Abstract

Research Article

Preclinical stiff heart is a marker of cardiovascular morbimortality in apparently healthy population

Charles Fauvel, Michael Bubenheim, Olivier Raitière, Charlotte Vallet, Nassima Si Belkacem and Fabrice Bauer*

Published: 31 July, 2019 | Volume 4 - Issue 2 | Pages: 083-089

Background: The prognostic significance of impaired left ventricular (LV) relaxation and increased LV stiffness as precursor of heart failure with preserved ejection fraction and death is still largely unknown in apparently healthy subjects.

Methods: We constituted a cohort of 353 patients with normal ejection fraction (>45%) and no significant heart disease, based on a total of 3,575 consecutive left-sided heart catheterizations performed. We measured peak negative first derivative of LV pressure (-dP/dt) and operating chamber stiffness (Κ) using a validated equation. Patients were categorized as having: 1) normal diastolic function, 2) isolated relaxation abnormalities (-dP/dt > 1860mm Hg/sec and K <0.025mm Hg/ml), or 3) predominant stiff heart (K ≥0.025mm Hg/ml).

Results: During a follow-up of at least 5 years, the incidence of the primary composite endpoint (death, major arterial event, heart failure, and arrhythmia) was 23.2% (82 patients). Compared to isolated relaxation abnormalities, predominant stiff heart showed stronger prognostic significance for all events (p=0.002), namely heart failure (HR, 2.9; p=0.0499), cardiac death (HR, 5.8; p=0.03), and heart failure and cardiac death combined (HR, 3.7; p=0.003).

Conclusion: In this apparently healthy population referred to our center for cardiac catheterization, the prevalence of diastolic dysfunction was very high. Moreover, predominant stiff heart was a better predictor of cardiovascular outcomes than isolated relaxation abnormalities.

Read Full Article HTML DOI: 10.29328/journal.jccm.1001045 Cite this Article Read Full Article PDF

Keywords:

Heart failure; Preserved ejection fraction; Prognosis; Stiff heart; Preclinical; Relaxation

References

  1. Wisneski JA, Bristow JD. Left ventricular stiffness. Annu Rev Med. 1978; 29: 475-483. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/348043
  2. Sinning D, Kasner M, Westermann D, Schulze K, Schultheiss HP, et al. Increased left ventricular stiffness impairs exercise capacity in patients with heart failure symptoms despite normal left ventricular ejection fraction. Cardiol Res Pract. 2011; 2011: 692-862. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21403885
  3. Westermann D, Kasner M, Steendijk P, Spillmann F, Riad A, et al. Role of left ventricular stiffness in heart failure with normal ejection fraction. Circulation. 2008; 117: 2051-2060. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18413502
  4. Masuyama T, Yamamoto K, Sakata Y, Doi R, Nishikawa N, et al. Evolving changes in doppler mitral flow velocity pattern in rats with hypertensive hypertrophy. J Am Coll Cardiol. 2000; 36: 2333-2338. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11127481
  5. Pernot M, Couade M, Mateo P, Crozatier B, Fischmeister R, et al. Real-time assessment of myocardial contractility using shear wave imaging. J Am Coll Cardiol. 2011; 58: 65-72. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21700091
  6. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2009; 22: 107-133. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27037982
  7. Soyama Y, Mano T, Goda A, Sugahara M, Masai K, et al. Prognostic value of diastolic wall strain in patients with chronic heart failure with reduced ejection fraction. Heart Vessels. 2017; 32: 68-75. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27115147
  8. Minamisawa M, Miura T, Motoki H, Ueki Y, Shimizu K, et al. Prognostic impact of diastolic wall strain in patients at risk for heart failure. Int Heart J. 2017; 58: 250-256. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28320997
  9. Kang MK, Ju S, Mun HS, Choi S, Cho JR, et al. Decreased diastolic wall strain is associated with adverse left ventricular remodeling even in patients with normal left ventricular diastolic function. J Echocardiogr. 2015; 13: 35-42. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25750578
  10. Song P, Bi X, Mellema DC, Manduca A, Urban MW, et al. Quantitative assessment of left ventricular diastolic stiffness using cardiac shear wave elastography: A pilot study. J Ultrasound Med. 2016; 35: 1419-1427. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27208201
  11. Sakata Y, Ohtani T, Takeda Y, Yamamoto K, Mano T. Left ventricular stiffening as therapeutic target for heart failure with preserved ejection fraction. Circ J. 2013; 77: 886-892. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23486165
  12. Zile MR, Baicu CF, Gaasch WH. Diastolic heart failure--abnormalities in active relaxation and passive stiffness of the left ventricle. N Engl J Med. 2004; 350: 1953-1959. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15128895
  13. Grossman W. Evaluation of the systolic and diastolic function of the ventricles and the myocardium. in: Grossman W (ed): Grossman's cardiac catheterization, angiography, and intervention, Volume 1. 7th ed lippincott williams & wilkins. 2006: 315-331.
  14. Zafrir B, Paz H, Wolff R, Salman N, Merhavi D, et al. Mortality rates and modes of death in heart failure patients with reduced versus preserved systolic function. Eur J Intern Med. 2011; 22: 53-56. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21238894
  15. Klein AL, Burstow DJ, Tajik AJ, Zachariah PK, Bailey KR, et al. Effects of age on left ventricular dimensions and filling dynamics in 117 normal persons. Mayo Clin Proc. 1994; 69: 212-224. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/8133658
  16. Nagueh SF, Smiseth OA, Appleton CP, Byrd BF, Dokainish H, et al. 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. 2016; 29: 277-314. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27037982
  17. Aurigemma GP, Gottdiener JS, Shemanski L, Gardin J, Kitzman D. Predictive value of systolic and diastolic function for incident congestive heart failure in the elderly: The cardiovascular health study. J Am Coll Cardiol. 2001; 37:1042-1048. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11263606
  18. Redfield MM, Jacobsen SJ, Burnett JC Jr., Mahoney DW, Bailey KR, et al. Burden of systolic and diastolic ventricular dysfunction in the community: Appreciating the scope of the heart failure epidemic. JAMA. 2003; 289: 194-202. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12517230
  19. Lam CS, Lyass A, Kraigher-Krainer E, Massaro JM, Lee DS, et al. Cardiac dysfunction and noncardiac dysfunction as precursors of heart failure with reduced and preserved ejection fraction in the community. Circulation. 2011; 124: 24-30. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21670229
  20. Tschope C, Paulus WJ. Is echocardiographic evaluation of diastolic function useful in determining clinical care? Doppler echocardiography yields dubious estimates of left ventricular diastolic pressures. Circulation. 2009; 120: 810-820. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19720947
  21. Appleton CP, Hatle LK, Popp RL. 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. 1988; 12: 426-440. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/3392336
  22. Mullens W, Borowski AG, Curtin RJ, Thomas JD, Tang WH. Tissue Doppler imaging in the estimation of intracardiac filling pressure in decompensated patients with advanced systolic heart failure. Circulation. 2009; 119: 62-70. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19075104
  23. Geske JB, Sorajja P, Nishimura RA, Ommen SR. Evaluation of left ventricular filling pressures by doppler echocardiography in patients with hypertrophic cardiomyopathy: Correlation with direct left atrial pressure measurement at cardiac catheterization. Circulation. 2007; 116: 2702-2708. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18025528
  24. Dzau VJ, Antman EM, Black HR, Hayes DL, Manson JE, et al. The cardiovascular disease continuum validated: Clinical evidence of improved patient outcomes: Part i: Pathophysiology and clinical trial evidence (risk factors through stable coronary artery disease). Circulation. 2006; 114: 2850-2870. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17179034
  25. Burlew BS, Weber KT. Cardiac fibrosis as a cause of diastolic dysfunction. Herz. 2002; 27: 92-98. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12025467
  26. van Heerebeek L, Hamdani N, Handoko ML, Falcao-Pires I, Musters RJ, et al. Diastolic stiffness of the failing diabetic heart: Importance of fibrosis, advanced glycation end products, and myocyte resting tension. Circulation. 2008; 117: 43-51. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18071071
  27. Krum H, Elsik M, Schneider HG, Ptaszynska A, Black M, et al. Relation of peripheral collagen markers to death and hospitalization in patients with heart failure and preserved ejection fraction: Results of the I-PRESERVE collagen sub-study. Circ Heart Fail. 2011; 4: 561-568. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21750125
  28. Zile MR, Gaasch WH, Anand IS, Haass M, Little WC, et al. Mode of death in patients with heart failure and a preserved ejection fraction: Results from the irbesartan in heart failure with preserved ejection fraction study (i-preserve) trial. Circulation. 2010; 121: 1393-1405. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20231531
  29. Zizek B, Poredos P. Increased left ventricular mass and diastolic dysfunction are associated with endothelial dysfunction in normotensive offspring of subjects with essential hypertension. Blood Press. 2007; 16: 36-44. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17453750
  30. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, et al. J. Heart disease and stroke statistics--2011 update: A report from the American heart association. Circulation. 2011; 123: e18-e209
  31. Hildebrandt P. Systolic and non-systolic heart failure: Equally serious threats. JAMA. 2006; 296: 2259-2260. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21160056
  32. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European society of cardiology. Developed in collaboration with the heart failure association (hfa) of the esc. Eur Heart J. 2012; 33: 1787-1847. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22611136
  33. Fitzgibbons TP, Meyer TE, Aurigemma GP. Mortality in diastolic heart failure: An update. Cardiol Rev. 2009; 17: 51-55. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19367145
  34. Caudron J, Fares J, Bauer F, Dacher JN. Evaluation of left ventricular diastolic function with cardiac MR imaging. Radiographics. 2011; 31: 239-259. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21257944
  35. Borbely A, van der Velden J, Papp Z, Bronzwaer JG, Edes I, et al. Cardiomyocyte stiffness in diastolic heart failure. Circulation. 2005; 111: 774-781. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15699264
  36. Zile MR, Baicu CF, Ikonomidis JS, Stroud RE, Nietert PJ, et al. Myocardial stiffness in patients with heart failure and a preserved ejection fraction: Contributions of collagen and titin. Circulation. 2015; 131: 1247-1259. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25637629

Figures:

Figure 1

Figure 1

Figure 1

Figure 2

Figure 1

Figure 3

Similar Articles

Recently Viewed

Read More

Most Viewed

Read More

Help ?