Pulmonal hypertensjon. Arne K. Andreassen Kardiologisk avdeling Oslo Universitetssykehus Rikshospitalet
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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 hypoxemia 4. Pulmonary hypertension due to chronic thromboembotic and/or embolic disease 5. Pulmonary hypertension with unclear and/or multifactorial mechanisms
3 Hemodynamic definitions of PH by RHC Definition Characteristics Clinical group(s) Pulmonary hypertension Mean PAP 25 mmhg All (PH) Pre-capillary PH Mean PAP 25 mmhg 1. Pulmonary arterial PWP 15 mmhg hypertension CO normal or reduced 3. PH due to lung diseases 4. Chronic thromboembolic PH 5. PH with other and/or multifactorial mechanisms Post-capillary Mean PAP 25 mmhg 2. PH due to left heart PWP 15 mmhg disease CO normal or reduced Passive Reactive (out of proportion) TPG 12 mmhg TPG 12 mmhg
4 Right heart catheterization (Swan-Ganz catheter)
5 Diagnostic algorithm for PH McLaughlin VV et al. Circulation 2006; 114:
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 hypoxemia 4. Pulmonary hypertension due to chronic thromboembotic and/or embolic disease 5. Pulmonary hypertension with unclear and/or multifactorial mechanisms
7 1. Pulmonary arterial hypertension 1.1 Idiopathic 1.2 Heritable BMPR ALK 1, endoglin (with or without HHT) Unknown 1.3 Drugs and toxins induced 1.4 Associated with (APAH) Connective tissue diseases HIV infection Portal hypertension Congenital heart disease Schistosomiasis Chronic hemolytic anemia 1.5 Persistent pulmonary hypertension of the newborn 1` Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis
8 Survival in IPAH Formula for survial: A(x,y,z) = e ( x y z) Where x = MAP y = RAP z = CI Percentage surviving Years of follow-up D`Alonzo GE et al. Ann Intern Med 1991; 115: 343-9
9 Patogenese ved PAH Gaine S. JAMA 2000; 284:
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 5-10 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 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:
15 Observed and estimated survival in IPAH N = 32 Andreassen AK et al Tidsskr Nor Legeforen 2011; 131:
16 Meta-analysis of randomized trials in PAH Trials: 21 N=3140 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 Christie JD et al. J Heart Lung Transplant 2011; 30:
18 WHO`s inndeling av pulmonal hypertensjon 1. Pulmonary arterial hypertension 2. Pulmonary hypertension with left heart disease 3. Pulmonary hypertension associated with lung disease and/or hypoxemia 4. Pulmonary hypertension resulting from chronic thromboembolic and/or embolic disease 5. Pulmonary hypertension with unclear and/or multifactorial mechanisms
19 RV failure added to LV failure N = 377 VVEF < 35% Ghio S et al. J Am Coll Cardiol 2001; 37: 183-8
20 Medikamentell behandling av venstresidig hjertesvikt 1. ACE-hemmere Ved ejeksjons- Alle pasienter som tolererer ACE-hemmere fraksjon <40% 2. Diuretika Vanligvis sammen med ACE-hemmer 3. Betablokkere Alle stabile pasienter med svikt på bakgrunn av koronarsykdom eller kardiomyopati 4. Digitalis Ved atrieflimmer Ved sinusrytme og atrieflimmer når annen behandling ikke gir tilstrekkelig effekt 5. Aldosteron- Lav dose spirinolakton antagonister (12,5-25 mg) kan gis 6. Langtidsvirkende Ved angina pectoris, Høy dose kan forsøkes nitrater vanlig dose 7. Acetylsalicylsyre Ved koronarsykdom (75 mgx1) 8. Warfarin Ved dilatert kardiomyopati, atrieflimmer og evt. VV-aneurisme, påviste ventrikkeltromber og etter infarkt 9. Statin Ved koronarsykdom NYHA klasse I II III IV
21 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 hypoxemia 4. Pulmonary hypertension due to chronic thromboembotic and/or embolic disease 5. Pulmonary hypertension with unclear and/or multifactorial mechanisms
22 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) 6 MAP (mmhg) 27 PCV (mmhg) 7 CI (L/min/m 2 ) 2,2 PAR (WU) 4,9 HR (min -1 ) 84 AP metn.(%) 57 Ao metn.(%) 90
23 PH severity in emphysema N = 215 mpap = 27±8 mmhg 4% with mpap > 45 mmhg Thabut G et al. Chest 2005; 127:
24 PAH and combined emphysema and lung fibrosis N = 61 PAH- PAH+ Cottin V et al. Eur Respir J 2005; 26:
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 hypoxemia 4. Pulmonary hypertension due to chronic thromboembotic and/or embolic disease 5. Pulmonary hypertension with unclear and/or multifactorial mechanisms
26 Pulmonary angiograms
27 Pulmonary endarterectomy
28 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
29 CTEPH international registry patient disposition Pepke-Zaba J et al. Circulation 2011;124:
30 Heart 2013;99: doi: /heartjnl
31 BPA of occluded vessels
32 Hemodynamics pre- and post-pba Andreassen AK et al. Heart 2013;99:
33 CT angiogram pre- and post BPA Kataoka M et al. Circ Cardiovasc Interv 2012;5:
34 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 hypoxemia 4. Pulmonary hypertension due to chronic thromboembotic and/or embolic disease 5. Pulmonary hypertension with unclear and/or multifactorial mechanisms
35 PH with unclear and/or multifactorial mechanisms 5.1 Hematological disorders: myeloprolifertaive disorders, splenectomy 5.2 Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis 5.3 Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disoreders 5.4 Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis
36 PH with unclear and/or multifactorial mechanisms: tumoral obstruction Freim Wahl SG et al. Tidsskr Nor Legeforen 2012;132:
37 Prognostic factors in PAH McLaughlin VV, McGoon MD. Circulation 2006; 114:
38 Early RV impairment in COPD Hilde JM et al. J Am Coll Cardiol 2013;62:
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