Transcript Diapositiva 1

Società Italiana di Ecografia Cardiovascolare
XV Congresso Nazionale Ecocardiografia – Napoli, Aprile 2011
Ecostress ed Ipertensione Arteriosa Polmonare
Utilità e Limiti
Eduardo Bossone, MD, Ph.D, FESC, FACC
Cardiology Division Cava de’ Tirreni and Amalfi Coast
University of Salerno, Italy
Vietri sul Mare, Amalfi Coast, Italy
Background
The pulmonary circulation is characterized by high flow and
by low pressure and low resistance, one-tenth of systemic
vascular resistance.
mPAP = PVR x Q + LAP
Background
Linear regressions relating mPAP to Q: on average, each liter per minute of
increase Q is accompanied by 1 mmHg increase in mPAP in young adult
men and women. Aging to 60-80 years was found to be associated with a
more than doubling of the slope of mPAP-Q relationships.
In young adults:
mPAP - Q  1 mmHg.min.L-1
In old adults:
mPAP - Q  2.5 mmHg.min.L-1
Reeves JT, Dempsey JA, Grover RF. Pulmonary circulation during exercise. In: Pulmonary Vascular Physiology
and Physiopathology. Edited by Weir EK and Reeves JT. New York, Marcel Dekker, 1989, chap 4, pp 107-133.
Hemodynamic Values for Normal Adult Males
at Rest and Moderate Exercise
REST
Cardiac output (liters/min)
Heart rate (beats/min)
Right atrial pressure (mmHg)
Pulmonary artery pressure (mmHg)
Systolic
Diastolic
Mean
Pulmonary wedge pressure (mmHg)
Systemic arterial pressure (mmHg)
Mean
Pulmonary vascular resistance (units)
6
80
4-6
20-25
10-12
14-18
6-9
20/180
90/100
0.70-0.95
EXERCISE
16
130
6-8
30-35
11-14
20-25
10-12
150/95
110/120
0.60-0.90
Relation between Pulmonary Artery Systolic Pressure and Age and BMI
The upper limit of PASP is
dependent on Age, Sex,
and BMI and may include
40 mmHg in some older
or obese subjects.
McQuillan BM. et al. Circulation 2001;104:2797-2802.
Reference Ranges for Normal Systolic Pressure Gradients Assessed
with Doppler between RV and RA (TIPG)
95% CI for TIPG (mmHg)
Age (yrs)
n
Women (n = 2,065)
Men (n = 1,147)
<20
865
8.6-24.2
8.2-26.2
20-29
669
9.2-24.4
9.9-26.3
30-39
650
9.3-25.7
8.7-27.5
40-49
494
9.9-27.5
9.1-28.3
50-59
344
10.2-29.4
11.0-30.6
>60
199
10.5-32.1
11.2-33.6
McQuillan BM. et al. Circulation 2001;104:2797-2802
STRENGTH ATHLETES
ENDURANCE ATHLETES
3,00
2,80
2,60
r = 0.64;
2,40
TRV (m/sec)
p<0.0001
p<0.0001
2,60
2,20
2,40
2,00
2,20
1,80
2,00
1,60
1,80
1,40
92,00
94,00
r = 0.59;
96,00
98,00
100,00
102,00
LV STROKE VOLUME (ml)
104,00
106,00
64,00
66,00
68,00
70,00
72,00
74,00
LV STROKE VOLUME (ml)
Also age (p<0,01), duration of training (p<0,01) and resistance training (p<0,01) were independent
predictors of TRV at the multivariate analysis.
D’Andrea A, Naeije R, D’Alto M, and Bossone E. Chest 2010.
76,00
*p < 0.01: endurance vs. strength and controls
Pulmonary Artery Systolic Pressure
in Highly-Trained Athletes *
Variable
TRV (m/sec)
PASP (mmHg)
Stroke Volume (ml)
Cardiac Index (ml/min/m2)
Peak E / Ea ratio
TRV/RVOTTVI (m/s/cm)
Controls (n=230)
Strength (n= 245)
Endurance (n=370)
1.8  0.7 (1.3-2.4)
1.9 0.5 (1.5-2.6)
2.30.5* (1.9-2.9)
17.6  4.6 (14 – 33)
19.4  8.1 (14 – 36)
26.1  6.6* (19 – 39)
63.4  5.9
69.43.3
98.4 6.2*
2.30.6
2.40.3
2.80.7*
5.5  1.5
5.3  1.3
0.12  0.04 (0.07 – 0.16)
0.13  0.05 (0.09 – 0.18)
4.9  1.4
0.13  0.04 (0.07 – 0.15)
*p < 0.01: endurance vs. strength and controls.
D’Andrea A, Naeije R, D’Alto M, and Bossone E. Chest 2010
Pulmonary Artery Systolic Pressure Response to Exercise:
The Physiologic Range
Physiology:
Pulmonary resistance
LV filling pressure
Cardiac Output
Bossone E. et al. J Am Coll Cardiol.1999; 33:1662-6.
Left Ventricular Filling Pressure during Exercise
A Cardiological Blind Spot
John B West, Chest 1998
Intense exercise
Increased cardiac output
Decreased pulmonary vascular resistance
Increased left ventricular filling pressure
Increased pulmonary artery pressure
Stress failure of pulmonary capillaries
Exercise - induced pulmonary hemorrhage
Pulmonary Artery Systolic Pressure Response to Exercise:
The Physiologic Range
Bossone E. et al. J Am Coll Cardiol.1999; 33:1662-6.
Pressure-Fow (P-Q) Relationship
The best adjustment for the
individual mPAP-Q relationships
was slightly curvilinear with a
distensibility alpha of
α = 1.7  1.8 %/mmHg
This result is in perfect
agreement with previous in vitro
and
invasive
in
vivo
measurements
Reeves JT et al. Am J Physiol Lung Cell Mol
Physiol. 2005; 288: L419-25.
Argiento P. et al. Eur Respir J. 2009; 35:1273-8.
Plots of increase in right ventricular systolic
pressure from rest to peak exercise on
room air in 11 normal control subjects (top
graph), 9 pts (COPD) with normal (≤ 30
mmHg) resting values for RVSP (middle
graph), and 23 pts with pulmonary
hypertension at rest (bottom graph). The
extent of increase in RVSP with exercise is
similar in group A and B pts and is
significantly graeter than control pts.
Himelman RB. et al. Circulation 1989;79:863-871.
Pulmonary Pressure Response to Ex-Doppler Echocardiography
in Patients with High Risk of PAH
Author
Year
Associated Disease
Patients/Gender
Age (years) Ex ercice protocol
H(cm)/W(kg)
RAP estimate
(mmHg)
Baseline PAPs
(mmHg)
Himelman et al.
1989
Oelberg et al.
1998
GrŸniget al.
2000
GrŸniget al.
2000
Collins et al.
2005
Alkotob et al.
2006
Kiencke et al.
2008
Steen et al.
2008
GrŸnig et al.
2009
Reichenberger et al.
2009
Mšller et al.
2010
Kovacs et al.
2010
DÕAlto et al.
2011
COPD
(n= 36; 15 female )
Asyntomatic ASD
(n= 10; 4: female)
HAPE-S
(n= 9 male)
Relatives of iPAH cases
(n= 52)
Scleroderma
(n= 51; 49 female)
Scleroderma
(n=65; 56 female)
HAPE-S
(n= 10)
Scleroderma
(n= 54; 51 female)
Relatives of iPAH cases
(n= 291; 125 female)
Scleroderma
(n= 33; 31 female)
ASD and VSD
(n= 44; 25 female)
Connective tissue disease
(n=52; 42 female)
Systemic Sclerosis (SS)
(n=172;155 female)
32-80
52.9 ± 11.2
167±7/82±20
45 ± 8
182±8/82±9
-
fro m IVC
46 ± 20
22 ± 4 (ctrl.)
31 ± 8
17 ± 8 (ctrl.)
28 ± 4
27 ± 4 (ctrl)
24 ± 4 (n.r.)
23 ± 3 (a.r.)
24 ± 8
83±30
31± 7
51±10
19±8
55±11
36 ± 3
37 ± 3 (n.r)
56 ± 11(a.r)
38 ± 12
25 ± 8
39 ± 8
19 ± 4
17± 3 (ctrl.)
34.5 ± 11.5
23±6
11±5
51.4
20.7±5.4
20.4±5.3 (ctrl.)
23 ± 8
39.5 ±5.6
35.5±5.4
40 ± 11
20.7±5,3
21.8±3.6 (ctrl.)
27±5 *
23±3 23±3à
26.2±5.3
20.6±3.7 (ctrl.)
37 (24-76)
39 (17-63)
55±10*
29±8 30±7à
36.9±8.7
25.9±3.3
Supine bicycle
(10 or 25 W/ 2 in.)
Upright bicycle
(10 W/2 in.)
Supine bicycle
(25 W/2 in.)
Supine bicycle
(25 W/2 in.)
53.9 ± 12.0
Treadmill
MET s 5.9 ± 1.9
51±12
Treadmill
METs 1 to 13.4
33 ± 2
supine bicycle
Treadmill
85% pred. max HR
37 ± 16
Supine bicycle
169±9/69 ±15 (25 W/2 in.)
54 ± 11
Supine bicycle
(30 W/2 in.)
17.5±3.3
Supine bicycle
167±8.8/59±11 (25 W/2 in.)
54±11
Supine bicycle
167±8/ 69±12 (25W /2 in.)
51.8±21.5
Supine bicycle
163±9/ 66 ±14 (25W /2 in.)
fro m IVC
Fixed value
(5 mmHg)
Fixed value
Fixed value
(10 mmHg)
Fixed value
(5 mmHg)
Fixed value
(10 mmHg)
fro m IVC
fro m IVC
fro m IVC
fro m IVC
fro m IVC
Peak PAPs
(mmHg)
Pulmonary Arterial Pressure Responses to Exercise.
Lewis GD. Advances in Pulmonary Hypertension. Summer 2010; Vol 9, N°2.
PAP-Flow Relationships based on serial measurements
of mPAP and CO during incremental exercise
Lewis GD. Advances in Pulmonary Hypertension. Summer 2010; Vol 9, N°2.
Clinical Assessment - ECG - Chest X- ray
Suspect PHtn
TTE – Doppler
Six month follow-up
-
Exercise TTE- Doppler
+
+
RIGHT HEART CATHETIRIZATION
ACUTE VASOREACTIVITY TESTING
Bossone E. et al. Echocardiography in pulmonary arterial hypertension: An essential tool. Chest 2007;131:339-41.
Who to screen for Ex-PHtn
•
•
•
•
•
•
Chronic obstructive pulmonary disease;
Heart transplantation;
Susceptibility to high altitude pulmonary edema;
Congenital heart disease;
Trombo-embolic pulmonary hypertension;
Scleroderma and relatives of patients with PAH.
Conclusions and Future Directions
• Exercise stress tests of the pulmonary circulation show promise for
the detection of early or latent pulmonary vascular disease, and may
help to understand the clinical evolution and effects of treatments in
patients with established disease.
• While the exercise stress test based solely on systolic PAP and
workload measurements may show interest in screening programs,
the approach is unsatisfactory because PAP is a flow-dependent
variable, and the cardiac output achieved at a give workload varies
from one subject to another .
Conclusions and Future Directions
• Furthermore, the maximum velocity of TR is markedly dependent on
stroke volume, so that a systolic PAP higher than 40 mmHg is easily
achieved by exercising athletes in whom this cut-off value is very
close to the upper limit of normal at rest . Systolic PAP increases in
the elderly, with an increased in BMI, , and in relation to decreased
left ventricular diastolic compliance and associated increase in LAP.
• Knowledge of the limits of normal and further validation of non
invasive approaches in various patient populations are needed.
Amate il Paese ove la Natura Vi ha fatto Nascere
e seconderete le Leggi dell’ Universo
Socrate agli Ateniesi
Atrani, Amalfi Coast,
Italy
Arrivederci!!!
Clinical Studies using Ex-Echo in the Setting of PAH
Author
Population
Ex. protocol
Baseline PAPs
(mmHg)
Peak PAPs
(mmHg)
Himelman et al.
COPD (n=36)
Supine bicycle 10/25W
46 ± 20 (COPD)
22 ± 4 (CRTL)
83 ± 30 (COPD)
31 ± 7(CRTL)
Oelberg et al.
ASD (n=10)
Upright bicycle
31 ± 8 (ASD)
17 ± 8 (CRTL)
51 ± 10 (ASD)
19 ± 8(CRTL)
Grunig et al.
HAPE-S (n=9)
Supine bicycle 25 W
28 ± 4 (HAPE-S)
27 ± 4 (CRTL)
55 ± 11 (HAPE-S)
36 ± 3 (CRTL)
Alkotob et al.
Scleroderma (n=65)
Treadmill
25 ± 8
39 ± 8
Collins et al.
Scleroderma (n=51)
Treadmill
24 ± 8
38 ± 12
Grunig et al.
Relatives of iPAH (n=52)
Supine bicycle 25 W
24 ± 4 (NR)
23 ± 3 (AR)
37 ± 3 (NR)
56 ± 11 (AR)
Modify from Vachiéry JL. and Pavelescu A. Eur Heart J. H28-H53, 2007.
Abnormal Pulmonary Artery Pressure Response in Asymptomatic Carriers of Primary
PulmonaryHypertension Gene
Grünig E. et al. , Circulation 2000;102:1145-1150.
Società Italiana di Ecografia Cardiovascolare
XV Congresso Nazionale Ecocardiografia – Napoli, Aprile 2011
Ecostress ed Ipertensione Arteriosa Polmonare
Utilità e Limiti e limiti
Pulmonary Arterial Hypertension
“ A Call to Arms”
Eduardo Bossone, MD, Ph.D, FCCP, FESC, FACC
Cardiology Division Cava de’ Tirreni and Amalfi Coast Hospital
University of Salerno, Italy
Arrivederci!!!
"Luna di Capri"
The Caprese Moon rising behind the island
PAH Progression
Pre-symptomatic/
Compensated
Symptomatic/
Decompensating
Declining/
Decompensated
CO
Symptom Threshold
PAP
Right Heart
Dysfunction
PVR
TIME
Rich et al. In: Harrison’s Principles of Internal Medicine. 15th ed. 2001:1506-1507.
Exercise Pulmonary Hypertension in Asymptomatic Degenerative Mitral regurgitation
Symptom-free survival according to resting (A) and exercise (B) PHT
Magne, J. et al.
Circulation 2010;122:33-41
Copyright ©2010 American Heart Association
Exercise stress tests of the pulmonary circulation show promise for the
detection of early or latent pulmonary vascular disease, and may help to
understand the clinical evolution and effects of treatments in patients
with established disease.
Knowledge of the limits of normal and further validation of non invasive
approaches in various patient populations are needed.
Conclusions and Future Directions
Conclusions and Future Directions
•
•
•
To choose the optimal exercise protocol.
Exercise has to be dynamic no resistive.
To define the full physiologic range of pulmonary pressure responses to exercise.
E Bossone, Bodini BD, Mazza A, Allegra L. Pulmonary arterial hypertension: the key role of echocardiography. Chest. 2005 May;127(5):1836-43.
E Bossone, Bodini BD, Mazza A, Allegra L. Pulmonary arterial hypertension: the key role of echocardiography. Chest. 2005 May;127(5):1836-43.
Exercise Induced Pulmonary
Hypertension
•
Pulmonary arterial hypertension (PAH) [mean pulmonary artery pressure (PAPm)
>25mmHg at rest, pulmonary wedge pressure ≤ 15 mmHg and pulmonary vascular
resistance > 3 mmHg/l/min (Wood units)] is a heterogeneous condition brought on by a
wide range of causes characterized by structural changes in small pulmonary arteries,
that produce a progressive increase in.pulmonary artery pressure and pulmonary
vascular resistance, ultimately leading to right ventricle failure and death.
•
A number of investigators have described subsets of patients with pathologic
pulmonary pressure responses during exercise and normal pulmonary pressure
at rest so called Exercise Induced Pulmonary Hypertension. Given the absence of
any specific symptoms or signs, ExPHtn is rarely considered, and a high degree of
clinical suspicion is necessary in certain subsets of patients, such as in those with a
history of pulmonary thromboemboli, mitral valve disease, the scleroderma spectrum of
disorders, and familial primary pulmonary hypertension.
ESC Guidelines on Diagnosis and Treatment of Pulmonary Arterial Hypertension, 2009
Bossone E. et al. Pulmonary Arterial Hypertension: The Key role of Echocardiography. Chest 2005;127:1836-43.
Tolle JJ et al, Circulation 2008; 118: 2183-9.
Oudiz RJ and Rubin LJ, Circulation 2008;118:2120-2121..
E Bossone, Bodini BD, Mazza A, Allegra L. Pulmonary arterial hypertension: the key role of echocardiography. Chest. 2005 May;127(5):1836-43.
E Bossone, Bodini BD, Mazza A, Allegra L. Pulmonary arterial hypertension: the key role of echocardiography. Chest. 2005 May;127(5):1836-43.
Exercise Induced Pulmonary
Hypertension
Recently Tolle et al using invasive maximum incremental cardiopulmonary
exercise testing fully phenotyped the patient with exercise induced PAH from
a large cohort of patients. In particular they demonstrated at maximum
exercise VO2 was lowest in resting PAH, intermediate in exercise-induced
PAH, and highest in normals, whereas mean pulmonary artery pressure and
pulmonary vascular resistance followed an opposite pattern. These results
support the notion that exercise induced PAH (EIPAH) represents a mild,
intermediate physiological stage of PAH characterized by less severe degrees
of pulmonary vascular disease.
Tolle JJ et al, Circulation 2008; 118: 2183-9.
Oudiz RJ and Rubin LJ, Circulation 2008;118:2120-2121.
Conclusions and Future Directions
Well designed longitudinal studies are warranted to investigate the natural
history of PHtn and whether preclinical treatment can prevent the
development of more severe forms of pulmonary vascular disease in
susceptible persons. Ex-PHtn remains a fascinating clinical condition and
Ex-echo a versatile tool “to look behind the scene” of otherwise
unexplained effort dyspnea.
Bossone E. et al. Latent Pulmonary Hypertension: Looking Beyond the Scene. Chest 2008;134:469-70.
“Principiis obsta; sero medicina paratur cum mala per longas convaluere moras”
Remedia Amoris 91-92
Publius Ovidius Naso
(Sulmona, 20 marzo 43 a.C. – Tomi, 18 d.C.)
“Stop it at the beginning; a cure is attempted too late when, through long delay, the illness has gained strength”