Gender particulars of morphological phenotypes of the right atrial appendage myocardium in patients with chronic heart failure who underwent an open heart surgery

Background: For many decades, women in all age groups have a high risk of mortality and perioperative complications of cardiac surgery (CS), with its cause being unclear until now. Preoperative prediction of cardiovascular complications (CVC), based only on the clinical and instrumental criteria without taking gender into account, also remains unsuccessful. There is an opinion that the structural and functional changes in the myocardium, which exist before the operation, could significantly affect the patient's condition after cardiac surgery.

Aim: To identify morphological and molecular predictors of unfavorable prognosis in chronic heart failure (CHF) patients of both genders after CS.

Materials and methods: The study included 87 CHF patients of both genders referred for an elective cardiac surgery. Before the operation, a standard examination and treatment of CHF and concomitant disorders were performed. A sample of the right atrial appendage (RAA) myocardium that had been resected during the CS, was studied by histological, immunohistochemical (IHC) (expression of caspase-3, bcl-2, MMP-2, TIMP-1, p38α, CD-34) and morphometric methods. At days 10 to 14 after CS, the presence of CVC was assessed in all the participants. We examined the relationship between the development of CVC and morphological changes in the RAA myocardium before surgery, taking into account the patients' gender.

Results: Compared to the group with the favorable postoperative course in the myocardium, in the male/female group with unfavorable post-CS course there was a significant reduction in the cardiomyocyte (CMC) diameter (13.26 ± 3.14; p < 0.01 / 13.99 ± 3.64; p < 0.01), the bulk density (BD) of CMC (55.4 ± 9.45; p < 0.01 / 51.22 ± 10.12; p < 0.01) vol. %, a trophic index (0.24 ± 0.1; p < 0.01 / 0.21 ± 0.06; p < 0.01), as well as a significant increase in the stromal BD (44.91 ± 9.23; p < 0.01 / 47.78 ± 10.12; p <0.01) vol. % and the Kernogan index (1.78 ± 0.49; p < 0.01 / 1.43 ± 0.64; p = 0.143). IHC analysis of the RAA myocardium in the male/female group with an unfavorable postoperative course showed an increase in the amount of caspase-3 (+) CMC (3.9 ± 0.46; p < 0.01 / 3.34 ± 0.4; p < 0.01), an increase in the activity of +/++/+++ p38α (3/30/69; p < 0.01 / 2/39/60; p < 0.01) %, the expression of MMP-2 (2/56/43; p < 0.01 / 0/68/31; p < 0.01) %, with a decrease in the expression of TIMP-1 (19/29/52; p < 0.01 / 8/24/67; p < 0.01) % and BD of CD-34 stromal cells (18.46 ± 8.5; p < 0.01 / 27.54 ± 5.88; p < 0.01) %, compared with groups with a favorable current.

Сonclusion: The study showed the role of caspase-3, MMP-2, and CD-34 in the RAA myocardium as prognostic markers of CVC in the early postoperative period, as well as gender differences in modulation of the apoptotic pathways and inefficiency of anti-apoptotic mechanisms in the RAA myocardium. Based on the assessment of the RAA myocardial reorganization, an integral prognostic picture of the structural and functional changes in the myocardium has been proposed, which makes it possible to identify a special patient cohort with an exceptionally high risk of unfavorable course of the post-CS period.