Bromocriptine for the treatment of peripartum cardiomyopathy: welcome on BOARD

Peripartum cardiomyopathy (PPCM), according to the actual definition proposed by the Study Group on PPCM of the Heart Failure Association of the European Society of Cardiology (ESC), is an idiopathic cardiomyopathy frequently presenting with left ventricular (LV) systolic dysfunction (LV ejection fraction <45%) towards the end of pregnancy or in the months following delivery in the absence of other causes. The most common clinical presentation consists of acute heart failure (AHF) occurring in the first weeks after delivery. The worldwide burden of PPCM is estimated based on singlecentre case series from Haiti, South Africa, and the USA showing incidences ranging from 1:3000 to 1:100 pregnancies. Women of African origin display a significantly higher risk of developing PPCM. The clinical outcome of women with PPCM seems to vary across the world, probably because of differences in ethnic and social factors and access to AHF treatment, but also due to heterogeneity in the inclusion criteria in the studies. Accordingly, reported mortality rates may vary from <5% up to 50%. Moreover, despite the fact that several publications reported rapid recovery of LV function (within 6 months after diagnosis) in the majority of patients, other studies reported delayed LV recovery in a significant proportion of patients. Notably, Afro-American women showed lower rates of recovery and worse prognosis compared with Caucasians. New insights into the epidemiology and outcome of PPCM from the EURObservational Research Programme of the ESC may, however, suggest comparable outcome between European and non-European regions. The management of women presenting with AHF due to PPCM remains very challenging. The initial treatment depends on the time point of onset and the ability to have a diagnosis. Women presenting with PPCM during pregnancy require joint cardiac and obstetric care, because therapeutic interventions need always to consider the health of both the mother and the foetus. Women presenting after delivery can generally be treated according to the ESC Guidelines for heart failure. Very recently, the Study Group on PPCM of the Heart Failure Association of the ESC published a practical guidance paper on the management of acute PPCM patients. The treatment of post-partal AHF due to PPCM consist—similarly to other forms of AHF—of (i) decongestive treatment via vasorelaxing agents, diuretics, and non-invasive ventilation to improve symptoms and reduce organ dysfunction; (ii) neuro-humoral inhibition via oral heart failure therapies (e.g. beta-blockers, ACE inhibitors, and mineralocorticoid receptor antagonists) to improve LV recovery and outcome; and (iii) in selected patients, device therapy to reduce symptoms and improve outcome. Ideally, a specific pathophysiologydirected therapy should complete the treatment: for that purpose, knowledge of mechanisms involved in disease onset is required. The paper by Hilfiker-Kleiner et al. in this issue of the journal confirmed that PPCM should be treated with bromocriptine as specific aetiological therapy for PPCM. In recent years, multiple mechanisms, in addition to general cardiovascular risk and pregnancy-related factors, have been described as having a role in the aetiology of PPCM, albeit that the exact pathophysiology remains poorly understood. A ‘double-hit’ model of angiogenic imbalance in the heart during the peripartal period has been proposed, combining systemic antiangiogenic signals during late pregnancy and host susceptibility through insufficient local proangiogenic defences in the heart. Evidence of dysregulated plasma levels of proand antiangiogenic factors supports early diagnosis of PPCM. Angiogenic imbalance can further be triggered by oxidative stress activating cathepsin D, a protease responsible for the cleavage of the nursing hormone prolactin into the angiostatic and proapoptotic 16 kDa subfragment. In a previous mouse model, suppression of prolactin production prevented the onset of PPCM. Bromocriptine, a substance used for many years to stop lactation in post-partum women by suppressing prolactin production, was evaluated as adjunctive treatment of PPCM in a proof-of-concept clinical