Ventricular–Vascular Interaction in Heart Failure
Section snippets
Ventricular–arterial coupling
The influence of ventricular and vascular stiffness on net cardiovascular function is most easily appreciated in the pressure–volume plane. Ventricular systolic stiffness (contractility) is expressed as end-systolic elastance (Ees; Fig. 1), the slope of the end-systolic pressure–volume relationship [1]. Cardiac afterload is often conceived of as being equivalent to systolic blood pressure—a practice that can lead to erroneous conclusions and interpretations. Systemic blood pressures are
Deconstructing afterload
Ea is dominated by nonpulsatile load—systemic vascular resistance (SVR)—but it is also altered by artery stiffening to increase pulsatile load. Blood pressure pulsatility increases with aging and this is reflected in the pressure–volume diagram in the elderly individual (Fig. 1C) by the greater increase in systolic pressure throughout ejection [10], [12], [13], [14], [15], [16]. Because Ea is determined by Pes/SV, the greater the disparity between Pes and mean arterial pressure (ie, the more
Ventricular–arterial stiffening in heart failure with a preserved ejection fraction
In patients who have HFpEF, the Ea/Ees ratio decreases compared with younger individuals, but is similar to that of asymptomatic hypertensive elderly patients [13], [15], [21], [22]. Importantly, it still falls in a range where external work and efficiency are not likely compromised [9]. Although the ratio itself is reduced, the absolute value of both numerator and denominator are significantly elevated. Patients who have HFpEF thus have elevated vascular stiffness and increased ventricular
Mechanisms of ventricular–vascular stiffening
Ees is determined by active and passive muscle properties. Passive behavior is somewhat of a misnomer, because diastolic tone is regulated in part by calcium handling and also by qualitative (including posttranslational phosphorylation state) and quantitative changes in multiple sarcomeric proteins [24]. Diastolic stiffening is related to properties of myocyte size, chamber geometry, intra-sarcomeric protein composition, cytosolic and membrane distensibility, and extracellular matrix
Systolic effects
Table 1 summarizes the effects of ventriculoarterial stiffening. One major consequence is increased blood pressure lability and sensitivity to volume and vascular loading [13]. In a normal heart–artery system, an increase in EDV results in a given increase in end-systolic pressure (see Fig. 3A). In a typical HFpEF patient, however, even if the coupling ratio is normal the same change in EDV leads to an exaggerated change in blood pressure (see Fig. 3B). The pressure–volume area or stroke work
Ventricular–arterial stiffening and exercise reserve
Increases in ventricular and vascular stiffness affect cardiovascular reserve function with exercise stress. Warner and colleagues [51] studied the effects of losartan on exercise performance in 20 asymptomatic subjects who had echo-Doppler diastolic dysfunction and a hypertensive response to exercise, suggesting increased ventricular–vascular stiffness. Although losartan had no effect on resting blood pressure, it blunted the peak systolic pressure during exercise, increased the time to blood
Therapeutic strategies targeting stiffness
Ventricular–vascular stiffening can be treated with agents that acutely modulate ventricular systolic and diastolic performance, vascular smooth muscle tone, and endothelial function. Verapamil, which acutely reduces ventricular and vascular stiffness, improves exercise capacity in patients who have HFpEF, hypertrophic cardiomyopathy, and elderly subjects who have hypertension and hypertrophy [55], [56], [57]. A recent trial in older hypertensive patients found that verapamil led to significant
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