PULMONARY HYPERTENSİON

Prof. Sevda Özdoğan

2013

DEFİNİTİON Pulmonary hypertension (PH) is characterized

by elevated pulmonary arterial pressure and secondary right ventricular failure (ie, cor pulmonale). It is a progressive, fatal disease if untreated, although the rate of progression is highly variable.

PAH is defined according to right heart catheterization. Mean pulmonary artery pressure (mPAP) >25 mmHg at rest

A mean pulmonary artery pressure of 8 to 20 mmHg at rest is considered normal, while a mean pulmonary artery pressure of 21 to 24 mmHg at rest has uncertain clinical implications.

CLASİFİCATİON: GROUP 1 PAH This group consists of sporadic IPAH,

heritable IPAH, and PAH due to diseases that localize to small pulmonary muscular arterioles

(eg: connective tissue diseases, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, chronic hemolytic anemia, persistent pulmonary hypertension of the newborn, pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis)

Abnormal bone morphogenetic protein receptor type II (BMPR2) appears to play an important role in the pathogenesis of IPAH.

In hereditary IPAH, the gene that encodes BMPR2 (IPAH1) appears to be transmitted as an autosomal dominant trait. It has been estimated that up to 80 percent of hereditary IPAH is due to mutations in BMPR2

Connective tissue diseases

Rheumatoid arthritis and systemic lupus erythematosus (SLE) can also lead to fibrous obliteration of the pulmonary vascular bed, with a marked female predominance

Drug- and toxin-induced PAH is also considered group 1 PAH.

(eg: aminorex, fenfluramine, dexfenfluramine, (appetite supressants) and toxic rapeseed oil)

Also amphetamines, cocaine (chronic use), L-tryptophan, phenylpropanolamine, chemotherapeutic agents (thyrosine kinase inhibitors, interferon), and selective serotonin reuptake inhibitors are considered likely to cause PAH

The cause of HIV-related PAH is uncertain, but viral and host factors both likely play an important role.

PAH associated with portal hypertension is referred to as portopulmonary hypertension (PPHTN), The most widely accepted hypothesis is that a humoral substance (which would normally be metabolized by the liver) is able to reach the pulmonary circulation through portosystemic collaterals, resulting in PPHTN.

PAH due to congenital heart disease is due to pulmonary blood volume overload due to intracardiac shunting. Left to right shunts are most common, especially due to large (nonrestrictive) ventricular septal defects (VSD). PAH also occurs in patients with atrial septal defects (ASD).

GROUP 2 PH

Pulmonary hypertension owing to left heart disease. (systolic dysfunction, diastolic dysfunction, or mitral and aortic valve disease, restrictive cardiomyopathy, constrictive pericarditis, and left atrial myxoma)

GROUP 3 PH Pulmonary hypertension owing to lung

diseases or hypoxemia.

This group includes PH due to severe chronic obstructive pulmonary disease, interstitial lung disease, pulmonary diseases with a mixed restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders

GROUP 4 PH Chronic thromboembolic pulmonary

hypertension

Pulmonary hypertension with unclear multifactorial mechanisms.

In: hematologic disorders (eg, myeloproliferative disorders), systemic disorders (eg, sarcoidosis), metabolic disorders (eg, glycogen storage disease), or miscellaneous causes (eg, sickle cell disease)

GROUP 5 PH

the prevalence of pulmonary hypertension in patients with SCD is 20 to 40 percent

Red cell hemolysis resulting in increased plasma levels of cell-free hemoglobin, which rapidly depletes the potent pulmonary vasodilator nitric oxide (NO) is the proposed mechanism of PH in SCD

CLİNİCAL MANİFESTATİONS Sypmptoms:

exertional dyspnea, lethargy, and fatigue

Symptoms and signs of PH may be difficult to recognize because they are nonspecific. These symptoms are frequently attributed incorrectly to age, deconditioning, or a coexisting medical condition.

The initial symptoms of PH are the result of an inability to adequately increase cardiac output during exercise

Exertional chest pain Subendocardial hypoperfusion Compression of the enlarged pulmonary

artery to left main coronary artery

Exertional syncope is due to the inability to increase cardiac output during activity.

Peripheral edema is due to increased right sided cardiac pressures

Anorexia and/or abdominal pain in the right upper quadrant due to passive hepatic congestion.

Less common symptoms:

cough, Hemoptysis, Hoarseness (caused by compression of the

left recurrent laryngeal nerve by a dilated main pulmonary artery)

PHYSİCAL EXAMİNATİON increased intensity of the pulmonic

component of the second heart sound Right-sided systolic ejection murmur A high-pitched systolic murmur of

tricuspid regurgitation. Signs of right ventricular failure:

Signs of elevated jugular venous pressureHepatomegaly, An enlarged and pulsatile liver, peripheral edema, ascites and pleural effusion may also exist

DİAGNOSİS

Diagnostic testing is indicated whenever PH is suspected.

The purpose of the diagnostic testing is to confirm that PH exists, determine its severity, and identify its cause

It has been estimated that more than 20 percent of patients have symptoms of PH for longer than two years before the PH is recognized

DİAGNOSTİC TESTS Chest X ray

enlargement of the central pulmonary arteries with attenuation of the peripheral vessels, resulting in oligemic lung fields

Right ventricular enlargement (diminished retrosternal space) and right atrial dilatation (prominent right heart border)

Signs of the underlying cause of the PH (eg, interstitial lung disease).

ECG Echocardiography Pulmonary Function Tests (to identify and

characterize underlying lung disease that may be contributing to PH)

Polysomnography V/Q scan/ CT Angiography/ Pulmoner

angiography Laboratory tests:

HIV serology Liver function tests Antinuclear antibody (ANA), rheumatoid

factor (RF), and antineutrophil cytoplasmic antibody (ANCA) titers

Exercise testsScreens for alternative causes of the

patient's symptomsDetermines the patient's functional capacity

which guides therapy Provides prognostic information, since a

longer distance walked during the 6MWT is associated with longer survival

Right Hearth CatheterizationNecessary to confirm the diagnosis of PH Helpful in distinguishing patients who have

PH due to left heart disease

PAH DİAGNOSİS

The diagnosis of PAH also requires right heart catheterization: Several criteria must be met:

Mean pulmonary artery pressure is ≥25 mmHg at rest

Mean pulmonary capillary wedge pressure <15 mmHg (to exclude PH owing to left heart disease

Chronic lung diseases and other causes of hypoxemia are mild or absent

Venous thromboembolic disease is absent

Certain miscellaneous disorders are absent, including systemic disorders (eg, sarcoidosis), hematologic disorders (eg, myeloproliferative diseases), and metabolic disorders (eg, glycogen storage disease).

DİFFERENTİAL DİAGNOSİS Asthma Chronic obstructive pulmonary disease

(COPD) Interstitial lung disease Myocardial dysfunction Obesity/deconditioning Liver disease Budd-Chiari syndrome (Thrombosis of hepatic

veins)

NATURAL HİSTORY AND PROGNOSİS PH is a progressive, fatal condition if untreated.

However, the rate of progression is highly variable and depends upon the type and severity of the PH.

Symptomatic patients with IPAH who do not receive treatment have a median survival of approximately three years. Symptomatic patients with PAH associated with another disease (eg, liver disease, systemic sclerosis [also called scleroderma]) generally have a worse prognosis

Patients with severe PAH or right heart failure die sooner without treatment (usually within one year) than patients with mild PAH or no right heart failure

The main cause of death in patients with PAH is thought to be right heart failure with circulatory collapse and superimposed respiratory failure.

Primary therapy is directed at the underlying cause of the PH.

Some patients progress to advanced therapy, which is therapy directed at the PH itself. It includes treatment with prostanoids, endothelin receptor antagonists, phosphodiesterase 5 inhibitors, or, rarely, certain calcium channel blockers.

TREATMENT

Diuretics — Diuretics are used to treat fluid retention due to PH because diuresis will diminish hepatic congestion and peripheral edema

Continuous oxygen administration remains the cornerstone of therapy in patients with group 3 PH

It is generally accepted that anticoagulation is indicated in patients with IPAH, hereditary pulmonary artery hypertension, drug-induced PAH, or group 4 PH (CTEPH).

Exercise training appears to be beneficial for

patients with PH

LOST??!!