Exercise Echo Assessment of the Right Ventricle and Pulmonary Pressure Prof. Patrizio LANCELLOTTI , MD, PhD GIGA Cardiovascular Sciences, Heart Valve Clinic, University of Liège, CHU Sart Tilman, BELGIUM
Physiology
Waxman et al. Progress Cardiovascular Diseases. 2012
The Right Heart (RH) Preload Hemodynamic stretch on the myocardium wall EDP EDV
Intrinsic contractiliy
Afterload hydraulic load imposed on RV during ejection TPVR = (mPAP- PWP)/CO
RV function
Waxman et al. Progress Cardiovascular Diseases. 2012
The Pulmonary Vascular Bed • Very low resistance • High compliance (Ca) • Ability to distend and to recruit its arterial vessels • To match the RH cardiac output (CO) and the pulmonary vascular resistance (PVR) • To accommodate increase in volume and flow
Waxman et al. Progress Cardiovascular Diseases. 2012
The Lung • Physiologic impact of the volume of gas in the lung on alveolar and extra-alveolar vessels – ↓ lung volume => reduced radial traction => decreased caliber of extra alveolar capillaries => ↑ PVR – hypoxia => vasoconstriction => ↑ PVR
Waxman et al. Progress Cardiovascular Diseases. 2012
The Left Heart LV systolic dysfunction
LV diastolic dysfunction
Valvular heart diseases
PWP
Waxman et al. Progress Cardiovascular Diseases. 2012
Physiology of the pulmonary circulation
mPAP = PVR x CO + LAP
Gold Standard RH Catheterization (RHC) • Normal value at rest – mean PAP (mPAP) < 20 mmHg at rest – Pulmonary hypertension (PH): mPAP ≥ 25 mmHg
• Normal value at exercise – Not validated – PH : mPAP > 30 mmHg Galiè et al. Guidelines for the diagnosis and treatment of PH. EHJ. 2009 McQuillan et al. Circulation. 2001
Exercise Evaluation : What Do We Know about Healthy Subjects?
Assessment of PAP During Exercise • Gold standard: Right Heart Catheterization • Echocardiography: – RAP is not well defined – PWP is not included in recommandations – Assessment of RVCO and PVR remain not validated
Normal Value of PAP and PWP During Exercise • Meta-analysis: 47 studies (RHC), n=1 187 • mPAP is 13.8 ± 3.1 mmHg (ULN 20 mmHg) • sPAP is 20.8 ± 4.4 mmHg (ULN 29.6 mmHg)
Rest
p < 0.01 p < 0.01
mPAP (mmHg)
Rest
Low Level
Peak Level
20.8 ±4
25.6 ± 5.6
Low exercise
Kovacs et al. Eur Respi J. 2009
Normal Value of PAP and PWP During Exercise 113 normal individuals
Slope < 3mmHg/L/min upper limits
Am J Physiol Lung Cell Mol Physiol.2005
Pulmonary Wedge Pressure p < 0.01
p = ns
PWP (mmHg)
Rest
Low
Max.
9.1 ± 4.2
14.9 ± 7.9
Max exercise
Kovacs et al. Eur Respi J. 2009
Study Conclusion • mPAP is affected – by workload and age – linear relationship with CO. – Low exercise: < 30 mmHg • > 30 mmHg in 47 % of healthy individuals > 50 yrs
– Max exercise: 40 mmHg? • > 40 mmHg in 21% of healthy individuals < 50 yrs
• Not one ULN for all subjects and level of exercise Kovacs et al. Eur Respi J. 2009
sPAP
• Exercise echocardiography • 70 healthy volunteers • sPAP > 60 mmHg • 36% of 60 to 70 yrs 142 ± 51 W • 50% > 70 yrs
Majhoub et al. Eur J of Echo. 2009
Pulmonary Vascular Resistance • Meta-analysis 24 studies (RHC), n=222 subjects • PVR = resistance of the precapillary pulmonary arteries • TPR = PVR + left ventricular filling resistance
Kovacs et al. Eur Respi J. 2011
Changes During Exercise Low level exercise
CO
mPAP LV Ca TPR
< 50 yrs
↑ 85 %
↑ 41 %
50-70 yrs
↑ 71 %
↑ 66 %
>70 yrs
↑ 88 %
↑↑ 119 %
↑ ↓
↓↓
PVR
↓ 25 %
↓ 12 %
≈
≈
↑ 17 %
≈
Kovacs et al. Eur Respi J. 2012
Study Conclusion • ≤ 50 yrs during exercise: – mPAP linear relationship with CO (Intensity of Exercise) – ↑ LV Ca : moderate ↑ of PWP (< 15 mmHg) – ↑ vascular pulmonary Ca: ↓ PVR (dilatation and recruitment )
• > 50 yrs during exercise: – different patterns of change in mPAP – ↓ vascular pulmonary Ca – ↓ LV Ca : ↑ of PWP during low levels (frequently > 20mmHg )
Kovacs et al. Eur Respi J. 2011
Assessment of RV Function During Exercise Exercise = RV Work
RV Function = PAP
La Gerche et al. JASE 2012
Disproportionate Increase in RV Work During Exercise
How long can the heart sustain this increased load ?
La Gerche et al. Med Scien Sports 2011
How long can the heart sustain this increased load ?
An healthy heart can support a 4-fold increase in RV work for a few hours
La Gerche A et al. Eur Heart J 2012
Exercise Evaluation : What do We Know about Pathological Conditions?
Do We Need an Exercise Evaluation ? • Yes • To “unmask” an abnormal phenotype not/weakly appreciated by resting haemodynamics • Especially in at-risk populations where earlier diagnosis may be beneficial • Daily life activity like Bonderman et al. Chest. 2011 Grünig et al. Circulation. 2009 Tolle et al. Circulation. 2008 Kovacs et al. Am J Respir Crit Care Med. 2009. Saggar et al. Arthritis Rheum. 2010 Proudman et al. Intern Med J. 2007
Scleroderma Study • 54 scleroderma patients with symptoms and at risk for PH • A positive exercise test: ↑ of RVSP ≥ 20 mmHg 44 % • RHC performed if + Exercise echocardiography 19 %
62 %
Steen et al. CHEST. 2008
Scleroderma Study • 65 patients with scleroderma – normal resting sPAP
46 % n = 30
– normal resting LV function
• Post-exercise Doppler echocardiography • Bruce protocole • EIPH is frequent/correlates with Exer. Capacity
Alkotob et al. Chest 2006
Study Conclusion • Exercise-induced PH is common in patients with scleroderma, even when resting sPAP is normal • Stress Doppler echocardiography identifies these patients • Peak sPAP is linearly related to exercise time and maximum workload achieved. •
Patients with EIPH are at higher risk of developing pulmonary vascular disease In a U.K. PH registry, one-fifth of SSc patients with exercise PH developed resting PAH after approximately 2.3 years
Alkotob et al. CHEST. 2006
Steen et al. CHEST. 2008
Exercise Induced Pulmonary PH In Systemic Sclerosis And Treatment With Ambrisentan: A Prospective Single Center, Open Label, Pilot Study Open-label study, 5-10 mg oral ambrisentan for 24 weeks, SSc-patients, Normal resting PAP but Exercise PH (RHC mPAP > 30 mmHg)
- Improvement in exercise hemodynamics and 6MW - Decrease in exercise PVR, total pulmonary resistance, and mPAP, and an increase in Q and SV - This needs to be validated by a larger placebo controlled randomized study
Saggar et al. Arthritis Rheum. 2012
LV Diastolic Dysfunction/Preserved LVEF n = 1 347 patients referred for diastolic stress echo Exclusion criteria
n = 498 patients
LVEF < 50% HCM Renal failure
Exercise echocardiography
No EIPH n = 327
65 %
EIPH n = 171
35 % sPAP >50 mmHg at 50 W
No ↑ LV filling pressure ↑ LV filling pressure + n = 122 n = 49 71 % 29%
E/e’ >15 at 50 W
Shim et al. Heart. 2011
Study Conclusion
â&#x20AC;˘ EIPH provides prognostic information â&#x20AC;˘ Worst outcomes for patients with an associated increase in LV filling pressure Shim et al. Heart. 2011
PH in Heart Failure with Preserved LVEF The relative contribution of pulmonary venous versus pulmonary arterial hypertension to PH in HFpEF is unknown PH out of proportion to LV dysfunction”, alternatively named “PH-LVD” or “mixed PH” RV Work
Guazzi et al, Cir 2011
Whether exercise hemodynamic responses can identify HFpEF subjects with earlier forms of abnormal RV-pulmonary vascular reserve capacity that will benefit from RV-PV directed interventions is being actively investigated
Valvular Heart Diseases Degenerative Mitral Regurgitation (DMR)
n = 78 patients Asymptomatic, â&#x2030;Ľ moderate DMR
Resting PHT sPAP > 50 mmHg n = 11 14 %
Exercise PHT sPAP > 50 mmHg n = 36 46 % Magne, Lancellotti, Pierard. Circ. 2010
Prognostic Significance of Exercise Induced RV Dysfunction in Asymptomatic DMR
Kusunose et al, Circ Imag 2013 in press
Prognostic Significance of Exercise Induced RV Dysfunction in Asymptomatic DMR
ExRVF, exercise TAPSE <19mm) and exercise PHT (ExPHT, SPAP >54mmHg
Kusunose et al, Circ Imag 2013 in press
Primary Mitral Regurgitation Indications for Mitral Valve Treatment ESC Guidelines Classa Surgery should be considered in asymptomatic patients with IIa preserved function and pulmonary hypertension at rest (>50 mmHg)
Levelb C
Surgery may be considered in asymptomatic patients with preserved IIb function, high likelihood of durable repair, and low surgical risk and pulmonary hypertension on exercise (SPAP â&#x2030;Ľ60 mmHg at exercise)
C
AHA/ACC Guidelines MV surgery is reasonable for asymptomatic patients with chronic severe MR,* preserved LV function, and pulmonary hypertension (> 50 mm Hg at rest or >60 mm Hg with exercise)
C
IIa
Valvular Heart Diseases Secondary MR and LV Dysfunction - 161 HF pts with ischemic LV dysdunction - SPAP > 61 mmHg at exercise: 38% of patients - Predictors of outcome: ERO diff, TTPG diff, ERO at rest
Patients with a SPAP > 60 mmHg interrupted more frequently exercise for dyspnea
Piérard - Lancellotti New Engl Jour Med 2004 Piérard - Lancellotti New Engl Jour Med 2006
Valvular Heart Diseases Secondary MR and LV Dysfunction Cardiac Correlates of EIPH
Resting LV asynchrony, impaired LV contractile reserve, and increase in LA dilatation correlate with the severity of exercise PH, while RVsystolic dysfunction is inversely related to the severity of exercise induced PH
MarĂŠchaux et al. Echocardiography 2008
Secondary MR Indications for Mitral Valve Surgery: Resting PHT is not a criterion Classa Surgery is indicated in patients with severe MR* undergoing I CABG, and LVEF >30%
Levelb C
Surgery should be considered in patients with moderate MR undergoing CABG (Exercise echo is recommended to identify dyspnea, increase in severity of MR and in SPAP)
IIa
C
Surgery should be considered in symptomatic patients with IIa severe MR, LVEF <30%, option for revascularization, and evidence of viability
C
Surgery may be considered in patients with severe MR, LVEF >30%, who remain symptomatic despite optimal medical management (including CRT if indicated) and have low comorbidity, when revascularization is not indicated
C
IIb
Valvular Heart Diseases Aortic Stenosis (AS) n = 105 Asymptomatic, severe AS, LVEFâ&#x2030;Ľ 55%
Resting PHT sPAP > 50 mmHg n=6 6%
Exercise PHT sPAP > 60 mmHg n = 58 32 %
Lancellotti et al. Circ. 2012
Mitral Stenosis (MS)
n = 48 Mitral Stenosis
No Exercise Dyspnea n = 26
54 %
Exercise Dysnea n = 22
46 %
Brochet et al. JASE. 2011
Threshold Values vs. Kinetic of Changes
Various Etiologies of PH n = 406 patients Exercise dyspnea Normal n = 16
48 %
PVH n = 196
Resting PH n = 15 16 %
Peripheral limitations n = 93
23 % PAH n = 93 EIPH n = 78
Plateau Pattern 45% n = 32
Cardio-Pulmonary Exercise Testing Radial and Pulmonary catheterization
Others n = 46
84 %
Resting PH: mPAP≥ 25 mmHg EIPH : mPAP at max exercise > 30 mmHg PWP < 20mmHg PVH : PWP ≥ 20 mmHg
Takeoff Pattern n = 40 55 %
Tolle et al.Circ. 2008
Various Etiologies of PH
Tolle et al.Circ. 2008
Various Etiologies of PH
Tolle et al. Circ. 2008
LV Systolic Dysfunction (LVSD) n = 79
n = 60 76 % LVSD
CEPT + RHC
n = 19 Controls 24 % Controls
LVSD (increment)
LVSD (plateau)
Lewis et al. Circ Heart Fail. 2011
Studies Conclusion • EIPH – Exists, mild, intermediate stage of PH
• Kinetics of change • The takeoff pattern – normal and less severe EIPH patients – inversely related to exercise capacity and survival
• The plateau pattern – More severely affected EIPH patients and resting PH – Failure to augment PAP/ RV stroke volume – Worst outcomes Tolle Circulation. 2008 Lewis et al. Circ Heart Fail. 2011
Key messages • Exercise changes in SPAP is affected by the complex interaction between the pulmonary vascular bed, the RV function, the LV function, and the presence of VHD • PH at exercise is common in elderly patients and in various cardiac condtions. However, its significance depends on several parameters: – Age, workload, type of pathology – Kinetic of changes – Pulmonary vascular response – RV function • Impact: Follow-up, specific target of PAH
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