William L. Winters

A new, simplified and accurate method for determining ejection fraction with two-dimensional echocardiography.

A new method to determine left ventricular (LV) ejection fraction (EF) with wide‐angle, twodimensional echocardiography (2‐D echo) has been developed using the parasternal long‐axis, apical fourchamber and apical long‐axis views. End‐diastolic and end‐systolic measurements of LV short axes at the base and mid‐LV cavity in the parasternal long‐axis view and at the upper, middle and lower thirds of the cavity in the apical views are made, from which an averaged minor axis at end‐diastole and at end‐systole is calculated. Fractional shortening of the LV long axis (ΔL) is estimated from apical contraction. Satisfactory 2‐D echoes were obtained in 55 of 58 nonselected patients (all three views in 32 patients, two views in 22 and one view in one); 42 of 55 patients had coronary artery disease. EF by 2‐D echo was compared with EF by gated cardiac blood pool imaging in all patients (r = 0.927, SEE = 6.7%) and to EF by single‐plane cineangiography (angio) in 35 of 55 patients (r = 0.913, SEE = 7.4%). LV dyssynergy was frequently present and involved the apex in 29 of 55 patients. Using angio as the standard for evaluating wall motion at the apex, 2‐D echo was 100% sensitive and specific in detecting abnormal apical wall motion. We condude that EF can be determined accurately with 2‐D echo in a large group of patients with and without dyssynergy by a simple method that eliminates the need for planimetry or computer assistance.

Dobutamine Echocardiography and Quantitative Rest-Redistribution 201Tl Tomography in Myocardial Hibernation Relation of Contractile Reserve to 201Tl Uptake and Comparative Prediction of Recovery of Function

BACKGROUNDnThe purposes of this study were to evaluate the comparative accuracy of dobutamine echocardiography and quantitative rest-redistribution 201Tl tomography in the prediction of recovery of function after revascularization and to assess the relation of contractile reserve to thallium uptake.nnnMETHODS AND RESULTSnThirty-four patients with stable coronary disease and regional dysfunction underwent dobutamine echocardiography (2.5 up to 40 micrograms.kg-1.min-1) and rest-redistribution 201Tl tomography 1 day before revascularization. Resting echocardiography and scintigraphy were repeated at > or = 6 weeks. Before revascularization, resting 201Tl uptake was similar in segments demonstrating biphasic or sustained improvement and was higher than in those exhibiting no change or worsening function during dobutamine. After revascularization, 201Tl uptake increased only in segments that showed a biphasic response (from 66 +/- 12% to 78 +/- 13%; P < .05). Biphasic response had a sensitivity of 74% and specificity of 89% for prediction of recovery. The use of biphasic or sustained improvement responses increased the sensitivity to 86% with a decrease in specificity to 68%. Qualitative thallium assessment provided a high sensitivity (98%) but poor specificity (27%). Quantification of thallium uptake, however, improved its accuracy: a maximal uptake (at rest or redistribution) of > or = 60% yielded a 90% sensitivity and a 56% specificity.nnnCONCLUSIONSnIn patients with myocardial hibernation, biphasic response during dobutamine is less sensitive but more specific for recovery of function, whereas indexes of 201Tl scintigraphy are in general more sensitive and less specific, the least accurate being a qualitative assessment of thallium uptake. The sensitivity and specificity of both methods, however, can be altered depending on the quantitative criteria of thallium uptake or combination of responses of the myocardium to dobutamine.

Identification of Hibernating Myocardium: Comparative Accuracy of Myocardial Contrast Echocardiography, Rest-Redistribution Thallium-201 Tomography and Dobutamine Echocardiography

OBJECTIVESnWe sought to evaluate the comparative accuracy of myocardial contrast echocardiography (MCE), quantitative rest-redistribution thallium-201 (Tl-201) tomography and low and high dose (up to 40 microg/kg body weight per min) dobutamine echocardiography (DE) in identifying myocardial hibernation.nnnBACKGROUNDnMyocardial contrast echocardiography can assess myocardial perfusion and may therefore be useful in predicting myocardial hibernation. However, its accuracy in comparison to myocardial perfusion scintigraphy and to that of high dose DE remains to be investigated.nnnMETHODSnEighteen patients (aged [+/- SD] 57 +/- 10 years) with stable coronary artery disease and ventricular dysfunction underwent the above three modalities before coronary revascularization. Myocardial contrast echocardiography was achieved with intracoronary Albunex. Rest echocardiographic and Tl-201 studies were repeated > or = 6 weeks after revascularization.nnnRESULTSnOf 109 revascularized segments with severe dysfunction, 46 (42%) improved. Left ventricular ejection fraction increased from 38 +/- 14% to 45 +/- 13% at follow-up (p = 0.003). Rest Tl-201 uptake and the ratio of peak contrast intensity of dysfunctional to normal segments with MCE were higher (p < 0.01) in segments that recovered function compared with those that did not. Myocardial contrast echocardiography, thallium scintigraphy and any contractile reserve during DE had a similar sensitivity (89% to 91%) with a lower specificity (43% to 66%) for recovery of function. A biphasic response during DE was the most specific (83%) and the least sensitive (68%) (p < 0.01). The best concordance with MCE was Tl-201 (80%, kappa 0.57). Changes in ejection fraction after revascularization related significantly to the number of viable dysfunctional segments by all modalities (r = 0.54 to 0.65).nnnCONCLUSIONSnIn myocardial hibernation, methods evaluating rest perfusion (MCE, Tl-201) or any contractile reserve have a similar high sensitivity but a low specificity for predicting recovery of function. A limited contractile reserve (biphasic response) increases the specificity of DE. Importantly, the three techniques identified all patients who had significant improvement in global ventricular function.

Detection of coronary artery disease with exercise two-dimensional echocardiography. Description of a clinically applicable method and comparison with radionuclide ventriculography.

Two-dimensional echocardiography (2-D echo) was performed in 73 patients evaluated for coronary artery disease (CAD) and in four normal volunteers before and immediately after a maximal treadmill exercise test. Diagnostic images were obtained from the apical and parasternal windows. In 17 patients with normal coronary arteriograms, ejection fraction (EF) increased from 66 9% (±4 SD) at rest to 73 8% after exercise (p < 0.001), while in 56 patients with proved CAD, EF fell from 56 13% at rest to 53 16% after exercise (p < 0.01). The sensitivity of postexercise 2-D echo for detecting CAD (based on abnormal EF response and/or regional dyssynergy) was 91% (51 of 56 patients) and the specificity was 88% (15 of 17). Sensitivity for one-, two- and three-vessel disease was 64% (seven of 11), 95% (20 of 21) and 100%, respectively. Patients with multivessel disease showed a significant fall in a wall motion score index, from 0.79 0.25 to 0.63 0.26. Exercise radionuclide ventriculography (RNV) was also performed in 41 of the subjects (17 normals and 24 CAD patients) on a bicycle ergometer. The overall sensitivity of 2-D echo in this subgroup was 92%, compared with 71% for RNV. The sensitivity of 2-D echo for one-vessel disease (n = 4) was 50%, that for two-vessel disease (n = 12) was 100% and that for three-vessel disease (n = 12) was 100%. Respective values for RNV were 0%, 80% and 90%. The specificity of 2-D echo was 88% and that of RNV was 82%. A significantly higher peak heart rate response was observed on the treadmill than on the bicycle ergometer in both CAD patients and normal subjects. We conclude that postexercise 2-D echo is a clinically applicable technique for the diagnosis and evaluation of CAD patients and compares favorably with exercise RNV.

End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation: Relation to rest-redistribution Tl-201 tomography and dobutamine stress echocardiography

OBJECTIVESnThe study assessed whether end-diastolic wall thickness (EDWT), measured with echocardiography, is an important marker of myocardial viability in patients with suspected myocardial hibernation, and it compared this index to currently established diagnostic modalities of dobutamine stress echocardiography (DSE) and rest-redistribution thallium-201 (T1-201) scintigraphy.nnnBACKGROUNDnBecause myocardial necrosis is associated with myocardial thinning, preserved EDWT may provide a simple index of myocardial viability that is readily available from the resting echocardiogram.nnnMETHODSnAccordingly, 45 patients with stable coronary artery disease and ventricular dysfunction underwent rest 2D echocardiograms, DSE and rest-redistribution T1-201 tomography before revascularization and a repeat resting echocardiogram > or =2 months later.nnnRESULTSnGlobal wall motion score index decreased from 2.38 +/- 0.73 to 1.94 +/- 0.82 after revascularization (p < 0.001). Thirty-eight percent of severely dysfunctional segments recovered resting function. Compared to segments without recovery of resting function, those with recovery had greater EDWT (0.94 +/- 0.18 cm vs. 0.67 +/- 0.22 cm, p < or = 0.0001) and a higher T1-201 uptake (78 +/- 13% vs. 59 +/- 21%; p < 0.0001). An EDWT >0.6 cm had a sensitivity of 94% and specificity of 48% for recovery of function. Similarly, a T1-201 maximal uptake of > or =60% had a sensitivity of 91% and specificity of 50%. Receiver operating characteristic curves for prediction of recovery of regional and global function were similar for EDWT and maximum T1-201 uptake. Combination of EDWT and any contractile reserve during DSE for recovery of regional function improved the specificity to 77% without a significant loss in sensitivity (88%).nnnCONCLUSIONSnEnd-diastolic wall thickness is an important marker of myocardial viability in patients with suspected hibernation, and it can predict recovery of function similar to T1-201 scintigraphy. Importantly, a simple measurement of EDWT < or =0.6 cm virtually excludes the potential for recovery of function and is a valuable adjunct to DSE in the assessment of myocardial viability.

Identification of Hibernating Myocardium With Quantitative Intravenous Myocardial Contrast Echocardiography Comparison With Dobutamine Echocardiography and Thallium-201 Scintigraphy

Background—There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl201) scintigraphy. Methods and Results—Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl201 tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in hibernating myocardium were similar to segments with normal function and higher than dysfunctional myocardium without recovery of function (P <0.001). The best MCE parameter for predicting functional recovery was Peak MCI×&bgr;, an index of myocardial blood flow (area under the curve, 0.83). MCE parameters were higher in segments with contractile reserve and Tl201 uptake ≥60% (P <0.05) and identified viable segments without contractile reserve by DE. The sensitivity of Peak MCI×&bgr; >1.5 dB/s for recovery of function was 90% and was similar to Tl201 scintigraphy (92%) and any contractile reserve (80%); specificity was higher than for Tl201 and DE (63%, 45%, and 54%, respectively;P <0.05). Conclusions—MCE with intravenous contrast identifies myocardial hibernation in humans. Prediction of viable myocardium with MCE is best using quantification of myocardial blood flow and provides improved accuracy compared with DE and Tl201 scintigraphy.

Microvascular Structural Correlates of Myocardial Contrast Echocardiography in Patients With Coronary Artery Disease and Left Ventricular Dysfunction Implications for the Assessment of Myocardial Hibernation

Background—Myocardial contrast echocardiography (MCE) has been used to evaluate myocardial viability. There are no data, however, on the pathological determinants of myocardial perfusion by MCE in humans and the implications of such determinants. Methods and Results—MCE was performed in 20 patients with coronary artery disease and ventricular dysfunction within 24 hours before myocardial biopsy at surgery using a continuous Optison infusion (12 to 16 cc/h), with intermittent pulse inversion harmonics and incremental triggering. Peak myocardial contrast intensity (MCI) and the rate of increase in MCI (&bgr;) were quantitated. Thirty-six transmural myocardial biopsies (2 per patient) were obtained by transesophageal echocardiography. Total microvascular (<100 &mgr;m) density, capillary density and area, arteriolar and venular density, and percent collagen content were quantitated with immunohistochemistry. Peak MCI correlated with microvascular density (r =0.59, P <0.001) and capillary area (r =0.64, P <0.001) and inversely correlated with percent collagen content (r =−0.45, P =<0.01). The best relation was observed when the ratio of peak MCI in the 2 biopsied segments in each patient was compared with the ratio of microvascular density and capillary area (r =0.84 and 0.87, respectively;P <0.001). A significant overlap in microvascular density was seen between segments with and without recovery of function. The new MCE indices of blood velocity (&bgr;) and flow (peak MCI×&bgr;) better identified recovery of function compared with microvascular density and the sole use of peak MCI. Conclusions—Microvascular integrity is a significant determinant of maximal MCI in humans. MCE indices of blood velocity and flow are important parameters that predict recovery of function after revascularization.

Supine bicycle versus post-treadmill exercise echocardiography in the detection of myocardial ischemia: a randomized single-blind crossover trial.

OBJECTIVESnWe sought to determine the comparative accuracy of supine bicycle exercise echocardiography (SBE) and posttreadmill exercise echocardiography (TME) in detecting myocardial ischemia in patients with known or suspected coronary artery disease (CAD).nnnBACKGROUNDnSupine bicycle echocardiography and TME have been used for evaluation of CAD. However, the comparative accuracy of these modalities in the detection of ischemia in the same patients is not known.nnnMETHODSnSeventy-four patients (age 59 +/- 9 years [mean +/- SD]) referred for evaluation of coronary disease underwent SBE (starting at 25 to 50 W with 25-W increment every 3 min) and post-TME (Bruce protocol) in a random sequence. Digitized images at baseline and maximal exercise were interpreted in a random and blinded fashion.nnnRESULTSnMaximal heart rate was higher during TME, whereas systolic blood pressure was higher during SBE, resulting in a similar double product. At quantitative angiography (n = 67), 57 patients had coronary stenosis (>50%). During SBE, ischemia was detected in 47 patients compared with 38 patients by TME (p < 0.001). Wall motion score index at maximal exercise was higher with SBE than with TME (1.48 +/- 0.51 vs. 1.38 +/- 0.43; p < 0.001). The extent of myocardial ischemia (number of ischemic segments) was higher during SBE compared with TME (3.3 +/- 3.4 vs. 2.3 +/- 2.9 segments; p = 0.004), whereas severity of abnormal wall motion was similar. The sensitivity of SBE and TME for CAD was 82% and 75% with a specificity of 80% and 90%, respectively. Image quality was similar with both techniques. Patients and sonographers favored SBE over TME.nnnCONCLUSIONSnDuring SBE and TME exercise, patients achieve a similar double product. During SBE, however, the detection of ischemia is more frequent and more extensive which, along with patient and sonographer preference, makes supine bicycle exercise a valuable stress echocardiographic modality.

Serial Changes in Response of Hibernating Myocardium to Inotropic Stimulation After Revascularization: A Dobutamine Echocardiographic Study

OBJECTIVESnWe sought to evaluate the serial changes in the response of the hibernating myocardium to dobutamine stimulation after revascularization.nnnBACKGROUNDnAn improvement in myocardial contraction during dobutamine stress echocardiography (DSE), particularly a biphasic response, predicts recovery of rest function. However, little is known about the changes in the response of the myocardium to dobutamine after revascularization.nnnMETHODSnThirty-four patients with stable coronary artery disease and regional left ventricular dysfunction underwent DSE before, early (within 1 week) and late (>6 weeks) after coronary angioplasty. Dobutamine was given in incremental doses from 2.5 to 40 microg/kg body weight per min.nnnRESULTSnOf 180 revascularized segments with severe rest dysfunction, recovery of rest function was seen in 56 segments (31%) late after angioplasty, 80% of which had early recovery. Ventricular function during DSE was similar early and late after revascularization. Patients who showed a biphasic response to DSE before revascularization (n = 12) had the most improvement in function at rest (mean [+/-SD] wall motion score index [WMSI] 1.98 +/- 0.75 vs. 1.35 +/- 0.54, p < 0.05) and during DSE (2.11 +/- 0.67 vs. 1.21 +/- 0.41, p < 0.05) late after revascularization. Patients with sustained improvement during DSE before revascularization had no significant change in wall motion during DSE after angioplasty. However, patients without improvement in function at low dose DSE, who demonstrated worsening of function at a high dose, had significant augmentation in wall motion during DSE after revascularization (WMSI 2.16 +/- 0.50 vs. 1.60 +/- 0.57, p < 0.05). Patients who had no recovery of rest function had significant improvement in wall motion response to DSE, particularly when ischemia was inducible before revascularization.nnnCONCLUSIONSnIn myocardial hibernation, the majority of recovery of rest function occurs early after revascularization. Although patients who recover rest function show the most marked improvement in wall motion during DSE, those without recovery of rest function also have improved function during DSE, particularly when there is evidence of ischemia before revascularization.

Increased Myocardial Gene Expression of Tumor Necrosis Factor-α and Nitric Oxide Synthase-2: A Potential Mechanism for Depressed Myocardial Function in Hibernating Myocardium in Humans

Background—Whether cardioinhibitory cytokines are elevated in regions of hibernating myocardium and account in part for the depression in resting function is currently not known. Methods and Results—Thirteen patients with stable ischemic ventricular dysfunction scheduled for bypass surgery underwent preoperative dobutamine echocardiography (DE) and intraoperative myocardial biopsies. The numbers of copies of mRNA for the negatively inotropic cytokines tumor necrosis factor-&agr; (TNF-&agr;) and inducible nitric oxide synthase (NOS2) were quantified by reverse transcription–polymerase chain reaction. In normal segments, myocardial TNF-&agr; was barely detectable (1.2±0.4 copies per 106 copies of &bgr;-actin). A 13.7-fold increase in myocardial TNF-&agr; was observed in dysfunctional segments with a biphasic response to DE (contractile reserve and ischemia) and was highest (45.5-fold) in segments with ischemia and without contractile reserve (P <0.001). A similar graded increase was seen for NOS2. Cytokine results were also similar if analysis was performed using recovery of function at 3 months as the index of viability. The change in serum TNF-&agr; and nitrite levels from baseline to 3 months after surgery correlated inversely with both the change in ejection fraction and the number of DE viable segments (r =−0.92 to −0.93;P <0.001). Conclusions—TNF-&agr; and NOS2 gene expression is regionally upregulated in hibernating myocardium to a level intermediate between that of normal regions and ischemic regions without contractile reserve. This, along with a decline in serum cytokine levels after revascularization proportional to the extent of myocardial viability, suggests a contributing role for cardioinhibitory cytokines in the observed depression of function seen in hibernating myocardium.