What Do We Know about Peripartum Cardiomyopathy? Yesterday, Today, Tomorrow

Abstract

Peripartum cardiomyopathy is a disease that occurs during or after pregnancy and leads to a significant decline in cardiac function in previously healthy women. Peripartum cardiomyopathy has a varying prevalence among women depending on the part of the world where they live, but it is associated with a significant mortality and morbidity in this population. Therefore, timely diagnosis, treatment, and monitoring of this disease from its onset are of utmost importance. Although many risk factors are associated with the occurrence of peripartum cardiomyopathy, such as conditions of life, age of the woman, nutrient deficiencies, or multiple pregnancies, the exact cause of its onset remains unknown. Advances in research on the genetic associations with cardiomyopathies have provided a wealth of data indicating a possible association with peripartum cardiomyopathy, but due to numerous mutations and data inconsistencies, the exact connection remains unclear. Significant insights into the pathophysiological mechanisms underlying peripartum cardiomyopathy have been provided by the theory of an abnormal 16-kDa prolactin, which may be generated in an oxidative stress environment and lead to vascular and consequently myocardial damage. Recent studies supporting this disease mechanism also include research on the efficacy of bromocriptine (a prolactin synthesis inhibitor) in restoring cardiac function in affected patients. Despite significant progress in the research of this disease, there are still insufficient data on the safety of use of certain drugs treating heart failure during pregnancy and breastfeeding. Considering the metabolic changes that occur in different stages of pregnancy and the postpartum period, determining the correct dosing regimen of medications is of utmost importance not only for better treatment and survival of mothers but also for reducing the risk of toxic effects on the fetus.

Keywords: heart failure; peripartum cardiomyopathy; pregnancy; prognosis; treatment.

Figure 1

Potential pathogenetic mechanisms in the development of peripartum cardiomyopathy. Legend: STAT—Signal Transducer and Activator of Transcription; MnSOD—Manganese SuperOxide Dismutase; ROS—Reactive Oxygen Species; microRNA—single-strand endogenous and non-coding RNA molecules; sFLT1—soluble Fms-Like Tyrosine kinase 1; VEGF—Vascular Endothelial Growth Factor; PPCM—PeriPartum CardioMyopathy; PRL—Prolactin; Cath D—Cathepsin D; − decrease; and + increase; The figure shows potential mechanisms that may be involved in the development of PPCM. Potential downregulation of STAT3 signaling pathways leads to a decrease in MnSOD synthesis leading to an increase in ROS. ROS can increase the synthesis of Cath D which further plays a role in the cleavage of prolactin 23 kDa to the highly reactive form 16 kDa PRL. This form of PRL can cause direct damage to the blood vessel endothelium, and potentiating the increase in microRNa-146 leads to cardiomyocyte apoptosis. As part of the hemodynamic changes during pregnancy, the heart muscle is loaded with volume, which is accompanied by hypertrophy and increased oxygen needs. Increased expression of sFLT1 (a known anti-angiogenic factor) in pregnancy leads to a decrease in VEGF, which definitely reduces the angiogenesis of volume-loaded cardiomyocytes. This anti-angiogenic environment may lead to additional cardiomyocyte apoptosis. Cardiotropic viruses can also be responsible for the development of PPCM, although their role in the development of this disease has not been fully investigated.