Positron emission tomography using(18)F-fluoro-deoxyglucose and euglycaemic hyperinsulinaemic glucose clamp: optimal criteria for the prediction of recovery of post-ischaemic left ventricular dysfunction. Results from the European Community Concerted Action Multicenter study on use of(18)F-fluoro-deoxyglucose Positron Emission Tomography for the Detection of Myocardial Viability.

AIMS: To assess the accuracy of positron emission tomography to predict recovery of global cardiac function after revascularization in patients with coronary artery disease. METHODS AND RESULTS: One hundred and seventy-eight patients (157 male, 58+/-10 years) with coronary artery disease and left ventricular dysfunction (mean ejection fraction 39+/-14%) were enrolled in six European centres. They underwent a common protocol for the assessment of viability using(18)F-fluoro-2-deoxyglucose (FDG) positron emission tomography during a standardized euglycaemic hyperinsulinaemic glucose clamp before revascularization by either surgery (n=140) or angioplasty (n=38). Seven patients were excluded because of incomplete revascularization of a dysfunctional region. Based on the recovery of global ejection fraction 2-6 months after revascularization, patients were classified into two groups: 82 patients who had a >5% improvement in ejection fraction postoperatively, and 89 patients without postoperative ejection fraction improvement. Optimal cut-off points for postoperative improvement of global cardiac function were computed, using receiver operating curve analysis. The highest sensitivity (79%) and specificity (55%) for predicting postoperative ejection fraction improvement by positron emission tomography was found when three or more dysfunctional segments had a relative FDG uptake >45% of normal remote myocardium (overall accuracy 67%). CONCLUSIONS: In a large cohort of coronary patients with impaired ejection fraction, FDG positron emission tomography demonstrated high sensitivity and moderate specificity to predict improvement of cardiac function after coronary revascularization.

Time course of functional recovery after coronary artery bypass graft surgery in patients with chronic left ventricular ischemic dysfunction.

Chronic left ventricular (LV) ischemic dysfunction, a condition often referred to as myocardial hibernation, is associated in humans with ultrastructural alterations of the myocytes, including the loss of myofilaments and the accumulation of glycogen. Given the severity of these structural changes, contractile function is unlikely to resume immediately upon revascularization. Therefore, the aim of the present study was to assess the time course of functional improvement after successful revascularization as well as its potential structural correlates. We studied 32 patients with coronary disease and chronic LV ischemic dysfunction who underwent bypass surgery. Dynamic positron emission tomography with N-13 ammonia and F-18 deoxyglucose to assess myocardial perfusion and glucose metabolism was performed in 29 patients. In all patients, a transmural biopsy was harvested from the center of the dysfunctional area, to quantify the increase in extracellular matrix and the presence of structurally altered cardiomyocytes. LV function was serially measured by digitized 2-dimensional echocardiography before and at 10 days, 2 months, and 6 months after revascularization. The time course of recovery of regional function was estimated from the monoexponential decrease in dysfunctional wall motion score. At follow-up, 19 patients had improved LV function, whereas 13 patients showed persistent dysfunction. Before revascularization, reversibly dysfunctional segments had higher myocardial blood flow (82 +/- 29 vs 53 +/- 21 ml. (min. 100 g)(-1), p = 0.044), higher glucose uptake (40 +/- 16 vs 21 +/- 9 micromol. (min. 100 g)(-1), p = 0.001), and less increase in extracellular matrix (25 +/- 15% vs 46 +/- 17%, p = 0.0008) than segments with persistent dysfunction. The extent to which function recovered was positively correlated with myocardial blood flow and negatively correlated with the increase in the extracellular matrix. In patients with reversible dysfunction, the return of segmental function was progressive and followed a monoexponential time course with a median time constant of 23 days (range 6 to 78). The rate of recovery correlated best with the proportion of altered cardiomyocytes in the biopsy. The present study thus indicates that the recovery of regional and global LV function after successful revascularization is progressive and follows a monoexponential time course that is influenced by the extent of the structural changes affecting cardiomyocytes.

Myocardial blood flow, glucose uptake, and recruitment of inotropic reserve in chronic left ventricular ischemic dysfunction. Implications for the pathophysiology of chronic myocardial hibernation.

BACKGROUND: Previous work has documented that dysfunctional noninfarcted collateral-dependent myocardium, a condition typical of myocardial hibernation, exhibited almost normal resting perfusion. The present study was designed to test whether these observations could be extended to unselected patients with chronic dysfunction and a previous infarction. METHODS AND RESULTS: Dynamic positron emission tomographic imaging with [13N]ammonia and [18F]fluorodeoxyglucose (FDG) to assess myocardial perfusion and glucose uptake was performed in 39 patients with chronic anterior wall dysfunction undergoing coronary revascularization. Left ventricular function was evaluated by echocardiography before (at rest and during low-dose dobutamine infusion) and 5 months after revascularization. At follow-up, wall motion was improved in 24 patients and unchanged in 15 patients. Before revascularization, absolute myocardial blood flow was higher (84 +/- 27 versus 60 +/- 26 mL.min-1 x 100 g-1, P = .007) in reversibly compared with persistently dysfunctional segments. In segments with reversible dysfunction, values of myocardial blood flow were similar to those in the remote segments of the same patients or in anterior segments of normal volunteers. During glucose clamp, FDG uptake was higher (69 +/- 17% versus 49 +/- 18%, P < .01) but myocardial glucose uptake was not different (38 +/- 20 versus 29 +/- 19 mumol.min-1.100 g-1, P = NS) in reversibly compared with persistently dysfunctional segments. A flow-metabolism mismatch was present in 18 of 24 reversibly injured but absent in 10 of 15 persistently dysfunctional segments. With dobutamine, wall motion improved in 17 of 24 reversibly dysfunctional segments and did not change in 13 of 15 segments with persistent dysfunction. CONCLUSIONS: This study indicates that chronic but reversible ischemic dysfunction is associated with almost normal resting myocardial perfusion, with maintained FDG uptake, and with recruitable inotropic reserve. These data support the contention that chronic hibernation is not the consequence of a permanent reduction of transmural myocardial perfusion at rest.

Preoperative selection of patients with severely impaired left ventricular function for coronary revascularization. Role of low-dose dobutamine echocardiography and exercise-redistribution-reinjection thallium SPECT.

BACKGROUND: Both thallium imaging and low-dose dobutamine echocardiography have been proposed to predict the reversibility of left ventricular (LV) dysfunction in patients with coronary disease. The present study was designed to evaluate whether the use of these techniques during the preoperative assessment of coronary patients with depressed LV function can improve our ability to identify those likely to have improved LV function after surgery. METHODS AND RESULTS: Forty consecutive patients (age, 60 +/- 10 years) with coronary disease and an ejection fraction < or = 35% underwent dobutamine echocardiography (10 micrograms/kg per minute) and exercise-redistribution-reinjection thallium single photon emission computed tomography (SPECT) before coronary revascularization by bypass surgery (n = 33) or angioplasty (n = 7). Recovery of LV function was evaluated by echocardiography 5.3 +/- 2.4 months after revascularization. According to the changes in end-systolic volume and ejection fraction after revascularization, the patients were categorized into groups with (n = 19) and without (n = 21) postoperative functional improvement, defined as a > 5% increase in ejection fraction and > 10 mL decrease in end-systolic volume. Before revascularization, patients with improved postoperative function had smaller end-diastolic volume and less wall motion abnormalities than those with persistent dysfunction. They also showed greater improvement of wall motion score with dobutamine (6.1 +/- 2.4 versus 1.8 +/- 4.2 grades, P < .001) and smaller thallium defect score after exercise (38 +/- 12 versus 47 +/- 14 grades, P = .04). Discriminant analysis selected the improvement in wall motion score with dobutamine and baseline end-diastolic volume as independent predictors of postoperative recovery. Consideration of both parameters allowed prediction of functional outcome in 84% of the patients with and 81% of those without postoperative improvement. CONCLUSIONS: Among the parameters commonly available before surgery in coronary patients with depressed LV function, the maintenance of significant inotropic reserve, the severity of LV remodeling, and the magnitude of the perfusion defect after exercise can predict the reversal of LV dysfunction after revascularization.