Biomarkers to Assess Right Heart Pressures in Recipients of a Heart Transplant: A Proof-of-Concept Study

Qi-Fang Huang; Sander Trenson; Zhen-Yu Zhang; Jan Van Keer; Lucas N. L. Van Aelst; Wen-Yi Yang; Esther Nkuipou-Kenfack; Lutgarde Thijs; Fang-Fei Wei; Blerim Mujaj; Agnieszka Ciarka; Walter Droogne; Johan Vanhaecke; Stefan Janssens; Johan Van Cleemput; Harald Mischak; Jan A. Staessen

doi:10.1097/TXD.0000000000000783

Biomarkers to Assess Right Heart Pressures in Recipients of a Heart Transplant: A Proof-of-Concept Study

Qi-Fang Huang, Sander Trenson, Zhen-Yu Zhang, Jan Van Keer, Lucas N. L. Van Aelst, Wen-Yi Yang, Esther Nkuipou-Kenfack, Lutgarde Thijs, Fang-Fei Wei, Blerim Mujaj, Agnieszka Ciarka, Walter Droogne, Johan Vanhaecke, Stefan Janssens, Johan Van Cleemput, Harald Mischak, Jan A. Staessen^*

^*Corresponding author for this work

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

Abstract

Background: This proof-of-concept study investigated the feasibility of using biomarkers to monitor right heart pressures (RHP) in heart transplanted (HTx) patients.

Methods: In 298 patients, we measured 7.6 years post-HTx mean pressures in the right atrium (mRAP) and pulmonary artery (mPAP) and capillaries (mPCWP) along with plasma high-sensitivity troponin T (hsTnT), a marker of cardiomyocyte injury, and the multidimensional urinary classifiers HF1 and HF2, mainly consisting of dysregulated collagen fragments.

Results: In multivariable models, mRAP and mPAP increased with hsTnT (per 1-SD, +0.91 and +1.26 mm Hg; P < 0.0001) and with HF2 (+0.42 and +0.62 mm Hg; P ≤ 0.035), but not with HF1. mPCWP increased with hsTnT (+1.16 mm Hg; P < 0.0001), but not with HF1 or HF2. The adjusted odds ratios for having elevated RHP (mRAP, mPAP or mPCWP ≥10, ≥24, ≥17 mm Hg, respectively) were 1.99 for hsTnT and 1.56 for HF2 ( P ≤ 0.005). In detecting elevated RHPs, areas under the curve were similar for hsTnT and HF2 (0.63 vs 0.65; P = 0.66). Adding hsTnT continuous or per threshold or HF2 continuous to a basic model including all covariables did not increase diagnostic accuracy ( P ≥ 0.11), whereas adding HF2 per optimized threshold increased both the integrated discrimination (+1.92%; P = 0.023) and net reclassification (+30.3%; P = 0.010) improvement.

Conclusions: Correlating RHPs with noninvasive biomarkers in HTx patients is feasible. However, further refinement and validation of such biomarkers is required before their clinical application can be considered.

Original language	English
Article number	346
Number of pages	10
Journal	Transplantation Direct
Volume	4
Issue number	5
DOIs	https://doi.org/10.1097/TXD.0000000000000783
Publication status	Published - 1 May 2018

Keywords

VENTRICULAR FILLING PRESSURES
URINARY PROTEOME ANALYSIS
CORONARY-ARTERY-DISEASE
TROPONIN-T ASSAY
CARDIAC TRANSPLANTATION
PULMONARY-HYPERTENSION
GENERAL-POPULATION
PROGNOSTIC VALUE
ACUTE REJECTION
DYSFUNCTION

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Cite this

Huang, Q.-F., Trenson, S., Zhang, Z.-Y., Van Keer, J., Van Aelst, L. N. L., Yang, W.-Y., Nkuipou-Kenfack, E., Thijs, L., Wei, F.-F., Mujaj, B., Ciarka, A., Droogne, W., Vanhaecke, J., Janssens, S., Van Cleemput, J., Mischak, H., & Staessen, J. A. (2018). Biomarkers to Assess Right Heart Pressures in Recipients of a Heart Transplant: A Proof-of-Concept Study. Transplantation Direct, 4(5), Article 346. https://doi.org/10.1097/TXD.0000000000000783

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title = "Biomarkers to Assess Right Heart Pressures in Recipients of a Heart Transplant: A Proof-of-Concept Study",

abstract = "Background: This proof-of-concept study investigated the feasibility of using biomarkers to monitor right heart pressures (RHP) in heart transplanted (HTx) patients.Methods: In 298 patients, we measured 7.6 years post-HTx mean pressures in the right atrium (mRAP) and pulmonary artery (mPAP) and capillaries (mPCWP) along with plasma high-sensitivity troponin T (hsTnT), a marker of cardiomyocyte injury, and the multidimensional urinary classifiers HF1 and HF2, mainly consisting of dysregulated collagen fragments.Results: In multivariable models, mRAP and mPAP increased with hsTnT (per 1-SD, +0.91 and +1.26 mm Hg; P < 0.0001) and with HF2 (+0.42 and +0.62 mm Hg; P ≤ 0.035), but not with HF1. mPCWP increased with hsTnT (+1.16 mm Hg; P < 0.0001), but not with HF1 or HF2. The adjusted odds ratios for having elevated RHP (mRAP, mPAP or mPCWP ≥10, ≥24, ≥17 mm Hg, respectively) were 1.99 for hsTnT and 1.56 for HF2 ( P ≤ 0.005). In detecting elevated RHPs, areas under the curve were similar for hsTnT and HF2 (0.63 vs 0.65; P = 0.66). Adding hsTnT continuous or per threshold or HF2 continuous to a basic model including all covariables did not increase diagnostic accuracy ( P ≥ 0.11), whereas adding HF2 per optimized threshold increased both the integrated discrimination (+1.92%; P = 0.023) and net reclassification (+30.3%; P = 0.010) improvement. Conclusions: Correlating RHPs with noninvasive biomarkers in HTx patients is feasible. However, further refinement and validation of such biomarkers is required before their clinical application can be considered.",

keywords = "VENTRICULAR FILLING PRESSURES, URINARY PROTEOME ANALYSIS, CORONARY-ARTERY-DISEASE, TROPONIN-T ASSAY, CARDIAC TRANSPLANTATION, PULMONARY-HYPERTENSION, GENERAL-POPULATION, PROGNOSTIC VALUE, ACUTE REJECTION, DYSFUNCTION",

author = "Qi-Fang Huang and Sander Trenson and Zhen-Yu Zhang and {Van Keer}, Jan and {Van Aelst}, {Lucas N. L.} and Wen-Yi Yang and Esther Nkuipou-Kenfack and Lutgarde Thijs and Fang-Fei Wei and Blerim Mujaj and Agnieszka Ciarka and Walter Droogne and Johan Vanhaecke and Stefan Janssens and {Van Cleemput}, Johan and Harald Mischak and Staessen, {Jan A.}",

year = "2018",

month = may,

day = "1",

doi = "10.1097/TXD.0000000000000783",

language = "English",

volume = "4",

journal = "Transplantation Direct",

issn = "2373-8731",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "5",

}

Huang, Q-F, Trenson, S, Zhang, Z-Y, Van Keer, J, Van Aelst, LNL, Yang, W-Y, Nkuipou-Kenfack, E, Thijs, L, Wei, F-F, Mujaj, B, Ciarka, A, Droogne, W, Vanhaecke, J, Janssens, S, Van Cleemput, J, Mischak, H & Staessen, JA 2018, 'Biomarkers to Assess Right Heart Pressures in Recipients of a Heart Transplant: A Proof-of-Concept Study', Transplantation Direct, vol. 4, no. 5, 346. https://doi.org/10.1097/TXD.0000000000000783

TY - JOUR

T1 - Biomarkers to Assess Right Heart Pressures in Recipients of a Heart Transplant

T2 - A Proof-of-Concept Study

AU - Huang, Qi-Fang

AU - Trenson, Sander

AU - Zhang, Zhen-Yu

AU - Van Keer, Jan

AU - Van Aelst, Lucas N. L.

AU - Yang, Wen-Yi

AU - Nkuipou-Kenfack, Esther

AU - Thijs, Lutgarde

AU - Wei, Fang-Fei

AU - Mujaj, Blerim

AU - Ciarka, Agnieszka

AU - Droogne, Walter

AU - Vanhaecke, Johan

AU - Janssens, Stefan

AU - Van Cleemput, Johan

AU - Mischak, Harald

AU - Staessen, Jan A.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Background: This proof-of-concept study investigated the feasibility of using biomarkers to monitor right heart pressures (RHP) in heart transplanted (HTx) patients.Methods: In 298 patients, we measured 7.6 years post-HTx mean pressures in the right atrium (mRAP) and pulmonary artery (mPAP) and capillaries (mPCWP) along with plasma high-sensitivity troponin T (hsTnT), a marker of cardiomyocyte injury, and the multidimensional urinary classifiers HF1 and HF2, mainly consisting of dysregulated collagen fragments.Results: In multivariable models, mRAP and mPAP increased with hsTnT (per 1-SD, +0.91 and +1.26 mm Hg; P < 0.0001) and with HF2 (+0.42 and +0.62 mm Hg; P ≤ 0.035), but not with HF1. mPCWP increased with hsTnT (+1.16 mm Hg; P < 0.0001), but not with HF1 or HF2. The adjusted odds ratios for having elevated RHP (mRAP, mPAP or mPCWP ≥10, ≥24, ≥17 mm Hg, respectively) were 1.99 for hsTnT and 1.56 for HF2 ( P ≤ 0.005). In detecting elevated RHPs, areas under the curve were similar for hsTnT and HF2 (0.63 vs 0.65; P = 0.66). Adding hsTnT continuous or per threshold or HF2 continuous to a basic model including all covariables did not increase diagnostic accuracy ( P ≥ 0.11), whereas adding HF2 per optimized threshold increased both the integrated discrimination (+1.92%; P = 0.023) and net reclassification (+30.3%; P = 0.010) improvement. Conclusions: Correlating RHPs with noninvasive biomarkers in HTx patients is feasible. However, further refinement and validation of such biomarkers is required before their clinical application can be considered.

AB - Background: This proof-of-concept study investigated the feasibility of using biomarkers to monitor right heart pressures (RHP) in heart transplanted (HTx) patients.Methods: In 298 patients, we measured 7.6 years post-HTx mean pressures in the right atrium (mRAP) and pulmonary artery (mPAP) and capillaries (mPCWP) along with plasma high-sensitivity troponin T (hsTnT), a marker of cardiomyocyte injury, and the multidimensional urinary classifiers HF1 and HF2, mainly consisting of dysregulated collagen fragments.Results: In multivariable models, mRAP and mPAP increased with hsTnT (per 1-SD, +0.91 and +1.26 mm Hg; P < 0.0001) and with HF2 (+0.42 and +0.62 mm Hg; P ≤ 0.035), but not with HF1. mPCWP increased with hsTnT (+1.16 mm Hg; P < 0.0001), but not with HF1 or HF2. The adjusted odds ratios for having elevated RHP (mRAP, mPAP or mPCWP ≥10, ≥24, ≥17 mm Hg, respectively) were 1.99 for hsTnT and 1.56 for HF2 ( P ≤ 0.005). In detecting elevated RHPs, areas under the curve were similar for hsTnT and HF2 (0.63 vs 0.65; P = 0.66). Adding hsTnT continuous or per threshold or HF2 continuous to a basic model including all covariables did not increase diagnostic accuracy ( P ≥ 0.11), whereas adding HF2 per optimized threshold increased both the integrated discrimination (+1.92%; P = 0.023) and net reclassification (+30.3%; P = 0.010) improvement. Conclusions: Correlating RHPs with noninvasive biomarkers in HTx patients is feasible. However, further refinement and validation of such biomarkers is required before their clinical application can be considered.

KW - VENTRICULAR FILLING PRESSURES

KW - URINARY PROTEOME ANALYSIS

KW - CORONARY-ARTERY-DISEASE

KW - TROPONIN-T ASSAY

KW - CARDIAC TRANSPLANTATION

KW - PULMONARY-HYPERTENSION

KW - GENERAL-POPULATION

KW - PROGNOSTIC VALUE

KW - ACUTE REJECTION

KW - DYSFUNCTION

U2 - 10.1097/TXD.0000000000000783

DO - 10.1097/TXD.0000000000000783

M3 - Article

C2 - 29796417

SN - 2373-8731

VL - 4

JO - Transplantation Direct

JF - Transplantation Direct

IS - 5

M1 - 346

ER -