Skip to main content
Log in

Left ventricular function in patients with hypertrophic cardiomyopathy and its relation to myocardial fibrosis and exercise tolerance

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

We sought to determine the relation between myocardial extracellular volume (ECV), left ventricular (LV) diastolic function, and exercise tolerance in patients with hypertrophic cardiomyopathy (HCM). Forty five HCM patients with an ejection fraction >50% and no previous septal reduction therapy underwent imaging by CMR and transthoracic echocardiography. CMR was used to quantify LV volumes, mass, EF, LA volumes, scar burden, pre and post contrast T1 relaxation times and ECV. Echocardiography was used to measure outflow tract gradients, mitral inflow and annular velocities, circumferential strain, systolic, early and late diastolic strain rates. Exercise duration and peak oxygen consumption were noted. HCM patients had increased native T1 relaxation time and ECV vs. controls [ECV controls: 24.7 (23.2–26.4) vs. HCM: 26.8 (24.6–31.3)%, P = 0.014]. Both parameters were significantly associated with LV diastolic dysfunction, circumferential strain, diastolic strain rate and peak oxygen consumption (r = −0.73, P < 0.001). Compared to controls, HCM patients have significantly longer native T1 relaxation time and higher ECV. These structural changes lead to worse LV global and segmental diastolic function and in turn reduced exercise tolerance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Maron MS, Appelbaum E, Harrigan CJ, Buros J, Gibson CM, Hanna C, Lesser JR, Udelson JE, Manning WJ, Maron BJ (2008) Clinical profile and significance of delayed enhancement in hypertrophic cardiomyopathy. Circ Heart Fail 1:184–191

    Article  PubMed  Google Scholar 

  2. Kwon DH, Smedira NG, Rodriguez ER, Tan C, Setser R, Thamilarasan M, Lytle BW, Lever HM, Desai MY (2009) Cardiac magnetic resonance detection of myocardial scarring in hypertrophic cardiomyopathy: correlation with histopathology and prevalence or ventricular tachycardia. J Am Coll Cardiol 54:242–249

    Article  PubMed  Google Scholar 

  3. Rubinshtein R, Glockner JF, Ommen SR, Araoz PA, Ackerman MJ, Sorajja P, Bos JM, Tajik AJ, Valeti US, Nishimura RA, Gersh BJ (2010) Characteristics and clinical significance of late gadolinium enhancement by contrast-enhanced magnetic resonance imaging in patients with hypertrophic cardiomyopathy. Circ Heart Fail 3:51–58

    Article  PubMed  Google Scholar 

  4. Bruder O, Wagner A, Jensen CJ, Schneider S, Ong P, Kispert EM, Nassenstein K, Schlosser T, Sabin GV, Sechtem U, Mahrholdt H (2010) Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 56:875–887

    Article  PubMed  Google Scholar 

  5. O’Hanlon R, Grasso A, Roughton M, Moon JC, Clark S, Wage R, Webb J, Kulkarni M, Dawson D, Sulaibeekh L, Chandrasekaran B, Bucciarelli-Ducci C, Pasquale F, Cowie MR, McKenna WJ, Sheppard MN, Elliott PM, Pennell DJ, Prasad SK (2010) Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol 56:867–874

    Article  PubMed  Google Scholar 

  6. Chan RH, Maron BJ, Olivotto I, Pencina MJ, Assenza GE, Haas T, Lesser JR, Gruner C, Crean AM, Rakowski H, Udelson JE, Rowin E, Lombardi M, Cecchi F, Tomberli B, Spirito P, Formisano F, Biagini E, Rapezzi C, De Cecco CN, Autore C, Cook EF, Hong SN, Gibson CM, Manning WJ, Appelbaum E, Maron MS (2014) Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy. Circulation 130:484–495

    Article  PubMed  Google Scholar 

  7. Iles L, Pfluger H, Phrommintikul A, Cherayath J, Aksit P, Gupta SN, Aksit P, Gupta SN, Kaye DM, Taylor AJ (2008) Evaluation of diffuse myocardial fi-brosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping. J Am Coll Cardiol 52:1574–1580

    Article  PubMed  Google Scholar 

  8. Sibley CT, Noureldin RA, Gai N, Nacif MS, Liu S, Turkbey EB, Mudd JO, van der Geest RJ, Lima JA, Halushka MK, Bluemke DA (2012) T1 Mapping in cardiomyopathy at cardiac MR: comparison with endomyocardial biopsy. Radiology 265:724–732

    Article  PubMed  PubMed Central  Google Scholar 

  9. Flett AS, Hayward MP, Ashworth MT, Hansen MS, Taylor AM, Elliott PM, McGregor C, Moon JC (2010) Equilibrium contrast car-diovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation 122:138–144

    Article  PubMed  Google Scholar 

  10. Broberg CS, Chugh S, Conklin C, Sahn DJ, Jerosch-Herold M (2010) Quantification of diffuse myocardial fibrosis and its association with myocardial dysfunction in congenital heart disease. Circ Cardiovasc Imaging 3:727–734

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ugander M, Oki AJ, Hsu LY, Kellman P, Greiser A, Aletras AH, Sibley CT, Chen MY, Bandettini WP, Arai AE (2012) Extracellular volume imaging by magnetic resonance imaging provides insights into overt and subclinical myocardial pathology. Eur Heart J 33:1268–1278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dass S, Suttie JJ, Piechnik SK, Ferreira VM, Holloway CJ, Banerjee R, Mahmod M, Cochlin L, Karamitsos TD, Robson MD, Watkins H, Neubauer S (2012) Myocardial tissue characterization using magnetic resonance noncontrast T1 mapping in hypertrophic and dilated cardiomyopathy. Circ Cardiovasc Imaging 5:726–733

    Article  PubMed  Google Scholar 

  13. Puntmann VO, Voigt T, Chen Z, Mayr M, Karim R, Rhode K, Pastor A, Carr-White G, Razavi R, Schaeffter T, Nagel E (2013) Native T1 mapping in differentiation of normal myocardium from diffuse disease in hypertrophic and dilated cardiomyopathy. J Am Coll Cardiol Imaging 6:475–484

    Article  Google Scholar 

  14. Ellims AH, Iles LM, Ling LH, Hare JL, Kaye DM, Taylor AJ (2012) Diffuse myocardial fibrosis in hypertrophic cardiomyopathy can be identified by cardiovascular magnetic resonance, and is associated with left ventricular diastolic dysfunction. J Cardiovasc Magn Reson 14:76

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ellims AH, Iles LM, Ling LH, Chong B, Macciocca I, Slavin GS, Hare JL, Kaye DM, Marasco SF, McLean CA, James PA, du Sart D, Taylor AJ (2014) A comprehensive evaluation of myocardial fibrosis in hypertrophic cardiomyopathy with cardiac magnetic resonance imaging: linking genotype with fibrotic phenotype. Eur Heart J Cardiovasc Imaging 15:1108–1116

    Article  PubMed  Google Scholar 

  16. Nucifora G, Muser D, Gianfagna P, Morocutti G, Proclemer A (2015) Systolic and diastolic myocardial mechanic in hypertrophic cardiomyopathy and their link to the extent of hypertrophy, replacement fibrosis and interstitial fibrosis. Int J Cardiovasc Imaging 31(8):1603–1610

    Article  PubMed  Google Scholar 

  17. Tham EB, Haykowsky MJ, Chow K, Spavor M, Kaneko S, Khoo NS, Pagano JJ, Mackie AS, Thompson RB (2013) Diffuse myocardial fibrosis by T1-mapping in children with subclinical anthracycline cardiotoxicity: relationship to exercise capacity, cumulative dose and remodeling. J Cardiovasc Magn Reson 15:48

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kramer CM, Barkhausen J, Flamm SD, Kim RJ, Nagel E (2008) Standardized cardiovascular magnetic resonance imaging (CMR) protocols, society for cardiovascular magnetic resonance: board of trustees task force on standardized protocols. J Cardiovasc Magn Reson 10:35

    Article  PubMed  PubMed Central  Google Scholar 

  19. Fine NM, Tandon S, Kim HW, Shah DJ, Thompson T, Drangova M, White JA (2013) Validation of sub-segmental visual scoring for the quantification of ischemic and nonischemic myocardial fibrosis using late gadolinium enhancement MRI. J Magn Reson Imaging 38:1369–1376

    Article  PubMed  Google Scholar 

  20. Moon JC, Messroghli DR, Kellman P, Piechnik SK, Robson MD, Ugander M, Gatehouse PD, Arai AE, Friedrich MG, Neubauer S, Schulz-Menger J, Schelbert EB (2013) Society for Cardiovascular Magnetic Resonance Imaging; Cardiovascular Magnetic Resonance Working Group of the European Society of Cardiology. Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement. J Cardiovasc Magn Reson 15:92.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Puntmann VO, Peker E, Chandrashekhar Y, Nagel E (2016) T1 mapping in characterizing myocardial disease: a comprehensive review. Circ Res 119:277–299

    Article  CAS  PubMed  Google Scholar 

  22. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS (2002) Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Int J Cardiovasc Imaging 18:539–542

    PubMed  Google Scholar 

  23. Nagueh SF, Bierig SM, Budoff MJ, Desai M, Dilsizian V, Eidem B, Goldstein SA, Hung J, Maron MS, Ommen SR, Woo A, American Society of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Magnetic Resonance, Society of Cardiovascular Computed Tomography, American Society of Echocardiography (2011). Clinical recommendations for multimodality cardiovascular imaging of patients with hypertrophic cardiomyopathy. Endorsed by the American Society of Nuclear Cardiology, Society for Cardiovascular Magnetic Resonance, and Society of Cardiovascular Computed Tomography. J Am Soc Echocardiogr 24:473–498

    Article  PubMed  Google Scholar 

  24. Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, Flachskampf FA, Gillebert TC, Klein AL, Lancellotti P, Marino P, Oh JK, Popescu BA, Waggoner AD (2016) Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 29:277–314

    Article  PubMed  Google Scholar 

  25. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD, Louie EK, Schiller NB (2010) Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 23:685–713

    Article  PubMed  Google Scholar 

  26. Mor-Avi V, Lang RM, Badano LP, Belohlavek M, Cardim NM, Derumeaux G, Galderisi M, Marwick T, Nagueh SF, Sengupta PP, Sicari R, Smiseth OA, Smulevitz B, Takeuchi M, Thomas JD, Vannan M, Voigt JU, Zamorano JL (2011) Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. J Am Soc Echocardiogr 24:277–313

    Article  PubMed  Google Scholar 

  27. Cordero-Reyes AM, Youker K, Hamilton DJ, Torre-Amione G, Marian AJ, Nagueh SF (2012) Molecular, cellular, and functional characterization of myocardial regions in hypertrophic cardiomyopathy. Circ Cardiovasc Imaging 5:419–422

    Article  PubMed  Google Scholar 

  28. Rommel KP, von Roeder M, Latuscynski K, Oberueck C, Blazek S, Fengler K, Besler C, Sandri M, Lücke C, Gutberlet M, Linke A, Schuler G, Lurz P (2016) Extracellular volume fraction for characterization of patients with heart failure and preserved ejection fraction. J Am Coll Cardiol 67:1815–1825

    Article  PubMed  Google Scholar 

  29. Methawasin M, Strom JG, Slater RE, Fernandez V, Saripalli C, Granzier H (2016) Experimentally increasing the compliance of titin through RNA Binding Motif-20 (RBM20) inhibition improves diastolic function in a mouse model of heart failure with preserved ejection fraction. Circulation 134:1085–1099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ohara T, Iwano H, Thohan V, Kitzman DW, Upadhya B, Pu M, Little WC (2015) Role of diastolic function in preserved exercise capacity in patients with reduced ejection fractions. J Am Soc Echocardiogr 28:1184–1193

    Article  PubMed  Google Scholar 

  31. Rovner A, Greenberg NL, Thomas JD, Garcia MJ (2005) Relationship of diastolic intraventricular pressure gradients and aerobic capacity in patients with diastolic heart failure. Am J Physiol Heart Circ Physiol 289:H2081–H2088

    Article  CAS  PubMed  Google Scholar 

  32. Wang J, Buergler JM, Veerasamy K, Ashton YP, Nagueh SF (2009) Delayed untwisting: the mechanistic link between dynamic obstruction and exercise tolerance in patients with hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 54:1326–1334

    Article  PubMed  Google Scholar 

  33. Maragiannis D, Alvarez PA, Schutt RC, Chin K, Buergler JM, Little SH, Shah DJ, Nagueh SF (2016) Vortex formation time index in patients with hypertrophic cardiomyopathy. JACC Cardiovasc Imaging 9:1229–1231

    Article  PubMed  Google Scholar 

  34. Choudhury L, Mahrholdt H, Wagner A, Choi KM, Elliott MD, Klocke FJ, Bonow RO, Judd RM, Kim RJ (2002) Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 40:2156–2164

    Article  PubMed  Google Scholar 

  35. Popović ZB, Kwon DH, Mishra M, Buakhamsri A, Greenberg NL, Thamilarasan M, Flamm SD, Thomas JD, Lever HM, Desai MY (2008) Association between regional ventricular function and myocardial fibrosis in hypertrophic cardiomyopathy assessed by speckle tracking echocardiography and delayed hyperenhancement magnetic resonance imaging. J Am Soc Echocardiogr 21:1299–1305

    Article  PubMed  Google Scholar 

  36. Nagueh SF, Kopelen HA, Lim DS, Zoghbi WA, Quiñones MA, Roberts R, Marian AJ (2000) Tissue Doppler imaging consistently detects myocardial contraction and relaxation abnormalities, irrespective of cardiac hypertrophy, in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circulation 102:1346–1350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Nagueh SF, Bachinski L, Meyer D, Hill R, Zoghbi WA, Tam JW, Quiñones MA, Roberts R, Marian AJ (2001) Tissue Doppler imaging consistently detects myocardial abnormalities in patients with familial hypertrophic cardiomyopathy and provides a novel means for an early diagnosis prior to an independent of hypertrophy. Circulation 104:128–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ho CY, Sweitzer NK, McDonough B, Maron BJ, Casey SA, Seidman JG, Seidman CE, Solomon SD (2002) Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy. Circulation 105:2992–2997

    Article  PubMed  Google Scholar 

  39. Nagueh SF, McFalls J, Meyer D, Hill R, Zoghbi WA, Tam JW, Quiñones MA, Roberts R, Marian AJ (2003) Tissue Doppler imaging predicts the development of hypertrophic cardiomyopathy in subjects with subclinical disease. Circulation 108:395–398

    Article  PubMed  PubMed Central  Google Scholar 

  40. Yiu KH, Atsma DE, Delgado V, Ng AC, Witkowski TG, Ewe SH, Auger D, Holman ER, van Mil AM, Breuning MH, Tse HF, Bax JJ, Schalij MJ, Marsan NA (2012) Myocardial structural alteration and systolic dysfunction in preclinical hypertrophic cardiomyopathy mutation carriers. PLoS ONE 7:e36115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Germans T, Rüssel IK, Götte MJ, Spreeuwenberg MD, Doevendans PA, Pinto YM, van der Geest RJ, van der Velden J, Wilde AA, van Rossum AC (2010) How do hypertrophic cardiomyopathy mutations affect myocardial function in carriers with normal wall thickness? Assessment with cardiovascular magnetic resonance. J Cardiovasc Magn Reson 12:13

    Article  PubMed  PubMed Central  Google Scholar 

  42. Liu CY, Liu YC, Wu C, Armstrong A, Volpe GJ, van der Geest RJ, Liu Y, Hundley WG, Gomes AS, Liu S, Nacif M, Bluemke DA, Lima JA (2013) Evaluation of age-related interstitial myocardial fibrosis with cardiac magnetic resonance contrast-enhanced T1 mapping: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol 62:1280–1287

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sherif F. Nagueh.

Ethics declarations

Conflict of interest

There are no conflicts of interest to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maragiannis, D., Alvarez, P.A., Ghosn, M.G. et al. Left ventricular function in patients with hypertrophic cardiomyopathy and its relation to myocardial fibrosis and exercise tolerance. Int J Cardiovasc Imaging 34, 121–129 (2018). https://doi.org/10.1007/s10554-017-1214-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-017-1214-z

Keywords

Navigation