Introduction
The term “viable myocardium” has been introduced in clinical practice to characterize dysfunctional tissue in patients with coronary artery disease (CAD) that has the potential to recover its function. Contractile dysfunction may be caused by necrotic myocardium or by viable myocardium. If the dysfunction is due to fibrosis, no recovery can be expected; if the dysfunction is due to viable myocardium, recovery can occur in some patients.[1,2]
Reversible dysfunction can be caused by several mechanisms including ischemia, hibernation, stunning and repetitive stunning. Figure 1 is a schematic representation of the relation between flow and function under these different conditions. 

Figure 1. Schematic representation of the relation between flow and function in different pathophysiological conditions. The arrow indicates restoration of normal flow. 

During episodes of ischemia function is depressed but returns to normal after disappearance of the ischemia. During prolonged episodes of ischemia followed by reperfusion, which may occur in the setting of acute myocardial infarction treated by reperfusion therapy, restoration of function may be considerably slower. In hibernating myocardium, function is adapted to a situation of chronic underperfusion. Finally, repetitively stunned myocardium denotes a progressive loss of function after repetitive episodes of ischemia. Although the exact pathophysiology of dysfunctional but viable myocardium is still unclear and remains controversial,[2–4] the potential for functional recovery has clinical relevance. Indeed, whatever the exact mechanism of reversible dysfunction, reperfusion in the acute stage of ischemic syndromes or revascularization in the chronic stage is required for functional recovery. 
The awareness that even severely dysfunctional myocardium in patients with CAD may show an improvement in functional state after revascularization has resulted in a tremendous amount of research to identify viable tissue by the optimal diagnostic approach. 

How to assess viability
A large number of techniques have been developed to identify dysfunctional but viable myocardium. An in-depth review of available techniques has been discussed in a previous issue of Heart and Metabolism by Senior and Lahiri[5] and in this issue by Bax et al., and include perfusion imaging (nuclear and echocardiography), metabolic imaging (nuclear) and imaging of contractile reserve (echocardiography and magnetic resonance imaging). However, most studied and commonly used in clinical practice are fluorine–18 fluorodeoxyglucose (FDG), thallium–201 (Tl-201) stress-redistribution-reinjection, Tl–201 rest-redistribution, technetium–99m (Tc-99m) sestamibi (MIBI) single photon emission computed tomography (SPECT) and low-dose dobutamine echocardiography (LDDE). Their relative advantages are outlined below.

FDG
Since the original observation by Marshall et al.[6] in 1983, considerable evidence has accumulated to show that FDG in combination with PET can detect viable myocardium. FDG is a glucose analog that traces exogenous glucose uptake by the myocardium. Viable myocardium is characterized by preserved FDG uptake in an area with depressed left ventricular (LV) function. Many studies have validated the use of FDG for the prediction of functional recovery in patients undergoing revascularization.[7]

Tl–201 scintigraphy
The initial uptake of Tl–201 by myocytes is mainly determined by regional perfusion, whereas the integrity of the cell membrane is predominantly important for delayed imaging of tracer retention. Although different Tl–201 protocols have been described,[8] mainly Tl–201 stress-redistribution-reinjection and Tl–201 rest-redistribution are currently used. Studies have shown[9] that after reinjection of 1 mCi of Tl-201 after 3–4 h redistribution imaging detects viability in more than one third of segments deemed irreversibly damaged because they showed a fixed defect on conventional stress-redistribution Tl–201 imaging. The ability to detect viable myocardium was demonstrated by several studies in which viability was compared with functional outcome after revascularization. 
Whereas Tl–201 stress-redistribution-reinjection scintigraphy provides information on both exercise-induced ischemia and viability, Tl–201 rest-redistribution provides information on viability only. A large number of studies have evaluated the use of Tl–201 rest-redistribution imaging in revascularized patients. Two studies[10,11] compared Tl–201 stress-redistribution-reinjection with Tl–201 rest-redistribution imaging and showed a concordance between the two techniques of 80%, at least when defect reversibility was considered an indicator of viability. When the severity of Tl–201 activity in irreversible defects was taken into account, the concordance increased to 94%.[10].

Tc–99m MIBI
Myocardial uptake of Tc–99m MIBI parallels regional perfusion and provides adequate information for the detection of CAD. The uptake and retention of Tc–99m MIBI is also dependent on cell membrane integrity and mitochondrial function (membrane potential)[12,13]and thus may reflect cellular viability. Many studies have compared Tc–99m MIBI imaging with other scintigraphic modalities, including Tl–201 stress-redistribution-reinjection,[14] Tl–201 rest-redistribution[15] and FDG PET.[16] These concordance studies were consistent in showing that Tc–99m MIBI was less accurate in the detection of myocardial viability. However, specificity of Tc–99m MIBI is higher than that of Tl–201 stress-redistribution-reinjection and Tl–201 rest-redistribution in detecting absence of functional recovery after revascularization. 

Low-dose dobutamine echocardiography 
Echocardiography during the infusion of low dose dobutamine (5–15 mg/kg body weight per min) has been proposed as an alternative method for assessing myocardial viability in patients with chronic ischemic heart disease.[17] The hallmark of viability is improved contraction of a dysfunctional segment after adrenergic stimulation. Available studies indicate that LDDE7 adequately detects recovery of contractile function after revascularization. Several studies have compared LDDE with other imaging modalities to assess viability, including FDG PET,[18] Tl–201 stress-redistribution-reinjection,[19] Tl–201 rest-redistribution[20] and Tc–99m MIBI,[21] showing good agreement in most studies.

Which technique to choose
Bax et al. performed a meta-analysis on the diagnostic value of the five above-mentioned, most clinically used techniques[7] to assess viability. In this meta-analysis the data publications were reanalyzed and the sensitivity and specificity plus the 95% confidence intervals of the techniques to predict presence and absence of recovery of regional function after revascularization were calculated. Recovery of function is considered to be the gold standard for assessing viability. The results, as previously published[7] and discussed in Heart and Metabolism by Senior and Lahiri[5] (Figure 2), showed that Tl–201 reinjection and Tl–201 rest-redistribution had a high sensitivity (90% and 86%, respectively) but a low specificity of 47% and 54%, respectively. 

Tc-99m MIBI had an intermediate specificity of 69%. LDDE had the highest specificity of 81%, but the sensitivity of FDG PET was higher (88%) than that of LDDE (84%). 
Do these results imply that Tl–201 techniques should not be used to assess viability? Although the specificity of Tl–201 reinjection and rest-redistribution were lower compared to the other techniques, the question is how clinically relevant this low specificity is. Because of the high sensitivities, the negative predictive value for functional outcome is high (assuming a balanced division between recoverable and non-recoverable regions in the study population).Thus, patients are probably correctly deferred from revascularization if no viable tissue is present and the cardiologist/ cardiac surgeon may take the risk of absence of functional recovery because patients are usually proposed for revascularization because of angina. 
In this respect it is worthwhile noting that the prevalence of recoverable segments after revascularization varied greatly between studies, ranging between 22% and 82%. This suggests major differences between populations studied.
Moreover, we have recently studied the diagnostic value of rest-redistribution Tl–201 SPECT for the prediction of global LV functional recovery after revascularization. The specificity for detecting absence of global functional improvement (defined as an improvement of at least 5 ejection fraction units) was 76%.[22] This implies that the Tl–201 techniques are adequate for the more clinically relevant global functional improvement after revascularization. Also, the presence of viable myocardium may have implications for, and may have long-term effects on, clinical factors that are independent from the resting functional state of the left ventricle. These factors include prognosis[23] (see below), the response during stress,[24] exercise capacity[25] and quality of life.[26] At present, the relative merits of the different viability techniques for the prediction of these clinical factors are largely unknown and should be prospectively evaluated in a large patient cohort.
Moreover, the meta-analysis of the published data revealed some of the weaknesses of the currently available evidence. The inclusion criteria varied considerably between studies, particularly with respect to the severity of baseline dysfunction. Ideally, only patients with a global ejection fraction <30–35% should be studied because these patients are likely both to benefit from and to have a greater risk during revascularization. Most studies included only a limited number of patients, suggesting inclusion bias. The majority of studies did not provide evidence of vessel or graft patency; reocclusion may prohibit viable segments from recovering, thereby underestimating the true specificity of all techniques. The optimal moment for the assessment of functional follow-up after revascularization is uncertain. Currently, follow-up is frequently performed 3 months after revascularization. However, preliminary data have demonstrated that full recovery is not expected to occur before 6 or even 12 months after revascularization. Importantly, global and regional function should be evaluated by an independent technique. Studies of LDDE have invariably used echocardiograms to evaluate the effect of revascularization. The use of an internally consistent standard may contribute in part to the excellent diagnostic value of this technique. In addition, the acquisition and interpretation of echocardiograms strongly depends on operator experience.
Thus, in practice, the choice between imaging modalities also depends on local availability, the status of the equipment, the waiting list, the prevalence of viable/non-viable tissue in the local population (largely influencing predictive values of functional improvement) and expertise in acquisition and interpretation, which is particularly critical for LDDE. 
Finally, it is obvious that the viability tests are not perfect and have different performance characteristics. Possibly, complementary techniques should be combined to obtain the best clinical prediction. Then strategies can be developed for a cost-effective use of tests in a sequential manner, as preliminary data suggest.[27]

Clinical value of viability testing
Viability detection can be used to clarify a number of clinical issues: 1) pre-operative detection of functional recovery after revascularization in patients with chronically depressed LV function, 2) determination of prognosis in patients with chronic CAD, 
3) peri-operative risk assessment in patients undergoing revascularization, 
4) prediction of reversal of LV dysfunction after acute myocardial infarction, and 
5) determination of prognosis after myocardial infarction.

Pre-operative detection of functional recovery after revascularization in patients with chronically depressed LV function
As discussed above and in this issue a large number of studies have been published showing that viable tissue is related to improvement of regional and global LV function after revascularization. Moreover, improvement of function is associated with improvement of heart failure symptoms and exercise capacity. Reversal of myocardial dysfunction is particularly relevant in patients with depressed ventricular function because surgical revascularization improves long-term survival in such patients.[28]
 
Determination of prognosis in patients with chronic CAD
In addition to the prediction of functional recovery after revascularization, viability imaging may also provide prognostic information on morbidity and mortality. In this issue Bax et al. show the data of FDG PET studies, indicating that the presence of viability in patients who are treated medically is associated with a high event rate, much higher than in patients with viable tissue who underwent revascularization, or in patients without viable tissue, independent of the revascularization. These findings have been confirmed by other techniques. Recently, similar results were published with Tl–201 rest-redistribution imaging. Gioia et al.[29] studied the prognosis of patients with severe LV dysfunction, who were treated medically. During a mean follow-up of 31 months, there were 11 cardiac deaths in patients with no redistribution (26%) on Tl–201 rest-redistribution imaging and 22 in patients with redistribution (58%), and multivariate Cox survival analysis on important clinical, angiographic and thallium variables showed that the presence of viability was an independent predictor of death. Meluzin et al.[30] divided revascularization patients into three groups: based on LDDE studies. Patients with extensive viable tissue had the lowest event rate, confirming previous findings.

Peri-operative risk assessment in patients undergoing revascularization
Not only is viability assessment useful for the long-term outcome after revascularization, but may also be used for perioperative risk assessment. Haas et al.[31] studied 76 patients with advanced CAD and poor LV function who underwent CABG. Of these patients 35 underwent CABG on the basis of clinical and angiographic data, while 41 also underwent FDG PET imaging. Patients without viability assessment had a significantly higher mortality (11%) compared with patients with viability assessment (0%). Postoperatively, viability-tested patients had a less complicated recovery. They required lower doses of catecholamines and demonstrated a significantly decreased incidence of low output syndrome. Although this was a retrospective study in which the reasons for performing FDG PET, the presence of viable tissue and the decision process for accepting patients are not given, the data suggest that, if cardiac surgeons include viability data in their patient management, peri- and postoperative outcome may be better than without the use of viability data. Larger, prospective studies are needed to confirm these findings.

Prediction of reversal of LV function after acute myocardial infarction
The presence of viability in patients with an acute myocardial infarction is associated with improvement of LV function during follow-up. Schwaiger et al. performed in 1986 a study in which patients underwent FDG imaging early after myocardial infarction.[32] They found that viable segments showed improvement of regional function during follow-up in 50%, in contrast to non-viable segments, which showed no improvement al all. These FDG findings were confirmed by Huitink et al.[33] Also, LDDE has been successfully employed to predict functional recovery after acute myocardial infarction.[33–37] Thus, viability in the infarct area is associated with spontaneous improvement of LV function and the absence of viability is strongly predictive of absence of recovery. 

Determination of prognosis after myocardial infarction
Data regarding the effect of viability on prognosis after acute myocardial infarction are conflicting: some studies associated viability with a poor prognosis and some with a good prognosis. 
Brown et al.[38] found that patients with viability had a higher risk of cardiac events. Similarly, Basu et al.[39] found in infarct patients treated with thrombolysis that the event-free survival of patients with reversible perfusion defects, detected by stress/nitroglycerine-enhanced rest Tl–201 imaging was significantly lower than in patients without reversible perfusion defects. Strikingly, Tl–201 stress-redistribution imaging (without the use of nitroglycerine) did not discriminate between event and event-free patients. At our institution two prognosis studies in patients admitted with an acute myocardial infarction were performed. Huitink et al.[40] performed planar FDG imaging and followed the infarct patients for a mean of 47 months (Figure 3). 

Figure 3. Viability and poor prognosis after myocardial infarction. Patients with viable tissue (solid line) had a significantly higher event rate than patients without viable tissue (dashed line). (With permission of the Am J Cardiol.)[40]

Patients with viable tissue had a 49% event rate, in contrast to 7% in patients without viability;p<0.009. Nijland et al.[41] studied the in-hospital event rate of admitted patients. Viability was assessed by LDDE early after infarction. They found in patients with viability an in-hospital event rate of 32% versus 10% in patients without viability; p<0.05. Thus, these data on patients with acute MI are in line with prognosis data in patients with chronic CAD (see above).
The small study by Yoshida and Gould using PET[42] and, especially, the study by Carlos et al. [43] using LDDE showed that viability, together with a small infarct size and absence of ischemia, was associated with a good prognosis after myocardial infarction (Figure 4). 

Figure 4. Viability and good prognosis after infarction. Patients with viable tissue as assessed by dobutamine regional wall thickening (DRWT) had a significantly lower event rate than patients without DRWT. Similarly, patients with a small infarct size (Inf Size) had a better event free survival. (With permission of Circulation).[43] 

Also, Picano et al.[44] found in medically treated patients that the presence of viable tissue exerted a protective effect after infarction by reducing death. Finally, Previtali et al.[45] also combined viability and ischemia detection in infarction patients. The combination of viability and ischemia had the highest hard and soft event rate after infarction, but multivariate analysis showed that the presence of ischemia was the most important predictor of events, while viability had no prognostic value. 
Thus, the data on the prognostic value of viability after infarction are conflicting. Prognosis after acute infarction depends on a large number of factors, including the site of infarction, extent of infarction/degree of LV dysfunction, extent of coronary artery disease and ischemia in and outside the infarction area, the choice of treatment in the acute phase and thereafter (medical, thrombolysis, PTCA) and many other clinical factors which have to be unaccounted for. All these factors may have a complicated interaction obscuring the contribution of one single parameter. Therefore, to assess the prognostic value of viability, randomized clinical trial are needed, comparing standard treatment of viability after infarction with PTCA of the infarct-related coronary artery. This trial is being setup in the Netherlands.

When to assess viability 
Using LDDE and PET, Pierard et al.[34] studied patients with acute anterior infarction, treated with thrombolysis. Functional recovery during follow-up was observed in all patients with normal perfusion and LDDE, viable segments. In patients with increased FDG uptake and contractile recovery during LDDE recovery of function during follow-up was observed in a minority of patients, whereas patients without signs of viability with either technique showed no recovery. These data were confirmed by Knudsen et al.[46]: see Figure 5. 

Figure 5. Time-course of viable tissue (LDDE +) in patients after infarction. In one third of patients with viable tissue, viability was lost during follow-up. (With permission of the Am Heart J.) [46]

Using LDDE, they found that one third of viable tissue early after infarction lost the ability to respond to dobutamine during follow-up, suggesting loss of viability in the time-course after infarction. In the study of Pierard et al.[34] this tissue was characterized by an increased FDG uptake, suggesting jeopardized myocardium that frequently loses viability in the absence of revascularization. Indeed, Barilla et al.[35] demonstrated that acute infarct patients with viable tissue who underwent coronary revascularization showed a better LV functional improvement during follow-up than infarct patients with viable tissue who were treated medically.
Similar findings were observed in patients with chronic LV dysfunction: Schwartz et al.[47] estimated the duration of viable tissue before revascularization and found that only in patients with viability of a short-time duration LV function improved after revascularization. Beanlands et al.[48] studied the duration of the waiting list and observed a significantly better improvement of LV function after revascularization in patients on a short waiting list. These data suggest that viable areas are at risk of deterioration. Probably, these patients merit early revascularization for improvement of LV function and thus prognosis. 

Which patients need viability testing
Based on the data presented above, viability testing is recommended in patients with chronic left ventricular dysfunction due to coronary artery disease. If extensive viable tissue is present, improvement of LV function, symptoms, exercise capacity, quality of life and prognosis is to be expected after revascularization. In clinical practice, however, a considerable number of these patients also have anginal complaints due to (exercise-induced) ischemia. If these patients are accepted for total revascularization (CABG), viability assessment may not be necessary because revascularization is performed both on vessels causing ischemia and on vessels causing chronic dysfunction. When in these anginal patients there is doubt about grafting an artery (e.g. after chronic infarction), then additional viability assessment needs to be performed. Finally, the cardiac surgeon may want viability assessment for peri-operative risk stratification. Nevertheless, a weakness of the above mentioned data in chronic CAD is that most of the studies on improvement of function and prognosis were retrospective in nature, possibly leading to patient bias. For example, improvement of function could only be assessed in patients who survived follow-up after revascularization. Also, major improvements in medical treatment have been obtained in the last decade by the standard treatment of heart failure with ACE-inhibitors and beta-blockers. Addition of beta-blockers on top of ACE-inhibitors and diuretics has been shown to improve both survival and left ventricular function. A meta-analysis of the available data on the effects of beta-blockers on left ventricular function showed that on average the ejection fraction rose more than 6%,[49] irrespective of the presence or absence of viable tissue in these patients! Therefore, a randomized trial is needed to show that revascularization of viable tissue is superior to optimal medical treatment in patients with chronic LV dysfunction and mild or no angina.
Another important group of patients are those in whom a choice has to be made between revascularization and cardiac transplantation. In these patients viability assessment should be an integral part of the diagnostic work-up, because of the potential improvement of function and prognosis of viable tissue as indicated above.
In patients after acute myocardial infarction, recommendations regarding routine assessment of viable tissue are less clear. Stunned myocardium may spontaneously improve over time, giving the cardiologist the opportunity for watchful waiting. On the other hand, initial studies in small numbers of patients suggest that viable tissue may deteriorate over time. Furthermore, data on the impact of viability on prognosis after infarction are conflicting as some of studies associate viability with a good prognosis and some with a poor prognosis. Therefore, further studies giving insight into which patient is at risk after infarction are clearly needed as well as a randomized revascularization trial of viable tissue.

REFERENCES

1: Circulation 1994 Aug;90(2):735-45

Related Articles, Books, LinkOut

Histological alterations in chronically hypoperfused myocardium. Correlation with PET findings.

Maes A, Flameng W, Nuyts J, Borgers M, Shivalkar B, Ausma J, Bormans G, Schiepers C, De Roo M, Mortelmans L.

Department of Nuclear Medicine, Katholieke Universiteit Leuven, Belgium.

BACKGROUND: In patients with chronic coronary artery disease (CAD) and left ventricular dysfunction, flow/metabolic studies of the myocardium with positron emission tomography (PET) are able to distinguish viable but dysfunctional myocardium from irreversible ischemic injury and scar tissue. In this study, PET findings of blood flow and metabolism in chronically hypoperfused myocardium were correlated with histology. METHODS AND RESULTS: We studied 33 patients suffering from CAD. In each patient, myocardial blood flow and metabolism were measured with PET 1 or 2 days before revascularization. During surgery, transmural biopsies were taken from the left ventricular anterior wall and planimetrically scored for the degree of myolysis (sarcomere loss). The amount of connective tissue was calculated using morphometric techniques. Contrast ventriculography demonstrated abnormal wall motion in 23 patients. Fourteen patients with a mismatch pattern (decreased flow with preserved metabolism) in the biopsy region after quantitative analysis of the PET data showed 11 +/- 6 vol% fibrosis and 25 +/- 13% cells with sarcomere loss. The space formerly occupied by sarcomeres was mainly replaced by glycogen and mitochondria. A significant wall motion improvement was noted 3 months after surgery. Nine patients showed a match pattern (concordant flow/metabolism defects). The biopsies revealed 35 +/- 25% fibrosis and 24 +/- 15% glycogen-storing cells. The biopsies of the 10 patients with normal anterior wall motion showed 8 +/- 4% fibrosis and 12 +/- 8% glycogen-accumulating cells. CONCLUSIONS: It can be concluded that areas with impaired wall motion and a PET match pattern show extensive fibrosis. Regions with reduced flow and preserved FDG metabolism, however, contain predominantly viable cells. In these regions, significant recovery of wall motion is found after revascularization. Regions with normal wall motion contain predominantly viable cells. Cells with reduced contractile material and increased glycogen content are mainly found in areas with wall motion impairment but are also present in areas with normal wall motion and a severe stenosis of the coronary vessel.

PMID: 8044942 [PubMed - indexed for MEDLINE]

 

2: Circulation 1993 May;87(5):1513-23

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Comment in:

• Circulation. 1993 May;87(5):1756-8.
• Circulation. 1994 Apr;89(4):1907-8.

Mechanisms of chronic regional postischemic dysfunction in humans. New insights from the study of noninfarcted collateral-dependent myocardium.

Vanoverschelde JL, Wijns W, Depre C, Essamri B, Heyndrickx GR, Borgers M, Bol A, Melin JA.

Division of Cardiology, University of Louvain Medical School, Brussels, Belgium.

BACKGROUND. Even in the absence of a previous myocardial infarction, patients with coronary artery disease often present with chronic regional wall motion abnormalities that are reversible spontaneously or after coronary revascularization. In these patients, regional dysfunction has been proposed to result either from prolonged postischemic dysfunction (myocardial "stunning") or from adaptation to chronic hypoperfusion (myocardial "hibernation"). This study examines which of these two mechanisms is responsible for the chronic regional dysfunction often detected in patients with angina and noninfarcted collateral-dependent myocardium. METHODS AND RESULTS. Twenty-six anginal patients (19 men; mean age, 60 +/- 9 years old) with chronic occlusion of a major coronary artery but without previous infarction were studied. Positron emission tomography was performed to measure absolute regional myocardial blood flow with 13N-ammonia at rest (n = 26) and after intravenous dipyridamole (n = 11). The kinetics of 18F-deoxyglucose and 11C-acetate were measured to calculate the rate of exogenous glucose uptake and the regional oxidative metabolism (n = 15). Global and regional left ventricular function was evaluated by contrast ventriculography at baseline (n = 26) and after revascularization (n = 12). Transmural myocardial biopsies from the collateral-dependent area were obtained in seven patients during bypass surgery and analyzed by optical and electron microscopy. According to resting regional wall motion, patients were separated into groups with and without dysfunction of the collateral-dependent segments. In patients with normal wall motion (n = 9), regional myocardial blood flow, oxidative metabolism, and glucose uptake were similar among collateral-dependent and remote segments. By contrast, in patients with regional dysfunction (n = 17), collateral-dependent segments had lower myocardial blood flow (77 +/- 25 versus 95 +/- 27 mL.min-1.100 g-1, p < 0.001), smaller k values (slope of 11C clearance reflecting oxidative metabolism, 0.049 +/- 0.015 versus 0.068 +/- 0.020 min-1, p < 0.001) and higher glucose uptake (relative 18F-deoxyglucose-to-flow ratio of 1.9 +/- 1.6 versus 1.2 +/- 0.2, p < 0.05) compared with remote segments. However, myocardial blood flow and k values were similar among collateral-dependent segments of patients with and without segmental dysfunction. After intravenous dipyridamole, collateral-dependent myocardial blood flow increased from 78 +/- 5 to 238 +/- 54 mL.min-1.100 g-1 in three patients with normal wall motion and from 88 +/- 17 to only 112 +/- 44 mL.min-1.100 g-1 in eight patients with regional dysfunction. There was a significant (r = -0.85, p < 0.001) inverse correlation between wall motion abnormality and collateral flow reserve. Analysis of the tissue samples obtained at the time of bypass surgery showed profound structural changes in dysfunctioning collateral-dependent areas, including cellular swelling, loss of myofibrillar content, and accumulation of glycogen. Despite these alterations, the regional wall motion score improved significantly in the patients studied before and after revascularization (from 3.8 +/- 1.3 to 0.8 +/- 0.9, p < 0.005). CONCLUSIONS. In a subgroup of patients with noninfarcted collateral-dependent myocardium, immature or insufficiently developed collaterals do not provide adequate flow reserve. Despite nearly normal resting flow and oxygen consumption, these collateral-dependent segments exhibit chronically depressed wall motion and demonstrate marked ultrastructural alterations on morphological analysis. We propose that these alterations result from repeated episodes of ischemia as opposed to chronic hypoperfusion and represent the flow, metabolic, and morphological correlates of myocardial "hibernation."

PMID: 8491006 [PubMed - indexed for MEDLINE]

 

3: Am Heart J 1989 Jan;117(1):211-21

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Comment in:

• Am Heart J. 1989 Dec;118(6):1361.

The hibernating myocardium.

Rahimtoola SH.

Department of Medicine, University of Southern California School of Medicine.

The hibernating myocardium refers to resting LV dysfunction due to reduced coronary blood flow that can be partially or completely reversed by myocardial revascularization and/or by reducing myocardial oxygen demand. It is different from the stunned myocardium. Methods for its detection are not yet perfect. Hibernating myocardium has been demonstrated to be present in several clinical subgroups of patients; however, currently its full clinical presence and impact are not adequately defined.

PMID: 2783527 [PubMed - indexed for MEDLINE]

 

4: Circulation 1992 Dec;86(6):1671-91

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Myocardial 'stunning' in man.

Bolli R.

Department of Medicine, Baylor College of Medicine, Houston, Tex. 77030.

Publication Types:

• Review
• Review, Tutorial

PMID: 1451239 [PubMed - indexed for MEDLINE]

5. Senior R, Lahiri A. Metabolic imaging: predicting recovery of function in heart failure. Heart and Metabolism 1999; 6: 12–17.

6: Circulation 1983 Apr;67(4):766-78

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Identification and differentiation of resting myocardial ischemia and infarction in man with positron computed tomography, 18F-labeled fluorodeoxyglucose and N-13 ammonia.

Marshall RC, Tillisch JH, Phelps ME, Huang SC, Carson R, Henze E, Schelbert HR.

Studies have shown that the extraction of glucose per unit flow is increased in moderately ischemic myocardium primarily due to anaerobic glucose metabolism manifested as lactate production, whereas myocardial infarction is characterized by the loss of metabolically active myocardium. To determine the feasibility of demonstrating these metabolic abnormalities reflecting both ischemia and infarction, we used positron computed tomography (PCT) to evaluate relative regional myocardial exogenous glucose utilization and perfusion in 15 patients with recent myocardial infarction. The positron-emitting tracers of glucose metabolism and perfusion, 18F-2-fluoro-2-deoxyglucose (FDG) and N-13 ammonia, respectively, were used. Fourteen of 19 documented infarctions were demonstrated by PCT to have concordantly decreased glucose utilization and perfusion. However, in an additional 11 regions, glucose utilization was disproportionately increased relative to perfusion, consistent with ischemic glucose consumption. These findings correlated with the presence of postinfarction angina, the site of ischemic electrocardiographic changes during chest pain, and the presence of regional left ventricular dysfunction and severe coronary artery disease. Because three ECG infarct zones not detected by PCT demonstrated ischemic glucose utilization, only two of 19 electrocardiographically defined infarctions had no detectable metabolic abnormality. We conclude that the changes in regional FDG and N-13 ammonia concentrations detected with PCT in patients who had had a recent myocardial infarction are consistent with regional exogenous glucose utilization and perfusion in moderately ischemic and irreversibly infarcted myocardium. This approach has the potential to identify and differentiate resting myocardial ischemia from infarction and to assess tissue viability after an ischemic event.

PMID: 6600659 [PubMed - indexed for MEDLINE]

 

7: J Am Coll Cardiol 1997 Nov 15;30(6):1451-60

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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.

Bax JJ, Wijns W, Cornel JH, Visser FC, Boersma E, Fioretti PM.

Department of Cardiology, Academic Hospital, Leiden, The Netherlands. bax@cardio.azl.nl

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.

Publication Types:

• Meta-Analysis

PMID: 9362401 [PubMed - indexed for MEDLINE]

 

8: Circulation 1993 Jan;87(1):1-20

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Erratum in:

• Circulation 1993 Jun;87(6):2070

Current diagnostic techniques of assessing myocardial viability in patients with hibernating and stunned myocardium.

Dilsizian V, Bonow RO.

Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.

Publication Types:

• Review
• Review, Tutorial

PMID: 8418996 [PubMed - indexed for MEDLINE]

 

9: N Engl J Med 1990 Jul 19;323(3):141-6

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Comment in:

• N Engl J Med. 1990 Jul 19;323(3):190-2.
• N Engl J Med. 1991 Jan 24;324(4):268-70.

Enhanced detection of ischemic but viable myocardium by the reinjection of thallium after stress-redistribution imaging.

Dilsizian V, Rocco TP, Freedman NM, Leon MB, Bonow RO.

Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md 20892.

BACKGROUND. The identification of ischemic but viable myocardium by thallium exercise scintigraphy is often imprecise, since many of the perfusion defects that develop in ischemic myocardium during exercise do not "fill in" on subsequent redistribution images. We hypothesized that a second injection of thallium given after the redistribution images were taken might improve the detection of ischemic but viable myocardium. METHODS. We studied 100 patients with coronary artery disease, using thallium exercise tomographic imaging and radionuclide angiography. Patients received 2 mCi of thallium intravenously during exercise, redistribution imaging was performed three to four hours later, and a second dose of 1 mCi of thallium was injected at rest immediately thereafter. The three sets of images (stress, redistribution, and reinjection) were then analyzed. RESULTS. Ninety-two of the 100 patients had exercise-induced perfusion defects. Of the 260 abnormal myocardial regions identified by stress imaging, 85 (33 percent) appeared to be irreversible on redistribution imaging three to four hours later. However, 42 of these apparently irreversible defects (49 percent) demonstrated improved or normal thallium uptake after the second injection of thallium, with an increase in mean regional uptake from 56 +/- 12 percent on redistribution studies to 64 +/- 10 percent on reinjection imaging (P less than 0.001). Twenty patients were restudied three to six months after coronary angioplasty. Of the 15 myocardial regions with defects on redistribution studies that were identified as viable by reinjection studies before angioplasty, 13 (87 percent) had normal thallium uptake and improved regional wall motion after angioplasty. In contrast, all eight regions with persistent defects on reinjection imaging before angioplasty had abnormal thallium uptake and abnormal regional wall motion after angioplasty. CONCLUSIONS. These data indicate that the reinjection of thallium improves the detection of ischemic myocardium and that myocardial regions with improved thallium uptake on reinjection imaging represent viable but jeopardized myocardium.

PMID: 2362606 [PubMed - indexed for MEDLINE]

 

10: Circulation 1993 Sep;88(3):941-52

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Concordance and discordance between stress-redistribution-reinjection and rest-redistribution thallium imaging for assessing viable myocardium. Comparison with metabolic activity by positron emission tomography.

Dilsizian V, Perrone-Filardi P, Arrighi JA, Bacharach SL, Quyyumi AA, Freedman NM, Bonow RO.

Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.

BACKGROUND: Stress thallium scintigraphy provides important diagnostic and prognostic information in patients with coronary artery disease by demonstrating regional myocardial ischemia. However, if the clinical question being addressed is whether a region is viable and not whether there is inducible ischemia, then it may be more reasonable to perform rest-redistribution imaging rather than stress-redistribution imaging followed by either reinjection or late redistribution. Therefore, we determined whether stress-redistribution-reinjection and rest-redistribution imaging provide the same information regarding myocardial viability. METHODS AND RESULTS. Both stress-redistribution-reinjection and rest-redistribution thallium single photon emission computed tomographic imaging was performed in 41 patients with chronic stable coronary artery disease, with quantitative analysis of regional thallium activity. Thallium reinjection was performed immediately after the 3- to 4-hour redistribution images were completed. Of the 155 myocardial regions with perfusion defects on the stress images, 91 (59%) were irreversible on conventional 3- to 4-hour redistribution images. When the outcomes of these irreversible regions were assessed after reinjection and compared with rest-redistribution images, there was concordance of data regarding myocardial viability (normal/reversible or irreversible) in 72 of the 91 (79%) irreversible defects. Twenty of the 41 patients also underwent positron emission tomography at rest with [18F]fluorodeoxyglucose and [15O]water. In these patients, stress-redistribution-reinjection and rest-redistribution imaging provided concordant information regarding myocardial viability in 427 (72%) of 594 myocardial regions and discordance in 167 regions. However, when irreversible thallium defects were further analyzed according to the severity of the thallium defect in these discordant regions, 149 of 167 (89%) demonstrated only mild-to-moderate reduction in thallium activity (51% to 85% of normal activity), and positron emission tomography verified 98% of these regions to be metabolically active and viable. Thus, when the severity of thallium activity was considered within irreversible thallium defects, the concordance between stress-redistribution-reinjection and rest-redistribution imaging regarding myocardial viability increased to 94%. CONCLUSIONS. These data indicate that one of two imaging modalities, either stress-redistribution-reinjection or rest-redistribution imaging, may be used for identifying viable myocardium. However, if there are no contraindications to stress testing, stress-redistribution-reinjection imaging provides a more comprehensive assessment of the extent and severity of coronary artery disease by demonstrating regional myocardial ischemia without jeopardizing information on myocardial viability.

PMID: 8353921 [PubMed - indexed for MEDLINE]

 

11: J Nucl Cardiol 1998 Jan-Feb;5(1):56-63

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Comparison of technetium 99m-tetrofosmin and thallium-201 single photon emission computed tomographic imaging for the assessment of viable myocardium in patients with left ventricular dysfunction.

Galassi AR, Tamburino C, Grassi R, Foti R, Mammana C, Virgilio A, Licciardello G, Musumeci S, Giuffrida G.

Institute of Cardiology, Ferrarotto Hospital, University of Catania, Italy. segcardi@mbox.unict.it

BACKGROUND: Tetrofosmin is a new technetium 99m-labeled myocardial perfusion agent that has demonstrated favorable imaging characteristics in recent clinical trials. However, it is not certain whether 99mTc-tetrofosmin compared with thallium 201 would underestimate myocardial viability in regions with left ventricular dysfunction. METHODS: To this end 15 patients (mean age 52+/-7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 35%+/-8%) documented on angiography underwent both quantitative rest-redistribution 201Tl and rest 99mTc-tetrofosmin single photon emission computed tomography imaging. RESULTS; Of 240 total segments on rest-redistribution 201Tl protocol 139 (58%) segments had irreversible 201Tl defects. Of these segments 79 (57%) had only mild to moderate reduction of 201Tl uptake (51% to 85% of normal uptake), whereas the remaining 60 (43%) had severely reduced tracer uptake (< or = 50% of normal uptake). On 99mTc-tetrofosmin protocol 180 (75%) segments had abnormal 99mTc-tetrofosmin uptake; of these segments 120 (67%) had mild to moderate reduction of 99mTc-tetrofosmin uptake, whereas 60 (33%) had severely reduced activity. Among hypokinetic regions concordance between 201Tl and 99mTc-tetrofosmin regarding myocardial viability with a cutoff point of 50% of peak activity was obtained in 28 (90%) of 31 segments (K' = 0.80), leaving only 3 of 31 regions discordant (p = NS). Similarly, among akinetic or dyskinetic regions concordance between the two tracers regarding myocardial viability was achieved in 54 (93%) regions (K' = 0.75), leaving only 4 of the 58 regions discordant (p = NS). CONCLUSIONS: These data show that when the severity of uptake was considered within abnormal segments, a similar amount of 201Tl viable regions were observed by 99mTc-tetrofosmin. Thus these two agents may provide comparable information about myocardial viability when quantitative analysis of defect severity is performed.

Publication Types:

• Clinical Trial

PMID: 9504874 [PubMed - indexed for MEDLINE]

 

12: Circulation 1990 Nov;82(5):1802-14

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Are the kinetics of technetium-99m methoxyisobutyl isonitrile affected by cell metabolism and viability?

Beanlands RS, Dawood F, Wen WH, McLaughlin PR, Butany J, D'Amati G, Liu PP.

Nuclear Cardiology Laboratory, Toronto Hospital, Canada.

To investigate the role of cell viability and metabolism on the myocardial kinetics of a new tracer, technetium-99m-methoxyisobutyl isonitrile (Tc-99m-MIBI), 250 microCi/l Tc-99m-MIBI was infused in isolated rat hearts under constant flow conditions. The hearts were studied after inducing irreversible damage by cytochrome c oxidase inhibitor sodium cyanide (n = 8) or sarcolemmal membrane detergent Triton X-100 (n = 8). The control hearts (n = 6) received no toxins. Mean Tc-99m-MIBI peak accumulation activity was significantly reduced after cyanide (51.1 +/- 44.2% of control, p less than 0.01) and Triton (13.8 +/- 2.7% of control, p less than 0.001) administration. Kinetic studies also showed marked reduction in accumulation rates and marked increase in clearance rates for cyanide (p less than 0.01) and Triton (p less than 0.01) groups compared with controls. Potential changes in regional flow distribution were assessed using microspheres. When peak accumulation activity was corrected for these changes, there remained significant differences between the groups. In the cyanide and Triton groups, irreversible cell injury was confirmed by creatine kinase and lactate dehydrogenase release, triphenyl tetrazolium chloride staining, and electron microscopy. All the cells were viable in the control group. We conclude that the accumulation and clearance kinetics of Tc-99m-MIBI are significantly affected by cell viability. Tc-99m-MIBI kinetics appear to be dependent on sarcolemmal integrity and to a lesser extent on aerobic metabolism.

PMID: 2225377 [PubMed - indexed for MEDLINE]

 

13: J Nucl Med 1991 Feb;32(2):292-8

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Comment in:

• J Nucl Med. 1991 Feb;32(2):298-9.

Effect of coronary occlusion and myocardial viability on myocardial activity of technetium-99m-sestamibi.

Freeman I, Grunwald AM, Hoory S, Bodenheimer MM.

Long Island Jewish Medical Center, Heart Institute, New Hyde Park, New York 11042.

The timing effect of sestamibi administration with respect to the onset of myocardial ischemia and reperfusion was studied in swine. In different groups of animals sestamibi was administered prior to coronary artery occlusion, during occlusion, or 1/2 hour following reperfusion. Sestamibi administered prior to coronary occlusion resulted in an insignificant decrease in 99mTc activity in the ischemic zone. However, infarct zone activity was reduced to 62 +/- 14% of the nonischemic zone. In contrast, administration during coronary occlusion resulted in similar significant reductions of both ischemic and infarct zone activity. Administration of sestamibi during reperfusion resulted in normal ischemic zone activity and markedly reduced activity in the infarct zone. Significantly reduced activity in the infarct zone was found to be independent of the timing of sestamibi administration with respect to the onset of myocardial ischemia and/or reperfusion. Thus, cell viability appears required for uptake and retention of isotope activity.

PMID: 1825111 [PubMed - indexed for MEDLINE]

 

14: Circulation 1994 Feb;89(2):578-87

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Erratum in:

• Circulation 1995 Jun 15;91(12):3026

Myocardial viability in patients with chronic coronary artery disease. Comparison of 99mTc-sestamibi with thallium reinjection and [18F]fluorodeoxyglucose.

Dilsizian V, Arrighi JA, Diodati JG, Quyyumi AA, Alavi K, Bacharach SL, Marin-Neto JA, Katsiyiannis PT, Bonow RO.

Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.

BACKGROUND: 99mTc-sestamibi and thallium imaging have similar accuracy when used for diagnostic purposes, but whether sestamibi provides accurate information regarding myocardial viability in patients with chronic coronary artery disease has not been established. Since there is minimal redistribution of sestamibi over time, it may overestimate nonviable myocardium in patients with left ventricular dysfunction, in whom blood flow may be reduced at rest. METHODS AND RESULTS: We studied 54 patients with chronic coronary artery disease with a mean ejection fraction of 34 +/- 14%. Patients underwent stress/redistribution/reinjection thallium tomography and, within a mean of 5 days, same-day rest/stress sestamibi imaging using the same exercise protocol and with patients achieving the same exercise duration. Of the 111 reversible thallium defects on either the redistribution or reinjection study, 40 (36%) were determined to be irreversible on the rest/stress sestamibi study, whereas only 3 of 63 irreversible thallium defects despite reinjection (5%) were classified to be reversible by sestamibi imaging. The concordance regarding reversibility of myocardial defects between thallium stress/redistribution/reinjection and same day rest/stress sestamibi studies was 75%. A subgroup of 25 patients also underwent positron emission tomography (PET) studies with 15O-labeled water and [18F]fluorodeoxyglucose (FDG) at rest after an oral glucose load. As in the overall group of 54 patients, there was concordance between thallium and sestamibi imaging regarding defect reversibility in 51 of 73 regions (70%). In the remaining 22 discordant regions (30%), 18 (82%) appeared irreversible by sestamibi imaging but were reversible by thallium imaging. Myocardial viability was confirmed in 17 of 18 regions, as evidenced by normal FDG uptake (10 regions) or FDG/blood flow mismatch (7 regions) on PET. These regions were present in 16 of the 25 patients studied (64%). We then explored methods to improve the sestamibi results. First, when the 18 discordant regions with irreversible sestamibi defects were further analyzed according to the severity of defects, 14 (78%) demonstrated only mild-to-moderate reduction in sestamibi activity (51% to 85% of normal activity), suggestive of predominantly viable myocardium, and the overall concordance between thallium and sestamibi studies increased to 93%. Second, when an additional 4-hour redistribution image was acquired in 18 patients after the injection of sestamibi at rest, 6 of 16 discordant irreversible regions (38%) on the rest/stress sestamibi study became reversible, thereby increasing the concordance between thallium and sestamibi studies to 82%. CONCLUSIONS: These data indicate that same-day rest/stress sestamibi imaging will incorrectly identify 36% of myocardial regions as being irreversibly impaired and nonviable compared with both thallium redistribution/reinjection and PET. However, the identification of reversible and viable myocardium can be greatly enhanced with sestamibi if an additional redistribution image is acquired after the rest sestamibi injection or if the severity of reduction in sestamibi activity within irreversible defects is considered.

PMID: 8313546 [PubMed - indexed for MEDLINE]

 

15: J Am Coll Cardiol 1996 Jun;27(7):1592-7

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Comment in:

• J Am Coll Cardiol. 1996 Jun;27(7):1598-600.

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.

Kauffman GJ, Boyne TS, Watson DD, Smith WH, Beller GA.

Cardiovascular Division, University of Virginia Health Sciences Center, Charlottesville 22908, USA.

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 singlephoton 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 < or = 75% and > or = 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.

Publication Types:

• Clinical Trial

PMID: 8636541 [PubMed - indexed for MEDLINE]

 

16: J Nucl Med 1994 Apr;35(4):569-74

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Significance of defect severity in technetium-99m-MIBI SPECT at rest to assess myocardial viability: comparison with fluorine-18-FDG PET.

Altehoefer C, vom Dahl J, Biedermann M, Uebis R, Beilin I, Sheehan F, Hanrath P, Buell U.

Department of Nuclear Medicine, University Hospital, Technical University Aachen, Germany.

The pathophysiological significance of 99mTc-MIBI uptake at rest for assessing myocardial viability in patients with coronary artery disease (CAD) is still controversial. Therefore, we studied the relationship of 99mTc-MIBI uptake at rest and preserved or absent uptake of 18FDG as assessed with PET in 111 consecutive patients after overnight withdrawal of their antianginal medication. METHODS: Each ventricle was evaluated in 13 segments derived from 25 regions of interest (ROIs) in short-axis cuts and 18FDG uptake was normalized to the intraindividual normal reference ROI (ROI with maximal = 100% 99mTc-MIBI uptake). Segments with a normalized 18FDG uptake > 70% were defined as viable while segments with a 18FDG uptake < 50% were defined as nonviable. RESULTS: Five to 11% of segments with 99mTc-MIBI uptake at rest < or = 30% of peak activity were viable and 80%-84% nonviable. Of moderate to severe 99mTc-MIBI defects at rest (31%-70% of peak), 13%-61% were viable. Segmental 99mTc-MIBI uptake and normalized 18FDG uptake were linearly correlated (r = 0.61, n = 1443, p < 0.001). In segments revealing severely reduced 99mTc-MIBI uptake (< or = 50% of peak) the correlation was considerably lower (r = 0.44, n = 295, p < 0.001). CONCLUSIONS: In patients with CAD, 99mTc-MIBI uptake underestimates myocardial viability in comparison to 18FDG-PET. Myocardial 99mTc-MIBI uptake therefore appears to reflect myocardial blood flow rather than myocardial viability. Patients with moderate and severe 99mTc-MIBI defects at rest may benefit from additional metabolic PET imaging prior to final therapeutic decisions.

PMID: 8151377 [PubMed - indexed for MEDLINE]

 

17: Circulation 1993 Aug;88(2):430-6

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Dobutamine stress echocardiography identifies hibernating myocardium and predicts recovery of left ventricular function after coronary revascularization.

Cigarroa CG, deFilippi CR, Brickner ME, Alvarez LG, Wait MA, Grayburn PA.

Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas.

BACKGROUND. The identification of hibernating myocardium is important in selecting patients who will benefit from coronary revascularization. This study was performed to determine whether dobutamine stress echocardiography (DSE) could identify hibernating myocardium and predict improvement in regional systolic wall thickening after revascularization. METHODS AND RESULTS. DSE was performed in 49 consecutive patients with multivessel coronary disease and depressed left ventricular function. Contractile reverse during DSE was defined by the presence of two criteria: (1) improved systolic wall thickening in at least two adjacent abnormal segments and (2) > or = 20% improvement in regional wall thickening score. Postoperative echocardiograms were evaluated for improved regional wall thickening in 25 patients at least 4 weeks after successful coronary revascularization. All studies were read in blinded fashion. Contractile reserve during DSE was present in 24 (49%) of 49 patients. The presence or absence of contractile reserve on preoperative DSE predicted recovery of ventricular function in the 25 patients who underwent successful revascularization. Thus, 9 of 11 patients with contractile reserve had improved systolic wall thickening after revascularization (hibernating myocardium), whereas 12 of 14 patients without contractile reserve did not improve (P = .003). CONCLUSIONS. Dobutamine stress echocardiography provides a simple, cost-effective, and widely available method of identifying hibernating myocardium and predicting improvement in regional left ventricular wall thickening after coronary revascularization. This technique may be clinically valuable in the selection of patients for coronary revascularization.

PMID: 8339406 [PubMed - indexed for MEDLINE]

18. Gerber BL, Vanoverschelde JL, Bol A, Michel C, Labar D, Wijns W, Melin JA. Myocardial blood flow, glucose uptake, and recruitment of inotropic reserve in chronic left ventricular ischemic dysfunction. Implications for the pathophysiology of chronic myocardial hibernation. Circulation 1996; 94: 651–659.

19: J Am Coll Cardiol 1996 Sep;28(3):558-64

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

Bax JJ, Cornel JH, Visser FC, Fioretti PM, van Lingen A, Reijs AE, Boersma E, Teule GJ, Visser CA.

Department of Cardiology, Free University Hospital Amsterdam, The Netherlands.

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.

PMID: 8772739 [PubMed - indexed for MEDLINE]

 

20: Circulation 1997 Feb 4;95(3):626-35

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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.

Qureshi U, Nagueh SF, Afridi I, Vaduganathan P, Blaustein A, Verani MS, Winters WL Jr, Zoghbi WA.

Department of Medicine, Baylor College of Medicine, Methodist Hospital Echocardiography, Houston, TX 77030, USA.

BACKGROUND: The 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. METHODS AND RESULTS: Thirty-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. CONCLUSIONS: In 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.

PMID: 9024150 [PubMed - indexed for MEDLINE]

 

21: Am J Cardiol 1993 Jan 15;71(2):166-72

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Value of rest thallium-201/technetium-99m sestamibi scans and dobutamine echocardiography for detecting myocardial viability.

Marzullo P, Parodi O, Reisenhofer B, Sambuceti G, Picano E, Distante A, Gimelli A, L'Abbate A.

CNR Institute of Clinical Physiology, Pisa, Italy.

The relation between radioisotopic and echocardiographic markers of myocardial viability and postrevascularization recovery of function is still to be defined. To this purpose, 14 patients (11 men, 3 women, aged 35 to 64 years, mean 54 +/- 7) with ventricular dysfunction were studied by a multiparametric approach. Each patient underwent, on separate days, rest thallium-201 and technetium-99m sestamibi scintigraphy, dobutamine echocardiography and coronary angiography. Coronary angiography was analyzed by a quantitative approach. Thallium uptake at rest was quantified from planar early (10-minute) and delayed (16-hour) thallium-201 images and expressed as a percentage of maximal activity in each projection using a 13-segment model. Sestamibi uptake was expressed in the same way. Dobutamine (up to 10 micrograms/kg/min) echocardiography was analyzed using a score index ranging from 1 (normokinesia) to 4 (dyskinesia) and a similar segmental model. Before revascularization 50 segments were grouped as normal (coronary stenosis < 50% and normal function, group 1); of the remaining 132 segments with > 50% coronary stenosis, 57 had normal wall motion (group 2) and 75 showed regional dyssynergies (group 3). Early and delayed thallium-201 regional percent activities did not differ in group 1 and in group 2 but were significantly less in group 3 segments. Sestamibi percent activity was more in group 1 and significantly reduced both in group 2 and 3 segments. Segments with improved wall motion after dobutamine had more early, delayed thallium-201 and sestamibi percent activities than unresponsive segments. Postrevascularization echocardiography was performed in all patients. Delayed thallium-201 scans and dobutamine echocardiography showed good sensitivity and specificity in detecting viable myocardium. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 8421978 [PubMed - indexed for MEDLINE]

22. Bax JJ, Cornel JH, Visser FC, Fioretti PM, Elhendy A, Visser CA. Thallium-201 rest-redistribution SPECT to predict improvement of global ventricular function after revascularization. J Am Coll Cardiol 1997; 29: 377A (Abstract)

23: J Am Coll Cardiol 1992 Sep;20(3):559-65

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Comment in:

• J Am Coll Cardiol. 1992 Sep;20(3):566-8.

Clinical outcome of patients with advanced coronary artery disease after viability studies with positron emission tomography.

Eitzman D, al-Aouar Z, Kanter HL, vom Dahl J, Kirsh M, Deeb GM, Schwaiger M.

Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0028.

OBJECTIVE. The aim of this study was to determine the prognostic significance of perfusion-metabolism imaging in patients undergoing positron emission tomography for myocardial viability assessment. BACKGROUND. Positron emission tomography using nitrogen-13 ammonia and 18fluorodeoxyglucose to assess myocardial blood flow and metabolism has been shown to predict improvement in wall motion after coronary artery revascularization. The prognostic implications of metabolic imaging in patients with advanced coronary artery disease have not been investigated. METHODS. Eighty-two patients with advanced coronary artery disease and impaired left ventricular function underwent positron emission tomographic imaging between August 1988 and March 1990 to assess myocardial viability before coronary artery revascularization. RESULTS. Forty patients underwent successful revascularization. Patients who exhibited evidence of metabolically compromised myocardium by positron emission tomography (decreased blood flow with preserved metabolism) who did not undergo subsequent revascularization were more likely to experience a myocardial infarction, death, cardiac arrest or late revascularization due to development of new symptoms than were the other patient groups (p less than 0.01). Concordantly decreased flow and metabolism in segments of previous infarction did not affect outcome in patients with or without subsequent revascularization. Those with a compromised myocardium who did undergo revascularization were more likely to experience an improvement in functional class than were patients with preoperative positron emission tomographic findings of concordant decrease in flow and metabolism. CONCLUSIONS. Positron emission tomographic myocardial viability imaging appears to identify patients at increased risk of having an adverse cardiac event or death. Patients with impaired left ventricular function and positron emission tomographic evidence for jeopardized myocardium appear to have the most benefit from a revascularization procedure.

PMID: 1512333 [PubMed - indexed for MEDLINE]

24. Kaul S. There may be more to myocardial viability than meets the eye. Circulation 1995; 92: 2790–2793.
25. Marwick TH, Nemec JJ, Lafont A, Salcedo EE, MacIntyre, WJ. Prediction by postexercise fluoro-18 deoxyglucose positron emission tomography of improvement in exercise capacity after revascularization. Am J Cardiol 1992; 69: 854–859.

26: Circulation 1995 Dec 15;92(12):3436-44

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Quantitative relation between myocardial viability and improvement in heart failure symptoms after revascularization in patients with ischemic cardiomyopathy.

Di Carli MF, Asgarzadie F, Schelbert HR, Brunken RC, Laks H, Phelps ME, Maddahi J.

Department of Medical and Molecular Pharmacology, University of California at Los Angeles, School of Medicine, USA.

BACKGROUND: Studies of patients with coronary artery disease and left ventricular dysfunction have shown that preoperative quantification of myocardial viability may be clinically useful to identify those patients who will benefit most from revascularization both functionally and prognostically. However, the relation between preoperative extent of viability and change in heart failure symptoms has not been documented carefully. We assessed the relation between the magnitude of improvement in heart failure symptoms after coronary artery bypass surgery (CABG) and the extent of myocardial viability as assessed by use of quantitative analysis of preoperative positron emission tomography (PET) images. METHODS AND RESULTS: We studied 36 patients with ischemic cardiomyopathy (mean left ventricular ejection fraction, 28 +/- 6%) undergoing CABG. Preoperative extent and severity of perfusion abnormalities and myocardial viability (flow-metabolism mismatch) were assessed by use of quantitative analysis of PET images with 13N ammonia and fluorine-18-deoxyglucose. Each patient's functional status was determined before and after CABG by use of a Specific Activity Scale. Mean perfusion defect size and severity were 63 +/- 13% and 33 +/- 12%, respectively. Total extent of a PET mismatch correlated linearly and significantly with percent improvement in functional status after CABG (r = .87, P < .0001). A blood flow-metabolism mismatch > or = 18% was associated with a sensitivity of 76% and a specificity of 78% for predicting a change in functional status after revascularization. Patients with large mismatches (> or = 18%) achieved a significantly higher functional status compared with those with minimal or no PET mismatch (< 5%) (5.7 +/- 0.8 versus 4.9 +/- 0.7 metabolic equivalents, P = .009). This resulted in an improvement of 107% in patients with large mismatches compared with only 34% in patients with minimal or no PET mismatch. CONCLUSIONS: In patients with ischemic cardiomyopathy, the magnitude of improvement in heart failure symptoms after CABG is related to the preoperative extent and magnitude of myocardial viability as assessed by use of PET imaging. Patients with large perfusion-metabolism mismatches exhibit the greatest clinical benefit after CABG.

PMID: 8521565 [PubMed - indexed for MEDLINE]

27. Gerber B, Vanoverschelde J-LJ, Robert A. Dobutamine echocardiography, 201-Thallium SPECT and positron emission tomography: which test for the prediction of myocardial viability [abstract]. Circulation 1994; 90 (suppl): 1134.

28: J Am Coll Cardiol 1985 May;5(5):1036-45

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Late results of surgical and medical therapy for patients with coronary artery disease and depressed left ventricular function.

Pigott JD, Kouchoukos NT, Oberman A, Cutter GR.

Late survival and freedom from myocardial infarction were determined for 192 patients with coronary artery disease and depressed left ventricular ejection fraction at rest (less than or equal to 35%) determined by biplane angiography who were evaluated between 1970 and 1977. Seventy-seven patients had coronary artery bypass grafting and 115 patients were treated medically and were considered surgical candidates. The medical and surgical groups were comparable in all baseline characteristics examined except frequency of three vessel disease and angina pectoris, which occurred in a significantly greater percent of the surgically treated patients (p less than 0.01). Only three medically treated patients (2.6%) underwent coronary bypass grafting in the follow-up period. Seven year actuarial survival was 63% in the surgical and 34% in the medical group (p less than 0.001). Ninety-three percent of patients in the surgical group and 81% of those in the medical group were free of nonfatal myocardial infarction (p = 0.01), and 62 and 33%, respectively, were alive and free of myocardial infarction (p less than 0.001) at 7 years. Significant differences in survival favoring surgical treatment were observed for the subsets of patients with an ejection fraction of 25% or less (p = 0.0002) and 26 to 35% (p = 0.01), and for the subsets with three vessel coronary disease (p less than 0.001), normal left ventricular end-diastolic volume (less than or equal to 100 ml/m2) (p = 0.005) and elevated end-diastolic volume (greater than 100 ml/m2)(p = 0.001). After adjustment for other important prognostic variables, the type of treatment remained significant in predicting the relative risk (medical to surgical) of mortality at 5 and 7 years (2.58 and 2.12, respectively). These data corroborate the trends observed in several randomized trials of medical and surgical therapy in patients with abnormal left ventricular function. If hospital mortality for coronary artery bypass grafting is less than 5%, substantial benefit can be anticipated for the majority of patients with depressed ventricular function.

PMID: 3872896 [PubMed - indexed for MEDLINE]

 

29: J Nucl Cardiol 1996 Mar-Apr;3(2):150-6

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Prognostic value of tomographic rest-redistribution thallium 201 imaging in medically treated patients with coronary artery disease and left ventricular dysfunction.

Gioia G, Milan E, Giubbini R, DePace N, Heo J, Iskandrian AS.

Philadelphia Heart Institute, Presbyterian Medical Center, Pa, USA.

BACKGROUND: Previous studies show that rest-redistribution thallium imaging is useful in the assessment of myocardial viability. The impact of such studies on patient outcome is not well defined. This study examined the prognostic value of tomographic rest-redistribution 201T1 imaging in 81 medically treated patients with coronary artery disease and left ventricular dysfunction. METHODS AND RESULTS: Rest-redistribution single-photon emission computed tomographic images were obtained and analyzed quantitatively. The segmental thallium uptake (20 segments per patient) was interpreted as normal, reversible defect, mild to moderate fixed defect, or severe fixed defect. The thallium images were abnormal in 80 patients, with no redistribution (no ischemia) in 43 patients and redistribution (ischemia) in 38 patients. The left ventricular ejection fraction was 27% +/- 8% in patients with no redistribution and 26% +/- 7% in patients with redistribution (difference not significant). In patients with no ischemia, there were 7 +/- 5 severe fixed defects and 5 +/- 4 mild to moderate fixed defects per patient. In patients with ischemia there were 7 +/- 4 reversible defects, 3 +/- 3 mild to moderate fixed defects, and 5 +/- 4 severe fixed defects per patient. The number of any abnormal segments was 11 +/- 5 in patients with no ischemia and 14 +/- 4 in patients with ischemia (p = 0.03). During a mean follow-up of 31 +/- 24 months, there were 11 cardiac deaths in patients with no ischemia (26%) and 22 in patients with ischemia (58%); the survival rate was worse in patients with than without ischemia (p < 0.05). Multivariate Cox survival analysis on important clinical, angiographic, and thallium variables showed that the presence of redistribution was an independent predictor of death (x2 = 5; p = 0.03). CONCLUSIONS: Patients with left ventricular dysfunction and redistribution on rest thallium imaging, a marker of hibernating myocardium, have a higher mortality rate with medical therapy than do patients with a comparable degree of left ventricular dysfunction but with fixed defects only. Thus observations similar to those made with positron emission tomography can be made in a much more straightforward, simple, and probably cost-effective manner with single-photon emission computed tomography.

PMID: 8799240 [PubMed - indexed for MEDLINE]

 

30: J Am Coll Cardiol 1998 Oct;32(4):912-20

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Prognostic value of the amount of dysfunctional but viable myocardium in revascularized patients with coronary artery disease and left ventricular dysfunction. Investigators of this Multicenter Study.

Meluzin J, Cerny J, Frelich M, Stetka F, Spinarova L, Popelova J, Stipal R.

1st Internal Department, St. Anna Hospital, Brno, Czech Republic. jtoman@med.muni.cz

OBJECTIVES: The purpose of our study was to assess the prognostic importance of the amount of dysfunctional but viable myocardium in revascularized patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction. BACKGROUND: The amount of dysfunctional but viable myocardium predicts the functional improvement after revascularization and may offer more precise risk stratification of patients referred for bypass surgery or coronary angioplasty. METHODS: Two hundred and seventy-four consecutive patients with CAD and LV ejection fraction < or =40% underwent low-dose dobutamine echocardiography for viability assessment. One hundred and thirty-three of them were revascularized using either coronary artery bypass surgery (118 patients) or coronary angioplasty (15 patients) and entered this study. To quantify the amount of dysfunctional but viable myocardium, wall motion was scored using 16-segment model. The dysfunctional segments were defined as viable if they exhibited improvement in their thickening by at least 1 grade with dobutamine infusion. The patients were followed up for a mean period of 20+/-12 months (range, 2 to 48) for cardiac mortality and nonfatal cardiac events including myocardial infarction, unstable angina pectoris requiring hospitalization and hospitalization for heart failure. Standard follow-up echocardiography was performed 3 to 6 months after revascularization. RESULTS: Twenty-nine patients exhibited a large amount of dysfunctional but viable myocardium (> or =6 segments, group A), 60 patients had a small amount of dysfunctional but viable myocardium (2 to 5 segments, group B) and 44 patients were found to have dysfunctional myocardium irreversibly damaged (group C). Similar prerevascularization LV ejection fractions of 35%+/-5%, 34%+/-4%, 36%+/-4% in groups A, B and C increased to 47%+/-6% (p < 0.01 vs. baseline, p < 0.01 vs. groups B and C), to 40%+/-5% (p < 0.01 vs. baseline) and to 37%+/-6% (p = NS vs baseline), respectively, after revascularization. The greatest functional improvement after revascularization in group A patients was accompanied by a lower rate of cardiac events during follow-up (2 vs. 18 in group B, p < 0.05, and vs. 17 in group C, p < 0.01) and better cardiac event-free survival according to Kaplan-Meier survival analysis (p < 0.05 vs. groups B and C, respectively). CONCLUSION: In revascularized patients with CAD and moderate or severe LV dysfunction, the presence of a large amount of dysfunctional but viable myocardium identifies patients with the best prognosis.

PMID: 9768711 [PubMed - indexed for MEDLINE]

 

31: J Am Coll Cardiol 1997 Dec;30(7):1693-700

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Comment in:

• J Am Coll Cardiol. 1997 Dec;30(7):1701-6.

Preoperative positron emission tomographic viability assessment and perioperative and postoperative risk in patients with advanced ischemic heart disease.

Haas F, Haehnel CJ, Picker W, Nekolla S, Martinoff S, Meisner H, Schwaiger M.

Department of Cardiovascular Surgery, Deutsches Herzzentrum Munchen, Munich, Germany.

OBJECTIVES: This study sought to investigate whether determination of tissue viability by means of positron emission tomography (PET) before coronary artery bypass graft surgery (CABG) affects clinical outcome with respect to both in-hospital mortality and 1-year survival rate. BACKGROUND: Patients with coronary artery disease (CAD) and severe left ventricular (LV) dysfunction are at higher risk for perioperative complications associated with CABG. Therefore, the selection of patients who will benefit from CABG is an important clinical issue. METHODS: This study retrospectively evaluated 76 patients with advanced CAD and LV dysfunction (LV ejection fraction < or = 0.35) who were considered candidates for CABG. Thirty-five patients were selected for CABG on the basis of clinical presentation and angiographic data (group A), and 34 of 41 patients were selected according to extent of viable tissue determined by PET (group B) in addition to clinical presentation and angiographic data. RESULTS: There were four in-hospital deaths (11.4%) in group A and none in group B (p = 0.04). After 12 months, the survival rate was 79% in group A and 97% in group B (p = 0.01). Postoperatively, group B patients had a less complicated recovery (p = 0.05). They required lower doses of catecholamines (p = 0.002) and demonstrated a significantly decreased incidence of low output syndrome (p = 0.05). CONCLUSIONS: This retrospective data analysis suggests that selection of patients with impaired LV function on the basis of extent of viability supplementary to clinical and angiographic data may lead to postoperative recovery with a low early mortality and promising short-term survival. Therefore, viability studies permit selection of patients who are at low risk for serious perioperative complications.

PMID: 9385895 [PubMed - indexed for MEDLINE]

 

32: J Am Coll Cardiol 1986 Oct;8(4):800-8

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Regional myocardial metabolism in patients with acute myocardial infarction assessed by positron emission tomography.

Schwaiger M, Brunken R, Grover-McKay M, Krivokapich J, Child J, Tillisch JH, Phelps ME, Schelbert HR.

Positron emission tomography has been shown to distinguish between reversible and irreversible ischemic tissue injury. Using this technique, 13 patients with acute myocardial infarction were studied within 72 hours of onset of symptoms to evaluate regional blood flow and glucose metabolism with nitrogen (N)-13 ammonia and fluorine (F)-18 deoxyglucose, respectively. Serial noninvasive assessment of wall motion was performed to determine the prognostic value of metabolic indexes for functional tissue recovery. Segmental blood flow and glucose utilization were evaluated using a circumferential profile technique and compared with previously established semiquantitative criteria. Relative N-13 ammonia uptake was depressed in 32 left ventricular segments. Sixteen segments demonstrated a concordant decrease in flow and glucose metabolism. Regional function did not change over time in these segments. In contrast, 16 other segments with reduced blood flow revealed maintained F-18 deoxyglucose uptake consistent with remaining viable tissue. The average wall motion score improved significantly in these segments (p less than 0.01), yet the degree of recovery varied considerably among patients. Coronary anatomy was defined in 9 of 13 patients: patent infarct vessels supplied 8 of 10 segments with F-18 deoxyglucose uptake, while 10 of 13 segments in the territory of an occluded vessel showed concordant decreases in flow and metabolism (p less than 0.01). Thus, positron emission tomography reveals a high incidence of residual tissue viability in ventricular segments with reduced flow and impaired function during the subacute phase of myocardial infarction. Absence of residual tissue metabolism is associated with irreversible injury, while preservation of metabolic activity identifies segments with a variable outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 3489746 [PubMed - indexed for MEDLINE]

 

33: Int J Cardiol 1996 Dec 13;57(3):271-81

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Course of impaired left ventricular function after acute myocardial infarction predicted with planar thallium-201 chloride and F18-fluorodeoxyglucose imaging.

Huitink JM, Visser FC, Bax JJ, van Lingen A, Visser CA.

Department of Cardiology, Free University, Amsterdam, The Netherlands.

Planar reset myocardial thallium-201 chloride (201Tl)/F18-fluorodeoxyglucose (FDG) imaging has been shown to distinguish between viable and non-viable tissue. Twenty-five patients (60 +/- 9 years) with acute myocardial infarction were studied using this technique within 6 +/- 2 days (T1) after infarction and again after 42 +/- 4 days (T6). Serial assessment of wall motion with 2D-echocardiography was performed to determine the predictive value of radionuclide indices for the course of impaired regional left ventricular function. No revascularization procedure was performed. Segmental 201Tl and FDG uptake was evaluated using circumferential profiles. Echocardiographic wall motion was scored as normal, hypokinetic or akinetic. Myocardial segments were considered non-viable if a match between 201Tl and FDG uptake was present, which is a concordant reduction in 201 Tl and FDG uptake (Group A). Myocardial segments were considered viable if: a mismatch was present between 201Tl and FDG uptake which was defined as a segmental FDG uptake exceeding 201Tl uptake by > or = 20% in a segment with reduced 201Tl uptake (Group B); a normal FDG uptake (> or = 75%) was present without a mismatch pattern in a segment with reduced 201Tl uptake (201Tl < 75% of peak activity) (Group C); a normal 201Tl uptake was present in the area of wall motion abnormality (Group D). Corresponding scintigraphic images obtained at T1 and T6 were compared. RESULTS: 51 segments were normokinetic, 37 were hypokinetic and 6 were akinetic at T1. Of the 63 segments with wall motion abnormalities at T1, 18 regions showed a match (FDG-201Tl < 20%) (Group A). Regional function improved in only one (6%) of these segments. In 19 regions a mismatch was present (FDG-201Tl > 20%) (Group B) of which three (16%) showed spontaneous improvement in function (p = NS vs. matched segments), although recovery varied considerably among patients. Regional function in two segments deteriorated. In 14 regions with reduced 201Tl uptake, FDG uptake was normal (Group C) of which five (36%) were improved after 6 weeks (p < 0.05 vs. match; p = NS vs. mismatched segments). Of the 12 segments with normal 201Tl uptake (Group D), seven (58%) showed improvement in function, whereas five (42%) did not show improvement (p < 0.05 vs. match). In addition, all scintigraphically selected viable segments were grouped (Group B + C + D) and compared with the non-viable segments (Group A). The predictive value of a positive viability test for spontaneous functional improvement was 33%. The predictive value of a negative viability test for lack of functional improvement was 94%. CONCLUSIONS: absence of residual FDG uptake shortly after infarction is associated with irreversible injury, while preservation of metabolic activity identifies segments with variable outcome. Wall motion alone is not a good indicator for the presence of viable tissue. Planar 201Tl/FDG imaging allows early identification of viable but jeopardized tissue and may help select patients who will benefit from aggressive therapy to salvage endangered myocardium.

PMID: 9024916 [PubMed - indexed for MEDLINE]

 

34: J Am Coll Cardiol 1990 Apr;15(5):1021-31

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Identification of viable myocardium by echocardiography during dobutamine infusion in patients with myocardial infarction after thrombolytic therapy: comparison with positron emission tomography.

Pierard LA, De Landsheere CM, Berthe C, Rigo P, Kulbertus HE.

Department of Medicine, University of Liege, Belgium.

To assess the presence of viable myocardium salvaged by coronary artery reperfusion, 17 patients with acute anterior myocardial infarction were studied. Each received intravenous thrombolysis within the first 3 h of symptoms and underwent two-dimensional echocardiography before and during dobutamine infusion (10 micrograms/kg per min) 7 +/- 4 days after admission and positron emission tomography 9 +/- 5 days after admission. Echocardiography and positron emission tomography were again performed 9 +/- 7 months later. Six comparable segments specific for the territory of the left anterior descending artery were selected for comparison of the two techniques. Wall thickening was evaluated by using an echocardiographic score index. Segmental perfusion and glucose uptake were measured and normalized to the peak activity. A ratio of glucose uptake to perfusion was calculated for each segment. Concordant interpretation of the two techniques was found in 79% of affected segments for both acute and follow-up studies. Positron emission tomography revealed the presence of viable myocardium in 11 patients (group 1); perfusion was within normal limits in 5 of these (group 1A). Myocardial thickening improved with dobutamine infusion in these five patients, the echocardiographic score index decreasing from 12 +/- 2 at rest to 7.8 +/- 1.3 during dobutamine infusion (p = 0.003). Functional recovery was demonstrated in all five patients (follow-up score index 7.4 +/- 1.7). Six patients exhibited decreased perfusion but an abnormally high glucose to perfusion ratio (group 1B); their score index improved with dobutamine from 14.8 +/- 2.2 to 12 +/- 2.1 (p = 0.05), but late functional recovery was found in only one of the six patients (mean follow-up score index in group 1B 16 +/- 1.7). In the six remaining patients in whom no viable myocardium was detected with positron emission tomography (group 2), the echocardiographic score index did not change with dobutamine (15 +/- 0.9 to 14.7 +/- 0.8, p = NS) and there was no functional recovery (follow-up score index 15.5 +/- 1.0). Echocardiography during dobutamine infusion is a promising method to unmask viable myocardium in acute myocardial infarction. Early recovery of perfusion in the area at risk is associated with a good functional outcome, whereas a high glucose to perfusion ratio indicates jeopardized myocardium that frequently loses viability.

PMID: 2312956 [PubMed - indexed for MEDLINE]

35. Barilla F, Gheorghiade M, Alam M, Khaja F, Goldstein S. Low-dose dobutamine in patients with acute myocardial infarction identifies viable but not contractile myocardium and predicts the magnitude of improvement in wall motion abnormalities in response to coronary revascularization. Am Heart J 1991; 122: 1522–1531.

36: Circulation 1993 Aug;88(2):405-15

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Comment in:

• Circulation. 1993 Aug;88(2):797-9.

Low-dose dobutamine echocardiography detects reversible dysfunction after thrombolytic therapy of acute myocardial infarction.

Smart SC, Sawada S, Ryan T, Segar D, Atherton L, Berkovitz K, Bourdillon PD, Feigenbaum H.

Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis.

BACKGROUND. Dysfunction after thrombolytic therapy of acute myocardial infarction (MI) may be reversible. Early after myocardial infarction, both reversible and irreversible injury may be manifested by regional wall motion abnormalities. Improved wall thickening during dobutamine infusion (dobutamine-responsive wall motion) may accurately identify reversibly injured segments. METHODS AND RESULTS. To determine whether dobutamine-responsive wall motion accurately detects reversible postischemic dysfunction irrespective of infarct location, multistage (baseline, 4 and 12 micrograms.kg-1.min-1, and peak) dobutamine echocardiography (DE) was performed within 7 days of thrombolytic therapy. Resting echocardiography was repeated > or = 4 weeks after MI, and reversible dysfunction was defined as improved wall motion. The accuracy of dobutamine-responsive wall motion was compared with that of signs of early reperfusion, non-Q-wave MI, and peak creatine kinase (CK). Sixty-three patients underwent DE without complications. Follow-up echocardiograms were done in 51 (81%) of these patients, and wall motion improved in 22 (41%). Dobutamine-responsive wall motion during all stages of DE was very specific for reversible dysfunction (90% to 93%) but sensitive (86%) only when hemodynamics were not altered (low dose, 4 micrograms.kg-1.min-1). Non-Q-wave MI and a low peak CK (< 1000 IU/mL) were also specific (89% to 93%) but less sensitive (64% [P = .16] and 55% [P < .05], respectively). Signs of early reperfusion did not identify postischemic dysfunction. Low-dose dobutamine-responsive wall motion and non-Q-wave MI independently identified reversible dysfunction, but only dobutamine-responsive wall motion was sensitive in all infarct locations. Non-Q-wave MI was sensitive only in anterior infarction. CONCLUSIONS. Multistage dobutamine echocardiography can be performed safely early after thrombolytic therapy. Low-dose dobutamine-responsive wall motion accurately detected reversible dysfunction in all infarct locations. Dobutamine-responsive wall motion and non-Q-wave infarction may be very useful for accurately identifying reversible dysfunction early after thrombolytic therapy for acute MI.

PMID: 8339404 [PubMed - indexed for MEDLINE]

 

37: J Am Coll Cardiol 1994 Sep;24(3):624-30

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Dobutamine stress echocardiography predicts reversible dysfunction and quantitates the extent of irreversibly damaged myocardium after reperfusion of anterior myocardial infarction.

Watada H, Ito H, Oh H, Masuyama T, Aburaya M, Hori M, Iwakura M, Higashino Y, Fujii K, Minamino T.

Division of Cardiology, Sakurabashi Watanabe Hospital, Osaka, Japan.

OBJECTIVES. This study was designed to evaluate dobutamine stress echocardiography in identifying reversible dysfunction and assessing the extent of irreversibly damaged myocardium early in acute myocardial infarction. BACKGROUND. Several experimental and clinical studies have suggested that dobutamine enhances contractile function of stunned or hibernating, or both, myocardium. It is important for clinical strategy to predict the magnitude of improvement in myocardial function early in acute myocardial infarction. METHODS. We studied 21 patients with a reperfused first anterior myocardial infarction. Two-dimensional echocardiography was performed before and during dobutamine infusion (10 micrograms/kg body weight per min) at a mean of 3 days after the infarction. Follow-up echocardiography was performed at a mean of 25 days later. To assess segmental wall motion, we divided the left ventricle into 17 segments and assigned a wall motion abnormality score: 3 = dyskinesia or akinesia; 0 = normal. Improvement in wall motion was indicated by a decrease of at least one grade in segmental score. For quantitative assessment, the ratio of endocardial length showing dyskinesia or akinesia to a left ventricular endocardial length (akinetic length ratio) was determined in the apical long-axis view at each stage. RESULTS. Sensitivity and specificity of dobutamine infusion in detecting improvement in wall motion at follow-up echocardiography were 83% (55 of 66 segments) and 86% (43 of 50 segments), respectively. Excellent correlation was found (r = 0.93, p < 0.001; absolute difference [mean +/- SD] 0.03 +/- 0.05) between the akinetic length ratios measured during dobutamine infusion and in the late convalescent stage. CONCLUSIONS. In the early stage of acute myocardial infarction, low dose dobutamine stress echocardiography provides a useful method for predicting reversible dysfunction with excellent sensitivity and specificity and can also be used to quantitate the extent of irreversibly damaged myocardium.

PMID: 8077530 [PubMed - indexed for MEDLINE]

 

38: Am J Cardiol 1987 Jul 1;60(1):15-9

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Usefulness of residual ischemic myocardium within prior infarct zone for identifying patients at high risk late after acute myocardial infarction.

Brown KA, Weiss RM, Clements JP, Wackers FJ.

This study examines the prognostic implications of ischemia within the territory of a prior acute myocardial infarction (AMI) vs ischemia at a distance, which develops late after AMI. Sixty-one consecutive patients who underwent both exercise thallium-201 (TI-201) imaging and cardiac catheterization for evaluation of chest pain that developed after discharge from the hospital for AMI form the study group. Mean interval between infarction to the TI-201 study was 10 +/- 17 months. Initial and 2-hour delay TI-201 images were analyzed quantitatively to determine the presence and location (within vs outside the prior infarct zone) of TI-201 redistribution, a marker of ischemic viable myocardium. TI-201 imaging results were separated into 3 groups based on presence and location of TI-201 redistribution: no significant TI-201 redistribution was found in 16 patients; in 29, TI-201 redistribution was confined to the infarct zone; and in 16, TI-201 redistribution was outside the infarct zone. Stepwise multivariate logistic regression analysis was used to examine the comparative ability of TI-201 results and other patient variables to predict cardiac events. For total cardiac events (cardiac death, recurrent nonfatal AMI, unstable angina and coronary revascularization), both the presence of any TI-201 redistribution and multivessel angiographic coronary artery disease were significant predictors. However, when coronary revascularization was excluded as an endpoint, TI-201 redistribution limited to the prior infarct zone was the only significant predictor of cardiac events. All 8 cardiac events occurred in patients with T1-201 redistribution limited to the infart zone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 3604929 [PubMed - indexed for MEDLINE]

 

39: Circulation 1997 Nov 4;96(9):2932-7

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Comment in:

• Circulation. 1997 Nov 4;96(9):2758-61.

Superiority of nitrate-enhanced 201Tl over conventional redistribution 201Tl imaging for prognostic evaluation after myocardial infarction and thrombolysis.

Basu S, Senior R, Raval U, Lahiri A.

Department of Cardiac Research, Northwick Park Hospital, and Institute for Medical Research, Harrow, Middlesex, UK.

BACKGROUND: 201Tl imaging has been widely used for postinfarction risk stratification. However, thrombolytic therapy and aspirin have significantly changed outcome, and there are few nuclear imaging studies that assess prognosis in such patients. Furthermore, newer techniques of 201Tl imaging, such as reinjection and nitrate-enhanced rest 201Tl imaging, have been shown to improve the detection of viable but jeopardized myocardium. METHODS AND RESULTS: We studied 100 consecutive patients, who remained event free 6 weeks after myocardial infarction and thrombolysis. Patients underwent conventional exercise and 4-hour redistribution imaging, followed on a separate day by nitrate-enhanced rest 201Tl study. Planar images were reported semiquantitatively by two experienced observers blinded to clinical data. Redistribution and rest injection images were classified as demonstrating reversible ischemia if they showed improvement in uptake by at least two grades in at least two segments in comparison with the initial exercise scintigram. Patients were followed up for 8 to 32 months (mean, 21 months); during this period, 37 patients had first cardiac events. Reversible ischemia was present in 29 patients on redistribution, of whom 14 (48%) had events; of 71 without reversible defects, 23 (32%) had events (hazard ratio, 1.5; 95% CI, 0.8 to 3.0; P=NS). Nitrate-enhanced rest 201Tl imaging detected reversible defects in 68 patients, of whom 33 (49%) had events, whereas of 32 without reversible defects, only 4 (13%) had subsequent cardiac events (hazard ratio, 8.1; 95% CI, 2.7 to 23.8; P<.001). CONCLUSIONS: Thus, after myocardial infarction and thrombolysis, even "stable" patients have a high (68%) incidence of viable but jeopardized myocardium, causing a high event rate. Those identified to be at high risk by perfusion imaging may benefit from early intervention.

PMID: 9386159 [PubMed - indexed for MEDLINE]

40. Huitink JM, Visser FC, Bax JJ, van Lingen A, Groeneveld ABJ, Teule GJJ. Predictive value of planar 18F-Fluorodeoxyglucose imaging for cardiac events after acute myocardial infarction. Am J Cardiol 1998; 81: 1072–1077.
41. Nijland F, Kamp O, Verhorst P, De Voogt WG, Carcagni A, Visser CA. Prognostic implications of low-dose dobutamine echocardiography early after myocardial infarction. Circulation 1996; 94 (suppl): I679(abstract)

42: J Am Coll Cardiol 1993 Oct;22(4):984-97

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Quantitative relation of myocardial infarct size and myocardial viability by positron emission tomography to left ventricular ejection fraction and 3-year mortality with and without revascularization.

Yoshida K, Gould KL.

Department of Medicine, University of Texas Medical School at Houston 77030.

OBJECTIVES. The purpose of this study was to determine the clinical prognostic value, with and without revascularization, of the size of myocardial infarction and viability as measured by positron emission tomography (PET). BACKGROUND. Poorly contracting but viable myocardium recovers contractile performance after revascularization. However, the quantitative relation among size of infarction and viability by PET, ejection fraction and long-term survival with and without revascularization in patients after myocardial infarction has not been previously reported. METHODS. Infarct size and viability imaged by PET using generator-produced rubidium-82 were quantified objectively by automated software and related to coronary arteriography, left ventricular ejection fraction, revascularization and 3-year mortality. RESULTS. Myocardial infarction or scar > or = 23% of the left ventricle was associated with a 3-year mortality rate of 43% versus that of 5% associated with scar < 23% of the left ventricle (p = 0.014). An ejection fraction < or = 43% correlated with a 3-year mortality rate of 38% compared with 6% for an ejection fraction > or = 43% (p = 0.029) because infarct size > or = 23% of the left ventricle was also associated with an ejection fraction < or = 43%. For patients with a low ejection fraction (< or = 43%) or large infarcts/scar (> or = 23% of the left ventricle), ejection fraction value or infarct size did not predict mortality. However, in patients with an ejection fraction < or = 43%, the absence of viable myocardium in arterial zones at risk was associated with a mortality rate of 63% versus 13% in subjects with viable myocardium, a difference with only a 5.9% probability of occurring by chance alone (p = 0.059). For all patients with viable myocardium in arterial zones at risk, the mortality rate was 8%, and 80% had revascularization over 3 years. For patients with only fixed scar in arterial zones at risk, the mortality rate was 50% versus 8% (p = 0.018), and 40% had revascularization, with no difference in mortality with or without revascularization, thereby suggesting no benefit in this subgroup. CONCLUSIONS. Size of scar and viable myocardium by PET in arterial zones at risk in patients after myocardial infarction are highly predictive of 3-year mortality, particularly in patients with low ejection fraction, and identify patients who are suitable candidates for revascularization after myocardial infarction.

PMID: 8409073 [PubMed - indexed for MEDLINE]

 

43: Circulation 1997 Mar 18;95(6):1402-10

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Comment in:

• Circulation. 1997 Mar 18;95(6):1352-4.

Dobutamine stress echocardiography for risk stratification after myocardial infarction.

Carlos ME, Smart SC, Wynsen JC, Sagar KB.

Division of Cardiology/Hypertension, Medical College of Wisconsin, Milwaukee 53226, USA.

BACKGROUND: Because dobutamine stress echocardiography (DSE) provides assessment of left ventricular function and ischemia at a distance, the major determinants of adverse outcome after acute myocardial infarction (AMI), we undertook this study to determine the role of DSE in risk stratification after AMI. METHODS AND RESULTS: A graded DSE in 5-minute stages was performed in 214 patients (age, 57 +/- 13 years [mean +/- SD]) at 2 to 7 days after AMI. Coronary angiography was performed in 193 patients. Follow-up data regarding major cardiac events were obtained through telephone interviews and chart reviews. All patients were followed for > or = 500 days or until a hard cardiac event occurred. The mean follow-up interval was 494 +/- 182 days after AMI. Peak heart rate and systolic blood pressure were 115 +/- 21 bpm and 135 +/- 29 mm Hg, respectively. An adverse outcome occurred in 80 of 214 patients; cardiac death occurred in 15, nonfatal AMI occurred in 15, sustained or symptomatic ventricular arrhythmia occurred in 5, congestive heart failure occurred in 14, and unstable angina occurred in 31. Significant predictors of adverse outcome by univariate analysis were prior myocardial infarction (P = .005), anterior infarction (P = .006), multivessel coronary artery disease (P < .0001), global resting left ventricular wall motion score index (P < .0001), infarction zone nonviability based on akinesis unresponsive to low-dose dobutamine (P < .0001), and ischemia/infarction at a distance (P < .0001). Furthermore, the extent of infarct zone and nonviability correlated with the severity of the cardiac event. Multivariate analysis of clinical, angiographic, and DSE variables revealed that the only independent predictors of adverse outcome were ischemia/infarction at a distance (P < .0001) and infarction zone nonviability (P < .0001). Multivessel disease identified through DSE was more predictive of adverse outcome than was angiographically determined multivessel disease. CONCLUSIONS: DSE can be used to predict adverse outcomes after AMI.

PMID: 9118506 [PubMed - indexed for MEDLINE]

44. Picano E, Sicari R, Landi P, Cortigiani L, Bigi R, Coletta C, Galati A, Heyman J, Mattioli R, Previtali M, Mathias WJ, Dodi C, Minardi G, Lowenstein J, Seveso G, Pingitore A, Salustri A, Raciti M. Prognostic value of myocardial viability in medically treated patients with global left ventricular dysfunction early after an acute uncomplicated myocardial infarction: a dobutamine stress echocardiographic study. Circulation 1998; 98: 1078–1084.

45: J Am Coll Cardiol 1998 Aug;32(2):380-6

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Prognostic value of myocardial viability and ischemia detected by dobutamine stress echocardiography early after acute myocardial infarction treated with thrombolysis.

Previtali M, Fetiveau R, Lanzarini L, Cavalotti C, Klersy C.

Department of Cardiology, IRCCS Policlinico San Matteo, University of Pavia School of Medicine, Italy. marprevi@tin.it

OBJECTIVES: The aim of the study was to assess the prognostic value of myocardial viability and ischemia detected by dobutamine stress echocardiography (DSE) in patients with acute myocardial infarction (AMI) treated with thrombolysis. BACKGROUND: DSE can detect myocardial viability and ischemia early after AMI, but the prognostic importance of viability and ischemia in these patients has yet to be assessed. METHODS: DSE was performed in 152 patients at a mean of 9 +/- 5 days after a first AMI treated with thrombolysis to evaluate myocardial viability and ischemia. The patients were followed up for 15 +/- 19 months. RESULTS: On the basis of DSE results three groups of patients were identified: group 1 (95 patients, 62.5%) with myocardial viability and ischemia, group 2 with myocardial viability without ischemia (32 patients, 21%) and group 3 (25 patients, 16.5%) with no myocardial viability. During follow-up 10 patients (6.5%) had hard events, 53 (35%) developed unstable angina and 67 (44%) underwent myocardial revascularization. The rate of hard events was 10% in group 1 and 0% in group 2 and 3 patients (p < 0.05 group 1 versus group 2); group 1 patients with viability and ischemia showed a significantly higher rate of recurrence of unstable angina and myocardial revascularization procedures (40% and 60%) compared to group 2 (22% and 16%) and group 3 patients (20% and 20%). Using the Cox multivariate stepwise model, only the extent of ischemic myocardium (hazard ratio (HR) = 21.7, p = 0.02) and angina during DSE (HR = 4.45, p = 0.03) were significant predictors of hard events; an ischemic response to DSE (HR = 2.92, p = 0.001) was the most important predictor of spontaneous events, followed by ST-segment depression during DSE (HR = 1.71, p = 0.04), angina during DSE (HR = 1.53, p = 0.19) and age (HR = 0.96, p = 0.05). CONCLUSIONS: In patients with a first AMI treated with thrombolysis the presence and extent of myocardial ischemia during DSE is the most important predictor of both hard and spontaneous cardiac events, whereas myocardial viability does not have an independent prognostic value.

PMID: 9708464 [PubMed - indexed for MEDLINE]

 

46: Am Heart J 1998 Jan;135(1):51-7

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Time course of myocardial viability after acute myocardial infarction: an echocardiographic study.

Knudsen AS, Darwish AZ, Norgaard A, Gotzsche O, Thygesen K.

Department of Medicine and Cardiology, Aarhus University, Denmark.

The recognition of dysfunctional but viable myocardium after acute myocardial infarction (MI) may be of importance for both patient prognostication and the decision for revascularization. Low-dose dobutamine echocardiography (LDDE) has been shown to be a reliable technique in detecting reversibility of dysfunctional myocardium. The aim of the present study was to assess by LDDE possible time-dependent changes in myocardial viability and to evaluate the value of LDDE used in the postinfarction period. Twenty-seven patients with acute MI underwent LDDE on day 6, 30, and 90. At LDDE day 6, 41% of the affected segments showed a positive response to LDDE. At later examination on day 30 and 90, only 32% and 18%, respectively, of the dysfunctioning segments responded to dobutamine stimulation, with a significant decline in response (p < 0.0001), indicating loss of viability. Spontaneous segmental outcome was significantly better for LDDE-responding segments than for nonresponding segments (p = 0.0001). This study indicated that myocardial viability may be temporary and that a time-dependent loss of viability may take place during the first months after MI.

PMID: 9453521 [PubMed - indexed for MEDLINE]

 

47: J Am Coll Cardiol 1998 Apr;31(5):1018-26

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Prolonged myocardial hibernation exacerbates cardiomyocyte degeneration and impairs recovery of function after revascularization.

Schwarz ER, Schoendube FA, Kostin S, Schmiedtke N, Schulz G, Buell U, Messmer BJ, Morrison J, Hanrath P, vom Dahl J.

Department of Cardiology, Medical Clinic I, Rheinisch-Westfalsche Technische Hochschule University Hospital Aachen, Germany. RSCH@PCSERVER.MKt.RWTH-aachen.de

OBJECTIVES: We sought to define the effects of time on contractile function, morphology and functional recovery after coronary revascularization in patients with dysfunctional but viable (hibernating) myocardium. BACKGROUND: Functional recovery after coronary artery bypass graft surgery in patients with chronic myocardial hibernation is incomplete or delayed. The proposed cause is a progressive temporal degeneration of cardiomyocytes. METHODS: In 32 patients with multivessel coronary disease, regional wall motion analysis was performed in hypoperfused but metabolically active areas before and 6 months after bypass surgery. During bypass surgery, transmural biopsy samples were obtained from the center of the hypokinetic zone for light and electron microscopic analyses. The proposed duration of myocardial hibernation was retrospectively assessed. RESULTS: Patients with a subacute hibernating condition (<50 days) demonstrated a higher preoperative ejection fraction (EF, 50+/-8%), and a better preserved wall motion (WM) in the supraapical wall (-1.4+/-0.4) than did patients with intermediate-term (>50 days, EF 37+/-9%, p < 0.05; WM -2.4+/-1.5, p = 0.08) or chronic (>6 months, EF 40+/-14%, WM -2.7+/-0.9, p < 0.005) ischemia. Structural degeneration correlated with the duration of ischemia (r = 0.56, p < 0.05). Postoperative recovery of function was enhanced in patients with a short history of hibernation compared with patients with an intermediate-term or chronic condition (EF 60+/-10% vs. 40+/-10%, p < 0.001, and vs. 47+/-14%, p < 0.05). CONCLUSIONS: Hibernating myocardium exhibits time-dependent deterioration due to progressive structural degeneration with enhanced fibrosis. Early revascularization should be attempted to salvage the jeopardized tissue and improve postoperative outcome.

PMID: 9562002 [PubMed - indexed for MEDLINE]

 

48: Circulation 1998 Nov 10;98(19 Suppl):II51-6

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Delay in revascularization is associated with increased mortality rate in patients with severe left ventricular dysfunction and viable myocardium on fluorine 18-fluorodeoxyglucose positron emission tomography imaging.

Beanlands RS, Hendry PJ, Masters RG, deKemp RA, Woodend K, Ruddy TD.

Cardiac PET Centre, University of Ottawa Heart Institute, Ontario, Canada. rbeanlan@heartinst.on.ca

BACKGROUND: The identification of high-risk patients who require early revascularization has become increasingly important with the present emphasis on reducing health care resources. This is particularly relevant to health care systems with prolonged waiting times for interventions. Myocardial viability imaging with the use of fluorine 18-fluorodeoxyglucose (FDG) PET may help to identify high-risk patients with severe left ventricular dysfunction. The aim of this study was to evaluate the consequences of prolonged waiting time on cardiac outcomes in patients with left ventricular dysfunction directed to revascularization based on FDG PET imaging. METHODS AND RESULTS: Forty-six patients with coronary disease and an ejection fraction of < or = 35% were considered candidates for revascularization based on FDG PET viability imaging. Thirty-five of 46 patients were subsequently accepted for revascularization. Patients were divided into 2 groups based on the median waiting time after PET: an early group (< 35 days; n = 18) and a late group (> or = 35 days; n = 17). Preoperative mortality rates were significantly increased in the late group (4 of 17 [24%] versus 0 of 18 in the early group; P < 0.05). In postoperative follow-up (17 +/- 7 months), cardiac events occurred in 2 of 18 (11%) and 1 of 13 (7.8%) patients in the early and late groups, respectively. Left ventricular ejection fraction increased after early revascularization (24 +/- 7% to 29 +/- 8%, P < 0.001, baseline versus 3 months) but not in the late group (27 +/- 5% to 28 +/- 6%, P = NS). CONCLUSIONS: Preoperative FDG PET can be used to identify a high-risk group of patients who may benefit from early revascularization. A long waiting time for revascularization is associated with a high mortality rate and suggests that early revascularization is desirable after the identification of hibernating viable myocardium.

PMID: 9852880 [PubMed - indexed for MEDLINE]

 

49: J Cardiovasc Pharmacol 1998;32 Suppl 1:S31-5

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Ejection fraction improvement by beta-blocker treatment in patients with heart failure: an analysis of studies published in the literature.

van Campen LC, Visser FC, Visser CA.

Department of Cardiology, Free University Hospital, Amsterdam, The Netherlands.

Because ejection fraction (EF) is one of the most important predictors of survival in patients with left ventricular (LV) dysfunction and because Packer showed a large reduction in mortality figures with carvedilol, in contrast to former studies with bisoprolol and metoprolol, we investigated if this difference in survival may be related to a difference in improvement of LV function by different beta-blockers. We searched the MEDLINE database and all reference lists of articles obtained through the search for the relation between beta-blocker treatment and improvement in EF. Forty-one studies met the criteria and we added two of our own studies. Four hundred and fifty-eight patients were treated with metoprolol with a mean follow-up of 9.5 months and a mean increase in EF of 7.4 EF units. One thousand thirty patients were treated with carvedilol with a mean follow up of 7 months and a mean increase in EF of 5.7 EF units. One hundred ninety-nine patients were treated with bucindolol with a mean follow-up of 4 months and a mean increase in EF of 4.6 EF units. Several small studies with nebivolol, atenolol, and propranolol were also studied and, when combined, the mean increase in EF was 8.6 EF units. When patients with idiopathic and ischemic cardiomyopathies were compared, the average increase in EF units was 8.5 vs. 6.0, respectively. The use of beta-blocker treatment in heart failure patients, irrespective of the etiology, improved LV function in almost all studies and it appears that the differences among beta-blockers and among etiologies is small and probably insignificant. However, there is a difference in survival rate when the various beta-blockers are compared, suggesting that mechanisms other than improvement of LV function by beta-blockers are responsible for the difference in survival.

Publication Types:

• Review
• Review, Multicase

PMID: 9731693 [PubMed - indexed for MEDLINE]