The Scientific Basis of Heart Failure

  • Giles Chick
  • Fotios G. Pitoulis
  • Liam CouchEmail author
Part of the Learning Materials in Biosciences book series (LMB)


The aim of this chapter is to discuss the current literature surrounding the science that underlies heart failure. This encompasses the natural history of the syndrome, namely, an initial myocardial insult, apparent recovery, decompensation and finally failure of the organ. We will then expand upon some of the post-infarction changes to ventricular performance in both the compensatory and failure stages, including their manifestations on the Frank–Starling curve. Finally, the topic of cardiac regeneration will briefly be analysed. Understanding the science behind regeneration will provide a foundation to appreciate the basis of novel therapies, discussed later.


  1. 1.
    Davis RC (2000) ABC of heart failure: history and epidemiology. BMJ 320:297CrossRefGoogle Scholar
  2. 2.
    Cowie MR (2017) The heart failure epidemic: a UK perspective. Echo Res Pract 4:R15CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bhatnagar P, Wickramasinghe K, Williams J, Rayner M, Townsend N (2015) The epidemiology of cardiovascular disease in the UK 2014. Heart 101:1182CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Azevedo PS, Polegato BF, Minicucci MF, Paiva SAR, Zornoff LAM (2016) Cardiac remodeling: concepts, clinical impact, pathophysiological mechanisms and pharmacologic treatment. Arq Bras Cardiol 106(1):62–69PubMedPubMedCentralGoogle Scholar
  5. 5.
    Pazos-López P, Peteiro-Vázquez J, Carcía-Campos A, García-Bueno L, de Torres JPA, Castro-Beiras A (2011) The causes, consequences, and treatment of left or right heart failure. Vasc Health Risk Manag 7:237–254PubMedPubMedCentralGoogle Scholar
  6. 6.
    Frangogiannis NG (2014) The inflammatory response in myocardial injury, repair, and remodelling. Nat Rev Cardiol 11:255CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Algranati D, Kassab GS, Lanir Y (2011) Why is the subendocardium more vulnerable to ischemia? A new paradigm. AJP Hear Circ Physiol 300:H1090CrossRefGoogle Scholar
  8. 8.
    Burchfield JS, Xie M, Hill JA (2013) Pathological ventricular remodeling: mechanisms: part 1 of 2. Circulation 128:388CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Davies CH, Davia K, Bennett JG, Pepper JR, Poole-Wilson PA, Harding SE (1995) Reduced contraction and altered frequency response of isolated ventricular myocytes from patients with heart failure. Circulation 92:2540CrossRefPubMedGoogle Scholar
  10. 10.
    Gerdes AM, Kellerman SE, Moore JA, Muffly KE, Clark LC, Reaves PY et al (1992) Structural remodeling of cardiac myocytes in patients with ischemic cardiomyopathy. Circulation 86:426CrossRefPubMedGoogle Scholar
  11. 11.
    Savinova OV, Gerdes AM (2012) Myocyte changes in heart failure. Heart Fail Clin 8:1CrossRefPubMedGoogle Scholar
  12. 12.
    Botchway AN, Turner MA, Sheridan DJ, Flores NA, Fry CH (2003) Electrophysiological effects accompanying regression of left ventricular hypertrophy. Cardiovasc Res 60:510CrossRefPubMedGoogle Scholar
  13. 13.
    Terracciano CMN, Hardy J, Birks EJ, Khaghani A, Banner NR, Yacoub MH (2004) Clinical recovery from end-stage heart failure using left-ventricular assist device and pharmacological therapy correlates with increased sarcoplasmic reticulum calcium content but not with regression of cellular hypertrophy. Circulation 109(19):2263–2265CrossRefPubMedGoogle Scholar
  14. 14.
    Cohn JN, Tognoni G (2001) (Val-HeFT Trial) a randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 345(23):1667–1675CrossRefPubMedGoogle Scholar
  15. 15.
    Cohn JN, Johnson GR, Shabetai R, Loeb H, Tristani F, Rector T et al (1993) Ejection fraction, peak exercise oxygen consumption, cardiothoracic ratio, ventricular arrhythmias, and plasma norepinephrine as determinants of prognosis in heart failure. The V-HeFT VA Cooperative Studies Group. Circulation 87(6 Suppl):VI5–V16PubMedGoogle Scholar
  16. 16.
    Bernstein D, Fajardo G, Zhao M (2011) The role of β-adrenergic receptors in heart failure: differential regulation of cardiotoxicity and cardioprotection. Prog Pediatr Cardiol 31:35CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Madamanchi A (2007) β-adrenergic receptor signaling in cardiac function and heart failure. McGill J Med 10(2):99–104PubMedPubMedCentralGoogle Scholar
  18. 18.
    He BJ, Joiner MLA, Singh MV, Luczak ED, Swaminathan PD, Koval OM et al (2011) Oxidation of CaMKII determines the cardiotoxic effects of aldosterone. Nat Med 17:1610CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Tan LB, Jalil JE, Pick R, Janicki JS, Weber KT (1991) Cardiac myocyte necrosis induced by angiotensin II. Circ Res 69:1185CrossRefPubMedGoogle Scholar
  20. 20.
    Ogawa M, Morita N, Tang L, Karagueuzian HS, Weiss JN, Lin SF et al (2009) Mechanisms of recurrent ventricular fibrillation in a rabbit model of pacing-induced heart failure. Hear Rhythm 6:784CrossRefGoogle Scholar
  21. 21.
    Borlaug BA, Paulus WJ (2011) Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J 32(6):670–679CrossRefPubMedGoogle Scholar
  22. 22.
    Nishimura RA, Jaber W (2007) Understanding “diastolic heart failure”. J Am Coll Cardiol 49:695CrossRefPubMedGoogle Scholar
  23. 23.
    Toischer K, Rokita AG, Unsöld B, Zhu W, Kararigas G, Sossalla S et al (2010) Differential cardiac remodeling in preload versus afterload. Circulation 122(10):993–1003CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Braunstein JB, Anderson GF, Gerstenblith G, Weller W, Niefeld M, Herbert R et al (2003) Noncardiac comorbidity increases preventable hospitalizations and mortality among medicare beneficiaries with chronic heart failure. J Am Coll Cardiol 42(7):1226–1233CrossRefPubMedGoogle Scholar
  25. 25.
    Van Deursen VM, Urso R, Laroche C, Damman K, Dahlström U, Tavazzi L et al (2014) Co-morbidities in patients with heart failure: an analysis of the European Heart Failure Pilot Survey. Eur J Heart Fail 16(1):103–111CrossRefPubMedGoogle Scholar
  26. 26.
    Arfè A, Scotti L, Varas-Lorenzo C, Nicotra F, Zambon A, Kollhorst B et al (2016) Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study. BMJ 354:i4857CrossRefPubMedGoogle Scholar
  27. 27.
    Crofford LJ (2013) Use of NSAIDs in treating patients with arthritis. Arthritis Res Ther 15(Suppl 3):S2PubMedPubMedCentralGoogle Scholar
  28. 28.
    Lymperopoulos A, Rengo G, Koch WJ (2013) Adrenergic nervous system in heart failure: pathophysiology and therapy. Circ Res 113(6):739–753CrossRefPubMedGoogle Scholar
  29. 29.
    Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heide F, Walsh S et al (2009) Evidence for cardiomyocyte renewal in humans. Science 324(5923):98–102CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Imperial College LondonLondonUK
  2. 2.National Heart and Lung Institute, Myocardial Function, Imperial College LondonLondonUK

Personalised recommendations