Novel role of phosphodiesterase inhibitors in the management of end-stage heart failure

Abstract

In advanced heart failure (HF), chronic inotropic therapy with intravenous milrinone, a phosphodiesterase III inhibitor, is used as a bridge to advanced management that includes transplantation, ventricular assist device implantation, or palliation. This is especially true when repeated attempts to wean off inotropic support result in symptomatic hypotension, worsened symptoms, and/or progressive organ dysfunction. Unfortunately, patients in this clinical predicament are considered hemodynamically labile and may escape the benefits of guideline-directed HF therapy. In this scenario, chronic milrinone infusion may be beneficial as a bridge to introduction of evidence based HF therapy. However, this strategy is not well studied, and in general, chronic inotropic infusion is discouraged due to potential cardiotoxicity that accelerates disease progression and proarrhythmic effects that increase sudden death. Alternatively, chronic inotropic support with milrinone infusion is a unique opportunity in advanced HF. This review discusses evidence that long-term intravenous milrinone support may allow introduction of beta blocker (BB) therapy. When used together, milrinone does not attenuate the clinical benefits of BB therapy while BB mitigates cardiotoxic effects of milrinone. In addition, BB therapy decreases the risk of adverse arrhythmias associated with milrinone. We propose that advanced HF patients who are intolerant to BB therapy may benefit from a trial of intravenous milrinone as a bridge to BB initiation. The discussed clinical scenarios demonstrate that concomitant treatment with milrinone infusion and BB therapy does not adversely impact standard HF therapy and may improve left ventricular function and morbidity associated with advanced HF.

Keywords: Milrinone; Advanced heart failure; Bridge to beta blocker; Combination therapy; Inotrope support

Core tip: Heart failure (HF) patients requiring chronic inotropic support are considered hemodynamically labile and may escape the benefits of evidence based HF therapy (HFTx). Chronic milrinone infusion may be beneficial as a bridge to introduction of HFTx. We discuss evidence that intravenous milrinone support may allow introduction of beta blocker (BB). We propose that HF patients who are intolerant to BB therapy may benefit from intravenous milrinone as a bridge to BB initiation. When used together, BB mitigates cardiotoxic effects and decreases the risk of arrhythmias associated with milrinone. Whereas, milrinone does not attenuate the clinical benefits of BB therapy.