Reproducibility of peak filling and peak emptying rate determined by cardiovascular magnetic resonance imaging for assessment of biventricular systolic and diastolic dysfunction in patients with pulmonary arterial hypertension

  • Christoffer Göransson
  • Niels Vejlstrup
  • Jørn Carlsen
Original Paper


Right ventricular (RV) and left ventricular (LV) diastolic stiffness may be independent contributors to disease progression in pulmonary arterial hypertension (PAH). The aims of this study are to assess reproducibility of peak emptying rate (PER) and early diastolic peak filling rate (PFR) for both the RV and the LV in PAH and study their relationship to stroke volume (SV). Triple weekly repetition of 20 (totalling 60) cardiovascular magnetic resonance (CMR) scans, were done on 10 patients with PAH and 10 healthy controls. RV and LV volumes were measured over the full cardiac cycle. PER and PFR were calculated as the first derivative of the time–volume relationship in both the RV and the LV and indexed to body surface area. Reproducibility and the relation to SV were studied in a mixed model. PFR was lower in PAH in both the RV (PAH = 170 mL/m2/s, controls = 236 mL/m2/s [p < 0.01]) and in the LV (PAH = 209 mL/m2/s, controls = 311 mL/m2/s [p < 0.01]). PERs were not significantly different between patients and controls. Reproducibility of PER and PFR was high. A trial targeting normalization of PFR requires a total sample size of < 20. PER and PFR in both ventricles were strongly associated with stroke volume (all four: p < 0.01). Biventricular diastolic dysfunctions are strongly associated with stroke volume, and CMR can quantify them with high reproducibility, enabling small sample sizes for trials of therapies targeting diastolic dysfunction to increase survival.


Pulmonary arterial hypertension Cardiovascular magnetic resonance imaging Diastolic dysfunction Cardiac variability Trial sample size 



This work was supported by an unrestricted grant from Actelion, Nordic. The sponsor did not participate in the study design, data collection, analysis interpretation, writing of the manuscript or decision to submit the manuscript for publication.

Compliance with ethical standards

Conflict of interest

The authors report no relationships that could be construed as a conflict of interest.


  1. 1.
    Farber HW, Loscalzo J (2004) Pulmonary arterial hypertension. N Engl J Med 351:1655–1665. CrossRefPubMedGoogle Scholar
  2. 2.
    Vonk-Noordegraaf A, Haddad F, Chin KM et al (2013) Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol 62:D22–D33. CrossRefPubMedGoogle Scholar
  3. 3.
    van Wolferen SA, Marcus JT, Boonstra A et al (2007) Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur Heart J 28:1250–1257. CrossRefPubMedGoogle Scholar
  4. 4.
    van de Veerdonk MC, Marcus JT, Westerhof N et al (2015) Signs of right ventricular deterioration in clinically stable patients with pulmonary arterial hypertension. Chest 147:1063–1071. CrossRefPubMedGoogle Scholar
  5. 5.
    van Wolferen SA, van de Veerdonk MC, Mauritz G-J et al (2011) CLinically significant change in stroke volume in pulmonary hypertension. Chest 139:1003–1009. CrossRefPubMedGoogle Scholar
  6. 6.
    Grossman W (1991) Diastolic dysfunction in congestive heart failure. N Engl J Med 325:1557–1564. CrossRefPubMedGoogle Scholar
  7. 7.
    Gan CT-J, Holverda S, Marcus JT et al (2007) Right ventricular diastolic dysfunction and the acute effects of sildenafil in pulmonary hypertension patients. Chest 132:11–17. CrossRefPubMedGoogle Scholar
  8. 8.
    Trip P, Rain S, Handoko ML et al (2015) Clinical relevance of right ventricular diastolic stiffness in pulmonary hypertension. Eur Respir J 45:1603–1612. CrossRefPubMedGoogle Scholar
  9. 9.
    Rain S, Handoko ML, Trip P et al (2013) Right ventricular diastolic impairment in patients with pulmonary arterial hypertension. Circulation 128:2016–2025. CrossRefPubMedGoogle Scholar
  10. 10.
    Mauritz G-J, Marcus JT, Westerhof N et al (2011) Prolonged right ventricular post-systolic isovolumic period in pulmonary arterial hypertension is not a reflection of diastolic dysfunction. Heart 97:473–478. CrossRefPubMedGoogle Scholar
  11. 11.
    Marcus JT, Gan CT-J, Zwanenburg JJM et al (2008) Interventricular mechanical asynchrony in pulmonary arterial hypertension: left-to-right delay in peak shortening is related to right ventricular overload and left ventricular underfilling. J Am Coll Cardiol 51:750–757. CrossRefPubMedGoogle Scholar
  12. 12.
    Vonk-Noordegraaf A, Marcus JT, Gan CT et al (2005) Interventricular mechanical asynchrony due to right ventricular pressure overload in pulmonary hypertension plays an important role in impaired left ventricular filling. Chest 128:628S–630S. CrossRefPubMedGoogle Scholar
  13. 13.
    Marcus JT, Vonk-Noordegraaf A, Roeleveld RJ et al (2001) Impaired left ventricular filling due to right ventricular pressure overload in primary pulmonary hypertension: noninvasive monitoring using MRI. Chest 119:1761–1765. CrossRefPubMedGoogle Scholar
  14. 14.
    Louie EK, Lin SS, Reynertson SI et al (1995) Pressure and volume loading of the right ventricle have opposite effects on left ventricular ejection fraction. Circulation 92:819–824. CrossRefPubMedGoogle Scholar
  15. 15.
    Lazar JM, Flores AR, Grandis DJ et al (1993) Effects of chronic right ventricular pressure overload on left ventricular diastolic function. Am J Cardiol 72:1179–1182. CrossRefPubMedGoogle Scholar
  16. 16.
    Knight DS, Steeden JA, Moledina S et al (2015) Left ventricular diastolic dysfunction in pulmonary hypertension predicts functional capacity and clinical worsening: a tissue phase mapping study. J Cardiovasc Magn Reson 17:116. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Hardegree EL, Sachdev A, Fenstad ER et al (2013) Impaired left ventricular mechanics in pulmonary arterial hypertension clinical perspective. Circulation 6:748–755. PubMedGoogle Scholar
  18. 18.
    Galiè N, Humbert M, Vachiéry J-L et al (2016) 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): endorsed by: association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J 37:67–119. CrossRefPubMedGoogle Scholar
  19. 19.
    Clarke CJ, Gurka MJ, Norton PT et al (2012) Assessment of the accuracy and reproducibility of RV volume measurements by CMR in congenital heart disease. JACC Cardiovasc Imaging 5:28–37. CrossRefPubMedGoogle Scholar
  20. 20.
    Schulz-Menger J, Bluemke DA, Bremerich J et al (2013) Standardized image interpretation and post processing in cardiovascular magnetic resonance: society for Cardiovascular Magnetic Resonance (SCMR) board of trustees task force on standardized post processing. 15:35.
  21. 21.
    Holst K, Scheike T, Gerds TA, Hjelmborg J (2015) Mets: analysis of multivariate event times, R package version 1.1. 1. Lifetime Data Anal 11:389–404. Google Scholar
  22. 22.
    Pinheiro J, Bates DM, Debroy S, Sarkar D (2010) Linear and nonlinear mixed effects models: package “nlme,” version 3.1-97Google Scholar
  23. 23.
    Bates D, Maechler M, Bolker B, Walker S (2013) lme4: linear mixed-effects models using Eigen and S4. R package version 1.0-5Google Scholar
  24. 24.
    Brant R Inference for means: comparing two independent samples. Accessed 10 Mar 2017
  25. 25.
    Klotz S, Hay I, Dickstein ML et al (2006) Single-beat estimation of end-diastolic pressure-volume relationship: a novel method with potential for noninvasive application. Am J Physiol 291:H403–H412. Google Scholar
  26. 26.
    Brimioulle S, Wauthy P, Ewalenko P et al (2003) Single-beat estimation of right ventricular end-systolic pressure-volume relationship. Am J Physiol 284:H1625–H1630. CrossRefGoogle Scholar
  27. 27.
    Bradlow WM, Hughes ML, Keenan NG et al (2009) Measuring the heart in pulmonary arterial hypertension (PAH): implications for trial study size. J Magn Reson Imaging 31:117–124. CrossRefGoogle Scholar
  28. 28.
    Avriel A, Klement AH, Johnson SR et al (2017) Impact of left ventricular diastolic dysfunction on lung transplantation outcome in patients with pulmonary arterial hypertension. Am J Transpl 32:965. Google Scholar
  29. 29.
    Ahtarovski KA, Iversen KK, Christensen TE et al (2014) Takotsubo cardiomyopathy, a two-stage recovery of left ventricular systolic and diastolic function as determined by cardiac magnetic resonance imaging. Eur Heart J 15:855–862. Google Scholar
  30. 30.
    Ahtarovski KA, Iversen KK, Lønborg JT et al (2013) Termination of dobutamine infusion causes transient rebound left heart diastolic dysfunction in healthy elderly women but not in men: a cardiac magnetic resonance study. Am J Physiol 305:H1098–H1103. CrossRefGoogle Scholar
  31. 31.
    Mahmud E, Raisinghani A, Hassankhani A et al (2002) Correlation of left ventricular diastolic filling characteristics with right ventricular overload and pulmonary artery pressure in chronic thromboembolic pulmonary hypertension. J Am Coll Cardiol 40:318–324CrossRefPubMedGoogle Scholar
  32. 32.
    Ritchie M, Waggoner AD, Dávila-Román VG et al (1993) Echocardiographic characterization of the improvement in right ventricular function in patients with severe pulmonary hypertension after single-lung transplantation. J Am Coll Cardiol 22:1170–1174CrossRefPubMedGoogle Scholar
  33. 33.
    Galiè N, Hinderliter AL, Torbicki A et al (2003) Effects of the oral endothelin-receptor antagonist bosentan on echocardiographic and doppler measures in patients with pulmonary arterial hypertension. J Am Coll Cardiol 41:1380–1386CrossRefPubMedGoogle Scholar
  34. 34.
    Maceira AM, Prasad SK, Khan M, Pennell DJ (2006) Normalized left ventricular systolic and diastolic function by steady state free precession cardiovascular magnetic resonance. J Cardiovasc Magn Reson 8:417–426CrossRefPubMedGoogle Scholar
  35. 35.
    Kawel-Boehm N, Maceira A, Valsangiacomo-Buechel ER et al (2015) Normal values for cardiovascular magnetic resonance in adults and children. J Cardiovasc Magn Reson 17:29. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Dawes TJW, de Marvao A, Shi W et al (2017) Machine learning of three-dimensional right ventricular motion enables outcome prediction in pulmonary hypertension: a cardiac MR imaging study. Radiology 283:381–390. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Krittanawong C, Zhang H, Wang Z et al (2017) Artificial intelligence in precision cardiovascular medicine. J Am Coll Cardiol 69:2657–2664. CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media B.V., part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of CardiologyCopenhagen University Hospital, RigshospitaletCopenhagenDenmark
  2. 2.Department of Cardiology, 2141Copenhagen University Hospital, RigshospitaletCopenhagenDenmark

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