Effects of GIK (glucose-insulin-potassium) on stress-induced myocardial ischaemia.

Despite the evidence in experimental animal models that insulin, or GIK (glucose-insulin-potassium), improves left ventricular function and perfusion during both acute and chronic ischaemia, clinical studies have generated conflicting results. We tested the hypothesis that pretreatment with GIK attenuates the vascular and functional effects of stress-induced myocardial ischaemia in humans. Twenty-two patients with evidence of inducible myocardial ischaemia were enrolled; 11 patients with normal ventricular function underwent two dipyridamole echocardiography tests, and 11 with regional contractility defects from previous myocardial infarction were submitted to two ECG exercise tests combined with 201Tl myocardial perfusion scintigraphy; the tests were preceded by 60 min of either normal saline or an isoglycaemic GIK infusion. On a stress echocardiogram, a 30% reduction in the severity of ischaemia was observed. On ECG ergometry, GIK infusion slightly increased the time to ischaemia (+0.6 min, P=0.07); however, the higher workload (+8%, P=0.07) was achieved at a similar rate-pressure plateau. On scintigraphy, an increase in ischaemic segments (+48%, P<0.001) was imaged mainly at the expense of viable (but non-ischaemic) and non-viable segments, which were reduced by 60%. GIK affected stress-induced left ventricular underperfusion only marginally (GIK: 39.7+/-2.5 compared with saline: 35.4+/-2.2 units, P<0.05), but significantly improved its acute reversibility (-42+/-4 compared with -25+/-4%, P<0.001). We conclude that GIK pretreatment attenuates the effect of ischaemia on myocardial contractility, slightly improves exercise tolerance and causes a more rapid and diffuse recovery of post-ischaemic reperfusion.

Prognostic value of combined perfusion and function by stress technetium-99m sestamibi gated SPECT myocardial perfusion imaging in patients with suspected or known coronary artery disease.

The incremental prognostic value of combined regional wall motion and perfusion over perfusion alone by gated single-photon emission computed tomographic myocardial perfusion scintigraphy has not been evaluated. Of the 402 consecutive patients who underwent stress single-photon emission computed tomographic myocardial perfusion scintigraphy for suspected myocardial ischemia, we identified 333 patients (217 men, mean age 63 +/- 10 years; exercise in 249 and dipyridamole adminstered to 84). Visual scoring of perfusion images and regional wall motion used 20 segments and a scale of 0 to 4. Resting and poststress left ventricular ejection fraction was automatically generated. On follow-up (median 13 months), 30 hard cardiac events (17 cardiac deaths, 13 nonfatal acute myocardial infarctions) and 66 total cardiac events (including hard events, 26 with unstable angina, and 10 who underwent late revascularization) occurred. After adjustment for prescan information, the best independent predictors of hard events were summed stress score for wall motion (Wald's chi-square 8.3, p <0.004) and several vascular territories with ischemia by perfusion/function (Wald's chi-square 6.2, p <0.01). The strongest predictors of all cardiac events were the number of ischemias (Wald's chi-square 32.1, p <0.0001) and the number of ischemic vascular territories by perfusion (Wald's chi-square 13.1, p <0.0001). Addition of function data to the combined model of perfusion data yielded an incremental value of 26% for predicting hard events but not for all events. In conclusion, the assessment of combined perfusion/function provides incremental prognostic information for further hard events with perfusion data alone; perfusion data best predict all cardiac events.

Predicting revascularization outcome in patients with coronary artery disease and left ventricular dysfunction (data from the SEMINATOR study).

A main goal of revascularization in patients with chronic ischemic cardiomyopathy is to improve global left ventricular (LV) function. This study aimed to verify whether it is possible to predict an increase in LV ejection fraction (EF) after revascularization on the basis of the extent of LV asynergy, myocardial viability, and revascularization completeness. We studied 77 patients with chronic LV ischemic dysfunction using baseline resting and nitrate-enhanced technetium-99m sestamibi single-photon emission computed tomography. Regional wall motion and global LVEF were assessed with echocardiography before and after revascularization, which was complete in 51 patients and incomplete in 26. The number of viable asynergic segments included in revascularized coronary artery territories was the strongest predictor of significant (> or = 5 EF U) functional improvement in univariate discriminant analysis. According to multivariate stepwise discriminant analysis, this parameter, together with the number of baseline asynergic segments, allowed the detection of patients with significant LVEF improvement with 75% accuracy. With use of a multivariate regression model, including the 2 mentioned variables, the measure of postrevascularization LVEF increase could be accurately quantified (R(2) 0.43, p <0.000001). In conclusion, this study suggests that the severity of baseline asynergy, the extent of myocardial viability, and the completeness of revascularization are the main determinants of postrevascularization functional recovery in patients with LV ischemic dysfunction, and that on the basis of these variables it is possible to predict the measure of LVEF increase.

Usefulness of dobutamine Tc-99m sestamibi-gated single-photon emission computed tomography for prediction of left ventricular ejection fraction outcome after coronary revascularization for ischemic cardiomyopathy.

Gated single-photon emission computed tomography (SPECT) imaging allows analysis of myocardial perfusion and assessment of baseline global and regional left ventricular (LV) function and their changes during low-dose dobutamine infusion. The study examined whether the changes in LV ejection fraction induced by dobutamine and evaluated using technetium-99m sestamibi- gated SPECT predict the evolution of ejection fraction after revascularization in patients with ischemic cardiomyopathy. Thirty-seven patients underwent resting and dobutamine nitrate-enhanced sestamibi-gated SPECT before revascularization and baseline-resting sestamibi gated SPECT after intervention to assess global functional changes. A postrevascularization improvement in ejection fraction > or =5 U was defined as significant. At follow-up, ejection fraction increased significantly in 19 patients. According to receiver-operating characteristic curve analysis, an increase in ejection fraction > or =5 U during dobutamine was the optimal cutoff value for predicting a significant postrevascularization improvement, with 79% sensitivity, 78% specificity, and 78% accuracy. A significant correlation was found between dobutamine and postrevascularization ejection fraction (r = 0.85; p <0.0001). The increase in ejection fraction during dobutamine is a good predictor of an improvement in ejection fraction after revascularization. This represents another important diagnostic contribution obtained using gated SPECT imaging for the assessment of myocardial viability in patients with ischemic cardiomyopathy.

Can the reversible regional wall motion abnormalities on stress gated Tc-99m sestamibi SPECT predict a future cardiac event?

BACKGROUND: Myocardial stunning has recently been demonstrated by use of stress gated technetium 99m sestamibi single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy. However, its prognostic value is less well determined. The aim of this study was to investigate the prognostic value of reversible regional wall motion abnormalities (RWMAs). METHODS AND RESULTS: We studied 303 consecutive subjects with known or suspected coronary artery disease who underwent 2-day stress-rest gated Tc-99m sestamibi SPECT and were followed up for 19 +/- 16 months. Clinical and test-derived variables were evaluated to predict cardiac death, nonfatal myocardial infarction (MI), unstable angina, and early or late coronary revascularization. Reversible RWMAs were identified in 102 patients. On Cox analysis, the presence, site, degree, and extent of reversible RWMAs did not identify an adverse outcome, except in patients without prior MI. After adjustment for prescan data, the strongest predictors of hard events and all cardiac events were poststress RWMAs and the amount of ischemia. The addition of poststress RWMAs to the combined model of prescan and perfusion data yielded incremental prognostic value. CONCLUSION: Poststress RWMAs and ischemia by perfusion were the most powerful predictive parameters of cardiac events. However, myocardial stunning should always be considered, particularly in patients without prior MI and in the referral of patients for early revascularization.

Low-dose dobutamine nitrate-enhanced technetium 99m sestamibi gated SPECT versus low-dose dobutamine echocardiography for detecting reversible dysfunction in ischemic cardiomyopathy.

BACKGROUND: The simultaneous assessment of perfusion and function with the use of technetium 99m sestamibi gated single photon emission computed tomography (SPECT) is helpful for the detection of myocardial viability, but its value in comparison with more established methods is not yet defined. METHODS AND RESULTS: This study compared low-dose dobutamine (LDD) nitrate-enhanced gated SPECT with LDD echocardiography for predicting recovery of regional ventricular function after revascularization in 25 patients with ischemic cardiomyopathy. In both studies, regional function (wall motion and thickening) at rest, during inotropic stimulation, and after revascularization was scored by a 4-point scale. In LDD echocardiography, the prediction of reversible dysfunction was based on the recognition of contractile reserve in asynergic (hypokinetic or a-dyskinetic) segments. In LDD gated sestamibi SPECT, reversible dysfunction was predicted on the basis of perfusion quantification (sestamibi uptake >or= 50%) in a-dyskinetic segments and on the basis of contractile reserve in hypokinetic segments. LDD echocardiography predicted reversible dysfunction with sensitivity, specificity, and global accuracy of 57%, 85%, and 75%, respectively. The sensitivity and specificity of LDD gated SPECT for identifying dysfunctional segments capable of functional recovery were 77% and 88%, respectively, with a diagnostic accuracy of 84% (P <.02 vs LDD echocardiography). CONCLUSIONS: The combined use of 2 different markers of viability, such as cellular integrity in a-dyskinetic segments and contractile reserve in hypokinetic segments, as permitted by LDD gated sestamibi SPECT, showed higher predictive accuracy for reversible dysfunction than the assessment of contractile reserve in all asynergic segments with LDD echocardiography.