Prognostic utility of left ventricular global longitudinal strain in patients with systemic amyloidosis

Abstract

Abstract Background Myocardial deposition of amyloid proteins results in restrictive cardiomyopathy. Left ventricular global longitudinal strain (GLS) has emerged as a sensitive measure for detecting subclinical cardiac dysfunction over traditional echocardiographic parameters. However, multiple studies have provided differing conclusions regarding prognostic utility of impaired GLS in patients with systemic amyloidosis. Purpose We conducted a systematic review and meta-analysis to evaluate whether impaired GLS was associated with increased mortality or major adverse cardiovascular events (MACE) in patients with systemic amyloidosis. Methods We performed a literature search of Embase, Medline and Web of Science databases to identify studies that reported the association of GLS with clinical outcomes in patients with systemic amyloidosis (light chain or TTR amyloidosis). Outcomes of interest included all-cause mortality and MACE, defined as a composite of death or heart transplant or heart failure hospitalization. Unadjusted and adjusted hazard ratio (uHR and aHR respectively) were pooled using a random effects model. Heterogeneity among the studies was assessed using the Higgins I2 value. Results Out of 2139 initial citations, 28 observational studies with a total of 2713 patients were included in the analysis. The mean age ranged between 58–78 years and 62% of the patients were male. Most patients had cardiac amyloidosis (83%) and light-chain amyloidosis accounted for 69% of cases. Mean follow-up ranged between 1 and 5 years. GLS was significantly higher (less negative) (mean difference (MD) −3.69 [−5.94, −1.44], I2=87, p<0.01) in non-survivors compared with survivors. Similarly, patients who experienced MACE had a significantly higher mean GLS (MD −3.22, [−5.21, −1.22,], I2=82, p<0.01]. The risk of both mortality and MACE increased significantly for every −1% increase in GLS. In unadjusted models, a GLS above the defined threshold value was associated with a significantly higher risk of mortality (uHR: 1.66 [1.22, 5.21], I2=85.2, p<0.01) and MACE (uHR: 2.24 [1.28, 3.92], I2=39, p<0.01). In multivariable models an increase in GLS by −1% was an independent predictor of mortality (aHR: 1.09 [1.01,1.16], I2=53, p=0.02) and MACE (aHR: 1.24 [1.14,1.36], I2=0, p<0.01). Conclusion In patient with amyloidosis, the baseline left ventricular GLS may help identify patients with a higher risk of mortality and MACE. Funding Acknowledgement Type of funding sources: None.