Therapy For Myocardial Infarction Research Articles

G-CSF and Erythropoietin Combination Therapy for Infarct Repair: Two Plus Two Equals Two?

G-CSF and Erythropoietin Combination Therapy for Infarct Repair: Two Plus Two Equals Two?

Early Therapy Following Myocardial Infarction: Arguments for and Against Implantable cardioverter-defibrillators

The implantable cardioverter-defibrillator (ICD), when implanted in the late phase of myocardial infarction (MI) in the primary prevention of sudden cardiac death, reduces total mortality by 23-31%. Current guidelines recommend ICD implantation at least 40 days after MI. Despite optimal MI therapy, the risk of sudden cardiac death or cardiac arrest remains highest within the first 30 days after index infarction. Two randomized trials with ICD implantation early after MI failed to show the reduction of total mortality in a long-term follow-up study. The decrease of sudden cardiac death incidence was counterbalanced by an increase of nonsudden deaths, which may have been caused by the augmentation of heart failure deaths in ICD groups, presumably due to ICD interventions. Therefore, optimizing ICD appears to be the most important issue influencing the long-term outcome.

Randomized controlled trials on the therapeutic effects of adult progenitor cells for myocardial infarction: meta-analysis

Objective: We performed a systematic meta-analysis to assess the therapeutic effects of progenitor cell therapy after myocardial infarction (MI). Research design/methods: Randomized controlled trials of progenitor cell therapy for MI were extracted from MEDLINE. We performed a prospective comparison of progenitor cell therapy versus placebo after acute or chronic MI, with changes in left venticular ejection fraction (LVEF) as the primary endpoint. We conducted random-effects meta-analyses to pool these outcomes across the studies. Results: A total of 980 patients from 18 studies were analysed. Seventeen trials used bone marrow-derived cells (BMCs). Overall, BMCs significantly increased LVEF, left ventricular end systolic volume and left ventricular end diastolic volume within six months of treatment, and the effect was sustained one year later. Following BMC transplantation regional myocardial anatomy displayed statistically and clinically significant improvements compared with controls, albeit without functional changes. Similar results were observed in the subgroup of patients with impaired LVEF at the baseline. The subgroup analysis suggested a benefit of BMCs on LVEF in acute but not chronic MI. LVEF enhancement seemed to correlate positively with dose and inversely with the storage duration of the BMCs. Conclusions: BMC transplantation for MI was able to deliver benefits over regular therapy even at an 18-month follow-up, particularly when used to treat acute MI. CD34+ cell therapy holds promise for MI treatment in the future.

Impact of Chronic Aspirin and Statin Therapy on Presentation of Patients With Acute Myocardial Infarction and Impaired Renal Function

Chronic use of aspirin and statins has been associated with reduced risk of subsequent myocardial infarction (MI). However, in patients with chronic kidney disease (CKD), the cardioprotective role of aspirin and statins seems to be reduced. To evaluate the impact of chronic aspirin and statin use on clinical presentation of acute MI according to renal function, the authors retrospectively analyzed 595 consecutive patients admitted to our hospital for acute MI. Renal function was normal in 404 patients and impaired in 191. Patients on therapy (113 patients) were less likely to have ST-segment elevation MI (STEMI) compared with patients not treated (36% vs 53%, respectively, P=.0002). These results have been confirmed in the population of patients with CKD (48% of STEMI in patients receiving chronic therapy and 67% in patients without therapy,P=.01). Multivariate analysis in the group of patients with CKD showed that use of aspirin or statins was an independent predictor of a decreased probability of STEMI (odds ratio, 0.5; 95% confidence interval, 0.2-1.0,P=.05). The authors' results suggest that in a community-based sample of patients with acute MI, chronic aspirin and statin therapy has a cardioprotective role that is evident also in patients with CKD.

Early Electrocardiographic Findings and MR Imaging-Verified Microvascular Injury and Myocardial Infarct Size

This study investigated early electrocardiographic findings in relation to left ventricular (LV) function, extent and size of infarction, and microvascular injury in patients with acute myocardial infarction (MI) treated with percutaneous coronary intervention (PCI). The electrocardiogram (ECG) is the most used and simplest clinical method to evaluate the risk for patients immediately after reperfusion therapy for acute MI. ST-segment resolution and residual ST-segment elevation have been used for prognosis in acute MI, whereas Q waves are related to outcome in chronic MI. We hypothesized that the combination of these electrocardiographic measures early after primary PCI would enhance risk stratification. We prospectively included 180 patients with a first acute ST-segment elevation MI to assess ST-segment resolution, residual ST-segment elevation, and number of Q waves using the 12-lead ECG acquired on admission and 1 h after successful PCI. The ECG findings were related to LV function, infarction size and transmurality, and microvascular injury as assessed with cine and gadolinium-enhanced cardiac magnetic resonance 4 +/- 2 days after reperfusion therapy. Residual ST-segment elevation (beta = -2.00, p = 0.004) and the number of Q waves (beta = -1.66, p = 0.005) were independent ECG predictors of LV ejection fraction. Although the number of Q waves was the only independent predictor of infarct size (beta = 2.01, p < 0.001) and transmural extent of infarction (beta = 0.60, p < 0.001), residual ST-segment elevation was the only independent predictor of microvascular injury (odds ratio: 19.1, 95% confidence interval: 2.4 to 154, p = 0.005) in multivariable analyses. The ST-segment resolution was neither associated with LV function, infarct size, or transmurality indexes, nor with microvascular injury in multivariable analysis. In patients after successful coronary intervention for acute MI, residual ST-segment elevation and the number of Q waves on the post-procedural ECG offer valuable complementary information on prediction of myocardial function and necrosis and its microvascular status.

HYPERBARIC OXYGENATION APPLIED IMMEDIATELY AFTER CORONARY OCCLUSION REDUCES MYOCARDIAL NECROSIS AND ACUTE MORTALITY IN RATS

1. Because in ischaemia there is a critical lack of O2, it has been reasoned that increasing O2 delivery to the ischaemic myocardium could serve as adjunctive therapy for acute myocardial infarction (MI). Accordingly, in the present study, the effect of early hyperbaric oxygenation (HBO) on mortality and MI size after coronary occlusion was examined in rats. 2. After coronary occlusion, male Wistar rats were randomly assigned to receive either HBO for 1 h in a hyperbaric chamber (100% O(2) at 253 kPa; n = 106) or ambient O2 as the control (n = 111). The extent of myocardial necrosis was assessed (triphenyltetrazolium) immediately after treatment in the HBO (n = 50) and control (n = 47) groups. The remaining rats were evaluated 24 h after occlusion to enable calculation of MI size and mortality. 3. Immediately after therapy, the size of the MI was significantly greater in the control group compared with that in the HBO group (40 +/- 3 vs 27 +/- 2% of the left ventricle (LV), respectively; P < 0.001). The 24 h mortality of control rats was higher than that of HBO rats (34 vs 16%, respectively; P = 0.02). Control rats that survived 24 h had a larger MI than did HBO rats that survived 24 h (40 +/- 4 vs 29 +/- 3% of the LV, respectively; P = 0.005). Furthermore, large necrotic areas (> 40% of the LV) were more frequent in control than HBO rats (55 vs 27% of infarcted hearts, respectively; P = 0.01). There was less pulmonary congestion observed in HBO rats compared with control rats. 4. In conclusion, early therapy with HBO during the onset of an acute ischaemic event decreases the necrotic area and reduces acute mortality. These data support further investigation of HBO as an adjuvant therapy for acute MI.

Establishment of a rat model of myocardial infarction with a high survival rate: A suitable model for evaluation of efficacy of stem cell therapy

The most common rat model of myocardial infarction (MI) is by ligation of left anterior descending (LAD) coronary artery but it is associated with high mortality and large variations in the infarct size. We evolved certain innovations/modifications in the existing technique including immobilization of the heart without exteriorization, identification of the LAD by pressing it proximal to the site of ligation by an ear-bud, and subsequently its ligation 8 mm from its origin, no touch technique of the lungs during surgery, removal of air from the chest cavity prior to its closure using an in-house tubing, and deflation of the lungs before extubation. We induced MI in 24 Sprague- Dawley (SD) rats using these modifications and carried out post-MI evaluation of hemodynamic parameters, serum cardiac enzymes and histological studies upto 90 days using 13 sham operated and 3 healthy SD rats as controls. Three of the 24 rats (13%) died <24 hours of MI, but thereafter no mortality was observed till the follow-up period of 90 days. The infarct size was consistent in all the rats (21±4% of left ventricular area). This model with low early and no long-term mortality may be suitable for studying efficacy of stem cell therapy in MI, where a follow-up of at least 13 weeks is required to assess myocardial regeneration.

Impact of Myocardial Salvage Assessed by 99mTc-Sestamibi Scintigraphy on Cardiac Autonomic Function in Patients Undergoing Mechanical Reperfusion Therapy for Acute Myocardial Infarction

The purpose of this study was to analyze the impact of myocardial salvage on cardiac autonomic function in patients undergoing mechanical reperfusion therapy for acute myocardial infarction (MI). Heart rate deceleration capacity (DC) and heart rate turbulence slope (TS) are strong predictors of post-MI mortality. Salvage of jeopardized myocardium is the main mechanism by which patients benefit from reperfusion therapy. The impact of myocardial salvage on DC and TS is unknown. The study enrolled 854 consecutive patients undergoing mechanical reperfusion therapy for first MI. Paired (99m)Tc-sestamibi scintigraphy studies (acute and 7 to 14 days after reperfusion) were used to calculate myocardial salvage index. DC and TS were assessed from Holter recordings 7 to 14 days after reperfusion. Patients were categorized into 3 groups by salvage index: <30% (n = 244), 30% to 60% (n = 257), and > or =60% (n = 353). In the 3 groups, DC was 5.2 (interquartile range 3.5 to 7.1) ms, 5.7 (4.1 to 7.3) ms, and 6.4 (5.0 to 8.0) ms, whereas TS was 5.3 (2.6 to 8.4) ms/R-R interval, 6.9 (3.2 to 11.7) ms/R-R interval, and 7.8 (4.1 to 13.2) ms/R-R interval, respectively (p < 0.0001 for both). After adjustment for left ventricular ejection fraction (LVEF), initial perfusion defect, creatine kinase, age, diabetes mellitus, sex, and medical therapy, patients with salvage index <30% had a 2.6-fold risk (95% confidence interval: 1.8 to 3.9, p < 0.001) of having abnormal DC (< or =4.5 ms) or TS (< or =2.5 ms/R-R interval) compared with patients with salvage index > or =60%. However, patients who had autonomic dysfunction defined by abnormal DC and TS had a poor prognosis independent of whether or not the salvage index was <30% (5-year mortality rates of 16.5% and 17.3%, respectively). In contrast, prognosis was excellent when both factors were normal (5-year mortality rates of 2.9% and 4.0%, respectively). Predictive value of impaired LVEF (< or =40%) was also independent of salvage index. Multivariably, both autonomic dysfunction and impaired LVEF were independent predictors of 5-year mortality. In patients undergoing mechanical reperfusion therapy for acute MI, salvage index is an independent predictor of autonomic dysfunction but does not affect its prognostic value.

Changing strategies in the management of acute myocardial infarction in modern China

Summary Ischaemic heart disease (IHD) is a common condition in China, accounting for more than 700,000 deaths each year mainly due to acute myocardial infarction (MI). Currently there is no nationally representative registry in China to provide data about the epidemiology, clinical management and prognosis of patients with MI. The present review has used information from a few large nationwide randomised trials and some small regional registries to assess the patterns of management of MI in China. As in many other countries, the management of acute MI in China has undergone a significant transformation during recent decades, due chiefly to an evidence-based approach to cardiovascular medicine. Antiplatelet therapy is now routinely given to almost all patients admitted with acute MI, using not only aspirin but increasingly combining it with clopidogrel. The overall use of reperfusion therapy is also consistent with that reported in Western populations, even though primary PCI is much less frequently used and the type of fibrinolytic agents commonly used may be less optimal in terms of the achieved patency rate of the infarct related artery. Anticoagulant therapy and ACE inhibitors are also used routinely in hospital, with about three-quarters of patients receiving such treatments consistently across different types of hospitals or regions. The use of beta-blocker therapy for acute MI in China has conventionally involved oral agents with little use of initial intravenous regimens, and this approach seems adequate for most patients with acute MI given the findings of the large COMMIT/CCS-2 trial in China. As a result of improved treatments, the hospital mortality for acute MI has declined significantly since the early 1990s. Despite a significant improvement in the general care of MI, there is still substantial under-, over- and inappropriate treatment of many patients in China. Further improvements, especially with respect to long-term management after MI, will rely not only on better implementation of the many established cost-effective treatments but also on improvements in the medical care system and more active engagement of the medical profession to improve risk factor management, such as smoking cessation.

Intracoronary KAI-9803 as an Adjunct to Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction

KAI-9803, a delta-protein kinase C inhibitor, has been shown to ameliorate injury associated with ischemia and reperfusion in animal models of acute myocardial infarction (MI). Direct Inhibition of delta-Protein Kinase C Enzyme to Limit Total Infarct Size in Acute Myocardial Infarction (DELTA MI) was a "first-in-human," dose-escalation study that evaluated the safety, tolerability, and activity of KAI-9803 for patients with acute anterior ST-segment elevation MI undergoing primary percutaneous coronary intervention. Patients who presented within 6 hours of symptom onset and had an occluded left anterior descending infarct artery on angiography were randomized in a 2:1 fashion to receive 1 of 4 doses of KAI-9803 (cohort 1, 0.05 mg; cohort 2, 0.5 mg; cohort 3, 1.25 mg; cohort 4, 5.0 mg) versus blinded concurrent placebo delivered in 2 divided doses via intracoronary injection before and after reestablishment of antegrade epicardial flow with percutaneous coronary intervention. Safety and biomarker end points were assessed. Overall, 154 patients were randomized and treated with study drug (37 in cohort 1, 38 in cohort 2, 38 in cohort 3, 41 in cohort 4). The incidence of serious adverse events was similar between patients treated with KAI-9803 versus placebo. Other safety end points, including changes in QT intervals and standard laboratory values after study drug administration, were similar between treatment groups. Although the study was not powered to demonstrate efficacy with the biomarker end points assessed, signs of drug activity with KAI-9803 were suggested by trends for consistent, nonsignificant reductions in creatine kinase-MB area under the curve and ST-recovery area under the curve values across all dosing cohorts with KAI-9803 compared with concurrent placebo, and similar trends were demonstrated for improvements in (99m)technetium sestamibi infarct size values with active study drug in cohorts 1, 2, and 3. KAI-9803 had an acceptable safety and tolerability profile when delivered via intracoronary injection during primary percutaneous coronary intervention for ST-segment elevation MI. Signs of potential drug activity were demonstrated with biomarker end points in this small exploratory study, indicating that further testing of KAI-9803 as an adjunctive therapy for ST-segment elevation MI is warranted.

Abstract 383: Heart-Kidney: Myocardial Infarction Mediates Renal Fibrosis and Activates Renal Molecular Remodeling in the Absence of Heart Failure

Background : Studies in human myocardial infarction (MI) suggest that even in the absence of heart failure (HF) alterations in renal function may occur and contribute to poor outcomes. After MI a decline in renal function may be seen acutely by mechanisms which are unclear. The long term consequences of MI upon renal function and structure remain poorly defined. We hypothesized that even without pre-existing renal disease, renal functional and structural changes would be present following MI. Methods : Cardiorenal function and structure were assessed in Wistar rats, Sham (S; n=10) and MI groups (n=9) 3 weeks after MI. GFR was determined by inulin clearance. Blood was obtained for PRA and aldosterone. Hearts and kidneys were harvested for histological analysis. Cardiac function was assessed by echo. Genome-wide microarray analysis was performed on kidney cortex (KC) and medulla (KM) (Affymetrix GeneChip® Rat Genome 230 2.0). Results : EF decreased after MI (S:62.8±2.3, MI:42.8±6.5 %, p&lt;0.01) and LVEDd increased (p&lt;0.005) PRA and aldosterone activation were absent. Blood pressure (BP) was not different between groups. There was no HF as sodium and water excretion was maintained. GFR tended to decrease (S:2.9±0.3, MI:2.4±0.2 ml/min, NS). Picrosirius Red staining for collagen in the KC and KM after MI showed greater fibrosis especially in the RM (KC S:1.1±0.2, MI:3.5±0.6 %, p&lt;0.001 and KM S:1±0.2, MI:18.8±6 %, p&lt;0.005). Microarray analysis revealed that 303 genes significantly changed in KM and 407 genes in the KC after MI (1.5 fold, P&lt;0.05). Gene dysregulation was related to cell proliferation, metabolic processes and cell communication (Z value&gt;2). Conclusion : We conclude that experimental MI results in renal structural remodeling characterized by renal cortical and medullary fibrosis with a mild reduction in GFR and extensive modulation of molecular pathways related to renal growth and metabolism. This investigation provides evidence for a heart-kidney connection after MI by mechanisms which remain to be defined. We also conclude that therapies for MI targeting the heart also should be evaluated for properties of renoprotection.

Ischaemic symptoms, quality of care and mortality during myocardial infarction

Objective:To study in myocardial infarction (MI) whether documentation of ischaemic symptoms is associated with quality of care and outcomes, and to compare patient reports of ischaemic symptoms during interviews with...

Myocardial infarction: contemporary management strategies

Myocardial infarction (MI) is a common clinical diagnosis, associated with significant morbidity and mortality, not only in the short term, but also years following the index event. A more complete understanding of the pathophysiology of MI has ushered the era of multipronged treatment approach, with a combination of goal-directed revascularization, a broad adjunctive pharmacological therapy and aggressive secondary prevention measures. The goals of this article are to review the basic pathophysiological processes, which lead up to a clinical diagnosis of MI, to highlight the essential elements of clinical presentation and to summarize the evidence for comprehensive therapy. Emphasis has been placed on the choice of primary reperfusion therapy for ST-elevation MI, on risk-stratification of patients with non-ST elevation MI, and on rationale behind the selection of anti-ischaemic and antithrombotic therapy. Finally, evidence-based approach to secondary prevention is outlined.

CARDIAC RUPTURE IN MYOCARDIAL INFARCTION: INCIDENCE AND PREDISPOSING FACTORS (15 YEAR FOLLOW-UP)

Aim. To evaluate the incidence of cardiac rupture (CR) in patients with acute myocardial infarction (MI) as well as predisposing factors during 15-year follow-up. Material and methods. 1453 patients with acute MI who were admitted to Krasnoyarsk cardiological center during 1989, 1993 and 2003 years were studied. All patients were divided into three groups: group I - 447 patients, who were on treatment in 1989, group II - 475 patients of 1993, and group III – 531 patients of 2003. There were no differences in groups on patient sex, location and depth of MI, previous MI, arrhythmias, heart failure and diabetes mellitus. Results. CR was found in 18 of 447 patients (4%) of group I (1989), in 16 of 475 patients (3,4%) of group II (1993) and in 10 of 531 patients (1,9%) of group 3 (2003), (p1,3 <0,05). Incidence of CR significantly decreased from 1989 to 2003 in female patients (7,2%; 5,7% and 1,6% in 1989, 1993 and 2003, respectively; p1,3 < 0,01, p2,3 < 0,05). Incidence of CR in male patients didn’t changed (2,5%, 1,8% and 2,1%, respectively). The average blood pressure (BP) during the first day of MI in female patients was higher than this in male ones in 1989 and 1993. There were no significant differences in BP between women and men in 2003. Heart rate (HR) during the first day of MI in female patients was higher than this in male patients in 1989. However in 1993 and 2003 there were no differences in HR between women and men. MI therapy more often included betablockers, angiotensin converting enzyme inhibitors, intravenous nitrates, statins, thrombolythics and anticoagulants in 2003 than in 1989 and 1993. Conclusion. Effective BP and HR control is the most effective way to prevent CR in patients with MI.

Short and long-term outcome in diabetic patients with acute myocardial infarction in the invasive era

Objectives. To investigate the outcome after acute myocardial infarction in diabetic patients compared with non-diabetic patients in a period with invasive treatment as the preferred treatment for acute myocardial infarction (MI). Design. Patient records for all patients admitted with an acute MI in a two-year period from July 1, 2001 to June 30, 2003 were reviewed. Results. A total of 334 patients entered the study: 48 with diabetes mellitus (DM) and 286 without diabetes. ST-elevation infarction occurred in 49% of non-diabetic patients and 36% of diabetic patients. In-hospital mortality was 23% among diabetic patients compared to 5% among non-diabetic patients (p < 0.001). Long-term mortality (median 2 years and 10 months) was 44% in diabetic-patients and 23% in non-diabetic patients (p = 0.001). Diabetic patients were older, more frequently had hypertension and three-vessel disease, but DM was found to be an independent risk factor for death after MI (p = 0.005). Conclusions. In an era of invasive therapy as the preferred therapy for acute MI, DM is still associated with considerably increased mortality after an acute MI.

Management of Perioperative Myocardial Infarction in Noncardiac Surgical Patients

Perioperative myocardial infarction (PMI) is a major cause of morbidity and mortality in patients undergoing noncardiac surgery. The incidence of PMI varies depending on the method used for diagnosis and is likely to increase as the population ages. Studies have examined different methods for prevention of myocardial infarction (MI), including the use of perioperative β-blockers, α₂-agonists, and statin therapy. However, few studies have focused on the treatment of PMI. Current therapy for acute MI generally involves anticoagulation and antiplatelet therapy, raising the potential for surgical site hemorrhage in this population. This article reviews the possible mechanisms, diagnosis, and treatment options for MI in the surgical setting. We also suggest algorithms for treatment.

DEVELOPMENT OFT‐WAVE ALTERNANS AND HEART RATE VARIABILITY AFTER MYOCARDIAL INFARCTION

The aim of the present study was to investigate T-wave alternans (μV-TWA) and heart rate variability (HRV), which have a prognostic value for sudden cardiac death, after myocardial infarction (MI). 17 patients of both sex with MI and thrombolytic therapy were included. The Frank ECG (lead x, y, z, vector) was measured within the first 8 and 24 hours, after 3 and 7 days as well as at day of release. Recording time was 10 min. μV-TWA was calculated according to Rosenbaum et al., N Engl J Med., 1994. Parameters were: maximal alternans of the repolarisation period in the ECG (MAR), integral of alternans-ratio of the repolarisation (IAR), and the frequency of significant alternans (MAR>3). HRV was analyzed using spectral analysis of heart period durations. Parameters were: power in low frequency (LF: 0.05–0.15 Hz) and high frequency range (HF: 0.15–2.0 Hz), ratio LF/HF and total power (TP: 0.05–2.0 Hz). μV-TWA occurred with a frequency between 27% (8 h) and 42% (7 d) after MI, taking all leads into consideration (ANOVA n.s.). μV-TWA occurred in at least one lead in 55% (8 h) to 79% (7 d) of the measurements (ANOVA n.s.). MAR, IAR, and MAR>3 did not change significantly during time after MI. LF/HF decreased in the course after MI. The results indicate that μV-TWA is possibly notrelated to the ischemic event. The development of LF/HF hints at an increase in vagal influences on the heart after MI.

Early intravenous then oral metoprolol in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial

Despite previous randomised trials of early beta-blocker therapy in the emergency treatment of myocardial infarction (MI), uncertainty has persisted about the value of adding it to current standard interventions (eg, aspirin and fibrinolytic therapy), and the balance of potential benefits and hazards is still unclear in high-risk patients. 45,852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were randomly allocated metoprolol (up to 15 mg intravenous then 200 mg oral daily; n=22,929) or matching placebo (n=22,923). 93% had ST-segment elevation or bundle branch block, and 7% had ST-segment depression. Treatment was to continue until discharge or up to 4 weeks in hospital (mean 15 days in survivors) and 89% completed it. The two prespecified co-primary outcomes were: (1) composite of death, reinfarction, or cardiac arrest; and (2) death from any cause during the scheduled treatment period. Comparisons were by intention to treat, and used the log-rank method. This study is registered with ClinicalTrials.gov, number NCT 00222573. Neither of the co-primary outcomes was significantly reduced by allocation to metoprolol. For death, reinfarction, or cardiac arrest, 2166 (9.4%) patients allocated metoprolol had at least one such event compared with 2261 (9.9%) allocated placebo (odds ratio [OR] 0.96, 95% CI 0.90-1.01; p=0.1). For death alone, there were 1774 (7.7%) deaths in the metoprolol group versus 1797 (7.8%) in the placebo group (OR 0.99, 0.92-1.05; p=0.69). Allocation to metoprolol was associated with five fewer people having reinfarction (464 [2.0%] metoprolol vs 568 [2.5%] placebo; OR 0.82, 0.72-0.92; p=0.001) and five fewer having ventricular fibrillation (581 [2.5%] vs 698 [3.0%]; OR 0.83, 0.75-0.93; p=0.001) per 1000 treated. Overall, these reductions were counterbalanced by 11 more per 1000 developing cardiogenic shock (1141 [5.0%] vs 885 [3.9%]; OR 1.30, 1.19-1.41; p<0.00001). This excess of cardiogenic shock was mainly during days 0-1 after admission, whereas the reductions in reinfarction and ventricular fibrillation emerged more gradually. Consequently, the overall effect on death, reinfarction, arrest, or shock was significantly adverse during days 0-1 and significantly beneficial thereafter. There was substantial net hazard in haemodynamically unstable patients, and moderate net benefit in those who were relatively stable (particularly after days 0-1). The use of early beta-blocker therapy in acute MI reduces the risks of reinfarction and ventricular fibrillation, but increases the risk of cardiogenic shock, especially during the first day or so after admission. Consequently, it might generally be prudent to consider starting beta-blocker therapy in hospital only when the haemodynamic condition after MI has stabilised.

Mesenchymal Stem Cells for Myocardial Infarction

Recent studies indicate that cardiac transfer of adult stem cells can have a favorable impact on tissue perfusion and contractile performance of the infarcted heart. Several cell sources are being explored in an effort to regenerate infarcted myocardium, including hematopoietic stem cells, endothelial progenitor cells, cardiac resident stem cells, bone marrow–derived multipotent stem cells, and mesenchymal stem cells (MSCs). Each of these cell types may have its own profile of advantages, limitations, and practicability issues in specific settings. Studies comparing the regenerative capacity of distinct cell populations are scarce. Most clinical investigators have therefore chosen a pragmatic approach by using unselected bone marrow cells that contain different stem cell populations. Basic scientists, by contrast, are focusing more on specific cell populations in a quest to understand the biological foundations of cell therapy and to identify the most promising stem cells for cardiac regeneration.1 See p 214 MSCs are a rare population of self-renewing, multipotent cells present in adult bone marrow. Although MSCs represent <0.01% of all nucleated bone marrow cells, they can be readily expanded in vitro. In defined culture media, MSCs differentiate into several mesenchymal cell lineages, including cardiomyocytes.2,3 When injected into normal adult myocardium, MSCs differentiate into cardiomyocyte-like cells with sarcomeric organization.4 In an earlier study in pigs with myocardial infarction (MI), MSCs grafted into the infarcted area were shown to express muscle-specific markers and to improve regional wall motion.5 Ease of isolation, high expansion capability, and cardiomyogenic potential have led to the proposition that MSCs may be a good choice for cell-based therapies of MI.6 In a report published in this issue of Circulation , Dai et al7 have …

Primary percutaneous coronary intervention for acute MI: improving access and outcomes.

Patients with acute myocardial infarction (MI) with ST-segment elevation have better outcomes with primary percutaneous coronary intervention (PCI) than with fibrinolytic therapy. Multiple clinical trials in the past 10 years have addressed ways to improve PCI as primary therapy for acute MI. Logistic strategies to improve access to PCI are being studied.