Myocardial beta-adrenoceptor downregulation in idiopathic dilated cardiomyopathy measured in vivo with PET using the new radioligand (S)-[11C]CGP12388

Purpose The -adrenoceptor (-AR) plays an important role in heart failure. Recently, the new tracer (S)-[¹¹C]CGP12388 has been developed. It displays excellent properties for investigation of the cardiac -ARs in vivo with positron emission tomography (PET). Furthermore, the simple production method allows its use in a routine clinical setting. The aim of this study was to investigate whether decreased myocardial -AR density in patients with idiopathic dilated cardiomyopathy (IDC) can be estimated using (S)-[¹¹C]CGP12388 PET.Methods Myocardial -AR density was investigated in six patients with IDC and six age-matched healthy controls, using (S)-[¹¹C]CGP12388 PET.Results -AR densities of 5.4±1.3 pmol/g (mean ± SD) were observed in patients; these values were significantly lower than those observed in healthy controls (8.4±1.5 pmol/g, p<0.005).Conclusion This study indicates that PET with (S)-[¹¹C]CGP12388 is applicable for the measurement of myocardial -AR density in patients. A highly significant reduction in -AR density was found in patients with IDC compared with healthy controls.     

Incidence of stunned, hibernating and scarred myocardium in ischaemic cardiomyopathy

Purpose Different criteria to identify residual viability in chronically dysfunctioning myocardium in patients with coronary artery disease (CAD) can be derived by the combined assessment of myocardial blood flow (MBF) and glucose utilisation (MRG) using positron emission tomography (PET). The aim of this study was to evaluate, in a large number of patients, the prevalence of these different patterns by purely quantitative means.Methods One hundred and sixteen consecutive patients with ischaemic cardiomyopathy (LVEF 40%) underwent resting 2D echocardiography to assess regional contractile function (16-segment model). PET with ¹⁵O-labelled water (H₂¹⁵O) and ¹⁸F-fluorodeoxyglucose (FDG) was used to quantify MBF and MRG during hyperinsulinaemic euglycaemic clamp. Dysfunctional segments with normal MBF (0.6 ml min^–1 g^–1) were classified as stunned, and segments with reduced MBF (<0.6 ml min^–1 g^–1) as hibernating if MRG was 0.25 mol min^–1 g^–1. Segments with reduced MBF and MRG <0.20 mol min^–1 g^–1 were classified as transmural scars and segments with reduced MBF and MRG between 0.20 and 0.25 mol min^–1 g^–1 as non-transmural scars.Results Eight hundred and thirty-four (46%) segments were dysfunctional. Of these, 601 (72%) were chronically stunned, with 368 (61%) having normal MRG (0.47±0.20 mol min^–1 g^–1) and 233 (39%) reduced MRG (0.16±0.05 mol min^–1 g^–1). Seventy-four (9%) segments with reduced MBF had preserved MRG (0.40±0.18 mol min^–1 g^–1) and were classified as hibernating myocardium. In addition, 15% of segments were classified as transmural and 4% as non-transmural scar. The mean MBF was highest in stunned myocardium (0.95±0.32 ml min^–1 g^–1), intermediate in hibernating myocardium and non-transmural scars (0.47±0.09 ml min^–1 g^–1 and 0.48±0.08 ml min^–1 g^–1, respectively), and lowest in transmural scars (0.40±0.14 ml min^–1 g^–1, P<0.01). MRG was comparable in hibernating and stunned myocardium with preserved MRG (0.40±0.19 mol min^–1 g^–1 vs 0.46±0.20 mol min^–1 g^–1, NS), and lowest in stunned myocardium with reduced MRG and transmural scars.Conclusion Chronic stunning is more prevalent than expected. The degree of MRG reduction in stunned myocardium may disclose segments at higher risk of permanent damage.     

Comparison of sestamibi,thallium, echocardiography and PET for the detection of hibernating myocardium

The detection of hibernating myocardium is important because revascularisation results in improved function and prognosis in patients with hibernation but not in those with non-viable myocardium. The primary aim of this study was to compare the diagnostic accuracy of four techniques with respect to hibernation in the same study population with 6–12 months of follow-up. Twenty-five males underwent rest-stress sestamibi and delayed (>18 h) thallium scintigraphy, high-dose dobutamine stress echocardiography and nitrogen-13 ammonia/fluorine-18 fluorodeoxyglucose (NH₃/FDG) positron emission tomography (PET). The pre-operative ejection fraction was 36.2% (±7.3%). Follow-up was 8.1 (±2.8) months. Using postoperative improvement in wall motion on echocardiography as the gold standard, 6/34 dysfunctional vascular territories were hibernating. The mean uptake of all tracers was significantly higher in hibernating than in non-viable territories (P<0.05). Normal perfusion or mismatch on PET (FDG>NH₃ uptake) and the pattern of response to dobutamine on echocardiography were also predictive of recovery (P<0.001 and P=0.02 respectively). Univariate logistic regression identified sestamibi, ammonia and FDG as independent predictors of hibernation. FDG-PET was, however, the only independent predictor using multivariate analysis. The nuclear techniques had high negative predictive values (NPV) of 95% but lower positive predictive values (PPV) of 45%–75% as compared with echocardiography, which had an NPV of 87% and a PPV of 100%. PET was the most powerful predictor of hibernation although the combination of a technique with a high PPV (echocardiography) and a high NPV (PET or sestamibi) may represent the optimal clinical choice.     

左卡尼汀治疗老年冠心病心衰的疗效观察

目的评价左卡尼汀（L-CN）对心病慢性心力衰竭的治疗效果。方法选择80例冠心病心衰患者,随机分为两组,每组40例：对照组予利尿剂、硝酸酯类药物、B受体阻滞剂、血管紧张素转化酶抑制剂或血管紧张素受体拮抗剂治疗;治疗组在此基础上加用左卡尼汀3．0g／d静点。1次／d,疗程15d。观察治疗前后心功能状况、左室射血分数、左室舒张末径及E／A等心功能参数的变化,并观察药物不良反应。结果①两组治疗后均有效;②治疗组的总有效率高于对照组（P〈0．05）,心功能改善更为鼎著（P〈0．05）,且未见不良反应。结论冠心病心衰患者短期适量补充外源性左卡尼汀有益于改善心功能。     

Pathophysiology and diagnosis of hibernating myocardium in patients with post-ischemic heart failure: the contribution of PET

Identification and treatment of hibernating myocardium (HM) lead to improvement in LV function and prognosis in patients with post-ischemic heart failure. Different techniques are used to diagnose HM: echocardiography, MRI, SPECT and PET and, in patients with moderate LV impairment, their predictive values are similar. There are few data on patients with severe LV dysfunction and heart failure in whom the greatest benefits are apparent after revascularization. Quantification of FDG uptake with PET during hyperinsulinemic euglycemic clamp is accurate in these patients with the greatest mortality risk in whom other techniques may give high false negative rates. The debate on whether resting myocardial blood flow to HM is reduced or not has stimulated new research on heart failure in patients with coronary artery disease. PET with H2(15)O or 13NH3 has been used for the absolute quantification of regional blood flow in human HM. When HM is properly identified, resting blood flow is not different from that in healthy volunteers although a reduction of approximately 20% can be demonstrated in a minority of cases. PET studies have shown that the main feature of HM is a severe impairment of coronary vasodilator reserve that improves after revascularization in parallel with LV function. Thus, the pathophysiology of HM is more complex than initially postulated. The recent evidence that repetitive ischemia in patients can be cumulative and lead to more severe and prolonged stunning, lends further support to the hypothesis that, at least initially, stunning and HM are two facets of the same coin.     

Association of left ventricular diastolic function with coronary artery calcium score: A Project Baseline Health Study

BackgroundCoronary artery calcium (CAC) and left ventricular diastolic dysfunction (LVDD) are strong predictors of cardiovascular events and share common risk factors. However, their independent association remains unclear.MethodsIn the Project Baseline Health Study (PBHS), 2082 participants underwent cardiac-gated, non-contrast chest computed tomography (CT) and echocardiography. The association between left ventricular (LV) diastolic function and CAC was assessed using multidimensional network and multivariable-adjusted regression analyses. Multivariable analysis was conducted on continuous LV diastolic parameters and categorical classification of LVDD and adjusted for traditional cardiometabolic risk factors. LVDD was defined using reference limits from a low-risk reference group without established cardiovascular disease, cardiovascular risk factors or evidence of CAC, (n ?= ?560). We also classified LVDD using the American Society of Echocardiography recommendations.ResultsThe mean age of the participants was 51 ?± ?17 years with 56.6% female and 62.6% non-Hispanic White. Overall, 38.1% had hypertension; 13.7% had diabetes; and 39.9% had CAC >0. An intertwined network was observed between diastolic parameters, CAC score, age, LV mass index, and pulse pressure. In the multivariable-adjusted analysis, e’, E/e’, and LV mass index were independently associated with CAC after adjustment for traditional risk factors. For both e’ and E/e’, the effect size and statistical significance were higher across increasing CAC tertiles. Other independent correlates of e’ and E/e’ included age, female sex, Black race, height, weight, pulse pressure, hemoglobin A1C, and HDL cholesterol. The independent association with CAC was confirmed using categorical analysis of LVDD, which occurred in 554 participants (26.6%) using population-derived thresholds.ConclusionIn the PBHS study, the subclinical coronary atherosclerotic disease burden detected using CAC scoring was independently associated with diastolic function.Clinicaltrials.gov identifierNCT03154346.     

Dual source computed tomography coronary angiography in new onset cardiomyopathy

AIM:To evaluate safety and utility of coronary computed tomography angiography(CCTA) compared to invasive coronary angiography(ICA) in new cardiomyopathy.METHODS:Eighteen patients(mean age 56.5 years,10 males) who presented for evaluation of new onset heart failure with evidence of systolic dysfunction(ejection fraction < 40%) on echocardiography and recent ICA were prospectively enrolled.Patients with known coronary artery disease,atrial fibrillation,creatinine > 1.5 g/dL,and contraindication to intravenous contrast administration were excluded.CCTA was performed using a dual source 64-slice scanner.Mean heart rate was 75 beats per minute.Stenosis was graded for each coronary segment as:none,mild(< 50%),moderate(50%-70%),severe(> 70%),or non-evaluable.Ischemic cardiomyopathy(ICM) was diagnosed if severe stenosis was present in the left main,proximal left anterior descending artery,or two or more major arteries.RESULTS:Two patients were diagnosed with ICM by ICA.CCTA correctly identified 2 patients with ICM and 16 patients as non-ICM.CCTA successfully evaluated 240/246 coronary segments with an accuracy of 97.5%,sensitivity 70%,specificity 98.7%,positive predictive value of 70%,and negative predictive value of 98.7% for identifying severe stenosis on a per-segment level.CONCLUSION:Dual source 64-slice multi-detector CCTA is a safe,accurate,and non-invasive technique for diagnosing ICM in patients presenting during the acute phase of newly diagnosed cardiomyopathy.     

导纳法在冠心病心绞痛左心功能检测中的应用

采用导纳法容积描记术对50例冠心病心绞痛患者的左心功能进行检测,并与40例健康者进行对照研究。结果表明,前者左心功能明显减退(P<0.01),且其左心功能受损程度随缺血部位和范围加大而加重。因此,导纳法容积描记术可作为冠心病左心功能测试与评价的手段之一。     

Evaluation of postmortem measurement of NT-proBNP as a marker for cardiac function

Clinical biomarkers of cardiac function could also be monitored postmortem. Among the natriuretic peptides, the aminoterminal portion of pro-brain natriuretic peptide (NT-proBNP) appears to be a more reliable postmortem tool than the BNP, owing to its longer half-life and greater stability. In living persons, NT-proBNP is considered to be a marker of heart failure, and its level rises after cardiac ischemia. The goal of this study was first to evaluate the postmortem stability of NT-proBNP, then to measure the NT-proBNP levels in postmortem cases of heart failure related to coronary ischemia. The goal of this study was also to evaluate the correlations between different specimens collected at autopsy (e.g. blood, serum, vitreous humor and pericardial fluid). The study included 96 cases, which were classified into 4 groups according to the autopsy and histological findings. The NT-proBNP levels were significantly higher in individuals who had suffered from chronic cardiac ischemia, with or without acute coronary events, than in either control cases or those who had suffered from acute thromboembolism or acute rupture of a plaque without chronic cardiac ischemia. The highest levels were registered in individuals who had suffered from acute coronary thromboembolism in association with chronic coronary ischemia. Good correlations in the NT-proBNP levels for the different specimens were observed between samples of femoral blood, serum, and pericardial fluid. Our data indicated that postmortem measurements of NT-proBNP are reliable and compatible with clinical findings.     

心衰患者心脏超声改变与心肌钙调神经磷酸酶的关系

目的探讨心衰患者的心脏超声改变与心肌钙调神经磷酸酶(Calcineurin)活性的关系。方法以因终末期心衰做心脏移植的患者为观察对象(男14例,女1例) ,因意外死亡而作为器官移植供体者作为对照(5例均为男性)。手术前给观察组病人作心脏超声,详细记录左心室大小及收缩舒张功能等指标,并搜集供体的生前心脏超声资料。对移植下来的心脏即刻取左心室游离壁,用色度法进行Calcineurin活性测定。分析超声提供的左室资料与Calcineurin活性之间的关系。结果与对照组相比,功能衰竭的左心室肌Calcineurin活性明显升高;且左室内径越大、左室射血分数越低、左室舒张末期压力越高,Calcineurin的活性越高。结论心肌Calcineurin活性与左室形态及收缩、舒张功能有关。     

Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart

Purpose We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic β-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. Methods Eight patients (aged 67 ± 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 ± 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [¹¹C]meta-hydroxy-ephedrine (HED) volume of distribution (V _d) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 ± 4 years, p < 0.01 vs patients) and HED (n = 8, aged 40 ± 6 years, p < 0.01 vs patients) data. Results MGU in patients was reduced in both normal remote (0.44 ± 0.14 μmol·min⁻¹·g⁻¹) and dysfunctional (0.49 ± 0.14 μmol·min⁻¹·g⁻¹) segments compared with controls (0.61 ± 0.7 μmol·min⁻¹·g⁻¹; p < 0.001 vs both). HED V _d was reduced in dysfunctional segments of patients (38.9 ± 21.2 ml·g⁻¹) compared with normal segments (52.2 ± 19.6 ml·g⁻¹) and compared with controls (62.7 ± 11.3 ml·g⁻¹). In patients, regional MGU was correlated with HED V _d. Conclusion The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts.     

Prognostic value of sympathetic innervation and cardiac asynchrony in dilated cardiomyopathy

Purpose  The purpose of the study is to examine prognostic values of cardiac I-123 metaiodobenzylguanidine (MIBG) uptake and cardiac dyssynchrony in patients with dilated cardiomyopathy (DCM). Materials and methods  Ninety-four patients with non-ischemic DCM underwent I-123 MIBG imaging for assessing cardiac sympathetic innervation and equilibrium radionuclide angiography. Mean phase angles and SD of the phase histogram were computed for both right ventricular (RV) and left ventricular (LV). Phase measures of interventricular (RV–LV) and intraventricular (SD–RV and SD–LV) asynchrony were computed. Results  Most patients were receiving beta-blockers (89%) and angiotensin-converting enzyme inhibitors (88%). One patient (1%) was lost to follow-up, six had cardiac death (6.4%), eight had heart transplantation (8.6%), and seven had unplanned hospitalization for heart failure (7.5%; mean follow-up: 37 ± 16 months). Patients with poor clinical outcome were older, had higher The New York Heart Association functional class, impaired right ventricular ejection fraction and left ventricular ejection fraction, and impaired cardiac I-123 MIBG uptake. On multivariate analysis, I-123 MIBG heart-to-mediastinum (H/M) uptake ratio <1.6 was the only predictor of both primary (cardiac death or heart transplantation, RR = 7.02, p < 0.01) and secondary (cardiac death, heart transplantation, or recurrent heart failure, RR = 8.10, p = 0.0008) end points. Conclusions  In patients receiving modern medical therapy involving beta-blockers, I-123 MIBG uptake, but not intra-LV asynchrony, was predictive of clinical outcome. The impact of beta-blockers on the prognostic value of ventricular asynchrony remains to be clarified.     

持续性+Gz暴露对心脏结构和功能的影响

目的 综述和分析持续性＋Gz暴露对心脏结构和功能影响的研究资料. 资料来源 与选择 该领域的研究论文、综述和论著. 资料引用 研究论文、综述48篇,论著1篇. 资料综合 将持续性＋Gz暴露对心脏结构和功能影响的动物及人体试验研究结果进行分析,介绍针对该问题的不同观点. 结论 持续性＋Gz暴露对心脏结构和功能影响的动物实验结果不能直接外延应用到人体;目前的研究表明,持续性＋Gz暴露不会对现有高性能战斗机飞行员的心脏造成病理性损伤,但是,随着下一代战斗机性能的提高及抗荷措施的不断改进,该问题仍值得继续关注并展开深入研究.     

运动试验心肌显像异常及其类型对冠心病患者预后判断的价值

目的评价运动试验心肌显像异常及其类型对判断冠心病患者预后的价值。方法对６９例冠心病患者进行运动负荷心肌显像及运动ＥＣＧ试验，心肌显像均有异常。４５例经冠状动脉造影证实为冠心病，随访时间６～１１０个月，未发生心脏事件者随访皆≥１２个月。结果随访中１５例发生心脏事件，发生率为８７％／年。经多因素Ｃｏｘ回归分析表明，心肌显像可逆缺损节段数与发生心脏事件有密切关系。１３例显像不可逆缺损范围不大者，与以往报道的正常组结果比较，未发生心脏事件率差异无显著性（χ２＝００９，Ｐ＞００５）。表明心肌显像正常或呈不可逆缺损范围不大者预后良好。结论可逆缺损节段数是预测冠心病患者日后发生心脏事件的较好指标。     

冠状动脉钙化CT检出率及其意义的探讨

我们使用ＥＬＳＣＩＮＴ２４００型全身ＣＴ扫描机，连续对２０５例胸部进行平扫检查，发现冠脉钙化４４例，占２１．５％。５０例４０岁以下者未发现冠脉钙化；１５５例４０岁以上者，冠脉钙化检出率随着年龄增加而增加，其中５８例诊断冠心病，４０例有冠脉钙化；９７例无冠心病者，４例有冠脉钙化。着重探讨冠脉钙化与冠心病的关系，其灵敏度、特异度及阳性予告值分别为６９％、９６％及９１％。ＣＴ检出冠脉钙化虽不很敏感，但却能说明发生冠心病的机率较高，因而仍应将它视为一种重要的非损伤性检查方法。     

孤立性心肌致密化不全的MRI诊断

目的探讨孤立性心肌致密化不全(INVM)的MRI表现及其对该病诊断的价值。方法12例INVM患者均经超声心动图诊断。采用MRI不同脉冲序列，分析INVM心室结构、运动功能及心肌灌注的MRI表现。结果(1)左心室单独受累9例，双室受累3例，未见右室单独受累者。左心室心尖段及前壁中间段为最常见受累部位(12例)；(2)心肌增厚并能分层，非致密化心肌信号不均匀，由多发、粗大、交错排列的肌小梁及小梁隐窝组成，致密心肌变薄，信号均匀；(3)小梁隐窝内血栓2例；(4)心肌灌注成像首过期，6例14段(14／99段)可见灌注缺损；延迟期左心室心肌强化4例23段(23／99段)，其中1例伴右室心尖心肌强化；(5)左心室普遍收缩功能不良4例，节段性功能不良5例。结论MRI能清晰显示INVM的形态学改变、心室节段性及整体运动功能异常、心肌血流灌注及纤维化的程度和范围，对INVM诊断及预后评估具有重要价值。     

MR多技术扫描检测活性心肌及其和心肌声学造影对比的临床研究

目的 评价MR多技术扫描和心肌声学造影（MCE）在检测心肌灌注、判断心肌存活中的作用。资料与方法 应用MR多技术扫描对36例冠心病患者进行检查,并将结果与冠状动脉造影、MCE结果对照。结果 共有81支冠状动脉狭窄≥70％,狭窄的冠状动脉供血区域为334个（57．99％）节段。MR心肌灌注扫描见268个（46．53％）节段呈缺血改变,MR心肌活性扫描见83个（14．4l％）节段心肌梗死。以冠状动脉造影结果为标准,MR心肌灌注扫描的敏感性为80．2％,特异性为100％,总符合率为88．5％,Kappa值为0．773。定性MCE检查共有202个（35．07％）节段呈缺血改变。以冠状动脉造影结果为标准,定性MCE的敏感性为60．5％,特异性为100％,总符合率为77．1％,Kappa值为0．563。MR心肌灌注扫描所发现的缺血节段比狭窄冠状动脉的供血节段少但无统计学意义（P=0．468）,MCE所发现的缺血节段比狭窄冠状动脉的供血节段少（P=0．000）;MR心肌灌注扫描检出缺血节段比MCE检出的多（P=0．000）。结论 MR多技术扫描可清晰显示心肌缺血或梗死的位置、程度,可重复性好,与冠状动脉造影结果的一致性较高。MCE为临床提供了元创、可重复地准确测定心肌缺血的新方法,但其评价方法具有一定主观性且低估心肌缺血的范围,检查者的经验和检查方法在一定程度上影响其准确性。     

Dual-source CT assessment of ventricular function in healthy and infarcted myocardium: An animal study

Purpose

To assess global and regional ventricular function in the presence of myocardial infarction (MI) using cardiac dual-source computed tomography (DSCT) in comparison to magnetic resonance (MR) imaging.

Materials and methods

Fourteen pigs (58.6 ± 8.9 kg) were included in this study. In seven animals acute MI was induced by temporary balloon occlusion of the left circumflex artery. Thereafter, DSCT and MR imaging were performed with standardized examination protocols. Left (LV) and right ventricular (RV) volumes, ejection fraction (EF), peak filling rate (PFR), and peak ejection rate (PER) as well as LV myocardial mass were calculated. LV wall motion was visually assessed from cine loops. Data was analyzed using Bland-Altman plots, Lin's concordance-correlation coefficient (ρ_c) and weighted kappa statistics.

Results

Ventricular volumes and mass as determined by DSCT correlated well with MR imaging. Mean LV-EF was 49.4 ± 16.5% on DSCT and 50.0 ± 16.1% on MR imaging (ρ_c = 0.9928). The corresponding mean RV-EF results were 45.9 ± 10.6% and 45.8 ± 10.6% (ρ_c = 0.9969), respectively. Bland-Altman plots revealed no systematic errors, but PER and PFR showed a relevant scattering. Regional wall motion scores agreed in 216/224 myocardial segments (κ = 0.925).

Conclusion

DSCT permits the reliable assessment of global and regional function in healthy and infarcted myocardium, but is not yet suited for the assessment of dynamic functional parameters like PER and PFR.     

门控99Tcm-MIBI/18F-FDG双核素同时采集显像评价左心室功能

目的探讨门控99Tcm-甲氧基异丁基异腈(MIBI)/18F-脱氧葡萄糖(FDG)双核素同时采集(DISA)显像评价左心室功能的临床价值.方法 77例冠心病患者行门控DISA,其中53例行X线左心室造影(LVG),分别比较LVG心室射血分数(EF)值和DISA法门控99Tcm-MIBI和18F-FDG 同时显像所得EF值.局部室壁运动行Kappa值比较.结果门控99Tcm-MIBI和门控18F-FDG显像所得EF值间相关性高(r=0.90,P<0.001).两者与LVG EF值相关性均高(r分别为0.86和0.85,P均<0.001).门控99Tcm-MIBI和18F-FDG显像与LVG比较Kappa值分别为0.765和0.742.结论门控99Tcm-MIBI/18F-FDG DISA可同时了解左室心肌灌注、代谢及功能,提供左心室功能的重要信息,有重要的临床价值.