Frans C. Visser

Accuracy of currently available techniques for prediction of functional recovery after revascularization in patients with left ventricular dysfunction due to chronic coronary artery disease: comparison of pooled data.

OBJECTIVES This study evaluated the relative merits of the most frequently used techniques for predicting improvement in regional contractile function after coronary revascularization in patients with left ventricular dysfunction due to chronic coronary artery disease. BACKGROUND Several techniques have been proposed for predicting improvement in regional contractile function after revascularization, including thallium-201 (Tl-201) stress-redistribution-reinjection, Tl-201 rest-redistribution, fluorine-18 fluorodeoxyglucose with positron emission tomography, technetium-99m sestamibi imaging and low dose dobutamine echocardiography (LDDE). METHODS A systematic review of all reports on prediction of functional recovery after revascularization in patients with chronic coronary artery disease (published between 1980 and March 1997) revealed 37 with sufficient details for calculating the sensitivity and specificity of each imaging modality. From the pooled data, 95% and 99% confidence intervals were also calculated. RESULTS Sensitivity for predicting regional functional recovery after revascularization was high for all techniques. The specificity of both Tl-201 protocols was significantly lower (p < 0.05) and LDDE significantly higher (p < 0.01) than that of the other techniques. CONCLUSIONS Pooled analysis of 37 studies showed that although all techniques accurately identify segments with improved contractile function after revascularization, the Tl-201 protocols may overestimate functional recovery. The evidence available thus far indicates that LDDE appears to have the highest predictive accuracy.

Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial

BACKGROUND A high plasma homocysteine concentration is associated with increased risk of atherothrombotic disease. We investigated the effects of homocysteine-lowering treatment (folic acid plus vitamin B6) on markers of subclinical atherosclerosis among healthy siblings of patients with premature atherothrombotic disease. METHODS We did a randomised, placebo-controlled trial among 158 healthy siblings of 167 patients with premature atherothrombotic disease. 80 were assigned placebo and 78 were assigned 5 mg folic acid and 250 mg vitamin B6 daily for 2 years. The primary endpoint was the development or progression of subclinical atherosclerosis as estimated from exercise electrocardiography, the ankle-brachial pressure index, and carotid and femoral ultrasonography. FINDINGS Ten participants in the treatment group, and 14 in the placebo group dropped out. Vitamin treatment, compared with placebo, was associated with a decrease in fasting homocysteine concentration (from 14.7 to 7.4 micromol/L vs from 14.7 to 12.0 micromol/L), and in postmethionine homocysteine concentration (from 64.9 to 34.9 micromol/L vs from 64.8 to 50.3 micromol/L). It was also associated with a decreased rate of abnormal exercise electrocardiography tests (odds ratio 0.40 [0.17-0.93]; p=0.035). There was no apparent effect of vitamin treatment on ankle-brachial pressure indices (0.87 [0.56-1.33]), or on carotid and peripheral-arterial outcome variables (1.02 [0.26-4.05] and 0.86 [0.47-1.59], respectively). INTERPRETATION Homocysteine-lowering treatment with folic acid plus vitamin B6 in healthy siblings of patients with premature atherothrombotic disease is associated with a decreased occurrence of abnormal exercise electrocardiography tests, which is consistent with a decreased risk of atherosclerotic coronary events.

Prediction of recovery of myocardial dysfunction after revascularization comparison of fluorine-18 fluorodeoxyglucose/thallium-201 SPECT, thallium-201 stress-reinjection SPECT and dobutamine echocardiography

OBJECTIVES We compared three techniques to predict functional recovery after revascularization. BACKGROUND Recently, fluorine-18 (F-18) fluorodeoxyglucose in combination with single-photon emission computed tomography (SPECT) has been proposed to identify viable myocardium, Thallium-201 reinjection and low dose dobutamine echocardiography are used routinely for this purpose. METHODS Seventeen patients (mean [+/- SD] left ventricular ejection fraction 36 +/- 11%) were studied. Regional and global ventricular function were evaluated before and 3 months after revascularization by echocardiography and radionuclide ventriculography, respectively. Myocardial F-18 fluorodeoxyglucose uptake (during hyperinsulinemic glucose clamping) was compared with rest perfusion assessed with early thallium-201 SPECT. On a separate day, low dose dobutamine echocardiography and post-stress thallium-201 reinjection SPECT were simultaneously performed. RESULTS The sensitivities for F-18 fluorodeoxyglucose/thallium-201, thallium-201 reinjection and low dose dobutamine echocardiography to assess recovery were 89%, 93% and 85%, respectively; specificities were 77%, 43% and 63%, respectively. Stepwise logistic regression indicated that F-18 fluorodeoxyglucose/ thallium-201 was the best predictor. In hypokinetic segments, the combination of F-18 fluorodeoxyglucose/thallium-201 and low dose dobutamine echocardiography was the best predictor. Global function improved (left ventricular ejection fraction increased > 5%) in 6 patients and remained unchanged in 11. All three techniques correctly identified five of six patients with improvement. Fluorine-18 fluorodeoxyglucose/thallium-201 identified all patients without improvement; low dose dobutamine echocardiography identified 9 of 11 without improvement; and thallium-201 reinjection identified 6 of 11 patients without improvement. CONCLUSIONS Fluorine-18 fluorodeoxyglucose/thallium-201 SPECT was superior to the other techniques in assessing functional recovery. Integration of metabolic and functional data is necessary, particularly in hypokinesia, for optimal prediction of improvement of regional function.

Myocardial viability in chronic ischemic heart disease: Comparison of contrast-enhanced magnetic resonance imaging with 18F-fluorodeoxyglucose positron emission tomography

OBJECTIVES We sought to compare contrast-enhanced magnetic resonance imaging (ceMRI) with nuclear metabolic imaging for the assessment of myocardial viability in patients with chronic ischemic heart disease and left ventricular (LV) dysfunction. BACKGROUND Contrast-enhanced MRI has been shown to identify scar tissue in ischemically damaged myocardium. METHODS Twenty-six patients with chronic coronary artery disease and LV dysfunction (mean ejection fraction 31 +/- 11%) underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET), technetium-99m tetrofosmin single-photon emission computed tomography (SPECT), and ceMRI. In a 17-segment model, the segmental extent of hyperenhancement (SEH) by ceMRI, defined as the relative amount of contrast-enhanced tissue per myocardial segment, was compared with segmental FDG and tetrofosmin uptake by PET and SPECT. RESULTS In severely dysfunctional segments (n = 165), SEH was 9 +/- 14%, 33 +/- 25% (p < 0.05), and 80 +/- 23% (p < 0.05) in segments with normal metabolism/perfusion, metabolism/perfusion mismatch, and matched defects, respectively. Segmental glucose uptake by PET was inversely correlated to SEH (r = -0.86, p < 0.001). By receiver operator characteristic curve analysis, the area under the curve was 0.95 for the differentiation between viable and non-viable segments. At a cutoff value of 37%, SEH optimally differentiated viable from non-viable segments defined by PET. Using this threshold, the sensitivity and specificity of ceMRI to detect non-viable myocardium as defined by PET were 96% and 84%, respectively. CONCLUSIONS Contrast-enhanced MRI allows assessment of myocardial viability with a high accuracy, compared with FDG-PET, in patients with chronic ischemic heart disease and LV dysfunction.

Usefulness of two-dimensional echocardiography for immediate detection of myocardial ischemia in the emergency room

Inappropriate discharge from the emergency room of patients with acute chest pain may have serious consequences. Regional asynergy is one of the first signs of myocardial ischemia and can be detected with 2-dimensional echocardiography (2-DE). This study determines the value of 2-DE in the emergency room for immediate detection of myocardial ischemia causing acute chest pain at the time the electrocardiogram was nondiagnostic. Forty-three patients (32 men and 11 women) with a normal or nondiagnostic electrocardiogram during acute chest pain were studied with 2-DE. Only patients without a previous myocardial infarction and without known coronary artery disease (CAD) were studied. The entire left ventricular wall was examined for presence of regional asynergy. Coronary angiography was performed within 3 weeks. Cardiac enzyme levels were measured serially to establish or rule out an acute myocardial infarction. Sensitivity of 2-DE for detection of myocardial ischemia was 88% (22 of 25), specificity 78% (14 of 18), negative predictive accuracy 82% (14 of 17) and positive predictive accuracy 85% (22 of 26). Sensitivity of 2-DE for detection of acute myocardial infarction was 92% (12 of 13), specificity 53% (16 of 30) and negative predictive accuracy 94% (16 of 17). Thus, 2-DE during pain and a nondiagnostic electrocardiogram can readily identify patients with CAD in the emergency room, and it can accurately rule out an acute myocardial infarction.

Evaluation of magnetic resonance imaging for determination of left ventricular ejection fraction and comparison with angiography.

Left ventricular ejection fraction was measured by magnetic resonance imaging (MRI) and compared with standard monoplane left ventriculography in 46 patients with various cardiac diseases. Two different MRI strategies were used. In 28 patients (group 1), ejection fraction was determined using a single slice comparable with the right anterior oblique projection of the ventriculogram. Comparison of left ventricular ejection fraction yielded a poor correlation between single slice MRI (y) and ventriculography (x) (y = 28.7 + 0.47 x, r = 0.65). In 18 patients (group 2), a multiple contiguous slice MRI technique was used to allow ejection fraction and stroke volume determination by summing up the volumes of ventricular cavity intersections. Regression analysis showed a high correlation between multiple slice MRI (y) and ventriculography (x) (y = 7.2 + 0.88 x, r = 0.98). Also, correlation between MRI right (y) and left (x) ventricular stroke volumes was satisfactory, (y = -12.8 + 1.09 x, r = 0.83). It is concluded that the multiple slice imaging technique in MRI provides an accurate noninvasive means for quantification of left ventricular ejection fraction that can be extended to the determination of left ventricular volume.

Impact of cardiac complications on outcome after aneurysmal subarachnoid hemorrhage A meta-analysis

Impact of cardiac complications after aneurysmal subarachnoid hemorrhage (SAH) remains controversial. We performed a meta-analysis to assess whether EKG changes, myocardial damage, or echocardiographic wall motion abnormalities (WMAs) are related to death, poor outcome (death or dependency), or delayed cerebral ischemia (DCI) after SAH. Methods: Articles on cardiac abnormalities after aneurysmal SAH that met predefined criteria and were published between 1960 and 2007 were retrieved. We assessed the quality of reports and extracted data on patient characteristics, cardiac abnormalities, and outcome measurements. Poor outcome was defined as death or dependence by the Glasgow Outcome Scale (dichotomized at ≤3) or the modified Rankin scale (dichotomized at >3). If studies used another dichotomy or another outcome scale, we used the numbers of patients with poor outcome provided by the authors. We calculated pooled relative risks (RRs) with corresponding 95% confidence intervals for the relation between cardiac abnormalities and outcome measurements. Results: We included 25 studies (16 prospective) with a total of 2,690 patients (mean age 53 years; 35% men). Mortality was associated with WMAs (RR 1.9), elevated troponin (RR 2.0) and brain natriuretic peptide (BNP) levels (RR 11.1), tachycardia (RR 3.9), Q waves (RR 2.9), ST-segment depression (RR 2.1), T-wave abnormalities (RR 1.8), and bradycardia (RR 0.6). Poor outcome was associated with elevated troponin (RR 2.3) and creatine kinase MB (CK-MB) levels (RR 2.3) and ST-segment depression (RR 2.4). Occurrence of DCI was associated with WMAs (RR 2.1), elevated troponin (RR 3.2), CK-MB (RR 2.9), and BNP levels (RR 4.5), and ST-segment depression (RR 2.4). All RRs were significant. Conclusion: Markers for cardiac damage and dysfunction are associated with an increased risk of death, poor outcome, and delayed cerebral ischemia after subarachnoid hemorrhage. Future research should establish whether these cardiac abnormalities are independent prognosticators and should be directed toward pathophysiologic mechanisms and potential treatment options.

Myocardial Energetics and Efficiency Current Status of the Noninvasive Approach

The heart is an aerobic organ that relies almost exclusively on the aerobic oxidation of substrates for generation of energy. Consequently, there is close coupling between myocardial oxygen consumption (MVo2) and the main determinants of systolic function: heart rate, contractile state, and wall stress.1 As in any mechanical pump, only part of the energy invested is converted to external power. In the case of the heart, the ratio of useful energy produced (ie, stroke work [SW]) to oxygen consumed is defined as mechanical efficiency, as originally proposed by Bing et al.2 Under normal conditions this ratio is ≈25%, and the residual energy mainly dissipates as heat.3 In pathophysiological disease states, such as heart failure, mechanical efficiency is reduced, and it has been hypothesized that the increased energy expenditure relative to work contributes to progression of the disease.4,5 Moreover, therapeutic interventions that enhance mechanical efficiency have proven to be beneficial with respect to outcome.6 It is therefore desirable to quantify efficiency of the heart to study disease processes and monitor interventions. Both cardiac oxidative metabolism and mechanical work, and thus efficiency, can be quantified through invasive measurements. Although these measurements are accurate and currently considered the gold standard, in clinical practice they are limited because of the need for dual-sided heart catheterization and selective catheterization of the coronary sinus. Recent advances in imaging techniques, however, offer the possibility to noninvasively estimate MVo2 and mechanical work by positron emission tomography and echocardiography or by magnetic resonance imaging, respectively. This review discusses the principles of mechanical efficiency, together with its invasive and noninvasive assessment, as well as their strengths and pitfalls. Finally, results from clinical pathophysiological studies are discussed. To calculate the efficiency of the heart, input and output energy must be obtained. The …

Effects of spontaneous and streptokinase-induced recanalization on left ventricular function after myocardial infarction.

The effect of recanalization of the “infarct vessel” on left ventricular (LV) function was assessed 6–8 weeks after acute myocardial infarction (MI) in two groups: patients who had streptokinaseinduced recanalization during the acute phase and control patients who had spontaneous recanalization. The ejection fraction and severity of LV wall motion abnormalities in 100 patients with recanalization were compared with those in 78 patients with persistent occlusion of the infarct vessel. Among patients with inferior MI, LV function was significantly better in those with spontaneous (n = 41, p < 0.05) and streptokinase-induced recanalization (n = 15, p < 0.02) than in those with persistent occlusion of the infarct vessel (n = 40) in the control group. The LV function was equally good in patients with spontaneous and streptokinase-induced recanalization. Among anterior MI patients, LV function was significantly better in those with streptokinase-induced recanalization (n = 10) than in those with spontaneous recanalization (n = 34, p < 0.01) or persistent occlusion in the control group (n = 28, p < 0.001). We conclude that recanalization has a beneficial effect on LV function in patients with MI.

Prediction of improvement of contractile function in patients with ischemic ventricular dysfunction after revascularization by fluorine-18 fluorodeoxyglucose single-photon emission computed tomography

OBJECTIVES We evaluated the use of fluorine-18 fluorodeoxyglucose (FDG) and single-photon emission computed tomography (SPECT) to predict improvement of left ventricular ejection fraction (LVEF) after revascularization. BACKGROUND FDG SPECT has recently been proposed for assessment of myocardial viability. However, FDG SPECT still awaits validation in terms of predicting improvement of contractile function after revascularization in patients with poor left ventricular (LV) function. METHODS Fifty-five patients with contractile dysfunction (including 22 with LVEF < 30%) underwent FDG SPECT during hyperinsulinemic glucose clamping and early thallium-201 SPECT (to assess perfusion). Improvement of LV function was evaluated 3 months after revascularization with echocardiography and radionuclide ventriculography. RESULTS The 55 patients were arbitrarily classified into two groups: 19 with three or more viable, dysfunctional segments on FDG SPECT and 36 with less than three viable, dysfunctional segments. LVEF increased significantly in the first group, from 28 +/- 8% (mean +/- SD) before to 35 +/- 9% (p < 0.01) after revascularization. In the second group, LVEF remained unchanged after revascularization (45 +/- 14% vs. 44 +/- 14%, p = NS). The 22 patients with severely depressed LV function were similarly classified into two groups: 14 with three or more viable segments on FDG SPECT in whom LVEF improved significantly (25 +/- 6% vs. 32 +/- 6%) and 8 with less than three viable segments in whom LVEF remained unchanged (24 +/- 6% vs. 25 +/- 6%). CONCLUSIONS This study shows that FDG SPECT can identify patients in whom LV function improves after revascularization. Because SPECT is widely available, this technique may contribute to more routine use of FDG for determination of viability.