mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis

Sarah Hoedemakers; Nicola Riccardo Pugliese; Jan Stassen; Arnaud Vanoppen; Jade Claessens; Tin Gojevic; Youri Bekhuis; Maarten Falter; Sara Moura Ferreira; Sebastiaan Dhont; Nicolò De Biase; Lavinia Del Punta; Valerio Di Fiore; Marco De Carlo; Cristina Giannini; Andrea Colli; Raluca Elena Dulgheru; Jolien Geers; Alaaddin Yilmaz; Guido Claessen; Philippe Bertrand; Steven Droogmans; Patrizio Lancellotti; Bernard Cosyns; Frederik H Verbrugge; Lieven Herbots; Stefano Masi; Jan Verwerft

doi:10.1161/CIRCULATIONAHA.123.067130

mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis

Sarah Hoedemakers, Nicola Riccardo Pugliese, Jan Stassen, Arnaud Vanoppen, Jade Claessens, Tin Gojevic, Youri Bekhuis, Maarten Falter, Sara Moura Ferreira, Sebastiaan Dhont, Nicolò De Biase, Lavinia Del Punta, Valerio Di Fiore, Marco De Carlo, Cristina Giannini, Andrea Colli, Raluca Elena Dulgheru, Jolien Geers, Alaaddin Yilmaz, Guido ClaessenPhilippe Bertrand, Steven Droogmans, Patrizio Lancellotti, Bernard Cosyns, Frederik H Verbrugge, Lieven Herbots, Stefano Masi, Jan Verwerft

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown.

METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141).

RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort.

CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

Original language	English
Pages (from-to)	1172-1182
Number of pages	11
Journal	Circulation
Volume	149
Issue number	15
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.123.067130
Publication status	Published - 9 Apr 2024

Bibliographical note

Funding Information:
This research is partially funded by the Limburg Clinical Research Center of Hasselt University, Jessa and ZOL (Belgium; PhD grant), and the research cluster Centrum voor Hart-en Vaatziekten en Klinische Farmacie (CHVZ-KFAR), van de Vrije Universiteit Brussel. The research leading to these results has received funding from the European Union\u2013NextGenerationEU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 project PE_00000019 \u201CHEAL ITALIA\u201D to Stefano Taddei, CUP I53C22001440006. The views and opinions expressed are those of the authors only and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them.

Funding Information:
This research is partially funded by the Limburg Clinical Research Center of Hasselt University, Jessa and ZOL (Belgium; PhD grant), and the research cluster Centrum voor Hart-en Vaatziekten en Klinische Farmacie (CHVZKFAR), van de Vrije Universiteit Brussel. The research leading to these results has received funding from the European Union NextGenerationEU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 project PE_00000019 HEAL ITALIA to Stefano Taddei, CUP I53C22001440006. The views and opinions expressed are those of the authors only and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them.

Publisher Copyright:
© 2024 Lippincott Williams and Wilkins. All rights reserved.

Keywords

Humans
Middle Aged
Aged
Aged, 80 and over
Prognosis
Echocardiography, Stress/methods
Atrial Fibrillation/diagnosis
Prospective Studies
Aortic Valve Stenosis/diagnosis
Cardiac Output
Heart Failure/complications
Oxygen

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Hoedemakers, S., Pugliese, N. R., Stassen, J., Vanoppen, A., Claessens, J., Gojevic, T., Bekhuis, Y., Falter, M., Moura Ferreira, S., Dhont, S., De Biase, N., Del Punta, L., Di Fiore, V., De Carlo, M., Giannini, C., Colli, A., Dulgheru, R. E., Geers, J., Yilmaz, A., ... Verwerft, J. (2024). mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis. Circulation, 149(15), 1172-1182. https://doi.org/10.1161/CIRCULATIONAHA.123.067130

Hoedemakers, Sarah ; Pugliese, Nicola Riccardo ; Stassen, Jan ; Vanoppen, Arnaud ; Claessens, Jade ; Gojevic, Tin ; Bekhuis, Youri ; Falter, Maarten ; Moura Ferreira, Sara ; Dhont, Sebastiaan ; De Biase, Nicolò ; Del Punta, Lavinia ; Di Fiore, Valerio ; De Carlo, Marco ; Giannini, Cristina ; Colli, Andrea ; Dulgheru, Raluca Elena ; Geers, Jolien ; Yilmaz, Alaaddin ; Claessen, Guido ; Bertrand, Philippe ; Droogmans, Steven ; Lancellotti, Patrizio ; Cosyns, Bernard ; Verbrugge, Frederik H ; Herbots, Lieven ; Masi, Stefano ; Verwerft, Jan. / mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis. In: Circulation. 2024 ; Vol. 149, No. 15. pp. 1172-1182.

@article{8618d88138a24a9e81397b0d06e3eb76,

title = "mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis",

abstract = "BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown.METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141).RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort.CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.",

keywords = "Humans, Middle Aged, Aged, Aged, 80 and over, Prognosis, Echocardiography, Stress/methods, Atrial Fibrillation/diagnosis, Prospective Studies, Aortic Valve Stenosis/diagnosis, Cardiac Output, Heart Failure/complications, Oxygen",

author = "Sarah Hoedemakers and Pugliese, {Nicola Riccardo} and Jan Stassen and Arnaud Vanoppen and Jade Claessens and Tin Gojevic and Youri Bekhuis and Maarten Falter and {Moura Ferreira}, Sara and Sebastiaan Dhont and {De Biase}, Nicol{\`o} and {Del Punta}, Lavinia and {Di Fiore}, Valerio and {De Carlo}, Marco and Cristina Giannini and Andrea Colli and Dulgheru, {Raluca Elena} and Jolien Geers and Alaaddin Yilmaz and Guido Claessen and Philippe Bertrand and Steven Droogmans and Patrizio Lancellotti and Bernard Cosyns and Verbrugge, {Frederik H} and Lieven Herbots and Stefano Masi and Jan Verwerft",

note = "Funding Information: This research is partially funded by the Limburg Clinical Research Center of Hasselt University, Jessa and ZOL (Belgium; PhD grant), and the research cluster Centrum voor Hart-en Vaatziekten en Klinische Farmacie (CHVZ-KFAR), van de Vrije Universiteit Brussel. The research leading to these results has received funding from the European Union\u2013NextGenerationEU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 project PE_00000019 \u201CHEAL ITALIA\u201D to Stefano Taddei, CUP I53C22001440006. The views and opinions expressed are those of the authors only and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them. Funding Information: This research is partially funded by the Limburg Clinical Research Center of Hasselt University, Jessa and ZOL (Belgium; PhD grant), and the research cluster Centrum voor Hart-en Vaatziekten en Klinische Farmacie (CHVZKFAR), van de Vrije Universiteit Brussel. The research leading to these results has received funding from the European Union NextGenerationEU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 project PE_00000019 HEAL ITALIA to Stefano Taddei, CUP I53C22001440006. The views and opinions expressed are those of the authors only and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them. Publisher Copyright: {\textcopyright} 2024 Lippincott Williams and Wilkins. All rights reserved.",

year = "2024",

month = apr,

day = "9",

doi = "10.1161/CIRCULATIONAHA.123.067130",

language = "English",

volume = "149",

pages = "1172--1182",

journal = "Circulation",

issn = "0009-7322",

publisher = "Lippincott Williams and Wilkins",

number = "15",

}

Hoedemakers, S, Pugliese, NR, Stassen, J, Vanoppen, A, Claessens, J, Gojevic, T, Bekhuis, Y, Falter, M, Moura Ferreira, S, Dhont, S, De Biase, N, Del Punta, L, Di Fiore, V, De Carlo, M, Giannini, C, Colli, A, Dulgheru, RE, Geers, J, Yilmaz, A, Claessen, G, Bertrand, P, Droogmans, S, Lancellotti, P, Cosyns, B , Verbrugge, FH, Herbots, L, Masi, S & Verwerft, J 2024, 'mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis', Circulation, vol. 149, no. 15, pp. 1172-1182. https://doi.org/10.1161/CIRCULATIONAHA.123.067130

mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis. / Hoedemakers, Sarah; Pugliese, Nicola Riccardo; Stassen, Jan; Vanoppen, Arnaud; Claessens, Jade; Gojevic, Tin; Bekhuis, Youri; Falter, Maarten; Moura Ferreira, Sara; Dhont, Sebastiaan; De Biase, Nicolò; Del Punta, Lavinia; Di Fiore, Valerio; De Carlo, Marco; Giannini, Cristina; Colli, Andrea; Dulgheru, Raluca Elena; Geers, Jolien; Yilmaz, Alaaddin; Claessen, Guido; Bertrand, Philippe; Droogmans, Steven; Lancellotti, Patrizio; Cosyns, Bernard ; Verbrugge, Frederik H; Herbots, Lieven; Masi, Stefano; Verwerft, Jan.

In: Circulation, Vol. 149, No. 15, 09.04.2024, p. 1172-1182.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis

AU - Hoedemakers, Sarah

AU - Pugliese, Nicola Riccardo

AU - Stassen, Jan

AU - Vanoppen, Arnaud

AU - Claessens, Jade

AU - Gojevic, Tin

AU - Bekhuis, Youri

AU - Falter, Maarten

AU - Moura Ferreira, Sara

AU - Dhont, Sebastiaan

AU - De Biase, Nicolò

AU - Del Punta, Lavinia

AU - Di Fiore, Valerio

AU - De Carlo, Marco

AU - Giannini, Cristina

AU - Colli, Andrea

AU - Dulgheru, Raluca Elena

AU - Geers, Jolien

AU - Yilmaz, Alaaddin

AU - Claessen, Guido

AU - Bertrand, Philippe

AU - Droogmans, Steven

AU - Lancellotti, Patrizio

AU - Cosyns, Bernard

AU - Verbrugge, Frederik H

AU - Herbots, Lieven

AU - Masi, Stefano

AU - Verwerft, Jan

N1 - Funding Information: This research is partially funded by the Limburg Clinical Research Center of Hasselt University, Jessa and ZOL (Belgium; PhD grant), and the research cluster Centrum voor Hart-en Vaatziekten en Klinische Farmacie (CHVZ-KFAR), van de Vrije Universiteit Brussel. The research leading to these results has received funding from the European Union\u2013NextGenerationEU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 project PE_00000019 \u201CHEAL ITALIA\u201D to Stefano Taddei, CUP I53C22001440006. The views and opinions expressed are those of the authors only and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them. Funding Information: This research is partially funded by the Limburg Clinical Research Center of Hasselt University, Jessa and ZOL (Belgium; PhD grant), and the research cluster Centrum voor Hart-en Vaatziekten en Klinische Farmacie (CHVZKFAR), van de Vrije Universiteit Brussel. The research leading to these results has received funding from the European Union NextGenerationEU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 project PE_00000019 HEAL ITALIA to Stefano Taddei, CUP I53C22001440006. The views and opinions expressed are those of the authors only and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them. Publisher Copyright: © 2024 Lippincott Williams and Wilkins. All rights reserved.

PY - 2024/4/9

Y1 - 2024/4/9

N2 - BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown.METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141).RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort.CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

AB - BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown.METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141).RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort.CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

KW - Humans

KW - Middle Aged

KW - Aged

KW - Aged, 80 and over

KW - Prognosis

KW - Echocardiography, Stress/methods

KW - Atrial Fibrillation/diagnosis

KW - Prospective Studies

KW - Aortic Valve Stenosis/diagnosis

KW - Cardiac Output

KW - Heart Failure/complications

KW - Oxygen

UR - http://www.scopus.com/inward/record.url?scp=85190125587&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.123.067130

DO - 10.1161/CIRCULATIONAHA.123.067130

M3 - Article

C2 - 38410954

VL - 149

SP - 1172

EP - 1182

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 15

ER -

mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis

Abstract

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