Combined Oral Positive Inotropic and Beta-Blocker Therapy for Treatment of Refractory Class IV Heart Failure

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 warranted.