Christine Archer-Chicko

Hemodynamics and survival of patients with portopulmonary hypertension.

It is not known whether patients with pulmonary arterial hypertension associated with portal hypertension (portopulmonary hypertension (PPHTN) have different disease characteristics from those of patients with other forms of pulmonary arterial hypertension. We performed a retrospective cohort study of patients with PPHTN and patients with pulmonary arterial hypertension that was idiopathic, familial, or associated with anorexigen use (IPAH) to determine whether hemodynamics or survival were different between these groups. We included consecutive patients who underwent initial pulmonary artery catheterization and vasodilator testing at our center between January 1997 and May 2001 and who were followed until January 2004. Patients with PPHTN (N = 13) had a higher cardiac index and lower pulmonary vascular resistance than patients with IPAH (N = 33) (P ≤ 0.001). Right atrial pressure and pulmonary artery pressure were similar between the groups. Patients with PPHTN had a higher risk of death in multivariate analysis (hazard ratio: [HR] = 2.8, 95% CI 1.04‐7.4; P = 0.04). These findings were not affected by adjustment for differences in laboratory values, hemodynamics, or therapy. In conclusion, patients with PPHTN have a higher risk of death than that of patients with IPAH, despite having a higher cardiac index and lower pulmonary vascular resistance. Future studies of the specific mechanisms of and therapy for pulmonary arterial hypertension should focus on the distinctions between the different forms of this disease. (Liver Transpl 2005;11:1107–1111.)

Anastrozole in Pulmonary Arterial Hypertension. A Randomized, Double-Blind, Placebo-controlled Trial.

Rationale: The aromatase inhibitor anastrozole blocks the conversion of androgens to estrogen and blunts pulmonary hypertension in animals, but its efficacy in treating patients with pulmonary arterial hypertension (PAH) is unknown. Objectives: We aimed to determine the safety and efficacy of anastrozole in PAH. Methods: We performed a randomized, double‐blind, placebo‐controlled trial of anastrozole in patients with PAH who received background therapy at two centers. Measurements and Main Results: A total of 18 patients with PAH were randomized to anastrozole 1 mg or matching placebo in a 2:1 ratio. The two co‐primary outcomes were percent change from baseline in 17&bgr;‐estradiol levels (E2) and tricuspid annular plane systolic excursion (TAPSE) at 3 months. Anastrozole significantly reduced E2 levels compared with placebo (percent change: −40%; interquartile range [IQR], −61 to −26% vs. −4%; IQR, −14 to +4%; P = 0.003), but there was no difference in TAPSE. Anastrozole significantly increased the 6‐minute‐walk distance (median change = +26 m) compared with placebo (median change = −12 m) (median percent change: anastrozole group, 8%; IQR, 2 to 17% vs. placebo −2%; IQR, −7 to +1%; P = 0.042). Anastrozole had no effect on circulating biomarkers, functional class, or health‐related quality of life. There was no difference in adverse events. Conclusions: Anastrozole significantly reduced E2 levels in patients with PAH but had no effect on TAPSE. Anastrozole was safe, well tolerated, and improved 6‐minute‐walk distance in this small “proof‐of‐principle” study. Larger and longer phase II clinical trials of anastrozole may be warranted in patients with PAH. Clinical trial registered with www.clinicaltrials.gov (NCT 1545336).

Interleukin-6 and tumor necrosis factor-α are associated with quality of life-related symptoms in pulmonary arterial hypertension.

RATIONALE Inflammation is associated with symptoms in many chronic illnesses; however, this link has not been established in pulmonary arterial hypertension. OBJECTIVES The objective of this study was to investigate the association between inflammatory markers and quality of life-related symptoms in patients with pulmonary arterial hypertension. We hypothesized that higher circulating IL-6 and tumor necrosis factor-α levels would be associated with worse quality of life-related symptoms. METHODS We performed a secondary analysis using baseline and 3-month assessments of 62 subjects in a clinical trial of aspirin and simvastatin to determine the association between plasma IL-6 and tumor necrosis factor-α levels and the Medical Outcomes Study Short Form-36 subscales (pain, vitality, mental health). MEASUREMENTS AND MAIN RESULTS The mean age was 49.7±13.4 years; 87% were female. Higher IL-6 levels were significantly associated with lower Medical Outcomes Study Short Form-36 subscale scores, indicating worse bodily pain, vitality, and mental health (all P<0.01). Higher tumor necrosis factor-α levels were significantly associated with increased bodily pain, but better mental health scores. CONCLUSIONS IL-6 and tumor necrosis factor-α levels are associated with certain quality of life domains in patients with pulmonary arterial hypertension. Clinical trial registered with www.clinicaltrials.gov (NCT00384865).

Nursing Care of Patients with Pulmonary Arterial Hypertension

Patients with pulmonary arterial hypertension (PAH) ultimately develop symptoms of right-sided heart failure as a result of low cardiac output and arterial hypoxemia. Patients typically manifest dyspnea with exertion or fatigue as the initial symptoms of PAH. In our clinic, patients report they have noticed changes in their breathing or exercise tolerance for periods ranging from several weeks to several months or even years before seeking evaluation by a physician. They tend to minimize the significance of their symptoms by relating them to increasing age, being overworked, not sleeping well, being out of shape, or being overweight As time passes, these symptoms persist and in many instances progress. Patients may experience any of the following symptoms with PAH (either at rest or upon exertion): fatigue, shortness of breath, edema, chest discomfort, palpitations, dizziness, presyncope, and syncope. Once diagnosed, patients should be referred to an experienced pulmonary hypertension (PH) center for further evaluation and management. PH program nurses are important in managing the care of patients. There are four specific roles that nurses assume: coordination of care, patient advocacy, patient assessment, and patient education. Patients need to understand PH as a disease process, the signs and symptoms that signify worsening, and the various treatment options. In addition, nurses provide ongoing emotional support to help patients, their families, and support persons to cope with living with this unpredictable chronic disease and to achieve the best quality of life possible. The benefits of good nursing care from an experienced PH center nurse are similar to those from advanced practice nurses managing congestive heart failure patients and they include improved quality of life, decreased number of hospital admissions, and prolonged survival. This chapter will focus specifically on the nursing care of PAH patients. It will highlight practical issues including assessing patients, developing a treatment plan, supporting patients and families/caregivers, handling special circumstances, and managing insurance issues.

Lower DHEA-S levels predict disease and worse outcomes in post-menopausal women with idiopathic, connective tissue disease- and congenital heart disease-associated pulmonary arterial hypertension

High oestradiol (E2) and low dehydroepiandrosterone-sulfate (DHEA-S) levels are risk factors for pulmonary arterial hypertension (PAH) in men, but whether sex hormones are related to PAH in women is unknown. Post-menopausal women aged ≥55 years with PAH were matched by age and body mass index to women without cardiovascular disease. Plasma sex hormone levels were measured by immunoassay. Lower levels of DHEA-S (p<0.001) and higher levels of E2 (p=0.02) were associated with PAH. In PAH cases (n=112), lower DHEA-S levels were associated with worse haemodynamics (all p<0.01) and more right ventricular dilatation and dysfunction (both p=0.001). Lower DHEA-S levels were associated with shorter 6-min walking distance (6MWD) (p=0.01) and worse functional class (p=0.004). Each Ln(1 µg·dL−1) decrease in DHEA-S was associated with a doubling in the risk of death (hazard ratio 2.0, 95% CI 1.5–2.7; p<0.001). Higher levels of E2 were associated with shorter 6MWD (p=0.03) and worse functional class (p=0.01). High E2 and low DHEA-S levels are associated with the risk and severity of PAH in post-menopausal women. Hormonal modulation should be studied as a treatment strategy in PAH. Lower levels of DHEA-S predict risk of disease, clinical severity and death in post-menopausal women with PAH http://ow.ly/jo6e30jOFni

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.

Slow-paced respiration therapy to treat symptoms in pulmonary arterial hypertension

Objective To determine the feasibility of using slow‐paced respiration therapy to treat symptoms in women with pulmonary arterial hypertension (PAH). Background People with PAH report increased dyspnea, fatigue and sleep disturbance that can impair health‐related quality of life (HRQOL). Methods Ten women with PAH received 8‐weeks of daily, 15 min sessions using slow‐paced respiration therapy via the RESPeRATE™ device. Participants had baseline and follow up assessments including plasma norepinephrine and interleukin‐6 (IL‐6), self‐report questionnaires to measure dyspnea, fatigue, depressive symptoms, sleep and HRQOL along with 7‐day actigraphy and sleep diaries. Results The mean age was 50 years. Adherence to the intervention was 92%. There was decrease in median IL‐6 levels [1.3 ± 0.5 to 1.1 ± 0.4, 95% CI (0.03–0.43)] over the study period. Sleep disturbance decreased, depressive symptoms decreased and HRQOL scores decreased (higher scores indicate worse HRQOL). Conclusions In this pilot study, slow‐paced respiration therapy is feasible in patients with PAH and may improve symptoms and lower IL‐6. HighlightsA pilot study of 10 women there was 100% retention and high adherence to the 8‐week slow‐paced respiration therapy intervention.Slow‐paced respiration therapy was associated with reduced plasma IL‐6 levels and no serious adverse events occurred.Preliminary results suggest decreased wake after sleep onset, increased sleep efficiency and increased total sleep time.Depressive symptoms decreased and HRQOL scores decreased (higher HRQOL scores indicate worse HRQOL.