Combined assessment of left ventricular and atrial function for transthyretin amyloid cardiomyopathy

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by progressive myocardial deposition of misfolded transthyretin protein, resulting in increased ventricular wall thickness, impaired myocardial deformation, and progressive HF. Although left ventricular (LV) dysfunction has traditionally been central to disease staging and risk stratification, amyloid infiltration also involves the left atrium (LA), leading to atrial mechanical dysfunction and arrhythmogenic substrate formation. Emerging data suggest that LA dysfunction may carry independent prognostic information. However, the clinical value of integrating both LV and LA functional assessment, particularly in patients receiving contemporary disease-modifying therapy, has not been fully established. Purpose To determine whether simultaneous evaluation of LV and LA function provides incremental prognostic value for cardiovascular outcomes in patients with ATTR-CM treated with disease-modifying therapy. Methods We retrospectively analyzed 139 patients with ATTR-CM treated with disease-modifying therapies. LV and LA function were assessed using global longitudinal strain (GLS) and LA reservoir strain via speckle-tracking echocardiography. Patients were categorized according to median GLS (10.9%) and LA strain (9.5%) into three groups: preserved both LV and LA function (n=50), preserved function in only one chamber (n=49), and impaired both LV and LA function (n=40). The primary endpoint was a composite of cardiovascular death or hospitalization for HF, with a median follow-up of 1.5 years after treatment initiation. Results During follow-up, 22 patients experienced the primary endpoint, including 9 cardiovascular deaths and 13 hospitalizations for HF. Patients with preserved both LV and LA function had a significantly lower incidence of composite cardiovascular events compared to those with impaired both LV and LA function (Figure 1). Additionally, patients with preserved function in only one chamber exhibited intermediate risk (Figure 1). When the two components of the composite endpoint including hospitalization for HF and cardiovascular death were analyzed separately, similar trends were observed. In the univariable analysis, GLS, LA strain, and impaired LV and LA function were each significantly associated with the composite cardiovascular outcome (Figure 2). Notably, in the multivariable analysis, only impairment in both LV and LA function remained independently associated with an increased risk of cardiovascular events (Figure 2). Conclusions In patients with ATTR-CM receiving disease-modifying therapy, combined assessment of LV and LA function provides incremental prognostic value beyond single-chamber evaluation. This approach may facilitate earlier identification of high-risk patients and support more tailored therapeutic strategies in clinical practice.