Relaxin-2 and Soluble Flt1 Levels in Peripartum Cardiomyopathy

Abstract

Background Peripartum cardiomyopathy (PPCM) is an uncommon disorder with unknown etiology. Angiogenic imbalance may contribute to its pathophysiology. We explore the association of vascular hormones with myocardial recovery and clinical outcomes in PPCM. Methods and Results In 98 women with newly diagnosed PPCM enrolled in the Investigation in Pregnancy Associated Cardiomyopathy (IPAC) study, serum was obtained at baseline for analysis of relaxin-2, prolactin, soluble fms-like tyrosine kinase 1 (sFlt1), and vascular endothelial growth factor (VEGF). Left ventricular ejection fraction (LVEF) was assessed by echocardiography at baseline and 2, 6 and 12 months. Mean age was 30 ± 6 years, with baseline LVEF 0.35 ± 0.09. Relaxin-2, prolactin, and sFlt1 were elevated in women presenting early postpartum, but declined rapidly and were inversely correlated with time from delivery to presentation. In tertile analysis, higher relaxin-2 was associated with smaller left ventricular systolic diameter (p=0.006) and higher LVEF at 2 months (p=0.01). This was particularly evident in women presenting soon after delivery (p=0.02). No relationship was evident for myocardial recovery and prolactin, sFlt1 or VEGF levels. sFlt1 levels were higher in women with higher New York Heart Association (NYHA) functional class (p=0.01) and adverse clinical events (p=0.004). Conclusions In women with newly diagnosed PPCM, higher relaxin-2 levels soon after delivery were associated with myocardial recovery at 2 months. In contrast, higher sFlt1 levels correlated with more severe symptoms and major adverse clinical events. Vascular mediators may contribute to development of PPCM and influence subsequent myocardial recovery. Clinical Trial Registration Information NCT01085955 https://clinicaltrials.gov/ct2/show/NCT01085955

Peripartum cardiomyopathy

“…In the IPAC cohort, the vasodilatory and pro-angiogenic hormone relaxin was associated with less left ventricular dilatation at diagnosis and earlier recovery of left ventricular function 64. In addition, an increase in troponin concentration is modestly associated with persistent left ventricular dysfunction.…”

“…SFlt-1 levels decline rapidly after delivery (after the placental source of sFlt-1 is removed) in healthy women but remain higher than the normal range in women with PPCM 6264. The source of persistently raised sFlt-1 postpartum is not currently known.…”

“…The source of persistently raised sFlt-1 postpartum is not currently known. In the IPAC cohort, the concentration of sFlt-1 at the time of the diagnosis of PPCM correlated with the patient’s New York Heart Association (NYHA) functional class and adverse events 64. It is notable that most women with PPCM present in the postpartum period65; maternal levels of sFlt-1 and other placental hormones peak during labor, and this peak may contribute to a syndrome that manifests postpartum 66.…”

Peripartum cardiomyopathy, what if your patient plans to reconceive?

“…These factors are diverse from being clinical, hormonal, or imaging modalities. Some examples include race, comorbidities, relaxin level, pro‐BNP titer, LV dimension in diastole, and global longitudinal strain 1, 2, 3, 4, 5. A consensus on how to estimate the risk of PPCM relapse is lacking.…”

Peripartum cardiomyopathy: diagnosis and management

“…It has a variety of haemodynamic effects, including increased cardiac output and decreased systemic vascular resistance, as well as anti-inflammatory and antifibrotic properties. Higher levels of relaxin-2 are associated with increased rates of myocardial recovery 16. A recent trial of relaxin in acute heart failure (not in PPCM) reported no reduction in cardiovascular death or worsening heart failure 17.…”