PAH ppt , causes of pah classification and management

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1. P u l m on a r y A r t e r i a l H y p e r t e n s i o n ( P AH ) 1

2. Pulmonary arterial hypertension is a progressive disease of pulmonary vasculature in which an ever increasing resistance to circulatory flow imposes a mounting afterload for right heart to overcome, which if not corrected would progress to right heart failure

3. W h a t i s P AH ? Progressive disease caused by narrowing or tightening of the pulmonary arteries Right side of the heart becomes enlarged due to the increased strain of pumping blood through the lungs Strain leads to the common symptoms of PAH (breathlessness, fatigue, weakness, angina and syncope) PAH is characterised by; m e a n P A P ≥ 25 mm H g a t r e s t mean PCWP ≤ 15mmHg PVR > 3 Woods units

4. Pathophysiology of PH Notes here 5 Underexpression of NO -> increased Endothelin-1 Remodelling of vessel wall Thrombus in situ TX- -Endothelin-1 Antagonist -PDE Inhibitors -increase NO (by increasing cGmp / prostacyclin

5. Clinical Features High resistance to blood flow through the lungs causes right heart dysfunction, decreased cardiac output and produces: dyspnoea fatigue dizziness syncope peripheral oedema chest pain, particularly during physical exercise

6. Clinical Signs ‘a’ Wave on JVP Clear bLungs Hepatomegaly , edema, cold extremities A2 Loud P2 Mild Loud P2-Moderate to severe Loud p2 with A1 P2 Hidening -RVF Palpable Epigastric impulse/ Left parasternal Heave Right Ventricle S3

7. Changes in the pulmonary arteries in PAH

8. Classification of PH Idiopathic PAH (IPAH) sporadic disease in which there is neither a family history of PAH nor an identified risk factor Heritable PAH (HPAH) accounts for at least 6% of cases of PAH a ss o c i a t ed w i t h m u t a t i o n s i n t h e b o n e m o r ph o ge n e t i c p r o t e i n r e c e p t o r 2 ( BM P R 2 ) , A L K - 1 Drug and toxin-induced rare side effect of certain anorexigenic agents, such as fenfluramine, toxin induced d/t crotolaria spectabilis

9. Classification of PH Associated PAH (APAH): PAH associated with connective tissue disease Well-recognised complication of connective tissue diseases, s u c h a s sy s t e m i c s c l e r o s i s ( SS c ) a n d sy s t e m i c l upu s erythematosus (SLE) PAH associated with HIV infection Relatively rare but well documented complication. Long-term conditions such as PAH increasingly responsible for HIV-associated morbidity and poor prognosis; not d/t direct viral infection of endothelial cells

10. Epidemiology of PAH More frequent in women ( ratio of 2:1) Mean age approx 50 yrs IPAH and CTD associated PAH are most commonly recognised patterns Notes here 12

11. W h y do e s P A H d e v e l op ? Exact causes unknown Complex, multi-factorial condition Endothelial dysfunction occurs early in disease pathogenesis and leads to: endothelial and smooth muscle proliferation remodelling of the vessel wall impaired production of vasodilators (NO, prostacyclin) o v ere xp r e s s i o n o f v a s o c o n s t r i c t o r s ( e n d o t h e l i n - 1)

12. The role of endothelin Endothelin-1 (ET-1) elevated levels are seen in PAH patients levels correlate with disease severity deleterious effects mediated through ET A and ET B receptors fibrosis hypertrophy and cell proliferation inflammation vasoconstriction endothelin receptor antagonists can block these effects

13. Diagnosing PAH

14. Clinical practice guidelines for the diagnosis of PAH ACCF/AHA Diagnostic Approach to PAH

15. Four stage approach to diagnosis Clinical suspicion of PAH s y m p t o ms , k n ow n r i s k f a c t o r s Exclusion of Group 2 (left heart disease) and Group 3 (lung disease) PH ECG, chest radiograph, echocardiography, PFTs, HRCT E x c l u s i o n o f G r o u p 4 ( C TE P H ) P H ventilation/perfusion lung scan PAH evaluation and characterisation CT pulmonary angiography, CMRI, haematology, biochemistry, serology, and ultrasonography functional class and exercise capacity right heart catheterisation (RHC)

16. R igh t h ea rt c a t h e t e r i s a t i o n – t h e d i a gn o s t i c g o l d standard 1

17. Screening for PAH Improving early diagnosis – screening high risk populations: family members of a patient with heritable PAH (HPAH) p a t i e nt s w i t h sy s t e m i c sc l e r o s i s (SS c ) patients with HIV patients with portopulmonary hypertension (PoPH) p a t i e nt s w i t h c o n ge n i t a l h e a r t d i s e a s e Right heart catheterisation required for definitive diagnosis

18. Treating PAH

19. How is PAH treated? Currently no cure for PAH Modern advanced PAH therapies can markedly improve a patient’s symptoms and slow the rate of clinical deterioration, Management is complex, involving use of a range of treatment options: general measures conventional or supportive therapy a d v a n c ed t h e r a p y ( P A H - s p e c i f i c t h e r a p y ) s u r g i c a l i n t er v e n t i o n

20. General measures and supportive therapy General measures limit effects of external circumstances a v oi d p re g n a n c y prevention and prompt treatment of chest infections awareness of the potential effects of altitude Conventional or supportive therapy p r o v i d e sy m p t o m a t i c b e n e f i t supplemental oxygen –indications –PaO2<60mmHg,Sys art saturation 90%; (exception- Eisenmengers $) oral anticoagulants diuretics CCBs ( particularly if acute vasoreactive response is demonstrated)

21. Advanced (PAH-specific) therapy Endothelin receptor antagonists (ERAs) oral treatments that act by blocking the binding of ET to its receptors Synthetic prostacyclins and prostacyclin analogues act by helping to correct the deficiency of endogenous prostacyclin seen in patients with PAH Phosphodiesterase-5 (PDE-5) inhibitors oral agents which act on NO pathway

22. E n d o t h e l i n r e c e p t o r a n t a g o n i s t s (E R A s ) Bosentan- nonpeptide ETA and ETB receptor antagonist Ambrisentan – specific ET A receptor antagonist Macitentan – non selective ET- A / ET- B receptor antagonist -greater tissue penetration relative to Bosentan Sitaxentan – ET 1 receptor antagonist (withdrawn as it caused acute liver failure)

23. Surgical intervention Balloon Atrial septostomy Lung or Heart lung transplant

24. Notes hre T H A N K Y O U