for infusion of prostacyclins.

Management of prostacyclin side effects in adult patients with pulmonary arterial hypertension

Therapies that target the prostacyclin pathway are considered effective, yet are complex to dose and may cause dose-limiting side effects for patients with pulmonary arterial hypertension (PAH). Careful side effect management and the ability to discern side effects from worsening disease are essential in order for patients to continue, and benefit from, prostacyclin therapy. This manuscript was developed through a collaborative effort of allied health providers with extensive experience in managing patients with PAH who are treated with medications that target the prostacyclin pathway. This article provides an overview of individual prostacyclin pathway therapies approved in the United States, side effects most commonly associated with these therapies, and practical suggestions for side effect management. Most patients will experience significant side effects on prostacyclin therapy. Creating a proactive and careful side effect management program will increase the likelihood that patients are able to stay on therapy and receive the benefits afforded by prostacyclin therapy.

Management of the patient with pulmonary arterial hypertension receiving intravenous prostacyclin: an expert nurse practical guide.

Pulmonary arterial hypertension (PAH) is a severely disabling disorder characterized by elevated pulmonary artery pressure ultimately leading to right heart failure and death. Treatment options have significantly increased over the past decade. Intravenous prostacyclins remain the treatment of choice for advanced PAH, leading to long-term clinical benefits and improved survival. Their administration requires a high level of nursing competency and presents considerable challenges for patients and caregivers. This article reviews the characteristics of currently available intravenous prostacyclins and provides a practical guide for nurses who may have had limited exposure to intravenous prostacyclins and their unique dosing, side effects, and titration characteristics.

Titration of pulmonary arterial hypertension therapeutics: Experience-based recommendations

The availability of new medications has improved exercise capacity, enhanced quality of life, and extended time to clinical worsening in patients with pulmonary arterial hypertension (PAH). For many of these medications, careful individualized dose titration is required to maximize therapeutic effectiveness while minimizing side effects. In addition, specific routes of administration, including intravenous (IV), subcutaneous (SC), and inhaled administration may present additional challenges for patients and healthcare providers. These challenges include the possibility of catheter-related infections (IV), infusion site pain (SC), and adherence to frequent dosing schedules (inhaled). Temporary discontinuations may require re-titration and, in some cases, may even be life threatening. Here, based on our clinical experience, we provide our recommendations for dose titration schemes for PAH medications that require individualized dosing in adult patients, including agents acting on the endothelin-1 pathway (bosentan and ambrisentan), the prostacyclin pathway (epoprostenol, treprostinil, and selexipag), and the nitric oxide pathway (tadalafil and the soluble guanylate cyclase stimulator riociguat). A case study that illustrates the application of best practices for PAH medication dose titration in a real-world setting is presented. Good two-way communication between specialty pharmacies and other healthcare providers promotes optimal medication usage and patient health. Experience has shown that slow, cautious up-titration is generally associated with better long-term outcomes. In all cases, patient education, frequent monitoring and careful management of side effects, and treatment adherence are critical.