Pulmonary arterial hypertension in adults with congenital heart disease: markers of disease severity, management of advanced heart failure and transplantation

ABSTRACT

Introduction

Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a progressive, life-limiting disease.

Areas covered

In this paper, we review the classification and pathophysiology of PAH-CHD, including the mechanisms of disease progression and multisystem effects of disease. We evaluate current strategies of risk stratification and the use of biological markers of disease severity, and review principles of management of PAH-CHD. The indications, timing, and the content of advanced heart failure assessment and transplant listing are discussed, along with a review of the types of transplant and other forms of available circulatory support in this group of patients. Finally, the integral role of advance care planning and palliative care is discussed.

Expert opinion/commentary

All patients with PAH-CHD should be followed up in expert centers, where they can receive appropriate risk assessment, PAH therapy, and supportive care. Referral for transplant assessment should be considered if there continue to be clinical high-risk features, persistent symptoms, or acute heart failure decompensation despite appropriate PAH specific therapy. Expert management of PAH-CHD patients, therefore, requires vigilance for these features, along with a close relationship with local advanced heart failure services and a working knowledge of listing criteria, which may disadvantage congenital heart disease patients.

KEYWORDS:

• Pulmonary arterial hypertension
• pulmonary vascular disease
• congenital heart disease
• eisenmenger syndrome
• advanced heart failure
• transplantation
• heart-lung transplant
• ventricular assist device
• extra-corporeal membrane oxygenation

Abbreviations

Table

Article highlights

• Pulmonary arterial hypertension (PAH) is a frequent complication of congenital heart disease (CHD), which can take one of several clinical categories, from Eisenmenger syndrome to PAH after CHD repair.

• Despite the advent and widespread uptake of PAH therapies, PAH associated with CHD (PAH-CHD) is still associated with significant morbidity and mortality.

• Disease progression in PAH-CHD is marked by heterometric right ventricular adaptation, with right ventricular dilatation and dysfunction, leading to heart failure and multi-organ dysfunction.

• Risk stratification tools for PAH-CHD have not been developed and validated, but several clinical and echocardiographic parameters have been associated with mortality in PAH-CHD and especially in Eisenmenger syndrome. Biochemical risk variables have also been identified, including B-type natriuretic peptide levels, hypoalbuminemia, hyponatremia, renal dysfunction, iron deficiency, thrombocytopenia and higher uric acid levels.

• The management of heart failure in PAH-CHD includes supportive care in an expert center, the use of PAH therapies and diuretics. Conventional heart failure therapies used in acquired heart failure are not effective in PAH-CHD.

• Patients with PAH-CHD on PAH therapy with persistent symptoms, progressive heart failure, persistent high-risk features or the need for parenteral PAH therapies should be referred to the advanced heart failure team to assess candidacy for transplantation or placement of mechanical circulatory support.

• The choice of heart-lung transplantation versus single or bilateral lung transplantation, with CHD repair if necessary, depends on the patient’s underlying anatomy, the expertise of the surgical center and organ allocation policy.

• Existing transplant listing criteria are derived from non-ACHD populations and may place PAH-CHD patients at a disadvantage; PAH-CHD-specific cut-offs for transplant listing are urgently needed.

• Advance care planning and palliative care input should be initiated early and as part of parallel planning with active management, e.g., escalation of PAH therapy, to reduce the symptom burden, improve quality of life and plan future care.

Declaration of interest

K. Jansen has received payment for lectures/educational events and non-financial support from Janssen-Cilag Ltd. A. Constantine has received an educational grant, payment for lectures/educational events and non-financial support from Janssen-Cilag Ltd. R. Condliffe has received nonfinancial support from Janssen-Cilag Ltd. and has received personal fees from Janssen-Cilag Ltd., Bayer, and GlaxoSmithKline. R. Tulloh has received nonfinancial support from Janssen-Cilag Limited; and has received personal fees from Janssen-Cilag Limited, Pfizer, Abbott International, GlaxoSmithKline, and Bayer. P. Clift has received nonfinancial support from Janssen-Cilag Limited; has received grants and personal fees from Janssen-Cilag Limited; and has received personal fees from Bayer. S. Moledina has received personal fees and non-financial support from Janssen-Cilag Ltd. S. J. Wort has received nonfinancial support from Janssen-Cilag Ltd.; has received grants and personal fees from Janssen-Cilag Ltd. and Bayer; and has received personal fees from GlaxoSmithKline. K. Dimopoulos has received nonfinancial support from Janssen-Cilag Ltd.; and has been a consultant to and received grants and personal fees from Janssen-Cilag Ltd., Pfizer, GlaxoSmithKline, and Bayer/MSD. The CHAMPION group is supported by Janssen-Cilag Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.