**5.6 Prolactin role**

Alteration in prolactin processing is involved in the pathogenesis of peripartum cardiomyopathy; animal with a knockout in the cardiac tissue-specific signal

**113**

**Figure 2.**

**7. Signs and symptoms**

*Pregnancy and occurrence of PPCM [19].*

*Peripartum Cardiomyopathy: Facts and Figures DOI: http://dx.doi.org/10.5772/intechopen.85718*

cardiomyopathies (**Figure 1**) [20].

**6. Clinical presentations**

transduction and activator of transcription 3 (STAT3) developed PPCM. Reduction in STAT3 leads to increased cleavage of prolactin into an anti-angiogenic and proapoptotic 16 kDa isoform by cathepsin D. The 16 kDa prolactin fragment (16K PRL) causes endothelial damage leading to myocardial dysfunction; 16K PRL induces microRNA-146a expression in endothelial cells, which leads to most of the anti-angiogenic effects of 16K PRL. Females with PPCM have elevated levels of microRNA-146a compared with healthy postpartum women or women with other

PPCM is common in first postpartum month; it is also rare before 36 weeks of gestation (**Figure 2**). The common presentations of PPCM are dyspnea, cough, orthopnea, and paroxysmal nocturnal dyspnea, which may be confused with the physiological changes of pregnancy. Initial diagnosis may be delayed since symptoms such as nonspecific fatigue, shortness of breath, and pedal edema are similar to those observed in normal pregnancy The patient may have arrhythmia and even cardiac arrest rarely [4]; PPCM can present with thromboembolic manifestations; patients with left ventricular ejection fraction (LVEF) < 35% are at risk for developing left ventricular thrombus. PPCM is manifested after 38 weeks of pregnancy, whereas pregnant patients with chronic heart disease develop sign and symptoms of heart failure in the second trimester of pregnancy due to stress of hemodynamic overload.

Signs and symptoms are variable and similar to that in other forms of systolic HF due to cardiomyopathy. Signs include an elevated jugular venous pressure, displaced apical impulse, a third heart sound, and a murmur of mitral regurgitation. Signs and symptoms of systemic or pulmonary thromboembolism may be present. Various studies have reported varying rates of thromboembolism, and further data are required to quantify the risk of this complication. Patients with PPCM left ventricular thrombus were identified by echocardiography in 16 of 100 patients

with PPCM (with mean LVEF of 26%) in a case series [2, 21].

**Figure 1.** *Summary of etiopathogenesis of PPCM (from [19]).*

*Peripartum Cardiomyopathy: Facts and Figures DOI: http://dx.doi.org/10.5772/intechopen.85718*

*Inflammatory Heart Diseases*

**5.4 Maladaptation to stress of pregnancy**

between preeclampsia and PPCM [17].

**5.5 Angiogenic imbalance and balance**

correlates with sFlt1 levels [18].

**5.6 Prolactin role**

The hyperdynamic circulation during pregnancy causes remodeling and transient hypertrophy of the left ventricle. The exaggerated reduction in left ventricular systolic function with stress of gestational hypertension may contribute to heart failure in PPCM patients. In pregnancy 40–50% increase in blood volume and cardiac output occurs which results in transient LV hypertrophy. The hemodynamic stress of gestational hypertension, may contribute to the development of PPCM and heart failure, with an angiogenic imbalance may better explain the association

Human and animal studies suggest that PPCM is caused by systemic angiogenic imbalance. Animals that lack cardiac PGC-1α, a regulator of proangiogenic factors such as VEGF, develop severe PPCM. These data may also explain why preeclampsia and multiple gestations are risk factors for PPCM. During late gestation, the human placenta secretes VEGF inhibitors such as soluble fms-like tyrosine kinase 1 (sFlt1), which damages the vasculature, with higher levels seen with multiple gestations or preeclampsia. Preeclampsia and multiple gestations are risk factors for PPCM as in these patients subclinical cardiac dysfunction

Alteration in prolactin processing is involved in the pathogenesis of peripartum

cardiomyopathy; animal with a knockout in the cardiac tissue-specific signal

**112**

**Figure 1.**

*Summary of etiopathogenesis of PPCM (from [19]).*

transduction and activator of transcription 3 (STAT3) developed PPCM. Reduction in STAT3 leads to increased cleavage of prolactin into an anti-angiogenic and proapoptotic 16 kDa isoform by cathepsin D. The 16 kDa prolactin fragment (16K PRL) causes endothelial damage leading to myocardial dysfunction; 16K PRL induces microRNA-146a expression in endothelial cells, which leads to most of the anti-angiogenic effects of 16K PRL. Females with PPCM have elevated levels of microRNA-146a compared with healthy postpartum women or women with other cardiomyopathies (**Figure 1**) [20].
