No abstract

Whereas end-systolic and end-diastolic pressure-volume relations (ESPVR, EDPVR) characterize left ventricular (LV) pump properties, clinical utility of these relations has been hampered by the need for invasive measurements over a range of pressure and volumes. We propose a single-beat approach to estimate the whole EDPVR from one measured volume-pressure (Vm and Pm) point. Ex vivo EDPVRs were measured from 80 human hearts of different etiologies (normal, congestive heart failure, left ventricular assist device support). Independent of etiology, when EDPVRs were normalized (EDPVRn) by appropriate scaling of LV volumes, EDPVRns were nearly identical and were optimally described by the relation EDP = An.EDV (Bn), with An = 28.2 mmHg and Bn = 2.79. V0 (the volume at the pressure of approximately 0 mmHg) was predicted by using the relation V0 = Vm.(0.6 - 0.006.Pm) and V30 by V30 = V0 + (Vm,n - V0)/(Pm/An) (1/Bn). The entire EDPVR of an individual heart was then predicted by forcing the curve through Vm, Pm, and the predicted V0 and V30. This technique was applied prospectively to the ex vivo human EDPVRs not used in determining optimal An and Bn values and to 36 in vivo human, 12 acute and 14 chronic canine, and 80 in vivo and ex vivo rat studies. The root-mean-square error (RMSE) in pressure between measured and predicted EDPVRs over the range of 0-40 mmHg was < 3 mmHg of measured EDPVR in all settings, indicating a good predictive value of this approach. Volume-normalized EDPVRs have a common shape, despite different etiology and species. This allows the entire curve to be predicted by a new method with a potential for noninvasive application. The results are most accurate when applied to groups of hearts rather than to individual hearts.

Background-Left ventricular assist devices (LVADs) induce reverse remodeling of the failing heart except for the extracellular matrix, which exhibits additional pathophysiological changes, although their mechanisms and functional consequences are unknown. Methods and Results-Hearts were obtained at transplant from patients with idiopathic dilated cardiomyopathy (DCM) not requiring LVAD support (nϭ30), patients requiring LVAD support (nϭ16; LVAD duration, 145Ϯ33 days), and 5 nonfailing hearts. Left (LV) and right ventricular (RV) ex vivo pressure-volume relationships were measured, and chamber and myocardial stiffness constants were determined. Myocardial tissue content of total and cross-linked collagen, collagen types I and III, MMP-1, MMP-9, TIMP-1, and angiotensin (Ang) I and II were measured. LV size, mass, and myocyte diameter decreased after LVAD compared with DCM without LVAD (PϽ0.05). Total and cross-linked collagen and ratio of type I to III collagen increased in DCM compared with nonfailing hearts and increased further after LVAD (PϽ0.05 versus DCM and nonfailing). Concomitantly, chamber and myocardial stiffness increased with LVAD. The ratio of MMP-1 to TIMP-1 increased in DCM and almost normalized after LVAD, favoring decreased collagen degradation. Tissue Ang I and II also increased during LVAD. There was no significant change in the RV of LVAD-supported heart compared with DCM. Conclusions-LVAD support increases LV collagen cross-linking and the ratio of collagen type I to III, which is associated with increased myocardial stiffness. Decreased tissue MMP-1-to-TIMP-1 ratio (decreased degradation) and increased Ang levels (stimulants of synthesis) are likely mechanisms for these changes. Lack of significant effects on the RV suggest that hemodynamic unloading of the LV (not provided to the RV) might be the primary factor that regulates these extracellular matrix changes. (Circulation. 2005;112:364-374.)Key Words: cardiomyopathy Ⅲ collagen Ⅲ heart-assist devices Ⅲ heart failure Ⅲ metalloproteinases L eft ventricular assist devices (LVADs) provide mechanical support for the end-stage failing human heart and have been used as a bridge to cardiac transplantation. We have demonstrated that LVAD support is associated with normalization of diastolic chamber properties as indexed by the passive pressure-volume relation. [1][2][3] This normalization of diastolic properties results from a regression of myocyte hypertrophy, including reduced LV mass, wall thickness, and myocyte diameter. 4,5 In addition, LVAD support has been associated with a trend toward normalization in cardiomyocyte function, 6 calcium cycling properties, 7 and expression of various genes. 8 In addition to changes in intrinsic myocardial properties, LVAD use is associated with changes in the characteristics and metabolism of the extracellular matrix (ECM). However, unlike almost all other aspects of reverse remodeling of the myocardium and ventricular chamber, the ECM changes do not uniformly reflect a return toward normal conditions. 9 -11...

The end-diastolic pressure-volume relation (EDPVR) is an important descriptor of passive cardiac pump properties. However, clinical utility has been limited by the need for measurement of pressures and volumes over relatively large ranges. In this protocol, we describe an algorithm to estimate the entire EDPVR in humans from a single measured pressure-volume (P-V) point. This algorithm was developed from observations made from accurately measured EDPVRs of human hearts, which indicated that when normalized by appropriate left ventricular volume scaling (to arrive at volume-normalized EDPVRs, EDPVR(n)) EDPVR(n)s were nearly identical in all patients. In this protocol, we demonstrate how to use EDPVR(n)s to predict a second P-V point on the EDPVR, in which case the entire EDPVR can then be predicted. With recent advances for accurate noninvasive measurement of end-diastolic pressure and volumes, this protocol permits the assessment of passive properties in a broader range of research and clinical settings.

The conductance catheter provides a continuous measure of right ventricular volume that was used to detect changes in right ventricular contractile state in pigs. This represents a promising and much needed method for the evaluation of right ventricular function.