Ventricular Systolic Stiffness Research Articles

Reduced renal function is associated with combined increases in ventricular-systolic stiffness and arterial load in patients undergoing cardiac catheterization for coronary artery disease

Although mildly reduced renal function is associated with increased risk for heart failure in patients with coronary artery disease (CAD), mechanisms underlying the association remain unclear. We tested the hypothesis that abnormal ventricular-arterial interaction may occur in mildly reduced renal function. We examined the relationships of the estimated glomerular filtration rate (eGFR) with various indices reflecting ventricular-arterial coupling [effective arterial elastance (the ratio of left ventricular (LV) end-systolic pressure to stroke volume, E (a)], LV end-systolic elastance (the ratio of LV end-systolic pressure to end-systolic volume, E (es)), and the total arterial compliance (the ratio of stroke volume to aortic pulse pressure)] and those of LV systolic and diastolic function [peak systolic and diastolic mitral annular velocities (S' and E') and the ratio of peak early diastolic mitral inflow to annular velocity (E/E')] in 320 consecutive patients who underwent cardiac catheterization for CAD and had normal (≥ 0.50) ejection fractions (EF). As eGFR decreased, E (a) and E (es) increased and total arterial compliance and E' decreased. eGFR did not correlate with E (a)/E (es), S', or E/E'. After adjusting for potential confounders, the findings were generally similar, but the correlation of eGFR with E' did not remain significant. In conclusion, reduced renal function may be associated with combined increases in ventricular-systolic stiffness and arterial load in known or suspected CAD patients with normal EF.

Ventricular–Vascular Stiffening in Patients With Repaired Coarctation of Aorta

Despite successful repair, patients with coarctation of the aorta (COA) often show persistent hypertension at rest and/or during exercise. Previous studies indicated that the hypertension is mainly due to abnormalities in the arterial bed and its regulatory systems. We hypothesized that ventricular systolic stiffness also contributes to the hypertensive state in these patients in addition to increased vascular stiffness. The study involved 43 patients with successfully repaired COA and 45 age-matched control subjects. Ventricular systolic stiffness (end systolic elastance) and arterial stiffness (effective arterial elastance) were measured invasively by ventricular pressure-area relationship during varying preload before and after beta-adrenergic stimulation. The mean systolic blood pressure was significantly higher with concomitant increases in both end systolic elastance and effective arterial elastance in patients with COA compared with control subjects (113.2+/-16.8 versus 91.0+/-9.1 mm Hg, 44.5+/-17.0 versus 19.2+/-6.7 mm Hg/mL/m(2), and 27.8+/-11.4 versus 20.2+/-4.8 mm Hg/mL/m(2), respectively; P<0.01 for each). End systolic elastance and effective arterial elastance of patients with COA showed exaggerated responses to beta-adrenergic stimulation, further amplifying blood pressure elevation. Quantification analyses assuming that ventricular systolic stiffness of patients with COA is equal to that of the control revealed that ventricular systolic stiffness accounts for approximately 50% to 70% of the elevated blood pressure in patients with COA. Furthermore, combined ventricular-arterial stiffening amplified systolic pressure sensitivity to increased preload during abdominal compression and limited stroke volume gain/relaxation improvement induced by beta-adrenergic stimulation. Increased ventricular systolic stiffness, coupled with increased arterial stiffness, plays important roles in hypertension in patients with repaired COA. Thus, ventricular systolic stiffness is a potentially suitable target for reduction of blood pressure and improvement of prognosis of patients with COA.

Mechanisms of Oxygen Demand/Supply Balance in the Right Ventricle

Few studies have investigated factors responsible for the O2 demand/supply balance in the right ventricle. Resting right coronary blood flow is lower than left coronary blood flow, which is consistent with the lesser work of the right ventricle. Because right and left coronary artery perfusion pressures are identical, right coronary conductance is less than left coronary conductance, but the signal relating this conductance to the lower right ventricular O2 demand has not been defined. At rest, the left ventricle extracts approximately 75% of the O2 delivered by coronary blood flow, whereas right ventricular O2 extraction is only ~50%. As a result, resting right coronary venous PO2 is approximately 30 mm Hg, whereas left coronary venous PO2 is approximately 20 mm Hg. Right coronary conductance does not sufficiently restrict flow to force the right ventricle to extract the same percentage of O2 as the left ventricle. Endogenous nitric oxide impacts the right ventricular O2 demand/supply balance by increasing the right coronary blood flow at rest and during acute pulmonary hypertension, systemic hypoxia, norepinephrine infusion, and coronary hypoperfusion. The substantial right ventricular O2 extraction reserve is used preferentially during exercise-induced increases in right ventricular myocardial O2 consumption. An augmented, sympathetic-mediated vasoconstrictor tone blunts metabolically mediated dilator mechanisms during exercise and forces the right ventricle to mobilize its O2 extraction reserve, but this tone does not limit resting right coronary flow. During exercise, right coronary vasodilation does not occur until right coronary venous PO2 decreases to approximately 20 mm Hg. The mechanism responsible for right coronary vasodilation at low PO2 has not been delineated. In the poorly autoregulating right coronary circulation, reduced coronary pressure unloads the coronary hydraulic skeleton and reduces right ventricular systolic stiffness. Thus, normal right ventricular external work and O2 demand/supply balance can be maintained during moderate coronary hypoperfusion.

Right coronary pressure modulates right ventricular systolic stiffness and oxygen consumption.

The low transmural pressure of the thin right ventricular (RV) wall may render it responsive to right coronary (RC) pressure-induced changes in systolic stiffness and account for the dependence of RV MVO2 on RC pressure (RCP). In eight dogs anesthetized with pentobarbital and fentanyl, RCP was lowered from the baseline to 30 mmHg in 10 mmHg steps by adjusting an occluder on the proximal RC. Myocardial segment length and isometric developed force were measured, and the slope of the force-length curve during ejection period (delta F/ delta SL) was used as an index of systolic myocardial stiffness. MVO2 was calculated from RC flow and arteriovenous O2 difference. As RCP was varied from 120 to 40 mmHg with positive lactate uptake, RC flow, maximum developed force (Fmax), delta F, and MVO2 decreased linearly, whereas end-diastolic length, delta SL, and other hemodynamic variables stayed constant. Thus, RV systolic stiffness fell linearly with RC pressure. When RCP was further lowered from 40 to 30 mmHg, Fmax and delta F continued to fall, end-diastolic segment length and right atrial pressure increased significantly, delta SL and RV dp/dtmax fell significantly, and delta F/delta SL reached its lowest value. RV systolic stiffness was 22% of previously reported left ventricular systolic stiffness for coronary perfusion pressure at 100 mmHg, and varied less steeply with coronary pressure. (1) Reductions in RV systolic stiffness preserve delta SL as coronary pressure is reduced over a wide range. (2) The resulting increase in RV efficiency reduces oxygen demand as oxygen supply is reduced, so ischemia is avoided. (3) RV systolic stiffness is much less than left ventricular stiffness, consistent with their anatomical and functional differences.

Coupled systolic-ventricular and vascular stiffening with age: Implications for pressure regulation and cardiac reserve in the elderly

Objectives. We tested the hypothesis that age-related arterial stiffening is matched by ventricular systolic stiffening, and that both enhance systolic pressure sensitivity to altered cardiac preload.Background. Arterial rigidity with age likely enhances blood pressure sensitivity to ventricular filling volume shifts. Tandem increases in ventricular systolic stiffness may also occur and could potentially enhance this sensitivity.Methods. Invasive left ventricular pressure-volume relations were measured by conductance catheter in 57 adults aged 19 to 93 years. Patients had normal heart function and no cardiac hypertrophy and were referred for catheterization to evaluate chest pain. Twenty-eight subjects had normal coronary angiography and hemodynamics, and the remaining had either systolic hypertension or coronary artery disease without infarction. Data recorded at rest and during transient preload reduction by inferior vena caval obstruction yielded systolic and diastolic left ventricular chamber and effective arterial stiffness and pulse pressure.Results. Left ventricular volumes, ejection fraction and heart rate were unaltered by age, whereas vascular load and stiffening increased (p < 0.008). Arterial stiffening (Ea) was matched by increased ventricular systolic stiffness (Ees): Ees=0.91·Ea+0.53, (r = 0.50, p < 0.0001), maintaining arterial-heart interaction (Ea/Eesratio) age-independent. Ventricular systolic and diastolic stiffnesses correlated (r = 0.51, p < 0.0001) and increased with age (p < 0.03). Both ventricular and vascular stiffening significantly increased systolic pressure sensitivity to cardiac preload (p < 0.006).Conclusions. Arterial stiffening with age is matched by ventricular systolic stiffening even without hypertrophy. The two effects contribute to elevating systolic pressure sensitivity to altered chamber filling. In addition to recognized baroreflex and autonomic dysfunction with age, combined stiffening could further enhance pressure lability with diuretics and postural shifts in the elderly.

Left ventricular active stiffness: dependency on time and inotropic state.

Left ventricular systolic stiffness was measured by rapidly changing ventricular volume (within 7 ms) of isovolumically contracting isolated rabbit hearts. Instantaneous pressure-volume relations were found to be linear with slopes that depended upon the moment during contraction at which the volume change was induced. These slopes were proportional to the total pressure developed in the ventricle just prior to the volume change. The same was found when the time course of pressure was influenced by changing the Ca++ content of the perfusate. An influence, however, also could be detected when end-diastolic volume was changed. At the same pre-release pressure a greater volume caused a decrease of active stiffness. The results indicate the possibility of an active component in ventricular systolic stiffness.