Association between echocardiographic E/e′ and invasive filling pressures at rest and exercise in transthyretin cardiac amyloidosis

Background

Echocardiographic left ventricular (LV) diastolic parameters such as E/e′ are widely used as non-invasive surrogates of LV filling pressure. While moderate correlations between E/e′ and pulmonary aterial wedge pressure (PAWP) have been reported in general heart failure populations, data in restrictive cardiomyopathies such as transthyretin amyloid cardiomyopathy (ATTR-CM) remain limited.1

Purpose

To evaluate the association between average E/e′ (lateral and septal) and simultaneous invasively measured PAWP at rest and during exercise in patients with ATTR-CM.

Methods

Patients with ATTR-CM undergoing echocardiography and simultaneous right heart catheterization (RHC) at rest, with a subset also undergoing semi-supine bicycle exercise testing, were included from two clinical trials (NCT05633563 and NCT04276220) conducted at our institution between 2019-2023. Demographic, echocardiographic, and RHC data was retrieved from the clinical trial report forms. Associations between aE/e′ and PAWP were assessed using Spearman correlation. Linear regression was performed as exploratory analysis to estimate effect size.

Results

A total of 51 patients were included (92% male, median age 82.6 years [IQR 75.1-84.7]); 98% had wild-type ATTR. Mean LVEF was 49 ± 9% and LV global longitudinal strain was −11.2 ± 3.1. Mean PAWP at rest was 13.1 ± 6.1 mmHg, with 18 patients (35%) having PAWP >15 mmHg. Median E/e′ at rest was 12.7 (IQR 8.1-17.7), and 16 patients (31%) had E/e′ >14. At rest, there was a weak association between E/e′ and PAWP (Spearman ρ = 0.32, 95% CI 0.03–0.56, p = 0.03) and linear regression demonstrated a weak but statistically significant relationship (β = 0.31, R² = 0.096, p = 0.038).

A subgroup of 24 patients (47%) underwent additional exercise testing with a mean peak exercise capacity of 87 ± 34 W. At peak exercise, mean PAWP was 30.3 ± 9.1 mmHg, with 22 patients (92%) having PAWP >15 mmHg. Median E/e′ was 12.6 (IQR 10.1-15.9), and 9 patients (38%) had E/e’ >14. There was no significant association between E/e′ and PAWP during exercise (Spearman ρ = 0.15, 95% CI −0.26–0.51, p = 0.48), and linear regression confirmed lack of relationship (β = 0.14, R² = 0.008, p = 0.67).

Conclusion

The E/e′ ratio demonstrates a weak monotonic association with invasively measured resting filling pressures and no association at peak exercise in patients with ATTR-CM. These findings highlight the limited reliability of E/e′ as a standalone non-invasive marker of filling pressures in this population and support the need for multiparametric or invasive assessment.Scatter plot: E/e' vs. PAWP at peak exerciseScatter plot: E/e' vs. PAWP at rest