Introduction
Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide although there have been substantial improvements in prognosis over the past decades [
1]. Efforts have been directed towards identification of novel non-invasive imaging parameters and indices for improved risk stratification enabling further optimized patient management. In this context, cardiovascular magnetic resonance (CMR) imaging has emerged as a key modality providing comprehensive possibilities for both functional and morphological myocardial assessment in patients following AMI [
2,
3]. Besides most commonly used left ventricular (LV) ejection fraction (LVEF), myocardial strain analyses have been proven to possess important and superior prognostic value for optimized risk assessment in AMI patients [
4,
5]. However, comprehensive strain analyses can be time-consuming and require additional post-processing software applications [
6,
7]. Recently, a new and simple approach of calculating a left atrioventricular coupling index (LACI) that is defined by the ratio between the left atrial (LA) end-diastolic volume (EDV) and the LV EDV has been introduced and demonstrated to be associated with the occurrence of cardiovascular events and to possess an incremental long-term prognostic value over and above traditional clinical risk factors in a large cohort of patients without any cardiovascular disease at study enrollment (Multi-Ethnic Study of Atherosclerosis [MESA study])[
8,
9].
Currently, little is known about the importance of left atrioventricular coupling and applicability and prognostic implications of LACI following AMI. Therefore, we aimed to assess the prognostic value of CMR-derived LACI in a large multicenter study of patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) treated by primary percutaneous coronary intervention (PCI).
Discussion
The aim of this work was to assess a novel CMR-derived LACI and confirm its prognostic value in a large cohort of patients with AMI.
Recently, LACI was defined and proven to possess prognostic value as well as to improve risk classifications in the multi-ethnic population of the MESA study. Likewise, the results of our study demonstrated prognostic implications of this novel index in a large AMI patient cohort. Especially in patients at high-risk according to reduced LVEF LACI evaluation enabled further risk stratification and therefore could optimize clinical patient management.
While commonly used volumetric analyses largely disregard the atrioventricular interplay, a combination of simultaneous LA and LV EDV measurements expressed by LACI can be suggested to allow evaluation of the holistic cardiac performance more accurately.
Currently, many guideline recommendations and clinical decisions (e.g. for ICD device therapy) are mainly based on a LVEF cut-off of 35% which alone may not be sufficient for this purpose [
16]. Consequently, there is a special interest to further improve and facilitate the identification of patients at higher risk [
17]. Similar to the findings of Pezel et al. [
8,
9], we demonstrated high associations of LACI with MACE in our study cohort. Importantly, LACI was shown to have a better prognostic value than individual LA or LV parameters measured separately in high-risk patients according to commonly used LVEF cut-off of 35%. In addition, a lower LACI almost eliminates the risk of MACE occurrence and provides further risk stratification in patients at relatively little risk according to LVEF > 35%. Conversely, the higher cut-off value for the overall cohort best enabled risk classification in patients at higher jeopardy (LVEF ≤ 35%).
Of note, the identified cut-off value of the current study was considerably higher than reported in previous literature [
9]. However, since preceding works mainly assessed populations without cardiovascular diseases, the identified value might be characteristic for post AMI patients and may further vary amongst other cardiovascular pathologies. The current findings therefore confirm and emphasize the important value of LACI assessment of recent studies and demonstrate their prognostic potential in an AMI cohort. Importantly, beyond previously identified associations of an increasing LACI with cardiovascular risk factors, markers of myocardial fibrosis and markers of heart failure [
18] the reported results are the first suggesting an additional prognostic benefit of LACI in patients with significantly reduced LVEF. Furthermore, with sex-specific pathophysiological features gaining increasing attention in different diseases [
19], very recently an association between LACI and sex hormone levels has been suggested influencing left atrioventricular coupling [
20]. In our study, LACI was associated with MACE and enabled additional identification of high-risk patients equally both in female and male patients suggesting uniform, accurate and gender independent risk assessment following AMI.
Since a greater LACI suggests an increased mismatch with a disproportionately enlarged LA in relation to LV, this index represents a simple approach to unmask several pathophysiological mechanisms of cardiac performance. LA size is considered as an appropriate barometer of LV filling pressure [
21]
. Furthermore, especially during end-diastole the LA is directly exposed to LV pressure making it an appropriate surrogate parameter for LV diastolic function [
22]. In this context, LACI has been shown to identify heart failure patients with preserved ejection fraction [
23] and besides indicating LV diastolic dysfunction to a certain extent [
24], both LA EDV and end-systolic volume (ESV) were demonstrated to possess important prognostic implications in patients following AMI with LA EDV being superior to ESV [
22,
25]. Whether these alterations of LA volumetric geometry occur merely in response to raised LV pressures or whether they also indicate intrinsic atrial processes leading to subsequent heart failure and atrial cardiomyopathy cannot be fully answered [
26]. However, it is interesting, that although there was no significant difference of LV EDV between patients suffering MACE and those without MACE during 1-year follow-up, LA volumes differed significantly and, therefore, divergent atrial responses and compensation capabilities can be assumed. Nevertheless, sole LA volume assessment did not allow further risk stratification amongst high-risk patients with a reduced LVEF ≤ 35% in our work. Recent studies identified various cardiovascular risk factors influencing LACI and its changes over time. Furthermore, LACI was demonstrated to be associated with myocardial fibrosis [
18] and to be superior for the prediction of new-onset atrial fibrillation compared to conventional risk factors and LA parameters [
27,
28]. Consequently, capturing myocardial volume distribution and relation between both LA and LV seems reasonable from a physiological point of view and also regarding improved prognostic stratification by combining prognostically powerful volumetric parameters.
It is noteworthy, that the alternatively calculated LACI ES showed no association with MACE in our study cohort, which, however, is in line with previous findings of the MESA study [
9] and underlines reports of other studies demonstrating LA EDV as superior parameter for reflecting LV filling pressure and for prognosticating clinical outcomes compared to LA ESV [
29,
30].
Similar to the calculation of LACI, first imaging studies already applied and implemented functional deformation assessments to evaluate the atrioventricular interplay for optimized diagnostic and prognostic purposes [
31,
32]. Especially the combination of CMR-derived LA and LV strain assessments revealed important insights to interrelated atrial dysfunction and ventricular systolic compensation mechanisms [
19]. It is important to mention, that both ventricular and atrial strain assessments have been shown to provide incremental prognostic value in patients following AMI outperforming myocardial volumetric analyses in several studies [
33,
34]. Besides the fact that comprehensive LA and LV strain assessments reflect cardiac performance over the whole cardiac cycle on both global and regional levels, it is also known that strain alterations precede myocardial geometric/ volumetric changes enabling earlier and more precise diagnosis of myocardial performance deterioration [
35]. In this context, previously LA total strain has even been shown to identify patients with diastolic heart failure more accurately than invasive pressure measurements [
36,
37] underlining the decisive and outclassing nature of strain evaluations compared to volumetric evaluations.
However, although LACI assessment per se cannot replace or achieve a similar level of prognostic power like LA or LV strain parameters can provide, it is important to consider its role as an index parameter measuring atrioventricular proportions and a growing volumetric mismatch could indicate an aspect of cardiac functional failure that might not be adequately captured by (isolated) LA and/or LV strain deterioration. Consequently, not only amongst LA and LV volumetric analyses but also in addition to strain measurements LACI calculation could give clinicians additional prognostic data to identify patients at higher risk for MACE.
Of note, deformation imaging relies on accurate data acquisition and compared to LACI calculation time-consuming post-processing [
38]. Furthermore, simple implementation of LACI in clinical routine is possible without any further post-processing work steps or software applications required making LACI an attractive software independent as well as cost- and time-saving imaging parameter with important diagnostic and prognostic implications. Due to the dimensionless nature of this index it might be even easily transferrable to commonly used echocardiographic volumetric assessments and could be directly comparable between different imaging modalities which has to be validated by future studies. However, a potential influence of methodologic variations on LA and LV volumes by using multislice approaches or biplane techniques should be considered. To obtain best comparable values, the application of a consistent and reproducible method in clinical trials or practice is highly desirable [
39,
40]. Against this background, future 3-dimensional and/or artificial intelligence based post-processing software algorithms might further standardize as well as improve volumetric analyses and could also automatically incorporate LACI calculations for the development of new risk prediction models [
41,
42].
Limitations
Our study has several limitations. CMR imaging was performed at several study sites using different CMR-vendors. However, all centers followed an identical study protocol and centralized image post-processing was performed in an experienced and blinded core laboratory. It is noteworthy, that an optimal timepoint for CMR imaging in patients following AMI is not known and, therefore, it cannot be excluded that further changes of atrioventricular coupling might occur at later stages after AMI. Due to contraindications and length of an CMR scanning procedure only stable and preselected patients were included in this study, which might lead to a selection bias with a lower event rate. Nevertheless, the study demonstrated significant associations of LACI with MACE which could be even more pronounced in the presence of more MACE.
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