Pulmonal hypertensjon
Arne K. Andreassen
Kardiologisk avdeling, Rikshospitalet
Oslo Universitetssykehus
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
Hemodynamic definitions of PH by RHC
Definition
Characteristics
Clinical group(s)
Pulmonary hypertension
(PH)
Mean PAP ≥ 25 mmHg
All
Pre-capillary PH
Mean PAP ≥ 25 mmHg
PWP ≤ 15 mmHg
CO normal or reduced
1. Pulmonary arterial
hypertension
3. PH due to lung diseases
4. Chronic thromboembolic
PH
5. PH with other and/or
multifactorial mechanisms
Post-capillary
Mean PAP ≥ 25 mmHg
PWP ≥ 15 mmHg
CO normal or reduced
2. PH due to left heart
disease
Passive
Reactive (out of proportion)
TPG ≤ 12 mmHg
TPG ≥ 12 mmHg
PAP in healthy subjects
47 publications
1187 subjects
>50 yrs
18-30 yrs
Kovacs et al. Eur Respir J 2009; 34: 888-94
The pulmonary artery catheterright heart catheterization
Chatterjee K. Circulation 2009; 119: 147-52
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
2. PH due to left heart disease
2.1 Systolic dysfunction
2.2 Diastolic dysfunction
2.3 Valvular disease
RV failure added to LV failure
N = 377
VVEF < 35%
Ghio S et al. J Am Coll Cardiol 2001; 37: 183-8
PH in heart failure with preserved EF
Lam CS et al. J Am Coll Cardiol 2009; 53: 1119-26
LV dysfunction and development of
pulmonary hypertension
Moares DL et al. Circulation 2000; 102: 1718-23
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
1. Pulmonary arterial hypertension
1.1 Idiopathic
1.2 Heritable
1.2.1 BMPR 2
1.2.2 ALK 1, endoglin (with or without HHT)
1.2.3 Unknown
1.3 Drugs and toxins induced
1.4 Associated with (APAH)
1.4.1
1.4.2
1.4.3
1.4.4
1.4.5
1.4.6
Bindevevssykdommer
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
Patogenese ved PAH
Gaine S. JAMA 2000; 284: 3160-4
Ekkokardiografi og histologi
Survival in IPAH
Percentage surviving
Formula for survial:
100
A(x,y,z) = e(0.007352x + 0.0526y – 0.3275z)
80
Where x = MAP
y = RAP
z = CI
60
40
20
1
2
3
4
5
Years of follow-up
D`Alonzo GE et al. Ann Intern Med 1991; 115: 343-9
PAH: A progressive disease
Pre-symptomatic/
Compensated
Symptomatic/
Decompensating
Declining/
Decompensated
CO
Symptom Threshold
PAP
PVR
s
tom
p
Sym
Right Heart
Dysfunction
Time
Hill NS. Pulmonary Hypertension Therapy. 1st Ed. 2006:7-28
Prevalence of PAH
French PAH registry; 674 patients:
15 cases/million adult inhabitants
Scottish Morbidity Record Scheme:
52 cases/million
Σ: 25-50 cases/million inhabitants(?)
Humbert M et al. Am J Respir Crit Care Med 2006; 173: 1023-30
Clubbing in Eisenmenger syndrome
Digital Vascular Injury in Scleroderma
Diagnostic algorithm for PAH
McLaughlin VV et al. Circulation 2006; 114: 1417-31
Right-heart catheterization
Akutt vasodilatasjonstest
Respondere
Ikke – respondere
MAP og
PAR
reduseres
til nær normale
verdier
Ca-blokkere
Endotelinblokkere
PDE-5 blokkere
Prostaglandiner
Functional testing in PAH
Miyamoto S et al. Am J Respir Crit Care 2000; 161: 487-92
Wensel R et al. Ciculation 2002; 106: 319-24
NT-proBNP and survival
Andreassen AK et al. Am J Cardiol 2006; 98: 525-9
Targets for current therapies in PAH
Targeted drug therapy in Norway
Drug
NYHA-class
Dosage
Calcium channel blockers
Endothelin receptor antagonists
Ambrisentan
Bosentan
Sitaxentan
II, III
II, III
III
5-10 mg X 1
125 mg X 2
100 mg X 1
Phosphodiesterase type-5 inhibitors
Sildenafil
II, III
20 mg X 3
Prostanoids
Epoprostenol (iv)
Iloprost (inh)
Treprostinil (iv,sc)
III-IV
III-IV
III
15-50 ng/kg/min
10µg X 6-9 inh
20-50 ng/kg/min
Observed and estimated survival
in IPAH
N = 32
Andreassen AK et al Akseptert for Tisskr Nor Legeforen 2010
Baseline IPAH hemodynamics
RA (mmHg)
7±4
mPAP (mmHg)
57±13
PWCP (mmHg)
7±4
Svo2 (%)
59±9
HR (beats/min)
80±11
Sao2 (%)
94±3
CO (l/min)
3.3±0.9
CI (l/min/m2)
1.8±0.5
PVR (WU)
16.1±5.3
Peak VO2 (ml/kg/min)
11.7±4.3
NT-proBNP (pmol/l)
373±451
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 0.35-0.92;
p=0.023)
Galié N et al. Eur Heart J 2009; 30; 394-403
Lung transplantation
Trulock EP et al. J Heart Lung Transplant 2005; 24: 956-67
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
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
PH severity in emphysema
N = 215
mPAP = 27±8 mmHg
4% with mPAP > 45 mmHg
Thabut G et al. Chest 2005; 127: 1531-6
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
Pulmonary angiograms
Thrombendarterectomy
Fedullo PF et al. N Engl J Med 2001: 1465-72
Thrombendarterectomy
Auger W/Newman JH. Am J Resp Crit Care 2005; 172; 1072-7