SHA24/080004

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

Join us in Istanbul!

11-14 December 2013 Main Themes Heart Failure Imaging in Interventional Cardiology Important deadlines Abstract Submission 31 May 2013 Early Registration 30 September 2013

Speaker

www.escardio.org/EACVI