Advertisement

European Radiology

, Volume 29, Issue 3, pp 1574–1585 | Cite as

Left ventricular extracellular volume fraction and atrioventricular interaction in hypertension

  • Jonathan C. L. RodriguesEmail author
  • Tamas Erdei
  • Amardeep Ghosh Dastidar
  • Gergley Szantho
  • Amy E. Burchell
  • Laura E. K. Ratcliffe
  • Emma C. Hart
  • Angus K. Nightingale
  • Julian F. R. Paton
  • Nathan E. Manghat
  • Mark C. K. Hamilton
Cardiac

Abstract

Objectives

Left atrial enlargement (LAE) predicts cardiovascular morbidity and mortality. Impaired LA function also confers poor prognosis. This study aimed to determine whether left ventricular (LV) interstitial fibrosis is associated with LAE and LA impairment in systemic hypertension.

Methods

Following informed written consent, a prospective observational study of 86 hypertensive patients (49 ± 15 years, 53% male, office SBP 168 ± 30 mmHg, office DBP 97 ± 4 mmHg) and 20 normotensive controls (48 ± 13 years, 55% male, office SBP 130 ± 13 mmHg, office DBP 80 ± 11 mmHg) at 1.5-T cardiovascular magnetic resonance was conducted. Extracellular volume fraction (ECV) was calculated by T1-mapping. LA volume (LAV) was measured with biplane area-length method. LA reservoir, conduit and pump function were calculated with the phasic volumetric method.

Results

Indexed LAV correlated with indexed LV mass (R = 0.376, p < 0.0001) and ECV (R = 0.359, p = 0.001). However, ECV was the strongest significant predictor of LAE in multivariate regression analysis (odds ratio [95th confidence interval] 1.24 [1.04–1.48], p = 0.017). Indexed myocardial interstitial volume was associated with significant reductions in LA reservoir (R = -0.437, p < 0.0001) and conduit (R = -0.316, p = 0.003) but not pump (R = -0.167, p = 0.125) function. Multiple linear regression, correcting for age, gender, BMI, BP and diabetes, showed an independent decrease of 3.5% LA total emptying fraction for each 10 ml/m2 increase in myocardial interstitial volume (standard β coefficient -3.54, p = 0.002).

Conclusions

LV extracellular expansion is associated with LAE and impaired LA reservoir and conduit function. Future studies should identify if targeting diffuse LV fibrosis is beneficial in reverse remodelling of LA structural and functional pathological abnormalities in hypertension.

Key Points

• Left atrial enlargement (LAE) and impairment are markers of adverse prognosis in systemic hypertension but their pathophysiology is poorly understood.

• Left ventricular extracellular volume fraction was the strongest independent multivariate predictor of LAE and was associated with impaired left atrial reservoir and conduit function.

• LV interstitial expansion may play a central role in the pathophysiology of adverse atrioventricular interaction in systemic hypertension.

Keywords

Cardiac imaging techniques Magnetic resonance imaging Hypertension Fibrosis Strain 

Abbreviations

ANOVA

Analysis of ariance

BMI

Body mass index

CMR

Cardiovascular magnetic resonance

DBP

Diastolic blood pressure

ECV

Extracellular volume fraction

EDV

End-diastolic volume

ESC

European Society of Cardiology

ESV

End-systolic volume

LA

Left atrial

LAE

Left atrial enlargement

LAV

Left atrial volume

LAVmax

Maximal left atrial volume

LAVmin

Minimal left atrial volume

LAVpre-A

Left atrial volume just prior to left atrial contraction

LV

Left ventricular

LVH

Left ventricular hypertrophy

LVM

Left ventricular mass

ROI

Region of interest

SBP

Systolic blood pressure

SSFP

Steady state free precession

SV

Stroke volume

Notes

Acknowledgements

This work was supported by the Bristol National Institute for Health Research (NIHR) Cardiovascular Biomedical Research Unit at the Bristol Heart Institute. The views expressed are those of the authors and not necessarily those of the National Health Service, NIHR, or Department of Health.

We thank Christopher Lawton, Superintendent Radiographer, and the Bristol Heart Institute CMR radiographers for their expertise in performing the CMRs. JCLR: Clinical Society of Bath Postgraduate Research Bursary 2014 and Royal College of Radiologists Kodak Research Scholarship 2014. ECH and JFRP are funded by the British Heart Foundation.

Funding

This study has received funding by The Royal College of Radiologists Kodak Research Scholarship 2014.

Compliance with ethical standards

Guarantor

The scientific guarantor of this publication is Dr Mark Hamilton.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional review board approval was obtained.

Methodology

• prospective

• observational

• performed at one institution

References

  1. 1.
    Cuspidi C, Rescaldani M, Sala C (2013) Prevalence of echocardiographic left-atrial enlargement in hypertension: a systematic review of recent clinical studies. Am J Hypertens 26:456–464CrossRefGoogle Scholar
  2. 2.
    Shigematsu Y, Norimatsu S, Ogimoto A, Ohtsuka T, Okayama H, Higaki J (2009) The influence of insulin resistance and obesity on left atrial size in Japanese hypertensive patients. Hypertens Res 32:500–504Google Scholar
  3. 3.
    Modena MG, Muia N, Sgura FA, Molinari R, Castella A, Rossi R (1997) Left atrial size is the major predictor of cardiac death and overall clinical outcome in patients with dilated cardiomyopathy: a long-term follow-up study. Clin Cardiol 20:553–560Google Scholar
  4. 4.
    Appleton CP, Hatle LK, Popp RL (1988) Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol 12:426–440CrossRefGoogle Scholar
  5. 5.
    Prioli A, Marino P, Lanzoni L, Zardini P (1998) Increasing degrees of left ventricular filling impairment modulate left atrial function in humans. Am J Cardiol 82:756–761CrossRefGoogle Scholar
  6. 6.
    Kaminski M, Steel K, Jerosch-Herold M et al (2011) Strong cardiovascular prognostic implication of quantitative left atrial contractile function assessed by cardiac magnetic resonance imaging in patients with chronic hypertension. J Cardiovasc Magn Reson 13:42CrossRefGoogle Scholar
  7. 7.
    Mancia G, Fagard R, Narkiewicz K et al (2013) 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 34:2159–2219CrossRefGoogle Scholar
  8. 8.
    Maceira A, Prasad S, Khan M, Pennell D (2006) Normalized left ventricular systolic and diastolic function by steady state free precession cardiovascular magnetic resonance. J Cardiovasc Magn Reson 8:417–426CrossRefGoogle Scholar
  9. 9.
    Sievers B, Kirchberg S, Addo M, Bakan A, Brandts B, Trappe HJ (2004) Assessment of left atrial volumes in sinus rhythm and atrial fibrillation using the biplane area-length method and cardiovascular magnetic resonance imaging with TrueFISP. J Cardiovasc Magn Reson 6:855–863Google Scholar
  10. 10.
    Blume GG, Mcleod CJ, Barnes ME et al (2011) Left atrial function: physiology, assessment, and clinical implications. Eur J Echocardiogr 12:421–430CrossRefGoogle Scholar
  11. 11.
    Hsiao SH, Chiou KR (2013) Left atrial expansion index predicts all-cause mortality and heart failure admissions in dyspnoea. Eur J Heart Fail 15:1245–1252CrossRefGoogle Scholar
  12. 12.
    Hsiao SH, Chu KA, Wu CJ, Chiou KR (2016) Left atrial expansion index predicts left ventricular filling pressure and adverse events in acute heart failure with severe left ventricular dysfunction. J Card Fail 22:272–279CrossRefGoogle Scholar
  13. 13.
    Hsiao SH, Chiou KR (2016) Diastolic heart failure predicted by left atrial expansion index in patients with severe diastolic dysfunction. PLoS One 11:e0162599CrossRefGoogle Scholar
  14. 14.
    Paulus WJ, Tschöpe C, Sanderson JE et al (2007) How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 28:2539–2550CrossRefGoogle Scholar
  15. 15.
    Järvinen VM, Kupari MM, Hekali PE, Poutanen VP (1994) Right atrial MR imaging studies of cadaveric atrial casts and comparison with right and left atrial volumes and function in healthy subjects. Radiology 191:137–142CrossRefGoogle Scholar
  16. 16.
    Tseng WY, Liao TY, Wang JL (2002) Normal systolic and diastolic functions of the left ventricle and left atrium by cine magnetic resonance imaging. J Cardiovasc Magn Reson 4:443–457CrossRefGoogle Scholar
  17. 17.
    Petersen SE, Aung N, Sanghvi MM et al (2017) Reference ranges for cardiac structure and function using cardiovascular magnetic resonance (CMR) in Caucasians from the UK Biobank population cohort. J Cardiovasc Magn Reson 19:18CrossRefGoogle Scholar
  18. 18.
    Childs H, Ma L, Ma M et al (2011) Comparison of long and short axis quantification of left ventricular volume parameters by cardiovascular magnetic resonance, with ex-vivo validation. J Cardiovasc Magn Reson 13:40CrossRefGoogle Scholar
  19. 19.
    Pica S, Sado DM, Maestrini V et al (2014) Reproducibility of native myocardial T1 mapping in the assessment of Fabry disease and its role in early detection of cardiac involvement by cardiovascular magnetic resonance. J Cardiovasc Magn Reson 16:99CrossRefGoogle Scholar
  20. 20.
    Flett AS, Sado DM, Quarta G et al (2012) Diffuse myocardial fibrosis in severe aortic stenosis: an equilibrium contrast cardiovascular magnetic resonance study. Eur Heart J Cardiovasc Imaging 13:819–826CrossRefGoogle Scholar
  21. 21.
    Bistoquet A, Oshinski J, Skrinjar O (2007) Left ventricular deformation recovery from cine MRI using an incompressible model. IEEE Trans Med Imaging 26:1136–1153CrossRefGoogle Scholar
  22. 22.
    Bistoquet A, Oshinski J, Skrinjar O (2008) Myocardial deformation recovery from cine MRI using a nearly incompressible biventricular model. Med Image Anal 12:69–85CrossRefGoogle Scholar
  23. 23.
    Kuruvilla S, Janardhanan R, Antkowiak P et al (2015) Increased extracellular volume and altered mechanics are associated with LVH in hypertensive heart disease, not hypertension alone. JACC Cardiovasc Imaging 8:172–180CrossRefGoogle Scholar
  24. 24.
    Hinojar R, Varma N, Child N et al (2015) T1 mapping in discrimination of hypertrophic phenotypes: hypertensive heart disease and hypertrophic cardiomyopathy: findings from the international T1 multicenter cardiovascular magnetic resonance study. Circ Cardiovasc Imaging 8:e003285CrossRefGoogle Scholar
  25. 25.
    Treibel TA, Zemrak F, Sado DM et al (2015) Extracellular volume quantification in isolated hypertension - changes at the detectable limits? J Cardiovasc Magn Reson 17:74CrossRefGoogle Scholar
  26. 26.
    Rodrigues JC, Amadu AM, Dastidar AG et al (2016) Comprehensive characterisation of hypertensive heart disease left ventricular phenotypes. Heart 102:1671–1679CrossRefGoogle Scholar
  27. 27.
    Rodrigues JC, Amadu AM, Ghosh Dastidar A et al (2017) ECG strain pattern in hypertension is associated with myocardial cellular expansion and diffuse interstitial fibrosis: a multi-parametric cardiac magnetic resonance study. Eur Hear J Cardiovasc Imaging 18:441–450CrossRefGoogle Scholar
  28. 28.
    Miyoshi H, Oishi Y, Mizuguchi Y et al (2015) Association of left atrial reservoir function with left atrial structural remodeling related to left ventricular dysfunction in asymptomatic patients with hypertension: evaluation by two-dimensional speckle-tracking echocardiography. Clin Exp Hypertens 37:155–165CrossRefGoogle Scholar
  29. 29.
    Matsuyama N, Tsutsumi T, Kubota N, Nakajima T, Suzuki H, Takeyama Y (2009) Direct action of an angiotensin II receptor blocker on angiotensin II-induced left atrial conduction delay in spontaneously hypertensive rats. Hypertens Res 32:721–726Google Scholar
  30. 30.
    Dernellis JM, Vyssoulis GP, Zacharoulis AA, Toutouzas PK (1996) Effects of antihypertensive therapy on left atrial function. J Hum Hypertens 10:789–794Google Scholar
  31. 31.
    Coelho-Filho OR, Shah RV, Neilan TG et al (2014) Cardiac magnetic resonance assessment of interstitial myocardial fibrosis and cardiomyocyte hypertrophy in hypertensive mice treated with spironolactone. J Am Heart Assoc 3:e000790CrossRefGoogle Scholar
  32. 32.
    Tsang TS, Barnes ME, Gersh BJ et al (2003) Prediction of risk for first age-related cardiovascular events in an elderly population: the incremental value of echocardiography. J Am Coll Cardiol 42:1199–1205CrossRefGoogle Scholar
  33. 33.
    Leung DY, Boyd A, Ng AA, Chi C, Thomas L (2008) Echocardiographic evaluation of left atrial size and function: current understanding, pathophysiologic correlates, and prognostic implications. Am Heart J 156:1056–1064Google Scholar
  34. 34.
    Posina K, McLaughlin J, Rhee P et al (2013) Relationship of phasic left atrial volume and emptying function to left ventricular filling pressure: a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 15:99CrossRefGoogle Scholar
  35. 35.
    Russo C, Jin Z, Homma S et al (2012) Left atrial minimum volume and reservoir function as correlates of left ventricular diastolic function: impact of left ventricular systolic function. Heart 98:813–820CrossRefGoogle Scholar
  36. 36.
    Gupta S, Matulevicius SA, Ayers CR et al (2013) Left atrial structure and function and clinical outcomes in the general population. Eur Heart J 34:278–285CrossRefGoogle Scholar
  37. 37.
    Schafer S, Viswanathan S, Widjaja AA et al (2017) IL11 is a crucial determinant of cardiovascular fibrosis. Nature 552:110–115Google Scholar
  38. 38.
    Rogers T, Puntmann VO (2014) T1 mapping - beware regional variations. Eur Heart J Cardiovasc Imaging 15:1302–1302CrossRefGoogle Scholar
  39. 39.
    Treibel TA, Kozor R, Schofield R et al (2018) Reverse myocardial remodeling following valve replacement in patients with aortic stenosis. J Am Coll Cardiol 71:860–871CrossRefGoogle Scholar
  40. 40.
    De Marvao A, Dawes TJ, Shi W et al (2015) Precursors of hypertensive heart phenotype develop in healthy adults. JACC Cardiovasc Imaging 8:1260–1269CrossRefGoogle Scholar
  41. 41.
    Habibi M, Samiei S, Ambale Venkatesh B et al (2016) Cardiac magnetic resonance-measured left atrial volume and function and incident atrial fibrillation: results from MESA (Multi-Ethnic Study of Atherosclerosis). Circ Cardiovasc Imaging 9:e004299CrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Jonathan C. L. Rodrigues
    • 1
    • 2
    • 3
    Email author
  • Tamas Erdei
    • 1
  • Amardeep Ghosh Dastidar
    • 1
  • Gergley Szantho
    • 1
  • Amy E. Burchell
    • 4
  • Laura E. K. Ratcliffe
    • 4
  • Emma C. Hart
    • 2
    • 4
  • Angus K. Nightingale
    • 4
  • Julian F. R. Paton
    • 2
    • 4
  • Nathan E. Manghat
    • 5
  • Mark C. K. Hamilton
    • 5
  1. 1.Department of Cardiovascular Magnetic Resonance, Bristol Cardiovascular Biomedical Research Unit, Bristol Heart InstituteUniversity Hospitals Bristol NHS Foundation TrustBristolUK
  2. 2.School of Physiology, Pharmacology & Neuroscience, Faculty of Biomedical ScienceUniversity of BristolBristolUK
  3. 3.Department of RadiologyRoyal United Hospitals Bath NHS Foundation TrustBathUK
  4. 4.BHI CardioNomics Research Group, Clinical Research and Imaging Centre-BristolUniversity of BristolBristolUK
  5. 5.Department of Radiology, Bristol Royal InfirmaryUniversity Bristol NHS Foundation TrustBristolUK

Personalised recommendations