• Heart Failure
• Cardiology Clinical Trials
• Cardiology Genomics
• Inflammatory Disease

• Heart Failure
• Cardiology Clinical Trials
• Cardiology Genomics
• Inflammatory Disease
• Cardiology

Peripartum cardiomyopathy (PPCM) is a potentially life-threatening disease that is manifest as heart failure (HF) with left ventricular systolic dysfunction that occurs toward the end of pregnancy or in the months following delivery. It is associated with significant mortality and morbidity. Although its etiology has recently been the subject of much study, PPCM remains a diagnosis of exclusion. Karen Sliwa, MD, PhD, Hatter Institute for Cardiovascular Research in Africa, University of Cape Town, South Africa, discussed 2 potential biomarkers for PPCM that may improve diagnosis and thus treatment outcomes.

PPCM occurs more frequently in women with preeclampsia and/or multiple gestation [Patten IS et al. Nature 2012]. Although the diagnosis of preeclampsia has improved with the recent discovery of the imbalance between substances promoting and antagonizing angiogenesis, there remains a need to identify biomarkers for PPCM, as it can be difficult to differentiate symptomatic HF from physiologic symptoms of pregnancy such as dyspnea, edema, and palpitations.

Relaxin-2 is a naturally occurring peptide that is important to the hemodynamic and renal adjustments required during pregnancy. Myocardial expression of relaxin-2 is upregulated in congestive HF [Dschietzig T et al. FASEB J 2001]. Serelaxin is a relaxin-2 analogue that has recently been shown to improve clinical symptoms, organ function, and survival when administered intravenously to hospitalized patients admitted with nonperipartum acute HF [Teerlink JR et al. Lancet 2013].

The objective of the study presented by Professor Sliwa was to assess whether plasma angiogenesis and relaxin-2 are altered in women with PPCM. The study population included 160 peripartum women (77 with PPCM, 75 healthy breastfeeding mothers, and 8 with stable non-PPCM cardiac disease) and 94 nonperipartum participants (29 healthy women and 65 men and women with acute HF; Table 1).

Cardiovascular (N-terminal pro–brain natriuretic peptide, copeptin, midregional proadrenomedullin, and soluble ST2) and angiogenic (placenta-inhibiting growth factor, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, relaxin-2, etc) biomarkers were measured.

Compared with the other groups, subjects with PPCM had significantly higher levels of N-terminal pro–brain natriuretic peptide and lower levels of plasma relaxin-2 (Table 2). Plasma relaxin-2 was much lower among women with PPCM compared with healthy breastfeeding mothers (Table 2) and undetectable in 50% of patients with PPCM compared with 4% of healthy breastfeeding mothers.

The ratio of soluble fms-like tyrosine kinase 1 to placenta-inhibiting growth factor was lower among women with PPCM (1.3; range, 0.9–2.8) compared with the group of healthy breastfeeding mothers (52.8; range, 20.6–116.2). Receiver operating characteristic curve analysis confirmed that the lowest level of plasma relaxin-2 or soluble fms-like tyrosine kinase 1/placenta-inhibiting growth factor ratio and the highest level of plasma N-terminal pro–brain natriuretic peptide were all associated with PPCM, with areas under the curve of about 0.95. Combining these biomarkers for the diagnosis of PPCM in peripartum women had specificity of 0.75, sensitivity of 0.74, positive predictive value of 0.92, and negative predictive value of 0.82.

These results suggest that angiogenic and relaxin-2 pathways are altered in patients with PPCM, providing a novel biomarker strategy to aid in diagnosis. These findings also raise the question of whether women with PPCM may benefit from adjunctive therapy with serelaxin in addition to standard care.

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