Sacubitril-valsartan was associated with improved myocardial sympathetic activity in HFrEF patients, increasing the late H/M ratio from 1.39 to 1.52 at 3 months (p<0.001).
Observational (n=40)
Does sacubitril-valsartan improve myocardial sympathetic innervation in patients with stable chronic HFrEF?
Sacubitril-valsartan significantly improves myocardial sympathetic innervation and correlates with reverse remodeling in patients with HFrEF, providing mechanistic insight into its clinical benefits.
p-value: p=<0.001
BackgroundIn chronic heart failure (HF) with reduced ejection fraction (HFrEF), diminished cardiac output triggers neurohormonal activation that worsens cardiac dysfunction.Sacubitril-valsartan improves morbidity and mortality in HFrEF, potentially by modulating sympathetic nervous system activity. ObjectivesTo evaluate the effects of sacubitril-valsartan on myocardial sympathetic innervation using 123meta-iodobenzylguanidine (MIBG) scintigraphy in patients with stable chronic HFrEF. MethodsThe REMODEL study is a prospective, single-arm study including patients with NYHA Class II-IV symptoms and LVEF 25-40%.Participants underwent 123-meta-iodobenzylguanidine (MIBG) scintigraphy a noninvasive measure of myocardial sympathetic innervation assessed by the heart-to-mediastinum (H/M) uptake ratio and washout rate (WR), along with echocardiography, cardiopulmonary testing, biomarker analysis, and quality of life assessment at baseline, 3, 6, and 12 months after initiating sacubitril-valsartan. Sacubitril-valsartan was initiated at 24/26 mg or 49/51 mg twice daily and uptitrated to 97/103 mg twice daily over approximately 2 weeks.The primary endpoint was change in late H/M ratio from baseline to 3 months, assessed using the Wilcoxon signed-rank test and Spearman rank correlations. ResultsAmong 40 enrolled patients, 39 completed baseline and 3-month MIBG imaging; 26 completed 12-month follow-up.At 3 months, MIBG parameters improved: late H/M ratio increased from 1.39 0.19 to 1.52 0.19 (p<0.001) and washout rate declined from 48.1 13.8% to 32.1 7.8% (p<0.001).Biomarker: NT-proBNP decreased from 333 to 210 79-760 pg/mL (p<0.001).Functional: 6MWT improved (431 341-500 to 442 359-522 m, p=0.006); peak VO increased nonsignificantly (17.6 to 18.7 mL/kg/min, p=0.11).Change in washout rate was statistically correlated with NT-proBNP change (Spearman's rho = 0.44, p = 0.005), but not with functional measures.At 12 months, VO improved to 19.8 mL/kg/min (p=0.019) and 6MWT increased by 56.4 m (p<0.001), while NT-proBNP decline was nonsignificant. ConclusionsIn this single-arm study, sacubitril-valsartan was associated with improved myocardial sympathetic activity in HFrEF patients.Changes in washout rate were statistically correlated with improvements in NT-proBNP (Spearman rho=0.44,p=0.005), and changes in late H/M ratio were statistically correlated with reduction in LVEDD (rho= -0.35, p=0.030).However, these changes did not correlate with functional measures.In the absence of a control arm, causal attribution to sacubitril-valsartan cannot be established.These findings suggest the need for further investigation into the prognostic relevance of MIBG-derived sympathetic activity markers.
Oren et al. (Fri,) conducted a observational in chronic heart failure with reduced ejection fraction (HFrEF) (n=40). Sacubitril-valsartan was evaluated on change in late H/M ratio from baseline to 3 months (p=<0.001). Sacubitril-valsartan was associated with improved myocardial sympathetic activity in HFrEF patients, increasing the late H/M ratio from 1.39 to 1.52 at 3 months (p<0.001).