Advances and Clinical Utility of Ambulatory ECG Monitoring
World Small Animal Veterinary Association World Congress Proceedings, 2006
N. Sydney Moise, DVM, MS, DACVIM (Cardiology, Internal Medicine)
Professor of Medicine, Cornell University, Ithaca, NY, USA

Frequently the routine ECG is inadequate to determine the need for and the response to antiarrhythmic therapy. The 24-hour ambulatory ECG or Holter monitor is better suited for these determinations. The technology for Holter monitoring has made advances relative to the digitalization of the recordings, yet the accuracy of the analysis is still lacking for many of the arrhythmias that dogs and cats display. Despite the latter difficulty, it is still evident that to make the best judgments with regards to the management of arrhythmias, there is no replacement for this diagnostic ability.

During this brief communication the use of the Holter monitor will be demonstrated. An actual analysis will be demonstrated. Also, the results from patients will be used to illustrate the utility of this important diagnostic tool.

Reduction of Heart Rate as an Indicator of Oxygen Consumption

In both reported major studies above, as well as in previously published canine studies and in humans, heart failure therapy with Pimobendan is not associated with an increase in heart rate. In contrary, heart rate usually drops a bit with the general improvement of the patient and the reduction of signs of heart failure.


Sensitized to proarrhythmic effects of the PDE III-inhibitor Milrinone found in the Promise trial (Packer et al 1991), Pimobendan therapy was carefully observed for proarrhythmia in several studies (the Pico trial 1996, Remme et al 1994, the Epoch study 2002). Convincing evidence about increased ventricular tachyarrhythmias with clinical significance could not be found. A veterinary study (Rosenthal 2006) revealed increased VPC's in 6/8 dogs with DCM investigated with Holter-ECG's approx. 3 weeks after initiation of Pimobendan-therapy.

In the major multicenter trials cited above (PiTCH, VetScope) however, no proarrhythmic effect was found.

Comparison to Another Calcium Sensitizer Drug Levosimendan

Levosimendan is a very similar compound that has similar cardiovascular effects, but more calcium sensitizing and less vasodilating effects through PDE III-inhibition than Pimobendan. Levosimendan is used by intravenous infusions, and prolonged lasting effects up to several weeks after discontinuation of the drip are attributed to one of its metabolites OR-1896 in man (Kivikko et al 2003). This drug is being studied and prepared for licensing for the veterinary market as well, but results haven't been published yet. Apparently, dogs metabolize the drug differently without the presence of this effective metabolite.


1.  Asanoi H, Ishizaka S, Kameyama T, et al. Disparate inotropic and lusitropic response to pimobendan in conscious dogs with tachycardia-induced heart failure. J Cardiovasc Pharmacol 1994; 23: 268-274.

2.  Bastida E, Escolar G, Rodriguez-Gomez J, et al. UD-CG 115, a benzimidazole-pyridazinone compound with cardiovascular activity inhibits platelet thrombus formation. Abstract. Thrombosis Res 1986; 42(Suppl 6): 145.

3.  Baumann G, Ningel K, Permanetter B. Cardiovascular profile of UD-CG 115BS - pimobendane and reversibility of catecholamine subsensitivity in sever congestive heart failure secondary to idiopathic dilated cardiomyopathy. J Cardiovasc Pharmacol 1989; 13: 730-738.

4.  Bohm M, Morano I, Pieske B, et al. Contribution of cAMP phosphodiesterase inhibition and sensitization of the contractile proteins for calcium to the inotropic effect of pimobendan in the failing human myocardium. Circ Res 1991; 68: 689-701.

5.  Buchanan JW, Bucheler J. Vertebral scale system for cardiac mensuration. J Amer Vet Med Assoc 1995; 206: 194.

6.  The EPOCH Study Group. Effects of pimobendan on adverse cardiac events and physical activities in patients with mild-to-moderate heart failure - The effects of pimobendan on chronic heart failure study. Circ J 2002; 66; 149-157.

7.  Erlemeier HH, Kupper W, Bleifield W. Comparison of hormonal and hemodynamic changes after long-term therapy with pimobendan or enalapril--a double-blind randomised study. Euro Heart J 1991; 12: 889-899.

8.  Gwathmey JK, Copelas L, MacKinnon R, et al. Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res 1987; 61; 70-76.

9.  Iwasaki A, Matsumori A, Yamada T, et al. Pimobendan inhibits the production of proinflammatory cytokines and gene expression of inducible nitric oxide synthase in a murine model of viral myocarditis. J Amer Coll Cardio 1999; 33: 1400-1407.

10. Kivikko M, Lehtonen L, Colucci WS. Sustained hemodynamic effects of intravenous Levosimendan. Circulation 2003; 107: 81-86

11. Lombard CW: Pimobendan in congestive heart failure. Proc 21th ACVIM Forum: 104, 2003

12. Lombard CW, Jöns O, Bussadori CM: Clinical efficacy of Pimobendan versus Benazepril for the treatment of acquired atrioventricular valvular disease in dogs. J Am Anim Hosp Assoc 2006; 42: 249-261

13. Luis Fuentes VL, Corcoran B, French A, Schober KE, Kleeman R, Justus C. A double-blind, randomized, placebo-controlled study of pimobendan in dogs with dilated cardiomyopathy. J Vet Int Med 2002; 16: 255-261.

14. Meel JC, Dierden W. Hemodynamic profile of the cardiotonic agent pimobendan. J Cardiovasc Pharmacol 1989; 14(Suppl 2) :S1-S6.

15. Morgan JP. Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. N Engl J Med 1991; 325: 625-632.

16. O'Grady MR, Minors SL, O'Sullivan LM, Horne R. Evaluation of the efficacy of pimobendan to reduce mortality and morbidity in Doberman pinchers with congestive heart failure due to dilated cardiomyopathy. Abstract 248. Proceedings 21st ACVIM Forum 2003; 1011

17. Packer M, Carver JR, Rodeheffer RJ, et al. for the PROMISE study research group. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 1991; 325: 1468-1475.

18. The PICO-trial: Effect of Pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial. Heart 1996; 76: 223-31

19. Remme WJ, Krayenbühl HP, Baumann G et al. Longterm efficacy and safety of Pimobendan in moderate heart failure Europ Heart J 1994, 15: 947-56

20. Rosenthal SL, Ferguson MJ, Lefbom BK et al. Association of Pimobendan with ventricular arrhythmias in dogs with congestive heart failure. Proceedings 24th ACVIM Forum 2006; 756.

21. Sasaki T, Kubo T, Komamura K, Nishikimi T. Effect of long-term treatment with pimobendan on neurohumoral factors in patients with non-ischemic chronic moderate heart failure. J Cardio 1999; 33: 317-325.

22. Verdouw PD, Hartog JM, Duncker DJ, et al. Cardiovascular profile of pimobendan, a benzimidazole-pyridazinone derivative with vasodilating and inotropic properties. Eur J Pharmacol 1986; 126: 21-20.

Speaker Information
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N. Sydney Moise, DVM, MS, DACVIM (Cardiology and Internal Medicine)
Cornell University
Ithaca, New York, USA

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