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Imbalanced Angiogenesis in Peripartum Cardiomyopathy - Diagnostic Value of Placenta Growth Factor
Alexandre Mebazaa1,2,3, Marie-France Seronde1,4, Etienne Gayat1,2,3
1UMR-S 942 INSERM, Lariboisière Hospital.
Insights
Peripartum cardiomyopathy (PPCM) is linked to an imbalance in angiogenesis. Elevated placenta growth factor (PlGF) and low soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio may help diagnose PPCM.
Area of Science:
- Cardiovascular Medicine
- Reproductive Biology
- Biochemistry
Background:
- Peripartum cardiomyopathy (PPCM) is a rare form of heart failure.
- Alterations in anti-angiogenic factors like soluble fms-like tyrosine kinase-1 (sFlt-1) are observed in PPCM.
- The balance of angiogenic factors is critical in PPCM pathophysiology.
Purpose of the Study:
- To investigate the changes in the angiogenesis balance in patients with PPCM.
- To compare angiogenic factor concentrations in PPCM patients with healthy controls and acute heart failure (AHF) patients.
- To evaluate the diagnostic potential of angiogenic factors in distinguishing PPCM.
Main Methods:
- Plasma concentrations of sFlt-1 and placenta growth factor (PlGF) were measured in PPCM patients (n=83), healthy women (n=30), and AHF patients (n=65).
- Exclusion criteria included prepartum cardiac failure or hypertension (e.g., pre-eclampsia).
- Plasma concentrations of relaxin-2 were also assessed.
Main Results:
- PPCM patients exhibited significantly higher PlGF and lower sFlt-1/PlGF ratios compared to normal deliveries and AHF patients.
- The sFlt-1/PlGF ratio was markedly lower in PPCM (1.2) versus normal deliveries (94.8).
- PlGF (cut-off: 50 ng/mL) and sFlt-1/PlGF ratio (cut-off: 4) demonstrated high diagnostic accuracy (>0.94 AUC) for PPCM.
Conclusions:
- Plasma from PPCM patients demonstrates an imbalanced angiogenesis.
- Elevated PlGF and/or a low sFlt-1/PlGF ratio show potential as diagnostic markers for PPCM.
- Lower concentrations of relaxin-2 were observed in PPCM and AHF compared to normal deliveries.
Background:
Concentrations of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) are altered in peripartum cardiomyopathy (PPCM). In this study we investigated changes in the angiogenesis balance in PPCM.
Methods And Results:
Plasma concentrations of sFlt-1 and the pro-angiogenic placenta growth factor (PlGF) were determined in patients with PPCM during the post-partum phase (n=83), in healthy women at delivery (n=30), and in patients with acute heart failure (AHF; n=65). Women with cardiac failure prepartum or associated with any form of hypertension, including pre-eclampsia, were excluded. Compared with non-pregnant women, in women with AHF and PPCM, median PlGF concentrations were greater (19 [IQR 16-22] and 98 [IQR 78-126] ng/mL, respectively; P<0.001) and the sFlt-1/PlGF ratio was lower (9.8 [6.6-11.3] and 1.2 [0.9-2.8], respectively; P<0.001). The sFlt-1/PlGF ratio was lower in PPCM than in normal deliveries (1.2 [0.9-2.8] vs. 94.8 [68.8-194.1], respectively; P<0.0001). The area under the curve for PlGF (cut-off value: 50ng/mL) and/or the sFlt-1/PlGF ratio (cut-off value: 4) to distinguish PPCM from either normal delivery or AHF was >0.94. Median plasma concentrations of the anti-angiogenic factor relaxin-2 were lower in PPCM and AHF (0.3 [IQR 0.3-1.7] and 0.3 [IQR 0.3-1] ng/mL, respectively) compared with normal deliveries (1,807 [IQR 1,101-4,050] ng/mL; P<0.001).
Conclusions:
Plasma of PPCM patients shows imbalanced angiogenesis. High PlGF and/or low sFlt-1/PlGF may be used to diagnose PPCM.
