Acute aortic dissection (AAD) is a rare but highly lethal disease, with severe chest, back pain and a tearing sensation as the primary clinical manifestation [1]. AAD is usually divided into two categories; Stanford type A and B. Stanford type A involves the ascending aorta, and its treatment is primarily by surgical repair (replacement of the ascending aorta). For type A aortic coarctation, treatment can be delayed with a semi-elective surgical approach unless cardiac tamponade or malperfusion syndrome is present. Timely diagnosis and surgical treatment are important to improve the survival rate [1]. Stanford type B is based on the fact that the ascending aorta proximal to the innominate artery is not involved in the process, and its treatment is mainly medical therapy, focusing on controlling blood pressure and heart rate (HR) [2, 3]. Over time, thoracic endovascular aortic repair (TEVAR) has been recommended for complex type B AAD. However, TEVAR carries certain perioperative complications, and the timing of the treatment must be determined based on the patient’s specific condition. This typically involves monitoring the aortic diameter and assessing any new complications [4]. The comprehensive treatment for AAD has improved over the past two decades, but the mortality rates of diagnosis and treatment in hospital remain relatively high [5, 6], reaching approximately 27.4% [7].

Several factors, such as advanced age, arterial hypertension, and aortic aneurysm, are associated with adverse outcomes of AAD [8, 9]. Although the mechanisms underlying its progression remain unclear, timely and accurate diagnosis is crucial because of the exceedingly high AAD mortality rate, with an hourly death rate of 0.5%, particularly within the first 48 h after symptom onset, in which the mortality rate reaches 23.7% [1, 5]. Biomarkers, such as D-dimer [10], tenascin-C [11], and smooth muscle myosin heavy chain [12], have good diagnostic value for AAD. However, the treatment time of AAD is urgent, and the reference range of biomarkers was not completely effective in diagnosing AAD [13]. Therefore, exploring risk factors and identifying promising biomarkers to immediately identify and diagnose high-risk patients are essential.

Increased resting HR is a major risk factor for cardiovascular disease and is associated with mortality [14, 15]. Variation of HR increased the mortality of coronary heart disease, stroke, heart failure, and other cardiovascular diseases [16]. Several studies have indicated that HR is a powerful predictor of long-term mortality and may be used as a significant risk marker to predict the prognosis of patients with AAD [17, 18]. For instance, Zhou et al. [17] proved that HR was an independent risk factor for patients with AAD and positively correlated with long-term mortality. However, the retrospective observation in this study may cause bias, and the influence of preoperative medication on the study was overlooked. Krenz et al. [19] found that controlling HR through esmolol treatment could achieve the treatment of patients with AAD and evaluate the safety of this treatment method; however, this study lacked a multicenter analysis. Considering the limitations of these studies and the potential benefits of focusing on the relationship between HR and cardiovascular health for patient care [18], the association between HR and AAD should be comprehensively assessed. Here, we conducted a meta-analysis to assess HR and AAD mortality risk.

Recently, meta-analyses have focused on the surgical treatment scheme and prognosis of AAD [13, 35, 36]. Accurate early diagnosis and effective treatment of AAD remains of paramount importance to improve the survival rate of patients. Missed diagnosis of patients with AAD carries a significant mortality risk [20]. Our study showed that increased HR was significantly correlated with increased AAD mortality risk. However, the heterogeneity of the selected studies was significant regarding timing of HR monitoring, AAD type, and follow-up, which may affect the correlation strength and significance between HR and AAD. It is suggested that the follow-up study should form a unified standard for HR measurement time, grouping threshold, and study outcome evaluation to evaluate the relationship between them more accurately.

Currently, computed tomography (CT), magnetic resonance imaging (MRI), and transesophageal echocardiography (TEE) are usually performed to identify or exclude the AAD of patients, which are regarded as a grade I recommendation (evidence grade B) [37]. Besides the concerns caused by transferring potentially critical patients to radiology, the disadvantages of TEE, CT, and MRI mainly include the risk of venography and ionizing radiation. Consultation is not widely provided in many emergency departments [38]. Aside from imaging, biomarkers, such as D-dimer, troponins, and serum calcium, have been used to aid in AAD diagnosis. The potential problem of applying D-dimer in clinical practice lies in its poor specificity and lack of prospective verification of its application in decision-making [20, 39]. Other biomarkers, such as troponins [40] and serum calcium [41], exhibited the potential of risk stratification in the diagnosis of patients with AAD. However, it is expensive and inefficient for doctors and patients to use imaging techniques and biomarker detection to diagnose AAD, and not all hospitals are equipped with them. Therefore, a rapid, economical, and convenient diagnosis and prediction method is needed.

Resting HR is the core of cardiac output and is influenced by the changes in many diseases. Abnormal HR usually affects the amplitude and frequency of tensile stress on arterial wall and local hemodynamic environment, resulting in changes in endothelial cell structure and functions [42]. The imbalance of the autonomic nervous system, increased sympathetic nerve activity, and/or decreased parasympathetic nerve activity may be related to the pathogenesis of increased HR, increased blood pressure, diabetes, and obesity in some patients [43]. In the case of aortic coarctation, this autonomic imbalance may exacerbate tensile stresses on the arterial wall and changes in the local hemodynamic environment, thereby affecting endothelial cell structure and function. Current evidence shows that HR is an important indicator of cardiovascular diseases, including heart failure and AAD [44]. For example, Oliva et al. [45] expounded that HR can be used as a prognostic biomarker and is strongly associated with the prognosis of heart failure and acute heart failure. A retrospective study found that patients with sinus rhythm could significantly benefit from reduced HR. A large-scale meta-analysis (including 46 studies, including 1,246,203 patients) showed that increased HR was positively correlated with all-cause mortality and cardiovascular mortality, and the HR increased by 10 times/min. The overall all-cause mortality RR was 1.09 and 95% CI was 1.07–1.12, which showed that the mortality risk increased significantly. The RR of cardiovascular mortality was 1.08 and 95% CI was 1.06–1.10, indicating that the risk rate of cardiovascular mortality is obviously increased [46]. This suggests that HR control is critical for improving the prognosis of patients with cardiovascular diseases. Here, we demonstrated that HR is an influential independent risk factor for AAD. Chen et al. [28] found that HR ($>$90 bpm) was independently related to the high mortality of patients with severe AAD and had potential value in predicting the short- and long-term prognosis of patients with AAD. Hagiya et al. [29] suggested that patients with AAD after surgical treatment were more likely to have long-term aortic events in their HR at discharge $\ge$84 beats/min. These findings underscore the significance of HR control in preventing long-term complications in patients with aortic dissection. In the treatment of AAD, HR control may be a critical factor. Studies suggest that reducing HR can improve patient outcomes [17]. Patients benefit from reduced HR if it is controlled 80 bpm upon emergency department arrival. This study indicates a significant positive correlation between increased HR and AAD mortality risk. The association between HR and aortic dissection may operate through effects on autonomic balance, exacerbation of hemodynamic changes in the arterial wall, and impact on the prognosis of cardiovascular diseases. Therefore, HR control may be an important therapeutic strategy for improving the prognosis of patients with AAD.

Additionally, meta-subgroup analysis showed that China, RCS, Stanford type A, the study of measuring HR before treatment, the study after multi-factor correction, hospital mortality, and high-quality research had significant effects on heterogeneity (p 0.05). The difference of regional heterogeneity may be that the detection of AAD in China was more sensitive than that in other regions. In the subgroup analysis of these variables, the between-group differences were not statistically significant (p $>$ 0.05), indicating that none of these were a major cause of statistical precision. Contrastingly, HR, as a continuous or categorical variable, had a statistically significant between-group difference (p = 0.032), suggesting that it was a cause of statistical precision, thereby affecting the effect values. The sample size of our research was large. The heterogeneity test of statistical indicators improved the internal authenticity of the study.

Our study provided new insights into the risk management of AAD and helped to predict the diagnosis and progression in patients with AAD, thereby improving the survival rate of AAD. In 2010, the American Heart Association (AHA) guidelines [47] formally proposed that the initial treatment of Stanford type B AAD should reduce the stress of the aortic wall by controlling HR and blood pressure. However, further randomized controlled trials are needed to validate these results. This study laid a foundation for further research, particularly in determining that early detection and control of HR can help reduce AAD mortality. Our study was used to comprehensively evaluate the relationship between HR and AAD mortality risk, and subgroup analysis was used to evaluate the influence on the results. Although there was a significant publication bias, the clipping method results suggested that publication bias had little influence on the merger results. The one-by-one exclusion method demonstrated good stability of the meta-analysis.

This study has some limitations. The heterogeneity of included studies was significant, and subgroup analysis did not identify any significant influencing factors. Most of the included studies were retrospective, and there were many confounding factors, which may affect the authenticity of the results. Moreover, the included studies came from Asian countries, and more high-quality studies were needed to verify the extrapolation of the results. Therefore, more studies with a large sample, randomized and blind study design are required to explore the correlation between HR and AAD diagnosis to make the results more clinically significant.

This meta-analysis revealed a positive relationship between increased HR and increased mortality in patients with AAD. HR has convenient and excellent diagnostic performance in AAD diagnosis, and monitoring of HR may improve the prognosis of patients with AAD.

The datasets used in our study are available from the corresponding author on reasonable request.

Conception and design of the research: TYW and YSW. Acquisition of data: LS. Analysis and interpretation of the data: ZZN. Statistical analysis: JXW. Writing of the manuscript: TYW and LS. Critical revision of the manuscript for intellectual content: YSW, ZZN and JXW. 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.

Not applicable.

This research received no external funding.

The authors declare no conflict of interest.