1. Pulmonary HypertensionBy
Dr Sajid Ali
MO/PGR
Pulmonology
SZMC/H RYK

2. A 24 year old girl from Quetta presented with 6 months history of exertional dyspnoea and chest pain.a cardiologist ruled out cardiac cause for the dyspnoea and reffered to you because echocardiography showed markely elevated pulmonary arterial pressure,
What two furhter investigation would you like to do in this patient.
Name five medicine which are valuable in the management of pulmonary hypertention.

3. Two investigations
HRCT with contrast
Right cardiac cathetrization

4. Five valuable drugs.
Diuretics
Calcium channel blockers
Prostcycline antalogs(Epoprostenol (Flolan)., Treprostinil, Iloprost)
Endothelin receptor antagonists(Bosentan)
Phoshodiesterase inhibitors(sildenafil)

5. Pulmonary Hypertension
It is defined as a mean pulmonary artery pressure greater than 25mmHg at rest, or greater than 30mmHg with exercise.

6. CorPulmonale
It is an enlargement of the right ventricle due to derangements in the structure or function of the respiratory system. Cor pulmonale is a complication of pulmonary hypertension.

7. Clinical Classification of Pulmonary Hypertension
Group 1. Pulmonary arterial hypertension (PAH)
Idiopathic PAH
Familial PAH
Associated with (APAH):
Collagen vascular disease
Congenital systemic to pulmonary shunts (large, small, repaired, or non repaired)
Portal hypertension
HIV infection
Drugs and toxins
Other (glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies,myeloproliferative disorders, splenectomy)
Associated with significant venous or capillary involvement
Pulmonary veno-occlusive disease
Pulmonary capillary hemangiomatosis

8. Clinical Classification of Pulmonary Hypertension
Group 2. Pulmonary venous hypertension
Left-sided atrial or ventricular heart disease
Left-sided valvular heart disease
Group 3. Pulmonary hypertension associated with hypoxemia
COPD
Interstitial lung disease
Sleep-disordered breathing
Alveolar hypoventilation disorders
Chronic exposure to high altitude

9. Clinical Classification of Pulmonary Hypertension
Group 4. Pulmonary hypertension due to chronic thrombotic and/or embolic disease
Thromboembolic obstruction of proximal pulmonary arteries
Thromboembolic obstruction of distal pulmonary arteries
Pulmonary embolism (tumor, parasites, foreign material)
Group 5.Miscellaneous
Sarcoidosis, histiocytosis X, lymphangiomatosis, compression of pulmonary vessels (adenopathy, tumor, fibrosing
mediastinitis)

10. Functional Classification of Pulmonary hypertention
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.

11. Functional Classification of Pulmonary hypertention
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

12. Risk Factors of Pulmonary Hypertension
Drugs and toxins
Definite
Aminorex
Fenfluramine
Dexfenfluramine
Toxic rapeseed oil
Very likely
Amphetamines
L-Tryptophan
Possible
Meta-amphetamines
Cocaine
Chemotherapeutic agents
Unlikely
Antidepressants
Oral contraceptives
Estrogen therapy
Cigarette smoking

13. Risk Factors of Pulmonary Hypertension
Demographic and medical conditions
Definite
Gender
Possible
Pregnancy
Systemic hypertension
Unlikely
Obesity

14. Risk Factors ofPulmonary Hypertension
Diseases
Definite
HIV infection
Very likely
Portal hypertension/liver disease
Collagen vascular diseases
Congenital systemic-pulmonary-cardiac shunts
Possible
Thyroid disorders

15. Proposed pathogenesis of PAH.

16. FIGURE Pulmonary arteriole showing the medial hypertrophy
and concentric intimal narrowing that occur as a result of vascular
remodeling in pulmonary arterial hypertension.

18. Examination Cyanosis clubbing Raised JVP, with giant V waves
Right ventricular heave and tapping apex beat
Wide splitting of S2 with loud P2
Murmur of tricuspid regurgitation
Hepatomegaly
Ascites
Peripheral oedema.

19. Evaluation of Patients with Pulmonary Hypertension
Detection of
pulmonary
hypertension
Detailed history and physical examination
Electrocardiogram
Chest radiograph
Echocardiogram (at rest, to consider repeat
with exertion)
Suspicion of pulmonary hypertension and
possible causes/association
Exclude other causes of cardiopulmonary
Symptoms
Evaluate for presence of pulmonary
hypertension, assess chamber sizes and
function, valvular abnormalities, contrast
(“bubble”) study to evaluate possible shunt

20. Essential testing Pulmonary function testing Overnight oximetry
Lung (V/Q) scan
Blood serologies (e.g., CBC, liver function,
renal function, HIV, ANA,
antiphospholipid antibodies)
Oxygen desaturation study
6-Minute walk test
Right cardiac catheterization
Exclude instrinsic lung disease
Screen for sleep disordered breathing
Exclude thromboembolism
Exclude collagen vascular
disease, liver
disease, infection and other possible causes
of pulmonary hypertension
Assess need for supplemental oxygen (rest and exertion)
Establish baseline
Confirm diagnosis, assess other cardiac causes
(shunt); consider left heart catheterization)

21. Contingent testing Transesophageal echocardiogram C.T scan chest
Polysomnogram
Pulmonary angiogram
Lung biopsy
Assess patent foramen ovale (PFO)
Characterize valvular function
Assess interstitial lung disease, adenopathy
Diagnosis and treatment of sleep-disordered
Breathing
Assess presence and location of clot and
suitability for pulmonary
Thromboendarterectomy
Exclude subtle interstitial lung disease
vasculitis and other uncommon diseases
(PVOD, PCH) to assist planning

23. Diagnosis Electrocardiogram.
Abnormal in85% of patients with established PAH.
Right-axis deviation with evidence of right ventricular and/or right atrial hypertrophy and right ventricular strain.

25. Chest Radiography
Shows abnormalities in more than 90% of patients with idiopathic PAH.
Prominence of the main pulmonary arteries (90%)
Enlargement of the hilar vessels (80%)
Peripheral pruning (51%)

26. FIGURE Chest radiograph in pulmonary arterial hypertension.
Enlargement of the proximal pulmonary arteries .

28. FIGURE Chest radiograph in pulmonary arterial hypertension.
Enlargement of the proximal pulmonary arteries .

29. High-Resolution Computed Tomography.
exclude parenchymal lung disease as the cause of the PAH.
HRCT is particularly important in the diagnosis of PVOD.

30. Continuous Volume (Spiral) CT Pulmonary Angiography
Pulmonary angiography is considered the “gold standard” for the investigation of patients with CTEPH

31. Spiral computed tomography with contrast
Spiral computed tomography with contrast. A, Massive filling defect in the main pulmonary artery (arrow). B, Filling defects in lobar (large arrow) and segmental (small arrows) pulmonary arteries

32. Spiral CT scan (2-mm collimation, pitch of 2, 24% iodinated contrast agent) obtained at the level of the right upper lobe in a 65-year-old patient with acute onset of dyspnea.
Spiral CT scan (2-mm collimation, pitch of 2, 24% iodinated contrast agent) obtained at the level of the right upper lobe in a 65-year-old patient with acute onset of dyspnea. There are multiple partial filling defects at the level of the anterior (arrowhead) and posterior (arrow) segmental arteries of the right upper lobe. Note the additional presence of bilateral pleural effusion.
Remy-Jardin M , Remy J Radiology 1999;212:
©1999 by Radiological Society of North America

33. Pulmonary angiograms. A, Normal and, B, in pulmonary arterial hypertension, with marked pruning of peripheral vasculature.

34. Echocardiography. The screening tool of choice for PAH.
LV dysfunction/valve abnormalities
Intracardiac shunt
RVSP and RH function

35. Severe right chamber dilation

36. Ventilation and Perfusion ( V/Q) Lung Scanning
FIGURE Normal ventilation scans. C and D, Multiple segmental (or larger) defects oncorresponding perfusion scans.

37. Cardiac Magnetic Resonance Imaging (MRI)
Most accurate than echocardiography .
Accurate estimates of ventricular size and mass, as well as pulmonary blood flow.
Cardiac MRI is now used to monitor disease-targeted therapy

38. Biomarkers Brain natriuretic peptide (BNP)
Elevated in idiopathic PAH and associated with interstitial lung disease, COPD, congenital heart disease, CTEPH, and scleroderma.

39. Evaluation of Functional Class and Severity of PAH
6MWT.
Cardiopulmonary Exercise Testing (CPET).
Right Heart Catheterization

40. Management

41. General management. Education Long-term oxygen Diuretics and digoxin
Anticoagulation

42. vasodilator therapy Vasodilator responsiveness. Responders
non-responders

43. CalciumChannel Blockers
CCBs are used in higher doses then systemic hypertention and coronary heart disease.
240 mg/day of nifedipine or 900 mg/day of diltiazem can be tolerated with careful monitoring.
Verapamil has significant negative inotropic effects and should be avoided

44. Disease-Targeted Therapies
Prostacyclin (and analogs)
Endothelin receptor antagonists
Phosphodiesterase inhibitors

45. Prostacyclin and Analogs
PAH have deficient production of prostacyclin.
very short circulating half-life, a continuous intravenous infusion is necessary,
Epoprostenol (Flolan)., Treprostinil, Iloprost

46. Endothelin Receptor Antagonist
A Bosentan novel oral endothelin receptor A and B antagonist.
Sitaxsentan,an ET-A receptor antagonist recently improved for class III patients.

47. Phosphodiesterase Inhibitors
Inhibition of type 5 PDEs with selective drugs, such as sildenafil, increase cyclic GMP and induce a fall in intracellular calcium concentration with consequent vasodilatation.

50. Surgical treatments
Balloon Atrial Septostomy .
Lung Transplantation