Are We Ready to Monitor the Atrium? From Ventricular‐Centric to Chamber‐Integrated Cardiotoxicity Surveillance: The Emerging Role of Left Atrial Strain

Patients with diffuse large B-cell lymphoma (DLBCL) treated with the R-CHOP chemotherapy regimen represent a population at substantial risk of cancer therapy–related cardiac dysfunction (CTRCD) [1, 2]. Nearly 29% of patients developed a reduction in left ventricular systolic function during active treatment, highlighting cardiotoxicity as an early and clinically relevant complication of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy [3]. Traditionally, left ventricular ejection fraction (LVEF) has served as the sole echocardiographic criterion for diagnosing CTRCD [4]. More recently, the 2022 ESC Cardio-Oncology Guidelines introduced left ventricular global longitudinal strain (LV-GLS) as an additional primary diagnostic parameter, acknowledging the limitations of LVEF in detecting early myocardial injury [1]. However, both indices primarily focus on ventricular systolic mechanics and may overlook early diastolic and left atrial (LA) involvement. This observation provides a strong rationale for refining cardiovascular monitoring strategies beyond conventional parameters. Most of the available evidence on LA function during cardiotoxic treatments originates from studies in breast cancer populations, resulting in heterogeneous conclusions [5, 6]. In this context, the study by Wang provides timely and clinically relevant insights into the role of LA function assessed by speckle-tracking echocardiography (STE) in patients with DLBCL treated with R-CHOP chemotherapy, shifting attention toward a chamber that plays a central role in cardiovascular hemodynamics and disease progression [7]. Assessment of LA phasic function has the potential to improve both the diagnostic accuracy and prognostic relevance of diastolic dysfunction and heart failure (HF), particularly heart failure with preserved ejection fraction (HFpEF) [8]. Left ventricular diastolic dysfunction generally precedes systolic dysfunction across a wide range of clinical settings and has been consistently established as an independent predictor of all-cause mortality with a 3.53-fold increased risk of cardiovascular events or death [9]. Within this framework, LA strain, especially reservoir strain (LASr), acts as an integrated marker of chronic filling pressure elevation, myocardial stiffness, and impaired ventricular–atrial coupling [10]. The authors demonstrate a significant deterioration of LA strain parameters following R-CHOP therapy, even in patients without overt systolic impairment. This finding reinforces the concept that atrial dysfunction may represent one of the earliest manifestations of CTRCD, preceding changes in LVEF and potentially even LV-GLS [7]. Notably, the authors provide robust validation of this approach by demonstrating that an LASr >35% cut-off showed substantial agreement with the 2016 ASE/EACVI diastolic dysfunction algorithm, with a kappa value of 0.765 (p < 0.05) [11]. This level of concordance supports the clinical reliability of LA strain as a surrogate marker of diastolic function and strengthens the translational value of the findings. The mechanisms underlying CTRCD remain incompletely understood, but growing evidence suggests a central role for oxidative stress, driven by an imbalance between reactive oxygen species (ROS) and antioxidant defenses [12]. This process leads to cardiomyocyte injury, mitochondrial dysfunction, and progressive myocardial remodeling [12]. In DLBCL patients treated with R-CHOP, LA dysfunction may arise through two complementary mechanisms: elevated filling pressures secondary to impaired ventricular relaxation and direct cytotoxic effects of chemotherapy on the atrial myocardium itself. Importantly, cardiomyocyte injury should be viewed as a global myocardial phenomenon, affecting not only the ventricle but also the atrial myocardium. The observed impairment in LA strain in the absence of significant changes in LA volume supports this hypothesis and highlights the vulnerability of atrial tissue to early toxic injury [12]. LA enlargement is a well-established marker of adverse cardiovascular outcomes; however, it reflects a chronic and relatively late remodeling process that develops after prolonged exposure to pressure or volume overload. Consequently, left atrial volume index (LAVi) lacks sensitivity for detecting subtle or early functional alterations [10]. Consistent with previous studies, the authors report no significant changes in LAVi after completion of chemotherapy, despite clear impairment in LA strain [7]. This dissociation underscores the superiority of deformation imaging over volumetric assessment in the early phases of cardiotoxicity and supports the routine inclusion of LA strain in cardio-oncology echocardiographic protocols [13]. Nevertheless, the interpretation of the LA strain requires careful clinical contextualization. Age-related atrial stiffening, systemic hypertension, and common cardiovascular comorbidities may all influence baseline atrial mechanics, potentially reducing the discriminative value of fixed LASr cut-offs. Moreover, conditions such as atrial fibrillation or frequent atrial ectopy not only act as major confounders but may also preclude reliable strain acquisition altogether, limiting the applicability of this technique in a substantial proportion of real-world oncology patients. In such patients, an LASr value below conventional thresholds may reflect pre-existing atrial remodeling rather than chemotherapy-induced injury [14]. Additional methodological considerations further complicate interpretation. Variability across vendors and software platforms remains an unresolved issue, and the choice of the electrocardiographic reference point for strain analysis continues to be debated. While P-wave–based timing may better reflect atrial electromechanical coupling, QRS-based gating offers greater feasibility and reproducibility in routine practice, particularly in oncologic populations where ECG quality, rhythm stability, and heart rate variability may be suboptimal. Taken together, these factors highlight the need for larger, multicenter registries and studies conducted across diverse clinical settings to establish age-adjusted and context-specific reference values, refine acquisition protocols, and improve risk stratification in heterogeneous cardio-oncology populations. Only through such efforts can LA strain be fully integrated into personalized surveillance strategies while avoiding overinterpretation in patients with competing sources of atrial dysfunction. The study by Wang and colleagues supports a paradigm shift toward a more comprehensive, chamber-integrated approach to cardiotoxicity surveillance, in which the left heart is no longer viewed as two distinct anatomical units but rather as a single, functionally interconnected system. In this context, LA strain should not be considered merely an ancillary parameter, but part of a broader assessment of global left heart mechanics. The emerging concept of global atrioventricular strain (GAVS), by integrating atrial and ventricular deformation, may further refine early detection of myocardial involvement, effectively bridging subclinical diastolic dysfunction and the development of overt HF [15]. In patients with DLBCL undergoing R-CHOP therapy, LA dysfunction detected by STE represents an early and clinically meaningful signal of chemotherapy-related cardiac involvement. By demonstrating strong agreement between LASr and established diastolic dysfunction algorithms, and by highlighting atrial vulnerability beyond volumetric changes, the present study contributes substantially to the evolving landscape of cardio-oncology imaging. Incorporating LA strain into routine practice may enhance early detection, refine risk stratification, and ultimately improve cardiovascular outcomes in this high-risk population (Figure 1). Open access publishing facilitated by Universita degli Studi di Palermo, as part of the Wiley - CRUI-CARE agreement. The authors have nothing to report.