Pulmonary Hypertension and Various Treatment Options Presented by: Cory Johanboeke

Overview Pulmonary hypertension is characterized by increased pulmonary arterial pressure and secondary right ventricular failure. PH is defined as a mean pulmonary artery pressure greater 25mmHg at rest or 30mmHg with exercise. Classified into 5 groups according to the mechanistic basis of the disease.

Classification Group I – Pulmonary arterial hypertension (PAH), this group includes those with sporadic idiopathic pulmonary arterial hypertension, PAH due to collagen vascular disease (RA, SLE, scleroderma), congenital heart defects causing systemic to pulmonary shunt (ASD, VSD), portal hypertension. Pulmonary vascular resistance (PVR) >120dynes/sec/cm, Pulmonary capillary wedge pressure (PCWP)<15

Classification Group II – pulmonary venous hypertension, which is pulmonary hypertension due to left atrial, ventricular, or valvular heart disease. Group III - pulmonary hypertension is due to disorders of the respiratory system or hypoxemia (COPD, sleep apnea). Group IV – pulmonary hypertension is due to chronic thrombotic or embolic disease of the pulmonary vasculature

Classification Group V – pulmonary hypertension due to inflammation, mechanical obstruction, or extrinsic compression of the pulmonary vasculature ( sarcoidosis, and fibrosing mediastinitis)

Pathophysiology Increased blood flow in the pulmonary circulation Hypoxic vasoconstriction Vascular fibrosis Inflammatory mediators causing vasoconstriction and activating platelets Smooth muscle cell propagation Increased vasculature pressure Right heart hypertrophy and failure

Diagnostic test Chest X-ray- enlargement of the central pulmonary arteries, enlargement of the right ventricle EKG- signs of right atrial and ventricular hypertrophy, right axis deviation Echocardiography- used to estimate pulmonary artery systolic pressure, and right ventricle size and thickness, check for shunts, valve function, and pericardial effusions.

Diagnostic test Pulmonary function test- to determine lung disease as a cause. Overnight oximetry- check for obstructive sleep apnea V/Q scan- check for thromboembolic disease. Six minute walk to evaluate which NYHA functional class the patient is in. Right heart catheterization to confirm diagnosis

Treatment options primary therapy Divided into two groups primary therapy and advanced therapy. Primary therapy is directed at resolving the underlying cause. Fix the underlying heart defect for those in group 2 Diagnosis and treat the underlying lung condition for those in group 3

Treatment options primary therapy Anticoagulation with warfarin for those in class 4 (consider using with all classes) INR goal of 2 Reversal of or treatment of underlying cause in group 5 Use diuretics for peripheral edema and hepatic congestion. Oxygen 1-4 liters to maintain Sats. of 90% or higher. Exercise to improve functional capacity

Treatment options advanced therapy Indicated for all patients in New York Heart Association (NYHA) functional class levels 3 or 4 (usually those with IPAH). CCBs, Nifedipine and diltiazem, titrated up to reduce patient to functional class 1 or 2 Prostonoid drugs, induce smooth muscle relaxation and inhibit smooth muscle cell and platelet aggregation. IV Epoprostenol, SQ Treprostinil, inhaled Iloprost

Advanced therapy Bosentan- Non-selective endothelin receptor blocker (endothelin potent vasoconstrictor) Sixtaxentan, ambrisentan- selective endothelin type A antagonist ( won’t block the vasodilator effects mediated by type b receptors). These drugs still under review by FDA

Advanced treatment Sildenafil- phosphodiesterase type 5 inhibitor, prolongs the vasodilator effects of Nitric oxide. Milirone - phosphodiesterase type 3 inhibitor (vasodilator effect on both large and small pulmonary arteries) Nicorandil- potassium channel opener with nitrate properties. (hyperpolarizes the smooth muscle wall and calcium antagonist).

Advanced therapy Fasudil- approved to treat vasospasm after arachnoid hemorrhage in Japan, blocks Rho-kinase which is a mediator of smooth muscle contraction.

Surgical treatment options Atrial septostomy- creates a right to left shunt this increase systemic blood flow and reduces pulmonary congestion. Cadaveric lung transplantation Living donor lobar lung transplantation- harvesting lower lobes from healthy donors and implanting them in the patient.