Reduced haemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension

Alessandro Bellofiore, Eric Dinges, Robert Naeije, Hamorabi Mkrdichian, Lauren Beussink-Nelson, Melissa Bailey, Michael J Cuttica, Ranya Nabil Sweis, James R. Runo, Jon G. Keevil, Christopher J. Francois, Sanjiv J Shah, Naomi C. Chesler*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective Inadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterisation with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH. Methods Twenty-six subjects with PAH were prospectively recruited to undergo right heart catheterisation and Doppler echocardiography at rest and during incremental exercise, and cardiac MRI at rest. Measurements at rest included basic haemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z0), characteristic impedance (ZC, a measure of proximal PA stiffness) and proximal and distal PA compliance (CPA). Results In patients with PAH, the proximal PAs were significantly stiffer at maximum exercise (Z C =2.31±0.38 vs 1.33±0.15 WU×m2 at rest; p=0.003) and PA compliance was decreased (CPA =0.88±0.10 vs 1.32±0.17 mL/mm Hg/m2 at rest; p=0.0002). Z0 did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (0.67±0.05 vs 1.00±0.07 s at rest; p<10-6). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited C PA reduction at maximum exercise. Conclusions In PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z0 results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor haemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated.

Original languageEnglish (US)
Pages (from-to)421-427
Number of pages7
JournalHeart
Volume103
Issue number6
DOIs
StatePublished - Mar 1 2017

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Pulmonary Hypertension
Blood Vessels
Hemodynamics
Exercise
Lung
Compliance
Lung Compliance
Right Ventricular Function
Vascular Stiffness
Doppler Echocardiography
Cardiac Catheterization
Electric Impedance
Catheterization
Vascular Resistance
Echocardiography

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Bellofiore, A., Dinges, E., Naeije, R., Mkrdichian, H., Beussink-Nelson, L., Bailey, M., ... Chesler, N. C. (2017). Reduced haemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension. Heart, 103(6), 421-427. https://doi.org/10.1136/heartjnl-2016-309906
Bellofiore, Alessandro ; Dinges, Eric ; Naeije, Robert ; Mkrdichian, Hamorabi ; Beussink-Nelson, Lauren ; Bailey, Melissa ; Cuttica, Michael J ; Sweis, Ranya Nabil ; Runo, James R. ; Keevil, Jon G. ; Francois, Christopher J. ; Shah, Sanjiv J ; Chesler, Naomi C. / Reduced haemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension. In: Heart. 2017 ; Vol. 103, No. 6. pp. 421-427.
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abstract = "Objective Inadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterisation with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH. Methods Twenty-six subjects with PAH were prospectively recruited to undergo right heart catheterisation and Doppler echocardiography at rest and during incremental exercise, and cardiac MRI at rest. Measurements at rest included basic haemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z0), characteristic impedance (ZC, a measure of proximal PA stiffness) and proximal and distal PA compliance (CPA). Results In patients with PAH, the proximal PAs were significantly stiffer at maximum exercise (Z C =2.31±0.38 vs 1.33±0.15 WU×m2 at rest; p=0.003) and PA compliance was decreased (CPA =0.88±0.10 vs 1.32±0.17 mL/mm Hg/m2 at rest; p=0.0002). Z0 did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (0.67±0.05 vs 1.00±0.07 s at rest; p<10-6). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited C PA reduction at maximum exercise. Conclusions In PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z0 results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor haemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated.",
author = "Alessandro Bellofiore and Eric Dinges and Robert Naeije and Hamorabi Mkrdichian and Lauren Beussink-Nelson and Melissa Bailey and Cuttica, {Michael J} and Sweis, {Ranya Nabil} and Runo, {James R.} and Keevil, {Jon G.} and Francois, {Christopher J.} and Shah, {Sanjiv J} and Chesler, {Naomi C.}",
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Bellofiore, A, Dinges, E, Naeije, R, Mkrdichian, H, Beussink-Nelson, L, Bailey, M, Cuttica, MJ, Sweis, RN, Runo, JR, Keevil, JG, Francois, CJ, Shah, SJ & Chesler, NC 2017, 'Reduced haemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension', Heart, vol. 103, no. 6, pp. 421-427. https://doi.org/10.1136/heartjnl-2016-309906

Reduced haemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension. / Bellofiore, Alessandro; Dinges, Eric; Naeije, Robert; Mkrdichian, Hamorabi; Beussink-Nelson, Lauren; Bailey, Melissa; Cuttica, Michael J; Sweis, Ranya Nabil; Runo, James R.; Keevil, Jon G.; Francois, Christopher J.; Shah, Sanjiv J; Chesler, Naomi C.

In: Heart, Vol. 103, No. 6, 01.03.2017, p. 421-427.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Reduced haemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension

AU - Bellofiore, Alessandro

AU - Dinges, Eric

AU - Naeije, Robert

AU - Mkrdichian, Hamorabi

AU - Beussink-Nelson, Lauren

AU - Bailey, Melissa

AU - Cuttica, Michael J

AU - Sweis, Ranya Nabil

AU - Runo, James R.

AU - Keevil, Jon G.

AU - Francois, Christopher J.

AU - Shah, Sanjiv J

AU - Chesler, Naomi C.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Objective Inadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterisation with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH. Methods Twenty-six subjects with PAH were prospectively recruited to undergo right heart catheterisation and Doppler echocardiography at rest and during incremental exercise, and cardiac MRI at rest. Measurements at rest included basic haemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z0), characteristic impedance (ZC, a measure of proximal PA stiffness) and proximal and distal PA compliance (CPA). Results In patients with PAH, the proximal PAs were significantly stiffer at maximum exercise (Z C =2.31±0.38 vs 1.33±0.15 WU×m2 at rest; p=0.003) and PA compliance was decreased (CPA =0.88±0.10 vs 1.32±0.17 mL/mm Hg/m2 at rest; p=0.0002). Z0 did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (0.67±0.05 vs 1.00±0.07 s at rest; p<10-6). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited C PA reduction at maximum exercise. Conclusions In PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z0 results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor haemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated.

AB - Objective Inadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterisation with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH. Methods Twenty-six subjects with PAH were prospectively recruited to undergo right heart catheterisation and Doppler echocardiography at rest and during incremental exercise, and cardiac MRI at rest. Measurements at rest included basic haemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z0), characteristic impedance (ZC, a measure of proximal PA stiffness) and proximal and distal PA compliance (CPA). Results In patients with PAH, the proximal PAs were significantly stiffer at maximum exercise (Z C =2.31±0.38 vs 1.33±0.15 WU×m2 at rest; p=0.003) and PA compliance was decreased (CPA =0.88±0.10 vs 1.32±0.17 mL/mm Hg/m2 at rest; p=0.0002). Z0 did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (0.67±0.05 vs 1.00±0.07 s at rest; p<10-6). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited C PA reduction at maximum exercise. Conclusions In PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z0 results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor haemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated.

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Bellofiore A, Dinges E, Naeije R, Mkrdichian H, Beussink-Nelson L, Bailey M et al. Reduced haemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension. Heart. 2017 Mar 1;103(6):421-427. https://doi.org/10.1136/heartjnl-2016-309906