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Mechanical alternans in human idiopathic dilated cardiomyopathy is caused with impaired force–frequency relationship and enhanced poststimulation potentiation

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Abstract

Mechanical alternans (MA) is frequently observed in patients with heart failure, and is a predictor of cardiac events. However, there have been controversies regarding the conditions and mechanisms of MA. To clarify heart rate-dependent contractile properties related to MA, we performed incremental right atrial pacing in 17 idiopathic dilated cardiomyopathy (DCM) patients and in six control patients. The maximal increase in left ventricular dP/dt during pacing-induced tachycardia was assessed as the force gain in the force–frequency relationship (FG-FFR), and the maximal increase in left ventricular dP/dt of the first post-pacing beats was examined as the force gain in poststimulation potentiation (FG-PSP). As a result, MA was induced in 9 DCM patients (DCM MA(+)) but not in the other 8 DCM patients (DCM MA(−)), and not in any of the control patients. DCM MA(+) had significantly lower FG-FFR (34.7 ± 40.9 vs 159.4 ± 103.9 mmHg/s, P = 0.0091) and higher FG-PSP (500.0 ± 96.8 vs 321.9 ± 94.9 mmHg/s, P = 0.0017), and accordingly a wider gap between FG-PSP and FG-FFR (465.3 ± 119.4 vs 162.5 ± 123.6 mmHg/s, P = 0.0001) than DCM MA(−) patients. These characteristics of DCM MA(+) showed clear contrasts to those of the control patients. In conclusion, MA is caused with an impaired force–frequency relationship despite significant poststimulation potentiation, suggesting that MA reflects ineffective utilization of the potentiated intrinsic force during tachycardia.

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References

  1. Heusch G (2011) Heart rate and heart failure. Not a simple relationship. Circ J 75:229–236

    Article  PubMed  Google Scholar 

  2. Hirashiki A, Izawa H, Somura F, Obata K, Kato T, Nishizawa T, Yamada A, Asano H, Ohshima S, Noda A, Iino S, Nagata K, Okumura K, Murohara T, Yokota M (2006) Prognostic value of pacing-induced mechanical alternans in patients with mild-to-moderate idiopathic dilated cardiomyopathy in sinus rhythm. J Am Coll Cardiol 47:1382–1389

    Article  PubMed  Google Scholar 

  3. Kodama M, Kato K, Hirono S, Okura Y, Hanawa H, Ito M, Fuse K, Shiono T, Watanabe K, Aizawa Y (2001) Mechanical alternans in patients with chronic heart failure. J Card Fail 7:138–145

    Article  PubMed  CAS  Google Scholar 

  4. Traube L (1872) Ein Fall von Pulsus bigeminus nebst Bemerhungen uber die Lebershwellungen bei Klappenfehlain und uber akute Leberatrophic. Ber Klin Wochenschr 9:185–188

    Google Scholar 

  5. Ryan JM, Schieve JF, Hull HB, Oser BM (1955) The influence of advanced congestive heart failure on pulsus alternans. Circulation 12:60–63

    Article  PubMed  CAS  Google Scholar 

  6. Hull HB, Oser BM, Ryan JM, Schieve JF (1956) Experiences with pulsus alternans; ventricular alternation and the stage of heart failure. Circulation 14:1099–1103

    Article  PubMed  CAS  Google Scholar 

  7. Díaz ME, O’Neill SC, Eisner DA (2004) Sarcoplasmic reticulum calcium content fluctuation is the key to cardiac alternans. Circ Res 94:650–656

    Article  PubMed  Google Scholar 

  8. Picht E, DeSantiago J, Blatter LA, Bers DM (2006) Cardiac alternans do not rely on diastolic sarcoplasmic reticulum calcium content fluctuations. Circ Res 99:740–748

    Article  PubMed  CAS  Google Scholar 

  9. Rovetti R, Cui X, Garfinkel A, Weiss JN, Qu Z (2010) Spark-induced sparks as a mechanism of intracellular calcium alternans in cardiac myocytes. Circ Res 106:1582–1591

    Article  PubMed  CAS  Google Scholar 

  10. Weiss JN, Nivala M, Garfinkel A, Qu Z (2011) Alternans and arrhythmias: from cell to heart. Circ Res 108:98–112

    Article  PubMed  CAS  Google Scholar 

  11. Pieske B, Kretschmann B, Meyer M, Holubarsch C, Weirich J, Posival H, Minami K, Just H, Hasenfuss G (1995) Alterations in intracellular calcium handling associated with the inverse force–frequency relation in human dilated cardiomyopathy. Circulation 92:1169–1178

    Article  PubMed  CAS  Google Scholar 

  12. Tanaka K, Kodama M, Ito M, Hoyano M, Mitsuma W, Ramadan MM, Kashimura T, Hirono S, Okura Y, Kato K, Hanawa H, Aizawa Y (2010) Force–frequency relationship as a predictor of long-term prognosis in patients with heart diseases. Heart Vessels 26:153–159

    Article  PubMed  Google Scholar 

  13. Narayan P, McCune SA, Robitaille PM, Hohl CM, Altschuld RA (1995) Mechanical alternans and the force–frequency relationship in failing rat hearts. J Mol Cell Cardiol 27:523–530

    Article  PubMed  CAS  Google Scholar 

  14. Schmidt AG, Kadambi VJ, Ball N, Sato Y, Walsh RA, Kranias EG, Hoit BD (2000) Cardiac-specific overexpression of calsequestrin results in left ventricular hypertrophy, depressed force–frequency relation and pulsus alternans in vivo. J Mol Cell Cardiol 32:1735–1744

    Article  PubMed  CAS  Google Scholar 

  15. Mahler F, Yoran C, Ross J Jr (1974) Intropic effect of tachycardia and poststimulation potentiation in the conscious dog. Am J Physiol 227:569–575

    PubMed  CAS  Google Scholar 

  16. Gomes JA, Carambas CR, Matthews LM, Moran HE, Damato AN (1979) Inotropic effect of post-stimulation potentiation in man: an echocardiographic study. Am J Cardiol 43:745–752

    Article  PubMed  CAS  Google Scholar 

  17. Nayler WG (1961) The importance of calcium in poststimulation potentiation. J Gen Physiol 44:1059–1072

    Article  PubMed  CAS  Google Scholar 

  18. Kodama M, Kato K, Hirono S, Hanawa H, Okura Y, Ito M, Fuse K, Shiono T, Tachikawa H, Hayashi M, Abe S, Yoshida T, Aizawa Y (2001) Changes in the occurrence of mechanical alternans after long-term beta-blocker therapy in patients with chronic heart failure. Jpn Circ J 65:711–716

    Article  PubMed  CAS  Google Scholar 

  19. Kodama M, Kato K, Hirono S, Okura Y, Hanawa H, Yoshida T, Hayashi M, Tachikawa H, Kashimura T, Watanabe K, Aizawa Y (2004) Linkage between mechanical and electrical alternans in patients with chronic heart failure. J Cardiovasc Electrophysiol 15:295–299

    Article  PubMed  Google Scholar 

  20. Ricci DR, Orlick AE, Alderman EL, Ingels NB Jr, Daughters GT 2nd, Kusnick CA, Reitz BA, Stinson EB (1979) Role of tachycardia as an inotropic stimulus in man. J Clin Invest 63:695–703

    Article  PubMed  CAS  Google Scholar 

  21. Givertz MM, Andreou C, Conrad CH, Colucci WS (2007) Direct myocardial effects of levosimendan in humans with left ventricular dysfunction: alteration of force–frequency and relaxation–frequency relationships. Circulation 115:1218–1224

    PubMed  CAS  Google Scholar 

  22. Kawasaki H, Seki M, Saiki H, Masutani S, Senzaki H (2011) Noninvasive assessment of left ventricular contractility in pediatric patients using the maximum rate of pressure rise in peripheral arteries. Heart Vessels. doi: 10.1007/s00380-011-0162-0

  23. Friedman B, Daily WM, Sheffield RS (1953) Orthostatic factors in pulsus alternans. Circulation 8:864–873

    Article  PubMed  CAS  Google Scholar 

  24. Bashore TM, Walker S, Van Fossen D, Shaffer PB, Fontana ME, Unverferth DV (1988) Pulsus alternans induced by inferior vena caval occlusion in man. Cathet Cardiovasc Diagn 14:24–32

    Article  PubMed  CAS  Google Scholar 

  25. Hirashiki A, Izawa H, Cheng XW, Unno K, Ohshima S, Murohara T (2010) Dobutamine-induced mechanical alternans is a marker of poor prognosis in idiopathic dilated cardiomyopathy. Clin Exp Pharmacol Physiol 37:1004–1009

    Article  PubMed  CAS  Google Scholar 

  26. Ellis CH (1960) Antagonism of drug-induced pulsus alternans in dogs. Am J Physiol 199:167–173

    PubMed  CAS  Google Scholar 

  27. Cournand A, Ferrer MI, Harvey RM, Richards DW (1956) Cardiocirculatory studies in pulsus alternans of the systemic and pulmonary circulations. Circulation 14:163–174

    Article  PubMed  CAS  Google Scholar 

  28. McGaughey MD, Maughan WL, Sunagawa K, Sagawa K (1985) Alternating contractility in pulsus alternans studied in the isolated canine heart. Circulation 71:357–362

    Article  PubMed  CAS  Google Scholar 

  29. Kashimura T, Kodama M, Aizawa Y (2007) Left ventricular pressure–volume loops during mechanical alternans in a patient with dilated cardiomyopathy. Heart 93:151

    Article  PubMed  CAS  Google Scholar 

  30. Bers DM (2002) Cardiac excitation–contraction coupling. Nature 415:198–205

    Article  PubMed  CAS  Google Scholar 

  31. Pieske B, Maier LS, Bers DM, Hasenfuss G (1999) Ca2+ handling and sarcoplasmic reticulum Ca2+ content in isolated failing and nonfailing human myocardium. Circ Res 85:38–46

    Article  PubMed  CAS  Google Scholar 

  32. Díaz ME, Eisner DA, O’Neill SC (2002) Depressed ryanodine receptor activity increases variability and duration of the systolic Ca2+ transient in rat ventricular myocytes. Circ Res 91:585–593

    Article  PubMed  Google Scholar 

  33. Restrepo JG, Weiss JN, Karma A (2008) Calsequestrin-mediated mechanism for cellular calcium transient alternans. Biophys J 95:3767–3789

    Article  PubMed  CAS  Google Scholar 

  34. Surawicz B, Fisch C (1992) Cardiac alternans: diverse mechanisms and clinical manifestations. J Am Coll Cardiol 20:483–499

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported in part by the Grants-in-Aid for Scientific Research (18590763, 22590805) from the Ministry of Education, Science, Sports, Culture and Technology of Japan.

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Correspondence to Takeshi Kashimura.

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Kashimura, T., Kodama, M., Tanaka, K. et al. Mechanical alternans in human idiopathic dilated cardiomyopathy is caused with impaired force–frequency relationship and enhanced poststimulation potentiation. Heart Vessels 28, 336–344 (2013). https://doi.org/10.1007/s00380-012-0251-8

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  • DOI: https://doi.org/10.1007/s00380-012-0251-8

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