The persistence of hibernating myocardium after acute myocardial infarction

Objective To establish the persistence of hibernating myocardium initiallydetected after myocardial infarction treated with thrombolysis. Methods and results Fourteen patients underwent gated positron emission tomographywith 18-fluoro-deoxyglucose and N13-ammonia at a median of 8days after first myocardial infarction. Repeat scans were performedat a median of 13 weeks post-infarction. A total of 148 (30·9%)myocardial segments showed reduced N13-ammonia uptake at thetime of the first scan compared with 154·5 (32·2%)segments at the time of repeat imaging. The median change inthe number of segments with reduced perfusion was –1·0.Initially 13 subjects had hibernating myocardium, seven patientshad large areas and six had smaller regions. Six (46·2%)subjects had repeat scans showing unchanged areas of hibernatingtissue and seven had second scans demonstrating changes in thesize of the region of hibernating myocardium. One patient hadno hibernating myocardium on either scan. Conclusions Positron emission tomography performed several months aftermyocardial infarction demonstrates significant changes in myocardialperfusion. However, a reduction in the number of segments withreduced perfusion does not always result in an improvement inmyocardial metabolism and contraction. Whilst most regions ofhibernating myocardium were still present several months afterinfarction, in only approximately half was the size of the mismatchedregion unchanged. Therefore it is not possible to predict thefate of hibernating myocardium which is present after infarction.     

Efficacy of coronary angioplasty for the treatment of hibernating myocardium

OBJECTIVES: To determine the efficacy of coronary angioplasty as the sole method of revascularisation in patients with coronary artery disease and chronically dysfunctional but viable myocardium (hibernating myocardium), and to assess the effect of restenosis on functional outcome. DESIGN AND PATIENTS: 24 consecutive patients with hibernating myocardium were studied. Positron emission tomography was used to assess myocardial viability, blood flow, and flow reserve. One patient refused angioplasty, one had bypass surgery, and one died while waiting for an elective procedure. The procedure failed in three patients. The remaining 18 patients had repeat echocardiography, 15 had repeat coronary angiography, and nine had repeat assessments of blood flow and flow reserve at mean (SD) 17 (2) weeks after angioplasty. In three patients restenosis was documented. RESULTS: The wall motion score index in the revascularised territories improved from 1.71 (0.37) to 1.34 (0.47) (p = 0.008). Thirty of 51 dysfunctional segments improved in territories without restenosis compared with three of 14 in restenosed territories (p = 0.001). Hibernating and normal segments had comparable flows (0.82 (0.26) v 0.89 (0.24) ml/min/g; NS) while flow reserve was lower in hibernating segments (1.55 (0.68) v 2.07 (1.08); p = 0.03). In segments without restenosis flow reserve improved from 2.03 (1.25) to 2.33 (1.4) (p = 0.03). Sensitivity, specificity, and positive and negative predictive accuracy of the viability study were 97%, 77%, 82%, and 96%, respectively. After excluding patients with restenosis, specificity and positive predictive accuracy improved to 90% and 93%. CONCLUSIONS: Angioplasty improves function in hibernating myocardium, and restenosis prevents recovery; hibernating myocardium is characterised by an impairment of flow reserve; restenosis affects the diagnostic accuracy of viability studies.     

Qualitative and quantitative real time myocardial contrast echocardiography for detecting hibernating myocardium

Background: Real time myocardial contrast echocardiography (RTMCE) is an emerging imaging modality for assessing myocardial perfusion that allows for noninvasive quantification of regional myocardial blood flow (MBF). Aim: We sought to assess the value of qualitative analysis of myocardial perfusion and quantitative assessment of myocardial blood flow (MBF) by RTMCE for predicting regional function recovery in patients with ischemic heart disease who underwent coronary artery bypass grafting (CABG). Methods: Twenty‐four patients with coronary disease and left ventricular systolic dysfunction (ejection fraction <45%) underwent RTMCE before and 3 months after CABG. RTMCE was performed using continuous intravenous infusion of commercially available contrast agent with low mechanical index power modulation imaging. Viability was defined by qualitative assessment of myocardial perfusion as homogenous opacification at rest in ≥2 segments of anterior or ≥1 segment of posterior territory. Viability by quantitative assessment of MBF was determined by receiver‐operating characteristics curve analysis. Results: Regional function recovery was observed in 74% of territories considered viable by qualitative analysis of myocardial perfusion and 40% of nonviable (P = 0.03). Sensitivity, specificity, positive and negative predictive values of qualitative RTMCE for detecting regional function recovery were 74%, 60%, 77%, and 56%, respectively. Cutoff value of MBF for predicting regional function recovery was 1.76 (AUC = 0.77; 95% CI = 0.62–0.92). MBF obtained by RTMCE had sensitivity of 91%, specificity of 50%, positive predictive value of 75%, and negative predictive value of 78%. Conclusion: Qualitative and quantitative RTMCE provide good accuracy for predicting regional function recovery after CABG. Determination of MBF increases the sensitivity for detecting hibernating myocardium. (Echocardiography 2011;28:342‐349)     

Prevalence of hibernating myocardium in patients with severely impaired ischaemic left ventricles

OBJECTIVE: Severe impairment of left ventricular (LV) contraction is associated with an adverse prognosis in patients with ischaemic heart disease. Revascularisation may improve the impaired LV contraction if hibernating myocardium is present. The proportion of patients likely to benefit from this intervention is unknown. Therefore, the prevalence of hibernating myocardium in patients with ischaemic heart disease and severe impairment of LV contraction was assessed. DESIGN: From a consecutive series of patients undergoing coronary angiography for the investigation of chest pain or LV impairment, all patients with ischaemic heart disease and an LV ejection fraction (LVEF) < or = 30% were identified. These patients underwent positron emission tomography (PET) to detect hibernating myocardium, identified by perfusion metabolism mismatch. SETTING: A teaching hospital directly serving 500,000 people. RESULTS: Of a total of 301 patients, 36 had ischaemic heart disease and an LVEF < or = 30%. Twenty-seven patients had PET images, while nine patients were not imaged because of emergency revascularisation (three), loss to follow up (one), inability to give consent (four), and age < 50 years (one, ethics committee guidelines). Imaged and non-imaged groups were similar in LV impairment, demographic characteristics, and risk factor profile. Fourteen patients (52% of the imaged or 39% of all patients with ischaemic heart disease and LVEF < or = 30%) had significant areas of hibernating myocardium on PET. CONCLUSION: It is possible that up to 50% of patients with ischaemic heart disease and severely impaired left ventricles have hibernating myocardium.     

Coronary revascularisation for postischaemic heart failure: how myocardial viability affects survival

OBJECTIVE—To assess the impact of revascularisation of viable myocardium on survival in patients with postischaemic heart failure.
METHODS—35 patients (mean (SD) age 58 (7) years) with severe heart failure (New York Heart Association (NYHA) functional class ⩾ III), mean left ventricular ejection fraction (LVEF) 24 (7)% (range 10-35%), and limited exercise capacity (peak oxygen consumption (VO₂) 15 (4) ml/kg/min) were studied. 21/35 patients had no angina. Myocardial viability was assessed with quantitative positron emission tomography and the glucose analogue ¹⁸F-fluorodeoxyglucose (FDG) (viable segment = FDG uptake ⩾ 0.25 µmol/min/g) in all patients before coronary artery bypass grafting. Patients were divided into two groups: group 1, ⩾ 8 viable dysfunctional segments (mean 12 (2), range 8-15); and group 2, < 8 viable dysfunctional segments (mean 3.5 (3), range 0-7). The two groups were comparable for age, sex, NYHA class, LVEF, and peak VO₂.
RESULTS—Two patients died perioperatively and seven patients died during follow up (mean 33 (14) months). All deaths were from cardiac causes. Kaplan-Meyer survival analysis showed 86% survival for group 1 patients versus 57% for group 2 (p = 0.03). Analysis by Cox proportional hazard model revealed three independent factors for cardiac event free survival: presence of ⩾ 8 viable segments (p = 0.006); preoperative LVEF (p = 0.002); and patient age (p = 0.01).
CONCLUSION—Revascularisation for postischaemic heart failure can be associated with good survival, which is critically dependent upon the amount of viable myocardium.


     

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

Summary Medical treatment of angina pectoris is largely based on the use of beta-blocking agents, calcium antagonists, and nitrates. Oxyfedrine, an amino ketone derivative and partial agonist at beta receptors, has been shown to have potent antianginal properties and to increase coronary blood flow in normal and ischemic myocardial regions in experimental studies. We assessed the effects of intravenous oxyfedrine on regional myocardial blood flow, using positron emission tomography (15-oxygen water), in six patients with chronic stable angina, positive exercise tests, and documented coronary artery disease. Myocardial blood flow was measured in all patients before (baseline) and 10 minutes after the intravenous administration of a single bolus (0.11–0.13 mg/kg) of oxyfedrine. Compared to baseline, heart rate and systolic blood pressure remained almost unchanged after the administration of oxyfedrine. Mean baseline myocardial blood flow was 0.90±0.15 ml/g/min in areas supplied by arteries with significant coronary stenosis and 1.08±0.19 ml/g/min in areas supplied by nonstenotic coronary vessels (p<0.05). After the adminsitration of oxyfedrine, myocardial blood flow increased significantly in both the regions supplied by stenotic vessels (by 25%; from 0.90±0.15 to 1.20±0.31 ml/g/min; p=0.002) and in areas supplied by angiographically normal coronary vessels (by 22%; from 1.08±0.19 to 1.38±0.49 ml/g/min; p<0.05). The results of this study indicate that in patients with coronary artery disease, intravenous oxyfedrine significantly increases regional myocardial blood flow, both in areas supplied by critically obstructed vessels and in areas supplied by normal or less severely narrowed coronary arteries.     

Inotropic reserve and histological appearance of hibernating myocardium in conscious pigs with ameroid-induced coronary stenosis

Inotropic reserve, demonstrated with administration of sympathomimetic amines, is characteristic of hibernating myocardium. The goal of this study was to determine whether inotropic reserve was present following chronic coronary artery constriction in the pig, which is one potential model of hibernating myocardium. The effects of isoproterenol were examined in five conscious pigs 21±2.1 days after ameroid implantation on the left circumflex coronary artery on measurements of left ventricular (LV) pressure, LV dP/dt, and regional wall thickening in the ameroid-dependent zone (posterior wall) and contralateral non-ischemic zone (anterior wall). Isoproterenol, 0.1 g/kg/min, increased LV dP/dt by 96±11%, heart rate by 43±13 beats/min, and normalized systolic wall thickening, slightly, but not significantly more in the ameroid-dependent zone (+1.57±0.31 mm) than in the contralateral non-ischemic zone (+1.04±031 mm), although the baseline wall thickening was reduced significantly in the ameroid-dependent zone. This occurred at a time when baseline myocardial blood flow was preserved and myocardial perfusion in the ameroid-dependent zone was derived in part from the native coronary circulation and also through collateral channels. Two weeks later histological evidence of lesions characteristics of hibernating myocardium, i.e., myofibrolysis and increased glycogen deposition, were observed. Thus, these histological changes and the confluence of chronically depressed regional function and residual inotropic reserve in the conscious pig with chronic ameroid-induced coronary constriction support this model for further study of hibernating myocardium.Supported in part by USPHS grants HL 33065, 33107 and 38070     

Hibernating myocardium: morphological correlates of inotropic stimulation and glucose uptake

BACKGROUND—In patients with postischaemic left ventricular dysfunction, segments recovering function after revascularisation (hibernating myocardium) may not respond during dobutamine echocardiography, despite preserved [¹⁸F] 2-fluoro-2-deoxy-D-glucose (FDG) uptake at positron emission tomography.
OBJECTIVE—To investigate whether this lack of response might reflect the degree of ultrastructural change in hibernating myocardium.
METHODS—Transmural biopsies were obtained from 22 dysfunctional segments in 22 patients during coronary artery bypass grafting and examined by light and electron microscopy. Wall motion scores and coronary vasodilator reserve were assessed before and after coronary artery bypass grafting (CABG).
RESULTS—Mean (SD) wall motion score improved in all segments following CABG (from 2.24 (0.4) to 1.55 (0.4); p < 0.0001), confirming hibernating myocardium. In these segments myocardial blood flow (positron emission tomography with H₂¹⁵O) before CABG was similar to that in normal volunteers (1.02 (0.24) v 1.02 (0.23) ml/min/g), while the coronary vasodilator reserve was blunted (1.26 (0.7) v 3.2 (1.6); p < 0.0001). Myocardial blood flow was unchanged after CABG, whereas coronary vasodilator reserve increased to 2.10 (0.90) (p < 0.0007). In hibernating myocardium myofibrillar loss, interstitial fibrosis, and glycogen-rich myocytes were more marked than in control donor hearts. On the basis of the response to dobutamine before CABG, two functional groups were identified: group A, segments with inotropic reserve (n = 15); group B, segments without inotropic reserve (n = 7). FDG uptake was similar in group A and group B (0.40 (0.1) v 0.44 (0.1) µmol/min/g). In group B there was more myofibrillar loss (26 (8)% v 11 (5)%; p = 0.0009) and glycogen-rich myocytes (28 (11)% v 17 (10)%; p = 0.02), whereas interstitial fibrosis, myocardial blood flow, and coronary vasodilator reserve were similar in the two groups. Myofibrillar loss was the only independent predictor of inotropic reserve (p = 0.01).
CONCLUSIONS—Hibernating myocardium is characterised by a reduced coronary vasodilator reserve which improves on revascularisation and shows a spectrum of ultrastructural changes that influence the response to dobutamine, while FDG uptake is invariably preserved.


Keywords: coronary artery disease; heart failure; myocardial viability; myocardial blood flow; positron emission tomography     

左旋精氨酸对犬实验性冬眠心肌的保护作用

目的 :观察左旋精氨酸对冬眠心肌功能、代谢与结构的影响。方法 :30只犬短期冬眠心肌模型随机分为 3组 :A组 （n=14）灌注生理盐水 ;B组 （n=8）灌注左旋精氨酸 ;C组 （n=8）灌注 L- MNNA。结果 :3组间左心室舒张末期压、血乳酸、ATP含量及电镜下结构改变差异显著。左旋精氨酸组明显优于其他两组。结论 :左旋精氨酸可改善冬眠心肌、代谢与功能结构。     

Commentary on hibernating myocardium and its clinical relevance

Conclusion The discovery by Rahimtoola that chronic left ventricular regional dysfunction due to prolonged hypoperfusion can recover after full reperfusion has radically changed the current physiopathological concept of myocardial ischaemia and the actual treatment of CAD patients. We need, however, proper studies aimed to evaluate the role of the different diagnostic metodologies for detection of myocardial hibernation and to assess the clinical efficacy of revascularization of hibernating myocardium in terms of reduction of morbidity and mortality. From the clinical point of view attention and resorces should be concentrated on those case with large extension of hibernating myocardium, in which the differentiation of viable from non-viable myocardium and the stratification of operative risk is the real overriding clinical concern. It is this subset of patients which will justify further investigation in this fascinating field and which hopefully, will improve our therapeutical possibility.     

The non-invasive assessment of hibernating myocardium in ischaemic cardiomyopathy--a myriad of techniques

Heart failure is placing an ever-increasing burden on society. Many subjects with heart failure and underlying coronary artery disease have a significant amount of akinetic but viable myocardium that is able to contract should myocardial perfusion improve (hibernating myocardium). Non-randomised studies have shown prognostic benefit in subjects with hibernating myocardium undergoing revascularisation. Several non-invasive techniques have been developed to assess the presence or absence of hibernating myocardium. This review will examine the epidemiology and underlying pathogenesis of hibernating myocardium; evaluate the non-invasive techniques for diagnosing hibernating myocardium, and look at therapeutic intervention in subjects with hibernating myocardium.     

Effects of right ventricular pacing on regional myocardial glucose metabolism.

AIMS: Permanent right ventricular apical pacing (RVP) is associated with a wide range of myocardial abnormalities. The purpose of this study was to determine the changes over time of RVP on myocardial blood flow (MBF) and glucose metabolism as assessed by positron emission tomography (PET). METHODS: In eight candidates for permanent pacemaker implantation PET imaging was performed with 13N-ammonia and 18F-Fluorodeoxyglucose (FDG) to assess MBF and glucose metabolism before (PET1) and repeated after 3 months of RVP (PET2). For the analysis, the left ventricle was divided into three parts (apex, mid-ventricular and base) and subdivided into six segments (inferior, posterior, lateral, anterior, antero-septal and infero-septal). RESULTS: After RVP, defects of FDG uptake were found in the left ventricle near the stimulation site, without corresponding changes in MBF. Changes over time in the mean FDG uptake were statistically significant between PET1 and PET2 in the apical inferior, apical-posterior, apical-anterior, apical antero-septal, apical infero-septal, mid-inferior and mid-infero-septal segments. CONCLUSIONS: This study shows that RVP induces major changes in the distribution of FDG uptake in the left ventricular myocardium. FDG uptake significantly decreases in the regions surrounding the pacing site.     

Relevance of apoptosis in influencing recovery of hibernating myocardium

BACKGROUND: Hibernating myocardium (HM) is viable but dysfunctional myocardium which can recover following revascularization. Myocyte necrosis is virtually absent in HM; however, cellular loss may take place by apoptosis, although this is controversial. AIM: To assess the presence of apoptosis and its relevance in HM. METHODS: During coronary artery by-pass surgery (CABG), 21 patients underwent transmural biopsy in the dysfunctional left anterior descending artery tributary area of the left ventricle (LV), with kinetic recovery at follow-up, thus fulfilling the HM criteria. All patients underwent echocardiographic follow-up at 12 months. All biopsies were evaluated by light microscopy, electron microscopy (EM), and molecular analysis. RESULTS: All biopsies were structurally altered, showing increased fibrosis and myocytes with variable size. Myocyte dedifferentiation was not detected by immunohistochemistry or EM. On stepwise linear regression, 1 year LVEF was predicted by the apoptotic index (beta=-0.973, p=0.002), the normotrophic cell percentage (beta=0.449, p=0.038), and mean fibrosis (beta=-0.412, p=0.51). CONCLUSIONS: Our biopsy study detected a wide range of morphological substrate heterogeneity in HM with degenerative features. We have demonstrated for the first time in humans that myocyte apoptosis is an important phenomenon in HM, negatively influencing LV functional recovery after CABG.     

核素心肌显像测定MBF和CFR在冠心病的诊断价值及展望

心血管疾病是世界范围内最主要的死亡原因,其治疗和诊断的经济成本很高,在过去的20年里,对冠心病患者诊断、评估及治疗越来越准确和有效。正电子发射断层显像技术是一种强大而多功能的无创性影像学检查,特别是通过量化心肌血流量(MBF)及冠状动脉血流储备(CFR)可以更好地描述冠状动脉疾病的特征,在冠状动脉微血管病变及缺血性心肌病的早期诊断、分级及治疗中发挥着重大作用。     

Myocardial blood flow in dilated cardiomyopathy

Myocardial blood flow (MBF) impairment has been documented in advanced idiopathic dilated cardiomyopathy (IDC) where different factors may secondarily affect myocardial perfusion. In failing hearts, explanted from patients with end-stage IDC, MBF is markedly depressed; however, a preferential flow to the subendocardium is preserved; furthermore, the severity of perfusion impairment does not correlate with the extent of fibrosis quantitatively determined by biochemical assessment or evaluated by histologic criteria. Thus, other mechanisms, besides myocardial hemodynamic and structural derangement, seem to operate in determining resting MBF impairment in advanced IDC. Abnormalities in the absolute levels of myocardial perfusion and in regional MBF distribution can also be detected in an early phase of IDC preceeding the development of severe ventricular dysfunction and the clinical appearance of overt heart failure. In patients with subclinical IDC, regional and global myocardial perfusion, as evaluated by positron emission tomography, is frequently impaired both at rest and in response to different vasodilating stimuli such as pacing tachycardia, dipyridamole or adenosine infusion. The presence of an additional coronary resistance, at the microcirculatory level, not sensitive to adenosine, is a possible mechanism causing depressed MBF in subclinical IDC. Progression of the discase is associated with a further impairment in myocardial perfusion.     

Hibernation and myocardial ischemia: Clinical detection by positron emission tomography

Summary Regions of myocardium supplied by severely diseased epicardial arteries may develop chronic ischemia at rest and exhibit reduced contractility, contributing to a reduction in global left ventricular function. However, after revascularization, contractility in these regions may return to normal. These regions of asynergy are described as hibernating myocardium. Such myocardium in which normal contractility may be restored often coexists with areas of infarcted, or scar, tissue, leading to the definition of hypoperfused hibernating myocardium as viable myocardium. It is important to identify viable myocardium, as revascularization of these areas should lead to the greatest improvement in left ventricular function and, thus, improvement in survival. Positron emission tomography is the best noninvasive method for quantifying regional myocardial blood flow and metabolism. Using ¹⁸F-fluorodeoxyglucose, which measures myocardial glucose utilization, it is possible to identify myocardial tissue that is hypoperfused at rest with preserved or increased glucose uptake. This mismatch of blood flow to metabolism has a high predictive accuracy in the recovery of contractile function. In order to reduce the need for metabolic imaging in documenting myocardial viability, a regional index of perfusable tissue derived from imaging with ¹⁵O water has been recently developed that also allows the quantification of tissue viability.     

心肌血流储备分数在急性冠状动脉综合征中的应用现状

<正>自从冠状动脉造影技术问世以来,它已经成为解剖学上评价冠状动脉病变的重要方法,以及对病变进行冠状动脉介入治疗的重要依据,然而,冠状动脉造影术并不能准确评价冠状动脉狭窄病变引起血流功能性变化。1993年,Pijls