Clinical Utility of Atrioventricular Coupling Index in Cardiovascular Disease

Abstract

Atrioventricular coupling refers to the synchronized interaction between the atrial and ventricular phases of contraction and relaxation within the cardiac cycle. Atrioventricular coupling can be assessed by the left atrioventricular coupling index and right atrioventricular coupling index. These indices provide a comprehensive assessment of the functional interdependence between the atrial and ventricular chambers, and offer insights into cardiac performance beyond traditional markers. Atrioventricular coupling indices are critical for aiding in risk stratification and clinical decision‐making, ultimately improving patient outcomes. This review focuses on the clinical utility of atrioventricular coupling in various cardiac pathologies.

Nonstandard Abbreviations and Acronyms

AL‐CA

light‐chain cardiac amyloidosis

DCM

dilated cardiomyopathy

HCM

hypertrophic cardiomyopathy

HFpEF

heart failure with preserved ejection fraction

LACI

left atrioventricular coupling index

LAEDV

left atrial end‐diastolic volume

LAV_max

maximum left atrial volume

RACI

right atrioventricular coupling index

STE

speckle‐tracking echocardiography

Atrioventricular coupling is characterized as the functional synchronization between the atrial and ventricular phases of systole and diastole in the cardiac cycle and plays a pivotal role in various cardiac pathologies. Atrial and ventricular performance are intricately linked. Numerous studies have demonstrated the complex coupling relationship between the structural and functional aspects of the atrium and ventricle. ¹ , ² , ³ , ⁴ , ⁵ , ⁶ In fact, atrioventricular coupling appears to be complicated because the processes of chamber filling, emptying, and active contraction are not synchronized in time. ⁷ The atria fill with blood as the ventricles contract and eject blood into the circulatory system. They discharge their content as the ventricles enter a state of relaxation but contract at the end of the ventricular diastolic phase in a sinus rhythm. To resolve temporal discordance in atrioventricular activities, atrioventricular coupling parameters in this review were temporally anchored to the end‐diastolic phase, using mitral valve closure as the fiducial marker. The atrioventricular coupling can be divided into two distinct categories: left atrioventricular coupling between the left atrium and the left ventricle, and the right atrioventricular coupling between the right atrium and the right ventricle. A unified parameter encompassing both atrial and ventricular function may more effectively capture the physiological interdependence and more accurately indicate any dysfunction. ⁸ , ⁹ The left atrioventricular coupling index (LACI) has been developed to measure the degree of left atrioventricular coupling. ⁷ , ¹⁰ Correspondingly, the right atrioventricular coupling index (RACI) is employed to assess the right‐sided atrioventricular coupling. This article reviews the basic principles, underlying mechanisms, and clinical relevance associated with the 2 types of atrioventricular coupling. It also summarizes the current clinical applications and research advances of LACI and RACI in the context of cardiovascular pathologies.

INTERACTION MECHANISMS OF ATRIOVENTRICULAR COUPLING

The left atrium is characterized by phasic activity making it inaccurate to depict the atrium as a passive component within the complex dynamics of the cardiac cycle. Indeed, the left atrium is intimately linked to the left ventricle function throughout the entire cycle. ¹¹ The role of the left atrium varies at different phases of the cardiac cycle, leading to the categorization of its function into 3 distinct modes: reservoir, conduit, and booster. ¹² The ventricular systole mechanically affects atrial performance by ejecting blood from the ventricles. Following the QRS complex on the ECG, the base of the heart descends as a result of the longitudinal fiber contraction associated with left ventricular (LV) systole, which facilitates left atrial (LA) filling from the pulmonary veins (reservoir function). LA reservoir capacity is primarily determined by LV contraction, which influences the upward movement of the mitral annulus. Additionally, although to a lesser extent, relaxation, and compliance of the LA myocardium also play a role. ⁴ , ¹¹ During early and middiastole, the atrium plays a passive role in LV filling, acting as a conduit. In the absence of mitral stenosis, the conduit role of the left atrium is mainly determined by the LV relaxation but is also influenced by the preload. ⁵ As diastole progresses into its late phase, the atrium becomes an active participant in ventricular filling, performing a pumping function that is critical for LV diastolic filling. A robust atrial systole can increase ventricular preload and improve ventricular contractility. ¹¹ LA pumping is determined by LA intrinsic contractile properties, LV compliance, filling pressures (LA afterload), and the capacity of the pulmonary vasculature. ¹³ In early diastolic dysfunction, reduced ventricular compliance and elevated filling pressures reduce early transmitral passive diastolic flow, causing the atrial pump function to compensate for LV filling. As LV distensibility further declines, atrial pressure increases to maintain cardiac output until the LA compliance also decreases. This means that the dysfunction of these 2 chambers is closely linked and can mutually affect each other's performance, leading to a worsening atrioventricular function and increased filling pressures. ¹⁴ The functional interaction between these 2 cardiac chambers represents their mechanical coupling.

LEFT ATRIOVENTRICULAR COUPLING INDEX

Definition

LACI is a novel echocardiographic parameter that holds promise for predicting patient outcomes across various clinical settings. ¹⁵ It is calculated by dividing the minimal LA end‐diastolic volume (LAEDV) by the LV end‐diastolic volume, with both measurements serving as independent indicators of heart failure (HF) severity. ³ , ¹⁶ The measurement of left atrium‐left ventricle coupling could provide a more precise indication of left atrioventricular dysfunction, and the LACI may serve as a superior predictor of outcome than the individual LA and LV assessment. ¹⁷

In fact, the emphasis on atrial function represents a major step forward in the analysis of cardiac performance, providing important prognostic information that is frequently ignored in conventional cardiac evaluation. ¹⁸ , ¹⁹ , ²⁰ Maximum LA volume (LAV_max) has been identified as an indicator of persistently elevated LV filling pressure. This metric has been established as a robust prognostic marker in patients undergoing echocardiography as well as in the general population. ²¹ , ²² Emerging evidence suggested that the LAEDV, a component of the LACI calculation, may better reflect invasively measured LA pressure compared with LAV_max. This means that LAEDV may be a more accurate indicator of instantaneous LV filling pressures. ³ , ²³ Unlike LAV_max, LAEDV is more directly subject to the LV end‐diastolic pressure and has been shown to be a better predictor of LA mechanical function than LAV_max. ²⁴ , ²⁵ In addition, a piece of research has shown that LAEDV has a stronger relationship with the E/e' ratio than LAV_max in a nonhospital setting, suggesting that LAEDV may be a more consistent marker of elevated LV filling pressures than LAV_max. ²⁶

As LAEDV increases relative to LVEDV, LACI is predicted to increase, indicating a greater degree of LV diastolic dysfunction. When LACI is presented as a percentage, higher values indicate a greater imbalance between LA and LV volumes at the end of diastole, indicating a more pronounced impairment of left atrioventricular coupling ⁷ (Figure 1). Essentially, LACI is emerging as a favorable echocardiographic gauge for predicting patient outcomes in cardiovascular disease, particularly in the context of HF.¹⁵ LACI allows for a more nuanced and comprehensive evaluation of cardiac function, offering significant prognostic insight that surpass the assessment of individual heart chambers performance. ¹⁰ , ²⁷ , ²⁸

Figure 1. Examples of patients with preserved and impaired atrioventricular coupling.

A and B, An example of patient with preserved atrioventricular coupling assessed by 2‐dimensional echocardiography and 3‐dimensional echocardiography. C and D, An example of a patient with impaired atrioventricular coupling assessed by 2‐dimensional echocardiography and 3‐dimensional echocardiography. LA indicates left atrial; LACI, left atrioventricular coupling index; LAEDV, left atrial end‐diastolic volume; LV, left ventricular; and LVEDV, left ventricular end‐diastolic volume.

Measurement

LACI can be measured by several imaging modalities (Figure 2), such as echocardiography, cardiac computed tomography (CT) or cardiovascular magnetic resonance (CMR). ²⁹ Echocardiography is considered as the most widely used noninvasive imaging modality for cardiac structure and function assessment owing to its unique capacity to provide real‐time visualization of the beating heart, coupled with its widespread availability and portability. The advanced techniques include real‐time 3‐dimensional echocardiography for volumetric quantification and speckle‐tracking imaging for myocardial deformation analysis. ³⁰ In recent years, advancements in CT technology have significantly progressed, providing a robust foundation for the use of cardiac CT in the diagnosis and prognosis of heart diseases. Current imaging guidelines mandate cardiac CT acquisition protocols to prioritize the 75% temporal window of the cardiac cycle for coronary artery analysis. This phase‐specific optimization aligns inherently with LACI quantification, which derives from end‐diastolic chamber volumetrics, thereby enabling direct LACI assessment from standard coronary CT data sets without protocol modification. ²⁹ Besides, CMR is considered as the gold‐standard imaging modality in cardiovascular medicine because its unrivaled spatial resolution for quantifying chamber volumetrics, systolic performance, and myocardial tissue architecture. ³¹ However, high cost, longer scan time, limited availability, and patients with claustrophobia or implanted cardiac devices limit the widespread use of CMR. ²⁹ Therefore, rigorous comparative studies are warranted to evaluate the diagnostic concordance among echocardiography, CT, and CMR imaging in the assessment of LACI. However, no study so far assesses the intermodality variability in both RACI and LACI. ³¹

Figure 2. Measurement of LACI using CMR, echocardiography, and CT.

A and B, LVEDV (yellow dashed line) and LAEDV (red dashed line) are measured in the apical 2‐chamber and 4‐chamber views using CMR. C and D, LVEDV (blue dashed line) and LAEDV (green dashed line) are measured in the apical 2‐chamber and 4‐chamber views using echocardiography. E and F, LVEDV (purple dashed line) and LAEDV (orange dashed line) are measured in the apical 2‐chamber and 4‐chamber views using CT. 2‐ch indicates apical 2‐chamber; 4‐ch, apical 4‐chamber; CMR, cardiovascular magnetic resonance; CT, cardiac computed tomography; LACI, left atrioventricular coupling index; LAEDV, left atrial end‐diastolic volume; and LVEDV, left ventricular end‐diastolic volume.

Echocardiography

Transthoracic echocardiography is a commonly used imaging modality to measure LACI. End‐diastolic and end‐systolic LA and LV volumes, and the LV ejection fraction (LVEF) were measured using the modified Simpson's biplane approach from the apical imaging planes ³² and then indexed to the body surface area. The LACI is determined as the ratio of LAEDV to LVEDV. The measurements of the LA and LV volumes were synchronized to the end‐diastolic phase, which is marked by the mitral valve closure. Given that the long axes of the left ventricle and left atrium are typically not aligned in the same plane, efforts were made to enhance the accuracy of the volume measurements by performing specific acquisitions for the left atrium or focused views. In these acquisitions, care was taken to maximize the length of the long axis and the base area of the left atrium in both the apical 4‐chamber and 2‐chamber views to avoid underestimation due to foreshortening. ¹⁷ Three‐dimensional echocardiography provides enhanced precision in the quantification of LV systolic and diastolic volumes compared with conventional 2‐dimensional methods, owing to its ability to perform volumetric analysis without geometric assumptions. ³³ Using an ultrasound system equipped with a matrix array probe, full‐volume scanning mode is employed to acquire full‐volume 3‐dimensional echocardiographic data sets from an apical approach, in accordance with standard recommendations. Four to 6 consecutive cardiac cycles are gated and captured in the apical 4‐chamber view, ensuring complete inclusion of the LA and LV cavities. The acquired data sets are then subjected to volumetric quantification using dedicated 3‐dimensional analysis software. This modality is recommended as the preferred echocardiographic approach for ventricular volumetry when high‐quality image acquisition is achievable and validated against CMR imaging, provided that adequate technical expertise and imaging instrumentation are accessible. ³³ It is noteworthy that all patients undergo echocardiographic examination in sinus rhythm. However, in the setting of persistent atrial fibrillation (AF), it is challenging to obtain sufficiently long periods of sinus rhythm. Therefore, for patients with AF, data are acquired from at least 5 consecutive cardiac cycles, and the mean value is calculated. ³⁴ , ³⁵

Computed Tomography

Cardiac CT can be used to evaluate the LACI. ²⁹ Regarding the cardiac CT examination protocol, CT scans are performed on either 64‐row or 80‐row multidetector CT scanners. The imaging protocols are in accordance with the Society of Cardiovascular Computed Tomography recommendations for the suitability and performance of cardiac CT at the time of scaning. ³⁶ For the acquisition process, both retrospective and prospective modes, complete with padding and dose adaptation, are applied to assess the LVEF. LA and LV volumes are measured from the 2‐ and 4‐chamber views using the biplane Simpson's method, as previously described. ⁷ These volumes are acquired in the same end‐diastolic phase, identified by the maximum LV volume.

Cardiac Magnetic Resonance

CMR is the most widely applied imaging modality for measuring LACI. In prior investigations, LACI is determined by the ratio of LAEDV to LVEDV end‐diastolic volume measured by CMR. ⁷ Initially, CMR is conducted using 1.5 T MR scanners. Long‐axis Cine images are acquired from both 2‐chamber and 4‐chamber perspectives using ECG‐triggered fast gradient‐echo pulse sequences. A series of short‐axis cine images are obtained to cover both ventricles, and LVEDV is determined using dedicated cardiac imaging software. The temporal resolution for all cine images was approximately ~50 ms. Comprehensive details regarding the CMR protocol, image analysis, data quality assurance, and calculation of LVEF, LV mass, and volumes, LA volumes, and the reproducibility of these metrics, have been documented in prior publications. ³⁷ Advanced tissue tracking software is used to assess LA volume and strain from the 2‐chamber and 4‐chamber cine CMR images. LV volume is calculated from the set of short‐axis cine images, and the LA volume is evaluated from the 2‐ and 4‐chamber perspectives according to previously described techniques. ⁷

CLINICAL UTILITY

Healthy Individuals

In a CMR‐based analysis of 31 healthy Asian adults, Tseng et al. found that LV peak‐filling rate and time to LA peak‐emptying rate were almost similar, demonstrating a mechanical coupling between the left ventricle and left atrium during diastole. This study provided normative data on LV and LA function and their relationship in healthy Asian adults. ³⁸ Meloni et al. assessed the LACI in a cohort of 32 healthy individuals and revealed an average LACI of 16.05%±5.28%. This analysis demonstrated a significant correlation between LACI and age, whereas no gender differences in LACI were identified among the healthy participants. ⁸ Despite its widespread application in the assessment and follow‐up of diastolic dysfunction in adults, LACI has limited use in children. Linden et al. studied left atrium‐left ventricle coupling parameters in a large group of healthy children using noninvasive real‐time 3‐dimensional echocardiography. The research provided reference values for left atrium‐left ventricle coupling in healthy White infants and children. ³⁹

Heart Failure

LACI holds promise in predicting the trajectory of cardiovascular conditions. Currently, a variety of research endeavors have used LACI for prognostic assessment in patients with HF (Table 1). According to international standards, HF is categorized into 3 subtypes: HF with preserved EF (HFpEF, LVEF ≥50%), HF with midrange EF (LVEF between 40% and 50%), and HF with reduced EF (LVEF <40%). ¹² , ⁴⁰ , ⁴¹ HF, which represents the culmination of many cardiovascular diseases, has become a significant public health challenge on a global scale. Thus, accurate assessment of cardiac function is crucial for definitive diagnosis, clinical decision making, risk stratification, and serial follow‐up in patients with HF. ¹² As an emerging echocardiographic index, LACI holds promise for predicting the clinical course of patients with cardiovascular morbidity, with a particular emphasis on HF.¹⁵ Although LA and LV metrics independently predict HF, their close physiological relationship suggests that assessment of left atrium‐left ventricle coupling may provide a more accurate indication of left atrioventricular dysfunction and a more reliable HF prognosis. ¹⁰ Lange and colleagues performed CMR imaging in a group of 22 patients with HFpEF, 17 patients with HF with midrange EF, 15 patients with HF with reduced EF, and 19 healthy individuals, focusing on the assessment of LA and LV volumes together with LACI. ²⁸ The study revealed that patients with HF with midrange EF exhibited an enlarged left ventricle but preserved LA function, accompanied by increased LA booster pump function. Given the left atrium is directly exposed to LV pressure, especially at end‐diastole, LA volume measurement serves as an indirect indicator of LV diastolic function and reflect LV filling pressures. Patients with HFpEF predominantly experienced atrial dysfunction and an elevated LACI in comparison to healthy individuals, suggesting an imbalanced expansion of the left atrium relative to the left ventricle in this patient group. A disruption in atrioventricular coupling, primarily arising from the left atrium and signified by an elevated LACI, stands out as a specific characteristic of diastolic dysfunction. ²⁸ , ⁴² In a recent investigation by Kasa et al., it was demonstrated that among patients with HF and LVEF <50%, LACI serves as an independent predictor of adverse cardiovascular outcomes. Specifically, those with the most impaired left atrioventricular coupling, as indicated by elevated LACI values, exhibit the most unfavorable clinical outcomes. ⁴³ In HF with reduced EF, both LA and LV dysfunction have been observed. Impaired LA reservoir and conduit function are considered the most sensitive indicators of diastolic dysfunction, and have been shown to precede LA geometric changes. ²⁸ , ⁴⁴ The researchers led by Backhaus et al. suggested that LACI obtained by CMR may reveal the underlying pathophysiological changes in HFpEF and may be applicable to CMR imaging during both resting and exercise conditions. The researchers found that HFpEF is characterized by poor atrioventricular coupling both at rest and during exercise, with LACI correlating with pulmonary capillary wedge pressure under these conditions. LACI was the only volumetry‐derived parameter that could discriminate patients with noncardiac dyspnea from those with HFpEF, using thresholds established by exercise stress. Additionally, median LACI values at rest and during exercise were associated with overall cardiovascular health. LACI measurement is a simple and efficient method to quantify left atrium‐left ventricle coupling and rapidly identify cases of HFpEF. The high diagnostic accuracy of LACI in rest and exercise‐stress CMR imaging protocols is comparable to that of LA EF under stress. This emphasizes the potential of LACI as a practical and cost‐effective diagnostic tool for diastolic dysfunction that could help guide patients to specialized testing and therapies. ⁴⁵ In a retrospective cohort study conducted by Fortuni and colleagues, comprehensive echocardiographic evaluation of 1158 clinically stable patients with HF receiving guideline‐directed medical therapy revealed that LACI correlates with the severity of diastolic dysfunction and serves as an independent prognosticator of outcome in stable patients with HF. ¹⁷ Besides, Pezel et al. demonstrated novel prognostic utility of stress CMR‐derived LACI in acute HF. Elevated LACI values, reflecting impaired left atrioventricular coupling, independently correlated with increased risk of acute HF hospitalization or cardiovascular mortality in patients with both preserved and impaired myocardial perfusion reserves. Stress CMR‐quantified LACI emerged as a robust predictor of acute HF events, surpassing conventional ventricular functional metrics. ⁴⁶ Although these studies establish the utility of LACI across HF states, its application in acute HF remains nascent compared with stable settings. The limited application of LACI in acute HF can be attributed to the distinct pathophysiological mechanisms underlying acute and stable HF. In addition, a study by Pezel et al. demonstrated that LACI and its changes (ΔLACI) are each independently associated with incident HF in multiethnic cohorts. These factors provide additional prognostic insight into HF risk beyond traditional predictive indicators. ¹⁰ Taken together, these findings position LACI as a pivotal parameter in the comprehensive assessment of HF and warrant its integration into prognostic algorithms and therapeutic decision‐making processes.

Table 1.

Clinical Application of LACI in Heart Failure

Author	Sample size	Population	Age, y	Men (%)	Method	Main findings
Pezel et al. 10	2250	2250 participants free of HF and cardiovascular disease	59.3±9.3	47.6	CMR	LACI and its alteration (ΔLACI) are each independently associated with the onset of HF.
Fortuni et al. 17	1158	1158 patients with stable HF	66±12	75	Echocardiogram	LACI is an independent predictor of outcomes in patients with HF.
Lange et al. 28	73	22 patients with HF with preserved EF 17 patients with HF with midrange EF 15 patients with HF with reduced EF 19 healthy controls	Not reported	Not reported	CMR	LACI was significantly higher in patients with HF and major adverse cardiac events
Kasa et al. 43	478	478 patients with HF and LVEF <50%	62±12	78	CMR	LACI is independently associated with adverse events in patients with HF and LVEF <50%
Backhaus et al. 45	68	34 patients with HF with preserved EF, 34 patients with noncardiac dyspnea	69 (67–77) 66 (52–73)	26.5 44.1	Echocardiogram	HF with preserved EF is characterized by poor atrioventricular coupling both at rest and during physical exertion
Pezel et al. 46	2134	1067 with normal and 1067 with abnormal CMR	65±12	77	CMR	LACI is independently associated with hospitalization for HF and cardiovascular death in patients

CMR indicates cardiovascular magnetic resonance; EF, ejection fraction; HF, heart failure; LACI, left atrioventricular coupling index; and LVEF, left ventricular ejection fraction.

Atrial Fibrillation

AF, recognized as the predominant supraventricular tachyarrhythmia, which is a key risk factor for ischemic stroke, leading to increased morbidity and mortality, and causing a significant economic burden. ⁴⁷ , ⁴⁸ In individuals with no history of cardiovascular disease, LACI was found to predict the likelihood of developing AF in a large cohort study. ⁷ The development of AF is likely to be influenced by more than just structural or functional impairment of the left atrium or left ventricle; it may also be related to the decoupling of these cardiac structures, suggesting early signs of LV diastolic dysfunction or LA myopathy. ⁴⁹ , ⁵⁰ , ⁵¹ LACI, which gauges early LV diastolic dysfunction and LA myopathy, more accurately reflects LV diastolic pressure–volume relationships from a pathophysiological standpoint. ⁵² Thus, LACI provides a more complete picture of changes in left heart structure and function than individual LA or LV parameters, improving the prediction of AF occurrence. ⁵³ In a population‐based analysis from the Multi‐Ethnic Study of Atherosclerosis, Pezel et al. used cardiac magnetic resonance imaging to determine the prognostic significance of LACI and ΔLACI in predicting the onset of AF. They found that, controlling for traditional risk factors, higher LACI and ΔLACI values were independently correlated with AF risk. This demonstrated that both baseline LACI and its annual variation were robust predictors of AF in a multiethnic population. These indicators provided incremental prognostic value over traditional risk factors and outperformed the CHARGE‐AF (Cohorts for Heart and Aging Research in Genomic Epidemiology Model for Atrial Fibrillation) score as well as isolated measures of LA or LV parameters in terms of predictive accuracy. ⁵³ In a study evaluating the postoperative recurrence of paroxysmal AF, Li et al. examined 164 patients who had undergone catheter ablation. They found that patients with paroxysmal AF recurrence had reduced LA EF and elevated LACI, indicating that elevated levels of LACI are significantly correlated with the risk of postoperative recurrence in patients with paroxysmal AF, providing additional predictive power for AF recurrence. ³⁵ Consequently, accurate evaluation of LACI may prove beneficial in facilitating the prediction of AF occurrence and clinical outcomes, as well as aiding in the stratification of pathological conditions.

Myocardial Infarction

Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide, despite significant advances in diagnosis and treatment over the past few decades. ⁵⁴ Investigations are being directed toward the discovery of new noninvasive imaging parameters to improve risk stratification and optimize patient management. ⁵⁵ CMR imaging has become a central technique for detailed assessment of myocardial function and structure in patients after MI. ⁵⁶ Apart from the commonly used LVEF, myocardial strain analysis has been shown to have substantial and superior prognostic value for refining risk stratification in patients with MI. ⁵⁷ However, these strain analyses can be labor intensive and require additional postprocessing software. ⁵⁶ , ⁵⁸ Recently, LACI has been demonstrated to correlate with the occurrence of cardiovascular event and to provide additional long‐term prognostic value beyond traditional clinical risk factors in a large group of patients without cardiovascular disease at baseline, as seen in the Multi‐Ethnic Study of Atherosclerosis study. ⁷ , ¹⁰ Previous investigations have identified the metabolic syndrome as an indicator of adverse cardiovascular events in patients with MI, suggesting that improved risk factor management may be beneficial. ⁵⁹ , ⁶⁰ Consequently, it is important to explore the pathways by which metabolic syndrome may worsen clinical outcomes in patients with MI. Liu et al. found that patients with MI with or without metabolic syndrome exhibited reduced LA function in all phases (reservoir, conduit, and bump) and diminished LV deformation compared with a control group. They also observed increased LACI in these patients, indicating potential links between metabolic syndrome and LA and LV dysfunction in patients with MI. ⁶¹ A study by Lange et al. investigated the diagnostic and prognostic value of LACI using CMR imaging in 1046 patients undergoing percutaneous coronary intervention post MI. The research revealed that LACI was considerably higher in patients with major adverse cardiac events compared with those without. The Youden Index identified 34.7% as the ideal LACI threshold to identify patients at higher risk. An increased LACI was linked to major adverse cardiac events in both univariate and multivariate regression analyses, adjusting for baseline factors and LVEF. Additionally, LACI helped to further stratify risk in patients with reduced LV systolic function who were already identified as being at a higher risk. The findings indicated that CMR‐derived LACI is a more accurate predictor of patient outcomes than LVEF, particularly for those at higher risk after MI. ⁵⁵

Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a prevalent form of genetic heart muscle disease characterized by diverse clinical risks. ⁶² , ⁶³ Predicting which patients are at higher risk for HF progression is a major challenge. Improved risk assessment for cardiovascular complications in patients with HCM might improve the prediction of serious health issues. ⁶³ , ⁶⁴ In a study by Tran et al., 32 patients with HCM were evaluated for cardiac function using LACI. It was noted that individuals with coronary microvascular dysfunction had a significantly higher LACI, indicating worse cardiac function. A comprehensive logistic regression analysis confirmed that coronary microvascular dysfunction was an independent factor influencing LACI. This finding suggests that a multimodal imaging approach can effectively identify coronary microvascular dysfunction in patients with HCM who are likely to have a greater degree of cardiac dysfunction as indicated by an increased LACI. ⁶⁴ In the study by Meucci et al., a cohort of 373 patients with HCM and no prior history of AF underwent transthoracic echocardiographic assessment. The investigators revealed that among patients with HCM, LACI exhibited superior predictive power for the occurrence of new‐onset AF compared with conventional LA parameters. ⁶⁵

Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a common and diverse disease that continues to cause significant health problems and deaths worldwide. ⁶⁶ Initially considered primarily as an LV problem, the majority of studies have focused on assessing LV performance, with LVEF recognized for its predictive value in DCM outcomes. ⁴⁰ , ⁶⁷ However, recent evidence indicates a strong interplay between ventricular and atrial function. The LA dimensions and mechanical properties are now recognized both as a reflection of LV diastolic impairment and as independent prognostic markers in the context of HF. ³ , ⁶⁸ Vîjîiac et al. conducted a study using echocardiography to evaluate the predictive value of the LACI, RACI, and a newly defined combined atrioventricular coupling index in patients with DCM. Combined atrioventricular coupling index was calculated as the sum of LACI and RACI. The study found that all 3 indices were significantly reduced in those who experienced major cardiac events, with combined atrioventricular coupling index exhibiting the highest predictive accuracy. In a multivariable Cox regression analysis, each index emerged as an independent predictor of outcome. The findings indicate that both LACI and RACI, as well as their combined index combined atrioventricular coupling index, are independent predictors of adverse events in DCM and provide additional prognostic information beyond conventional risk factors. ⁶⁹

Cardiac Amyloidosis

Light‐chain cardiac amyloidosis (AL‐CA) characteristically manifests myocardial infiltration through deposition of amyloid fibrils in all 4 cardiac chambers, with the LA and LV exhibiting prominent involvement as pathognomonic targets of proteotoxicity. Therefore, both the LA and LV exhibit significant structural and functional alterations in AL‐CA. ⁷⁰ , ⁷¹ Previous research has demonstrated that structural and functional parameters of the left atrium and left ventricle hold independent prognostic significance in AL‐CA. ⁷² Given the intrinsic anatomical and physiological interconnections between these chambers, the assessment of left atrium‐left ventriclecoupling may offer a more comprehensive reflection of left atrioventricular dysfunction, potentially providing additional prognostic value in AL‐CA. Meng et al. provide mechanistic validation that 3‐dimensional echocardiography‐derived LACI emerges as an independent predictor of all‐cause mortality in AL‐CA. In this cohort study of 67 patients with biopsy‐confirmed AL‐CA undergoing comprehensive echocardiographic evaluation by Meng et al., LACI exceeding 0.57 provides robust risk stratification for all‐cause mortality. This finding established LACI quantification as an essential component of contemporary risk assessment in AL‐CA, potentially guiding therapeutic intensification strategies and clinical trial stratification, ⁷⁰ which differs in HCM. Recent translational investigations have validated the prognostic utility of LACI in HCM, demonstrating its independent association with incident AF. ⁴³ , ⁶⁵ These findings collectively position LACI as a multimodal biomarker demonstrating pleiotropic utility across distinct cardiomyopathic substrates, thereby advancing precision‐based risk stratification paradigms for divergent myocardial disease causes.

Hypertension

Hypertension frequently leads to cardiac damage, with a particular emphasis on changes in the left ventricle and, more recently, the left atrium. Historically, research has focused on the impacts of systemic arterial hypertension on the left ventricle, but there is a growing interest in the structural and functional changes observed in the left atrium of patients with hypertension. ⁷³ An increasing number of researchers are delving into the left atrial‐ventricular coupling in the context of hypertension (Table 2). In a comparative analysis, Soullier et al. examined 30 individuals with hypertension and LV hypertrophy and a control group of 29 normotensive individuals. They used speckle‐tracking echocardiography (STE) to assess cardiac performance and found that hypertension with LV hypertrophy had a notable decrease in LA reservoir, conduit, and booster pump function, as well as increased LA stiffness. These changes were associated with LV hypertrophy and dysfunction, highlighting the importance of left atrial‐left ventricular coupling and suggesting a link to fibrotic changes in the left atrium. ⁷³ Evidence suggests that hypertension is an independent factor that can increase LACI in patients with diabetes. ⁷⁴ Li et al found that patients with hypertension and type 2 diabetes (T2D) had more severe LA phasic dysfunction, possibly related to more severe LV systolic or diastolic dysfunction. This indicates a deleterious AV coupling and highlights the importance of interventions to improve patient outcomes, especially in those with T2D. ⁷⁵ It is encouraging to see significant progress in the treatment of hypertension, many individuals are still not adequately treated and are unable to achieve their blood pressure goals. ⁷⁶ In particular, individuals with resistant hypertension exhibit uncontrolled blood pressure even when taking 3 or more different types of optimally dosed antihypertensive medications, including a diuretic. ⁷⁷ The study by Girard et al. showed that the administration of spironolactone for the treatment of resistant hypertension correlates with the improvement of LA function, as well as the optimization of atrioventricular coupling. ⁷⁸ Therefore, atrioventricular coupling may serve as a predictive tool for higher risk of cardiovascular event in hypertension and plays a pivotal role in therapeutic decision‐making.

Table 2.

Clinical Application of LACI in Hypertension

Author	Population	Age, y	Men n (%)	SBP (mmHg)	DBP (mmHg)	Method	Main findings
Soullier et al. 73	30 patients with hypertension 29 HCs	59±8 59±11	24 (80) 20 (70)	47±25 119±11	86±12 71±7	Speckle‐tracking echocardiography	Patients with hypertension experience impairment of LA functions, underlining the importance of LA‐left ventricular coupling
Shi et al. 74	103 with hypertension and diabetes 73 with hypertension without diabetes	61±11 57±11	60 (58) 39 (53)	134±25 125±14	80±12 78±12	CMR	Hypertension was found to exacerbate the decline in LA booster strain and increase LACI in patients with diabetets
Li et al. 75	89 with hypertension without diabetes 62 with hypertension and diabetes 70 matched HCs	58.4±11.9 58.5±9.1 55±9.6	48 (53.9) 32 (51.6) 37 (52.9)	139.4±19.5 139.6±17.2 118.8±13.3	84.9±15.5 84.2±10.8 74.3±9.1	CMR	There was more severe LA dysfunction in hypertension with diabetes, suggesting adverse atrioventricular coupling
Girard et al. 78	36 patients with resistant hypertension	55±7	24 (66.7)	/	/	CMR	Spironolactone can improve atrioventricular coupling of resistant hypertension

CMR indicates cardiac magnetic resonance; DBP, diastolic blood pressure; HCs, healthy controls; LA, left atrial; LACI, left atrioventricular coupling index; and SBP, systolic blood pressure.

Diabetes

The incidence of LV diastolic dysfunction in patients with diabetesis significantly increased compared with the general population. ⁷⁹ LA remodeling has been shown to have a significant prognostic impact on patients with diabetes, given the pivotal role of LA structural, functional, and mechanical alterations in the development of diabetic cardiomyopathy. Historically, echocardiographic studies in the diabetic population have focused primarily on LV structure and function; however, atrioventricular coupling has been identified as a major predictor of cardiovascular morbidity and mortality in patients with diabetes. ⁸⁰ The assessment of LA function and LACI is gaining increasing recognition as crucial indicators of cardiovascular disease in patients with diabetes. ⁸¹ Research by Dang et al. revealed that individuals with diabetes had increased LA stiffness and LV stiffness and a higher LACI compared with the control group. In addition, a positive association between LACI and LA and LV stiffness indices was observed. ⁸² In the research conducted by Shi et al., hypertension was found to contribute to a more pronounced reduction in LA booster strain and a concomitant increase in LACI in patients with diabetes, suggesting a possible deleterious atrioventricular coupling in the group with diabetes. ⁷⁴ Consistent with this, a contemporary investigation including individuals with both diabetes and hypertension confirmed unfavorable atrioventricular coupling in the cohort with diabetes. ⁷⁵ In a retrospective cohort of 35 individuals with prediabetes, 32 with diabetes, and 84 healthy controls, the results indicated that patients with prediabetes or diabetes exhibited reduced LA reservoir and conduit strains, but maintained a relatively stable LACI compared with healthy controls. ⁸¹ Furthermore, diabetes has been shown to be an independent predictor of the LACI in a Multi‐Ethnic Study of Atherosclerosis study. ⁸³ In conclusion, atrioventricular coupling is important for risk stratification and outcome prediction in diabetic patients.

Chronic Kidney Disease

Chronic kidney disease (CKD) and end‐stage renal disease induce significant changes in cardiac and vascular function, culminating in heart failure—a prevalent complication and leading cause of mortality in these patient populations. ⁸⁴ , ⁸⁵ Recent evidence suggests that LA dysfunction in patients with CKD is independently associated with renal function, potentially indicating the presence of CKD‐related atrial myopathy. ⁸⁶ In a cohort of patients with CKD, Ji et al. found that LACI could serve as a valuable metric for evaluating LA function in patients with CKD, potentially providing prognostic assessments and aiding in clinical decision making in this population. ⁸⁷ In another study by Demir et al. LACI was shown to be an independent and robust predictor of HFpEF in patients with end‐stage renal disease. ⁸⁸ LACI outperforms conventional LA parameters in identifying early LA remodeling and is easily assessed by rapid, straightforward echocardiographic methods, offering significant clinical potential. In short, LACI assessment is critical for predicting cardiovascular complications and improving the clinical outcomes for patients with CKD.

Application of New Technologies

The burgeoning integration of artificial intelligence into various medical disciplines, including radiology and ultrasound medicine, is playing a pivotal role. ⁸⁹ Recently, some studies have applied this emerging technology to evaluate atrioventricular coupling. Pezel et al conducted a study to determine the incremental prognostic value of fully automated artificial intelligence–derived LACI in predicting HF among patients undergoing stress CMR. The study encompassed a longitudinal analysis of 2134 patients matched for those with normal and abnormal stress CMR to assess the relationship between LACI and the risk of hospitalization for HF or cardiovascular death. The results showed that LACI positively correlates with these adverse outcomes and provides prognostic value beyond traditional risk factors, including inducible ischemia and late gadolinium enhancement. ⁴⁶ Salden et al. employed computational modeling with the CircAdapt framework to simulate the cardiac circulation under normal and failing states to elucidate the hemodynamic outcomes and mechanisms associated with the restoration of atrioventricular coupling. Their research convincingly demonstrated that biventricular pacing, in restoring atrioventricular coupling, confers significant hemodynamic benefits in hearts with atrioventricular dyssynchrony. ⁹⁰ In essence, the use of new technologies, including artificial intelligence, enables the extraction of relevant features from large image data sets, automates the analysis of these images, and improves both the accuracy and efficiency of atrioventricular coupling assessment. Besides, another new technique, STE, an advanced ultrasound modality enabling high‐resolution myocardial strain analysis, has established itself as a pivotal noninvasive tool for detecting subclinical cardiac remodeling and myocardial dysfunction. Its unique capacity to quantify phasic strain parameters offer novel insights into diastolic impairment progression. STE‐derived parameters provide quantitative assessments of dynamic atrial phasic function, with particular diagnostic value in refining the evaluation of ventricular diastolic dysfunction. The 3 main phases of LA strain are the reservoir phase (occurring during ventricular systole), conduit phase (occurring during early ventricular diastole), and booster phase (occurring during late ventricular diastole), each of which reflects the dynamic left atrium‐left ventricle relationship. Similarly, right atrial (RA) phasic strain include RA reservoir strain, conduit strain, and booster strain. Atrial reservoir strain is modulated by atrial compliance and relaxation, and conduit strain is governed primarily by ventricular relaxation and chamber stiffness. booster strain is influenced by atrial contractile properties. Especially left atrial reservoir strain, a noninvasive biomarker quantifying reservoir phase mechanics, demonstrates superior prognostic efficacy in stratifying cardiovascular risk trajectories. ³³ , ⁹¹ Also RA reservoir strain exhibits enhanced discriminative capacity for detecting elevated RA pressures and relatively stronger diagnostic performance compared with conventional echocardiographic parameters. It may be useful as a novel noninvasive estimate of RA function. ³³ , ⁹² Therefore, STE holds considerable potential for the assessment of dynamic biatrial phasic function. Fan et al. investigated the characteristics of LA function and LACI in early‐stage Fabry disease patients using 2‐dimensional STE and underscored the potential of LACI as an early marker of left atrium‐left ventricle coupling dysfunction in Fabry disease. ⁹³ Gao et al. explored the impact of LACI in CKD with T2D using STE and found that patients with CKD with T2D had significantly higher LACI values compared with those without T2D, indicating impaired left atrium‐left ventricle coupling. Elevated LACI was independently associated with an increased risk of major adverse cardiac events during follow‐up. ⁹⁴ As previously mentioned, STE‐derived parameters and LACI have been further validated in populations with diabetes and hypertension, with studies demonstrating its incremental prognostic utility in predicting adverse cardiovascular outcomes. ⁷³ , ⁸² All these findings underscore the capacity of LACI to enhance risk stratification beyond traditional biomarkers, solidifying its role as a critical noninvasive metric for early identification of cardiac dysfunction and adverse remodeling in high‐risk cohorts.

Right Atrioventricular Coupling Index

The right atrium and right ventricle exhibit a degree of functional interaction, similar to the left chambers. This interaction is characterized by the closed tricuspid valve at the end of systole, which separates them, and their direct connection at the end of diastole, which allows tight coupling in the absence of tricuspid stenosis. To measure the extent of this right atrioventricular coupling, a novel metric known as the RACI has been introduced, which was defined by calculating the ratio of the RAEDV to the right ventricular (RV) EDV (Figure 3). The RACI is primarily assessed using CMR and echo. Unlike the LACI, for the right chambers, images are obtained from an apical RV–focused view. Here, the 3‐dimensional echocardiographic volumetric analysis method for RACI assessment is introduced, following standardized protocols. Full‐volume data sets of the right atrium and right ventricle are acquired using a 2.5‐MHz matrix‐array transducer, 6 consecutive cardiac cycles gated to the ECG to ensure complete inclusion of both chambers. The right ventricle data set is analyzed using dedicated software, which automatically delineate endocardial borders throughout the cardiac cycle. Manual adjustments are performed to ensure accurate tracking of the trabeculated RV free wall, with particular attention to the tricuspid annular plane and RV apex. The software is also used to measure RAEDV and RVEDV with orthogonal planes adjusted to exclude the inferior vena cava and coronary sinus ostium. This approach is consistent with prior validations of 3‐dimensional echocardiography for biventricular and biatrial volumetric quantification. ⁶⁹ , ⁹⁵ At present, there is a limited understanding of the right atrioventricular coupling. Table 3 summarizes the clinical applications of RACI.

Figure 3. Measurement of RACI using CMR and echocardiography.

A, RVEDV (yellow dashed line) and RAEDV (red dashed line) are measured in the apical 4‐chamber view using CMR. B, RVEDV (blue dashed line) and RAEDV (green dashed line) are measured in the apical 4‐chamber view using echocardiography. CMR indicates cardiovascular magnetic resonance; RACI, right atrioventricular coupling index; RAEDV, right atrial end‐diastolic volume; and RVEDV, right ventricular end‐diastolic volume.

Table 3.

Clinical Application of RACI

Author	Population	Age, y	Men n (%)	Method	RACI (%)	Main findings
Meloni et al. 8	292 with beta‐thalassemia major 32 healthy controls	36.72±11.76 40.78±14.35	140 (47.9) 20 (62.5)	CMR	27.84±10.30 17.06±5.03	Patients with cardiac complications had markedly elevated RACI levels
Vîjîac et al. 69	121 with DCM	59±14	89 (74)	Echocardiogram	23 (16–40)	RACI is an independent predictor of unfavorable outcomes in DCM
Wessels et al. 96	39 with low RV end‐diastolic elastance 41 with high RV end‐diastolic elastance 20 HCs	55.6±17.6 57.8±17.6 46.6±15.5	14 (36) 12 (29) 8 (40)	CMR	43 (36–53) 52 (40–73) 36 (33–39)	Those with severe RV diastolic stiffness exhibited increased right atrial stiffness and a poorer RACI
Gunsaulus et al. 97	63 patients with rTOF	16.4 (12.9, 18.7)	37 (59)	CMR	15.0 (10.5,22.1)	In patients with rTOF, RACI was the most effective predictor of a high‐risk Importance Factor Score.

CMR indicates cardiovascular magnetic resonance; DCM, dilated cardiomyopathy; RACI, right atrioventricular coupling index; rTOF: repaired tetralogy of Fallot; and RV, right ventricular.

In the study conducted by Wessels et al., RA stiffness and RACI were evaluated in patients with precapillary pulmonary hypertension using CMR and catheterization. Patients with severe RV diastolic stiffness exhibited increased RA stiffness and a poorer RACI, indicating that RACI may serve as an indicator to predict impaired functional coordination between the right atrium and right ventricle. ⁹⁶ Meloni et al. performed a cross‐sectional analysis to investigate the association of LACI and RACI with numerous risk factors including cardiac complications in a cohort of patients with beta‐thalassemia major. Their findings revealed that patients with cardiac complications had markedly elevated LACI and RACI levels compared with those without complications. In patients with beta‐thalassemia major, both LACI and RACI were significantly associated with the presence of late gadolinium enhancement in the left ventricle. Additionally, it was observed that patients with cardiac complications exhibited impaired LACI and RACI, indicating that the LACI and RACI may act as supplementary tools to improve the clinical management of patients with beta‐thalassemia major. ⁸ A prior investigation demonstrated that RACI serves as an independent predictor of unfavorable outcomes in DCM and offers additional prognostic insight beyond standard risk factors. ⁶⁹ Additionally, another study suggests that RACI could potentially aid in the risk stratification for patients with repaired tetralogy of Fallot. In the study by Gunsaulus et al., patients were stratified into risk groups using a previously established importance factor score to predict life‐threatening arrhythmias in repaired tetralogy of Fallot. Patients with a high‐risk importance factor score (>2) exhibited significantly greater minimum RA volume and RACI compared with individuals with a score of ≤2. Receiver operating characteristic analysis indicated that RACI was the most effective predictor of a high‐risk importance factor score. Older age at the time of repair and a diagnosis of pulmonary atresia were associated with increased RACI values. ⁹⁷ Overall, RACI offers valuable insights for assessing atrioventricular dynamics and categorizing patient risk levels. Individuals with elevated RACI are at greater risk and should be closely monitored for potential adverse outcomes. Another relevant parameter for RV coupling is the ratio of tricuspid annular plane systolic excursion to systolic pulmonary artery pressure, which reflects the relationship between RV contractility and RV afterload and is increasingly recognized as an accurate indicator of RV function and provides prognostic information in patients with HF, pulmonary arterial hypertension, or tricuspid regurgitation. ⁹⁸ , ⁹⁹ A lower tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio indicates poorer right ventricle‐pulmonary artery coupling and is associated with adverse outcomes. ⁹⁸ , ¹⁰⁰ Despite the established prognostic utility of right atrioventricular and right ventricle‐pulmonary artery coupling indices in isolation, a critical gap persists in contemporary cardiopulmonary research: no studies have systematically compared or integrated their synergistic predictive capacity for RV dysfunction. This uncharted territory warrants multidisciplinary investigations to elucidate the mechanistic interplay between the right atrium‐right ventricule and right ventricle‐pulmonary artery coupling axes, and may unveil novel therapeutic targets at the nexus of atrial‐ventricular‐arterial dyssynchrony, ultimately refining precise prognostication in cardiopulmonary disorders.

CONCLUSIONS

The study highlights the significance of atrioventricular coupling indices, including LACI and RACI, in assessing cardiac function and predicting outcomes in a variety of cardiovascular conditions. The findings underscore the potential of these indices to provide more accurate and comprehensive insights into atrioventricular interactions compared with traditional markers. By offering superior predictive capabilities, LACI and RACI may improve risk stratification and guide clinical decision‐making, ultimately improving patient care and outcomes. Future research should continue to explore the application of these indices in various patient populations and clinical settings to fully realize their clinical utility.

Sources of Funding

The study was supported by the National Natural Science Foundation of China (Grant Nos. 82371991, 82230066, 82371990, 82201408) and the Natural Science Foundation of Hubei Province (grant no. 2023AFB898).

Disclosures

None.