These differences in outcomes included a 20% reduction in sudden cardiac death. Symptomatic hypotension was more common with sacubitril/valsartan (14.% vs. 9.2%; p < 0.001) but was not associated with a worsening of renal function. Angioe- dema was numerically higher but not statistically signif- icantly different from enalapril in the sacubitril/valsartan group. The 2016 update to the HF guidelines (6) recom- mended an ARNI, ACEI, or ARB to reduce morbidity and mortality in patients with chronic HFrEF and that patients with NYHA class II to III symptoms who can tolerate an ACEI or ARB should transition to an ARNI to further reduce morbidity and mortality (Class I, Level of Evi- dence: B-R) (3,4,7,8). ARNIs have been associated with improvement in diastolic function, left ventricular (LV) function, quality of life, and burden of ventricular ar- rhythmias (8,10,11,18,19). In the PROVE-HF (Prospective Study of Biomarkers, Symptom Improvement, and Ven- tricular Remodeling During Sacubitril/Valsartan Therapy for HF) study, after 12 months of therapy with sacubitril/ valsartan, the median LVEF increased from 28.2% to 0.001), while the median LV end-diastolic volume index [interquartile range: 12.92 to 11.58]; p < 0.001) and the median LV end-systolic volume index decreased [95% CI: 16.03 to 14.55]; p < 0.001). Indexed left atrial volume by body surface area and the E/e0 ratio also decreased signi cantly (11). These results were demon- strated in important subgroups not represented in the PARADIGM-HF trial, such as those with de novo HF or naive to ACEIs/ARBs, those with lower enrollment N-ter- minal pro B-type natriuretic peptide (NT-proBNP) con- centrations, or those not attaining the target dose in the course of the study. 