Comparison of dobutamine echocardiography and positron emission tomography in patients with chronic ischemic left ventricular dysfunction

Objectives. The aim of this study was to correlate dobutamine-induced contractile reserve as detected by echocardiography with findings on positron emission tomography in patients with chronic ischemic left ventricular dysfunction.

Background. Contractile reserve induced by low dose dobutamine infusion has been proposed as a marker of myocardial viability.

Methods. Sixty patients with stable coronary artery disease and left ventricular dysfunction (mean ejection fraction [± SD] 29 ± 10%) underwent transthoracic echocardiography with dobutamine infusion (up to 10 μg/kg body weight per min) and positron emission tomography with nitrogen-13 ammonia and fluorine-18 (F-18) fluorodeoxyglucose as a perfusion and a metabolic tracer, respectively. Regional wall motion, perfusion and metabolism were analyzed semiquantitatively by using a 16-segment model. Segments with F-18 fluorodeoxyglucose uptake > 50% were considered viable on positron emission tomography.

Results. After dobutamine infusion, hemodynamic variables changed significantly, and myocardial ischemia was evident in 17 patients. All 60 patients had dysfunctional myocardium considered viable on positron emission tomography (8 ± 4 segments/patient), whereas 52 patients had dysfunctional myocardium with contractile enhancement by dobutamine echocardiography (4 ± 2 segments/patient, P = 0.01). The extent of dysfunctional myocardium with contractile reserve appeared to correlate less closely with the total extent of viable dysfunctional myocardium identified by positron emission tomography than with the number of such segments associated with a pattern of perfusion-metabolism mismatch.

Conclusions. In patients with chronic ischemic left ventricular dysfunction, echocardiography can be used to identify enhancement in the contractile function of viable dysfunctional myocardium after infusion of low dose dobutamine. In this study, the presence and extent of such enhancement were relatively less than the values obtained from positron emission tomography.     

Relation Between Contractile Reserve and Positron Emission Tomographic Patterns of Perfusion and Glucose Utilization in Chronic Ischemic Left Ventricular Dysfunction: Implications for Identification of Myocardial Viability

Objectives. This study sought to determine the incidence and extent of dobutamine-induced contractile reserve in myocardial regions characterized by classical and new positron emission tomographic (PET) patterns in patients with chronic ischemic left ventricular dysfunction.

Background. PET is considered the most accurate method for assessment of myocardial viability, which is traditionally identified by perfusion–metabolism mismatch.

Methods. In 23 patients, segmental wall thickening expressed by four echocardiographic scores at rest and during low dose (5 and 10 μg/kg body weight per min) dobutamine infusion and regional myocardial uptake of potassium-38 and fluorine-18 fluorodeoxyglucose (F-18 FDG) during glucose clamp were compared in 16 corresponding segments.

Results. Of a total of 368 segments, data analysis focused on 214 (58%) dyssynergic segments at baseline. Contractile reserve was identified with increasing incidence according to the six following PET patterns: 1) diminished perfusion and moderate reduction of F-18 FDG uptake (3 [11%] of 28 segments); 2) proportional reduction of perfusion and F-18 FDG uptake (10 [23%] of 43 segments); 3) perfusion–metabolism mismatch (19 [46%] of 41 segments); 4) preserved perfusion but moderate reduction of F-18 FDG uptake (13 [46%] of 27 segments); 5) preserved perfusion and F-18 FDG uptake (37 [59%] of 63 segments) compared with our normal database; and 6) normal perfusion but absolute increased F-18 FDG uptake (8 [73%] of 11 segments). In the latter category, only 7 of 24 segments had normal rest function. In dyssynergic segments with F-18 FDG uptake ≥50% supplied by vessels with ≥75% stenosis, improvement in contractility during dobutamine correlated with the presence of collateral channels.

Conclusions. Myocardial regions with the traditional mismatch pattern of viability show contractile reserve in slightly <50%. In segments with moderate reduction of F-18 FDG uptake, the contractile response to dobutamine is linked to the level of rest perfusion. Most segments with preserved perfusion and increased F-18 FDG uptake have impaired rest function, but contractile reserve is still present. These data suggest that in chronic ischemic left ventricular dysfunction, myocardial hibernation is a heterogeneous condition.     

Transmural contractile reserve after reperfused myocardial infarction in dogs

OBJECTIVES

The goal of this study was to characterize detailed transmural left ventricular (LV) function at rest and during dobutamine stimulation in subendocardial and transmural experimental infarcts.

BACKGROUND

The relation between segmental LV function and the transmural extent of myocardial necrosis is complex. However, its detailed understanding is crucial for the diagnosis of myocardial viability as assessed by inotropic stimulation.

METHODS

Short-axis tagged magnetic resonance images were acquired at five to seven levels encompassing the LV from base to apex in seven dogs 2 days after a 90-min closed-chest left anterior descending coronary occlusion, followed by reflow. Myocardial strains were measured transmurally in the entire LV by harmonic phase imaging at rest and 5 ig.kg⁻¹.min⁻¹ dobutamine. Risk regions were assessed by radioactive microspheres, and the transmural extent of the infarct was assessed by 2,3,5 triphenyltetrazolium chloride staining.

RESULTS

Circumferential shortening (Ecc), radial thickening (Err) and maximal shortening at rest were greater in segments with subendocardial versus transmural infarcts, both in subepicardium (−1.1 ± 1.0 vs. 2.5 ± 0.6% for Ecc, −0.5 ± 1.9 vs. −1.8 ± 1.0% for Err, p < 0.05) and subendocardium (−2.0 ± 1.4 vs. 2.8 ± 0.8%, 2.4 ± 1.7 vs. 0.0 ± 0.9%, respectively, p < 0.05). Under inotropic stimulation, risk regions retained maximal contractile reserve. Recruitable deformation was found in outer layers of subendocardial infarcts (p < 0.01 for Ecc and Err) but also in inner layers (p < 0.01). Conversely, no contractile reserve was observed in segments with transmural infarcts.

CONCLUSIONS

Under dobutamine challenge, recruitment of myofiber shortening and thickening was observed in inner layers of segments with subendocardial infarcts. These results may have important clinical implications for the detection of myocardial viability.     

Myocardial perfusion and oxygen consumption in reperfused noninfarcted dysfunctional myocardium after unstable angina: direct evidence for myocardial stunning in humans

OBJECTIVES

To positively establish the diagnosis of myocardial stunning in patients with unstable angina and persistent wall motion abnormalities after reperfusion by coronary angioplasty.

BACKGROUND

Although myocardial stunning is thought to occur in several clinical conditions, definite proof of its existence in humans is still lacking, owing to the difficulty of measuring myocardial blood flow (MBF) in absolute terms.

METHODS

We studied 14 patients with unstable angina due to proximal left anterior descending coronary artery disease who presented persistent anterior wall motion abnormalities despite revascularization of the culprit lesion by percutaneous coronary angioplasty (PTCA) and who did not have clinical evidence of necrosis. Dynamic positron emission tomography (PET) with [¹³N]-ammonia and [¹¹C]-acetate was performed 48 h after PTCA to determine absolute MBF and oxygen consumption (MVO₂). Regional wall thickening and regional cardiac work were determined using two-dimensional echocardiography. Improvement of segmental wall motion abnormalities was followed for a median of 4 months (1.5 to 14 months).

RESULTS

As judged from the changes in segmental wall motion score, regional dysfunction was spontaneously reversible in 12/14 patients and improved from 2.2 ± 0.3 to 1.2 ± 0.3 at late follow-up (p < 0.001). With PET, [¹³N]-ammonia MBF was similar among dysfunctional and remote normally contracting segments (85 ± 29 vs. 99 ± 20 ml·min⁻¹·100g⁻¹, p = not significant [n.s.]), thus demonstrating a perfusion-contraction mismatch. Despite the reduced contractile function, dysfunctional myocardium presented near normal levels of MVO₂ (6.5 ± 4.2 vs. 8.0 ± 1.9 ml·min⁻¹·100g⁻¹, p = n.s.). Consequently, the regional myocardial efficiency (regional work divided by MVO₂) of the dysfunctional myocardium was found to be markedly decreased as compared with normally contracting myocardium (6 ± 6% vs. 26 ± 6%, p < 0.001).

CONCLUSIONS

This study demonstrates that human dysfunctional myocardium capable of spontaneously recovering contractile function after unstable angina endures a state of perfusion-contraction mismatch. These data for the first time provide unequivocal direct evidence for the existence of acute myocardial stunning in humans.     

Comparison of sestamibi single-photon emission computed tomography with positron emission tomography for estimating left ventricular myocarclial viability

Technetium-99m methoxyisobutyl isonitrile (technetium-99m sestamibi [MIBI]) is distributed in the myocardium according to blood flow. Reports comparing stress rest sestamibi protocols with reinfection thallium or resting fluorodeoxyglucose (FDG), or both, in patients with coronary artery disease have shown appreciable discordance regarding myocardial viability in these settings. We performed this analysis with regard to regional comparisons within discordant segments and made comparisons in a subset of patients who underwent revascularization. Thirty-seven patients with coronary artery disease had single-photon emission computed tomography MIBI, N-13 ammonia/¹⁸FDG positron emission tomography (PET), and radionuclide ventriculography performed at rest. One hundred two segments were viable and 29 were nonviable by both MIBI and FDG. The concordance was 71%. In MIBI nonviable/ FDG viable segments, most of the discordance was in the inferior wall. In MIBI nonviable discordant segments, FDG accurately predicted an increase in percent regional ejection fraction (preoperative 36% [± 5 SE] to postoperative 48% [± 5.5 SE] [p < 0.0006]). MIBI underestimates myocardial viability as assessed by PET. Seventy-one percent of myocardial segments were concordant by both quantitative sestamibi single-photon emission computed tomography and FDG PET. Discordance in MIBI nonviable segments was predominantly in the inferior wall. PET can be helpful in detecting myocardial viability in patients suspected of having had MIBI nonviability in the inferior wall.     

Use of cyclic variation of integrated backscatter to assess contractile reserve and myocardial viability in chronic ischemic left ventricular dysfunction

The detection of viable myocardium has important implications for management, but use of stress echocardiography to detect this is subjective and requires exposure to dobutamine. We investigated whether cyclic variation (CV) of integrated backscatter (IB) from the apical views could provide a resting study for detection of contractile reserve (CR) and prediction of myocardial viability in 27 patients with chronic ischemic left ventricular (LV) dysfunction. Repeat echocardiography was performed after 6.7 +/- 3.8 months of follow-up; 14 patients underwent revascularization and 13 were treated medically. Using a standardized dobutamine echocardiography (DbE) protocol, images from three apical views were acquired at 80-120 frames/sec at rest and during stress. CR was identified if improvement of wall motion was observed at low dose (5 or 10 microg/kg/min) DbE. Myocardial viability was characterized by improvement at follow-up echocardiography in patients with revascularization. CVIB at rest and low dose dobutamine were assessed in 194 segments with resting asynergy (severe hypokinesis or akinesis), of which 88 (45%) were in patients who underwent revascularization. Of these, CVIB could be measured in 190 (98%) segments at rest and 185 (95%) at low dose dobutamine. Sixty-two (33%) segments had CR during low dose DbE and 50 (57%) segments showed wall-motion recovery (myocardial viability) at follow-up echocardiography. Segments with CR had significantly higher CVIB at rest (P < 0.001) and low dose dobutamine (P = 0.005) than segments without CR. Using optimal thresholds of CVIB (> 8.2 dB) at rest, the accuracy of CVIB for detecting CR was 70%. Compared with nonviable segments, viable segments had significantly higher CVIB at rest (P < 0.001) and low dose dobutamine (P < 0.001). Using optimal thresholds of CVIB (> 5.3 dB) at rest, the accuracy of CVIB for detecting myocardial viability was 85%, which was higher than that in conventional DbE (62%, P < 0.01). Thus, assessment of CVIB from the apical views is a feasible and accurate tool for detecting CR and predicting myocardial viability in chronic LV dysfunction.     

Response to incremental doses of dobutamine early after reperfusion is predictive of the degree of myocardial salvage in dogs with experimental acute myocardial infarction

OBJECTIVES

We sought to determine whether the inotropic response to dobutamine might be useful for estimating the extent of viable myocardium soon after reperfusion.

BACKGROUND

Early identification of viable myocardium in the presence of severe left ventricular dysfunction after reperfusion is important for clinical decision making.

METHODS

Nine open-chest dogs had left anterior descending coronary artery occlusion for 40 to 180 min, followed by gradual reperfusion. The systolic thickening response to incremental dobutamine doses was measured with ultrasonic crystals and regional flow by microspheres.

RESULTS

Dogs were divided into two groups based on triphenyl tetralozium chloride infarct size (group 1: 9.3 ± 3.0% risk area; group 2: 51.1 ± 4.8%). In group 2 dogs with larger infarcts, regional flow during peak dobutamine was lower than it was in group 1 in endocardial (1.15 ± 0.22 vs. 2.64 ± 0.33 mL·min⁻¹·g⁻¹) and midwall (1.47 ± 0.32 vs. 2.92 ± 0.36 mL·min⁻¹·g⁻¹) layers, and endocardial flow in group 2 failed to increase from baseline (0.96 ± 0.07 vs. 1.15 ± 0.22 mL·min⁻¹·g⁻¹). Group 1 dogs demonstrated a dose dependent increase in systolic thickening with dobutamine versus a blunted response in group 2. The inotropic response to only 10 μg·kg⁻¹·min⁻¹ of dobutamine was predictive of the degree of myocardial salvage.

CONCLUSIONS

In the early postischemic stunning phase of reperfusion, the inotropic response to dobutamine is predictive of the degree of myocardial salvage and ultimate infarct size. The ability to distinguish between stunned versus necrotic myocardium early after reperfusion was most likely due to the presence of subendocardial flow reserve during dobutamine in dogs with predominantly salvaged myocardium.     

Regional myocardial perfusion and metabolism assessed by positron emission tomography in children with Kawasaki disease and significance of abnormal Q waves and their disappearance

To clarify the significance of newly appearing abnormal Q waves and their disappearance in patients with Kawasaki disease, regional myocardial perfusion and glucose metabolism at rest in the fasting condition were assessed by positron emission tomography (PET) with ¹³N-ammonia and ¹⁸F-fluorodeoxyglucose (FDG), and regional wall motion by left ventriculography in regions with persistent and transient abnormal Q waves in 14 patients. PET identified 3 groups of abnormal myocardial segments: segments with hypoperfusion without increased FDG uptake, those with hypoperfusion and increased FDG uptake, and those with normal perfusion and increased FDG uptake. Almost all the segments with persistent or transient abnormal Q waves had abnormal PET findings. PET demonstrated evidence of metabolic activity in 57% of segments with persistent abnormal Q waves and 67% of those with transient abnormal Q waves. Regional wall motion, scored from 0 (normal) to 4 (dyskinesia), was not significantly different between segments with persistent and transient abnormal Q waves (2.3 ± 1.3 vs 2.2 ± 1.2). The persistence of abnormal Q waves on serial electrocardiograms was significantly shorter in metabolically active than in inactive segments (19 ± 17 vs 92 ± 27 months). In conclusion, in patients with Kawasaki disease, the new appearance of abnormal Q waves is a reliable clue to the presence of ischemic myocardial injury and a high proportion of them are associated with metabolically active myocardial regions. The disappearance of abnormal Q waves does not necessarily mean the normalization of regional myocardial perfusion, metabolism or function, and their early disappearance may imply “viability” in the associated myocardial region.     

Myocardial Contrast Echocardiography Versus Dobutamine Echocardiography for Predicting Functional Recovery After Acute Myocardial Infarction Treated With Primary Coronary Angioplasty

Objectives. We sought to compare myocardial contrast echocardiography with low dose dobutamine echocardiography for predicting 1-month recovery of ventricular function in acute myocardial infarction treated with primary coronary angioplasty.

Background. The relation between myocardial perfusion and contractile reserve in patients with acute myocardial infarction, in whom anterograde flow is fully restored without significant residual stenosis, is still unclear.

Methods. Thirty patients with acute myocardial infarction treated successfully with primary coronary angioplasty underwent intracoronary contrast echocardiography before and after angioplasty and dobutamine echocardiography 3 days after the index infarction. One month later, two-dimensional echocardiography and coronary angiography were repeated in all patients and contrast echocardiography in 18 patients.

Results. After coronary recanalization, 26 patients showed myocardial reperfusion within the risk area, although 4 did not. At 1-month follow-up, all patients had a patent infarct-related artery without significant restenosis. Both left ventricular ejection fraction and wall motion score index within the risk area significantly improved in the patients with reperfusion ([mean ± SD] 38 ± 8% vs. 48 ± 12%, p < 0.005; and 2.35 ± 0.5 vs. 2 ± 0.6, p < 0.001, respectively), but not in those with no reflow. Of the 72 nonperfused segments before angioplasty, 27 showed functional improvement at follow-up. Myocardial contrast echocardiography had a sensitivity and a negative predictive value similar to dobutamine echocardiography in predicting late functional recovery (96% vs. 89% and 89% vs. 93%, respectively), but a lower specificity (18% vs. 91%, p < 0.001), positive predictive value (41% vs. 86%, p < 0.001) and overall accuracy (47% vs. 90%, p < 0.001).

Conclusions. Microvascular integrity is a prerequisite for myocardial viability after acute myocardial infarction. However, contrast enhancement shortly after recanalization does not necessarily imply a late functional improvement. Thus, contractile reserve elicited by low dose dobutamine is a more accurate predictor of regional functional recovery after reperfused acute myocardial infarction than microvascular integrity.

(J Am Coll Cardiol 1996;28:1677–83)>     

Clinical relevance of hibernating myocardium in ischemic left ventricular dysfunction

Patients with chronic ischemic left ventricular dysfunction may have a substantial amount of viable, hibernating myocardium, which is a state of chronic contractile dysfunction with reduced blood flow at rest. Coronary revascularization in these patients may result in improvement of left ventricular function; in the absence of viability, left ventricular function will not improve postrevascularization. Various noninvasive imaging techniques are available for detection of viable myocardium, including magnetic resonance imaging, dobutamine stress echocardiography, and nuclear imaging with single photon emission computed tomography or positron emission tomography. Because these techniques probe different characteristics of viable myocardium, the sensitivities and specificities of the techniques are not precisely identical; in general, dobutamine stress echocardiography has the highest specificity, whereas the nuclear techniques have the highest sensitivity. The presence of myocardial viability also is related to prognosis: patients with viable myocardium who undergo revascularization have a good prognosis, whereas patients with viable myocardium who are treated medically have poor outcome. Accordingly, assessment of viability is important in the therapeutic decision-making process of patients with chronic ischemic left ventricular dysfunction.     

Prognostic significance of the dobutamine echocardiography test in idiopathic dilated cardiomyopathy

Dobutamine stress echo provides potentially useful information on idiopathic dilated cardiomyopathy (IDC). From February 1, 1997, to October 1, 1999, 186 patients (131 men and 55 women, mean age 56 ± 12 years) with IDC, ejection fraction <35%, and angiographically normal coronary arteries were studied by high-dose (up to 40 μ/kg/min) dobutamine echo in 6 centers, all quality controlled for stress echo reading. In all patients, wall motion score index (WMSI) (from 1 = normal to 4 = dyskinetic in a 16- segment model of the left ventricle) was evaluated by echo at baseline and peak dobutamine. One hundred eighty-four patients were followed up (mean 15 ± 13 months) and only cardiac death was considered as an end point. There were 29 cardiac deaths. Significant parameters for survival prediction at univariate analysis are: ΔWMSI (chi-square 20.1; p <0.0000), New York Heart Association (NYHA) class (chi-square 17.57; p <0.0000), rest ejection fraction (chi-square 10.41; P = 0.0013), angiotensin-converting enzyme inhibitors (chi-square 8.23; P = 0.0041), and hypertension (chi-square 8.08, P = 0.0045). In the multivariate stepwise analysis only ΔWMSI and NYHA were independent predictors of outcome (ΔWMSI = hazard ratio 0.02, p <0.0000; NYHA CLASS = hazard ratio 3.83, p <0.0000). Kaplan-Meier survival estimates showed a better outcome for patients with a large inotropic response (ΔWMSI ≥0.44, a cutoff identified by receiver-operating characteristic curves analysis) than for those with a small or no myocardial inotropic response to dobutamine (93.6% vs 69.4%, P = 0.00033). Thus, in patients with IDC, an extensive contractile reserve identified by high-dose dobutamine stress echocardiography is associated with a better survival.     

Comparison of rest thallium-201 imaging and rest technetium-99m sestamibi imaging for assessment of myocardial viability in patients with coronary artery disease and severe left ventricular dysfunction

Objectives. We prospectively compared myocardial uptake of thallium-201 (²⁰¹Tl) at rest with rest technetium-99m (^99mTc) sestamibi uptake in the same patients, using quantitative single-photon emission computed tomography (SPECT).

Background. Because of only slightly delayed redistribution, ^99mTc-sestamibi uptake at rest may be less than ²⁰¹Tl uptake, thereby underestimating the extent of viability.

Methods. Twenty patients (2.25 stenoses per patient) with a mean left ventricular ejection fraction of 33 ± 2% underwent early and 3-h delayed rest ²⁰¹Tl SPECT, rest ^99mTc-sestamibi SPECT and two-dimensional echocardiography.

Results. The 280 scan segments were classified as either a normal, mild reduction in viability, defined as delayed ²⁰¹Tl uptake ≤75% and ≥5%, or a severe reduction in viability, defined as delayed ²⁰¹Tl uptake <50%. Mild and severe defects were further classified as fixed or having rest ²⁰¹Tl redistribution. Comparisons by patients were made using repeated measures analysis of variance and Dunnett's multiple comparisons test to compare ^99mTc-sestamibi with initial rest ²⁰¹Tl and delayed ²⁰¹Tl uptake. Twenty patients had at least one mild fixed defect (95 total segments). The average percent uptake in these defects for initial ²⁰¹Tl, delayed ²⁰¹Tl and ^99mTc-sestamibi was 62.5 ± 2.7%, 63.1 ± 7.1% and 67.3 ± 9.7%, respectively (p = NS). Twelve patients (27 segments) had mild redistribution defects on serial rest ²⁰¹Tl imaging. The average percent uptake was 61.6 ± 5.2% for initial ²⁰¹Tl, 67.0 ± 9.1% for delayed ²⁰¹Tl and 67.7 ± 12.4% for ^99mTc-sestamibi defects. Technetium-99m sestamibi uptake was not significantly different than that for delayed ²⁰¹Tl but was significantly greater than initial ²⁰¹Tl uptake. Seventeen patients (52 segments) had severe fixed ²⁰¹Tl defects. The average percent uptake was 38.9 ± 7.3% for initial ²⁰¹Tl, 38.3 ± 12.2% for delayed ²⁰¹Tl and 42.7 ± 14.2% for ^99mTc-sestamibi defects in these patients (p = NS). Ten patients (19 segments) had severe redistribution defects on rest ²⁰¹Tl imaging. The average percent uptake was 37.0 ± 8.5% for initial ²⁰¹Tl, 42.9 ± 8.6% for delayed ²⁰¹Tl and 44.5 ± 11.3% for ^99mTc-sestamibi defects. As was seen for mild ²⁰¹Tl redistribution defects, ^99mTc-sestamibi uptake was significantly higher than initial ²⁰¹Tl uptake, but not significantly different than delayed ²⁰¹Tl uptake in these severe defects.

Conclusions. Technetium-99m sestamibi uptake after injection at rest is comparable to ²⁰¹Tl uptake after injection at rest in patients with severe coronary artery disease and left ventricular dysfunction, suggesting comparable worth for viability assessment.     

Relation between coronary "steal" and contractile function at rest in collateral-dependent myocardium of humans with ischemic heart disease.

BACKGROUND: We tested the hypothesis that rest asynergy in collateral-dependent myocardium correlates with coronary steal. METHODS AND RESULTS: PET with [13N]ammonia measured myocardial blood flow and flow reserve in 15 patients with symptomatic chronic ischemic heart disease. Coronary angiography assessed stenosis severity and collateral blood supply. Echocardiography or contrast ventriculography evaluated regional wall motion. Collateral-dependent segments with normal flow at rest and supplied by coronary vessels having /=0.15 mL. min-1. g-1 versus rest. Blood flow at rest in asynergic, collateral-dependent segments with steal (1.15+/-0.35 mL. min-1. g-1) exceeded (P<0.0001) that of asynergic segments without steal (0.81+/-0.24) and those with normal contraction (0.77+/-0.18). Although the flow reserve ratio of segments with normal contraction (1.8+/-0.8) exceeded that of asynergic ones with (0.6+/-0.1) or without (1.3+/-0.4) steal, overlap was great. Correlation between basal contraction and flow reserve ratio in collateral-dependent myocardium was significant but weak (r=0.45, P<0.001). However, segments demonstrating "steal" with adenosine manifested asynergy in 22 of 23 collateral-dependent segments versus 24 of 39 nonsteal segments (chi2=7.10, P<0.01). CONCLUSIONS: Although myocardial flow reserve in collateral-dependent segments with normal contraction exceeded that of asynergic segments, overlap was great. However, in patients with angina or congestive heart failure, left ventricular segments demonstrating steal with adenosine almost always exhibit asynergy at rest. Thus, coronary steal may play an important role in the pathogenesis of chronic contractile impairment at rest, whereas simple reduction of flow reserve may be less important in selected patients.     

Repeated stunning precedes myocardial hibernation in progressive multiple coronary artery obstruction

OBJECTIVE

The aim of this study was to characterize a regional myocardial flow-function relationship in collateral dependent myocardium produced by multiple coronary artery obstruction.

METHODS

Ameroid constrictors were placed around the proximal right (RC) and circumflex (CX) coronary arteries and a silicon tubing cuff around the proximal LAD (left anterior descending artery) (luminal stenosis ±77%) in 18 dogs. Weekly two-dimensional echocardiography was performed for regional function (anterior [A], inferoposterior [IP], wall thickening [WT]), and fractional shortening (FS). Colored microspheres injected at baseline and before sacrifice, before and after dipyridamole (0.5 mg/kg) injection, determined resting flow (RF) and coronary reserve (CR), respectively.

RESULTS

Coronary angiography performed at four weeks after surgery confirmed occlusion of RC and CX with collateralization and a tight stenosis of LAD. Initially, an episodic reduction in A and IP WT was observed which became persistent later (AWT: 16 ± 3%; IPWT: 16 ± 4%, FS: 20 ± 4%, p < 0.005 vs. baseline [BS]). With dobutamine a biphasic response (improvement in A and IP WT between 5–15 and dysfunction between 20–30 μg/kg/min) was observed. Seven dogs were sacrificed at eight weeks and showed normal RF but reduced transmural CR (A: 75 ± 18%; IP: 46 ± 22% of control). Seven dogs underwent PTCA of the LAD at eight weeks and showed gradual improvement in AWT with normalization at 12 weeks (AWT: 30 ± 5%, p < 0.001 vs. eight weeks). At sacrifice RF and CR in the A wall were normal but there was reduced subendocardial RF in the IP region (64% of BS). Further, biopsy samples showed normal histological findings and high energy phosphate content in all dogs. Radioligand binding assays using ¹²⁵I-iodocyanopindolol showed downregulation of beta-adrenergic receptor density in the dysfunctional regions compared with control.

CONCLUSIONS

In this canine model of viable, collateral dependent and reversibly dysfunctional myocardium, there was early episodic dysfunction followed by persistent dysfunction which was initially associated with normal RF and later with subendocardial hypoperfusion.     

Scintigraphic Assessment of Regionalized Defects in Myocardial Sympathetic Innervation and Blood Flow Regulation in Diabetic Patients With Autonomic Neuropathy

Objectives. This study sought to evaluate whether regional sympathetic myocardial denervation in diabetes is associated with abnormal myocardial blood flow under rest and adenosine-stimulated conditions.

Background. Diabetic autonomic neuropathy (DAN) has been invoked as a cause of unexplained sudden cardiac death, potentially by altering electrical stability or impairing myocardial blood flow, or both. The effects of denervation on cardiac blood flow in diabetes are unknown.

Methods. We studied 14 diabetic subjects (7 without DAN, 7 with advanced DAN) and 13 nondiabetic control subjects without known coronary artery disease. Positron emission tomography using carbon-11 hydroxyephedrine was used to characterize left ventricular cardiac sympathetic innervation and nitrogen-13 ammonia to measure myocardial blood flow at rest and after intravenous administration of adenosine (140 μg/kg body weight per min).

Results. Persistent sympathetic left ventricular proximal wall innervation was observed, even in advanced neuropathy. Rest myocardial blood flow was higher in the neuropathic subjects (109 ± 29 ml/100 g per min) than in either the nondiabetic (69 ± 8 ml/100 g per min, p < 0.01) or the nonneuropathic diabetic subjects (79 ± 23 ml/100 g per min, p < 0.05). During adenosine infusion, global left ventricular myocardial blood flow was significantly less in the neuropathic subjects (204 ± 73 ml/100 g per min) than in the nonneuropathic diabetic group (324 ± 135 ml/100 g per min, p < 0.05). Coronary flow reserve was also decreased in the neuropathic subjects, who achieved only 46% (p < 0.01) and 44% (p < 0.01) of the values measured in nondiabetic and nonneuropathic diabetic subjects, respectively. Assessment of the myocardial innervation/blood flow relation during adenosine infusion showed that myocardial blood flow in neuropathic subjects was virtually identical to that in nonneuropathic diabetic subjects in the distal denervated myocardium but was 43% (p < 0.05) lower than that in the nonneuropathic diabetic subjects in the proximal innervated segments.

Conclusions. DAN is associated with altered myocardial blood flow, with regions of persistent sympathetic innervation exhibiting the greatest deficits of vasodilator reserve. Future studies are required to evaluate the etiology of these abnormalities and to evaluate the contribution of the persistent islands of innervation to sudden cardiac death complicating diabetes.     

Effects of tadalafil on myocardial blood flow in patients with coronary artery disease

OBJECTIVE: Erectile dysfunction and coronary artery disease share similar risk factors. Although phosphodiesterase-5 inhibitors used to treat erectile dysfunction do not adversely affect hemodynamic parameters in patients with coronary artery disease, their effects on myocardial blood flow are unknown. METHODS: In a randomized, double-blind, crossover study we examined the effects of tadalafil, 20 mg, compared with placebo on myocardial blood flow in patients with stable coronary artery disease (n=7, 52-73 years old). After tadalafil or placebo, myocardial blood flow was measured with positron emission tomography (nine-segment model) at rest, during maximal coronary hyperemia with adenosine, and during increased myocardial work with dobutamine. Abnormal flow was defined as myocardial blood flow <75% of maximum perfusion during adenosine plus placebo (46 normal/17 abnormal segments dentified). RESULTS: Compared with placebo, tadalafil had no significant effect on global myocardial blood flow at rest, during adenosine infusion, or during dobutamine infusion. Similarly, in normal and abnormal segments, tadalafil versus placebo had no significant effect on resting myocardial blood flow or on adenosine-induced increases in myocardial blood flow. In normal segments, myocardial blood flow with dobutamine plus tadalafil was greater than that with dobutamine plus placebo (1.79+/-0.56 versus 1.56+/-0.37 ml/g per min, P<0.01), and in abnormal segments, there was a trend for tadalafil compared with placebo to increase myocardial blood flow during dobutamine infusion (1.46+/-0.44 versus 1.36+/-0.36 ml/g per min, P=0.7). CONCLUSIONS: Tadalafil had no significant effect on global myocardial blood flow at rest, during adenosine infusion, or during dobutamine infusion. Compared with placebo, tadalafil significantly augmented myocardial blood flow during increased workload in normal regions, with a trend toward improving myocardial blood flow in poorly perfused regions.     

Myocardial flow reserve in patients with a systemic right ventricle after atrial switch repair

OBJECTIVES

The purpose of this study was to assess myocardial blood flow (MBF) and flow reserve in systemic right ventricles (RV) in long-term survivors of the Mustard operation.

BACKGROUND

There is a high prevalence of systemic RV dysfunction and impaired exercise performance in long-term survivors of the Mustard operation. A mismatch between myocardial blood supply and systemic ventricular work demand has been proposed as a potential mechanism.

METHODS

We assessed MBF at rest and during intravenous adenosine hyperemia in 11 long-term survivors of a Mustard repair (age 18 ± 5 years, median age at repair 0.7 years, follow-up after repair 17 ± 5 years) and 13 healthy control subjects (age 23 ± 7 years), using N-13 ammonia and positron emission tomography imaging.

RESULTS

There was no difference in basal MBF between the systemic RV of survivors of the Mustard operation and the systemic left ventricle (LV) of healthy control subjects (0.80 ± 0.19 vs. 0.74 ± 0.15 ml/g/min, respectively, P = NS). However, the hyperemic flows were significantly lower in systemic RVs than they were in systemic LVs (2.34 ± 0.0.69 vs. 3.44 ± 0.62 ml/g/min respectively, p < 0.01). As a result, myocardial flow reserve was lower in systemic RVs than it was in systemic LVs (2.93 ± 0.63 vs. 4.74 ± 1.09, respectively, p < 0.01).

CONCLUSIONS

Myocardial flow reserve is impaired in systemic RVs in survivors of the Mustard operation. This may contribute to systemic ventricular dysfunction in these patients.     

Prognostic implications of evaluation of contractile reserve in akinetic and hypokinetic segments during low dose dobutamine echocardiography in patients with acute myocardial infarction

Background: Previous studies have reported the prognostic value of myocardial viability (MV) detected using low-dose dobutamine echocardiography (DbE). However, viability was frequently evaluated as improvement in regional wall motion score index, which includes increased function in hypokinetic segments, in which viable myocardium is necessarily present. It is not known whether an evaluation focusing on akinetic segments, in which the possible presence of viable myocardium is unknown, might have more prognostic value. The aim of this study was to compare the prognostic value of the improvement of myocardial function during dobutamine infusion in akinetic and hypokinetic regions in patients with acute myocardial infarction (AMI). Methods: 191 patients with uncomplicated AMI and at least one akinetic segment were retrospectively selected from those consecutively examined at our echo-laboratory to evaluate MV using DbE. Myocardial viability was evaluated both as an increment in RWMSI (ΔRWMSI), which takes into consideration improvement in both akinetic and hypokinetic regions, and as an improvement of function in akinetic (Δ akinetic) and hypokinetic (Δ hypokinetic), segments considered separately. Follow-up evaluation was performed at 30±13 months. Results: On the basis of the ΔRWMSI, 94/191 patients were judged to have myocardial viability, whereas considering myocardial viability in akinetic segments only, 72/191 patients showed viability. At follow-up 18 patients had died (six viable considering ΔRWMSI; three viable considering Δ akinetic). The presence of a previous AMI, the site of AMI, RWMSI and the number of akinetic segments, and ΔRWMSI and Δ akinetic were related to mortality at univariate Cox analysis. At multivariate stepwise Cox regression analysis Δ akinetic, but not Δ hypokinetic proved to be significantly related to mortality. The Kaplan–Meier survival curves were no different in patients with or without viable myocardium evaluated as ΔRWMSI, while they were significantly different considering patients with or without viability in akinetic segments (P=0.04). Conclusion: In conclusion our study confirms the prognostic importance of the evaluation of myocardial viability in infarcted patients. However, it points out that it is the presence of viability in akinetic segments that affects long-term survival in these patients. This supports the hypothesis that other mechanisms, above and beyond the effect on regional wall motion, are involved in the beneficial effects of myocardial viability.     

Effects of inotropic stimulation on segmental left ventricular relaxation quantified by color kinesis

Although myocardial ischemia impairs left ventricular (LV) relaxation before contractile function, regional LV diastolic dysfunction is difficult to evaluate by conventional echocardiography. Because β-adrenergic stimulation enhances myocardial relaxation, we sought to characterize segmental LV diastolic function (by color kinesis) during dobutamine stress echocardiography and compare it with independently assessed segmental systolic function. We studied 22 patients with suspected coronary artery disease with color kinesis by acquiring digital images with endocardial motion display throughout diastole. Quantification of LV segmental diastolic peak filling rate (SPFR, normalized to segmental end-diastolic area/s) was obtained at rest, low-dose, and peak dobutamine infusion in myocardial segments visualized from the short-axis and/or apical 4-chamber views. In patients with resting normal LV systolic function and a dobutamine-induced hypercontractile response (group I, n = 13 patients; 102 segments), progressive increases in SPFR (p <0.001) were seen in all segments. However, in LV segments with resting systolic wall motion abnormalities (group II, n = 9 patients; 74 segments) SPFR measured at rest was significantly lower than that in group I (p <0.005) and did not increase significantly in response to dobutamine. In both groups of patients, LV myocardial segments (n = 528; rest and after dobutamine)—systolic and quantitative diastolic function—were concordant in 84% and 77% as viewed from short-axis and apical views, respectively. Thus, segmental LV diastolic function can be measured with color kinesis at rest and after inotropic stimulation, allowing comparison with segmental systolic function during pharmacologic stress testing.     

Assessment of myocardial vitality with dobutamine echocardiography: current review

Myocardial stunning (contractile dysfunction in the presence of normalized perfusion) and myocardial hibernation (contractile dysfunction matching reduced perfusion) have represented separate concepts of viable, but dyssynergic myocardium in the past. However, in vivo experimental and clinical work suggests that repetitive ischemia due to coronary artery disease may induce a gradual transition between stunned and hibernating myocardium. Myocardial hibernation itself can result from a spectrum of ischemic conditions ranging from impaired myocardial blood flow reserve to frank hypoperfusion. With increasing severity and duration of ischemia, degeneration of cardiac myocytes, accumulation of glycogen and cell death ensue. Additionally, there is an increase of extracellular matrix protein content leading to reparative fibrosis, which in turn limits functional recovery. In the light of these structural features, the available methods for detection of viable myocardium, in particular dobutamine echocardiography and nuclear imaging techniques, offer complementary rather than contradictory information. Dobutamine echo has satisfactory sensitivity, excellent specificity, and high diagnostic accuracy for the detection of viable dyssynergic myocardium. While in the past only its predictive accuracy for segmental recovery has been validated, newer data show an improved survival after revascularization if at least four viable dyssynergic left ventricular segments in a 16 segment model can be identified by dobutamine echocardiography. The complete (low and high dose) dobutamine protocol can elicit several types of contractile responses (sustained improvement in contraction or monophasic response, biphasic response, new wall motion abnormality) which should be interpreted in view of other clinical data including a previous infarction. The test protocol can be used safely at the end of the first week after myocardial infarction. If ischemia or viability is documented, revascularization should be performed promptly. A similar strategy should be followed in the setting of chronic coronary heart disease with left ventricular dysfunction. Since the structural changes of hibernating myocardium are progressive, time to revascularization is critical. On the other hand, responsible therapeutic planning requires proof of ischemia or viability before initiating a potentially hazardous revascularization procedure.