LV volume and EF have long been recognized as hallmark parameters of cardiovascular disease (CVD), in contrast to LA, which has only gradually walked into the popular view in the last decade. There is currently growing interest in the structure, function, and remodeling of the LA, particularly in identifying high-risk individuals through LA, diagnosing the underlying disease, and targeting LA as a potential therapeutic target. The mechanical function of the LA is primarily reflected in the three aspects: acting as a reservoir for pulmonary venous blood return when the LV is contracting, as a channel for blood flow when the LV is diastolic and as a booster pump assisting in the filling of the LA.[8, 9] Not only that, LA has other functions including endocrine functions: synthesis and secretion of atrial natriuretic peptide (ANP);regulatory function: modulation of autonomic activity, control of circulatory reflexes, ANP independent vasopressin (ADH) secretion.
In a clinical study evaluating the morphological and functional impact of physiological aging and gender on the LA, it was found that there was a trend toward progressive enlargement of the LA with age. Other studies have also confirmed that LAE is more common in the elderly.[3, 12] This is consistent with the conclusions of our study. Undeniably, with advancing age, the heart undergoes structural and functional alterations even in the absence of other contributing factors. This is usually accompanied by thickening and stiffening of the LV wall, dilation of the LV, and aggravation of the degree of cardiac fibrosis during normal ageing. This may be associated with reduced regenerative capacity of senescent cardiomyocytes, age-related mitochondrial dysfunction, deleterious paracrine effects of senescent cells, and inflammatory responses.
It is worth noting that in this study, female patients are more likely to develop LAE. In studies[3, 18, 19] based on the general population, it was found that female patients are closely related to the increased risk of LAE. Not only that, a study on the relationship between LAd and cardiovascular death in women with AF also reached conclusions about the relationship between female gender and LAE. However, the exact cause of women and LAE is still inconclusive, and some studies speculate that it may be related to a higher degree of inflammation in female patients. There is also other study considering that the higher prevalence of LAE in women may be related to higher systolic blood pressure, mean arterial pressure, and higher left ventricular mass index.
In a study exploring the prevalence of LAE and its risk factors in the general population of China, it was noted that female gender, advanced age, and BMI were all risk factors for LAE. In particular, in a report by Stritzke et al.,obesity appeared to be the most important risk factor for LAE in the general population. Evidence showed that epicardial fat was associated with BMI. A correlation between epicardial fat and LA size was also found in the study of Iacobellis et al. It is currently hypothesized that epicardial fat is related to the secretion of local pro-inflammatory activity, oxidative stress, and the infiltration and change of atrial cell characteristics and conduction velocity.In view of the increasing prevalence of obesity, early intervention, especially for young obese people, is essential to prevent the premature occurrence of heart remodeling at the atrial level.
The Killip classification was proposed as early as 1967, and the current Killip classification is a useful tool for early risk stratification of acute myocardial infarction(AMI) patients. According to the presence or absence of HF and the severity of hemodynamic changes, HF caused by AMI can be divided into four levels according to Killip classification. As an adaptation to the decreased ventricular compliance after AMI, it will inevitably lead to increased LA internal pressure, increased wall tension, and atrial muscle extension. If there is LAE, the acute LV diastolic and systolic dysfunction caused by AMI can make LA still compensable and eventually mechanical failure. This also further aggravated pump failure. This also explains the difference in the proportion of Killip classification between the two groups of subjects in this study. The global registry of acute coronary events (GRACE) risk scoring system is currently one of the most widely used and influential assessment systems for the assessment of the severity of acute coronary syndrome(ACS) conditions worldwide. As we have speculated, the LAdI, like the GRACE score, may predict long-term outcome in patients with STEMI.
The LA, like the LV, undergoes remodeling in response to specific stressors, and, for the LA, the most common cause of remodeling is volume and / or pressure load overload. The LA remodeling responds to altered tissue architecture and electrophysiology. Not only that, myocardial energy production and utilization are altered, and neurohormonal secretion is variably affected. However, unlike the ventricular myocardium, the atrial myocardium cells appear more vulnerable and sensitive when pathologically stimulated. This is also a possible mechanism by which LAE occurs with increased MACEs. In a retrospective cohort study involving 321 patients with HF, it was shown that lad was an independent risk factor for adverse cardiovascular events and that the severity of LAd and HF was positively correlated. Considerable literature suggests that LA is a powerful prognostic indicator in patients with HF, underscoring the importance of utilizing the LA to assess patient outcomes. [29, 30] Moreover, the occurrence and development of AF, considered a marker of atrial structural remodeling, underlies the persistence of AF. Which may be related to the heterogeneity of impulse conduction caused by atrial fibrosis. LAE is not only an independent predictor of AF recurrence,[32–34] relevant literature also points out that LAE would increase the incidence of thrombus formation from the left atrial appendage(LAA) in patients with AF.
Impaired LV systolic and diastolic function are common clinical manifestations of patients after AMI. LV contractility decreases, stroke volume decreases, and the echocardiogram shows a decrease in LVEF and fraction short (FS). The diastolic dysfunction of LV prevents LA emptying and overloads the preload. According to the Frank-Starling law, the above will lead to an increase in the initial length of LA. In the long run, LA will lose its flexibility and eventually lead to LAE. It can be manifested as an increase in LAd, LVEDd, and RVd on the echocardiogram.
Before doing the logistic regression analysis, we made the diagnosis of collinearity. The explanatory variable FS was discarded because of its severe collinearity (VIF > 10) between FS and EF to avoid model distortion.
Our study shows that EF and LAdI are independent risk factors for MACEs, which is consistent with most current studies.[37, 38] Although the American Society of echocardiography recommended to estimate the size of LA with LAV as early as 2005, the complexity of operation limits the application of LAV. Cardiac computed tomography (CCT) and cardiovascular magnetic resonance imaging (CMRI) have their own defects and can not be applied in clinic on a large scale. We excluded patients with hypertension. Although this made us exclude many research objects, we avoided the impact of difficult backtracking of course time, inaccurate medication records and incomplete mastery of blood pressure control in patients with hypertension, making the research results more real and effective. Moreover, we index LAd by BSA to further avoid the impact of body shape change on LA, which proves the good prediction ability of LAdI on MACEs. At present, there has been relevant literature that shows that the application of ACEI and ARB treatment can improve the function of LA and reverse the reconstruction of LA, which further illustrates that accurate and repeatable quantitative LA is of great significance in clinical practice.