PULMONARY ARTERIAL HYPERTENTION.....pptx

Pulmonary hypertension

1. PULMONARY ARTERIAL HYPERTENTION DR TOQEER HUSSAIN PGR MEDICINE SKBZ CMH MZD

2. INTRODUCTION/DEFINITION PAH is define as a sustained elevation in resting mPAP ≥25 mmHg or left ventricle end diastolic pressure of ≤15 mmHg based on a right heart catheterization. Idiopathic pulmonary arterial hypertension (IPAH) is a progressive disease that leads to right heart failure and death PAH associated with HIV, connective tissue disease(systemic sclerosis),and portal hypertension

3. Classification - PH is subcategorized into five major groups : Group I— Pulmonary arterial hypertension (PAH) Group II— PH due to left heart disease Group III — PH due to lung diseases and/or hypoxemia(COPD, Interstitial lung disease) Group IV — Chronic thromboembolic pulmonary hypertension (CTEPH) Group V — PH with unclear mechanisms

4. Clinical presentation Symptoms of PH-  The symptoms of PH are often nonspecific and variable  include dyspnea (most common),  exercise intolerance,  fatigue,  palpitations,  syncope,  chest pain,  lower extremity swelling,

5. On examination Evidence of right heart failure- Elevated jugular venous pressure, Lower extremity edema , and ascites. cardiovascular examination- prominent second heart sound (loud S2) with loud P2 component and, a right-sided S3 or S4, and a holosystolic tricuspid regurgitant murmur clubbing in chronic lung diseases, sclerodactyly and telangiectasia in scleroderma, and crackles and systemic hypertension in left-sided systolic or diastolic heart failure

6. DIAGNOSTIC TESTING Echocardiogram –(TTE ) Is screening test Shows hypertrophied and dilated right ventricle with elevated estimated pulmonary artery systolic pressure Identify causes of PH -left ventricular systolic and diastolic dysfunction, valvular disease Right heart catheterization - for definitive diagnosis Measure cardiac output and mean right atrial pressure (RAP) and asses severity condition

7. Diagnostic Testing contd … Chest x-ray- Large central pulmonary arteries with “vascular pruning,” Cardiomegaly due to enlarged RA ,RV Regional oligemia of pulmonary vasculature (chronic thromboembolic disease) Interstitial infiltrates (ILD) Hyperinflated lungs(chronic obstructive lung disease). HRCT- Enlarged pulmonary arteries , peripheral pruning of the small vessels,and enlarged right ventricle and atrium Centrilobular ground-glass infiltrate Ventilation–Perfusion (V/Q) lung scan- Used for excluding chronic thromboembolic disease

8. Diagnostic Testing contd … Pulmonary Function Testing Spirometry and lung volumes to assess for COPD or restrictive- interstitial lung disease [ILD]) Diffusing capacity for carbon monoxide (DLCO ) reduced in parenchymal lung diseases Arterial blood gas (ABG ): Elevated PaCO2 is found in hypoventilation syndrome. Six-minute walk (6MW) or simple exercise test- to evaluate the degree of exertional hypoxemia and to monitor progression and response to therapy Nocturnal oximetry :. Nocturnal desaturations is common finding in PAH

9. Diagnostic Testing contd.. ECG- RVH, right atrial enlargement, right bundle branch block, and right ventricular strain pattern Acute vasodilator testing .- Performed with a short-acting vasodilator, such as intravenous adenosine, intravenous epoprostenol , or inhaled nitric oxide. Definition of a responder is decrease in mPAP by ≥10 mm Hg to an absolute level ≤ 40 mm Hg without a decrese in CO. responders are considered for long-term treatment with CCBs

10. Diagnostic Testing contd.. Laboratories  Complete blood counts (CBCs)  Blood urea nitrogen, serum creatinine  Hepatic function tests  B-type natriuretic peptide (BNP)  Human immunodeficiency virus (HIV) serology  Thyroid-stimulating hormone (TSH)  Antinuclear antibody (ANA)  Antitopoisomerase antibodies and anticentromere antibodies  hepatitis B and C serologies

11. COMPLICATIONS  Right-sided heart enlargement and heart failure  Blood clots(Pulmonary Embolism)  Arrhythmia  Bleeding

12. TREATMENT General measures- Avoid pregnancy Immunization for respiratory illness influenza and pneumovax vaccination Minimize valsalva maneuvers -increase risk of Syncope cough, constipation,heavy lifting stop cigarette smoking

13. Classes of therapy MEDICAL- Diuretics Fluid restriction Anticoagulants Inotropic agents Long-term oxygen therapy PAH specific therapy SURGICAL THERAPY-  Lung transplantation or heart–lung transplantation  Atrial septostomy  Septal defect closure

14. Treatment contd … DIURETICS- Principally to treat edema from right heart failure May need to combine classes(loop diuretic +aldosterone antagonist+ thiazides) Careful to avoid too much preload reduction ANTICOAGULANT S- Warfarin is dosed to target international normalized ratio (INR) of 1.5 to 2.5 INOTROPIC AGENT improves right heart function, cardiac output, and symptoms. Dobutamine and milrinone are best for short-term use in extremely decompensated states

15. PAH SPECIFIC THERAPY Calcium Channel blocker Endothelin receptor antagonists - Bosentan , ambrisentan , masitentan Phosphodiesterase-5 inhibitors - Sildenafil,tadalafil Prostanoids - epoprostenol,Treprostinil guanylyl cyclase stimulator - riociguat

16. Treatment contd … CCBs- Used only in showing positive vasodilator response Diltiazem or nifedipine preferred Endothelin receptor antagonists- Endothelin receptor antagonists target endothelin-1 (ET1), a potent endogenous vasoconstrictor Bosentan : 62.5 mg PO bid x 4 wks and then 125 mg bid Ambrisentan : 5 or 10 mg PO qd

17. Treatment contd … Phosphodiesterase-5 inhibitors- block the enzyme that shuts down nitric oxide–mediated vasodilation and platelet inhibition Sildenafil ( Revatio ): 10 mg IV tid or 20 mg PO tid (4-6 hr apart) Tadalafil ( Adcirca ): 40 mg PO qd or 20 mg PO qd Guanylyl cyclase stimulator- Stimulator of nitric oxide receptor Riociguat is an oral soluble guanylyl cyclase stimulator Riociguat (Adempas): 1 mg PO TID approved for the treatment of PAH

18. Treatment contd …. Prostanoids : Epoprostenol ( Flolan , Veletri ): 2 ng/kg/min IV infusion every 15 min (initial) Treprostinil ( Remodulin , Tyvasco ): • Remodulin (IV) = 1.25 ng/kg/min continuous SC or central line IV infusion Iloprost ( Ventavis ): 2.5 -5 mcg/inhalation 6- 9x/day

19. Acute vasoreactive testing (IPAH or APAH, ONLY ) Positive : use high dose oral CCB ( ie . nifedipine, diltiazem, or amlodipine) Negative : depends on risk Low RISK : Endothelin receptor antagonist (ERA) or Phosphodiesterase Type 5 (PDE5) Inhibitors (oral), Soluble guanylate cyclase ( sGC ) Stimulators Low or intermediate ris k: monotherapy or oral combination therapy High risk: combination therapy including IV prostacyclin analogs

20. Take home message-  Idiopathic pulmonary arterial hypertension is a progressive disease  Transthoracic Echocardiography is screening test  Definitive diagnosis by right heart catheterization  there is no cure for PAH , current pharmacologic therapies improve morbidity and, in some cases mortality  Improved awareness among clinicians and patients could lead to more timely diagnosis that will affect the response to therapy and survival

21. THANK YOU