Pulmonary Artery Hypertension

Dr. Rikin Hasnani

Introduction • Definition : • Pulmonary Hypertension is defined by a mean pulmonary

artery pressure more than or equal to 25 mmHg at rest. • Pulmonary Artery Hypertension is characterised

hemodynamically by presence of pre capillary PH including an end expiratory pulmonary wedge pressure less than 15mmhg and a pulmonary vascular resistance (PVR) more than 3 wood unit.

• Incidence of PH range between 2.4 and 7.6 cases per million people.

• Prevalence estimates range between 15 and 26 cases per million people.

Pathophysiology

• The pulmonary circulation normally is a high-flow, low-resistance, low-pressure system.

• PAP is the product of cardiac output (CO) and pulmonary vascular resistance (PVR), where PVR is the vascular resistance of the entire lung, including the pulmonary arteries, capillaries, and veins.

Regulation of PVR

• Normal pulmonary artery pressure 25/10 mmHg

• mPAP 15 mmHh• PVR in PA 2mmHg/lit/mt• Increase in CO no effect on PAP in normal

Adult , due to recruitment of non perfused vessels

• Exercise – increases CO

• NO, Endothelin 1 , prostaglandins , o2 plays important role in maintaining PVR.

• Endothelin 1 –activates protien kinase c – causes opening of calcium channel , increases intracellular calcium.

• NO – stimulates gaunylate cyclase - inc. cGMP – dec intracellular calcium.

• PGI2- activates adenylate cyclase – inc. cAMP- dec calcium.• Hypoxia – closes k+ channel – depolarisation of cell – Ca2+

influx – vasoconstriction.• Endothelin 1 increases NO while NO decreases Endothelin1

Structural changes in pulmonary vessels

• Sustained vasoconstriction• Vascular remodelling • In situ Thrombosis• Increased arterial wall stiffness• plexiform lesions

Pathogenic Mechanism

Genetics of PAH• Bone Morphogenic Protien (BMP) : it inhibits proliferation

and induces apoptosis of smooth muscle cells.• This ability of BMP is suppressed in cells isolated

specifically from smaller pulmonary vessels in patients with IPAH.

• BMPR2 gene mutation : BMP receptor acts as receptor both for BMP and TGFbeta. BMPR2 gene mutation is found in 70% pt with familial PAH and 20% of pt with IPAH.

• Others – activin receptor kinase-like 1 (ALK1), endoglin (Eng), and Smad 8.

Clinical features

• Mild breathlessness • Dyspnoea on exertion • Cough • Fatigue• Dizziness • Swelling of leg• Syncope , chest pain, palpitation• Asymptomatic

World Health Organization Functional Classification of Patients with Pulmonary Hypertension

• Class I: 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.

• 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. Discomfort is increased by any physical activity.

• If PH is suspected or diagnosed , Patients should be asked about important symptoms or risk factors that might suggest cause of pulmonary hypertension. This include

• symptoms of collagen vascular disease• sleep apnea• history of risks for thromboembolism, HIV infection, liver

disease, or anorectic agent use. • A history of tobacco use and chronic sputum production, or a

known history of asthma with poor control might be important clues to the presence of obstructive airway disease and hypoxia as the cause of pulmonary hypertension.

• A history of interstitial lung disease or any cause of chronic hypoxia must be noted. A careful family history should be taken.

Physical examination

• Cyanosis, raised JVP, pedal edema, ascites , pulsatile Hepatomegaly – indicates right heart failure.

• CVS Examination – loud s2, ejection systolic murmur, left parasternal heave, Rvs4

• Signs suggestive of moderate to sever PAH : Pan systolic murmur of TR,Rvs3, Hepatojugular reflex, invreased v wave of JVP, hypotension, low pulse pressure.

Diagnostic studies

• to confirm the presence of pulmonary hypertension,

• identify the etiology,• assess severity and prognosis, and• to help guide appropriate therapy

Chest x ray – dilated pulmonary artery

ECG

Echocardiography • Doppler examination is able to quantify the tricuspid

regurgitant jet in the majority of cases.• A modified Bernoulli equation is used to estimate right

ventricular systolic (RVSP = 4v2 + right atrial pressure) and is assumed equal to the pulmonary artery systolic pressure.

• Normal RVSP has been reported as 28 ± 5 mm Hg.• It may also identify cause of PH.• Recent methods to evaluate RV function - tricuspid annular

plane systolic excursion, tissue Doppler imaging, and myocardial performance index (Tei-Doppler index).

• After diagnosis of PH is made next step to find out cause of PH

• PFT• V/Q scan • Overnight pulse oxymetry or

polysomnography

V/Q scan in CTEPH

Lab Testing

• HIV antibody, • rheumatologic serologies (e.g., ANA),• liver function tests, and • complete blood count• Exercise testing : 6MWT

Cardiac Catheterisation• Right heart cardiac catheterization is required to confirm the

diagnosis of pulmonary hypertension, test for important cardiac causes, and perform vasodilator trials to determine an initial approach to therapy.

• LVEDP• PAWP• Blood gases• Cardiac Output is obtained by either thermodilution or use of

measured arterial and venous hemoglobin saturations and the Fick principle.

• The PVR is calculated as (mean PA pressure – PCWP)/CO

• PH with normal PVR – inc. CO or postcapillary HTN,• PH, elevated PVR, and a variable CO – portopulmonary

HTN.• Acute vasodilator trial – it is only done in experimental

centres . Agents used areinhaled nitric oxide, intravenous adenosine, or epoprostenol.

• a decrease in the mPAP of at least 10 mm Hg to a value less than 40 mm Hg, together with a CO that is unchanged or increased (but not decreased) is generally considered a “positive” acute vasodilator response.

Treatment of PAH

GENERAL MANANGEMENT• Exercise and the Avoidance of Deconditioning• Oxygen Therapy• Air Travel• Immunizations• Fluid Management and Diuretics• Anticoagulation• Contraception and Pregnancy

• PAH-SPECIFIC PHARMACOTHERAPY• 1. calcium channel antagonist• 2. Endothelin Receptor Antagonist• bosentan• ambrisentan, Sitaxsentan, • 3. Specific inhibitors of phosphodiesterase type 5 (e.g.,

sildenafil, vardenafil, and tadalafil)• Prostenoid Therapies : formulations available are continuous

intravenous infusion (epoprostenol and treprostinil), subcutaneous infusion (treprostinil), and via inhalation (treprostinil and iloprost).

• Epoprostenol therapy is initiated at 1 to 4 ng/kg/min and progressively increased in 0.5 to 1 ng/kg/min increments at intervals dictated by patient response and side effects.

• Treprostinil is initiated at 0.625 or 1.25 ng/kg/min and similarly increased as dictated by clinical response, typically in increments of 1.25 ng/kg/min

• Iloprost inhalational therapy is initiated at a dosage of 2.5 and increased to 5 μg with the subsequent dose if tolerated.

• Treprostinil is started at 18 μg (3 breaths) four times a day, with dose escalation suggested every 1 to 2 weeks to a maximum and target dose of 54 μg (nine breaths) four times daily.

• Prostenoid side effects are seen with inhalational therapy, including headache, nausea, diarrhea, flushing, and jaw discomfort.

Lung tansplantation

Prognosis

Prognosis

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