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Short-term effects of oral enoximone on hemodynamics, exercise capacity, anaerobic threshold, and arrhythmias in congestive heart failure

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Summary

Enoximone, a phosphodiesterase-inhibitor, is a potent inotropic vasodilator agent that causes a marked improvement in hemodynamics in patients with congestive heart failure. The acute effects of oral enoximone on rest and exercise hemodynamics, ejection fraction, aerobic metabolism, exercise capacity, and arrhythmias were studied in 11 patients with moderate to moderately severe dilative cardiomyopathy after 8 days of enoximone (100 mg tid) in addition to baseline therapy (diuretics and digitalis).

The cardiac index increased from 2.44±0.45 to 2.72±0.50 l/min/m2 (p<0.01) at rest and from 4.00±0.96 to 4.75±0.95 l/min/m2 (p<0.005) during exercise. Pulmonary wedge pressure decreased from 16.8±7.3 to 12.5±6.5 mmHg (p<0.005) at rest and from 28.2±8.0 to 24.5±10.3 mmHg (p< 0.05) during exercise. Systemic vascular resistance decreased from 1608±243 to 1495±300 dynes*sec*cm−5 (p<0.05) at rest and from 1152±155 to 1027±236 dynes*sec*cm−5 (ns) during exercise. The anaerobic threshold, which was recorded simultaneously, increased from 13.2±2.7 to 15.5± 2.5ml/kg/min VO2 (p<0.02). The radionuclide ventriculography ejection fraction improved from 21.7±5.0 to 28.1±9.1% (p<0.01) during exercise; the changes at rest were not significant (20.8±6.2 vs 25.8±8.4%). Exercise tolerance showed an increase of 16% (492±133 to 573±135 sec, p< 0.005). The resting heart rate remained unchanged (81.8±13.4 vs 81.8±11.9). Interestingly, 24-h Holter monitoring revealed more or new repetitive arrhythmias in 9/11 patients.

Short-term therapy with oral enoximone enhances ventricular performance by increasing cardiac contractility and lowering vascular resistance, both of which extend exercise tolerance and improve aerobic metabolism. Potential proarrhythmic effects need further evaluation, however.

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Abbreviations

AMP:

adenosine monophosphate

PDE:

phosphodiesterase

VCO2 :

carbon dioxide production

VPB:

ventricular premature beat

VE:

minute ventilation

VO2 :

oxygen uptake

References

  1. Amin DK, Shah PK, Hulse S, Shellok FG, Swan HJC (1984) Myocardial metabolic and hemodynamic effects of intravenous MDL-17,043, a new cardiotonic drug, in patients with severe chronic heart failure. Am Heart J 108:1285–1292

    Article  CAS  PubMed  Google Scholar 

  2. Bigger JT Jr (1989) Why patients with congestive heart failure die: arrhythmias and sudden cardiac death. Circulation 75 [Suppl IV]:28–35

    Google Scholar 

  3. Choraria SK, Taylor D, Pilcher J (1987) Double-blind crossover comparison of enoximone and placebo in patients with congestive heart failure. Circulation 76:1307–1311

    Article  CAS  PubMed  Google Scholar 

  4. Cowley AJ, Stainer K, Rowley JM, Hampton JR (1986) Abnormalities of the peripheral circulation and respiratory function in patients with severe heart failure. Br Heart J 55:75–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Crawford MH, Richards KL, Sodums MT, Kennedy GT (1984) Positive inotropic and vasodilator effects of MDL 17,043 in patients with reduced left ventricular performance. Am J Cardiol 53:1051–1053

    Article  CAS  PubMed  Google Scholar 

  6. Dage RC, Roebel LE, Hsieh CP, Weiner DL, Woodward JK (1982) Cardiovascular properties of a new cardiotonic agent: MDL 17.043 (1,3-dihydro-4-methyl-5-(4-(methylthio)-benzoyl)-2H-imidazol-2-one). J Cardiovasc Pharmacol 4:500–508

    Article  CAS  PubMed  Google Scholar 

  7. Dickstein K, Barvik S, Aarsland T, Snapinn S, Karlsson J (1990) A comparison of methodologies in detection of the anaerobic threshold. Circulation 81 [Suppl II]:38–46

    Google Scholar 

  8. Janicki JS, Shroff SG, Weber KT (1987) Physiologic response to the inotropic and vasodilator properties of enoximone. Am J Cardiol 60:15C-20C

    Article  CAS  PubMed  Google Scholar 

  9. Kariya T, Wille LJ, Dage RC (1982) Biochemical studies on the mechanism of cardiotonic activity of MDL 17,043. J Cardiovasc Pharmacol 4:509–514

    Article  CAS  PubMed  Google Scholar 

  10. Kereiakes DJ, Chatterjee K, Parmley WW, Atherton B, Curran D, Kereiakes A, Spangenberg R (1984) Intravenous and oral MDL 17043 (a new inotropic-vasodilator agent) in congestive heart failure: hemodynamic and clinical evaluation in 38 patients. J Am Coll Cardiol 4:884–889

    Article  CAS  PubMed  Google Scholar 

  11. Kereiakes DJ, Viquerat C, Lanzer P, Botvinick EH, Spangenberg R, Buckingham M, Parmley WW, Chatterje K (1984) Mechanism of improved left ventricular function following intravenous MDL 17,043 in patients with severe chronic heart failure. Am Heart J 108:1278–1284

    Article  CAS  PubMed  Google Scholar 

  12. Leier CV, Binkley PF, Starling RC, Huss-Randolph P (1989) Disparity between improvement in left ventricular function and changes in clinical status and exercise capacity during chronic enoximone therapy. Am Heart J 117:1092–1098

    Article  CAS  PubMed  Google Scholar 

  13. Lubbe WF, Podzuweit T, Daries PS, Opie LH (1978) The role of cyclic adenosine monophosphate in adrenergic effects on ventricular vulnerabilty to fibrillation in the isolated perfused rat heart. J Clin Invest 61:1260–1271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Martin JL, Likoff MJ, Janicki JS, Laskey WK, Hirshfeld JW, Weber KT (1988) Myocardial energetics and clinical response to the cardiotonic agent MDL 17043 in advanced heart failure. J Am Coll Cardiol 4:875–883

    Article  Google Scholar 

  15. Matsumura N, Nishijima H, Kojima S, Hashimoto F, Minami M, Yasuda H (1983) Determination of anaerobic threshold for assessment of functional state in patients with chronic heart failure. Circulation 68:360–367

    Article  CAS  PubMed  Google Scholar 

  16. Miles WM, Herger JJ, Minardo JD, Klein LS, Prystowsky EN, Zipes DP (1989) The electrophysiologic effects of enoximone in patients with preexisting ventricular tachyaarhythmias. Am Heart J 117:112–121

    Article  CAS  PubMed  Google Scholar 

  17. Murali S, Uretsky BF, Betschart AR, Tokarczyk TR, Kolesar JA, Reddy PS (1990) Differential hemodynamic effects of oral enoximone in severe congestive heart failure. Am J Cardiol 55:515–519

    Article  Google Scholar 

  18. Packer M (1989) Effect of phosphodiesterase inhibitors on survival of patients with chronic heart failure. Am J Cardiol 63:41A-45A

    Article  CAS  PubMed  Google Scholar 

  19. Rubin SA, Tabak L (1985) MDL 17,043: short- and long- term cardiopulmonary and clinical effects in patients with heart failure. J Am Coll Cardiol 5:1422–1427

    Article  CAS  PubMed  Google Scholar 

  20. Shah PK, Amin DK, Hulse S, Shellock F, Swan HJC (1985) Inotropic therapy for refractory congestive heart failure with oral fenoximone (MDL-17,043): poor long-term results despite early hemodynamic and clinical improvement. Circulation 71:326–331

    Article  CAS  PubMed  Google Scholar 

  21. Sullivan MJ, Cobb FR (1990) The anaerobic threshold in chronic heart failure — relation to blood lactate, ventilatory basis, reproducibility, and response to exercise training. Circulation 81 [Suppl II]:47–58

    Google Scholar 

  22. Treese N, Rhein S, Werneyer A, Erbel R, v. Olshausen K, Pop T, Meyer J (1988) Der Einfluß oraler Enoximon-Langzeittherapie auf das Arrhythmieprofil bei chronischer Herzinsuffizienz. Z Kardiol 77:653–659

    CAS  PubMed  Google Scholar 

  23. Uretsky BF, Jessup M, Konstam MA, Dec GW, Leier CV, Benotti J, Murali S, Herrmann HC, Sandberg JA (1990) Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure. Circulation 82:774–780

    Article  CAS  PubMed  Google Scholar 

  24. Weber KT, Janicki JS, Jain MC (1986) Enoximone (MDL 17,043), a phosphodiesterase inhibitor, in the treatment of advanced, unstable chronic heart failure. J Heart Transplant 5:105–112

    CAS  PubMed  Google Scholar 

  25. Weber KT, Janicki JS, Maskin CS (1986) Effects of new inotropic agents on exercise performance. Circulation 73 [Suppl III]:196–204

    Google Scholar 

  26. Weber KT, Kinasewitz GT, Janicki JS, Fishman AP (1982) Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure. Circulation 65:1213–1223

    Article  CAS  PubMed  Google Scholar 

  27. Wilson JR, Martin JL, Schwartz D, Ferraro N (1984) Exercise intolerance in patients with chronic heart failure: role of impaired nutritive flow to skeletal muscle. Circulation 69:1079–1087

    Article  CAS  PubMed  Google Scholar 

  28. Zipperle G, Butzer F, Dieterich HA, Heinrich F (1987) A double-blind dose response comparison of oral enoximone and placebo for congestive heart failure. Am J Cardiol 60:72C-74C

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Medizinische Klinik, Klinikum Innenstadt der Universität München, Deutschland

    V. Klauss, W. Zwehl, H. Mudra, R. Huber, R. Schmidt, M. Scheininger, A. Vogler, O. Tschaidse, H. A. Dieterich & K. Theisen

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  1. V. Klauss
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  2. W. Zwehl
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  3. H. Mudra
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  4. R. Huber
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  5. R. Schmidt
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  6. M. Scheininger
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  7. A. Vogler
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  8. O. Tschaidse
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  9. H. A. Dieterich
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  10. K. Theisen
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Dedicated to Professor Jahrmärker on the occasion of his seventieth birthday

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Klauss, V., Zwehl, W., Mudra, H. et al. Short-term effects of oral enoximone on hemodynamics, exercise capacity, anaerobic threshold, and arrhythmias in congestive heart failure. Klin Wochenschr 69, 430–435 (1991). https://doi.org/10.1007/BF01666828

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  • DOI: https://doi.org/10.1007/BF01666828

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