Pulmonal hypertensjon Arne K. Andreassen Kardiologisk avdeling Oslo Universitetssykehus Rikshospitalet

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

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

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

Right heart catheterization (Swan-Ganz catheter)

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

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

Patogenese ved PAH Gaine S. JAMA 2000; 284: 3160-4

Survival in IPAH Percentage surviving Years of follow-up Formula for survial: A(x,y,z) = e(0.007352x + 0.0526y – 0.3275z) Where x = MAP y = RAP z = CI 100 80 60 Percentage surviving 40 20 1 2 3 4 5 Years of follow-up D`Alonzo GE et al. Ann Intern Med 1991; 115: 343-9

Ekkokardiografi og histologi

Right-heart catheterization

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

Targets for current therapies in PAH

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 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 1600 mg X 2 Prostanoids Epoprostenol (iv) III-IV 15-50 ng/kg/min Iloprost (inh) III-IV 10µg X 6-9 inh Treprostinil (iv,sc) III 20-50 ng/kg/min Andreassen AK et al Tidsskr Nor Legeforen 2011;131:1285-8

Observed and estimated survival in IPAH Andreassen AK et al Tidsskr Nor Legeforen 2011; 131: 1285-8

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 0.35-0.92; p=0.023) Galié N et al. Eur Heart J 2009; 30; 394-403

Lung transplantation Yusen RD, et al. J Heart Lung Transplant 2013; 32: 965-78

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

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

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

Treatment algorithm for systolic heart failure McMurray JJ. N Engl J Med 2010; 362: 228-38

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

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/m2) 2,2 PAR (WU) 4,9 HR (min-1) 84 AP metn.(%) 57 Ao metn.(%) 90

COPD and PH Distribution of PH Partial pressures of O2 and CO2 LTx 1991-2010 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

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

Pulmonary angiograms

Pulmonary endarterectomy

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

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

CTEPH international registry – patient disposition Pepke-Zaba J et al. Circulation 2011;124:1973-81

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

BPA of occluded vessels

Hemodynamics pre- and post-PBA Andreassen AK et al. Heart 2013;99:1415-20

RV following BPA: reverse remodeling

CT angiogram pre- and post BPA Kataoka M et al. Circ Cardiovasc Interv 2012;5:756-762

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

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

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

PH with unclear and/or multifactorial mechanisms: tumoral obstruction Freim Wahl SG et al. Tidsskr Nor Legeforen 2012;132:1877-80

Diagnostic algorithm for PH McLaughlin VV et al. Circulation 2006; 114: 1417-31