pulmonary hypertension.pptx

Pulmonary Artery Hypertension

1. PULMONARY HYPERTENSION Dr Awadhesh Sharma

2. INTRODUCTION CLASSIFICATION PATHOPHYSIOLOGY/ GENETICS CLINICAL PRESENTATION DIAGNOSTIC WORKUP RISK STRATIFICATION MANAGEMENT

3. INTRODUCTION : Pulmonary circulation is high blood flow, low pressure ,low resistance system Offers less than 10% resistance to flow than systemic circulation PH refer to high pulmonary vascular pressure Definition is based on hemodynamic assessment by right heart characterization. Normal mean PAP – 14.0±3.3mmhg 2SD of Mean PAP 20 mmhg

4. RECENT HEMODYNAMIC DEFINITION : mPAP >20mmhg at rest PVR > 2 wood units PVR = ( mPAP – PAWP)/ CO TVR= mPAP /CO

5. Unclassified PH Pt with mPAP > 20mmhg but low PVR <2WU and low PAWP <15mmhg These group have elevated pulmonary blood flow Cause have congenital heart disease Hyperthyroidism Liver disease

6. Etiological Classification In to five groups Group 1: pulmonary arterial hypertension Group 2 : PH due to left heart disease Group 3: PH associated with lung disease Group 4 : PH associated with pulmonary arterial obstruction Group 5 : PH with unclear / multifactorial mechanism

7. Pathophysiology :

8. GENETICS : BMPR2 was identified as a first PAH predisposing gene Detected in 75% familial PAH 20% in sporadic cases Other gene associations : Endoglin (ENG) ALK1 TGF –B pathway SMAD9 BMPR1b KCNK3 channelopathy EIF2AK4 BMPR2 carrier vs IPAH younger age at dx sever hemodynamic compromise Lower likelihood of acute vasodilator response

9. PULMONARY ARTERIAL HYPERTENSION CAUSES : IPAH – Most common cause of PAH no family history no identified risk factor F:M = 4:1 ( REVEAL registry ) Heritable PAH – 6 to 10 % pt of PAH BMPR2 mutation : autosomal dominant with incomplete penetrance Connective tissue disease Schistosomiasis HIV

10. Drug induced PAH

11. Pulmonary veno occlusive disease Micro vasculopathy affecting septal and pre septal venules Risk factors : consanguinity alkylating agents (mitomycin , cyclophosphamide ) systemic sclerosis organic solvent exposure Familial cases : EIF2AK4 mutation Definite dx by lung biopsy Some times first clue for dx – rapid development of pulmonary edema after start of PAH therpay

12. CLINICAL PRESENTATION

13. SYMPTOMS Are mainly linked to RV dysfunction Initially exertional Symptoms due to pulmonary artery dilatation Symptoms of underlying cause

14. DIAGNOSTIC WORKUP

15. Neither sensitive nor specific for PAH dx Normal ECG not exclude dx

16. CHEST X RAY

17. MPA dilatation Dilated RPA PBF/PRESSURE LPA dilatation Yes NO ?End on vessel + - nt Increase PBF PAH Sign of PVH + nt - nt C pre and post capillary htn Pre capillary + nt - nt Valvular PS IDPA

18. ECHOCARDIOGRAPHY

19. Provide noninvasive quantitative data use to screen patient for PH . One third of patient with proven PH sufficient TR jet is lacking and PASP is unmeasurable. Echo alone is insufficient for dx and classifying . By using echo we can measure PASP : 4 *TRV 2 + RA pressure dPAP : 4 PR end diastolic velocity 2 + RA pressure mPAP : by chemla formula 0.61* pasp + 2mmhg RV dysfunction Associated Left heart disease /shunt lesions

20. RIGHT HEART CATHETERIZATION

21. Gold standard test of dx and classifying PH All patient with suspected PAH after non invasive test should undergo RHC. Essential measurements include- 1)Oxygen saturation (SVC,RA ,IVC,PA) 2)RA/RV /PA pressure 3)Left side filling pressure (PCWP) 4)PVR 5)Response to acute vasodilators Most feared complication is perforation of PA

22. VASOREACTIVE TESTING

23. Purpose is to identify candidates of PH who may respond to long term CCBs therapy .(Class I) Only recommended in IPAH ,HPAP,DPAH .(Class I) Drug used are : Nitric oxide, inhaled iloprost ,iv epoprostenol Adenosine is no longer recommended due to frequent side effects. Positive response – reduction in mPAP by >10mmhg to absolute value <40mmhg with increased or unchanged CO. < 10% patient shows vasodilator response .

24. Additional acute vasoreactive testing should be performed at re evaluation to detect persistent response. In patient without showing clinical and hemodynamic improvement on subsequent visit alternate therapy should be instituted. Satisfactory response- WHO FC I/II mPAP < 30 PVR<4 WU

25. OTHER MISCELLANEOUS TESTS : Pulmonary function test (DL CO) Ventilation perfusion imaging Cardiopulmonary exercise testing Fluid challenge Blood investigation immunology Cardiac CT MRI Ct pulmonary angio /DSA

26. RISK STRATIFICATION:

27. Reveal 2.0 Score

28. ESC /ERS risk stratification

29. TREATMENT OPTIONS

30. CCBs Long acting CCBs are used . Only in patients showing acute vasodilator response Very few patients (<7%) of IPAH shows promising improvement over longterm CCBs .

31. ENDOTHELIN RECEPTOR ANTAGONIST (ERA) Acts on ET1 AND ET 2 receptor Antagonised endothelin mediated vasoconstriction / fibrosis / thrombogenic effects BOSENTAN – dual ERA 125mg BD dosing evaluated in BREATH 1 study cause dose dependent increase in liver transaminase (10%), reversible so monthly LFT monitoring needed drug interaction : lower warfarin, sildenafil, tadalafil level

32. BREATH Study Result

33. AMBRISENTAN : preferentially blocks endothelin A receptor . No liver enzyme derangement No LFT monitoring needed Ambition TRIAL 5 to 10 mg od dose S/E – peripheral edema , headach MACITENTAN : Dual ERA 10mg od No LFT monitoring Reduction in Hb to<8 observed in 4.3 % patients

34. ARIES TRIAL RESULT

35. PDE 5 inhibitors Potent vasodilator by inhibiting degradation of c GMP. Sildenafil 20mg TDS Tadalafil 40mg OD S/E due to vasodilation includes headache ,flushing , dyspepsia , epistaxis rare episode of sudden hearing and vision loss noted

36. SUPER 1 TRIAL

37. Soluble guanylate cyclase stimulator Directly stimulate sGC independent of NO Riociguat first such agent Dose – 1 to 2.5 mg tds S/E : hypotension , peripheral edema , headache Should not be used in combination with PDE 5 inhibitors

38. PATENT TRIAL

39. PROSTACYCLIN ANALOGUES : Counterbalance reduced prostacyclin I2 level ,which are reduced in PAH patients . Epoprostenol : first FDA approved agent short half life 3 to 5 min Given by continuous iv infusion pump Dose – 2 to40 ng/kg/min Have positive inotropic effect S/E – jaw pain flushing, diarrhea , rash delivery site infection

40. TREPROSTINIL: Stable analogue Longer half life (4hr) Route – i /v , s/c , oral ,inhalation Iv Treprostinil is associated with higher incidence of gram negative sepsis than iv epoprostenol Dose: 1.25 to 60ng/kg/min iv or sc 0.25mg bd oral 18ug 4 times a day inhalation ILOPROST : administers by inhalation route 2.5ug 6 to 9 times per day

41. SELEXIPAG Oral ,selective prostacyclin receptor agonist Dose : 200 to 1600 ug bd Side effects profile similar to other prostacyclins .

42. AMBITION TRIAL

43. TRITON TRIAL

44. GRIPHON TRIAL

45. INTERVENTIONAL THERAPY Atrial septostomy to create R to L shunt . It decreases right side filling pressure . Recommended in sever PAH and intractable Right HF despite OMT. It is bridge therapy to transplant Contraindications are – RA pressure more than 20mmhg oxygen saturation less than 90 RA LVEDP > 18mmhg

46. LUNG TRANSPLANTATION Treatment option for pt with refractory PAH. Patient with disease variant that poorly respond to medical therapy , PVOD/PCH.

47. CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION

48. Long term complication of pulmonary embolism. Based on the findings described after at least 3 months of effective anticoagulation: a) precapillary PH b) at least one segmental perfusion defect detected by lung scanning, MDCT angiography, pulmonary angiography In CTEPH PH is consequence of both: PA obstruction from organized clot associated microvasculopathy

49. RISK FACTORS Acute venous thromboembolism Lupus anticoagulant/ antiphospholipid antibodies(10% of CTEPH patient ) Coagulation factor VIII Splenectomy Ventriculoatrial shunt for hydrocephalus therapy Inflammatory bowel disease Malignancy

50. Equal in both sexes All age groups can be affected ( median age is 63 years) CLINICAL SYMPTOMS: similar to IPAH (edema and hemoptysis more common in CTEPH ; syncope more common in IPAH)

51. DIAGNOSIS Ventilation perfusion lung scan : main imaging modality ( at least one defect encompassing at least half a segment with normal ventilation) high NPV RHC : precapillary PH PVR : predictor of prognosis for surgical candidates HRCT chest Classic side selective pulmonary angiography in anterioposterior and lateral projections for confirming the diagnosis ring like stenosis ,web ,slits , pouches tapered lesion Assessing most proximal involvement Evaluating for surgical complexity and accessibility Negative CTPA does not exclude disease as distal disease may be missed

52. TYPES OF CTEPH

53. TREATMENT SURGERY ( PULMONARY ENDARTERECTOMY) : treatment of choice Patients having proximal disease are best suited for surgery Patients with significant PH but little or no obstruction are poor candidates for surgery BALLOON PULMONARY ANGIOPLASTY (BPA); inoperable CTEPH with persistent /recurrent disease after PEA MEDICAL TREATMENT : Anticoagulants, diuretics and oxygen in cases of heart failure Lifelong anticoagulation ( VKA , for NOACs no RCT) after pulmonary endarterectomy

54. Medical therapy……. Target Microvascular component of CTEPH. Useful in inoperable cases , and pt with persistent /recurrent disease after PEA. Approved drugs are Riociguat (class I) sc Treprostinil (class IIb) Also helpful in high risk patient prior to planned intervention. Medical rx recommended for Patient with mPAP >30mmhg post PEA.

55. Balloon pulmonary angioplasty : Staged procedure with limited number of dilatation PA segments per session . Medical pre treatment is needed prior to BPA in Patients with PVR >4

56. Multimodal approach is needed as some patient have mixed anatomical lesion : surgical correctable lesion in one lung inoperable lesion in other .

57. Thanks