PULMONARY HYPERTENSION BY DR CHARLES.pptx

Cardiology

1. Pulmonary Hypertension Dr Charles Okorie

2. Outline Introduction Classification Epidemiology Clinical features Investigations Treatment Prognosis

3. Introduction Pulmonary hypertension is defined by a mean pulmonary arterial pressure ( mPAP ) >20 mmHg at rest by RHC. Previous guidelines was 20mmHg but the reduction is to enhance early detection as delay in diagnosis has important implications for both quality of life and life span

4. According to different combinations of values of pulmonary wedge pressure, pulmonary vascular resistance and cardiac output; a hemodynamic classification of pHTN has been proposed; Postcapillary: Due to increase in pulmonary venous pressure seen in left-sided heart diseases. Precapillary: caused by pulmonary vascular remodeling leading to increased pulmonary vascular resistance. Differentiation between these 2 conditions is based on whether pulmonary artery wedge pressure (PAWP) or left ventricular (LV) end-diastolic pressure (LVEDP) is elevated >15 mm Hg.

5. The normal mean pulmonary artery pressure ( mPAP ) at rest is 14 ±  3.3  mmHg with an upper limit of normal of 20  mmHg. The normal values for mean capillary wedge pressure ( mPCWP ) and cardiac output (CO) are 6 ± 2 mmHg and 5 L/min, respectively. The fall in pressure across the lung circulation is known as the transpulmonary gradient and reflects the difference between mPAP and mPCWP . The normal transpulmonary gradient is 6 ±  2 mmHg. 08/02/2024 5

6. The pulm vascular resistance (PVR) is calculated by the formula: ( mPAP-mPWCP )/CO. It is normally about 1.5mmHg/L per min(1.5 Wood units) 08/02/2024 6

7. Exercise Pulmonary Hypertension Exercise PH, defined by an mPAP /cardiac output (CO) slope 3 mmHg/L/min between rest and exercise. The mPAP /CO slope is strongly age dependent and its upper limit of normal ranges from 1.6–3.3 mmHg/L/min in the supine position. A pathological increase in pulmonary pressure during exercise is associated with impaired prognosis in patients with exercise dyspnoea and in several cardiovascular conditions.

8. Classification

9. Classification contd.

10. Epidemiology Pulmonary hypertension is a major global health issue. All age groups are affected. Estimates suggest a PH prevalence of 1% of the global population. Due to the presence of cardiac and pulmonary causes of PH, prevalence is higher in individuals aged >65 years. Globally, LHD is the leading cause of PH. Lung disease, especially COPD is the second most common cause. In developing countries, CHD, some infectious diseases (schistosomiasis, HIV) and high altitude represent important but under-studied causes of PH.

11. Clinical features Dyspnoea- 60% Fatigue- 19% Near syncope/syncope- 13% Chest pain- 7% Palpitations- 5% Leg edema - 3% 08/02/2024 12

12. Signs Pulse- low volume carotid pulse with a normal upstroke Large a wave in the JVP, prominent v waves (severe PH) Left parasternal heave Palpable P2, loud P2 S4 of right ventricular origin S3 of RV origin (from pulm regurg or tricuspid regurg ) Tricuspid regurgitation is a reflection of right ventricular dilatation 08/02/2024 14

13. Later- signs of rt ventricular failure- hepatomegaly, peripheral edema , ascites- may be present Cyanosis- lung dx; reduced CO and systemic vasoconstriction with V/Q mismatch Ortner’s syndrome- left laryngeal nerve becomes paralysed as a result of compression by a dilated pulmonary artery 08/02/2024 15

14. Signs of disease severity Dyspnoea at rest Low cardiac output with metabolic acidosis Hypoxemia Signs of RV failure Syncope Chest pain (secondary to RV ischemia) 08/02/2024 16

15. Investigations Routine blood tests- serological screening for HIV, hepatitis and underlying autoimmune dx, renal and liver chemistry, thyroid function test, BNP Chest x-ray ECG Echocardiography CMR Pulmonary function tests Abdominal liver ultrasound Right heart catheterisation 08/02/2024 18

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17. CXR Chest radiography presents abnormal findings in most patients with PH; however, a normal chest X-ray does not exclude PH. Radiographic signs of PH include a characteristic configuration of the cardiac silhouette due to right heart (RA/RV) and PA enlargement, sometimes with pruning of the peripheral vessels. In addition, signs of the underlying cause of PH, such as LHD or lung disease, may be found

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21. ECG

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24. Echo

25. Echo contd.

26. Echo – probability of Phtn

27. Echo ( contd ) Also aids in determining the diagnosis in Type 2 PHTN and may also show signs suggestive of type 4. Mcconnel /60:60 sign

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32. Right Heart Catheterisation Gold standard Requires expertise and meticulous methodology following standardized protocols. Clinical indications include diagnosing and classifying PH, haemodynamic assessment of heart or LTx candidates evaluating congenital cardiac shunts. When performed in PH centres , the frequencies of serious adverse events (1.1%) and procedure-related mortality (0.055%) are low.

33. RHC contd Contraindications to RHC A known thrombus or tumour in the RV or RA Recently implanted (1 month) pacemaker, Mechanical right heart valve TriClip , Acute infection The most feared complication of RHC is perforation of a PA.

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35. Vasoreactivity testing The purpose of vasoreactivity testing in PAH is to identify acute vasoresponders who may be candidates for treatment with high-dose calcium channel blockers (CCBs). Pulmonary vasoreactivity testing is only recommended in patients with IPAH, HPAH, or DPAH. i.e Group 1 only! Inhaled nitric oxide or inhaled iloprost are the recommended drugs vasoreactivity testing. Adenosine i.v. is no longer recommended due to frequent side effects. A positive acute response is defined as a reduction in mPAP by ≥10 mmHg to reach an absolute value ≤40 mmHg, with increased or unchanged CO. In patients with PH-LHD, vasoreactivity testing is restricted to evaluating heart transplantation candidacy. in patients with PH in the context of CHD with initial systemic-to-pulmonary shunting, vasoreactivity testing can be performed to evaluate the possibility of defect closure

36. Cardiopulmonary exercise testing Cardiopulmonary exercise testing (CPET) is a useful tool to assess the underlying pathophysiologic mechanisms leading to exercise intolerance. Patients with PAH show a typical pattern, with a low endtidal partial pressure of carbon dioxide (PETCO2), high ventilatory equivalent for carbon dioxide (VE/VCO2), low oxygen pulse (VO2/HR) low peak oxygen uptake (VO2). These findings should prompt consideration of PVD. In patients with LHD or COPD, such a pattern may indicate an additional pulmonary vascular limitation.

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40. Non-contrast and contrast-enhanced chest computed tomography examination CT imaging may provide important information for patients with unexplained dyspnoea or suspected/confirmed PH. The CT signs suggesting the presence of PH include an enlarged PA diameter a PA-to-aorta ratio .0.9 and enlarged right heart chambers. A combination of three parameters (PA diameter ≥30 mm, RVOT wall thickness ≥6 mm, and septal deviation ≥140° [or RV:LV ratio ≥1] is highly predictive of PH.

41. Non-contrast chest CT can help determine the cause of PH when there are features of parenchymal lung disease. CTPA is mainly used to detect direct or indirect signs of CTEPH, such as filling defects (including thrombus adhering to the vascular wall), webs or bands in the PAs, PA retraction/dilatation, mosaic perfusion, and enlarged bronchial arteries. CTPA may also be used to detect other cardiovascular abnormalities, including intracardiac shunts, abnormal pulmonary venous return, patent ductus arteriosus and PAVMs.

42. Other Investigations Abdominal USS: Portal HTN; other intra abdominal complications.

43. Treatment - General measures It is recommended that they avoid pregnancy Immunisation against influenza and pneumococcal infection Psychological support Supervised exercise training, excessive physical activity is not recommended In-flight oxygen therapy should be considered for patients WHO FC 3 and 4 and those with Pao2 consistently 8kPa (60mmHg) In elective surgery, epidural rather than general anaesthesia is advised 08/02/2024 48

44. Supportive therapy Diuretics- typically to treat symptoms from rt heart failure; may need to combine classes; caution to avoid too much pre-load reduction Anticoagulants-studies show benefit in IPAH, based on improved survival. Generally, to keep INR btw 2.0-2.5 to lessen in-situ thrombosis Digoxin- increases CO by about 10%, reduces circulating norepinephrine Oxygen- to maintain oxygen saturation above 90% 08/02/2024 49

45. PAH SPECIFIC THERAPY 08/02/2024 50

46. Calcium channel blockers effective in high doses in selected patients with IPAH, assess response to therapy in 3-4months E.g amlodipine 20-30mg/day; nifedipine 180-240mg/day, diltiazem 720-960mg/day. When patients respond favourably, quality, quality of life is restored, with improved functional class and survival (94% at 5yrs) is improved when compared with nonresponders 08/02/2024 51

47. Prostanoids prostacyclin, produced by vascular endoth cells, has potent vasodilator and inhibits platelet aggregation and cell proliferation. Epoprostenol and selexipag are other examples- given by IV or subcute infusion or regular aerosol inhalation Complications- catheter related infections and pump malfunction Side effects- headache, flushing, diarrhoea, chronic foot pain, diffuse rash 08/02/2024 52

48. Prostanoids - continued Treprostinil - stable prostacycline analogue, longer halflife , given by continuous subcutaneous infusion, 75-150ng/kg/min; infusion site pain is common. Iloprost - approved for inhalational use, requires frequent inhalations; 2.5-5.0ug ampoules via a dedicated nebulizer that limits the dose of drug that can be delivered. Beraprost - orally active prostacycline analogue, only approved for use in Japan. In a European trial improved exercise capacity and symptoms over a 12 week period. 08/02/2024 53

49. Endothelin receptor antagonists Endothelin has vasoconstrictor and mitogenic effect and is activated in PAH Endothelin receptors A and B Bosentan is a dual antagonist, improves 6minute walk distance after 16weeks; approved dose- 125mg twice daily Selective A receptor antagonists ambisentran - 5-10mg daily, Sitaxsentran - 100mg daily, Side effects- peripheral edema ; liver toxicity; interaction with warfarin, cyclosporine, ketoconazole (CYP3A4 inhibitor), omeprazole (CYP2C19) 08/02/2024 54

50. Phosphodiesterase type 5 inhibitors Promote vasodilation in the pulmonary vasculature and reduce cellular proliferation by promoting an enhanced and sustained level of cGMP . Sildenafil has preferential effect on the pulm vasculature due to the high expression of the PDE5 isoform in the lung. PDE5 inhibitors may improve cardiac function by direct effects on the myocardium Sildenafil is given at 20mg tds but may be given in doses as high as 80mg tds with safety Tadalafil is long-acting, effective at 40mg daily Side effects- headache, flushing, nasal congestion 08/02/2024 55

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52. Surgical therapy Atrial septostomy Lung transplantation 08/02/2024 57

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54. prognosis Prognosis is variable and depends on the etiology , severity and treatment In the US, 5 year survival rate is 57% without treatment from the time of diagnostic RHC In general, male sex, age >50yrs, worse WHO functional status and right ventricular dysfunction confer a worse prognosis. For example pts with RSHF survive approx 1yr without treatment Since the introduction of better pharmacotherapy, scleroderma associated PAH, has seen an improved outcome. 08/02/2024 59

55. Conclusion Pulmonary hypertension is a hemodynamic syndrome that has various causes and requires a multi-pronged approach at management and hence the need for high index of suspicion for early diagnosis, prompt and appropriate therapy so as to improve the outcome. 08/02/2024 60

56. Thank you 08/02/2024 61