ischemia and interstitial fibrosis, impair myocardial relaxation, and reduce ventricular compliance.588,593 Arterial stiffening is also associated with left ventricular systolic function In adults with594 and without589 coronary artery disease, aortic and conduit arterial stiffness has also been inversely related to long-axis systolic left ventricular function In adults with coronary artery disease, an inverse relationship between brachial-ankle pulse-wave velocity and left ventricular ejection fraction has been reported.594 Effect of Ventricular Dysfunction on the Systemic Circulation Systemic ventricular dysfunction with development of heart failure is associated with sympathoadrenal activation, activation of the renin-angiotensin system, systemic inflammation, and increased oxidative stress.595,596 Although left ventricular dysfunction occurs most commonly in acquired conditions, such as ischemic heart disease and dilated cardiomyopathy, the syndrome of heart failure related to systemic ventricular dysfunction in congenital heart patients is increasingly recognized.597,598 In the expanding population of older children and adults with congenital heart disease, heart failure has become an important problem.599 Arterial dysfunction in adults with chronic heart failure is well documented In these patients, increased brachioradial arterial pulse-wave velocity600 and reduced radial, carotid, and aortic distensibility have also been shown.601 Progressive arterial stiffening is found in adults with worsening New York Heart Association functional class.600 Furthermore, in adults with heart failure, reduced endothelium-dependent increase in forearm blood flow602–604 and dilation of femoral arteries605 have been demonstrated Several mechanisms may account for systemic arterial dysfunction in heart failure Increased degradation of nitric oxide occurs in heart failure due to its inactivation by reactive oxygen species.606 Increased angiotensin-converting enzyme activity in heart failure increases the breakdown of kinins, which may further lead to a reduction in nitric oxide release.607 The increase in endothelin1, which is related to severity of hemodynamic disturbance and symptoms,608–610 augments the vascular tone and arterial stiffness in adults with heart failure Elevation of circulating proinflammatory cytokine tumor necrosis factor-α in heart failure611 contributes to arterial dysfunction through increased production of reactive oxygen species, blockage of activation of endothelial nitric oxide synthase, and direct degradation of endothelial nitric oxide messenger RNA.612,613 Ventriculoarterial Coupling It is obvious from the preceding discussions that reciprocal interactions between the arterial system and systemic ventricle, if unfavorable, may set up a vicious cycle (Fig 74.13) Interactions between the left ventricle and the systemic circulation have been studied under frameworks of ventriculoarterial coupling.614–617 Analysis of the forward- and backward-traveling wave energy has also been used to assess ventriculoarterial interaction.618,619 The framework proposed by Sunagawa et al (see also Chapter 76) has been used most commonly by far for the analysis of ventriculoarterial coupling in humans in health and disease.614 In this framework, the systemic ventricle and the arterial system are considered as two elastic chambers (Fig 74.14) Coupling is studied in terms of the pressure-volume relationship (Fig 74.15) The volume of blood transferred from one chamber to the other is determined by their relative elastance, expressed as the ratio of Ea to Ees FIG 74.13 Unfavorable interactions in the presence of arterial dysfunction between the systemic circulation and left ventricle The setting up of vicious cycles (dashed lines) may aggravate preexisting arterial and ventricular dysfunction