Echocardiographic measures in patients treated with ARNI early after high-risk AMI

Introduction and methods

Background

ACE inhibitors such as ramipril not only reduce the risk of adverse outcomes, but also attenuate left ventricular (LV) remodeling and systolic dysfunction after high-risk acute myocardial infarction (AMI) [1-3]. Preclinical studies suggest similar effects of the ARNI sacubitril/valsartan after experimentally induced AMI [4-6]. However, treatment with sacubitril/valsartan is not associated with improvements in left ventricular ejection fraction (LVEF) and LV and left atrial (LA) size in patients with asymptomatic LV dysfunction late after AMI, compared with valsartan [7]. It is unclear whether treatment with sacubitril/valsartan early after high-risk AMI improves cardiac structures and functions, compared with ACE inhibition.

Aim of the study

The aim of this substudy of the PARADISE-MI trial was to test the hypothesis that treatment with sacubitril/valsartan improves LV function and attenuates adverse remodeling in patients with high-risk AMI, compared with ramipril.

Methods

The investigators conducted the PARADISE-MI Echo Study, a prespecified substudy of the PARADISE-MI trial in which 544 of the 5661 trial participants (mean age: 64 years; 26% female) underwent protocol echocardiography at randomization and after 8 months. Patients with spontaneous AMI complicated by LV dysfunction or pulmonary congestion were randomized within 0.5-7 days of presentation to receive a target dose of sacubitril/valsartan 200 mg or ramipril 5 mg twice daily. Additional inclusion criteria specific to this substudy were: (a) sinus rhythm at the time of randomization; and (b) adequate quality of echocardiogram to determine LVEF and left atrial volume (LAV). Echocardiography was performed in 457 (84%) of 544 patients after 8 months.

Outcomes

The coprimary outcomes were change in LVEF and LAV from baseline to 8 months. Predefined secondary outcomes were change in left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) from baseline to 8 months.

Main results

Changes in echocardiographic measures from baseline to 8 months

• The change in LVEF (P=0.79) and LAV (P=0.62) from baseline to 8 months did not differ significantly between treatment groups.

• Patients treated with sacubitril/valsartan demonstrated less increase in LVEDV (P=0.025) and greater decline in LV mass index from baseline to 8 months than patients receiving ramipril.
• The change in LVESV (P=0.26) from baseline to 8 months did not differ significantly between treatment groups.
• There was a greater increase in tissue Doppler e’lat and decrease in E/e’lat, increase in e’ave, and decrease in tricuspid regurgitation peak velocity in the group with sacubitril/valsartan compared with those on ramipril.
• After correction for baseline characteristics, associations persisted.

Association of echocardiographic measures and clinical outcomes

• There was an association between lower LVEF, larger LVEDV and LVESV, greater LV mass index, greater LAV and higher E wave and E/e’ ratio with higher risk of the composite outcome of investigator-reported CV death, HF hospitalization or outpatient HF.

Conclusion

References

Find this article online at Circulation.