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Internal Medicine

Primary pulmonary hypertension (PPH)

Rare disorder characterised by raised pulmonary-artery pressure in the absence of secondary causes.

Rare disorder characterised by raised pulmonary-artery pressure in the absence of secondary causes.

Pathophysiology

Characterised by intimal fibrosis, in situ thrombosis, and hypertrophy of the smooth muscle cells of the media.

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Cross section of a pulmonary artery (approximately 125 μm) in a patient with severe pulmonary hypertension showing thickening of all three layers of the vessel. Possible mechanisms for these changes are suggested. 1=intima; 2=media; 3=adrentitia. | Peacock, A. J. (1999). Primary pulmonary hypertension. Thorax, 54(12), 1107 LP – 1118. https://doi.org/10.1136/thx.54.12.1107

Pathological subtypes:

  1. Plexogenic arteriopathy (50% cases, worst prognosis)
    • Associated with the plexiform lesion, an unusual pathological entity consisting of a mass of disorganised vessels associated with endothelial cells, smooth muscle cells, and myofibroblasts (angiogenic response to underlying vascular injury).
  2. Thrombotic arteriopathy
    • Similar pulmonary vascular histology with multiple thrombi (give the abnormal patchy appearance seen in a ventilation perfusion scan and may be a consequence of endothelial injury).
    • Anticoagulants improve survival
  3. Pulmonary veno-occlusive disease (< 10% cases)
    • Separate entity with intimal proliferation of the intrapulmonary veins rather than arteries. 

Clinical features

It is a progressive disease usually affecting the arterial side of the pulmonary circulation and, if untreated, progresses to severe pulmonary hypertension and, finally, right heart failure.

  • Breathlessness with no other obvious cause (M/C symptom at presentation)

Specific signs of pulmonary hypertension:

  • Loud pulmonary second sound
  • Right ventricular heave
  • Pulmonary flow murmur

Signs of right heart dysfunction:

  • Raised jugular venous pressure
  • V-waves in the neck
  • Hepatic pulsation
  • Swollen ankles

Other features:

  • Signs of co-existent disease: Primary pulmonary, cardiac, or liver disease
  • Evidence of: venous thrombosis or connective tissue, thyroid or HIV disease).

Diagnosis

May take up to 18 months to diagnose and, following diagnosis, the median survival is under two years.

Right heart catheterization (DIAGNOSTIC):

Usually performed using a Swan Ganz triple lumen thermodynamic catheter inserted under fluoroscopic control via the right femoral vein.
  • Mean PAP >25 mmHg at rest and >30 mmHg during exercise, with a normal pulmonary capillary wedge pressure.

Chest radiograph:

Of limited benefit but may show enlargement of the heart or main pulmonary artery or peripheral pruning of vessels.
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Chest radiograph from a patient with PPH showing the enlarged main pulmonary artery and enlarged heart. | Peacock, A. J. (1999). Primary pulmonary hypertension. Thorax, 54(12), 1107 LP – 1118. https://doi.org/10.1136/thx.54.12.1107

Ventilation-perfusion scan:

May show the presence of mismatched defects indicating possible underlying thromboembolism, but defects may also be seen in pure intrinsic vascular disease, particularly the thrombotic variant. The ventilation scan will be normal but the perfusion scan may show patchy loss consistent with vascular obstruction.
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Ventilation-perfusion scan from the patient in fig 1showing (A) normal ventilation but (B) patchy loss of perfusion due to vascular obstruction. Pulmonary embolism should be excluded. | Peacock, A. J. (1999). Primary pulmonary hypertension. Thorax, 54(12), 1107 LP – 1118. https://doi.org/10.1136/thx.54.12.1107

Computed tomographic (CT) angiogram:

Exclude parenchymal lung disease but volume scans of the central pulmonary arteries after injection of contrast may help to demonstrate major intravascular clot.
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Computed tomographic (CT) angiogram of the patient (in chest radiograph image) showing large pulmonary arteries and absence of intravascular clot. | Peacock, A. J. (1999). Primary pulmonary hypertension. Thorax, 54(12), 1107 LP – 1118. https://doi.org/10.1136/thx.54.12.1107

Selective pulmonary angiography:

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(A) Right and (B) left selective pulmonary angiograms from the patient in fig 1 showing large central pulmonary vessels but peripheral pruning and no evidence of pulmonary embolism. | Peacock, A. J. (1999). Primary pulmonary hypertension. Thorax, 54(12), 1107 LP – 1118. https://doi.org/10.1136/thx.54.12.1107

Management

Treatment aimed at lowering PAP, increasing cardiac output, and decreasing in situ thrombosis.

Anticoagulants (prevent in situ thrombosis):

  • Long-term treatment with warfarin improves the prognosis in PPH.
  • Treatment goal: To achieve an international normalised ratio (INR) of 2

Calcium channel blockers (CCB) (oral drug of choice as vasodilators):

  • High-dose dihydropyridine blockers:
    • Diltiazem (up to 720 mg daily)
    • Nifedipine (up to 300 mg daily)
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Calcium-channel blockers, warfarin, and prostacyclin improve survival in PPH. A, PPH patients who have an acute, favorable response to calcium blockers have improved survival compared with those who do not. Warfarin is particularly beneficial in patients who are nonresponders. Reproduced with permission from Reference 81. B, Compared with conventional therapy (calcium-channel blockers and warfarin), prostacyclin improves prognosis in patients with PPH. | Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension: the Primary Pulmonary Hypertension Study Group. N Engl J Med.1996; 334:296–302.

Other vasodilators:

  • Diazoxide, captopril, and hydralazine
  • Prostacyclins

Inotropic agents:

Used once maximum vasodilation has been achieved (particularly if there is concomitant use of CCBs which are known to be negatively inotropic) since right heart dysfunction is a sequel of severe pulmonary hypertension.

Lung transplantation

Last resort

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