Focused Treatment of Heart Failure with Reduced Ejection Fraction Using Sacubitril/Valsartan

Fig. 1. Pressure–volume graphs illustrating the key biomechanical principle governing the function of the heart. In these illustrations, the green curves represent the end diastolic pressure–volume relationship, which determines diastolic function. The yellow lines represent the end systolic pressure–volume relationship, which determines the degree of systolic function. The slopes of the yellow lines are known as the end systolic slopes and the angle of the slopes indicates the contractile function of the heart. a Pressure–volume loop representing a normal heart. b Pressure–volume loop in a heart with systolic dysfunction. In a heart with systolic dysfunction, the slope of the yellow line is less steep, indicating depressed left ventricular (LV) contractility. The impaired contractility shifts the whole loop to the right because incomplete LV emptying leads to a higher remaining volume at end systole. Altogether, the stroke volume is diminished (represented by a shorter and narrower loop with reduced total area) as a result of systolic dysfunction

Fig. 2. Mechanism of action of sacubitril/valsartan [21]. The inhibition of neprilysin works synergistically with the inhibition of angiotensin receptors by valsartan. ANP/BNP atrial natriuretic peptide/brain natriuretic peptide, ARB angiotensin receptor blocker, AT1R angiotensin II type 1 receptor, NEP neprilysin, NPS natriuretic peptide system, RAAS renin–angiotensin aldosterone system. Adapted with permission from J Am Coll Cardiol 2015;65(10):1029–41. Copyright 2015: American College of Cardiology Foundation