Pulmonary arterial hypertension associated with congenital heart disease: Recent advances and future directions

Highlights

• Congenital heart defects can cause pulmonary arterial hypertension.

• Treatments are available although more evidence for novel therapies is needed.

• Prognostic factors are different to other forms of pulmonary arterial hypertension.

Abstract

Congenital heart disease (CHD), the most common inborn defect, affects approximately 1% of all newborns worldwide. Advances in its diagnosis and treatment have led to a dramatic improvement in patients' quality of life and long-term survival prospects. However, recently it has been realised that many of these patients are affected by ongoing and life-long cardiac issues, namely residual and progressive haemodynamic lesions, arrhythmia and sudden cardiac death, as well as the development of chronic heart failure and pulmonary arterial hypertension (PAH) — all of which merit tertiary care. Unfortunately, many patients with CHD are lost to follow-up, due to the assumption that their initial response to surgical and or catheter intervention in childhood led to cure. Furthermore, there are many patients with undiagnosed or unoperated CHD in the developing world coming to medical attention during adulthood. Our article focuses on advances in the management of PAH associated with CHD, a common association with an adverse impact on quality of life and survival prospects that affects approximately 10% of patients with CHD. Much of the recent progress in PAH–CHD has focused on the extreme end of the disease spectrum, namely on Eisenmenger syndrome. Herein we discuss this progress and future directions for this emerging cardiovascular field.

Introduction

Pulmonary arterial hypertension (PAH), defined as a pulmonary arterial pressure of ≥ 25 mm Hg at rest in the presence of normal pulmonary capillary wedge pressure (i.e. ≤ 15 mm Hg), is relatively common amongst patients with congenital heart disease (CHD) [1]. Recent prevalence data on PAH in adult CHD patients report rates between 4.2% (in a national CHD registry [2]) and 28% (in a cohort of tertiary European CHD centres) [3]. Although the exact prevalence of PAH in association with CHD (PAH–CHD) in the community remains unknown, many patients with CHD have sadly been lost to specialist follow-up [4]. Furthermore, severity of PAH and its rate of progression often remain largely unknown, even amongst patients with CHD who are currently under specialist cardiac care. This lack of information occurs because the urgency to prevent the development of PAH in infancy and early childhood in the developed world at least tends to relax once the diagnosis is made and early surgery or catheter intervention is performed. However, a proportion of patients who have received seemingly appropriate childhood therapy go on to develop late PAH for reasons that are not well understood. There may be an as yet undefined genetic susceptibility to develop PAH amongst patients with CHD, which persists even after haemodynamic intervention in early childhood. Furthermore, patients with anatomically complex CHD, who are now surviving into adulthood following improvements in palliative procedures and patients from developing countries, who have not received an early diagnosis (and repair) of CHD contribute to the pool of patients who go on to develop PAH.

Irrespective of pathogenetic mechanism(s), current evidence suggests that the presence of PAH in the CHD setting has an adverse impact on both quality of life and survival [3]. Eisenmenger syndrome (ES) represents the extreme end of the PAH–CHD spectrum and displays a prevalence of 1.1% to 12.3% amongst CHD patients [2], [3], and a prevalence of 0.001% in the general population [5]. The exact number of patients with ES worldwide remains unknown [6]. We have observed a trend of an approximate 9% year-on-year increase in the number of patients with ES attending our designated tertiary CHD–PAH service over the past 8 years (personal communication, Professor Gatzoulis, Royal Brompton Hospital, London, UK). We submit this reflects improving awareness of the condition in the community and availability of therapy, rather than increasing numbers of patients with ES in the UK. Nevertheless, the anticipated growth in numbers and complexity of adult patients with CHD [7], including those with PAH, means the need for information on how to care for these patients will become increasingly relevant and pressing for cardiologists and other healthcare professionals alike.

Clinical and academic interest in PAH–CHD as a disease entity has grown in recent years [8]. Considerable progress has been made; but there remain multiple challenges concerning optimal classification, monitoring and therapy. A meeting was held in Vienna (February 2011) in which 63 PAH–CHD experts from around the world gathered to discuss the most salient of these issues. In this article, we, the Scientific Committee of the meeting, report on some of the meeting's debates and supplement this with our personal experiences and the very latest literature in this rapidly expanding field of cardiovascular medicine.