Postinfarction Left Ventricular Dysfunction Research Articles

Dietary selenium intake influences Cx43 dephosphorylation, TNF‐α expression and cardiac remodeling after reperfused infarction

Post-infarct left ventricular dysfunction and cardiac remodeling are the primary causes of chronic heart failure in industrialized countries. In the present study, we examined the influence of dietary selenium intake on cardiac remodeling after reperfused myocardial infarction and explored one of the possible mechanisms. Rats were fed a diet containing either 0.05 mg/kg (Low-Se, group of rats receiving the low-selenium diet) or 1.50 mg/kg (group of rats receiving the high-selenium diet) selenium. At the end of the 5th week of the diet, rats were subjected to transient (1 h) coronary ligation followed by 8 days of reperfusion. Infarct size and cardiac passive compliance were increased in the Low-Se group compared with group of rats receiving the high-selenium diet. Similarly, indices of cardiac remodeling (thinning index and expansion index) were more altered in Low-Se hearts. These adverse effects of the Low-Se diet on cardiac remodeling were accompanied by an increase in cardiac TNF-α content, a decreased activity of antioxidant seleno-enzymes and an increase in connexin-43 dephosphorylation. Dietary selenium intake influences post-infarct cardiac remodeling even when provided within the range of physiological values. Our data suggest that the cardioprotective effect of selenium might be mediated by a reduced oxidative stress, a lower connexin-43 dephosphorylation, and a decreased TNF-α expression.

Polyethylenimine-mediated gene delivery into human bone marrow mesenchymal stem cells from patients

Transplantation of mesenchymal stem cells (MSCs) derived from adult bone marrow has been proposed as a potential therapeutic approach for post-infarction left ventricular (LV) dysfunction. However, age-related functional decline of stem cells has restricted their clinical benefits after transplantation into the infarcted myocardium. The limitations imposed on patient cells could be addressed by genetic modification of stem cells. This study was designed to improve our understanding of genetic modification of human bone marrow derived mesenchymal stem cells (hMSCs) by polyethylenimine (PEI, branched with Mw 25 kD), one of non-viral vectors that show promise in stem cell genetic modification, in the context of cardiac regeneration for patients. We optimized the PEI-mediated reporter gene transfection into hMSCs, evaluated whether transfection efficiency is associated with gender or age of the cell donors, analysed the influence of cell cycle on transfection and investigated the transfer of therapeutic vascular endothelial growth factor gene (VEGF). hMSCs were isolated from patients with cardiovascular disease aged from 41 to 85 years. Optimization of gene delivery to hMSCs was carried out based on the particle size of the PEI/DNA complexes, N/P ratio of complexes, DNA dosage and cell viability. The highest efficiency with the cell viability near 60% was achieved at N/P ratio 2 and 6.0 μg DNA/cm2. The average transfection efficiency for all tested samples, middle-age group (<65 years), old-age group (>65 years), female group and male group was 4.32%, 3.85%, 4.52%, 4.14% and 4.38%, respectively. The transfection efficiency did not show any correlation either with the age or the gender of the donors. Statistically, there were two subpopulations in the donors; and transfection efficiency in each subpopulation was linearly related to the cell percentage in S phase. No significant phenotypic differences were observed between these two subpopulations. Furthermore, PEI-mediated therapeutic gene VEGF transfer could significantly enhance the expression level.

Cardioprotective and Antiapoptotic Effects of Heme Oxygenase-1 in the Failing Heart

Heme oxygenase-1 (HO-1) is an inducible stress-response protein that imparts antioxidant and antiapoptotic effects. However, its pathophysiological role in cardiac remodeling and chronic heart failure (HF) is unknown. We hypothesized that induction of HO-1 in HF alleviates pathological remodeling. Adult male nontransgenic and myocyte-restricted HO-1 transgenic mice underwent either sham operation or coronary ligation to induce HF. Four weeks after ligation, nontransgenic HF mice exhibited postinfarction left ventricular (LV) remodeling and dysfunction, hypertrophy, fibrosis, oxidative stress, apoptosis, and reduced capillary density, associated with a 2-fold increase in HO-1 expression in noninfarcted myocardium. Compared with nontransgenic mice, HO-1 transgenic HF mice exhibited significantly (P<0.05) improved postinfarction survival (94% versus 57%) and less LV dilatation (end-diastolic volume, 46+/-8 versus 85+/-32 microL), mechanical dysfunction (ejection fraction, 65+/-9% versus 49+/-16%), hypertrophy (LV/tibia length 4.4+/-0.4 versus 5.2+/-0.6 mg/mm), interstitial fibrosis (11.2+/-3.1% versus 18.5+/-3.5%), and oxidative stress (3-fold reduction in tissue malondialdehyde). Moreover, myocyte-specific HO-1 overexpression in HF promoted tissue neovascularization and ameliorated myocardial p53 expression (2-fold reduction) and apoptosis. In isolated mitochondria, mitochondrial permeability transition was inhibited by HO-1 in a carbon monoxide (CO)-dependent manner and was recapitulated by the CO donor tricarbonylchloro(glycinato)ruthenium(II) (CORM-3). HO-1-derived CO also prevented H2O2-induced cardiomyocyte apoptosis and cell death. Finally, in vivo treatment with CORM-3 alleviated postinfarction LV remodeling, p53 expression, and apoptosis. HO-1 induction in the failing heart is an important cardioprotective adaptation that opposes pathological LV remodeling, and this effect is mediated, at least in part, by CO-dependent inhibition of mitochondrial permeability transition and apoptosis. Augmentation of HO-1 or its product, CO, may represent a novel therapeutic strategy for ameliorating HF.

Prediction of left ventricular dysfunction progression in patients with a first ST-elevation myocardial infarction – contribution of cystatin C assessment

Left ventricular (LV) dysfunction is a major cause of poor outcome after myocardial infarction. We sought to investigate the factors that might contribute to the prediction of postinfarct LV dysfunction progression, and whether the addition of cystatin C (CystC) to this assessment might be useful. NT-proBNP, CRP, CystC, and troponin I were measured in 150 patients with a first ST-elevation myocardial infarction (STEMI) who were followed up for 6 months. Echocardiography was performed at discharge and follow-up. In multivariable logistic regression, LV ejection fraction decrease at follow-up exceeding 0.2 was independently predicted by CRP [odds ratio (OR): 1.09, 95% confidence interval (CI): 1.05-1.13, P<0.0001], multivessel disease (OR: 8.83, 95% CI: 4.01-19.41, P<0.001), and left anterior descending artery involvement (OR: 5.09, 95% CI: 1.60-16.22, P<0.006); whereas peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity ratio (E/E') exceeding 15 indicating elevated LV filling pressure by CystC (OR: 3.53, 95% CI: 1.11-11.26, P<0.01), diabetes (OR: 4.04, 95% CI: 1.58-10.58, P<0.005), and multivessel disease (OR: 4.09, 95% CI: 1.52-11.05, P<0.006). CRP, NT-proBNP, and CystC were among the independent determinants of clinical outcomes (heart failure hospitalizations, mortality, and recurrent ischemic events). Receiver operator characteristic analyses identified CRP being the most valuable in discriminating LV ejection fraction decrease exceeding 0.2 and CystC in discriminating E/E' exceeding 15. Using multiple biomarkers may contribute to the better prediction of LV dysfunction progression and the risk of adverse cardiac events in patients with STEMI. CystC may improve this evaluation, especially with regard to the development of echocardiographic features of elevated LV filling pressure.

Treatment of Acute Myocardial Infarction With Sirolimus-Eluting Stents Results in Chronic Endothelial Dysfunction in the Infarct-Related Coronary Artery

Sirolimus-eluting stent (SES) implantation aggravated endothelial vasomotor dysfunction in infarct-related coronary arteries. This study examined the effect of SES implantation on the duration of reperfusion-induced endothelial vasomotor dysfunction in infarct-related coronary arteries and on postinfarct left ventricular dysfunction in acute myocardial infarction (AMI). Patients with a first AMI due to occlusion of the left anterior descending coronary artery and successful reperfusion using SES (n=15) or bare metal stents (BMS; n=18) were examined. The vasomotor response of the left anterior descending coronary artery to acetylcholine and left ventriculography were examined 2 weeks and 6 months after AMI. At 6 months after AMI, the impairment of epicardial coronary artery dilation and coronary blood flow increase in response to acetylcholine was recovered from 2 weeks after AMI in BMS-treated patients, whereas the responses of SES-treated patients improved but remained impaired compared with BMS-treated patients (% increase in blood flow, 77+/-12% in SES versus 116+/-15% in BMS at 10 microg/min of acetylcholine, P<0.01). Left ventricular regional wall dysfunction in the left anterior descending coronary artery territory improved from 2 weeks to 6 months after AMI in BMS-treated patients but not in SES-treated patients (% improvement of average SD/chord, 6% in SES versus 19% in BMS, P<0.05), although left ventricular global ejection fraction was similar between the groups at any time points. SES implantation may delay recovery of reperfusion-induced endothelial vasomotor dysfunction in infarct-related coronary arteries and left ventricular regional dysfunction for at least 6 months after AMI.

Engraftment, Differentiation, and Functional Benefits of Autologous Cardiosphere-Derived Cells in Porcine Ischemic Cardiomyopathy

Cardiosphere-derived cells (CDCs) isolated from human endomyocardial biopsies reduce infarct size and improve cardiac function in mice. Safety and efficacy testing in large animals is necessary for clinical translation. Mesenchymal stem cells, which resemble CDCs in size and thrombogenicity, have been associated with infarction after intracoronary infusion. To maximize CDC engraftment while avoiding infarction, we optimized the infusion protocol in 19 healthy pigs. A modified cocktail of CDCs in calcium-free PBS, 100 U/mL of heparin, and 250 microg/mL of nitroglycerin eliminated infusion-related infarction. Subsequent infusion experiments in 17 pigs with postinfarct left ventricular dysfunction showed CDC doses > or =10(7) but <2.5 x 10(7) result in new myocardial tissue formation without infarction. In a pivotal randomized study, 7 infarcted pigs received 300,000 CDCs/kg (approximately 10(7) total) and 7 received placebo (vehicle alone). Cardiac magnetic resonance imaging 8 weeks later showed CDC treatment decreased relative infarct size (19.2% to 14.2% of left ventricle infarcted, P=0.01), whereas placebo did not (17.7% to 15.3%, P=0.22). End-diastolic volume increased in placebo, but not in CDC-treated animals. Hemodynamically, the rate of pressure change (dP/dt) maximum and dP/dt minimum were significantly better with CDC infusion. There was no difference between groups in the ability to induce ventricular tachycardia, nor was there any tumor or ectopic tissue formation. Intracoronary delivery of CDCs in a preclinical model of postinfarct left ventricular dysfunction results in formation of new cardiac tissue, reduces relative infarct size, attenuates adverse remodeling, and improves hemodynamics. The evidence of efficacy without obvious safety concerns at 8 weeks of follow-up motivates human studies in patients after myocardial infarction and in chronic ischemic cardiomyopathy.

Transplantation of progenitor cells and regeneration of damaged myocardium: more facts or doubts? Insights from experimental and clinical studies

The development of postinfarction left ventricular dysfunction, particularly in patients with a large myocardial infarction, remains a major challenge. Recent experimental studies, showing that bone marrow cells may repair cardiac tissue, have offered renewed hopes for the prevention of this ominous occurrence. This optimism is further supported by encouraging results from some clinical trials in both acute myocardial infarction and in chronic cardiomyopathy, although the degree of benefits, the underlying mechanisms, and the cell types involved remain to be elucidated. This review summarizes the most relevant experimental experiences and all clinical studies supporting but also questioning the use of bone marrow cells in myocardial repair.

The beneficial effects of postinfarct cytokine combination therapy are sustained during long-term follow-up

We have previously reported that administration of granulocyte colony-stimulating factor (G-CSF) + Flt-3 ligand (FL) or G-CSF + stem cell factor (SCF) improves left ventricular (LV) function and halts LV remodeling at 35 d after myocardial infarction (MI). In the current study, we investigated whether these beneficial effects are sustained in the long term — an issue of fundamental importance for clinical translation. Mice undergoing a 30-min coronary occlusion followed by reperfusion received vehicle (group I), G-CSF + FL (group II), G-CSF + SCF (group III), or G-CSF alone (group IV) starting 4 h after reperfusion and were euthanized 48 wk later. LV structure and function were assessed by serial echocardiography before and at 48 h and 4, 8, 16, 32, and 48 wk after MI. During follow-up, mice in group I exhibited worsening of LV function and progressive LV remodeling. Compared with group I, both groups II and III exhibited improved LV EF at 4 wk after MI; however, only in group II was this improvement sustained at 48 wk. Group II was also the only group in which the decrease in infarct wall thickening fraction, the LV dilatation, and the increase in LV mass were attenuated vs. group I. We conclude that the beneficial effect of G-CSF+FL on postinfarction LV dysfunction and remodeling is sustained for at least 11 months, and thus is likely to be permanent. In contrast, the effect of G-CSF + SCF was not sustained beyond the first few weeks, and G-CSF alone is ineffective. To our knowledge, this is the first long-term study of cytokines in postinfarction LV remodeling. The results reveal heretofore unknown differential actions of cytokines and have important translational implications.

The arrythmogenic potential of post-myocardial infarction cytokine treatment

a front page story in The New York Times ([22][1]) at the end of March 2001 reported that “the basis of a possible revolution in treating heart attack patients has been laid by three reports of using stem cells from bone marrow to repair heart tissue in animals.” Those three reports ([11][2], [

Surgical ventricular restoration combined with mitral valve procedure for endstage ischemic cardiomyopathy☆

A poor functioning dilated left ventricle with mitral regurgitation is the worst condition in chronic ischemic heart failure. Our 7-year experience in combined mitral valve and left ventricular reconstruction was evaluated. Among 246 patients having undergone a left ventriculoplasty for postinfarction left ventricular dysfunction in our experience, there were 76 patients with advanced heart failure due to dilated ischemic cardiomyopathy with mitral regurgitation (70 males and 6 females with a mean age of 60 years). All patients had NYHA class III (n = 41) or IV (n = 35) heart failure, including 26 patients (34%) with inotropic support before the operation. All patients had a mitral regurgitation of more than 2+ and 46 patients (61%) had 3+ or more. Mitral reconstruction (61 repairs, 15 replacements) and left ventriculoplasty (Dor 34, SAVE 36, PLV 6) were undergone in combination with CABG (74%). Operative mortality was 7.9% (5.0% in 60 elective and 18.8% in 16 emergency operations). The ejection fraction and cardiac index increased from 24.9 +/- 7.0% to 33.3 +/- 8.7%, and 2.0 +/- 0.4 l/min/m2 to 2.6 +/- 0.4 l/min/m2, respectively (p < 0.001). The endodiastolic and endosystolic volume indices, and diastolic dimension decreased from 165.9 +/- 43.2 ml/m2 to 121.2 +/- 31.1 ml/m2, 123.3 +/- 38.9 ml/m2 to 74.0 +/- 27.5 ml/m2, and 69.5 +/- 7.7 mm to 61.2 +/- 7.1 mm, respectively (p < 0.001). Late deaths were noted in 13 patients (17.1%), with 10 cardiac deaths. One- and 5-year survival rates were 80.2% and 67.7%, respectively. The mean NYHA class improved from 3.5 to 1.4 among the survivors. Multivariate analysis showed that patients with a mitral regurgitation of 3+ or more and preoperative endosystolic volume index were significant predictors for postoperative mortality. However, age, preoperative inotropes and pulmonary hypertension did not show any significant differences. Combined mitral and left ventricular reconstruction is effective in treating advanced heart failure with endstage ischemic cardiomyopathy associated with a dilated left ventricle and mitral regurgitation.

Strain Rate Analysis and Levosimendan Improve Detection of Myocardial Viability by Dobutamine Echocardiography in Patients With Post-Infarction Left Ventricular Dysfunction: A Pilot Study

The assessment of myocardial viability by wall motion (WM) analysis on dobutamine echocardiography is subjective and provides suboptimal results. The aim of this study was to test the hypothesis that the prediction of functional recovery after revascularization can be improved by combining strain rate (SR) imaging, an objective method to quantify regional function, and levosimendan, a positive inotropic and vasodilator agent with no adrenergic effects. Thirty postinfarction patients (mean age, 65 +/- 13 years) underwent, off drug, dobutamine (5-40 mug/kg/min) and then levosimendan (24 mug/kg in 10 minutes) echocardiography before percutaneous coronary intervention. WM score, peak systolic SR (SRs), end-systolic strain (Ses), and postsystolic strain (Sps) were assessed in all segments. Regional left ventricular functional recovery was identified by >/=1-point improvement in WM as assessed using the standard 16-segment model. Of 215 segments with abnormal resting function, 102 (47%) showed improvement in WM 8 months after revascularization. Functional recovery was predicted in 60 segments with dobutamine and in 76 segments with levosimendan (sensitivity, 59% vs 75%; P = .026), while failure to recover was identified in 93 segments with dobutamine and 90 segments with levosimendan (specificity, 82% vs 80%, P = NS). Overall there was significant agreement between the 2 tests (kappa = 0.73; P < .0001). Peak SRs in segments with functional recovery improved significantly (P = .001) with both dobutamine and levosimendan (from -1.36 +/- 0.41 to -1.87 +/- 0.59 and -1.99 +/- 0.49, respectively) but did not change in regions with unchanged WM at follow-up. There were no significant differences in Ses and Sps between rest and pharmacologic tests, with either dobutamine or levosimendan. Of note, an increment in peak SRs > -0.29 s(-1) after levosimendan had the highest specificity (93%) for predicting segmental functional recovery at follow-up (P = .001). The combination of a newer quantitative echocardiographic technique (SR analysis) and a newer pharmacologic agent (levosimendan) improves the sensitivity of viability assessment compared with conventional dobutamine echocardiography.

Uncertainty on the Use of Aldosterone Antagonists for Primary Therapy for Sudden Cardiac Death in the Setting of Implanted Devices

In the early development of therapy for acute myocardial infarction, it was thought that once the necrotic process had been completed (usually within 24 hours of coronary artery occlusion), additional therapies could not affect outcome. However, after completion of the necrotic process, the myocardial infarction may thin and stretch (involving lengthwise slippage of myocytes), a phenomenon referred to as myocardial infarct expansion. This process causes local left ventricular cavity dilatation followed by gradual global left ventricular dilatation and lengthwise (eccentric) hypertrophy of the noninfarcted tissue. Apoptosis (programmed cell death) and some attempt of the myocardium to regenerate, especially at the infarct border zone, may also contribute to this remodeling process of the ventricle. If the left ventricle remodels in such a way that it becomes very dilated, then the prognosis is poor, and heart failure is more likely to occur.1 These later processes of myocardial infarct expansion and left ventricular remodeling became the target of therapies such as angiotensin-converting enzyme (ACE) inhibition that could be initiated after 24 hours of coronary occlusion. ACE inhibition, angiotensin receptor blockade, and long-term β-blockade have become standard pharmacological approaches for postinfarction left ventricular dysfunction and heart failure. Response by Pitt and Pitt p 2989 Ventricular arrhythmias can occur in both the acute and chronic phases of acute myocardial infarction and can lead to sudden cardiac death (SCD). Reentrant arrhythmias may arise at the border zone of infarcts, causing monomorphic ventricular tachycardia that may occur years after the index infarction. Recurrent myocardial ischemia resulting in an unstable substrate may contribute to polymorphic ventricular tachycardia or ventricular fibrillation. Agents such as β-blockers that are anti-ischemic may reduce sudden death by quieting this unstable substrate. In the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II, implantable defibrillators were shown to reduce mortality in post–myocardial infarction patients with …

Bcl-2 Engineered MSCs Inhibited Apoptosis and Improved Heart Function

Engraftment of mesenchymal stem cells (MSCs) derived from adult bone marrow has been proposed as a potential therapeutic approach for postinfarction left ventricular dysfunction. However, limited cell viability after transplantation into the myocardium has restricted its regenerative capacity. In this study, we genetically modified MSCs with an antiapoptotic Bcl-2 gene and evaluated cell survival, engraftment, revascularization, and functional improvement in a rat left anterior descending ligation model via intracardiac injection. Rat MSCs were manipulated to overexpress the Bcl-2 gene. In vitro, the antiapoptotic and paracrine effects were assessed under hypoxic conditions. In vivo, the Bcl-2 gene-modified MSCs (Bcl-2-MSCs) were injected after myocardial infarction. The surviving cells were tracked after transplantation. Capillary density was quantified after 3 weeks. The left ventricular function was evaluated by pressure-volume loops. The Bcl-2 gene protected MSCs against apoptosis. In vitro, Bcl-2 overexpression reduced MSC apoptosis by 32% and enhanced vascular endothelial growth factor secretion by more than 60% under hypoxic conditions. Transplantation with Bcl-2-MSCs increased 2.2-fold, 1.9-fold, and 1.2-fold of the cellular survival at 4 days, 3 weeks, and 6 weeks, respectively, compared with the vector-MSC group. Capillary density in the infarct border zone was 15% higher in Bcl-2-MSC transplanted animals than in vector-MSC treated animals. Furthermore, Bcl-2-MSC transplanted animals had 17% smaller infarct size than vector-MSC treated animals and exhibited functional recovery remarkably. Our current findings support the premise that transplantation of antiapoptotic gene-modified MSCs may have values for mediating substantial functional recovery after acute myocardial infarction.

Cardiac 64-Slice Multi-Detector Computed Tomography Detection of Infarct Size in Patients with Post-Infarct Left Ventricular Dysfunction: A Comparative Study with SPECT Imaging and Cardiac Biomarkers

Cardiac 64-Slice Multi-Detector Computed Tomography Detection of Infarct Size in Patients with Post-Infarct Left Ventricular Dysfunction: A Comparative Study with SPECT Imaging and Cardiac Biomarkers

Cardiac Stem Cell Therapy

Cardiovascular disease remains the number one cause of morbidity and mortality in the United States and Europe. In the United States alone, ≈1 million patients suffer a myocardial infarction every year, with an associated mortality of 25% at 3 years.1 A more sobering statistic is the fact that there are ≈5 million Americans with congestive heart failure, with an associated 20% mortality per year. This remains the case despite advances in pharmacotherapy, cardiac resynchronization therapies, and the use of implantable cardioverter-defibrillators.2 Some patients with end-stage congestive heart failure are considered for cardiac transplantation, but the demand for this therapeutic approach greatly outweighs the availability of donor hearts. Over the past few years, several animal studies and a few clinical trials have supported the use of stem cells as a potential therapeutic modality to address this unmet clinical need. Response by Boyle et al p 358 Several different types of cells have been used in both animal studies and patients to promote the repair of damaged myocardium. The 2 main sources of stem cells are adult stem and embryonic stem (ES) cells. ### ES Cells ES cells are derived from the inner mass of developing embryos during the blastocyst stage. Characteristic features of ES cells include their proliferative and self-renewing properties and their ability to differentiate into a wide variety of cell types, including cardiac myocytes.3 The major concerns with their use in human trials include the formation of teratomas when ES cells are injected into immunocompromised animals. This is particularly important because the ES cells currently available for use in humans would be of allogeneic origin and therefore would require immunosuppression. As nuclear transfer techniques improve, they will provide a way of generating an unlimited supply of histocompatible ES cells using the nuclei of cells obtained directly from the recipient …

Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial

The benefit of reperfusion therapies for ST-elevation acute myocardial infarction (STEMI) is limited by post-infarction left-ventricular (LV) dysfunction. Our aim was to investigate the effect of autologous bone marrow-derived stem cell (BMSC) transfer in the infarct-related artery on LV function and structure. We did a randomised, double-blind, placebo-controlled study in 67 patients from whom we harvested bone marrow 1 day after successful percutaneous coronary intervention for STEMI. We assigned patients optimum medical treatment and infusion of placebo (n=34) or BMSC (n=33). Our primary endpoint was the increase in LV ejection fraction and our secondary endpoints were change in infarct size and regional LV function at 4 months' follow-up, all assessed by MRI. We assessed changes in myocardial perfusion and oxidative metabolism with serial 1-[11C]acetate PET. Analyses were per protocol. This study is registered with , number NCT00264316. Mean global LV ejection fraction 4 days after percutaneous coronary intervention was 46.9% (SD 8.2) in controls and 48.5% (7.2) in BMSC patients, and increased after 4 months to 49.1% (10.7) and 51.8% (8.8; OR for treatment effect 1.036, 95% CI 0.961-1.118, p=0.36). Compared with placebo infusion, BMSC transfer was associated with a significant reduction in myocardial infarct size (BMSC treatment effect 28%, p=0.036) and a better recovery of regional systolic function. Myocardial perfusion and metabolism increased similarly in both groups. We noted no complications associated with BMSC transfer and all but one patient in the BMSC group completed the 4 months' follow-up. Intracoronary transfer of autologous bone marrow cells within 24 h of optimum reperfusion therapy does not augment recovery of global LV function after myocardial infarction, but could favourably affect infarct remodelling.

Echocardiographic Strain Imaging for Myocardial Viability

Echocardiographic strain imaging was introduced by Heimdal et al in 19981 as a means to calculate myocardial regional function from tissue Doppler velocity data.2,3 Strain imaging is a variation of the previous concept of tissue Doppler myocardial velocity gradient, which calculates regional thickening independent of passive whole heart motion.4,5 Because routine clinical evaluation of regional function is usually by visual wall-motion assessment, strain imaging has great promise to improve objective quantification of regional function. Strain imaging calculates deformation, which translates clinically to percent shortening in the longitudinal dimension (assessed from apical views) or percent thickening in the radial dimension (assessed from parasternal views).1,6,7 Theoretically, it has the important advantage of differentiating active myocardial motion from passive translational or tethering movements that other echocardiographic-Doppler approaches cannot differentiate. Indeed, there have been literally hundreds of publications over the last 10 years detailing a wide range of experimental and potential clinical applications of strain imaging; however, currently, few centers have adopted strain imaging in their routine clinical practice, preferring visual “eyeball” assessment, even though this is inherently subjective and requires a high level of experience and training.8 An important question remains: Is it now time for strain imaging to be adopted in a widespread clinical sense? Articles pp 3892 and 3901 Two important articles are contained in this issue of Circulation that address the application of strain imaging as a tool to assess myocardial viability: an animal study of experimental ischemia and infarction by Lyseggen et al9 and a clinical study using dobutamine echocardiography with outcome data after revascularization by Hanekom et al.10 The article by Lyseggen et al illustrates the additive value of strain imaging in an elegant open-chest animal model of coronary occlusion and reperfusion. Echocardiographic strain imaging was performed along with simultaneous dimensional …

881 Improvement of regional myocardial function following long-term aldosterone blockade in patients with post-infarction left ventricular dysfunction

s $133 purpose of this study was to evaluate long-term clinical and echocardiogrphic results in patients with severely depressed left ventricular (LV) function (EF <35%). Methods; From January 1999 to April 2004, Jatene procedure was performed in 43 patients with EF <35% (males/females 31/12, mean age 65.3+8.9 years). All the patients suffered from a myocardial infarction, 26 of them presented angina. Nine (21%) patients were in NYHA class I, 14 (32%) in II, 18 (42%) in III and 2 (5%) in IV. The presence of a LV aneurysm was assessed by ventriculography. Before the procedure, all the patients underwent echocardiographic examination for the assessment of LV volumes and ejection fraction by modified Simpson's rule, sphericity index and mitral regurgitation. Results: The preoperative and postoperative LV volumes, ejection fractions and sphericity index are shown in table 1 .Ten patients presented a mild to moderate mitral regurgitation for which valve replacement was not indicated. Concomitant coronary artery bypass grafting was performed in all the patients. Three (6.97%) in hospital deaths occurred for multi organ failure. All the remaining 40 patients underwent clinical and echocardiegraphic follow-up evaluation. The mean period of follow-up was 34.4±17.3 months. At the time of fellow-up, 27 (67.5%) patients were in NYHA class I and 13 (32.5%) in II; nobody presented angina.

Promotion of Cardiac Regeneration by Cardiac Stem Cells

See related article, pages 663–673 Research on myocardial regeneration is an exciting and promising area, which challenges the dogma that the heart is a nonregenerating organ. Recently, several methods of stem cell therapy have been developed. One method is to transplant cells into the infarcted area of the myocardium. Currently, clinical trials of autologous skeletal myoblast transplantation into the failed heart are underway and have been reported to improve the cardiac function.1 However, the mechanism of its efficacy is unknown, and there are some questions about the safety because myoblasts do not transdifferentiate into cardiomyocytes and may induce lethal arrhythmia.1 In this point, embryonic stem (ES) cells that can differentiate into cardiomyocytes are thought to be more promising.2 For patients experiencing extensive myocardial infarction or dilated cardiomyopathy, however, the effectiveness of cell transplantation is questionable. Bone marrow-derived cells have been reported to transdifferentiate into various types of cells in situ. Indeed, bone marrow-derived stem cells were reported to prevent left ventricular remodeling after myocardial infarction and improve cardiac function by their differentiation into cardiomyocytes.3 However, recent accumulating evidence has indicated that very few bone marrow cells, if any, transdifferentiate into cardiomyocytes.4–6 Cytokine therapy using G-CSF strongly prevents ventricular remodeling after myocardial infarction by antiapoptotic and angiogenic effects, but not by recruitment of bone marrow cells.7 Over the past few years, adult hearts have been reported to contain the cardiac stem/progenitor cells such as c-kit+,8 Sca-1+,9,10 isl-1+,11 and side population cells.12 Because these cells have the ability to proliferate and …

Beware of Cells Bearing Gifts

See related article, pages 159–167 Heart failure is a major worldwide health problem that is growing in prevalence despite recent treatment advances. Patients with heart failure ultimately die from either pump failure or cardiac arrhythmia, and there is a link between the degree of contractile dysfunction and arrhythmic risk. Since the 1960s, the definitive therapy for heart failure has been cardiac transplantation, but the limited supply of organs has restricted the impact of this therapy. Starting in the mid-1990s, a series of observations has led to the concept that cells might be used to repair myocardial damage. Subsequently, this therapy has shown promise in ischemic and nonischemic forms of myocardial injury. The increased availability of cells as compared with organs has driven an exuberant search for the right replacement cells. Nevertheless, after intense study, there is no obvious frontrunner.1 The concept driving the cell selection process has been the need for a sufficient number of immune compatible, contractile cells. Proposed cell sources have included skeletal myoblasts,2 bone marrow–derived progenitor cells,3 and embryonic stem cells.4 These 3 cell types have been shown to improve myocardial function in animal models, and the first 2 have shown promise in human clinical trials.5 Generally, the effects of these 2 cell types on myocardial function have been similar.6 If they are to fulfill their promise as replacement myocytes, it is important that the …