Superresponse to cardiac resynchronization therapy: clinical outcomes and predictors
Authors: Brandao M , Goncalves Almeida J , Fonseca P , Rosas F , Santos E , Ribeiro J , Oliveira M , Goncalves H , Fontes-Carvalho R , Primo J 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

BACKGROUND
Resynchronization therapy (CRT) reduces morbidity and mortality in selected patients with heart failure with reduced ejection fraction (HFrEF). Patients that experience significant reverse remodelling and left ventricular (LV) ejection fraction (LVEF) improvement have been called "superresponders".

AIM
To describe a cohort of superresponders and identify predictors of superresponse to CRT.

METHODS
Single-center retrospective study of consecutive patients submitted to CRT implantation (2007-2018). Patients underwent echocardiographic (echo) assessment at baseline, 6-months and 1-year. Superresponse was defined as LVEF≥50% during the 1st year of follow-up (FU). Major adverse cardiac events (MACE) included heart failure hospitalization or all-cause mortality. Multivariate logistic regression was performed to identify predictors of superresponse. Survival analysis with Kaplan-Meier method and Log-rank test was performed to compare outcomes between superresponders and non-superresponders.

RESULTS
295 CRT patients (70.5% male, mean age 67 ± 11 years) were included. Fifty-nine (21.4%) patients were superresponders. Superresponders were more often female (42.4% vs 25.8%, p=.021), tended to be older (69.6 vs 66.7 years, p=.054) and had lower rates of coronary disease (17.2% vs 32.9%, p=.032), atrial fibrillation (20.3% vs 38.0%, p=.018), valve disease (13.6% vs 30.0%, p=.018) and chronic kidney disease (6.9% vs 26.0%, p=.003). Superresponders had higher rates of non-ischemic HF (88.1% vs 69.1%, p=.006) and were more often implanted with CRT-P (69.5% vs 37.8%, p&lt;.001). HFrEF medication did not differ between groups.
Superresponders had lower baseline LV end-systolic volumes (115.5 vs 166.2 ml, p&lt;.001) and N-terminal pro B-type natriuretic peptide (NT-proBNP) values (1232.6 vs 5252 pg/ml, p&lt;.001). Baseline QRS duration did not differ (171.7 vs 171.3 ms, p=.883). During a median FU of 3 ± 5 years, there were no differences in terms of ventricular arrythmias (5.3% vs 6.8%, p=.913) or appropriate defibrillator therapies (1.8% vs 6.8%, p=.147) between groups. In addition to LVEF improvement (53.7% vs 35.3%, p&lt;.001), superresponders also showed higher tricuspid annular plane systolic excursion values (22.1 vs 19.8 mm, p=.004) during FU. MACE occurred less frequently (Log-rank test, p=.003) and all-cause mortality (Log-rank test, p &lt; 0.001) was lower in superresponders.
Multivariate analysis identified female gender (odds ratio [OR] 5.7, 95% confidence interval [CI] 1.03-31.73, p=.045), older age (OR 1.1, 95% CI 1.02-1.24, p=.017) and lower baseline NT-proBNP (OR 0.9, 95% CI 0.99-1.00, p=.011) as independent predictors of superresponse to CRT.

CONCLUSION
In superresponders, in addition to a significant improvement in LVEF, we observed an improvement in right ventricular function. As expected, MACE and all-cause mortality were lower. Female gender, older age and lower baseline NT-proBNP predicted super-response to CRT.