BackgroundHeart failure (HF) is associated with cardiac autonomic denervation (AD), which can be non-invasively assessed by 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy and has prognostic implications. We aimed to study the relationship between myocardial contractility assessed by global longitudinal strain (GLS) and AD assessed by 123I-mIBG scintigraphy in advanced HF. Methods/ResultsBETTER-HF is a prospective randomized clinical trial including HF patients (pts) submitted to cardiac resynchronization therapy (CRT) who are submitted to a clinical, echocardiographic, and scintigraphic assessment before and 6 months after CRT. 81 pts were included. An echocardiographic response (absolute increase in left ventricular ejection fraction ≥ 10%) was observed in 73.7% of pts. A higher baseline late heart-to-mediastinum ratio (HMR) was associated with a better echocardiographic response. There was a significant association between late HMR and GLS at baseline and 6 months. At baseline, GLS had an AUC of 0.715 for discrimination for a late HMR < 1.6. A GLS cut-off of − 9% maximized the likelihood of correctly classifying a pt as having severe AD (HMR < 1.6). ConclusionMyocardial contractility as assessed by GLS is moderately correlated with AD as assessed by 123I-mIBG scintigraphy and has a good discrimination for the identification of severe cardiac denervation. GLS may allow for a more readily accessible estimation of the degree of AD in advanced HF pts.