Peripartum Cardiomyopathy: a Review

Mitochondrial Function and Dysfunction in Dilated Cardiomyopathy

“…More recent studies have reported that mutations in cardiac sarcomere proteins are a pathogenic cause of PPCM. These mutations include deleterious truncations in the titin encoding TTN gene that is a clinical feature shared with idiopathic DCM ( van Spaendonck-Zwarts et al, 2014 ; Ware et al, 2016 ; Ballard, 2019 ). Titin is part of the structural organization and assembly of the sarcomere from the Z-disc to the M-line along with other developmental, regulatory and mechanical functions in cardiac and skeletal muscle ( Lee and Judge, 2017 ).…”

“…β-MHC forms the heavy chain structure of type II myosin in sarcomeres, which in a sliding mechanism with actin filaments, generates the mechanical forces needed for muscle contraction. Mutations in the STAT3 gene have also been found to contribute to PPCM ( Ballard, 2019 ; Harhous et al, 2019 ). Other genes in which mutations have been reported to be associated with PPCM onset and progression include truncations in DMD (dystrophin that causes Duchenne’s Muscular Dystrophy) ( Cheng and Prior, 2013 ; Ahmed et al, 2016 ), DSP (desmoplakin) ( Ware et al, 2016 ), TPM1 (α-tropomyosin)( Ware et al, 2016 ), and missense mutations in MYBPC3 (cardiac myosin binding protein C) ( Morales et al, 2010 ), TNNC1 (cardiac troponin C) ( Mestroni et al, 1994 ), TNNT2 (cardiac troponin T) ( Morales et al, 2010 ), and LAMP2 (lysosome-associated membrane protein) ( Ware et al, 2016 ).…”

“…Other genes in which mutations have been reported to be associated with PPCM onset and progression include truncations in DMD (dystrophin that causes Duchenne’s Muscular Dystrophy) ( Cheng and Prior, 2013 ; Ahmed et al, 2016 ), DSP (desmoplakin) ( Ware et al, 2016 ), TPM1 (α-tropomyosin)( Ware et al, 2016 ), and missense mutations in MYBPC3 (cardiac myosin binding protein C) ( Morales et al, 2010 ), TNNC1 (cardiac troponin C) ( Mestroni et al, 1994 ), TNNT2 (cardiac troponin T) ( Morales et al, 2010 ), and LAMP2 (lysosome-associated membrane protein) ( Ware et al, 2016 ). This list of gene mutations causing PPCM continues to grow as more genes are identified ( Lee and Judge, 2017 ; Ballard, 2019 ). Additional evidence supporting an involvement of gene mutations in PPCM includes familial incidence, genome-wide association studies and variability of occurrence of PPCM among women from different regions and ethnicities ( Lee and Judge, 2017 ).…”

Peripartum cardiomyopathy

“…Therefore, the disease timeline does not correlate. 7,8 The true overarching pathophysiology is now considered to be multifactorial, with a single theory unlikely to provide unification. Recent attempts at exploring PPCM aetiology have proposed a 'two-hit' model 9 of genetic predisposition combined with a vascular hormonal insult to the maternal heart in and around term, as illustrated in Figure 1.…”

“…9 Administration of bromocriptine, a prolactin antagonist, appeared to reverse systolic impairment in STAT3 deficient mice; the current clinical use of bromocriptine is based upon this theory. 8,12 The 16-kDa fragment also increases levels of microRNA-146a, which blocks several signalling cascade pathways, eventually contributing to cardiac myocyte death. 9 The placenta secretes exponentially increasing concentrations of soluble fms-like tyrosine kinase receptor 1 (sFlt-1) towards the end of pregnancy as part of the adaptive process to minimise the likelihood of haemorrhage in labour.…”