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

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 guidelinedirected 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.

Nonobstructive Coronary Artery Disease in Women:Risk Factors and Noninvasive Diagnostic Assessment

Sex-specific differences in the epidemiology and pathophysiology of coronary artery disease and ischemic heart disease are now well recognized.Women with angina more often have nonobstructive coronary artery disease(NOCAD)compared with men.This patient population carries a significant risk of future cardiovascular events that is not commonly appreciated,often leading to delayed diagnosis and treatment.While coronary microvascular dysfunction plays a central role in the pathophysiology of NOCAD in women,other mechanisms of myocardial ischemia are now recognized.Risk factors such as hypertension and obesity disparately affect women and are likely to account for a signifi cant proportion of NOCAD in the coming years.Vascular inflammation is an important pathophysiologic pathway in NOCAD and is a potential therapeutic target.Coronary CT angiography provides a comprehensive assessment of coronary anatomy and plaque morphology and is a reasonable screening test of choice for NOCAD.