LAA is the derivative of the primitive fetal atrium, aside from known electrical and mechanical/reservoir properties4,10, the current studies have also shown the LAA has important neurohormonal function4,6,7. LAA is a well-known source of Atrial natriuretic peptide (ANP) and approximately 30% of total ANP is stored in the LAA within ANP-producing granulocytes. The secretion of ANP and BNP is stimulated by various factors and the most sensitive of which is the distention in the LAA wall12,13. After being secreted into the circulation from the heart, ANP and BNP produce diuretic, natriuretic, and hypotensive activity via affecting the vessel, kidney, and functionally antagonizing the renin-angiotensin-aldosterone system (RAAS) 14,15. In the patients with heart failure, the increase of ANP and BNP induce natriuresis and diuresis resulting in the normalization of sodium levels and blood pressure. However, in a non-heart failure state, serum ANP and BNP elevation can induce hyponatremia and unwanted hypotension16.
In our study, we observed that the SBP increased immediately postoperation, then return to the baseline level on the 1st day postoperative, and have no significant difference with the baseline at discharge. DBP showed the familiar trend with SBP, except only increased a little immediately postoperation. The outcomes of patients undergoing the E-clip procedure we observed are different from the past studies about the changes of BP in the patients following on others epicardial left atrial appendage closure8,17. Maybrook et8 announced that LAA exclusion through LARIAT suture delivery device results in an early and persistent decrease in systolic BP, Maybrook et8 observed a significant reduction of systolic BP (mmHg) at 24 h (113.3 ± 16.0; p < 0.0001) and 72 h (119.0 ± 18.4 mmHg; p < 0.0001) post-LARIAT when compared with pre-LARIAT BP (138.2 ± 21.3). The reduction in systolic BP persisted at 6-month follow-up (128.8 ± 17.3; p = 0.0005). In the study that included 38 patients who underwent epicardial LAAE, about blood pressure change following epicardial LAA exclusion, Turagam et18 also observed a significant decrease in SBP both at 3-month follow-up, and it's worth noting that compared to the baseline level(137.50 mmHg), SBP was significantly decreased immediately postoperation(115.40 mmHg). In our study, the E-clip procedure was performed in patients thoracoscopically which means there was no extracorporeal circulation, and no sternotomy was performed in operation. Furthermore, as mentioned above, the procedure of epicardial LAAC includes closure, suture ligation, stapling, and excision. The different procedures lead to different physiological changes in LAA postoperation, in our study, the LAA in the patients who underwent the E-clip procedure will present with situ ischemic necrosis and fibrosis. Compared with the studies which mixed multiple kind procedures of epicardial LAAC into one group, and performed other cardiac surgery procedures simultaneously, the outcome we observed in our study may represent the blood pressure changes of patients undergoing stand-alone thoracoscopic left atrial appendage clipping by E-clip more accurate. Based on the phenomenon we observed, we hypothesized that stand-alone thoracoscopic left atrial appendage clipping may not result in a long-term decrease in blood pressure, but long-term follow-up is needed to prove this perspective. It should be noted that although the blood pressure of patients following the epicardial LAAC had returned to baseline at discharge, the acute decline of MAP was commonly observed among most patients. This fluctuation of the mean arterial pressure we observed in the study is significant, and the maximum reduction is 27 mmHg within 48 hours postoperative, which suggest surgeons should be more cautious on the postoperative fluid management and beware of all kinds of complications due to the lack of organ perfusion caused by an intense decrease in mean arterial pressure.
In our study, the acute decline of serum sodium was commonly observed among most patients which were also pronounced in past studies8,18,19. Remarkably, Holmes etl10 observed that among the AF patients after epicardial LAA closure by Lariat, the average serum sodium level decreased by 4.98 ± 3.74mmol/L within 48 hours postprocedure; and there were 32 patients (52.4%) decreased ≥ 4mmol/L, and 6 patients (9.8%) decreased ≥ 10 mmol/L. In our study, a more significant decrease was observed: the average serum sodium level decreased by 5.65 ± 2.61 mmol/L within 48 hours postprocedure, and there were 13 patients (61.9%) who decreased ≥ 4mmol/L, and 3 patients (14.29%) decreased ≥ 10 mmol/L. As a common postoperative complication, hyponatremia could induce severe central nervous system dysfunction including headache, nausea, lethargy, disorientation, or depressed reflexes20. Additionally, the cerebral edema induced by rapid and significant fluctuations in serum sodium levels can lead to serious complications including seizures, coma, brain damage, and brain-stem herniation due to cerebral edema20. The predictable decline of serum sodium, we observed, secondary to the stand-alone thoracoscopic left atrial appendage clipping, could elucidate the early, unexplained postoperative serum sodium decline and may obviate further expensive and unnecessary investigation. Through our study, we suggest that for patients with pre-existing hyponatremia or who are on diuretics, the postoperative fluid management should be appropriate or reduce the use of diuretics, otherwise, it may prolong the hospital stay of patients.
Currently, it's generally believed that changes in RAAS caused by changes in ANP and BNP following epicardial LAAC induce fluctuations in homeostasis. However, the specific changes of ANP and BNP postoperative and the actual mechanism of perioperative changes in homeostasis are still unclear. In our study, although BNP was only measured in some patients, it still showed a trend that was different from past studies21,22,23. In addition, a significant increase in glucose was observed among most of the patients, while Lakkureddy et9 announced that insulin significantly increased in patients who underwent epicardial LAAC procedure at 24 hours postoperation and 3 months follow-up when compared with the baseline level. But interestingly, there was no significant change in glucose at 24 hours postoperation and 3 months follow-up.
4.2 Study limitations
There are several important limitations of the study. This is a single-center study with all the inherent limitations of retrospective and observational studies. The study is also limited by sample size. First and foremost, cause of lack of long-term follow-up data, thus it is unclear whether the aforementioned changes are long-term or temporary. In addition, the direct and real-time measurement of the level of ANP and the expression of the RAAS system was not performed, and the sample size of the BNP level is small. Consequently, we can only make a hypothesis and infer the relation based on the data we collected. Besides, the changes mentioned above about electrolytes and hemodynamics are susceptible to diuretics use, fluid management, and patients' psychological factors. Therefore, more studies are needed to explain the accurate and further mechanism.