Introduction

Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-associated systolic heart failure that typically presents toward the end of pregnancy or in the months after delivery and is characterized by reduced left ventricular systolic function, commonly defined by left ventricular ejection fraction (LVEF) below 45% in the absence of another identifiable cause [1,2]. Contemporary pregnancy-specific guidance emphasizes early recognition, echocardiographic confirmation, multidisciplinary care, and treatment that is compatible with pregnancy and lactation, while general heart failure guidance for reduced ejection fraction identifies four foundational drug classes when they are clinically appropriate and not contraindicated [2,3]. Because symptoms such as dyspnea, fatigue, edema, and reduced exercise tolerance may resemble late-pregnancy changes, delayed recognition can increase the risk of pulmonary edema, arrhythmia, thromboembolism, cardiogenic shock, and persistent ventricular dysfunction [4,5].

PPCM is a global disorder with heterogeneous presentation, treatment, and recovery. In the European Society of Cardiology (ESC) EURObservational Research Programme (EORP) PPCM registry, clinical presentation and management varied across regions, and myocardial recovery was incomplete in a substantial proportion of patients at follow-up [6]. A subsequent one-year analysis from the same registry showed continued maternal risk, including mortality, thromboembolic events, and incomplete left ventricular recovery in a clinically important subset [7]. These data support the need for optimized, context-appropriate management strategies while recognizing that treatment effects may be difficult to interpret without comparable baseline risk profiles.

The disease is biologically and clinically heterogeneous. Hypertensive disorders of pregnancy frequently coexist with PPCM and may define a distinct phenotype with different recovery patterns [8]. Genetic susceptibility is also increasingly recognized, with evidence of shared predisposition between PPCM and dilated cardiomyopathy, including truncating variants in genes related to myocardial structure and function [9]. These factors may influence baseline severity, hemodynamic load, and the trajectory of recovery independent of any specific intervention.

One mechanistic hypothesis links oxidative stress to cleavage of prolactin into a 16 kDa fragment with anti-angiogenic and cardiotoxic properties [10]. Bromocriptine, a dopamine receptor agonist that inhibits prolactin release, has therefore been investigated as an adjunct to standard heart failure therapy in PPCM [11]. A German multicenter randomized trial compared one-week and eight-week bromocriptine regimens. Left ventricular ejection fraction improved substantially in both groups, with no statistically significant difference in the change in left ventricular ejection fraction between the two regimens [12]. The previously published rationale-and-design article for the same registered trial (NCT00998556) specified prophylactic-dose anticoagulation during the period of bromocriptine treatment in both groups [13]. An editorial proposed the BOARD acronym for a combined peripartum cardiomyopathy management approach comprising bromocriptine, oral heart-failure therapies, anticoagulants, vasorelaxing agents, and diuretics [14]. A subsequent systematic review and meta-analysis found that prolactin inhibition was associated with improved left ventricular ejection fraction and greater odds of left ventricular recovery, but not with a significant reduction in all-cause mortality; the authors therefore emphasized the need for larger multicenter studies with longer follow-up [15]. Proteomic analyses from contemporary registries further support a role for inflammatory, vascular, fibrotic, and coagulation pathways in PPCM biology [16].

The present study was designed to compare early LVEF recovery among patients with PPCM who received low-dose short-course bromocriptine in addition to standard therapy versus those who received standard therapy alone. The primary objective was to compare LVEF at discharge and one month between treatment groups. Secondary objectives were to describe maternal, obstetric, and neonatal outcomes and to identify baseline factors that may affect interpretation of group comparisons. Serum prolactin was not analyzed because prolactin data were not available in the analyzable dataset.