Once the patient has undergone all investigations necessary to establish a precise diagnosis of pulmonary hypertension, with any associated conditions identified and a clear haemodynamic profile understood, then a treatment plan can be arranged. Patients with pulmonary arterial hypertension will be considered for evidence-based disease-targeted drug therapy, as shown in figure 1.1
Patients with chronic thromboembolic hypertension should be discussed with a pulmonary endarterectomy surgeon.
Patients with pulmonary hypertension related to left heart disease, lung disease and hypoxia should be managed by a cardiologist or respiratory physician. Disease-targeted therapy for PAH may potentially cause harm in these patients: there is currently no evidence for the use of the disease-targeted therapies discussed below in these patients.
The management of PAH consists of general and supportive measures plus selection of evidence-based drug treatment. Modern drug therapy leads to a significant improvement in patient symptoms and a slower rate of clinical deterioration (ESC 2015 guidelines).1 It should be appreciated that the treatment algorithm is based mainly on clinical trials in patients with idiopathic, heritable and anorexigen-induced PAH. Some trials have included CTD, congenital heart disease with a shunt and HIV. Although some drugs are licensed for use in PAH as a group, they do not necessarily have an evidence base in each of the subclasses. There are no large head-to-head trials of disease-targeted therapies. The choice of therapy depends on the circumstances of an individual patient as well as drug availability and licensing.
The current treatment strategy can be divided in to three main steps
1. General measures, supportive therapy and referral to expert centres
Initial therapy with high dose calcium channel blockers in vasoreactive patients or disease targeted therapies according to the prognostic risk (low, intermediate or high) of the patient and the grade of recommendation for each individual drug or combination of drugs. Therapy can be initial monotherapy with sequential combination therapy, or initial combination therapy. This will be discussed further in this module.
2. Assessment of the response to the initial treatment and in the case of inadequate response, the role of additional combination therapy and lung transplantation
The overall treatment goal in patients with PAH is achieving a low-risk status (see module 2), which means bringing and/or keeping the patient in WHO-FC II. The current guidelines suggest a threshold of >440 m in the 6MWD, however, individual factors must be considered as this target may be too low or too high for younger and older patients respectively. CPET should be regularly used in these cases to provide objective information on exercise capacity and right ventricular (RV) function.
General measures in treating PAH
The objectives for treatment of pulmonary hypertension are to improve survival, to return the patient to work, education or to a useful role in society, to enable the patient to live independently, and to improve symptoms and quality of life. Patients need general support and specific advice about the general activities of daily life, time off work, travel and insurance.
Physical activity and rehabilitation
Selected patients can be encouraged to be physically active, within safe limits: mild exertion and breathlessness are acceptable, but exercise that leads to severe dyspnoea, dizziness or chest pain is excessive. Caution with exercise prescription should be taken in patients who drop their systemic arterial pressure on exercise. Heavy physical exercise and isometric exercise are not recommended since they can lead to syncope. Tai Chi and yoga may be of benefit in some patients. In those who are physically unfit, supervised rehabilitation may be considered.
Three randomised controlled trials (RCTs) have shown that trained PAH patients reach longer 6MWT distances, have improved cardio-respiratory function, a better quality of life, reach higher levels of physicial activity, have reduced fatigue severity and improved functional class. In a subsequent study different types of pulmonary hypertension appeared to respond equally well to exercise training, but there was a significant proportion of patients who developed a complication of this intervention.4
There are gaps in the knowledge in regards to the optimal method of exercise, intensity and duration, as well as the effects on prognosis. Exercise training programmes should be commenced in centres experienced in both PAH patient care and rehabilitation.
A sodium-restricted diet is advised in patients with right ventricular failure. Fluid restriction is sometimes needed also but should not normally be less than 1.5 litres per day. Renal function may suddenly deteriorate dramatically as a consequence of a reduction of cardiac output if patients become even mildly dehydrated. Routine immunisations for patients against influenza and pneumococcal pneumonia are also advised.
Pregnancy and contraception in PAH
Pregnancy in women with PAH is associated with maternal mortality estimated at between 20 and 55%. PAH is a contra-indication to pregnancy38 and it is recommended that early termination should be offered if a woman becomes pregnant. Women with PAH should be counselled about the risks of pregnancy, and effective contraception should be offered at the time of diagnosis. Saying that, recent reports indicate that when PAH is well controlled, pregnancy outcomes have improved. However, this must be confirmed in larger series before the recommendation to avoid pregnancy in all patients with PAH is reconsidered.
The choice of contraceptive preparation should be managed by a family planning doctor who understands the issues of PAH. Progesterone-only contraceptive preparations are one favoured option39 (note that bosentan may reduce the efficacy of hormonal contraceptive agents). The Mirena coil is effective but the vasovagal reaction that may occur with device insertion can be hazardous in these patients. Sterilisation is rarely used in these patients because of the risks of surgery. Barrier contraceptives are safe for the patient, but less effective.
When a woman with PAH chooses to continue her pregnancy, she will need to be managed closely in a multidisciplinary setting, incorporating both a complex pregnancy team and a pulmonary hypertension team. She will need frequent visits and likely hospitalisation during the third trimester40 with planned elective delivery and continuation of disease-targeted therapies. The optimal mode of delivery remains a subject of debate.
Most maternal deaths occur within the first month from delivery. The main cause of peripartum death has been reported as refractory right heart failure.
In patients who undergo elective surgery, care must be taken to ensure maintenance of oxygenation, a stable circulating volume and avoidance of acid-base disturbance. Systemic hypotension and large swings in circulating volume may precipitate dangerous haemodynamic instability. All patients should be managed by an anaesthetist with experience in managing these patients. Regional anaesthesia is probably better tolerated than general anaesthesia but this depends on the surgery being undertaken. Disease-targeted therapies for PAH must not be discontinued in the perioperative period. Consideration should be given to admitting these patients to the intensive care unit in the immediate postoperative period. Elective surgery carries a significantly higher risk in PAH patients than in the general population.
Pneumonia is the cause of death in 7% of patients with PAH. It is recommended to vaccinate against influenza and pneumococcal pneumonia.
The diagnosis brings with it a degree of social isolation, and many patients develop psychological symptoms such as depression and anxiety.2 Patient support groups can help patients and their families to cope with the disease, by providing helpful and practical information. Some may need referral to a psychologist. Proactive advanced care planning is also recommended.
There are no studies in patients with PAH to determine the need for supplemental oxygen during prolonged flights. However, in flight oxygen administration should be considered for patients in WHO FC III and IV and those with an arterial blood oxygen pressure <60 mmHg. Furthermore, these patients should avoid going to altitudes >1500–2000 m without supplemental oxygen.
Genetic counselling and family based risk assessments should be undertaken by genetic services in selected PAH patients. Patients with a family history of PAH should be offered this service, which may include molecular genetic testing after comprehensive genetic counselling. At-risk relatives may wish to receive genetic counselling and clinical monitoring for early detection of disease, as well as know their mutation status for family planning options. First degree relatives of patients with iPAH should be provided with information about the genetic basis for this disorder, including recognition of the low recurrence and offspring risk.
- The psychological wellbeing of PH patients is fundamental
- Lifestyle advice may include a physical exercise programme tailored to individual patients
- Pregnancy should be avoided in women with PAH