scholarly journals The effect of intracoronary infusion of bone marrow-derived mononuclear cells on all-cause mortality in acute myocardial infarction: the BAMI trial

2020 ◽  
Vol 41 (38) ◽  
pp. 3702-3710 ◽  
Author(s):  
Anthony Mathur ◽  
Francisco Fernández-Avilés ◽  
Jozef Bartunek ◽  
Ann Belmans ◽  
Filippo Crea ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Bone Marrow ◽  
Adverse Events ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Intracoronary Infusion ◽  
All Cause Mortality

Abstract Aims  Bone marrow-derived mononuclear cell (BM-MNC) therapy may improve myocardial recovery in patients following acute myocardial infarction (AMI), though existing trial results are inconsistent. Methods and results  Originally an open-label, multicentre Phase III trial, BAMI was designed to demonstrate the safety and efficacy of intracoronary infusion of BM-MNCs in reducing the time to all-cause mortality in patients with reduced left ventricular ejection fraction (LVEF, ≤45%) after primary angioplasty (PPCI) for ST-elevation AMI. Unexpectedly low recruitment means the trial no longer qualifies as a hypothesis-testing trial, but is instead an observational study with no definitive conclusions possible from statistical analysis. In total, 375 patients were recruited: 185 patients were randomized to the treatment arm (intracoronary infusion of BM-MNCs 2–8 days after PPCI) and 190 patients to the control arm (optimal medical therapy). All-cause mortality at 2 years was 3.26% [6 deaths; 95% confidence interval (CI): 1.48–7.12%] in the BM-MNC group and 3.82% (7 deaths; 95% CI: 1.84–7.84%) in the control group. Five patients (2.7%, 95% CI: 1.0–5.9%) in the BM-MNC group and 15 patients (8.1%, CI : 4.7–12.5%) in the control group were hospitalized for heart failure during 2 years of follow-up. Neither adverse events nor serious adverse events differed between the two groups. There were no patients hospitalized for stroke in the control group and 4 (2.2%) patients hospitalized for stroke in the BM-MNC group. Conclusions  Although BAMI is the largest trial of autologous cell-based therapy in the treatment of AMI, unexpectedly low recruitment and event rates preclude any meaningful group comparisons and interpretation of the observed results.

scholarly journals Aldosterone Blockade in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Qiao Chen ◽  
Die Zhao ◽  
Jie Sun ◽  
Chengzhi Lu
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Adverse Events ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cochrane Library ◽  
Ventricular Ejection Fraction ◽  
All Cause Mortality

Background. A comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists (MRA) in acute myocardial infarction (AMI) patients is lacking. Objective. To summarize the evidence on the efficacy and safety of MRA in patients admitted for AMI. Methods. Articles were identified through PubMed, Embase, Cochrane Library, Ovid (Medline1946-2021), and ClinicalTrials.gov databases from their inception to December 31, 2020. Results. 15 articles with a total of 11,861 patients were included. MRA reduced the risk of all-cause mortality by 16% (relative ratio (RR): 0.84; 95% confidence interval (CI) (0.76, 0.94); P = 0.002 ) and the incidence of cardiovascular adverse events by 12% (RR: 0.88, 95% CI (0.83, 0.93), P < 0.00001 ) in post-AMI patients, and further analysis demonstrated that early administration of MRA within 7 days after AMI resulted in a greater reduction in all-cause mortality (RR: 0.72, 95% CI (0.61, 0.85), P < 0.0001 ). Subgroup analyses showed that post-STEMI patients without left ventricular systolic dysfunction (LVSD) treated with MRA had a 36% reduction in all-cause mortality (RR: 0.64, 95% CI (0.46, 0.89), P = 0.007 ) and a 22% reduction in cardiovascular adverse events (RR: 0.78, 95% CI (0.67, 0.91), P = 0.002 ). Meanwhile, post-STEMI patients without LVSD treated with MRA get significant improvements in left ventricular ejection fraction (mean difference (MD): 2.69, 95% CI (2.44, 2.93), P < 0.00001 ), left ventricular end-systolic index (MD: -4.52 ml/m2, 95% CI (-8.21, -0.83), P = 0.02 ), and left ventricular end-diastolic diameter (MD: -0.11 cm, 95% CI (-0.22, 0.00), P = 0.05 ). The corresponding RR were 1.72 (95% CI (1.43, 2.07), P < 0.00001 ) for considered common adverse events (hyperkalemia, gynecomastia, and renal dysfunction). Conclusions. Our findings suggest that MRA treatment reduces all-cause mortality and cardiovascular adverse events in post-AMI patients, which is more significant in patients after STEMI without LVSD. In addition, MRA treatment may exert beneficial effects on the reversal of cardiac remodeling in patients after STEMI without LVSD.

Randomized, double blind, placebo-controlled, safety and efficacy study of dutogliptin in combination with filgrastim in early recovery post-MI: rationale, design and first interim analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Von Lewinski ◽  
B Merkely ◽  
I Buysschaert ◽  
R.A Schatz ◽  
G.G Nagy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Adverse Events ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Early Recovery ◽  
Ventricular Ejection Fraction ◽  
Combined Application

Abstract Background Regenerative therapies offer new approaches to improve cardiac function after acute ST-elevation myocardial infarction (STEMI). Mobilization of stem cells and homing within the infarcted area have been identified as the key mechanisms for successful treatment. Application of granulocyte-colony stimulating factor (G-CSF) is the least invasive way to mobilize stem cells while DDP4-inhibitor facilitates homing via stromal cell-derived factor 1 alpha (SDF-1α). Dutogliptin, a novel DPP4 inhibitor, combined with stem cell mobilization using G-CSF significantly improved survival and reduced infarct size in a murine model. Purpose We initiated a phase II, multicenter, randomized, placebo-controlled efficacy and safety study (N=140) analyzing the effect of combined application of G-CSF and dutogliptin, a small molecule DPP-IV-inhibitor for subcutaneous use after acute myocardial infarction. Methods The primary objective of the study is to evaluate the safety and tolerability of dutogliptin (14 days) in combination with filgrastim (5 days) in patients with STEMI (EF &lt;45%) following percutaneous coronary intervention (PCI). Preliminary efficacy will be analyzed using cardiac magnetic resonance imaging (cMRI) to detect &gt;3.8% improvement in left ventricular ejection fraction (LV-EF). 140 subjects will be randomized to filgrastim plus dutogliptin or matching placebos. Results Baseline characteristics of the first 26 patients randomized (24 treated) in this trial reveal a majority of male patients (70.8%) and a medium age of 58.4 years (37 to 84). During the 2-week active treatment period, 35 adverse events occurred in 13 patients, with 4 rated as serious (hospitalization due to pneumonia N=3, hospitalization due to acute myocardial infarction N=1), and 1 adverse event was rated as severe (fatal pneumonia), 9 moderate, and 25 as mild. 6 adverse events were considered possibly related to the study medication, including cases of increased hepatic enzymes (N=3), nausea (N=1), subcutaneous node/suffusion (N=1) and syncope (N=1). Conclusions Our data demonstrate that the combined application of dutogliptin and G-CSF appears to be safe on the short term and feasible after acute myocardial infarction and may represent a new therapeutic option in future. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This research is funded by the sponsor RECARDIO, Inc., 1 Market Street San Francisco, CA 94150, USA. RECARDIO Inc. is funding the complete study. The Scientific Board of RECARDIO designed the study. Data Collection is at the participating sites. Interpretation of the data by the Scientific Board and Manuscript written by the authors and approved by the Sponsor

Abstract 20556: Safety and Efficacy of Intracoronary Hypoxia-PrecondItioned Bone Marrow Mononuclear Cells Administration for Acute Myocardial Infarction Patients

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Xin Yang Hu ◽  
Xin Huang ◽  
Qian Yang ◽  
Lihan Wang ◽  
Jianzhong Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Bone Marrow ◽  
Primary Endpoint ◽  
Perfusion Defect ◽  
Mononuclear Cells ◽  
Left Ventricular ◽  
Bone Marrow Mononuclear Cells ◽  
Safety And Efficacy ◽  
Intracoronary Infusion

IMPORTANCE: Cell therapy has been a potential approach for ST-segment elevation acute myocardial infarction (STEMI). To improve the therapeutic oucome, the safety and efficacy of hypoxia-preconditioned (H-) bone marrow mononuclear cells (BMCs) in AMI patients need further evaluation. OBJECTIVE: To investigate the safety and efficacy of H-BMCs therapy in AMI patients. DESIGN: A phase 1, randomized and blinded study (February, 2011~ March, 2012) with one-year of follow-up. SETTING: A single center for hospitalized care. PARTICIPANTS: 22 Patients with an acute ST elevation myocardial infarction were recruited and randomized to two groups: normoxia BMCs (N-, n=11) and H-BMCs (n=11). INTERVENTIONS: Intracoronary infusion of H-BMCs or N-BMCs within 5-7 days after treatment with percutaneous transluminal coronary intervention (PCI). Patients were similarly treated by a stop-flow technique through an over-the-wire balloon catheter. MAIN OUTCOMES AND MEASURES: Primary endpoint was Treatment-emergent 30-day serious adverse event rate defined as a composite of death, MI, sustained ventricular tachycardia, stroke, hospitalization for worsening heart failure and revascularization. Secondary endpoints were change of myocardium perfusion, global left ventricular ejection fraction and left ventricular volumes. RESULTS: The primary endpoint events was none for N-BMCs and 9.1% (95% CI, 0.2%-41.3%) for H-BMCs. There was significant increase in the change of LVEF of H-BMCs group at 6 month. The change of end diastolic volume (EDV) and end systolic volume (ESV) in H-BMCs at 12 month were significantly decreased. Ratio of myocardium perfusion defect by Single-Photon Emission Computed Tomography (SPECT) was significantly reduced in H-BMCs group at 6 months, and score of myocardium perfusion defect by SPECT was significantly reduced than that of baseline in H-BMCs group at 6 and 12 months, unlike N- group. CONCLUSIONS AND RELEVANCE: Intracoronary infusion with H-BMCs appeared to be safe and effective for patients with AMI. Although the sample size precludes a definitive statement about safety and efficacy, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach.

scholarly journals Impella versus IABP in acute myocardial infarction complicated by cardiogenic shock

Open Heart ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. e000987 ◽  
Author(s):  
Brunilda Alushi ◽  
Andel Douedari ◽  
Georg Froehlig ◽  
Wulf Knie ◽  
Thomas H Wurster ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cardiogenic Shock ◽  
Primary Outcome ◽  
Left Ventricular ◽  
Cox Proportional Hazards ◽  
Left Ventricular Ejection ◽  
Bleeding Complications ◽  
Ventricular Ejection Fraction ◽  
All Cause Mortality

ObjectiveWe investigated the benefit of Impella, a modern percutaneous mechanical support (pMCS) device, versus former standard intra-aortic balloon pump (IABP) in acute myocardial infarction complicated by cardiogenic shock (AMICS).MethodsThis single-centre, retrospective study included patients with AMICS receiving pMCS with either Impella or IABP. Disease severity at baseline was assessed with the IABP-SHOCK II score. The primary outcome was all-cause mortality at 30 days. Secondary outcomes were parameters of shock severity at the early postimplantation phase. Adjusted Cox proportional hazards models identified independent predictors of the primary outcome.ResultsOf 116 included patients, 62 (53%) received Impella and 54 (47%) IABP. Despite similar baseline mortality risk (IABP-SHOCK II high-risk score of 18 % vs 20 %; p = 0.76), Impella significantly reduced the inotropic score (p < 0.001), lactate levels (p < 0.001) and SAPS II (p =0.02) and improved left ventricular ejection fraction (p = 0.01). All-cause mortality at 30 days was similar with Impella and IABP (52 % and 67 %, respectively; p = 0.13), but bleeding complications were more frequent in the Impella group (3 vs 4 units of transfused erythrocytes concentrates due to bleeding complications, p = 0.03). Previous cardiopulmonary resuscitation (HR 3.22, 95% CI 1.76 to 5.89; p < 0.01) and an estimated intermediate (HR 2.77, 95% CI 1.42 to 5.40; p < 0.01) and high (HR 4.32 95% CI 2.03 to 9.24; p = 0.01) IABP-SHOCK II score were independent predictors of all-cause mortality.ConclusionsIn patients with AMICS, haemodynamic support with the Impella device had no significant effect on 30-day mortality as compared with IABP. In these patients, large randomised trials are warranted to ascertain the effect of Impella on the outcome.

scholarly journals Prognostic impacts of prehospital age shock index in patients with acute myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Hirota ◽  
K Moriwaki ◽  
A Takasaki ◽  
T Takamura ◽  
T Kurita ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
High Risk ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Shock Index ◽  
Significant Independent Predictor ◽  
Ventricular Ejection Fraction ◽  
All Cause Mortality ◽  
Chi Squared

Abstract Introduction Early identification of high-risk patients is the cornerstone of managing patients with acute myocardial infarction (AMI). Age Shock index (ASI; age multiplied by the ratio of heart rate/systolic blood pressure) has been reported to be similar to Global Registry of Acute Coronary Events (GRACE) risk score for predicting mortality in patients with AMI. However, prognostic impacts of prehospital ASI (pre-ASI) in patients with AMI remain unknown. Methods We analyzed of 2578 AMI patients who underwent emergency primary percutaneous coronary intervention (PCI) from January 2013 to March 2018, using data from Mie ACS Registry, a prospective and multicenter registry in Japan. Pre-ASI was recorded by emergency medical services at the first contact with the patient before admission, and in-hospital ASI (in-ASI) was recorded prior to PCI at admission. The primary end point was defined as all-cause death. Results Median follow-up duration was 753 days (497–838 days). All-cause death was observed in 230 (8.9%) patients. The ROC-AUC (Receiver operating characteristic-area under the curve) of pre-ASI for all- cause death was 0.76 (p&lt;0.001), which was similar to that of in-ASI (0.78, p&lt;0.001) (p=0.25 for pre-ASI versus in-ASI). The cut-off value for pre-ASI and in-ASI was for the prediction of all-cause death was both 45 with a sensitivity of 0.66 and a specificity of 0.78, with a sensitivity of 0.68 and a specificity of 0.76 respectively. According to the Kaplan-Meier survival analysis by combination of pre-ASI≥45 and in-ASI≥45, the patients with pre-ASI≥45 and in-ASI≥45 showed significantly higher all-cause mortality compared to the patients with pre-ASI≥45 and in-ASI&lt;45, the patients with pre-ASI&lt;45 and in-ASI≥45, and the patients with pre-ASI&lt;45 and in-ASI&lt;45 (p&lt;0.001) (Figure). The addition of pre-ASI≥45 to in-ASI≥45 (global chi-squared score: 205) resulted in a significantly increased global chi-squared score, suggesting the incremental prognostic value of pre-ASI (267; p&lt;0.001). Multivariate cox proportional hazard regression analysis for all-cause mortality demonstrated pre-ASI≥45 was a significant independent predictor (HR: 4.86; 95% CI: 3.36 to 7.02, p&lt;0.001). It was strongest predictor compared to left ventricular ejection fraction&lt;40% (HR: 2.45; 95% CI 1.67 to 3.58, p&lt;0.001), hemodialysis (HR: 3.45; 95% CI 1.66 to 7.17, p=0.001), door to balloon time&gt;90 minutes (HR: 1.66; 95% CI 1.18 to 2.34, p=0.004). Conclusions High pre-ASI predict increase mortality and assessment of both high pre-ASI and high in-ASI enhance risk stratification in patients with AMI. Early recognizing high pre-ASI may help us make better strategies and improve prognosis for high-risk AMI patients. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals Rational Route of Delivery Mesenchymal Stem Cell Therapy for Acute Myocardial Infarction (AMI) and Chronic Ischemic Cardiomyopathy (ICM): a Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Huang Yan ting ◽  
Lin Weizhao ◽  
Yang Xiangbin ◽  
Chen Shuqing ◽  
Gao Kai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Systematic Review ◽  
Acute Myocardial Infarction ◽  
Stem Cell ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Secondary Outcome ◽  
Intracoronary Infusion ◽  
Route Of Delivery

Abstract Background: Recent studies suggest that mesenchymal stem cells (MSCs) may have therapeutic potential for both acute myocardial infarction (AMI) and chronic ischemic cardiomyopathy (ICM). However, the rational route of delivery MSC therapy has not reached consensus. We performed a systematic review of clinical trials evaluating the rational route of delivery MSCs for AMI or ICM.Methods: Databases including Embase, PubMed, and Cochrane Central Register of Controlled Trials were searched from inception to February 2021. Studies that examined the use of MSCs in adults with AMI or ICM were eligible. Bias of included studies were assessed by the Cochrane risk of bias tool. The primary outcome was cardiac function assessed by left ventricular ejection fraction (LVEF) and the secondary outcome was cardiac remodeling which was assessed by left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV), we also explored the safety between different routes. Results: 18 studies fulfilled eligibility criteria, which consist of 11 studies evaluated AMI and 7 studies evaluated ICM. In AMI group, only when patients received intracoronary infusion(IC) can improve LVEF (SMD 0.88, 95% CI 0.64-1.12), and there was a decrease in LVEDV&LVESV when administered IC or intravenous infusion (IV). While in ICM group, no significant difference in LVEF was noted no matter administered which route, and transendocardial stem cell injection(TESI) seems to be effective in decreasing LVEDV&LVESV. Safety appeared no difference between different routes. Conclusions: Results from our systematic review suggest that intracoronary infusion seems more effective for MSC’s delivery in AMI group, while in ICM group, TESI better.

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