Atrial fibrillation (AF) is a common cardiac arrhythmia with an overall prevalence of 1–2%. The incidence of AF increases by 1% annually with advancing age, reaching 15% in individuals aged $\ge$70 years [1, 2, 3]. AF primarily predisposes to left atrial thrombus formation, with $>$90% of thrombi originating in the left atrial appendage (LAA) [4, 5]. Dislodgement of these thrombi may lead to stroke or systemic embolism [6]. Current guidelines recommend anticoagulation therapy for patients with a high thromboembolic risk (CHA₂DS₂-VASc score $\ge$2) [7]. Commonly used anticoagulants include warfarin and direct oral anticoagulants (DOACs) [8]. However, AF patients with a high bleeding risk (HAS-BLED score $>$3) cannot tolerate long-term anticoagulation. In such cases, left atrial appendage clipping (LAAC) serves as an alternative mechanical strategy to reduce stroke risk [9], providing an option when anticoagulation is contraindicated (HAS-BLED indicates Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly). The procedure for LAA closure involves epicardial blunt clipping of the LAA, thereby isolating it from the left atrium and reducing thrombotic risk [10, 11]. The evidence to date indicates that AF patients may experience reduced blood pressure following LAAC [12], possibly because blunt compression from the LAA clip on the tissue leads to massive release of B-type natriuretic peptide (BNP) into the bloodstream. Nevertheless, the intrinsic mechanism for the decrease in blood pressure remains unclear. The aim of this study was therefore to investigate the impact of LAAC on blood pressure and to explore the potential underlying mechanisms.

The principal thromboembolic complications of AF stem from left atrial thrombus formation and subsequent systemic embolization, manifesting as cerebral infarction, peripheral arterial embolism, or visceral organ ischemia [13]. Current pharmacological prophylaxis relies on anticoagulant therapy, including warfarin and DOACs such as rivaroxaban and edoxaban [14, 15]. However, patients with an elevated risk of bleeding (HAS-BLED score $>$3) face significant hemorrhagic complications with anticoagulation, necessitating alternative mechanical approaches for thromboembolic prevention [16].

Hemodynamic studies have shown that approximately 90% of left atrial thrombi originate in the LAA due to blood stasis during AF. This pathophysiological mechanism supports LAA closure as a targeted intervention, where physical isolation of the appendage from the circulatory system achieves thromboprophylaxis [17]. Totally thoracoscopic LAAC represents a minimally invasive surgical technique that results in complete anatomical exclusion of the LAA, while avoiding the morbidity associated with open cardiac procedures [18].

Our findings align with previous research by Turagam et al. [12], who compared 247 patients undergoing LAAC with 124 patients receiving transcatheter left atrial appendage occlusion (LAAO). These authors found a significant postoperative decrease in blood pressure in the LAAC group compared to the LAAO group, which persisted for more than a year [12]. Similarly, Maybrook et al. [19] observed a postoperative decrease in blood pressure in a cohort of 76 patients undergoing percutaneous LAA ligation. Both authors postulated that BNP may be a key regulatory mediator in the reduction of blood pressure, although neither investigated the specific underlying mechanisms. The LAA possesses endocrine function, with its primary secretory product being BNP. In humans, the majority of BNP is derived from atrial and ventricular tissues. When atrial pressure increases, the appendage releases BNP into the bloodstream to regulate water and sodium metabolism. Elevated BNP levels inhibit aldosterone production, leading to reduced levels of systemic aldosterone [20]. Decreased aldosterone levels subsequently promote sodium retention, water reabsorption, and potassium excretion, leading to enhanced sodium excretion, increased urine output, and reduced blood volume, potentially contributing to lower blood pressure [21]. In addition, the vasodilatory effects of BNP can further reduce blood pressure [22]. The proposed mechanism for LAAC-induced blood pressure reduction is shown in Fig. 2.

Fig. 2.

Potential mechanistic pathway for LAAC-induced reduction of blood pressure. Down arrows: After LAAC, LAA releases BNP into the bloodstream. Elevated BNP promotes vasodilation and inhibits aldosterone production. The decrease in aldosterone levels subsequently promotes natriuresis and diuresis, leading to reduced blood volume and ultimately contributing to lower blood pressure.

The current study found that BNP levels increased significantly after LAA clip placement (150.9 [IQR 77.8, 260.7] vs. 316.2 [IQR 197.5, 466.8] pg/mL, p 0.001), possibly due to the blunt clipping effect of the device causing mechanical compression of the appendage tissue and inducing the release of stored BNP into the circulation. BNP may also be released through degranulation following ischemic necrosis of the LAA. Over time, the clipped LAA undergoes progressive atrophy and fibrosis, and the BNP-releasing effect gradually subsides [23]. In contrast, postoperative BNP elevation was not observed in patients undergoing LAA surgical amputation [24], since complete resection of the appendage using a surgical stapler prevents the release of BNP contained within the LAA tissue into the systemic circulation. Unlike transcatheter LAA occlusion, no elevation in BNP level was observed following implantation of the LAA occlusion device [25]. This is probably because the occluder blocks the appendage orifice without compressing the appendage tissue itself. Our study observed BNP elevation rather than LAA occlusion. This may be attributed to the significant clamping force applied by the LAA clip at the appendage base, causing a different impact on appendage exclusion than that achieved by occlusion devices.

BNP has been shown to decrease the expression of aldosterone synthase mRNA, thus reducing the production of aldosterone [26]. In the present study, the increase in BNP led to a reduction in aldosterone (5.5 [IQR 3.0, 8.7] vs. 2.5 [IQR 1.4, 3.4] ng/dL, p 0.001), thereby promoting natriuresis and diuresis and likely contributing to the observed decrease in serum sodium concentration (142.0 $\pm$ 2.5 vs. 137.6 $\pm$ 2.8 mmol/L, p 0.001). Since aldosterone also has antidiuretic effects, its decrease promoted diuresis, thereby reducing the effective blood volume and possibly explaining the observed decline in postoperative blood pressure (SBP: 127.3 $\pm$ 12.3 vs. 116.9 $\pm$ 12.4 mmHg; DBP: 80.7 $\pm$ 7.7 vs. 67.4 $\pm$ 9.3 mmHg; p 0.001).

The significant postoperative reductions in the use of ACEI/ARB (33.3% to 13.1%, p = 0.001) and CCB (29.2% to 16.1%, p = 0.027) likely reflect the proactive management of LAAC-induced hemodynamic alterations by clinicians. However, our binary logistic regression analysis indicated that adjustments in these antihypertensive medications were not independent predictors of reduced blood pressure. Given the association of the LAAC procedure with BNP-mediated volume depletion and vasodilation, continued administration of antihypertensive agents could risk potentiating severe hypotension. Conversely, the continued use of beta-blockers (64.6% to 63.6%, p = 0.882) prioritizes ventricular rate control without exacerbating a reduction in vascular tone. These coordinated adjustments in medication represent a meticulous clinical response to LAAC-induced hypotension effects. At the 6-month follow-up, the use of ACEI/ARB remained lower than the preoperative level, while the use of CCB approached preoperative rates. Collectively, this demonstrates a reduced intensity of antihypertensive medication compared with the preoperative period.

Furthermore, LAAC did not significantly alter cardiac structure [27], as evidenced by unchanged left ventricular end-diastolic diameter, left atrial anteroposterior diameter, and left ventricular ejection fraction compared to preoperative measurements. These findings suggest that LAAC does not impair cardiac systolic function or left atrial architecture, indicating the observed decrease in blood pressure is unlikely to be related to cardiac functional changes.

The hemodynamic alterations following LAAC were characterized by a distinct pattern of blood pressure changes. The most pronounced reduction in SBP was observed on postoperative day 3. Although a partial recovery was noted by the time of discharge, SBP levels remained lower than preoperative baseline values. In contrast, the peak decline in DBP occurred earlier, on postoperative day 1, with DBP returning to near-baseline levels upon discharge. Severe hypotension, defined as SBP 90 mmHg requiring vasoactive medication support (e.g., dopamine, norepinephrine), occurred in 5 (5.1%) patients. Fortunately, the majority of these episodes were transient and not associated with significant adverse clinical outcomes. The impact of LAAC on blood pressure demonstrated a degree of persistence. At the 6-month follow-up, both SBP and DBP remained lower than their respective preoperative levels. This sustained effect was further reflected in the reduced intensity of antihypertensive medication regimens. Specifically, the use of ACEI/ARB was lower compared to the preoperative period, and adjustments in antihypertensive therapy were consistent with the observed decline in blood pressure. It is important to note that while our results and those of others [12] suggest the effects are potentially sustained, the lack of long-term follow-up of our cohort precludes definitive conclusions about the durability of this hypotensive response. Whether this effect is transient or long-lasting is a critical question that should be addressed by future studies with longer follow-up.

The male predominance of our cohort aligns with the epidemiology of AF in older patients undergoing invasive interventions, but limits the generalizability of the results to women [28]. Moreover, our cohort had a high proportion of patients with a history of stroke, which is characteristic of the elevated thromboembolic and bleeding risk profile typical of candidates for LAAC.

We acknowledge that the hemodynamic changes observed in this study are likely to be multifactorial. The significant postoperative reduction in ACEI/ARB and CCB use is undoubtedly due to the decline in blood pressure. However, the rapid and substantial rise in BNP and fall in aldosterone occurred in the immediate postoperative period, temporally preceding or coinciding with adjustments in medication. This sequence suggests that hormonal changes may be the primary instigator, with drug de-escalation representing a prudent clinical response to the observed hemodynamic shifts. Furthermore, other perioperative factors, including anesthesia, fluid balance, and the physiological stress response to surgery, may have contributed to the initial changes. While our study design cannot definitively isolate the effect of LAAC from all potential confounders, the strong and consistent hormonal and electrolyte pattern strongly supports a specific role for LAA compression.

Our study has several limitations that should be considered. Its retrospective, single-center design and modest sample size may limit the generalizability of the findings and introduce potential for selection bias. The lack of long-term follow-up data prevents assessment of whether the hypotensive effect was sustained. Although we have proposed a BNP-aldosterone mediated mechanism, the absence of data on other RAAS components (e.g., renin, angiotensin II) means the hormonal cascade cannot be fully characterized. Finally, the potential influence of unmeasured confounders cannot be entirely ruled out, despite the compelling hormonal data. Taken together, current evidence suggests that LAAC may influence blood pressure through BNP-mediated RAAS suppression, however its precise mechanism requires validation through multicenter controlled studies.

Our findings indicate that LAAC is associated with a significant postoperative decline in blood pressure. The observed increase in BNP level and concurrent decrease in aldosterone suggest a potential mechanism involving BNP-mediated natriuresis and vasodilation. While BNP elevation may contribute to this hypotensive effect, other perioperative factors could also play a role. Consequently, proactive management is often required, including de-escalation of antihypertensive medication and vigilance for severe hypotensive events in the postoperative period. Nevertheless, the increase in BNP level remains a potential contributing factor to the postoperative decrease in blood pressure after LAAC.

AF, atrial fibrillation; LAA, left atrial appendage; LAAC, left atrial appendage clipping; BNP, B-type natriuretic peptide; LAAPD, left atrial anteroposterior diameter; LVEDD, left ventricular end-diastolic diameter; EF, ejection fraction; SBP, systolic blood pressure; DBP, diastolic blood pressure.

The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.

QY designed the research study and wrote the manuscript. FL contributed to the study design, data analysis, and manuscript writing and revision. HM was involved in data acquisition, data analysis, and manuscript writing and revision. DX contributed to data analysis and manuscript writing, and revision. All authors contributed to the critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Beijing Tiantan Hospital, Capital Medical University (No. KY2022-013-02). Written informed consent was obtained from all participating patients prior to data collection and analysis.

Not applicable.

This research received no external funding.

The authors declare no conflict of interest.