Carl Harries

Long-term safety, tolerability and efficacy of bosentan in adults with pulmonary arterial hypertension associated with congenital heart disease

Objective: To examine long-term safety and efficacy of bosentan—an oral dual endothelin receptor antagonist—in patients with pulmonary hypertension associated with congenital heart disease or Eisenmenger’s syndrome. Design: Retrospective study. Setting: Tertiary cardiology referral centre. Patients: All adult patients with pulmonary arterial hypertension associated with congenital heart disease treated with bosentan at the Royal Brompton Adult Congenital Heart Centre were included. Main outcome measures: Oxygen saturation, functional (WHO) class, 6-minute walk test distance and liver enzymes were analysed. Results: Eighteen patients (14 female) with pulmonary arterial hypertension associated with congenital heart disease (15 patients with Eisenmenger’s syndrome) with a mean (SD) age of 41 (9) years (range 23–69) were included. Median follow-up was 29 months (range 1–39). One patient died during follow-up. Patients tolerated bosentan well and no significant rise in liver transaminases was seen. Arterial oxygen saturation remained stable throughout follow-up. Mean (SD) functional class (p = 0.001) and the 6-minute walk test distance improved compared with baseline (284 (144) vs 363 (124) m, 380 (91) m and 408 (114) m at baseline, 0–6 months, 6–12 months and 1–2 years of treatment, respectively; p<0.05 for each). Conclusions: Bosentan appears to be safe and well tolerated in adults with pulmonary arterial hypertension associated with congenital heart disease or Eisenmenger’s syndrome during mid- to long-term follow-up. In addition, functional class and the 6-minute walk test distance improved and this effect was maintained for up to 2 years of bosentan treatment.

Quality of life and functional capacity can be improved in patients with Eisenmenger syndrome with oral sildenafil therapy.

BACKGROUND Patients with Eisenmenger syndrome (ES) have a decreased exercise capacity and poor quality of life (QoL). While patients may survive to middle adulthood, the burden of disease is disabling. Sildenafil seems to improve exercise tolerance and hemodynamics, but there is no data to date on its impact on QoL. METHODS Eisenmenger patients in New York Heart Association (NYHA) class III were recruited in a prospective study of efficacy and safety of oral sildenafil. The QoL endpoint was assessed using a disease-specific questionnaire (CAMPHOR). Exercise capacity was assessed by means of six minute walk test (6MWT). All patients underwent comprehensive assessment at baseline and after 3months of treatment. RESULTS Twelve patients (mean age was 34.3±10.2, 83% female) with various cardiac anatomies were recruited. No major adverse events during the follow-up or significant drop in resting oxygen saturation were recorded. After 3months of oral sildenafil therapy, all patients improved to NYHA II with a concomitant improvement in 6MWT distance (347.3±80.7 to 392.5±82.0m, p=0.002). All components of the CAMPHOR score, relating to symptoms, activity and QoL, improved significantly resulting in substantial improvement in the total CAMPHOR score (27.6±10.5 to 15.8±10.4, p=0.002). CONCLUSIONS Three months of sildenafil therapy in adults with ES was well tolerated and associated with significant improvement in the QoL CAMPHOR questionnaire and in NYHA class and exercise capacity. Larger studies are warranted to assess long term efficacy of oral sildenafil and potential impact on survival.

Disease targeting therapies in patients with Eisenmenger syndrome: response to treatment and long-term efficiency.

OBJECTIVES To examine long-term efficacy of disease targeting therapies (DTT) in patients with Eisenmenger syndrome. METHODS All adult patients with Eisenmenger syndrome treated with DTT at our institution were included. Functional class (FC), oxygen saturation and 6-minute walk test distance (6 MWTd) were analysed retrospectively. RESULTS Between 2002 and 2010, 79 Eisenmenger patients (21 males, 16 with Down syndrome) aged 34 ± 10 years (range 17-68 years) were included. Median follow-up was 3.3 years (range 0.2 to 8.9 years). 6 MWTd increased early after initiation of DTT, with a plateau after approximately 3 years and no obvious trend towards a deterioration on average during longer-term follow-up. Two patients died during follow-up and escalation of treatment was required in 18 patients after a median period of 2.5 years. Escalation of therapy was also associated with an increase in 6 MWTd. In addition, FC improved on DTT and oxygen saturation, increased, both at rest and peak exercise. This effect was more pronounced in the patients with the lowest baseline oxygen saturation at rest. CONCLUSIONS Long-term DTT is safe and improves objective exercise capacity and subjective symptoms. Response to DTT was typically observed early after initiation of DTT and was, on average, maintained longer-term. However, 1 in 5 patients required escalation of DTT, with time, due to symptomatic deterioration and this was associated with an afresh improvement in 6 MWTd.

emPHasis-10: development of a health-related quality of life measure in pulmonary hypertension

The aim of this study was to develop a measure of the impact of pulmonary hypertension (PH) on health-related quality of life (HRQoL) as there is a need for a short, validated instrument that can be used in routine clinical practice. Interviews were conducted with 30 PH patients to derive 32 statements, which were presented as a semantic differential six-point scale (0–5), with contrasting adjectives at each end. This item list was completed by patients attending PH clinics across the UK and Ireland. Rasch analysis was applied to identify items fitting a uni-dimensional model. 226 patients (mean age 55.6±14 years; 70% female) with PH (82% had pulmonary arterial hypertension) completed the study questionnaires. 10 of the 32 items demonstrated fit to the Rasch model (Chi-squared 16; p>0.05) and generated the emPHasis-10 questionnaire. Test–retest (intraclass correlation coefficient 0.95, n=33) and internal consistency (Chronbach’s &agr;=0.9) were strong. emPHasis-10 scores correlated consistently with other relevant measures and discriminated subgroups of patients stratified by World Health Organization functional class (ANOVA F=1.73; p<0.001). The emPHasis-10 is a short questionnaire for assessing HRQoL in pulmonary arterial hypertension. It has excellent measurement properties and is sensitive to differences in relevant clinical parameters. It is freely available for clinical and academic use. emPHasis-10 is a short, valid tool for routine assessment of health-related quality of life in pulmonary hypertension http://ow.ly/qv75v

The use of sildenafil to treat pulmonary hypertension associated with interstitial lung disease.

Background and objective:  Limited data suggest a benefit following sildenafil treatment in patients with pulmonary hypertension (PH) and interstitial lung disease (ILD). The role of sildenafil in the management of PH in ILD is not clear. We report our experience of ILD patients with PH after 6‐month sildenafil therapy.

A review of the management of pulmonary arterial hypertension associated with congenital heart disease.

Approximately 5–10% of adolescent and adult patients with congenital heart disease (CHD) will develop pulmonary arterial hypertension (PAH). Patients with PAH associated with CHD (PAH–CHD) exhibit several similarities to those with idiopathic and other associated forms of PAH, especially with regards to their non-specific, cardinal symptoms. The development of PAH–CHD can lead to lifelong impairment although, paradoxically, survival may be better versus idiopathic PAH. Patients with PAH–CHD may experience social limitations, and emotional and psychological issues, arising from their disease burden. Nurses and other allied healthcare professionals are well placed to deliver the individually-tailored care that patients with PAH–CHD require. Activities known to be of particular benefit include patient engagement and education, patient empowerment, colleague training, and ensuring effective communication across the multidisciplinary team. Recent developments in the management of PAH–CHD have led to changes in the medical needs and optimal care of this patient population. This review aims to provide an overview of the natural course, diagnosis, symptoms and impact of PAH–CHD. We also aim to communicate the current standards in management of patients with PAH–CHD, and how their outlook can be improved in the future.

Eisenmenger syndrome: current perspectives

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Conservative Management and Recommendations for Pulmonary Arterial Hypertension Related to Congenital Heart Disease

Pulmonary arterial hypertension (PAH) in congenital heart disease (PAH–CHD) is the result of numerous pathomechanistic pathways affecting the pulmonary vascular bed and leading to a rise in pulmonary vascular resistance (PVR), right heart failure and premature death. Depending on the type of underlying defect or previous repair (timing and method used), patients can present with diverse anatomy and pathophysiology. At the extreme end of the spectrum is Eisenmenger syndrome (ES), which is characterized by pulmonary arterial pressure elevated to near-systemic levels with shunt reversal and cyanosis. It is a multisystem disorder driven by slow progressive chronic hypoxemia and the persistence of a shunt, resulting in coagulation disorders, iron deficiency anaemia, renal dysfunction, hypertrophic osteoarthropathy, paradoxical emboli and heart failure. Differences between various types of PAH–CHD are not purely academic, but significantly impact on presentation, treatment and outcome. This chapter covers the conservative management of PAH–CHD, with a specific focus on Eisenmenger syndrome.

The spectrum of pulmonary arterial hypertension in adults with congenital heart disease: management from a physician and nurse specialist perspective

Congenital heart disease (CHD) is one of the most common causes of pulmonary arterial hypertension (PAH), with a prevalence nearing that of idiopathic PAH in registries. Despite similarities in pulmonary vascular pathology, PAH-CHD differs from idiopathic PAH and other types of PAH. In fact, PAH-CHD is a term that includes a wide spectrum of conditions and pathophysiologies, ranging from Eisenmenger syndrome to milder forms of PAH with systemic-to-pulmonary shunts, to those with previously repaired defects. Significant expertise in both CHD and PAH is required to manage these patients. We provide an overview of the modern management of the wide spectrum of PAH-CHD in adults, both from a physician and clinical nurse specialist perspective.

Intravenous prostacyclin for pulmonary hypertension: Patient's perspective on complications

Introduction: Intravenous (IV) prostacyclin therapy in patients with severe pulmonary arterial hypertension can be associated with life-threatening complications. Patient education and confidence in local healthcare services is critical to ensuring prompt treatment of such complications. We evaluated patient9s understanding of potential complications and their attitudes towards local healthcare services. Methods: Patients established on IV prostacyclin therapy were identified. Patients were counselled prior to receiving IV prostacyclin and subsequently completed a questionnaire assessing their level of understanding. Results: Ten patients were identified and agreed to participate; median distance from home to their specialist centre was 35 miles. All patients agreed or strongly agreed that they were confident in managing their pump. 8 patients reported not being aware of how long it was safe to keep their pump disconnected. 3 patients were not aware of the correct course of action to take in the event of pump failure and 3 patients did not know their correct dose. Only 3 patients felt confident in their local emergency department being able to manage any complications. Conclusions: Patients seem to require additional education. Strategies to ensure prompt recognition of complications and enhance patient confidence with local healthcare is necessary. We present a patient information card, which may assist achieving these goals. .