Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure

Simon F. Shakar, William T. Abraham, Edward M. Gilbert, Alastair D. Robertson, Brian D. Lowes, Lawrence S. Zisman, Debra A. Ferguson, Michael R. Bristow

Research output: Contribution to journalArticle

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Abstract

Objectives. We sought to assess the effects of combined oral positive inotropic and beta-blocker therapy in patients with severe heart failure. Background. Patients with severe, class IV heart failure who receive standard medical therapy exhibit a 1-year mortality rate >50%. Moreover, such patients generally do not tolerate beta-blockade, a promising new therapy for chronic heart failure. Positive inotropes, including phosphodiesterase inhibitors, are associated with increased mortality when administered over the long term in these patients. The addition of a beta-blocker to positive inotropic therapy might attenuate this adverse effect, although long-term oral inotropic therapy might serve as a bridge to beta-blockade. Methods. Thirty patients with severe heart failure (left ventricular ejection fraction [LVEF] 17.2 ± 1.2%, cardiac index 1.6 ± 0.1 liter/min per m2) were treated with the combination of oral enoximone (a phosphodiesterase inhibitor) and oral metoprolol at two institutions. Enoximone was given at a dose of ≤1 mg/kg body weight three times a day. After clinical stabilization, metoprolol was initiated at 6.25 mg twice a day and slowly titrated up to a target dose of 100 to 200 mg/day. Results. Ninety-six percent of the patients tolerated enoximone, whereas 80% tolerated the addition of metoprolol. The mean duration of combination therapy was 9.4 ± 1.8 months. The mean length of follow-up was 20.9 ± 3.9 months. Of the 23 patients receiving the combination therapy, 48% were weaned off enoximone over the long term. The LVEF increased significantly, from 17.7 ± 1.6% to 27.6 ± 3.4% (p = 0.01), whereas the New York Heart Association functional class improved from 4 ± 0 to 2.8 ± 0.1 (p = 0.0001). The number of hospital admissions tended to decrease during therapy (p = 0.06). The estimated probability of survival at 1 year was 81 ± 9%. Heart transplantation was performed successfully in nine patients (30%). Conclusions. Combination therapy with a positive inotrope and a beta-blocker appears to be useful in the treatment of severe, class IV heart failure. It may be used as a palliative measure when transplantation is not an option or as a bridge to heart transplantation. Further study of this form of combined therapy is war ranted.

Original languageEnglish (US)
Pages (from-to)1336-1340
Number of pages5
JournalJournal of the American College of Cardiology
Volume31
Issue number6
DOIs
StatePublished - May 1998

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Heart Failure
Enoximone
Metoprolol
Therapeutics
Phosphodiesterase Inhibitors
Heart Transplantation
Stroke Volume
Mortality
Transplantation
Body Weight
Survival

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure. / Shakar, Simon F.; Abraham, William T.; Gilbert, Edward M.; Robertson, Alastair D.; Lowes, Brian D.; Zisman, Lawrence S.; Ferguson, Debra A.; Bristow, Michael R.

In: Journal of the American College of Cardiology, Vol. 31, No. 6, 05.1998, p. 1336-1340.

Research output: Contribution to journalArticle

Shakar, Simon F. ; Abraham, William T. ; Gilbert, Edward M. ; Robertson, Alastair D. ; Lowes, Brian D. ; Zisman, Lawrence S. ; Ferguson, Debra A. ; Bristow, Michael R. / Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure. In: Journal of the American College of Cardiology. 1998 ; Vol. 31, No. 6. pp. 1336-1340.
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title = "Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure",
abstract = "Objectives. We sought to assess the effects of combined oral positive inotropic and beta-blocker therapy in patients with severe heart failure. Background. Patients with severe, class IV heart failure who receive standard medical therapy exhibit a 1-year mortality rate >50{\%}. Moreover, such patients generally do not tolerate beta-blockade, a promising new therapy for chronic heart failure. Positive inotropes, including phosphodiesterase inhibitors, are associated with increased mortality when administered over the long term in these patients. The addition of a beta-blocker to positive inotropic therapy might attenuate this adverse effect, although long-term oral inotropic therapy might serve as a bridge to beta-blockade. Methods. Thirty patients with severe heart failure (left ventricular ejection fraction [LVEF] 17.2 ± 1.2{\%}, cardiac index 1.6 ± 0.1 liter/min per m2) were treated with the combination of oral enoximone (a phosphodiesterase inhibitor) and oral metoprolol at two institutions. Enoximone was given at a dose of ≤1 mg/kg body weight three times a day. After clinical stabilization, metoprolol was initiated at 6.25 mg twice a day and slowly titrated up to a target dose of 100 to 200 mg/day. Results. Ninety-six percent of the patients tolerated enoximone, whereas 80{\%} tolerated the addition of metoprolol. The mean duration of combination therapy was 9.4 ± 1.8 months. The mean length of follow-up was 20.9 ± 3.9 months. Of the 23 patients receiving the combination therapy, 48{\%} were weaned off enoximone over the long term. The LVEF increased significantly, from 17.7 ± 1.6{\%} to 27.6 ± 3.4{\%} (p = 0.01), whereas the New York Heart Association functional class improved from 4 ± 0 to 2.8 ± 0.1 (p = 0.0001). The number of hospital admissions tended to decrease during therapy (p = 0.06). The estimated probability of survival at 1 year was 81 ± 9{\%}. Heart transplantation was performed successfully in nine patients (30{\%}). Conclusions. Combination therapy with a positive inotrope and a beta-blocker appears to be useful in the treatment of severe, class IV heart failure. It may be used as a palliative measure when transplantation is not an option or as a bridge to heart transplantation. Further study of this form of combined therapy is war ranted.",
author = "Shakar, {Simon F.} and Abraham, {William T.} and Gilbert, {Edward M.} and Robertson, {Alastair D.} and Lowes, {Brian D.} and Zisman, {Lawrence S.} and Ferguson, {Debra A.} and Bristow, {Michael R.}",
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T1 - Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure

AU - Shakar, Simon F.

AU - Abraham, William T.

AU - Gilbert, Edward M.

AU - Robertson, Alastair D.

AU - Lowes, Brian D.

AU - Zisman, Lawrence S.

AU - Ferguson, Debra A.

AU - Bristow, Michael R.

PY - 1998/5

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N2 - Objectives. We sought to assess the effects of combined oral positive inotropic and beta-blocker therapy in patients with severe heart failure. Background. Patients with severe, class IV heart failure who receive standard medical therapy exhibit a 1-year mortality rate >50%. Moreover, such patients generally do not tolerate beta-blockade, a promising new therapy for chronic heart failure. Positive inotropes, including phosphodiesterase inhibitors, are associated with increased mortality when administered over the long term in these patients. The addition of a beta-blocker to positive inotropic therapy might attenuate this adverse effect, although long-term oral inotropic therapy might serve as a bridge to beta-blockade. Methods. Thirty patients with severe heart failure (left ventricular ejection fraction [LVEF] 17.2 ± 1.2%, cardiac index 1.6 ± 0.1 liter/min per m2) were treated with the combination of oral enoximone (a phosphodiesterase inhibitor) and oral metoprolol at two institutions. Enoximone was given at a dose of ≤1 mg/kg body weight three times a day. After clinical stabilization, metoprolol was initiated at 6.25 mg twice a day and slowly titrated up to a target dose of 100 to 200 mg/day. Results. Ninety-six percent of the patients tolerated enoximone, whereas 80% tolerated the addition of metoprolol. The mean duration of combination therapy was 9.4 ± 1.8 months. The mean length of follow-up was 20.9 ± 3.9 months. Of the 23 patients receiving the combination therapy, 48% were weaned off enoximone over the long term. The LVEF increased significantly, from 17.7 ± 1.6% to 27.6 ± 3.4% (p = 0.01), whereas the New York Heart Association functional class improved from 4 ± 0 to 2.8 ± 0.1 (p = 0.0001). The number of hospital admissions tended to decrease during therapy (p = 0.06). The estimated probability of survival at 1 year was 81 ± 9%. Heart transplantation was performed successfully in nine patients (30%). Conclusions. Combination therapy with a positive inotrope and a beta-blocker appears to be useful in the treatment of severe, class IV heart failure. It may be used as a palliative measure when transplantation is not an option or as a bridge to heart transplantation. Further study of this form of combined therapy is war ranted.

AB - Objectives. We sought to assess the effects of combined oral positive inotropic and beta-blocker therapy in patients with severe heart failure. Background. Patients with severe, class IV heart failure who receive standard medical therapy exhibit a 1-year mortality rate >50%. Moreover, such patients generally do not tolerate beta-blockade, a promising new therapy for chronic heart failure. Positive inotropes, including phosphodiesterase inhibitors, are associated with increased mortality when administered over the long term in these patients. The addition of a beta-blocker to positive inotropic therapy might attenuate this adverse effect, although long-term oral inotropic therapy might serve as a bridge to beta-blockade. Methods. Thirty patients with severe heart failure (left ventricular ejection fraction [LVEF] 17.2 ± 1.2%, cardiac index 1.6 ± 0.1 liter/min per m2) were treated with the combination of oral enoximone (a phosphodiesterase inhibitor) and oral metoprolol at two institutions. Enoximone was given at a dose of ≤1 mg/kg body weight three times a day. After clinical stabilization, metoprolol was initiated at 6.25 mg twice a day and slowly titrated up to a target dose of 100 to 200 mg/day. Results. Ninety-six percent of the patients tolerated enoximone, whereas 80% tolerated the addition of metoprolol. The mean duration of combination therapy was 9.4 ± 1.8 months. The mean length of follow-up was 20.9 ± 3.9 months. Of the 23 patients receiving the combination therapy, 48% were weaned off enoximone over the long term. The LVEF increased significantly, from 17.7 ± 1.6% to 27.6 ± 3.4% (p = 0.01), whereas the New York Heart Association functional class improved from 4 ± 0 to 2.8 ± 0.1 (p = 0.0001). The number of hospital admissions tended to decrease during therapy (p = 0.06). The estimated probability of survival at 1 year was 81 ± 9%. Heart transplantation was performed successfully in nine patients (30%). Conclusions. Combination therapy with a positive inotrope and a beta-blocker appears to be useful in the treatment of severe, class IV heart failure. It may be used as a palliative measure when transplantation is not an option or as a bridge to heart transplantation. Further study of this form of combined therapy is war ranted.

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