PRO: Vasodilators Remain an Indispensable Treatment for Acute Heart Failure | European Heart Journal. Acute Cardiovascular Care | Oxford Academic
Highlights
- SNP is a nitrosyl-containing salt that releases nitric oxide (NO) in an one-electron reduction step. This is readily and non-enzymatically accomplished by a variety of reductants in the circulation, interstitial space, and cells. Therefore, intravenous SNP releases NO throughout the circulation and potently dilates all vessels (View Highlight)
- Given the short half-life of NO, SNP-induced vasodilation is short lived. In addition, SNP has direct myocardial effects that lower the LV end-diastolic pressure–volume relationship (View Highlight)
- The immediate and short-lived simultaneous action on both the arterial and venous side, as well as the myocardium itself, the lack of tolerance with continued infusion, and the absence of significant limiting side effects, make SNP probably the preferred vasodilator in AHF. One exception might be significant underlying coronary disease without revascularization, where it may cause a coronary steal phenomenon due to its potent dilation of the small arteries. In such cases (which probably require revascularization in the first place), use of organic nitrates is preferred (View Highlight)
- some degree of compensatory arteriolar vasoconstriction may be desirable in case of increased ventricular interdependency to preserve adequate filling of the LV. Therefore, SNP should be used cautiously in severe right ventricular dysfunction (View Highlight)
- In contrast to SNP, nitroglycerin and other organic nitrates require a three-electron reduction to yield NO. This is largely accomplished by the mitochondrial enzyme aldehyde reductase-2. As a result, organic nitrates preferentially dilate veins and larger arteries, while having less impact on arterioles, particularly at lower doses (View Highlight)
- A major limitation to prolonged use of organic nitrates is the quick development of tolerance, which can only be overcome by intermittent dose interruptions. (View Highlight)
- Hydralazine’s exact working mechanism remains unclear, but probably relates to chelation of trace metals required for smooth-muscle contraction. Peripheral vasodilation with hydralazine is not uniform, favouring the coronary, cerebral, splanchnic, and renal circulations more than the skin and muscle beds (View Highlight)
- Effective arterial elastance (Ea) is the most accurate metric of LV afterload. It is defined as the LV end-systolic pressure over stroke volume and integrates both the resistive (i.e. downstream vascular resistance) and pulsatile (i.e. wave reflections) components of afterload (View Highlight)
- In patients with low CO and low stroke volume due to poor myocardial contractility indicated by a low end-systolic elastance (Ees), afterload is a major determinant of stroke volume, hence ventriculoarterial uncoupling. Lowering Ea with vasodilator therapy restores vascular coupling, resulting in a higher stroke volume with minimal impact on mean arterial pressure (View Highlight)
- The haemodynamic effects of vasodilator therapy when Ees is normal or only slightly reduced are completely different (Figure 2C and D). In this group with maintained ventriculoarterial coupling, afterload reduction has minimal impact on the stroke volume (View Highlight)
- the beneficial haemodynamic effects of vasodilator therapy are mainly expected in patients with low stroke volume, poor LV systolic function, and increased afterload because in this population they lead to an improvement in stroke volume and forward flow. (View Highlight)
- Although Ea can be approximated by 90% of the SBP over stroke volume, which suggests some dependency of afterload on SBP, stroke volume remains vital to the interpretation. When it is depressed, even low SBP may indicate substantially increased afterload (Ea) and ventriculoarterial uncoupling that is usually caused by maladaptive vasoconstriction (View Highlight)
- The ideal patient with AHF for treatment with vasodilators has a low stroke volume, low CO, elevated left-sided filling pressures, a relatively preserved right ventricle, and elevated to normal systemic vascular resistance (View Highlight)
- the true value of appropriately indicated vasodilator therapy most likely lays in stabilization of what is otherwise a progressive unstable condition through facilitating decongestion, preventing end-organ injury, enabling early optimization of medical therapy, avoiding the need for mechanical assist devices, and decreasing lung water to reduce surgical risk. (View Highlight)