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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Exercise MR-proANP unmasks latent right heart failure in CTEPH

  • Steffen D. Kriechbaum
    Correspondence
    Reprint requests: Steffen Kriechbaum, MD, Kerckhoff Heart and Thorax Center, Benekestrasse 2-8, 61231 Bad Nauheim, Germany. Telephone: +49 6032 996 2246. Fax: +49 6032 996 2313.
    Affiliations
    Campus Kerckhoff, University of Giessen, Heart and Thorax Center, Department of Cardiology, Bad Nauheim, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany
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  • Judith Birmes
    Affiliations
    Campus Kerckhoff, University of Giessen, Heart and Thorax Center, Department of Cardiology, Bad Nauheim, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany
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  • Christoph B. Wiedenroth
    Affiliations
    Campus Kerckhoff, University of Giessen, Heart and Thorax Center, Department of Thoracic Surgery, Bad Nauheim, Germany
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  • Miriam S.D. Adameit
    Affiliations
    Campus Kerckhoff, University of Giessen, Heart and Thorax Center, Department of Thoracic Surgery, Bad Nauheim, Germany
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  • Dimitri Gruen
    Affiliations
    Justus Liebig University Giessen, Medical Clinic I, Division of Cardiology, Giessen, Germany
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  • J. Vietheer
    Affiliations
    Campus Kerckhoff, University of Giessen, Heart and Thorax Center, Department of Cardiology, Bad Nauheim, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany
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  • Manuel J. Richter
    Affiliations
    Department of Pneumology, Kerckhoff-Klinik, Bad Nauheim, Germany

    Department of Internal Medicine, Justus Liebig University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany
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  • Stefan Guth
    Affiliations
    Campus Kerckhoff, University of Giessen, Heart and Thorax Center, Department of Thoracic Surgery, Bad Nauheim, Germany
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  • Fritz C. Roller
    Affiliations
    Justus Liebig University Giessen, Department of Radiology, Giessen, Germany
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  • Matthias Rademann
    Affiliations
    Campus Kerckhoff, University of Giessen, Heart and Thorax Center, Department of Cardiology, Bad Nauheim, Germany
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  • Ulrich Fischer-Rasokat
    Affiliations
    Campus Kerckhoff, University of Giessen, Heart and Thorax Center, Department of Cardiology, Bad Nauheim, Germany

    Justus Liebig University Giessen, Medical Clinic I, Division of Cardiology, Giessen, Germany
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  • Andreas Rolf
    Affiliations
    Campus Kerckhoff, University of Giessen, Heart and Thorax Center, Department of Cardiology, Bad Nauheim, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany

    Justus Liebig University Giessen, Medical Clinic I, Division of Cardiology, Giessen, Germany
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  • Christoph Liebetrau
    Affiliations
    Campus Kerckhoff, University of Giessen, Heart and Thorax Center, Department of Cardiology, Bad Nauheim, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany

    Cardioangiologisches Centrum Bethanien, Frankfurt am Main, Germany
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  • Christian W. Hamm
    Affiliations
    Campus Kerckhoff, University of Giessen, Heart and Thorax Center, Department of Cardiology, Bad Nauheim, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany

    Justus Liebig University Giessen, Medical Clinic I, Division of Cardiology, Giessen, Germany
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  • Author Footnotes
    # These authors contributed equally as last authors.
    Till Keller
    Footnotes
    # These authors contributed equally as last authors.
    Affiliations
    Campus Kerckhoff, University of Giessen, Heart and Thorax Center, Department of Cardiology, Bad Nauheim, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany

    Justus Liebig University Giessen, Medical Clinic I, Division of Cardiology, Giessen, Germany
    Search for articles by this author
  • Author Footnotes
    # These authors contributed equally as last authors.
    Andreas J. Rieth
    Footnotes
    # These authors contributed equally as last authors.
    Affiliations
    Campus Kerckhoff, University of Giessen, Heart and Thorax Center, Department of Cardiology, Bad Nauheim, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany
    Search for articles by this author
  • Author Footnotes
    # These authors contributed equally as last authors.

      Objective

      The present study was designed to investigate the dynamics of right atrial pressure (RAP) and mid-regional pro-atrial natriuretic peptide (MR-proANP) during physical exercise in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to determine whether these parameters might serve as a tool to measure exercise-dependent atrial stress as an indicator of right heart failure.

      Methods

      This prospective observational cohort study included 100 CTEPH patients who underwent right heart catheterization during physical exercise (eRHC). Blood samples for MR-proANP measurement were taken prior, during, and after eRHC. MR-proANP levels were correlated to RAP levels at rest, at peak exercise (eRAP), and during recovery. RAP at rest ≤7 mmHg was defined as normal and eRAP >15 mmHg as suggestive of right heart failure.

      Results

      During eRHC mean RAP increased from 6 mmHg (standard deviation, SD 4) to 16 mmHg (SD 7; p < 0.001). MR-proANP levels and dynamics correlated with RAP at rest (rs = 0.61; p < 0.001) and at peak exercise (rs = 0.66; p < 0.001). Logistic regression analysis revealed the peak MR-proANP level (B = 0.058; p = 0.004) and the right atrial area (B = 0.389; p < 0.001) to be associated with eRAP dynamics. A peak MR-proANP level ≥139 pmol/L (AUC = 0.81) and recovery level ≥159 pmol/L (AUC = 0.82) predicted an eRAP >15 mmHg. Physical exercise unmasked right heart failure in 39% of patients with normal RAP at rest; these patients were also characterized by a more distinct increase in MR-proANP levels (p = 0.005) and higher peak (p < 0.001) and recovery levels (p < 0.001).

      Conclusions

      RAP and MR-proANP dynamics unmask manifest and latent right heart failure in CTEPH patients.

      KEYWORDS

      Abbreviations:

      CI (cardiac index), CTEPH (chronic thromboembolic pulmonary hypertension), CTEPD (chronic thromboembolic pulmonary disease), mPAP (mean pulmonary artery pressure), MR-proANP (mid-regional pro-atrial natriuretic peptide), NT-proBNP (N-terminal pro-brain natriuretic peptide), PAPi (pulmonary artery pulsatility index), PCWP (pulmonary capillary wedge pressure), PH (pulmonary hypertension), PVR (pulmonary vascular resistance), (e)RAP ((exercise) right atrial pressure), (e)RHC ((exercise) right heart catheterization), RHF (right heart failure), RV (right ventricle), RVSWI (right ventricular stroke work index), SvO2 (mixed venous oxygen saturation), TPR (total pulmonary resistance)
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      References

        • Sanz J
        • Sánchez-Quintana D
        • Bossone E
        • et al.
        Anatomy, function, and dysfunction of the right ventricle: JACC state-of-the-art review.
        J Am Coll Cardiol United States. 2019; 73: 1463-1482
        • Simonneau G
        • Torbicki A
        • Dorfmuller P
        • et al.
        The pathophysiology of chronic thromboembolic pulmonary hypertension.
        Eur Respir Rev. 2017; 26 (2017/03/31)160112
        • van de Veerdonk MC
        • Bogaard HJ
        • Voelkel NF.
        The right ventricle and pulmonary hypertension.
        Hear Fail Rev. 2016; 21: 259-271
        • Cogswell R
        • Pritzker M
        • De Marco T.
        Performance of the REVEAL pulmonary arterial hypertension prediction model using non-invasive and routinely measured parameters.
        J. Hear Lung Transplant. 2014; 33: 382-387
        • D'Alonzo GE
        • Barst RJ
        • Ayres SM
        • et al.
        Survival in patients with primary pulmonary hypertension: results from a national prospective registry.
        Ann Intern Med. 1991; 115: 343-349
        • Shah SJ
        • Thenappan T
        • Rich S
        • et al.
        Association of serum creatinine with abnormal hemodynamics and mortality in pulmonary arterial hypertension.
        Circulation. 2008; 117: 2475-2483
        • Chakinala MM
        • Coyne DW
        • Benza RL
        • et al.
        Impact of declining renal function on outcomes in pulmonary arterial hypertension: a REVEAL registry analysis.
        J Hear Lung Transplant. 2018; 37: 696-705
        • Drazner MH
        • Rame JE
        • Stevenson LW
        • et al.
        Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure.
        N Engl J Med. 2001; 345: 574-581
        • Damman K
        • van Deursen VM
        • Navis G
        • et al.
        Increased central venous pressure is associated with impaired renal function and mortality in a broad spectrum of patients with cardiovascular disease.
        J Am Coll Cardiol. 2009; 53: 582-588
        • Galiè N
        • Humbert M
        • Vachiery J-L
        • et al.
        2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endor.
        Eur Hear J. 2016; 37: 67-119
        • Kovacs G
        • Herve P
        • Barbera JA
        • et al.
        An official European Respiratory Society statement: pulmonary haemodynamics during exercise.
        Eur Respir J. 2017; 501700578
        • Watts JA
        • Kelly FR
        • Bauch TD
        • et al.
        Rest and exercise hemodynamic and metabolic findings in active duty soldiers referred for cardiac catheterization to exclude heart disease: insights from past invasive cardiopulmonary exercise testing using multisensor high fidelity catheters.
        Catheter Cardiovasc Interv John Wiley Sons Ltd. 2018; 91: 35-46
        • Wolsk E
        • Bakkestrøm R
        • Thomsen JH
        • et al.
        The influence of age on hemodynamic parameters during rest and exercise in healthy individuals.
        JACC Hear Fail. 2017; 5: 337-346
        • Lichtblau M
        • Bader PR
        • Saxer S
        • et al.
        Right atrial pressure during exercise predicts survival in patients with pulmonary hypertension.
        J Am Heart Assoc Am Heart Assoc. 2020; 9e018123
        • Karunanithi Z
        • Andersen MJ
        • Mellemkjær S
        • et al.
        Elevated left and right atrial pressures long-term after atrial septal defect correction: an invasive exercise hemodynamic study.
        J Am Heart Assoc. 2021; 10e020692
        • Stickland MK
        • Welsh RC
        • Petersen SR
        • et al.
        Does fitness level modulate the cardiovascular hemodynamic response to exercise?.
        J Appl Physiol Am Physiol Soc. 2006; 100: 1895-1901
        • Mehra MR
        • Park MH
        • Landzberg MJ
        • et al.
        Right heart failure: toward a common language.
        Pulm Circ. 2013; 3: 963-967
        • Aslam MI
        • Jani V
        • Lin BL
        • et al.
        Pulmonary artery pulsatility index predicts right ventricular myofilament dysfunction in advanced human heart failure.
        Eur J Heart Fail. 2021; 23: 339-341
        • Gorter TM
        • Obokata M
        • Reddy YN V
        • et al.
        Exercise unmasks distinct pathophysiologic features in heart failure with preserved ejection fraction and pulmonary vascular disease.
        Eur Heart J. 2018; 39: 2825-2835
        • Nakagawa Y
        • Nishikimi T
        • Kuwahara K.
        Atrial and brain natriuretic peptides: hormones secreted from the heart.
        Peptides. 2019; 111: 18-25
        • Raine AEG
        • Erne P
        • Bürgisser E
        • et al.
        Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure.
        N Engl J Med. 1986; 315: 533-537
        • Kriechbaum SD
        • Scherwitz L
        • Wiedenroth CB
        • et al.
        Mid-regional pro-atrial natriuretic peptide and copeptin as indicators of disease severity and therapy response in CTEPH.
        ERJ Open Res. 2020; 6: 00356-02020
        • Kaiser R
        • Grotemeyer K
        • Lepper P
        • et al.
        Associations of circulating natriuretic peptides with haemodynamics in precapillary pulmonary hypertension.
        Respir Med. 2015; 109: 1213-1223
        • Völkers M
        • Rohde D
        • Zelniker T
        • et al.
        High-sensitive Troponin T increase after exercise in patients with pulmonary arterial hypertension.
        BMC Pulm Med. 2013; 13: 28
        • Grachtrup S
        • Brügel M
        • Pankau H
        • et al.
        Exercise Dependence of N-Terminal Pro-Brain Natriuretic Peptide in Patients with Precapillary Pulmonary Hypertension.
        Respiration. 2012; 84: 454-460
        • Kutsch J
        • Faul C
        • von Scheidt W
        • et al.
        The association of the N-terminal pro-brain-type natriuretic peptide response to exercise with disease severity in therapy-naive pulmonary arterial hypertension: a cohort study.
        Respir Res. 2018; 19: 8
        • Wiedenroth CB
        • Ghofrani HA
        • Adameit MSD
        • et al.
        Sequential treatment with riociguat and balloon pulmonary angioplasty for patients with inoperable chronic thromboembolic pulmonary hypertension.
        Pulm Circ. 2018; 82045894018783996https://doi.org/10.1177/2045894018783996
        • Lankeit M
        • Krieg V
        • Hobohm L
        • et al.
        Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension.
        J Hear Lung Transpl. 2017;
        • Rieth A
        • Richter MJ
        • Gall H
        • et al.
        Hemodynamic phenotyping based on exercise catheterization predicts outcome in patients with heart failure and reduced ejection fraction.
        J Hear Lung Transplant. 2017; 36: 880-889
        • Wiedenroth Christoph B.
        • Rieth Andreas J.
        • Kriechbaum Steffen
        • et al.
        Exercise right heart catheterization before and after balloon pulmonary angioplasty in inoperable patients with chronic thromboembolic pulmonary hypertension.
        Pulm Circ. 2020; 102045894020917884
        • Kovacs G
        • Avian A
        • Pienn M
        • et al.
        Reading pulmonary vascular pressure tracings. how to handle the problems of zero leveling and respiratory swings.
        Am J Respir Crit Care Med. 2014; 190: 252-257
        • Systrom D
        • Warren A
        • Naeije R.
        The role of exercise testing in pulmonary vascular disease: diagnosis and management.
        Clin Chest Med. 2021; 42: 113-123
        • Alenezi F
        • Mandawat A
        • Il'Giovine ZJ
        • et al.
        Clinical utility and prognostic value of right atrial function in pulmonary hypertension.
        Circ Cardiovasc Imaging. 2018; 11e006984
        • D'Alonzo GE
        • Barst RJ
        • Ayres SM
        • et al.
        Survival in patients with primary pulmonary hypertension: results from a national prospective registry.
        Ann Intern Med. 1991; 115: 343-349
        • Raymond RJ
        • Hinderliter AL
        • Willis IV PW
        • et al.
        Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension.
        J Am Coll Cardiol. 2002; 39: 1214-1219
        • Richter MJ
        • Zedler D
        • Berliner D
        • et al.
        Clinical relevance of right atrial functional response to treatment in pulmonary arterial hypertension.
        Front Cardiovasc Med. 2021; : 1758
        • Pellicori P
        • Carubelli V
        • Zhang J
        • et al.
        IVC diameter in patients with chronic heart failure: relationships and prognostic significance.
        JACC Cardiovasc Imaging. 2013; 6: 16-28
        • Lim DS
        • Kar S
        • Spargias K
        • et al.
        Transcatheter valve repair for patients with mitral regurgitation: 30-Day results of the CLASP study.
        JACC Cardiovasc Interv. 2019;
        • Jensen JK
        • Clemmensen TS
        • Frederiksen CA
        • et al.
        Clinical performance and exercise hemodynamics in patients with severe secondary tricuspid regurgitation and chronic atrial fibrillation.
        BMC Cardiovasc. Disord. 2021; 21: 276
        • Rieth AJ
        • Richter MJ
        • Tello K
        • et al.
        Exercise hemodynamics in heart failure patients with preserved and mid-range ejection fraction: key role of the right heart.
        Clin Res Cardiol. 2021;
        • Kato M
        • Kinugawa T
        • Ogino K
        • et al.
        Augmented response in plasma brain natriuretic peptide to dynamic exercise in patients with left ventricular dysfunction and congestive heart failure.
        J Intern Med. 2000; 248: 309-315
        • Kato M
        • Kinugawa T
        • Omodani H
        • et al.
        Augmented response in plasma atrial natriuretic peptide to dynamic exercise in patients with congestive heart failure.
        Jpn Circ J. 1996; 60: 909-916
        • Daniels LB
        • Clopton P
        • Potocki M
        • et al.
        Influence of age, race, sex, and body mass index on interpretation of midregional pro atrial natriuretic peptide for the diagnosis of acute heart failure: Results from the BACH multinational study.
        Eur J Heart Fail. 2012; 14: 22-31