Chronic Ischemic Left Ventricular Dysfunction Research Articles

Time course of functional recovery after coronary artery bypass graft surgery in patients with chronic left ventricular ischemic dysfunction

Chronic left ventricular (LV) ischemic dysfunction, a condition often referred to as myocardial hibernation, is associated in humans with ultrastructural alterations of the myocytes, including the loss of myofilaments and the accumulation of glycogen. Given the severity of these structural changes, contractile function is unlikely to resume immediately upon revascularization. Therefore, the aim of the present study was to assess the time course of functional improvement after successful revascularization as well as its potential structural correlates. We studied 32 patients with coronary disease and chronic LV ischemic dysfunction who underwent bypass surgery. Dynamic positron emission tomography with N-13 ammonia and F-18 deoxyglucose to assess myocardial perfusion and glucose metabolism was performed in 29 patients. In all patients, a transmural biopsy was harvested from the center of the dysfunctional area, to quantify the increase in extracellular matrix and the presence of structurally altered cardiomyocytes. LV function was serially measured by digitized 2-dimensional echocardiography before and at 10 days, 2 months, and 6 months after revascularization. The time course of recovery of regional function was estimated from the monoexponential decrease in dysfunctional wall motion score. At follow-up, 19 patients had improved LV function, whereas 13 patients showed persistent dysfunction. Before revascularization, reversibly dysfunctional segments had higher myocardial blood flow (82 ± 29 vs 53 ± 21 ml · (min · 100 g)−1, p = 0.044), higher glucose uptake (40 ± 16 vs 21 ± 9 μmol · (min · 100 g)−1, p = 0.001), and less increase in extracellular matrix (25 ± 15% vs 46 ± 17%, p = 0.0008) than segments with persistent dysfunction. The extent to which function recovered was positively correlated with myocardial blood flow and negatively correlated with the increase in the extracellular matrix. In patients with reversible dysfunction, the return of segmental function was progressive and followed a monoexponential time course with a median time constant of 23 days (range 6 to 78). The rate of recovery correlated best with the proportion of altered cardiomyocytes in the biopsy. The present study thus indicates that the recovery of regional and global LV function after successful revascularization is progressive and follows a monoexponential time course that is influenced by the extent of the structural changes affecting cardiomyocytes.

Technetium 99m furifosmin regional myocardial uptake in patients with previous myocardial infarction: relation to thallium-201 activity and left ventricular function.

This study was designed to compare the results of rest-redistribution thallium-201 imaging with those of rest technetium 99m furifosmin single photon emission computed tomography in the same patients with chronic ischemic left ventricular (LV) dysfunction. Twenty-one patients (mean age 62 +/- 9 years) with chronic myocardial infarction and LV dysfunction (mean LV ejection fraction 34% +/- 8%) underwent rest-redistribution thallium imaging and resting furifosmin single photon emission computed tomography on the same day. In each patient, regional thallium and furifosmin activity was quantitatively measured in 13 myocardial segments. Regional LV function was assessed in corresponding segments by echocardiography. At thallium imaging, 91 (33%) segments had normal uptake, 16 (6%) showed reversible defects, and the remaining 166 (61%) irreversible defects. Of these 166 irreversible defects, 74 (45%) had moderate (> or =58% of peak activity) and 92 (55%) severe (<58% of peak activity) reduction of thallium uptake. Regional furifosmin uptake was significantly related to both rest (r = 0.87, P < .0001) and redistribution (r = 0.90, P < .0001) thallium activity. Agreement in the evaluation of regional perfusion status between thallium and furifosmin imaging was observed in 70% of the 84 hypokinetic segments (kappa = 0.54) and in 76% of the 78 akinetic or dyskinetic segments (kappa = 0.60). Concordance in the detection of myocardial viability between thallium and furifosmin imaging was observed in 69 (82%) of hypokinetic regions (kappa = 0.60) and in 65 (83%) of akinetic or dyskinetic regions (kappa = 0.67). These results suggest that in patients with chronic coronary artery disease and LV dysfunction, quantitative rest-redistribution thallium scintigraphy and furifosmin tomography at rest provide similar results in the evaluation of perfusion status and in the detection of myocardial viability.

Quantitative thallium-201 and technetium 99m sestamibi tomography at rest in detection of myocardial viability in patients with chronic ischemic left ventricular dysfunction

Background. This study was designed to determine the most effective quantitative threshold for thallium-201 and technetium 99m sestamibi uptake on tomographic imaging after rest injection for the detection of myocardial viability in patients with chronic myocardial infarction. Methods and Results. Thallium and sestamibi cardiac tomography at rest was performed in 43 patients with chronic myocardial infarction and impaired left ventricular (LV) function undergoing coronary revascularization. In all patients, echocardiography and radionuclide angiography were performed at baseline and repeated 12 months later to evaluate recovery of regional LV function and LV ejection fraction, respectively. Optimal threshold cutoff points to separate reversible from irreversible dysfunction were determined by receiver operating characteristic analysis. When all dysfunctional segments were considered, the best cutoff point in the identification of reversible LV dysfunction for both thallium and sestamibi activity was 67%. When only akinetic or dyskinetic segments were considered, the best cutoff point in the identification of reversible LV dysfunction was 58% for thallium and 55% for sestamibi. In these segments, the area under the receiving operating characteristic curves constructed for thallium and sestamibi activity were 0.74 ± 0.05 and 0.75 ± 0.04, respectively (P = not significant). LV ejection fraction was 33% ± 7% at baseline and increased to 37% ± 7% after revascularization (P < .0001). A significant relation between the number of akinetic or dyskinetic but viable myocardial segments and revascularization-induced changes in LV ejection fraction was observed for both thallium (r = 0.60, P < .0001) and sestamibi (r = 0.64, P < .0001) imaging. Conclusions. In patients with chronic myocardial infarction, quantitative analysis of thallium and sestamibi activity on tomographic imaging at rest predicts recovery of regional and global LV dysfunction after revascularization procedures. The most effective quantitative threshold for detecting reversible LV dysfunction is comparable for thallium and sestamibi tomographic imaging. However, the optimal cutoff point is different for both tracers when all dysfunctional segments are considered or when the analysis is focused only on segments with more severe functional impairment (ie, akinetic or dyskinetic segments). (J Nucl Cardiol 2000;7:8–15.)

Assessment of myocardial viability by MRI

Assessment of myocardial viability has become an important issue in patients presenting with either acute myocardial infarction or presenting with chronic ischemic left ventricular dysfunction. In patients with viable myocardium recovery of left ventricular function can be anticipatedm, spontaneously in patients with acute myocardial infarction or following revascularization in patients with ischemic cardiomyopathy. In contrast, patients without viable tissue are not likely to improve in left ventricular function. Currently, nuclear imaging techniques and dobutamine stress echocardiography are used for assessment of viability; recent studies with magnetic resonance imaging (MRI) have however demonstrated the potential usefulness of this technique for the assessment of viability. Various parameters, derived from resting MRI, can be used as markers of myocardial viability, including the end-diastolic wall thickness, systolic wall thickening and signal intensity without contrast-enhancement. Other studies have combined the information from resting MRI with the assessment of contractile reserve during dobutamine stimulation. Finally, recent studies have evaluated the use of contrast-enhanced MRI to detect viable myocardium. All of these parameters are potentially useful and MRI provide an alternative approach for the assessment of viable myocardium.

Quantification of 99Tcm-sestamibi

Little is known about the usefulness of free fatty acid scintigraphy for assessing viability in chronic ischaemic heart disease. To investigate this, we quantified the uptake of 99Tcm-sestamibi and 123I-BMIPP at rest twice within 6 months in 20 patients with chronic ischaemic left ventricular dysfunction and infarction. Four patterns of the relative distribution of both tracers were observed and classified as normal, mismatched, matched and scar. The proportion of the left ventricular surface corresponding to each pattern was expressed as the percentage of the total surface using a polar map. Between the two studies, the patients either underwent revascularization or were treated conservatively. The quantitative results were compared with those of dobutamine stress echocardiography (DSE) in arterial territories with resting contractile dysfunction and correlated with the evolution of regional and global function at follow-up. At baseline, 25 arterial territories were analysed. Using sestamibi, on average one-third of their surface was considered to be normally perfused. No clear association was found between the percent normally perfused surface and the DSE findings. Adding BMIPP and using a value of > 7% of the arterial surface with BMIPP lower than sestamibi (mismatch) as the cut-off for the significance of viability, 14 of 18 mismatched regions were considered viable by DSE, and six of seven with < 7% mismatched surface or matching were not. Fifteen patients were viable, of whom 13 were revascularized (16 territories). At follow-up, global function improved in 11 of the 15 viable patients, all in the revascularized group. Regional improvement was noted in 11 of 16 revascularized territories, and was associated with a significant increase in sestamibi and BMIPP uptake and in the percent normally perfused myocardial surface. In the five patients without significant viability, no functional deterioration or changes in the quantitative parameters were observed during treatment. The results suggest that quantitative analysis of the uptake of sestamibi and BMIPP is a reliable method to objectively assess the presence of myocardial viability in chronic ischaemic heart disease and to predict functional improvement after revascularization.

Exercise-rest Tc-99m tetrofosmin SPECT in patients with chronic ischemic left ventricular dysfunction: Direct comparison with TI-201 reinjection

Background. This study was designed to compare the results of exercise-rest technetium-99m tetrofosmin single photon emission computed tomography (SPECT) with those of thallium-201 reinjection at rest after exercise-redistribution imaging in the same patients with chronic ischemic left ventricular (LV) dysfunction. Methods. Within 1 week, 33 patients with chronic myocardial infarction and LV dysfunction underwent exercise-rest tetrofosmin SPECT and TI-201 reinjection at rest after exercise-redistribution imaging. In each patient, regional tetrofosmin and TI-201 activity was quantitatively measured in 22 myocardial segments. Regional LV function was assessed in corresponding segments by echocardiography. Results. Agreement in the evaluation of regional perfusion status between tetrofosmin and TI-201 imaging was observed in 78% of the 726 total segments, with a κ value of 0.61. In segments with normal function at echocardiography ( n = 436), no difference between TI-201 and tetrofosmin uptake was observed. In hypokinetic segments ( n = 138), exercise tetrofosmin uptake was lower ( P < .01) as compared with exercise TI-201 activity, whereas no difference was observed between tetrofosmin uptake at rest as compared with TI-201 activity on redistribution and reinjection images. In segments with severe functional impairment (akinetic or dyskinetic, n = 152), tetrofosmin uptake on exercise images was reduced ( P < .01) as compared with exercise TI-201 activity; furthermore, tetrofosmin uptake at rest was lower ( P < .01) as compared with TI-201 activity on both redistribution and reinjection images. In these segments, concordance in the detection of myocardial viability between tetrofosmin and TI-201 imaging was observed in 138 (91%) of the 152 segments, with a κ value of 0.77. Conclusions. In patients with chronic coronary artery disease and LV dysfunction quantitative exercise-rest tetrofosmin and TI-201 reinjection SPECT provide similar information in the assessment of perfusion status and in the detection of myocardial viability.

A canine model of chronic ischemic cardiomyopathy: characterization of regional flow-function relations.

The controversy regarding the mechanism(s) of left ventricular (LV) dysfunction in chronic coronary artery disease is, in part, related to the lack of an appropriate animal model for this condition. We have developed such a model by placing Ameroid constrictors on proximal portions of coronary arteries in dogs who were euthanized (mean of 6 wk) after the development of severe global LV dysfunction noted on two-dimensional echocardiography. The LV end-systolic size nearly doubled (P < 0.001) over the observation period, and the percent change in LV size from end diastole to end systole decreased by >50% (P < 0.001). Regional dysfunction was noted in 23 of 24 myocardial beds analyzed within regions showing no gross evidence of infarction. In 10 of these beds, severe dysfunction was noted without a decrease in radiolabeled microsphere-derived myocardial blood flow (MBF). In 13 myocardial beds, decrease in function was associated with a decrease in MBF (P < 0.001), with close coupling noted between percent wall thickening and MBF. In the beds that exhibited an ultimate decrease in MBF, the decrease in function preceded the decrease in MBF. In conclusion, we describe chronic LV dysfunction in a canine model of multivessel stenosis that closely mimics chronic ischemic LV dysfunction in humans. Whereas regional function is severely reduced in this model, MBF is varied in different segments and at different times during the observation period. These results provide new insights regarding flow-function relations in chronic ischemic LV dysfunction.

Relation between Tc-99m furifosmin myocardial uptake and thallium-201 activity in patients with chronic ischemic left ventricular dysfunction

Relation between Tc-99m furifosmin myocardial uptake and thallium-201 activity in patients with chronic ischemic left ventricular dysfunction

Biphasic Response to Dobutamine Predicts Improvement of Global Left Ventricular Function After Surgical Revascularization in Patients With Stable Coronary Artery Disease: Implications of Time Course of Recovery on Diagnostic Accuracy

Objectives. This study sought to evaluate the time course of improvement of left ventricular (LV) dysfunction in stable patients and its implications on the accuracy of dobutamine echocardiography for predicting improvement after surgical revascularization.Background. Little is known about the optimal timing for evaluation of postrevascularization recovery of the contractile function of viable myocardium.Methods. Sixty-one patients with chronic ischemic LV dysfunction scheduled for elective surgical revascularization were prospectively selected. They underwent dobutamine echocardiography (5 to 40 μg/kg body weight per min) and radionuclide ventriculography both preoperatively and at 3-month follow-up. At 14 months, another evaluation of LV function was obtained. To analyze echocardiograms, a 16-segment model and a five-point scoring system were used. Dyssynergic segments were considered likely to recover in the presence of a biphasic contractile response to dobutamine. Improvement of global function was defined as a ≥5% increase in LV ejection fraction (LVEF).Results. Of the 61 patients, LVEF improved in 12 at 3 months and in 19 at late follow-up (from 32 ± 8% to 42 ± 9%, p < 0.0001). The frequency and time course of improvement of LVEF were similar in patients with mild and severe LV dysfunction. A biphasic response, identified in 186 of the 537 dyssynergic segments, was predictive of recovery in 63% at 3 months and in 75% at late follow-up. The positive predictive value was best in the most severe dyssynergic segments (90% vs. 67%). Other responses were highly predictive for nonrecovery (92%). The sensitivity and specificity for improvement of global function on a patient basis (≥4 biphasic segments) were 89% and 81%, respectively, at late follow-up.Conclusions. Serial postoperative follow-up studies demonstrate incomplete recovery of contractile function at 3 months. The diagnostic accuracy of dobutamine echocardiography for predicting recovery is dependent on three factors: the combining of low and high dobutamine dosages, the severity of regional dyssynergy and the timing of evaluation.

Morphologic alterations of myocardium under conditions of left ventricular assistance

Implantation of a left ventricular assist device (LVAD) is used as a bridge for patients expecting heart transplantation. By changing the loading conditions of the failing heart, the LVAD most probably alters heart structure. We report the pathologic examination of myocardium from a patient before and after 4 months of LVAD use. We show that unloading the heart with the LVAD leads to a dedifferentiation process of the cardiomyocytes comparable to that found in “hibernating” myocardium. Clinical summary. An 18-year-old male patient was seen for idiopathic dilated cardiomyopathy that did not improve with maximal drug therapy. Because of the unavailability of a compatible heart donor, the patient was surgically treated with partial left ventricular resection (resection of the anterolateral wall and correction of the mitral regurgitation). The lack of postoperative improvement led to the insertion of an implantable LVAD (Novacor; Baxter Healthcare Corp., Novacor Div., Oakland, Calif.). After 4 months of stabilization, the device was removed. Three months later, a heart donor was found and the patient underwent transplantation. Myocardial tissues retrieved during partial left ventricular resection, at explantation of the LVAD, and at transplantation were kept for pathologic examination. All tissue fragments were embedded in paraffin, cut in 7 μm thick sections, then stained with Masson trichrome stain and periodic acid-Schiff reaction. Results. Morphologic characteristics of the fragments retrieved during partial left ventricular resection were not different from normal tissue (Fig. 1, A). The cardiomyocytes covered 90% of the total surface, whereas extracellular matrix covered about 7%. Cardiomyocytes were globally normal in appearance on light-microscopic examination, with cytosol filled with myofilaments and nuclei with normal chromatin content (Fig. 1, A). About 15% of the cardiomyocytes showed slight accumulation of glycogen in the cytosol (Fig. 2, A). Fig. 2Glycogen accumulation in cardiomyocytes. A, A few cardiomyocytes show an intracellular accumulation of dark-red material compatible with glycogen. After 4 months of LVAD support, most cardiomyocytes display an important accumulation of glycogen in their cytosol. B, Periodic acid–Schiff reaction (original magnification ×20.)View Large Image Figure ViewerDownload (PPT)After 4 months with LVAD, morphologic inspection of the myocardial tissue revealed major differences (Fig. 1, Fig. 2). The cellular volume was increased compared with the previous fragments. The rod-shaped cells found initially were now potato-like in appearance, dilated and spherical (Fig. 2, A). Their myofilament content was dramatically decreased, and their nuclei were condensed and pyknotic (Fig. 1, B). The percentage of surface covered by extracellular matrix was increased to 13% (Fig. 1, B). About 95% of the cardiomyocytes showed an intracellular accumulation of glycogen (Fig. 2, B). In the fragments retrieved during transplantation, the cellular morphologic characteristics had returned to a normal pattern in most of the cells, but the percentage of intercellular fibrosis remained increased. Discussion. Our data thus show that heart structure may create important—albeit reversible—morphologic alterations after several months of LVAD implantation. These alterations are mainly a loss of myofilaments, an intracellular accumulation of glycogen, and an increase in extracellular matrix. The alterations that we found in this case are similar to those previously described in human “hibernating” myocardium.1Vanoverschelde JL Wijns W Depre C et al.Mechanisms of chronic regional post-ischemic dysfunction in humans: new insights from the study of non-infarcted collateral-dependent myocardium.Circulation. 1993; 87: 1513-1523Crossref PubMed Google Scholar, 2Depre C Vanoverschelde JL Melin JA et al.Structural and metabolic correlates of the reversibility of chronic left ventricular ischemic dysfunction in humans.Am J Physiol. 1995; 268: H1265-H1275PubMed Google Scholar Patients with hibernating myocardium in whom such morphologic alterations are found have functional improvement after revascularization,3Depre C Vanoverschelde JL Gerber B Borgers M Melin JA Dion R. Correlation of functional prognosis with myocardial morphology and metabolism in patients undergoing coronary bypass surgery.J Thorac Cardiovasc Surg. 1997; 113: 371-378Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar suggesting that these phenotypic alterations are potentially reversible. Such a phenotypic shift is still poorly understood. There is accumulating evidence that the structural changes observed are the consequence of a reverse differentiation process, because these altered cardiomyocytes are similar to fetal cardiomyocytes.4Ausma J Schaart G Thone F et al.Chronic ischemic viable myocardium in man: aspects of dedifferentiation.Cardiovasc Pathol. 1995; 4: 29-37Abstract Full Text PDF Scopus (86) Google Scholar It remains unknown, however, through what mechanisms unloading the heart with the LVAD induces such alterations and whether this adaptation is a prerequisite for subsequent functional improvement.

Relation of Ultrasonic Tissue Characterization With Integrated Backscatter to Contractile Reserve in Chronic Left Ventricular Ischemic Dysfunction

Previous studies have shown that viable but stunned myocardium displays contractile reserve and exhibits cardiac cycle-dependent variations of integrated backscatter, whereas infarcted myocardium does not. The present study was designed to evaluate whether integrated backscatter imaging could be useful in identifying segments with recruitable inotropic reserve in patients with chronic left ventricular (LV) ischemic dysfunction. We studied 15 patients (mean age 59 ± 10 years) with chronic coronary artery disease, anterior or inferior wall dysfunction, and depressed LV ejection fraction (35 ± 12%), and 6 noncardiac control subjects (mean age 49 ± 18 years). Cardiac cycle-dependent variations of integrated backscatter were measured in anterior and inferior segments during transesophageal echocardiography and compared with the contractile response (% wall thickening) of these segments to low doses of dobutamine (5 to 10 μg/kg/min). The average magnitude of cardiac cycle-dependent variations of integrated backscatter was greater among normally contracting segments of both patients and controls (5.67 ± 0.88 and 5.64 ± 2.26 dB, respectively, p = NS) than among dysfunctional segments (2.77 ± 3.05 dB, p <0.01 vs control and remote segments). Dysfunctional segments were further categorized into those with and without dobutamine-induced contractile reserve. At baseline, systolic wall thickening was similar among segments responding to dobutamine than among those that did not (3.6 ± 2.3% vs 2.9 ± 1.6%, p = NS). During dobutamine, systolic wall thickening increased only in segments showing improvement in wall motion score (to 24.5 ± 4.7%), whereas it remained unchanged in segments not responding to dobutamine (to 2.0 ± 3.7%, p <0.01). The magnitude of resting cardiac cycle-dependent variations of integrated backscatter was larger in segments responding to dobutamine than in those with persistent dysfunction (5.31 ± 2.06 vs 0.23 ± 0.94 dB, p <0.01) and correlated significantly (r = 0.74, p <0.01) with systolic wall thickening during dobutamine. Our data demonstrate that resting cardiac cycle-dependent variations of integrated backscatter closely parallel contractile reserve in patients with chronic LV ischemic dysfunction. This suggests that tissue characterization with integrated backscatter could be a useful adjunct to the delineation of myocardial viability in these patients.

Amlodipine in Ischaemic Left Ventricular Dysfunction with Mild to Moderate Heart Failure

In this study, we evaluated the effectiveness of amlodipine in patients with severe ischaemic left ventricular dysfunction (LVD) and mild to moderate heart failure, but not current angina, assessing the effects of the drug on symptoms, left ventricular function and exercise capacity. We studied 36 patients with ischaemic LVD (radionuclide ejection fraction <40%, left ventricular end-diastolic dimension >60mm) and mild to moderate heart failure (NYHA class II or III) without angina treated with ACE inhibitors (36 of 36), digitalis (34 of 36) and diuretics (30 of 36). Among the 36 recruited patients, 33 fulfilled the study protocol, including 2 weeks of run-in (standard therapy), 8 weeks of treatment (standard therapy + amlodipine 5mg once daily) and 2 weeks of washout (standard therapy). Symptoms graded on a 10-point scale (heart failure score; a higher score representing improvement in symptoms), radionuclide left ventricular ejection fraction (rLVEF), echocardiographic left ventricular end-diastolic dimension (LVEDD), peak aerobic capacity (VO(2max)), exercise time (ET) and total work load (TWL) were measured after run-in, treatment and washout periods. All patients underwent coronary angiography and (201)Thallium (Tl) myocardial scintigraphy. With respect to baseline and washout, after amlodipine treatment the HF score improved (6.6 +/- 1.3 after amlodipine vs 5.9 +/- 1 at baseline and 5.9 +/- 1.1 at washout; p < 0.02), rLVEF increased (33.12 +/- 9.02% vs 29.74 +/- 7.72% and 30.02 +/- 7.39%, respectively; p < 0.001), and VO(2max) (14.35 +/- 4.05 ml/kg/min vs 12.68 +/- 3.21 ml/kg/min and 12.62 +/- 3.59 ml/kg/min, respectively; p < 0.003), ET (440 +/- 169 sec vs 395 +/- 158 sec and 402 +/- 162 sec, respectively; p < 0.02) and TWL (2183.2 +/- 439 kpm vs 1615.5 +/- 427 kpm and 1708.8 +/- 437 kpm, respectively; p < 0.01) were also increased. The increase in VO(2max) was related to systolic blood pressure at rest and at the peak of exercise, and to the presence of viable and/or ischaemic myocardium at (201)Tl myocardial scintigraphy. Amlodipine, in addition to standard therapy (including in all cases an ACE inhibitor), reduced symptoms and improved exercise capacity and ventricular function in patients with mild to moderate heart failure due to myocardial ischaemia. Thus, amlodipine is useful in patients with ischaemic LVD and heart failure without angina. The improvement in exercise capacity was greater in patients with scintigraphic evidence of viable and/or ischaemic myocardium and higher blood pressure. However, our study presented some limitations (i.e. an open study with few patients), and only generated a hypothesis that could lead to a wider, multicentre, cooperative trial. Treatment of patients with chronic ischaemic left ventricular dysfunction (LVD) with heart failure symptoms but without angina is a difficult clinical problem. Despite the fact that surgical myocardial revascularisation may improve survival, most patients are not good candidates for surgery. Thus, 'polypharmacy' remains the principal option for these individuals. ACE inhibitors have become a cornerstone in the treatment of all forms of LVD, and have been demonstrated to improve functional class and survival. Nitrates, digitalis and diuretics are also commonly used for their effects on symptoms. Despite there being no evidence that calcium antagonists are useful for the treatment of heart failure or impaired ventricular function after myocardial infarction, these drugs are still prescribed to many patients with ischaemic LVD. However, it is possible that the concomitant administration of ACE inhibitors could reduce the reflex neurohumoral activity caused by some calcium antagonists, while preserving some of the beneficial properties of these agents. Among other calcium antagonists, amlodipine does not adversely affect the clinical status of patients. Some studies have shown that it reduces symptoms, improves exercise tolerance and does not result in neurohormonal stimulation. Moreover, amlodipine appears to have a mortality benefit in patients with dilated cardiomyopathy but not in patients with underlying coronary disease where it appears to have a 'neutral' effect. Thus, it is not clear whether amlodipine is useful in patients with ischaemic LVD, particularly in patients with silent coronary artery disease. In this study, we evaluated the effectiveness of amlodipine, in addition to standard therapy, in patients with ischaemic LVD and mild to moderate heart failure, assessing the effects of the drug on symptoms, LV function and exercise capacity.

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

Objectives. This study sought to determine the incidence and extent of dobutamine-induced contractile reserve in myocardial regions characterized by classical and new positron emission tomographic (PET) patterns in patients with chronic ischemic left ventricular dysfunction.Background. PET is considered the most accurate method for assessment of myocardial viability, which is traditionally identified by perfusion–metabolism mismatch.Methods. In 23 patients, segmental wall thickening expressed by four echocardiographic scores at rest and during low dose (5 and 10 μg/kg body weight per min) dobutamine infusion and regional myocardial uptake of potassium-38 and fluorine-18 fluorodeoxyglucose (F-18 FDG) during glucose clamp were compared in 16 corresponding segments.Results. Of a total of 368 segments, data analysis focused on 214 (58%) dyssynergic segments at baseline. Contractile reserve was identified with increasing incidence according to the six following PET patterns: 1) diminished perfusion and moderate reduction of F-18 FDG uptake (3 [11%] of 28 segments); 2) proportional reduction of perfusion and F-18 FDG uptake (10 [23%] of 43 segments); 3) perfusion–metabolism mismatch (19 [46%] of 41 segments); 4) preserved perfusion but moderate reduction of F-18 FDG uptake (13 [46%] of 27 segments); 5) preserved perfusion and F-18 FDG uptake (37 [59%] of 63 segments) compared with our normal database; and 6) normal perfusion but absolute increased F-18 FDG uptake (8 [73%] of 11 segments). In the latter category, only 7 of 24 segments had normal rest function. In dyssynergic segments with F-18 FDG uptake ≥50% supplied by vessels with ≥75% stenosis, improvement in contractility during dobutamine correlated with the presence of collateral channels.Conclusions. Myocardial regions with the traditional mismatch pattern of viability show contractile reserve in slightly <50%. In segments with moderate reduction of F-18 FDG uptake, the contractile response to dobutamine is linked to the level of rest perfusion. Most segments with preserved perfusion and increased F-18 FDG uptake have impaired rest function, but contractile reserve is still present. These data suggest that in chronic ischemic left ventricular dysfunction, myocardial hibernation is a heterogeneous condition.

Prognostic value of coronary angiography in patients with chronic ischemic left ventricular dysfunction and evidence of viable myocardium on thallium reinjection imaging

Background. We evaluated the independent and incremental prognostic value of cardiac catheterization and coronary angiographic data over thallium reinjection after stress redistribution imaging in patients with myocardial infarction and left ventricular dysfunction. Methods and Results. Sixty-nine patients with a first myocardial infarction (>8 weeks) and left ventricular ejection fraction ≤40% underwent thallium-201 reinjection after stress redistribution tomographic imaging and cardiac catheterization. During follow-up (mean 26 months) 11 cardiac events (8 cardiac deaths and 3 nonfatal myocardial infarctions) occurred. On Cox regression analysis independent predictors of cardiac events were the sum of reversible and moderately irreversible defects at thallium reinjection ( χ 2, 16.4, p < 0.005) and the number of reversible defects at stress redistribution ( χ 2, 5.1, p < 0.05). Moreover, thallium reinjection imaging improved the prognostic power of clinical, exercise, and stress redistribution data ( p < 0.01). The inclusion of left ventricular ejection fraction produced a borderline improvement ( p = 0.06), whereas the number of vessels with coronary disease did not. In contrast, in patients at high risk such as those with at least 25% of viable myocardium at reinjection, the number of diseased vessels provided additional prognostic information ( p < 0.05). Conclusions. In patients with chronic ischemic left ventricular dysfunction, left ventricular ejection fraction, but not the number of diseased vessels, provides additional prognostic information to thallium imaging. Therefore coronary angiography seems unnecessary in these patients, unless a significative amount of viable myocardium is detectable.

Chronic myocardial hibernation in humans. From bedside to bench.

Since the pioneering work of Tennant and Wiggers,1 it has been known that total ischemia leads to a prompt cessation of contraction and eventually results in the appearance of cell damage and irreversible myocardial necrosis. Accordingly, in the minds of many cardiologists, the discovery of an abnormal regional contraction in a patient with coronary artery disease has long been equated with the presence of irreversible myocardial necrosis. With the advent of recanalization therapy, however, evidence progressively accumulated that prolonged regional “ischemic” dysfunction did not always arise from irreversible tissue damage and, to some extent, could be reversed by restoration of blood flow.2 3 4 5 These observations have led to the speculation that chronically hypoperfused myocardium, which is often referred to as “hibernating,”2 3 4 5 6 could maintain viability by simply reducing its metabolic demand to match the decreased supply for as long as myocardial perfusion was inadequate. The chronic impairment of contractile function in this setting has been regarded as a protective mechanism by which the heart spontaneously downgrades its myocardial function, minimizes its energy requirements, and prevents the appearance of irreversible tissue damage.2 4 5 The concept of chronic hibernation thus consists of two parts: a unique clinical observation that bears important implications for the management of patients with chronic coronary artery disease2 3 4 5 6 and a pathophysiological hypothesis, yet to be demonstrated, implying that the chronic dysfunction is due to a chronic reduction of resting MBF.4 5 Other aspects that were not included in the original description, ie, the rapidity of mechanical recovery after successful revascularization7 and the response of dysfunctional myocardium to inotropic stimulation, are now also considered to be integral parts of this condition. The purpose of this discussion is to review some of the …

Correlation of functional recovery with myocardial blood flow, glucose uptake, and morphologic features in patients with chronic left ventricular ischemic dysfunction undergoing coronary artery bypass grafting

Objective: Our objective was to investigate the influence of preoperative myocardial ultrastructure and metabolism on recovery of contractile function after coronary artery bypass grafting in patients with coronary artery disease and left ventricular dysfunction. Methods: Dynamic positron emission tomography with 13N-ammonia and 18F-deoxyglucose was used to assess myocardial perfusion and glucose uptake in 53 patients scheduled for coronary revascularization because of coronary artery disease and left ventricular dysfunction. The degree of tissue fibrosis and the presence of potentially reversible alterations of cardiomyocytes (loss of myofilaments and accumulation of glycogen) were quantified from transmural biopsy specimens. These were harvested from the center of the dysfunctional area during the operation and analyzed with a light microscope. The recovery of contractile performance was assessed from the changes in left ventricular function at contrast ventriculography or echocardiography before and 6 months after the operation. Results: According to postoperative changes in regional wall motion, left ventricular function was considered to have improved in 34 patients, whereas dysfunction persisted in 19 patients. In patients with improved wall motion, ejection fraction rose by 12% and end-systolic volume decreased by 28%. By contrast, in patients with persistent dysfunction, ejection fraction decreased by 6% and end-systolic volume increased by 25%. Before revascularization, myocardium with reversible dysfunction displayed higher levels of absolute myocardial blood flow, higher myocardial glucose uptake, less tissue fibrosis, and more altered cardiomyocytes than myocardium with persistent dysfunction. Significant correlations were found between regional blood flow and the surface of the biopsy specimen covered by fibrosis, as well as between glucose uptake and the density of altered cardiomyocytes. Conclusion: In patients with left ventricular ischemic dysfunction, the recovery of regional and global left ventricular function after surgical revascularization is associated with higher preoperative blood flow and glucose uptake, with less tissue fibrosis and a higher amount of viable cardiomyocytes in the dysfunctional area. The current study thus confirms the value of noninvasive preoperative metabolic imaging for identification of residual viable myocardium and for prediction of the functional outcome after revascularization. (J Thorac Cardiovasc Surg 1997;113:379-89)

Outcome of bypass surgery in patients with chronic ischemic left ventricular dysfunction

Purpose: To determine the preoperative findings of MR imaging of the left ventricle (LV) that could best predict the functional outcome of the LV after surgical revascularization.Material and Methods: Patients with angina pectoris, previous myocardial infarction, and dysfunction of the LV, and who had a preoperative cine MR, were re-evaluated after bypass surgery with MR in a study on the effects of revascularization after mean 22 months.Results: Angina pectoris was relieved in all patients except one, but the maximum workload during the exercise test was increased in only 3 patients. Coronary angiography showed that 37 of 45 (82%) of the distal anastomoses were open. The LV ejection fraction was the same before and after operation both at angiography and MR imaging. MR showed LV end-diastolic volume to be increased from 190 ± 50 ml to 250 ± 70 ml. Compared to angiography, MR provided additional information regarding myocardial wall thickness and function, and the size of myocardial infarction. Improvemen...

Head-to-head comparison of exercise-redistribution-reinjection thallium single-photon emission computed tomography and low dose dobutamine echocardiography for prediction of reversibility of chronic left ventricular ischemic dysfunction

We sought to directly compare the diagnostic value of exercise-redistribution-reinjection thallium single-photon emission computed tomography (SPECT) and low dose dobutamine echocardiography for prediction of contractile recovery after revascularization. Both thallium SPECT and dobutamine echocardiography have been proposed to predict the reversibility of left ventricular dysfunction after revascularization. Although both techniques permit differentiation of viable from nonviable myocardium, few studies have directly compared their accuracy in the same patients. Seventy-three consecutive patients (mean [+/- SD] age 59 +/- 9 years) with coronary disease and regional left ventricular dysfunction underwent exercise-redistribution-reinjection thallium SPECT and dobutamine echocardiography before revascularization. Recovery of function was evaluated with echocardiography 5.5 +/- 2.5 months after revascularization. For analysis, the left ventricle was divided into 16 segments, in which percent thallium uptake was quantitated using circumferential profiles, and regional wall motion was graded semiquantitatively (normal = 1; akinetic = 3). The diagnostic performance of the two tests was investigated both for individual patients and for individual segments. Individual patient analysis showed that left ventricular ejection fraction improved > 5% after revascularization in 43 patients, whereas 30 showed no change. Receiver operating characteristic curves were used to select optimal criteria for prediction of functional recovery after revascularization. According to a mean thallium uptake > 54% at reinjection, SPECT had a sensitivity of 72%, a specificity of 73% and an overall accuracy of 73%. Similarly, according to an improvement in wall motion score > 3.5 grades during doubutamine echocardiography, echocardiography had a sensitivity of 88%, a specificity of 77% and an overall accuracy of 84% (p = NS vs. thallium). Segmental analysis showed that SPECT and dobutamine echocardiography had similar sensitivity (77% and 75%, respectively), but SPECT had lower specificity (56% vs. 86%, p < 0.01). Quantitative exercise-redistribution-reinjection thallium SPECT and dobutamine echocardiography have comparable accuracy for prediction of reversibility of global left ventricular dysfunction after revascularization. However, dobutamine echocardiography has greater specificity than thallium imaging for prediction of functional recovery on a segmental basis.

Head-to-Head Comparison of Exercise–Redistribution–Reinjection Thallium Single-Photon Emission Computed Tomography and Low Dose Dobutamine Echocardiography for Prediction of Reversibility of Chronic Left Ventricular Ischemic Dysfunction

Head-to-Head Comparison of Exercise–Redistribution–Reinjection Thallium Single-Photon Emission Computed Tomography and Low Dose Dobutamine Echocardiography for Prediction of Reversibility of Chronic Left Ventricular Ischemic Dysfunction

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

Objectives. The aim of this study was to correlate dobutamine-induced contractile reserve as detected by echocardiography with findings on positron emission tomography in patients with chronic ischemic left ventricular dysfunction.Background. Contractile reserve induced by low dose dobutamine infusion has been proposed as a marker of myocardial viability.Methods. Sixty patients with stable coronary artery disease and left ventricular dysfunction (mean ejection fraction [± SD] 29 ± 10%) underwent transthoracic echocardiography with dobutamine infusion (up to 10 μg/kg body weight per min) and positron emission tomography with nitrogen-13 ammonia and fluorine-18 (F-18) fluorodeoxyglucose as a perfusion and a metabolic tracer, respectively. Regional wall motion, perfusion and metabolism were analyzed semiquantitatively by using a 16-segment model. Segments with F-18 fluorodeoxyglucose uptake > 50% were considered viable on positron emission tomography.Results. After dobutamine infusion, hemodynamic variables changed significantly, and myocardial ischemia was evident in 17 patients. All 60 patients had dysfunctional myocardium considered viable on positron emission tomography (8 ± 4 segments/patient), whereas 52 patients had dysfunctional myocardium with contractile enhancement by dobutamine echocardiography (4 ± 2 segments/patient, p = 0.01). The extent of dysfunctional myocardium with contractile reserve appeared to correlate less closely with the total extent of viable dysfunctional myocardium identified by positron emission tomography than with the number of such segments associated with a pattern of perfusion-metabolism mismatch.Conclusions. In patients with chronic ischemic left ventricular dysfunction, echocardiography can be used to identify enhancement in the contractile function of viable dysfunctional myocardium after infusion of low dose dobutamine. In this study, the presence and extent of such enhancement were relatively less than the values obtained from positron emission tomography.