1. Pulmonal hypertensjon
Arne K. Andreassen
Kardiologisk avdeling
Oslo Universitetssykehus Rikshospitalet

2. Clinical classification of pulmonary hypertension
1. Pulmonary arterial hypertension (PAH)
2. Pulmonary hypertension due to left heart disease
3. Pulmonary hypertension due to lung diseases and/or hypoxia
4. Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions
5. Pulmonary hypertension with unclear and/or multifactorial mechanisms

3. Clinical classification of PH
Galie N, et al. Eur Heart J 2015; published August 29

4. Hemodynamic definitions of PH
Galie N, et al. Eur Heart J 2015; published August 29

5. Right heart catheterization (Swan-Ganz catheter)

6. Clinical classification of pulmonary hypertension
1. Pulmonary arterial hypertension (PAH)
2. Pulmonary hypertension due to left heart disease
3. Pulmonary hypertension due to lung diseases and/or hypoxia
4. Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions
5. Pulmonary hypertension with unclear and/or multifactorial mechanisms

7. Pulmonary arterial hypertension
Galie N, et al. Eur Heart J 2015; published August 29

8. Patogenese ved PAH
Gaine S. JAMA 2000; 284:

9. Survival in IPAH Percentage surviving Years of follow-up
Formula for survial:
A(x,y,z) = e( x y – z)
Where x = MAP
y = RAP
z = CI
100 80 60
Percentage surviving 40 20
Years of follow-up
D`Alonzo GE et al. Ann Intern Med 1991; 115: 343-9

10. Ekkokardiografi og histologi

11. Right-heart catheterization

12. Akutt vasodilatasjonstest
Respondere Ikke – respondere
MAP og
PAR
reduseres
til nær normale
verdier
Ca-blokkere Endotelinblokkere
PDE-5 blokkere
Prostaglandiner

13. Targets for current therapies in PAH

14. Targeted drug therapy in Norway
Drug NYHA-class Dosage
Calcium channel blockers
Endothelin receptor antagonists Ambrisentan II, III mg X 1 Bosentan II, III 125 mg X 2
Macitentan II, III 10 mg X 1
Phosphodiesterase type-5 inhibitors Sildenafil II, III 20 mg X 3
Tadalafil II, III 40 mg X 1
Soluble guanylate cyclase stimulators Riociguat II, III 2.5 mg X 3
IP-receptor stimulators Selexipag II, III mg X 2
Prostanoids Epoprostenol (iv) III-IV ng/kg/min
Iloprost (inh) III-IV 10µg X 6-9 inh
Treprostinil (iv,sc) III ng/kg/min
Andreassen AK et al Tidsskr Nor Legeforen 2011;131:1285-8

15. Observed and estimated survival in IPAH
Andreassen AK et al Tidsskr Nor Legeforen 2011; 131:

16. Meta-analysis of randomized trials in PAH
Duration 14.3 weeks
All-cause mortality
Among controls: 3.8%
Reduction in mortality: 43%
(RR 0.57; 95% CI ;
p=0.023)
Galié N et al. Eur Heart J 2009; 30;

17. Lung transplantation
Yusen RD, et al. J Heart Lung Transplant 2013; 32:

18. Clinical classification of pulmonary hypertension
1. Pulmonary arterial hypertension (PAH)
2. Pulmonary hypertension due to left heart disease
3. Pulmonary hypertension due to lung diseases and/or hypoxia
4. Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions
5. Pulmonary hypertension with unclear and/or multifactorial mechanisms

19. Left ventricular heart failure and PH
Rosenkranz S, et al. Eur Heart J 2016;37:942-54

20. RV failure added to LV failure
N = 377
VVEF < 35%
Ghio S et al. J Am Coll Cardiol 2001; 37: 183-8

21. Treatment algorithm for systolic heart failure
McMurray JJ. N Engl J Med 2010; 362:

22. Clinical classification of pulmonary hypertension
1. Pulmonary arterial hypertension (PAH)
2. Pulmonary hypertension due to left heart disease
3. Pulmonary hypertension due to lung diseases and/or hypoxia
4. Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions
5. Pulmonary hypertension with unclear and/or multifactorial mechanisms

23. Cor pulmonale
(WHO 1963): ”hypertrophy of the RV resulting from diseases affecting the function and/
or structure of the lungs, except when these pulmonary alterations are the result of
diseases that primarily affect the left side of the heart, as in congenital diseases”
Høyrekateterisering
(m/1 L O2)
RA (mmHg)
MAP (mmHg) 27
PCV (mmHg) 7
CI (L/min/m2) 2,2
PAR (WU) ,9
HR (min-1)
AP metn.(%) 57
Ao metn.(%) 90

24. COPD and PH Distribution of PH Partial pressures of O2 and CO2
LTx
Distribution of PH
Partial pressures of O2 and CO2
Accounted for mPAP variance
Survival
Andersen K, et al. J Heart Lung Transplant 2012;31:373-80

25. Clinical classification of pulmonary hypertension
1. Pulmonary arterial hypertension (PAH)
2. Pulmonary hypertension due to left heart disease
3. Pulmonary hypertension due to lung diseases and/or hypoxia
4. Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions
5. Pulmonary hypertension with unclear and/or multifactorial mechanisms

26. Pulmonary angiograms

27. Pulmonary endarterectomy

28. Long term outcome in CTEPH
Delcroix M, et al. Circulation 2016;133:859-71

29. Surgical specimen Type I disease (10 %) Type II disease (70 %)
Type III disease (20 %)
Madani M M and Jamieson SW. Advances in Pulmonary Hypertension 2007; 6(2): 83-91

30. CTEPH international registry – patient disposition
Pepke-Zaba J et al. Circulation 2011;124:

31. Heart 2013;99:1415–1420. doi:10.1136/heartjnl-2012-303549

32. BPA of occluded vessels

33. Hemodynamics pre- and post-PBA
Andreassen AK et al. Heart 2013;99:

34. RV following BPA: reverse remodeling

35. CT angiogram pre- and post BPA
Kataoka M et al. Circ Cardiovasc Interv 2012;5:

36. CHEST-1 (Riociguat: Adempas®)
Ghofrani H-A et al. N Engl J Med 2013;369:319-29

37. Clinical classification of pulmonary hypertension
1. Pulmonary arterial hypertension (PAH)
2. Pulmonary hypertension due to left heart disease
3. Pulmonary hypertension due to lung diseases and/or hypoxia
4. Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions
5. Pulmonary hypertension with unclear and/or multifactorial mechanisms

38. PH with unclear and/or multifactorial mechanisms
5.1 Hematological disorders: myeloprolifertaive
disorders, splenectomy, hemolytic anemia
5.2 Systemic disorders: sarcoidosis, pulmonary
Langerhans cell histiocytosis,
lymphangioleiomyomatosis, neurofibromatosis,
vasculitis
5.3 Metabolic disorders: glycogen storage disease,
Gaucher disease, thyroid disorders
5.4 Others: tumoral obstruction, fibrosing mediastinitis,
chronic renal failure on dialysis

39. PH with unclear and/or multifactorial mechanisms: tumoral obstruction
Freim Wahl SG et al. Tidsskr Nor Legeforen 2012;132:

40. Diagnostic algorithm for PH
McLaughlin VV et al. Circulation 2006; 114: