Pulmonary Hypertension By Dr Sajid Ali MO/PGR Pulmonology SZMC/H RYK

A 24 year old girl from Quetta presented with 6 months history of exertional dyspnoea and chest pain.a cardiologist ruled out cardiac cause for the dyspnoea and reffered to you because echocardiography showed markely elevated pulmonary arterial pressure, What two furhter investigation would you like to do in this patient. Name five medicine which are valuable in the management of pulmonary hypertention.

Two investigations HRCT with contrast Right cardiac cathetrization

Five valuable drugs. Diuretics Calcium channel blockers Prostcycline antalogs(Epoprostenol (Flolan)., Treprostinil, Iloprost) Endothelin receptor antagonists(Bosentan) Phoshodiesterase inhibitors(sildenafil)

Pulmonary Hypertension It is defined as a mean pulmonary artery pressure greater than 25mmHg at rest, or greater than 30mmHg with exercise.

CorPulmonale It is an enlargement of the right ventricle due to derangements in the structure or function of the respiratory system. Cor pulmonale is a complication of pulmonary hypertension.

Clinical Classification of Pulmonary Hypertension Group 1. Pulmonary arterial hypertension (PAH) Idiopathic PAH Familial PAH Associated with (APAH): Collagen vascular disease Congenital systemic to pulmonary shunts (large, small, repaired, or non repaired) Portal hypertension HIV infection Drugs and toxins Other (glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies,myeloproliferative disorders, splenectomy) Associated with significant venous or capillary involvement Pulmonary veno-occlusive disease Pulmonary capillary hemangiomatosis

Clinical Classification of Pulmonary Hypertension Group 2. Pulmonary venous hypertension Left-sided atrial or ventricular heart disease Left-sided valvular heart disease Group 3. Pulmonary hypertension associated with hypoxemia COPD Interstitial lung disease Sleep-disordered breathing Alveolar hypoventilation disorders Chronic exposure to high altitude

Clinical Classification of Pulmonary Hypertension Group 4. Pulmonary hypertension due to chronic thrombotic and/or embolic disease Thromboembolic obstruction of proximal pulmonary arteries Thromboembolic obstruction of distal pulmonary arteries Pulmonary embolism (tumor, parasites, foreign material) Group 5.Miscellaneous Sarcoidosis, histiocytosis X, lymphangiomatosis, compression of pulmonary vessels (adenopathy, tumor, fibrosing mediastinitis)

Functional Classification of Pulmonary hypertention Patients with PH but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope Class II: Patients with PH resulting in slight limitation of physical activity. They are comfortable at rest.Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope.

Functional Classification of Pulmonary hypertention Class III: Patients with PH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. Class IV: Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may even be present at rest

Risk Factors of Pulmonary Hypertension Drugs and toxins Definite Aminorex Fenfluramine Dexfenfluramine Toxic rapeseed oil Very likely Amphetamines L-Tryptophan Possible Meta-amphetamines Cocaine Chemotherapeutic agents Unlikely Antidepressants Oral contraceptives Estrogen therapy Cigarette smoking

Risk Factors of Pulmonary Hypertension Demographic and medical conditions Definite Gender Possible Pregnancy Systemic hypertension Unlikely Obesity

Risk Factors ofPulmonary Hypertension Diseases Definite HIV infection Very likely Portal hypertension/liver disease Collagen vascular diseases Congenital systemic-pulmonary-cardiac shunts Possible Thyroid disorders

Proposed pathogenesis of PAH.

FIGURE Pulmonary arteriole showing the medial hypertrophy and concentric intimal narrowing that occur as a result of vascular remodeling in pulmonary arterial hypertension.

Examination Cyanosis clubbing Raised JVP, with giant V waves Right ventricular heave and tapping apex beat Wide splitting of S2 with loud P2 Murmur of tricuspid regurgitation Hepatomegaly Ascites Peripheral oedema.

Evaluation of Patients with Pulmonary Hypertension Detection of pulmonary hypertension Detailed history and physical examination Electrocardiogram Chest radiograph Echocardiogram (at rest, to consider repeat with exertion) Suspicion of pulmonary hypertension and possible causes/association Exclude other causes of cardiopulmonary Symptoms Evaluate for presence of pulmonary hypertension, assess chamber sizes and function, valvular abnormalities, contrast (“bubble”) study to evaluate possible shunt

Essential testing Pulmonary function testing Overnight oximetry Lung (V/Q) scan Blood serologies (e.g., CBC, liver function, renal function, HIV, ANA, antiphospholipid antibodies) Oxygen desaturation study 6-Minute walk test Right cardiac catheterization Exclude instrinsic lung disease Screen for sleep disordered breathing Exclude thromboembolism Exclude collagen vascular disease, liver disease, infection and other possible causes of pulmonary hypertension Assess need for supplemental oxygen (rest and exertion) Establish baseline Confirm diagnosis, assess other cardiac causes (shunt); consider left heart catheterization)

Contingent testing Transesophageal echocardiogram C.T scan chest Polysomnogram Pulmonary angiogram Lung biopsy Assess patent foramen ovale (PFO) Characterize valvular function Assess interstitial lung disease, adenopathy Diagnosis and treatment of sleep-disordered Breathing Assess presence and location of clot and suitability for pulmonary Thromboendarterectomy Exclude subtle interstitial lung disease vasculitis and other uncommon diseases (PVOD, PCH) to assist planning

Diagnosis Electrocardiogram. Abnormal in85% of patients with established PAH. Right-axis deviation with evidence of right ventricular and/or right atrial hypertrophy and right ventricular strain.

Chest Radiography Shows abnormalities in more than 90% of patients with idiopathic PAH. Prominence of the main pulmonary arteries (90%) Enlargement of the hilar vessels (80%) Peripheral pruning (51%)

FIGURE Chest radiograph in pulmonary arterial hypertension. Enlargement of the proximal pulmonary arteries .

FIGURE Chest radiograph in pulmonary arterial hypertension. Enlargement of the proximal pulmonary arteries .

High-Resolution Computed Tomography. exclude parenchymal lung disease as the cause of the PAH. HRCT is particularly important in the diagnosis of PVOD.

Continuous Volume (Spiral) CT Pulmonary Angiography Pulmonary angiography is considered the “gold standard” for the investigation of patients with CTEPH

Spiral computed tomography with contrast Spiral computed tomography with contrast. A, Massive filling defect in the main pulmonary artery (arrow). B, Filling defects in lobar (large arrow) and segmental (small arrows) pulmonary arteries

Spiral CT scan (2-mm collimation, pitch of 2, 24% iodinated contrast agent) obtained at the level of the right upper lobe in a 65-year-old patient with acute onset of dyspnea. Spiral CT scan (2-mm collimation, pitch of 2, 24% iodinated contrast agent) obtained at the level of the right upper lobe in a 65-year-old patient with acute onset of dyspnea. There are multiple partial filling defects at the level of the anterior (arrowhead) and posterior (arrow) segmental arteries of the right upper lobe. Note the additional presence of bilateral pleural effusion. Remy-Jardin M , Remy J Radiology 1999;212:615-636 ©1999 by Radiological Society of North America

Pulmonary angiograms. A, Normal and, B, in pulmonary arterial hypertension, with marked pruning of peripheral vasculature.

Echocardiography. The screening tool of choice for PAH. LV dysfunction/valve abnormalities Intracardiac shunt RVSP and RH function

Severe right chamber dilation

Ventilation and Perfusion ( V/Q) Lung Scanning FIGURE Normal ventilation scans. C and D, Multiple segmental (or larger) defects oncorresponding perfusion scans.

Cardiac Magnetic Resonance Imaging (MRI) Most accurate than echocardiography . Accurate estimates of ventricular size and mass, as well as pulmonary blood flow. Cardiac MRI is now used to monitor disease-targeted therapy

Biomarkers Brain natriuretic peptide (BNP) Elevated in idiopathic PAH and associated with interstitial lung disease, COPD, congenital heart disease, CTEPH, and scleroderma.

Evaluation of Functional Class and Severity of PAH 6MWT. Cardiopulmonary Exercise Testing (CPET). Right Heart Catheterization

Management

General management. Education Long-term oxygen Diuretics and digoxin Anticoagulation

vasodilator therapy Vasodilator responsiveness. Responders non-responders

CalciumChannel Blockers CCBs are used in higher doses then systemic hypertention and coronary heart disease. 240 mg/day of nifedipine or 900 mg/day of diltiazem can be tolerated with careful monitoring. Verapamil has significant negative inotropic effects and should be avoided

Disease-Targeted Therapies Prostacyclin (and analogs) Endothelin receptor antagonists Phosphodiesterase inhibitors

Prostacyclin and Analogs PAH have deficient production of prostacyclin. very short circulating half-life, a continuous intravenous infusion is necessary, Epoprostenol (Flolan)., Treprostinil, Iloprost

Endothelin Receptor Antagonist A Bosentan novel oral endothelin receptor A and B antagonist. Sitaxsentan,an ET-A receptor antagonist recently improved for class III patients.

Phosphodiesterase Inhibitors Inhibition of type 5 PDEs with selective drugs, such as sildenafil, increase cyclic GMP and induce a fall in intracellular calcium concentration with consequent vasodilatation.

Surgical treatments Balloon Atrial Septostomy . Lung Transplantation