Journal of the New Zealand Medical Association, 18-June-2004, Vol 117 No 1196
Familial primary pulmonary hypertension
Dan Park, Lutz Beckert
Primary pulmonary hypertension (PPH) is a rare disorder of uncertain aetiology affecting 1–2 people per million. Possibly as many as 20% percent of cases are thought to be familial—defined as those affecting at least two first-degree relatives.1 PPH shows an autosomal dominant pattern of inheritance, with highly variable penetrance and genetic anticipation.
We present the first documented familial New Zealand case.
At the age of 29, the patient presented to her general practitioner with fatigue, headaches, weight gain, and episodic flushing. Her only past medical history was mild asthma. She was married without children. She had never smoked. As she was adopted, she was not initially aware of any family history. Later, however, it become apparent that her mother had died from PPH at the age of 26.
At the time of her presentation to a cardiologist, several classical signs of pulmonary hypertension were noted on physical examination, including narrow splitting of the second heart sound with gross accentuation of the pulmonary component. She had a right ventricular gallop and, although her jugular venous pressure (JVP) was not raised, she had mild peripheral oedema and a moderate degree of ascites.
Chest X-ray showed the characteristic pattern of cardiomegaly—markedly prominent central pulmonary arteries with clear lung fields. Electrocardiography demonstrated tall peaked P waves indicative of right atrial enlargement, and gross right axis deviation with 'clockwise rotation' of the chest leads indicative of right ventricular pressure overload.
Echocardiography revealed a normal left ventricular size and function, but her right heart was grossly dilated with mild incompetence of the pulmonary valve and moderate tricuspid regurgitation. This was confirmed by right heart catheterisation studies measuring the right atrial pressure at 19/25 mmHg (mean: 17 mmHg), and right ventricular pressure of 105/8 mmHg (mean: 25 mmHg). Pulmonary artery pressure was 107/56 mmHg (mean: 77 mmHg).
Repeated right heart catheterisation performed a few years later (when under the respiratory service) confirmed ongoing pulmonary artery hypertension measured at 108/40 mmHg (mean 70 mmHg), with a pulmonary artery resistance of 1352 dyne-s/cm5.
She was given a trial of two vasodilators—receiving intravenous adenosine at doses escalating up to 6000 mcg/min, and nebulised iloprost without side effects (see Figure 1). Neither the pulmonary artery pressure nor the pulmonary artery resistance changed significantly following either challenge.
Figure 1. The patient undergoing pulmonary artery pressure measurements and vasodilator testing a few weeks before her death
(It had been her wish that her case would be published to raise awareness of this fatal but treatable condition. Her husband signed the consent form to publish this photograph.)
Given the negative response, the patient was offered long-term oxygen and long-term warfarin therapy. She was considered for bilateral lung transplantation and bridging iloprost therapy, but unfortunately (a few weeks after lung transplantation was considered) she passed away due to right heart failure.
In the past, the therapeutic options for the management of treating pulmonary artery hypertension only included oxygen therapy, anticoagulation, and lung transplantation. Subsequently 10–15% of patients have been shown to respond to vasodilator administration; these patients have an almost 90% chance of surviving 5 years on high dose calcium antagonists.2
Over the last few years promising new vasodilator therapies have become available, with several different mechanisms of action. Treprostinal, beraprost, and iloprost are analogues of epoprostenol, which itself can be given by intravenous infusion. Bosentan blocks endothelin receptors A and B, and sildenfanil inhibits phosphodiesterase type 5. Epoprostenol has been proven to improve survival and exercise tolerance; iloprost and bosentan have been shown to improve exercise tolerance.3 Several trials of newer agents and combination of these agents are still ongoing.4 Currently epoprostenol, iloprost and bosentan are licensed for the treatment of PPH in New Zealand.
Our patient and her mother represent the first recorded cases of familial PPH in New Zealand. No other family members have so far been found to suffer from the disease.
Author information: Dan Park, Respiratory Registrar, Lutz Beckert, Respiratory Physician, Department of Respiratory Medicine, Christchurch Hospital, Christchurch
Correspondence: Lutz Beckert, Department of Respiratory Medicine, Christchurch Hospital, Private Bag 4710, Christchurch. Fax: (03) 364 0914; email: Lutz.Beckert@chhb.govt.nz
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