Screening and diagnosing PH - European Society of...
Transcript of Screening and diagnosing PH - European Society of...
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Screening and diagnosing PH
– still a challenge
Irene M Lang, MD, FESC
Professor of Vascular Biology
Department of Internal Medicine II, Division of Cardiology,
Medical University of Vienna, Austria
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Galiè N, et al. Eur Heart J 2009;30:2493-537.
CO: cardiac output
PAP: pulmonary arterial pressure
PCWP: pulmonary capillary wedge pressure
Definition Characteristics Clinical group(s)
PH Mean PAP ≥ 25 mmHg All
Pre-capillary PH Mean PAP ≥ 25 mmHg
PWP ≤ 15 mmHg
CO normal or reduced
1. PAH
3. PH due to lung disease
4. CTEPH
5. PH with unclear and/or
multifactorial mechanism
Post-capillary PH Mean PAP ≥ 25 mmHg
PWP > 15 mmHg
CO normal or reduced
2. PH due to LHD
Passive TPG ≤ 12 mmHg
Reactive (out of proportion) TPG > 12mmHg
Haemodynamic definition of PH
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1. Pulmonary Arterial Hypertension
• Idiopathic PAH
• Heritable PAH- BMPR-2 mutations- Alk-1/endoglin
- undefined
• Drug/toxin induced
• Related to:– Connective tissue diseases– schistosomiasis– HIV– Portal hypertension– systemic - to - pulmonary shunts– Hemolysis (SCD, thallassemia, PNH,
spherocytosis, stomatocytosis)
• PPHN
3. PH with Lung Diseases/Hypoxemia
• COPD
• Interstitial Lung Diseases
• Sleep-disordered breathing
• Hypoxia
4. CTEPH
Pulmonary Hypertension
Diagnostic Classification Dana Point 2008
5. Unclear or multifactorial mechanisms
•Hematologic
•Systemic
•Metabolic
•CHD other than systemic-to-pulmonary shunt
•others
1’. PVOD-PCH
2. PH with Left Heart Disease – systolic– diastolic– valvular
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Humbert et al. Eur Resp Rev. 2012; 21: 126, 306–312
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Screening
(early detection of PH)
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Who to screen?-1
• Prevalence of PAH in the general population
15–50 cases per million (0.0015–0.0050%)
• Prevalence of PAH in at risk populations
CHD: 4–15%
Systemic sclerosis: 8–10%
Portal hypertension: 0.5–10%
HIV: 0.5%
Sickle cell disease: 2%
BMPR2 mutation carriers: 20%
Prior appetite suppressant use (9.5%)
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Who to screen?-2
• Prevalence of CTEPH in the general population
3–30 cases per million (0.0003–0.0030%)
• Prevalence of CTEPH in at risk populations
after major symptomatic PE: 0.1–9.1%
after splenectomy: ~2.0%
in carriers of APL/LAK: ~2.0%
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Humbert et al. Eur Resp Rev. 2012; 21: 126, 306–312
Screened patients are different from
diagnosed patients
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100
90
80
70
60
50
40
30
20
10
0
0 1 3 5 8
Years of follow-up
100% 81%(IC 95% 51–93%)
73%(IC 95% 43–89%)
64%(IC 95% 33–84%)
75%(IC 95% 46–90%)
31%(IC 95% 11–54%)
17%(IC 95% 3–39%)
25%(IC 95% 8–47%)
P=0.0037
HR = 4.15
(95% CI 1.47–11.71
Su
rviv
al ra
te (
%)
Routine practice SSc-PAH patients
Detected SSc-PAH patients
Humbert et al. Arthritis Rheum. 2011 Nov;63(11):3522-30. doi: 10.1002/art.30541.
Early identification confers a benefit
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Histopathology of PAH (PPH):
plexogenic arteriopathy
Brenner et al, Arch Intern Med 1935; 56: 211-237, 457-497, 724-752, 976-1014, 1190-1241
Heath & Edwards, Circulation 1958; 18: 533-547 - Wagenvoort CA, Thorax 1994;49S:39-45
Early
Late
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Pulmonary artery pressure rise is a late event
Lau E M et al. Eur Heart J 2011;32:2489-2498
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Exercise-induced pulmonary hypertension
EI PH PAH normals
n=78 n=15 n=16
VO2max, %pred 67 16 56 20 92 14
PAP, mmHg 37 6 48 11 27 4
PVR, d.s.cm-5 161 60 294 258 62 20
Tolle et al, Circulation 2008;118: 2183 – 2189.
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0 4 8 12 16 20 24 28 320
10
20
30
40
Pulmonary blood flow, l.min-1
Pre
ssu
re, m
mH
g
Pap
P
w
Naeije et al J Appl Physiol 1993; 74: 1666-71
Papm > 30 mmHg
Pw > 15 mmHg
Levels of exercise in normal subjects
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Exercise haemodynamics in PAH
Castelain V et al. Am J Respir Crit Care Med 2002;165:338-340.
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Ideal screening test
–Sensitive
–Specific
–Non-invasive
–Widely available
–Inexpensive
–Able to detect disease at an early stage
Lau, et al. Eur Heart J (2011) 32 (20): 2489-2498.
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Established screening tools
• Resting echocardiography
• Pulmonary Function test
• Biomarkers
• V/Q
Neural networks
CART
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Maximum TRV values during hypoxia vs exercise
in relatives (yellow) and control subjects (blue)
Grünig E et al. Circulation 2009;119:1747-1757
During exercise, 32% of relatives but
only 10% of controls had TRV values
>3.08 m/s; and during hypoxia, 26% of
relatives had TRV values >3.08 m/s
compared with 10% of controls.
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Exercise echocardiography data represented as
multipoint pressure–flow relationship
Lau E M et al. Eur Heart J 2011;32:2489-2498
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The relationship between DLCO and the development
of SSc-associated PAH
Lau E M et al. Eur Heart J 2011;32:2489-2498
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Clinical suspicion
V/Q scan
CTEPH
ruled out
negative at least 1-2 segmental larger-sized defects
CTEPH likely
Right Heart Catheterization
and Pulmonary Angiography
Echo: TR >2.8m/s and >3 months of
effective anticoagulation
Indeterminate
CTEPH
uncertain
plus
Multidetector CT
Adapted from: Lang IM et al. JACC Cardiovasc Imaging. 2010;3:1287-95.
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La
ng e
t a
l.JA
CC
Card
iova
sc
Ima
gin
g. 2
01
0 D
ec;3
(12
):12
87
-95.
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La
ng e
t a
l.JA
CC
Card
iova
sc
Ima
gin
g. 2
01
0 D
ec;3
(12
):12
87
-95.
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ClassificAtion and Regression Tree
Parent F et al. N Engl J Med 2011; 365: 44–53.
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Baseline Year 1 Year 2Screening Year 3
Cross-sectional phase
To evaluate different
screening tests (individually
and combined) vs RHC for
PAH (primary objective) and
PH in SSc patients
Longitudinal cohort (follow-up)
To evaluate the incidence of PAH
and PH in a cohort of SSc patients
To determine the association of
potential prognostic or risk factors
(eg, biomarkers, 6MWD, PFTs etc)
and the development of PAH/PH
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Performance of an optimal screening tool
(96% sensitivity, 80% specificity)
Humbert, et al. Eur Respir Rev 2012; 21: 126, 306–312.
To detect one case of PAH-SCD: number needed to cath: 2.5
To detect one case of PAH-SLE: number needed to cath: 41
To detect one case of iPAH: number needed to cath: 101
To detect one case of CTEPH: number needed to cath: 50-500
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Diagnosis
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• L-S, 73-year old female
• SA: married, 1 daughter, retired,
• 162cm, 84kg
• Medical Hx: surgically corrected large ASD 1993 ablation of atrial fibrillation, pacemakerimplantation for Sick-Sinus-Syndrome, systemichypertension, hyperlipidemia, coronary disease
• Current medication: Phenprocoumon, Nicorandil10mg bid, Bisoprolol 5mg, Allopurinol 100mg, Escitalopram 10mg
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• NYHA III
• NT-BNP 3097pg/mL
• Echo sPAP 95mmHg
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precapillary PH?
RAP, mm Hg 32
PAPs/d-m, mmHg 110/44-73
PCWP, mmHg 40
TPG, mmHg 33
CO, L.min 6,1
CI, L.min.m² 2,5
PVR, WU (dyn.s.cm-
5)
5,9
(472)
SvO2, % 53
Hemodynamic parameters
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ECG
RVS
Precapillary PH likely
Patients with a clinical suspicion of precapillary PH
and TRV>2.8m/s
No RVS
NT-proBNP
Precapillary PH likelyPrecapillary PH unlikely
>80pg/mL≤ 80pg/mL
Bonderman, et al. Eur Resp J Eur Respir J. 2011 May;37(5):1096-103. doi: 10.1183/09031936.00089610.
Diagnosis tree based on echo, ECG and NT-BNP
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Factors increasing the likelihood of HF
with preserved EF (diastolic HF)
Eur Heart J 2009: 30: 2493-2537.
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• L-S, 73-year old female
• SA: married, 1 daughter, retired,
• 162cm, 84kg
• Medical Hx: surgically corrected large ASD 1993 ablation of atrial fibrillation, pacemakerimplantation for Sick-Sinus-Syndrome, systemichypertension, hyperlipidemia, coronary disease
• Current medication: Phenprocoumon, Nicorandil10mg bid, Bisoprolol 5mg, Allopurinol 100mg, Escitalopram 10mg
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HFPEF, Post-capillary
PH
RAP, mm Hg 32
PAPs/d-m, mmHg 110/44-73
PCWP, mmHg 40
TPG, mmHg 33
CO, L.min 6,1
CI, L.min.m² 2,5
PVR, WU (dyn.s.cm-
5)
5,9
(472)
SvO2, % 53
Hemodynamic parameters
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Galiè N, et al. Eur Heart J 2009;30:2493-537.
CO: cardiac output
PAP: pulmonary arterial pressure
PCWP: pulmonary capillary wedge pressure
Definition Characteristics Clinical group(s)
PH Mean PAP ≥ 25 mmHg All
Pre-capillary PH Mean PAP ≥ 25 mmHg
PWP ≤ 15 mmHg
CO normal or reduced
1. PAH
3. PH due to lung disease
4. CTEPH
5. PH with unclear and/or
multifactorial mechanism
Post-capillary PH Mean PAP ≥ 25 mmHg
PWP > 15 mmHg
CO normal or reduced
2. PH due to LHD
Passive TPG ≤ 12 mmHg
Reactive (out of proportion) TPG > 12mmHg
Haemodynamic definition of PH
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Diastolic Pressure Gradient
• DPG = dPAP - mPCWP
DPGDPG
normal values ≤5mmHg
DPG >5mmHg denotes pulmonary vascular disease
Buchbinder N and Ganz W. Anesthesiology 1976; 45(2): 146-55 Harvey RM, Enson Y and Ferrer MI. Chest 1971; 59(1): 82-94
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*
1.0
0.8
0.6
0.4
24 48 72 96 120 144 146
Time to last contact (months)
Cu
mu
lati
ve s
urv
ival
Pre-capillary
PH
PH due to
LHD with
TPG >12
& PVG
≥7mmHg
PH due to
LHD
(excluding
TPG >12 &
PVG
≥7mmHg)
Non-PH
*
0
DPG AND SURVIVAL
Gerges C et al. CHEST 2013; in press
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OOPPH in HFPEF,
low DPG
RAP, mm Hg 32
PAPs/d-m, mmHg 110/44-73
PCWP, mmHg 40
TPG, mmHg 33
DPG, mmHg 4
CI, L.min.m² 2,5
PVR, WU (dyn.s.cm-
5)
5,9
(472)
SvO2, % 53
A low DPG is a marker for a favorable prognosis
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►Resting echocardiography is currently the recommended
screening modality for high-risk population groups
►Exercise stress may unmask early pulmonary vascular
dysfunction but the definition, clinical significance, and
natural history of ‘exercise PAH’ remain undefined.
► Rise of resting PA pressures (and symptoms) are latesequelae of the pathobiological processes that begin in the distal pulmonary arteries
Screening and diagnosing PH
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► Early diagnosis of PAH is currently not possible
► A major contemporary diagnostic challenge is the distinction between pre- and postcapillary PH
Screening and diagnosing PH
– still a challenge
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Thank you for your attention