Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function

The ability of cardiac stem cells (CSCs) to promote myocardial repair under clinically relevant conditions (i.e., when delivered intravascularly after reperfusion) is unknown. Thus, rats were subjected to a 90-min coronary occlusion; at 4 h after reperfusion, CSCs were delivered to the coronary arteries via a catheter positioned into the aortic root. Echocardiographic analysis showed that injection of CSCs attenuated the increase in left ventricular (LV) end-diastolic dimensions and impairment in LV systolic performance at 5 weeks after myocardial infarction. Pathologic analysis showed that treated hearts exhibited a smaller increase in LV chamber diameter and volume and a higher wall thickness-to-chamber radius ratio and LV mass-to-chamber volume ratio. CSCs induced myocardial regeneration, decreasing infarct size by 29%. A diploid DNA content and only two chromosomes 12 were found in new cardiomyocytes, indicating that cell fusion did not contribute to tissue reconstitution. In conclusion, intravascular injection of CSCs after reperfusion limits infarct size, attenuates LV remodeling, and ameliorates LV function. This study demonstrates that CSCs are effective when delivered in a clinically relevant manner, a clear prerequisite for clinical translation, and that these beneficial effects are independent of cell fusion. The results establish CSCs as candidates for cardiac regeneration and support an approach in which the heart's own stem cells could be collected, expanded, and stored for subsequent therapeutic repair.     

Assessment of Myocardial Viability in Patients With Postischemic Left Ventricular Dysfunction: Role of Myocardial Contrast Echocardiography

The distinction between viable and nonviable dysfunctional left ventricular (LV) segments after acute myocardial infarction is very important, because revascularization increases survival only in patients with viable myocardial tissue. Recent studies have highlighted a mismatch between two highly specific investigations for viability assessment: dobutamine echocardiography, which measures inotropic reserve, and myocardial contrast echocardiography (MCE), which measures microvascular perfusion. Viability and functional reserve are not synonymous. Maintenance of microvascular perfusion, independently of functional reserve, attenuates left ventricular remodelling, reduces the risk of major cardiac events, and increases survival. MCE provides similar perfusion information as myocardial blush, but image quality is much higher. Quantitative analysis of digital data provides more accurate diagnostic MCE information than qualitative analysis of video signal intensity. In a recent study relating MCE findings to histologic data, MCE-derived quantitative data were closely correlated with microvascular density and capillary area, and inversely correlated with collagen content. One of the contrast agents routinely used for MCE is SonoVue, a second generation microbubble contrast agent, which is characterized by high response to ultrasound energy, ease of destruction at high energy, and strong harmonic signal at low energy. Recommendations for the assessment of postischemic LV dysfunction: routine use of MCE, followed by dobutamine echocardiography if perfusion is documented. If MCE is negative, revascularization is not indicated; if both tests are positive, revascularization is strongly recommended; if they are discordant, useful information can be obtained by assessing the extent of ²⁰¹T1 viability. (ECHOCARDIOGRAPHY, Volume 20, Supplement 1, 2003)     

Myocardial contrast echocardiography in acute myocardial infarction: Pathophysiological background and clinical applications

Myocardial contrast echocardiography is a technique used inexperimental and clinical settings in order to visualize thepattern of intramyocardial perfusion. In the acute phase ofmyocardial infarction, regional absence of flow during myocardialcontrast echocardiography delineates the area at risk of necrosis,while the definitive non-perfused area expresses infarct size.Reopening the infarct-related artery, which may be achievedspontaneously by thrombolysis or percutaneous transluminal coronaryangioplasty, is not a reliable indicator of intramyocardialreperfusion. If myocardial ischaemia due to coronary occlusionhas been sufficiently prolonged and severe, not only myocyteviability, but also microvascular integrity is lost. Myocardialcontrast echocardiography, using intracoronary injection ofsonicated contrast medium, gives information about microvascularintegrity and the effective presence of intramyocardial reflow.Anatomical integrity of microvasculature does not necessarilyimply preserved function, and thus the microvessel vasodilatingreserve may also be impaired. Myocardial contrast echocardiographyhas the potential to assess alterations in microvascular function,showing, in the myocardial area with reduced coronary reserve,a relatively reduced increase in echocontrast signal intensitywhen an intravenous vasodilator agent is administered. (Eur Heart J 1996; 17: 344–353)     

Assessment of myocardial blood flow and volume using myocardial contrast echocardiography

The development of new microbubble agents and ultrasound imaging modalities now allows the assessment of myocardial perfusion with echocardiography. Microbubbles also can be administered intravenously as constant infusions, which allows their concentration in blood to reach steady state. If the relation between microbubble concentration and video intensity is within the linear range, then myocardial video intensity will reflect the concentration of microbubbles in that region, which at steady state is the myocardial blood volume. The ability to destroy microbubbles and measure their replenishment into the ultrasound beam provides an opportunity to evaluate microbubble (or red blood cell) velocity. The product of myocardial blood volume and red blood cell velocity represents myocardial blood flow.     

负荷心肌灌注显像在心肌桥临床应用中的研究进展

负荷心肌灌注显像通过检测核素在心肌的分布,明确心肌缺血的部位和程度,因此,它能够评价冠状动脉心肌桥是否影响心肌供血及影响程度。负荷心肌灌注显像具有敏感性及特异性较高,且相对价廉、安全无创等优点,在评价心肌桥导致的心肌缺血及缺血的程度范围、判断预后及指导下一步治疗中具有重要的临床价值及应用前景。     

Multislice MR perfusion imaging and regional myocardial function analysis: complimentary findings in chronic myocardial ischemia

Purpose: The purpose of this study is to assess the reliability of multislice MR perfusion imaging in comparison to regional wall function and nuclear medicine and to test different qualitative and quantitative parameters for perfusion assessment. Material and methods: 15 patients with chronic myocardial ischemia underwent CINE and first-pass perfusion MR imaging. Functional myocardial imaging was performed using a segmented CINE FLASH sequence and systolic myocardial wall thickening was assessed after semiautomated segmentation. MR first-pass perfusion studies were performed using a multislice saturation recovery TurboFLASH sequence. Different parameters were calculated for assessment of hypoperfused segments and results of MR imaging compared to ^99mTc-SestaMIBI SPECT. Results: MR perfusion imaging showed a sensitivity of 72% and a specificity of 98%. In combination with MR CINE imaging and wall thickening analysis we calculated a sensitivity of 100% and a specificity of 93%. Qualitative and quantitative perfusion parameter analysis showed significant differences between normal and hypoperfused segments for the signal intensity increase (p < 0.001), the signal intensity upslope (p < 0.001) as well as for the myocardial mean transit time (p < 0.001). Conclusion: The combination of systolic wall thickening analysis and myocardial perfusion can markedly improve the sensitivity of MRI in depiction of LV myocardial perfusion abnormalities. For assessment of hypoperfusion, different quantitative and qualitative parameters can be calculated showing significant differences between normal state and hypoperfusion.     

Dobutamine stress echocardiography early after myocardial infarction treated with thrombolysis

The aim of the study was to assess the ability of dobutamine stress echocardiography to detect myocardial viability and ischemia in patients with acute myocardial infarction treated with thrombolysis and to correlate the acute response to dobutamine with late spontaneous functional recovery at follow-up.Forty-two consecutive patients with myocardial infarction treated with thrombolysis underwent low- (5 and 10 mcg/kg/min) and high-dose (20 to 40 mcg/kg/min) dobutamine stress echocardiography at a mean of 7 ± 3 days of the acute phase. A follow-up 2D-echocardiogram was performed in all patients to evaluate the spontaneous recovery of function in the infarct area.On the basis of the response to the test, 3 groups of patients were identified: group 1 included 7 patients showing an improvement in left ventricular asynergy score index at low doses (from 1.5±0.3 to 1.3±0.2, p<0.05) with no deterioration at high doses, indicative of myocardial viability without ischemia; group 2 (23 patients) showed a significant improvement in the asynergy index at low doses (from 1.58±0.3 to 1.32±0.32, p<0.05) followed by a deterioration at high doses (1.68±0.4, p<0.05 vs low-dose), suggestive of residual myocardial ischemia in the infarct zone; group 3 included 12 patients who showed no significant changes in the baseline asynergy score index (1.67±0.2) either at low or at high doses.The acute response to dobutamine stress echocardiography accurately predicted the spontaneous recovery of function in the infarct area at follow-up: both group 1 and group 2 patients showed a significant reduction in the asynergy score index (group 1: 1.16±0.3 vs 1.5±0.2, p<0.001; group 2: 1.43±0.3 vs 1.58±0.3, p<0.05), while group 3 had no recovery in the asynergy index (1.67±0.2 vs 1.67±0.2).Thus, in patients with acute myocardial infarction treated with thrombolysis dobutamine stress echocardiography can detect myocardial viability in 71% and ischemia in the infarct zone in 55% of patients; moreover, the response to the test during the acute phase is correlated with the degree of the late spontaneous recovery of function in the infarct area.     

Compensatory regional contraction following coronary artery occlusion depends on subendocardial hyperaemia and hyperkinesis.

The effects of circumflex coronary artery occlusion on regional myocardial performance and blood flow in the left ventricular anterior wall was studied, using 16 thoracotomized pentobarbital-anaesthetized cats. Two pairs of ultrasonic crystals were placed in the midwall; one segment (longitudinal) parallel to the subendocardial fibres, the other (circumferential) being aligned to the fibres of the outer half-layer. A shunt line from the right subclavian artery to the main left coronary artery was unrestricted in eight cats (Group A) and clamped in another eight cats (Group B) until coronary perfusion pressure was clearly reduced with only a minor reduction in shunt flow, but without changes in global cardiac function. After circumflex coronary occlusion hyperkinesis was most pronounced in segments parallel to subendocardial fibres (longitudinal), also validated as a marked leftward shift in the end-systolic pressure-length relation of these segments. Such a shift may indicate decreased regional afterloading along the cardiac major axis. Hyperkinesis of longitudinal segments was attenuated in Group B where a fixed shunt stenosis hampered subendocardial and mid-myocardial hyperaemia. The lesser hyperkinesis of Group B was associated with decreased left ventricular systolic pressure and cardiac output. Thus, impaired compensatory contraction outside an acute ischaemic region was produced by a significant coronary stenosis which precluded the subendocardial hyperaemia and hyperkinesis of that region.     

Stent implantation at the site of the myocardial bridge after myocardial infarction. Long-term results

Although myocardial bridge is asymptomatic in most patients, it can lead to myocardial ischemia, myocardial infarction, cardiac arrhythmias, and sudden death. The authors report the case of a symptomatic myocardial bridge treated by classical stenting of the mid left anterior descending artery. The outcome was good. A control coronary angiography performed 36 months later showed no significant restenosis. No recurrence of angina during five years follow-up was observed. (Int J Cardiovasc Intervent 2004; 6: 148-150)     

The accuracy of electrocardiographic Q waves for the detection of prior myocardial infarction as assessed by a novel standard of reference

BACKGROUND: The electrocardiogram (ECG) is valuable for the identification of prior myocardial infarction (MI) in individuals participating in epidemiologic studies or undergoing screening examinations. Although the Minnesota Code, a set of criteria for the interpretation of ECGs in such situations, is commonly used to identify MI in these settings, its accuracy is incompletely understood. HYPOTHESIS: We sought to test the accuracy of the Minnesota Code Q and QS criteria for MI against a new standard of reference, the presence of a perfusion defect on a resting myocardial scintigraphic image. METHODS: The resting myocardial scintigrams of all patients studied in our nuclear cardiology laboratory during 7 consecutive months were screened for the presence of perfusion defects. For each patient with such a defect, two individuals examined on the same day, who had no perfusion defect, were selected as controls. Electrocardiograms recorded within 30 days of the scintigraphy were read blindly by two of the authors using the Minnesota Code criteria for Q or QS waves indicative of MI. RESULTS: For 214 patients selected on the basis of their scintigraphic findings, a satisfactory ECG recorded within a month of the scintigraphy was also available. The overall sensitivity of the Q or QS criteria was 0.58 and the specificity was 0.75. As might be expected when only the most stringent criteria were applied, sensitivity was least and the specificity best. CONCLUSIONS: As in previous studies, in which necropsy material served as the standard of reference, sensitivity of the Q and QS criteria contained in the Minnesota Code is relatively modest and specificity is reasonable but not outstanding.     

Postinfarction Left Ventricular Pseudoaneurysm

Left ventricular wall rupture after myocardial infarction is a mechanical complication that may result in a pseudoaneurysm. Between January 1994 and October 1996, false or pseudoaneurysms were detected in 6 (0.0026%) of 2,600 consecutive patients (4 women, 2 men; mean age 59.4 years) undergoing cardiac catheterization at University Medical School, Debrecen, Hungary. All patients had a history of cardiovascular disease, with diagnosis of pseudoaneurysm confirmed by echocardiography. The average time from the occurrence of acute infarction to diagnosis was 37.0 days (range 3–80 days). All patients were in New York Heart Association functional class IV congestive heart failure; in four patients cardiogenic shock was present. Five patients underwent coronary angiography, which demonstrated multivessel disease and occlusion of the infarct–related artery (TIMI 0) without adequate collateral circulation (grade 0–1). Five patients had surgical repair of the false aneurysm, and, in three patients, concomitant coronary bypass grafting was performed. The 2-year mortality rate for all patients was 50%. Early diagnosis of false aneurysm is facilitated by echocardiography, and coronary angiography is required before surgery. Early surgical correction with coronary revascularization is advised.     

及时再灌注对急性心肌梗塞近期预后的影响

根据溶栓治疗后梗塞相关冠状动脉获开通的时间不同，将５９例急性心肌梗塞（ＡＭＩ）病人分为＜６小时组和＞６小时组，又根据溶栓后冠状动脉造影显示的冠状动脉通畅的程度不同，分为通畅组、基本通畅组和未通组，观察梗塞相关血管开通的不同时间和不同程度对心肌梗塞近期预后的影响。结果发现，６小时内开通者可明显降低心肌梗塞面积，改善梗塞后左室功能以及减少并发症的发生，＞６小时开通组与未通组相比，也有一定程度缩小梗塞面积和减少并发症的作用；基本通畅组近期心律失常、心绞痛以及再梗塞率高于通畅组和未通组，但基本通畅组和通畅组心肌梗塞缩小面积差异无显著性。提示ＡＭＩ后梗塞相关血管及时有效再灌注有利于改善心肌梗塞的近期预后。     

Postinfarction intramyocardial dissection,an interesting case report and systematic review

Intramyocardial dissection (IMD) with ventricular septal rupture (VSR) following myocardial infarction (MI) is a rare subacute form of cardiac rupture. The evidence available in this regard is scarce. We aimed to share our experience and conduct a systematic review of previous cases. We searched the literature and performed a systematic review of previous cases. A total of 37 cases of IMD with VSR were included (1 our original and 36 literature cases). Mean age was 68 ± 8 years and 20 (54.1%) patients were male. Anterior and inferior MI were observed in 14 (37.8%) and 23 (62.2%) cases, respectively. The dissected area was the septum, RV, both septum and RV, or LV apex in 21 (56.8%), 9 (24.3%), 5 (13.5%), and 2 (5.4%), respectively. Apicoseptal and inferoseptal VSR were observed in 15 (40.5%) and 22 (59.5%) cases, respectively. At least one occluded artery was observed in 29 (90.6%) of cases. Reperfusion therapy was done for 15 (40.5%) cases before the VSR occurred. Surgery, percutaneous, and medical therapy were done for 26 (70.3%), 3 (8.1%), and 7 (18.9%) cases, respectively. The mortality rate was significantly higher in the medical versus surgical-treated group (85.7% versus 42.3%, P = .027). There was a trend to higher mortality in the group with dissection of both septum and RV (P = .15). We concluded that echocardiography has a critical role in diagnosing this complication. Surgery is mandatory in IMD with VSR.     

Ventricular relaxation and myocardial ischemia: A comparison of different models of tau during coronary angioplasty

This study compares the sensitivity and variability of four models of tau, the time constant of ventricular relaxation, to detect the presence of myocardial ischemia. High fidelity left ventricular pressure recordings were obtained in ten patients undergoing coronary angioplasty at baseline, during balloon inflation, and at recovery. Four models of tau were considered: (1) a semilogarithmic, zero asymptote model (T_L), (2) a semilogarithmic model using data from the first 40 ms of isovolumic relaxation (T₄₀), (3) an exponential non-zero asymptote model (T_e), and (4) a derivative non-zero asymptote model (T_D). T_L, T₄₀, and T_E increased significantly during inflation and returned to near baseline values at recovery. T_D showed no change during inflation. Comparisons of T_L, T₄₀, and T_E using the derived relaxation half-time (T_1/2), failed to reveal significant differences between the models at baseline, during inflation, or at recovery. The non-zero asymptote models were associated with a greater beat-to-beat variability than the semilogarithmic models. Thus, T_1/2 using the semilogarithmic zero asymptote models (T_L and T₄₀) may be more useful and consistent when measuring the rate of isovolumic relaxation during myocardial ischemia.     

Assessment of regional myocardial blood flow with myocardial contrast echocardiography: an experimental study

OBJECTIVES: The aim of this study was to verify the accuracy of using myocardial contrast echocardiography (MCE), to quantify regional myocardial blood flow (MBF), and to evaluate myocardial viability in comparison to that measured by radiolabeled microsphere and pathologic examination. METHODS: Epicardial MCE was obtained in five myocardial ischemic dogs with constant microbubble intravenous infusion. After the video intensity (VI, y) versus pulsing interval plots derived from each myocardial pixel were fitted to an exponential function: y = A(1 - e(-beta t)), the MBF was calculated as the product of A (microvascular cross-sectional area or myocardial blood volume) and beta (mean myocardial microbubble velocity). The MBF was also obtained by radiolabeled microsphere method. RESULTS: The MBF derived by radiolabeled microsphere method in the normal, ischemic, and infarcted region was 1.5 +/- 0.3, 0.7 +/- 0.3, and 0.3 +/- 0.2 ml/min per gram, respectively; P < 0.01. The product of A and beta in those regions was 52.5 +/- 15.1, 24.4 +/- 3.9, and 3.7 +/- 3.8, respectively; P < 0.01. The normalized product of A and beta correlated well with normalized MBF (r = 0.81, P = 0.001). CONCLUSION: Our initial study demonstrated that MCE has an ability to assess MBF in ischemic myocardium in the experimental model. It may provide a potential capability to detect viable myocardium noninvasively after total persistent coronary occlusion in the clinical setting.     

TIMI myocardial perfusion frame count: A new method to assess myocardial perfusion and its predictive value for short‐term prognosis

Objectives: We sought to develop a new quantitative method to evaluate the degree of myocardial perfusion. Background: Currently available methods for assessing myocardial perfusion, both TIMI myocardial perfusion grading (TMPG) and myocardial blush grading (MBG), are subjective. Methods: TIMI Myocardial Perfusion Frame Count (TMPFC), an objective method that measures the filling and clearance of contrast in the myocardium using cine‐angiographic frame‐counting, was developed to quantify myocardial perfusion. Myocardial perfusion of 45 normal coronary arteries in 15 patients, and 137 culprit arteries in 137 patients immediately after primary angioplasty, was successfully assessed with TMPFC. Results: The mean TMPFC in the normal arteries was 83.47 ± 17.96 frames (95% CI: 78.07 frames ≤ TMPFC ≤ 88.86 frames). Therefore, TMPFC < 90 frames, a value representing the upper bound of the 95% CI for the TMPFC observed in normal arteries, was defined as normal myocardial perfusion. In 137 culprit arteries, the mean TMPFC values after primary angioplasty for the right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCX) were 141 ± 82.6, 112 ± 80.3, and 102 ± 37.5 frames, respectively. Patients with suboptimal myocardial perfusion (ex: TMPG ≤ 2 or MBG ≤ 2 grade) had higher levels of TMPFC. Furthermore, multivariate analysis shows that the TMPFC was an independent predictor for 30‐day (P = 0.0261) and 6‐month incidence of MACE (P = 0.0207). Conclusions: TMPFC is a quantitative index for the assessment of myocardial perfusion; it allows quantification of TMPG and may serve as a discerning tool to predict prognosis in patients undergoing primary angioplasty. © 2009 Wiley‐Liss, Inc.     

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.