DEFUNCT PAH module 1: introduction, classification and pathology

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General introduction

Dr Simon Gibbs

The condition of pulmonary hypertension may be associated with a very poor prognosis but is frequently treatable. It is important to arrive at an accurate diagnosis since treatments that have been developed for pulmonary hypertension can improve some forms of the disease and may worsen others.

Old perceptions that pulmonary hypertension was untreatable with the only treatment being lung transplantation are long since redundant. After a decade of randomised controlled trials (RCTs), we are starting to understand how to use disease-targeted drug therapies in pulmonary arterial hypertension (PAH). The diagnosis and treatment of patients with PH needs to be proactive. This means that it is important to recognise that the underlying disease process may rapidly or suddenly deteriorate, and it is crucial to anticipate such deteriorations, which may otherwise lose the patient important ground.

The potential to treat patients with pulmonary hypertension has invigorated basic science research. We can be hopeful of helpful advances in its molecular biology and cell biology during the foreseeable future. Unfortunately, there is no reliable animal model of the human pulmonary circulation and we are therefore entirely dependent on the results of clinical trials. This is the rationale for managing patients with treatable forms of pulmonary hypertension in high-volume centres, which can ensure best outcomes for patients. These centres must also undertake clinical trial research to find better treatments for future generations of patients.

Achieving the right diagnosis

Diagnosis requires invasive haemodynamic assessment using cardiac catheterisation.  To use this effectively, it is important to have an understanding of pulmonary haemodynamics. These are covered in some detail in this learning programme.

Historically, the prognosis has been very poor, with median survival shorter than three years in some patients. Effective treatment strategies that work on a number of disease pathways and molecular receptor sites have been developed over the past 20 years. These include calcium channel blockers, prostanoids, phosphodiesterase inhibitors and endothelin receptor antagonists. Some of these treatments not only improve symptoms but they also have been shown to affect morbidity and mortality.

Logical management

In turn, a more logical diagnostic evaluation pathway and a more logical evidence-based treatment strategy for the individual patient have been developed.

A precise diagnosis requires invasive haemodynamic investigation such as cardiac catheterisation, which can best be carried out at centres experienced in this procedure. Importantly, the earlier the stage at which the diagnosis is made, the better the prognosis and survival for the individual. Thus, the index of suspicion needs to be high for those working both in respiratory medicine and cardiology and, since the presenting symptoms are non-specific, for those working in primary care also. Typically, the patient may be a young woman with breathlessness and tiredness; and not unusually, it may take two years before the patient is referred.

The purpose of this programme is to introduce the disease to a non-specialist readership both in the community and in hospital and to provide helpful clinical advice about how to manage patients, including when to refer them to a designated centre. The first section describes the causes of the disease, and the patient populations in whom screening is suggested.  The haemodynamic definition of pulmonary hypertension is not a diagnosis without a definition of the underlying cause. The cause and severity of pulmonary hypertension determine the prognosis. Nonetheless, each patient tends to follow an individual natural history; and for an individual the prognosis may be difficult to predict.

The first section describes the causes of the disease, and the patient populations in whom screening is suggested, with later modules going on to discuss therapeutic approaches. These modules will highlight that the haemodynamic definition of pulmonary hypertension is not a clinical diagnosis. It is crucial to the successful management of any patient with suspected pulmonary hypertension to ascertain the underlying cause of the raised pulmonary artery pressure, as it is this that defines prognosis and response to treatment. The aim of this programme is to enable the reader to have a thorough understanding of how to approach the investigation of patients with suspected pulmonary hypertension in order to reach a diagnosis and commence appropriate therapy.

The second module goes on to describe clinical presentation and diagnosis. In the third module, you will learn about treatment: each patient will need an individual cocktail of lifestyle measures and appropriate drug treatment. Patients who are prescribed disease-targeted drug therapy for pulmonary hypertension require vigilant follow-up and reintervention as needed. The final module provides information on special groups of patients, and details of UK referral centres and patient support groups.

 Simon Gibbs
Lead Clinician
National Pulmonary Hypertension Service
Department of Cardiology, Hammersmith Hospital,
Du Cane Road, London W12 0HS.