Dr. Sahebjami suggests that because our study used a rapid transient intervention to identify the physiologic contributors to resting left ventricular diastolic pressure, the results are not relevant to clinical situations. We respectfully disagree. The resting end-diastolic pressures of the left ventricle reflect both intrinsic properties of the heart and extrinsic forces from pericardial and interventricular interactions. The former links altered transmural pressure to volume changes; the latter is associated with no change in transmural pressure but rather with altered pressures at the same volume. Our use of a rapid right heart unloading technique (such as obstruction of inferior vena caval inflow) was aimed at temporally separating the two factors. Near-complete separation did exist for only several seconds, but it was sufficient to yield an accurate quantitative assessment of the external forces other than filling of the left heart chamber. Importantly, this physiologic finding is not an artifact of the particular intervention. It is more precisely and cleanly delineated, however, by use of a rapid intervention.

Many previous studies [1-4] support the notion that right heart filling can be gradually decreased to obtain stable reductions of external cardiac forces; left ventricular pressures can therefore be substantially decreased without commensurate changes in filling. For example, Alderman and Glantz [1] decreased diastolic pressures by 43% with nitroprusside while stroke volume was unchanged; end-diastolic volume decreased by only 14%. The reduction in left ventricular diastolic pressure at preserved preload was not caused by enhanced ventricular performance as Dr. Sahebjami seems to imply, but rather by a decline in the loads external to the left heart. As with our data, these stable responses were principally due to a downward displacement of the diastolic pressure-volume relation. It is not always easy to selectively reduce right heart load without compromising left ventricular filling and transmural pressures. However, gentle titration of pharmacologic agents that are selective for systemic and pulmonary venous beds will probably achieve this result. Our data provide a real physiologic and relevant target at which to aim because they quantify the component of resting measured pressure that is probably due to factors other than direct myocardial stretch within the left ventricle. Successful translation of our results to the routine clinical setting depends primarily on the choice of agents and the care with which they are administered.