Afterload-induced left ventricular diastolic dysfunction during myocardial ischaemia and reperfusion.

NEW FINDINGS: What is the central question of this study? While the load dependence of the diastolic function is established for the normal heart, little is known about the response of the acutely ischaemic and reperfused myocardium to alterations in afterload. What is the main finding and its importance? Using a model that simulates the clinical scenario of acute ischaemia-reperfusion, we show that increased afterload aggravates diastolic dysfunction during both acute ischaemia and reperfusion. In addition, increased afterload induces diastolic dyssynchrony, which might be the underlying mechanism of the diastolic dysfunction of the ischaemic myocardium. These findings provide us with new information regarding how better to manage patients who undergo revascularization therapy after acute myocardial infarction. The effects of changes in left ventricular (LV) afterload on diastolic function of acutely ischaemic and reperfused myocardium have not been studied in depth. We examined the following factors: (i) the consequences of increasing the LV afterload on LV diastolic function during acute ischaemia and reperfusion; (ii) whether the myocardial response to afterload elevation is stable throughout a 2 h reperfusion period; and (iii) the role of LV wall synchrony in the development of afterload-induced diastolic dysfunction. We instrumented 12 anaesthetized, open-chest pigs with Millar pressure catheters and piezoelectric crystals before ligating mid-left anterior descending coronary artery for 1 h, followed by reperfusion for 2 h. Six of the animals survived throughout the 2 h of reperfusion, and their data were used for comparisons across the different experimental phases. Left ventricular afterload was increased by inflating an intra-aortic balloon. Data were recorded at baseline, after 20 min of coronary occlusion and at 30 and 90 min of myocardial reperfusion. The increased afterload for 2 min lengthened the isovolumic relaxation during ischaemia and during early and late reperfusion but had no significant effect on isovolumic relaxation before coronary artery occlusion. Increasing the afterload aggravated LV diastolic dyssynchrony during coronary artery occlusion, but not during reperfusion. The afterload-induced prolongation of isovolumic relaxation was positively correlated with afterload-induced diastolic dyssynchrony. These observations indicate that, during myocardial ischaemia and throughout reperfusion, LV diastolic function is afterload dependent. Afterload-induced diastolic dyssynchrony might be an underlying mechanism of diastolic dysfunction during acute ischaemia.

Elevated left ventricular filling pressures can be estimated with accuracy by a new mathematical model.

BACKGROUND: Although the clinical assessment of jugular venous pressure (JVP) provides accurate estimate of right atrial pressure (RAP), there is no reliable non-invasive method for assessing pulmonary capillary wedge pressure (PCWP). Our objective was to evaluate the sensitivity and specificity for detecting elevated left ventricular filling pressures using a model for PCWP estimation, based on the clinical assessment of RAP and association between RAP and PCWP, which is unique for each patient, identified in a recent right heart catheterization (RHC). METHODS: The study included 377 patients (age, 54.3 ± 13 years) with heart failure with reduced ejection fraction (left ventricular ejection fraction of 30.5 ± 10.8%) who underwent 2 RHCs within 1 year. In Group A (189 randomly selected patients), hemodynamic variables with significant correlation with the current wedge pressure (PCWP(2)) were identified and an equation estimating PCWP(2) based on these variables was formed. The validity of the equation was evaluated in the remaining 188 patients (Group B). The equation was also evaluated, prospectively in 39 new patients where RAP was estimated clinically, by physicians blinded to the results of the RHC. RESULTS: PCWP(2) in Group A correlated with RAP(1), systolic pulmonary artery pressure (SPAP(1)), and PCWP(1) of the first RHC and with RAP(2) and SPAP(2) of the second. The equation is PCWP(2) = [3RAP(2) + (PCWP(1) - RAP(1)) + 4]/2. In Group B, the sensitivity and specificity of estimated PCWP(2) for diagnosis of elevated LV filling pressures (invasive values >18 mm Hg) was significant, reflected by an area under the curve (AUC) of 0.954 (p < 0.001). In the prospective sub-group, where JVP was entered in the formula as an estimate of RAP(2), correlation between estimated and measured PCWP(2) was r = 0.803 (p < 0.001). CONCLUSIONS: The current PCWP of a patient with heart failure can be estimated accurately by a simple equation based on measurements of a previous RHC and the current value of clinically assessed JVP.