G-CSF Stimulation and Coronary Reinfusion of Mobilized Circulating Mononuclear Proangiogenic Cells in Patients with Chronic Ischemic Heart Disease: Five-Year Results of the TOPCARE-G-CSF Trial

2012 ◽  
Vol 21 (11) ◽  
pp. 2325-2337 ◽  
Author(s):  
Joerg Honold ◽  
Ulrich Fischer-Rasokat ◽  
Ralf Lehmann ◽  
David M. Leistner ◽  
Florian H. Seeger ◽  
...  

Prognosis of patients with heart failure remains poor despite improved conventional and interventional treatment regimens. The improvement of neovascularization and repair processes by administration of bone marrow-derived cells modestly improved the recovery after acute myocardial infarction. However, circulating patient-derived cells are reduced in number and function particularly in chronic heart failure. Therefore, we tested the hypothesis whether the mobilization of circulating mononuclear proangiogenic cells (CPCs) by G-CSF may overcome some of these limitations. In the present pilot study, 32 patients with at least 3-month-old myocardial infarction were randomized to G-CSF alone (G-CSF group) or intracoronary infusion of G-CSF-mobilized and cultured CPCs into the infarct-related artery (G-CSF/CPC group). Primary endpoint of the study was safety. Efficacy parameters included serial assessment of LV function, NT-proBNP levels, and cardiopulmonary exercise testing. G-CSF effectively mobilized circulating CD34+CD45+ cells after 5 days in all patients (408 ± 64%) without serious adverse events. At 3 months, NYHA class and global LV function did not show significant improvements in both treatment groups (G-CSF: ΔLVEF 1.6 ± 2.4%; p = 0.10; G-CSF/CPC: ΔLVEF 1.4 ± 4.1%; p = 0.16). In contrast, target area contractility improved significantly in the G-CSF/CPC group. During 5-year follow-up, one patient died after rehospitalization for worsening heart failure. Eleven patients underwent further revascularization procedures. NT-proBNP levels, cardiopulmonary exercise capacity, and NYHA class remained stable in both treatment groups. The results from our pilot trial indicate that administration of G-CSF alone or G-CSF-mobilized and cultured CPCs can be performed safely in patients with chronic ischemic heart disease. However, only minor effects on LV function, NT-proBNP levels, and NYHA classification were observed during follow-up, suggesting that the enhancement of CPCs by G-CSF alone does not substantially improve intracoronary cell therapy effects in patients with chronic ischemic heart failure.

2013 ◽  
Vol 3 (2) ◽  
pp. 50-56
Author(s):  
MBK Choudhury ◽  
MM Hossain ◽  
M Akhtaruzzaman ◽  
MM Jamal Uddin ◽  
MS Rahman ◽  
...  

Magnesium (Mg) and potassium (K) are the major intracellular cations whose presence in the serum are low, but minor changes of those may show a remarkable change in the various body functions specially in the heart. The study was designed to find out the correlation between serum Mg and K in acute myocardial infarction (AMI), chronic ischemic heart disease (CIHD) and normal healthy volunteers. It was carried out over a period of 18 months in the Department of Biochemistry, Bangabandhu Sheikh Mujib Medical University (BSMMU) in collaboration with Department of Cardiology, Sir Salimullah Medical College & Mitford Hospital (SSMC & MH) and Atomic Energy Center, Dhaka. A total of 101 subjects were included in which 32 subjects were AMI, 34 CIHD and 35 normal healthy volunteers. Serum glucose and serum creatinine were estimated to exclude diabetes and renal dystrophies. Estimation of serum CK-MB and ECG tracing were done as diagnostic tools of AMI and to categories the subjects into various groups. Serum Mg was estimated by Atomic absorption spectrophotometer and serum K by Ion sensitive electrode. The present study shows that there is a strong positive correlation of serum Mg and K in AMI, CIHD and healthy control subjects (r = 0.566, p<0.01 level). So it is suggested to estimate and supplement both Mg and K in IHD patients for their better management. DOI: http://dx.doi.org/10.3329/bjmb.v3i2.13812 Bangladesh J Med Biochem 2010; 3(2): 50-56


Author(s):  
Shannon M Dunlay ◽  
Susan Weston ◽  
Jill M Killian ◽  
Allan S Jaffe ◽  
Malcolm R Bell ◽  
...  

Background: Patients are surviving longer after myocardial infarction (MI), but little is known about the occurrence and predictors of subsequent hospitalizations. Methods: We identified all Olmsted Count residents with incident MI from 1987-2008 and evaluated Olmsted County hospitalizations through 2009. ICD-9 codes were used to determine the primary reason for hospitalization. To account for repeated events, Andersen-Gill models were used to examine the predictors of hospitalization post-MI. Patients were censored at death or last follow-up. Results: A total of 2617 patients (mean 67 years, 41% female, 32% with ST-elevation MI) were diagnosed with incident MI from 1987-2007 and survived MI hospitalization. Over a mean follow-up of 7.1 years, 10116 hospitalizations occurred equating to a median of 3 (range 0 to 43) per person. Only 37.5% (n=3793) of hospitalizations were due to cardiovascular causes, and of these, most were due to ischemic heart disease (n= 1865, 49.2%) and heart failure (n= 733, 19.3%). The proportion of non-cardiovascular hospitalizations increased over time and was higher in women than men, but did not differ by ST-segment status. Several factors were associated with the risk of hospitalization after adjusting for year of diagnosis and sex (Figure). Biomarker levels were not predictors of hospitalization risk. Conclusions: Two-thirds of hospitalizations among incident MI survivors in the community are for non-cardiovascular reasons, and this proportion has increased. Comorbidities are important predictors of recurrent hospitalizations. Therapies focused solely on MI management may be insufficient to prevent the majority of future admissions.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Yan Chaowu ◽  
Li Li ◽  
Fang Wei ◽  
Li Hua ◽  
Wang Yang

Introduction: Late gadolinium enhancement (LGE) has the potential to become an excellent technique in the diagnosis of right ventricular myocardial infarction (RVMI). However, the gold standard, pathological findings from patients, is still unavailable to validate the true value of LGE. Hypothesis: We hypothesized that LGE might correspond with histological infarction in RVMI. Methods: 36 transplant candidates (35 M /1F) with chronic ischemic heart disease were studied prospectively with LGE. According to the 12-segment-model, the pathological findings of RV were compared with the previous in vivo LGE after heart transplantation. Results: Histological RVMI was detected in 7 patients, and corresponded with all LGE segments (n=23) and 2 non-LGE segments. A generalize linear mix effect model showed non-significant difference (P=0.152) between the results of LGE and histological infraction. In identifying the RV segments with histological infarction, sensitivity and specificity of LGE was 92.0% (95%CI 74.0% to 99.0%) and 100% (95%CI 99.9% to 100.0%), respectively. Furthermore, RV segments without LGE mainly included two pathological patterns: histologically normal myocardium (n=372) or the admixture of viable myocardium and scattered replacement fibrosis (n=35). In the non-LGE RV segments, wall motion abnormality was associated with volume fraction of collagen (11.4±6.5% vs 4.3±2.2%, P<0.001) and the presence of ischemia (96.4% vs 1.7%, P<0.001). Conclusions: The RV segments with LGE corresponded closely with histological infarction in ischemic heart disease. However, RV segments without LGE might be histologically normal myocardium or intermixed with scattered replacement fibrosis. Further studies are required to evaluate the significance of scattered replacement fibrosis in the non-LGE segments.


Circulation ◽  
2020 ◽  
Vol 142 (9) ◽  
pp. 841-857 ◽  
Author(s):  
Sripal Bangalore ◽  
David J. Maron ◽  
Gregg W. Stone ◽  
Judith S. Hochman

Background: Revascularization is often performed in patients with stable ischemic heart disease. However, whether revascularization reduces death and other cardiovascular outcomes is uncertain. Methods: We conducted PUBMED/EMBASE/Cochrane Central Register of Controlled Trials searches for randomized trials comparing routine revascularization versus an initial conservative strategy in patients with stable ischemic heart disease. The primary outcome was death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), heart failure, stroke, unstable angina, and freedom from angina. Trials were stratified by percent stent use and by percent statin use to evaluate outcomes in contemporary trials. Results: Fourteen randomized clinical trials that enrolled 14 877 patients followed up for a weighted mean of 4.5 years with 64 678 patient-years of follow-up fulfilled our inclusion criteria. Most trials enrolled patients with preserved left ventricular systolic function and low symptom burden, and excluded patients with left main disease. Revascularization compared with medical therapy alone was not associated with a reduced risk of death (relative risk [RR], 0.99 [95% CI, 0.90–1.09]). Trial sequential analysis showed that the cumulative z-curve crossed the futility boundary, indicating firm evidence for lack of a 10% or greater reduction in death. Revascularization was associated with a reduced nonprocedural MI (RR, 0.76 [95% CI, 0.67–0.85]) but also with increased procedural MI (RR, 2.48 [95% CI, 1.86–3.31]) with no difference in overall MI (RR, 0.93 [95% CI, 0.83–1.03]). A significant reduction in unstable angina (RR, 0.64 [95% CI, 0.45–0.92]) and increase in freedom from angina (RR, 1.10 [95% CI, 1.05–1.15]) was also observed with revascularization. There were no treatment-related differences in the risk of heart failure or stroke. Conclusions: In patients with stable ischemic heart disease, routine revascularization was not associated with improved survival but was associated with a lower risk of nonprocedural MI and unstable angina with greater freedom from angina at the expense of higher rates of procedural MI. Longer-term follow-up of trials is needed to assess whether reduction in these nonfatal spontaneous events improves long-term survival.


2012 ◽  
Vol 17 (1) ◽  
pp. 33-36
Author(s):  
MBK Choudhury ◽  
MS Rahman ◽  
MM Hassan ◽  
R Begum ◽  
N Hoque ◽  
...  

The comparative study has been designed to estimate serum magnesium (Mg) and potassium (K) in patients with acute myocardial infarction (AMI) and chronic ischemic heart disease (CIHD). A total 61 subjects were selected and were divided as group-I (30 subjects of AMI) and group-II (31 subjects of CIHD). Laboratory investigations were done for estimation of serum glucose and serum creatinine to exclude the diabetes mellitus and renal disease. Serum Mg was estimated by atomic absorption spectrophotometer and serum K by ion selective electrode. This study showed that Mg and K level in serum is significantly lower in patients with AMI than that of CIHD subjects. Findings of the study suggested that significantly reduced serum level of Mg and K persists in AMI than those of CIHD, which may be the cause of further cardiac complications. So it may be recommended for estimation and supplementation of Mg and K in both the cases of AMI and CIHD patients for better management. DOI: http://dx.doi.org/10.3329/jdnmch.v17i1.12190 J. Dhaka National Med. Coll. Hos. 2011; 17 (01): 33-36


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Settergren ◽  
G Savarese ◽  
T Thorvaldsen ◽  
A Meyers ◽  
S Fazeli ◽  
...  

Abstract Background Comorbidities are associated with heart failure (HF) development, severity and outcomes, but may play different roles in HF with preserved (HFpEF) vs. mid-range (HFmrEF) vs. reduced ejection fraction (HFrEF). A detailed characterization of HF patients according to EF and comorbidities may improve prognostication and facilitate trial design. Purpose To investigate characteristics and outcomes in a large and unselected cohort of HF patients according to EF strata and presence/absence of concomitant type 2 diabetes (T2DM), atrial fibrillation (AF) and chronic kidney disease (CKD). Methods Patients enrolled in the Swedish HF registry between 2000–2012 were considered. Kaplan Meier curves and multivariable Cox regression models were fitted to assess risk and predictors of outcomes (HF and all-cause hospitalization; composite of cardiovascular (CV) death and HF hospitalization). Results Of 42,583 patients (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 49% CKD defined as eGFR&lt;60 ml/min/1.73m2, and 56% AF. T2DM, AF and CKD coexisted in 8% of the population with similar distribution across all EF strata. AF and CKD were the most likely to coexist. Prevalence of AF and/or CKD was highest in HFpEF and lowest in HFrEF, whereas prevalence of T2DM was similar across the EF spectrum (Figure). Compared to patients without T2DM and/or AF and/or CKD, those with any of them were more likely to suffer from other comorbidities (i.e. hypertension, anemia, COPD), to be inpatients, have more severe HF (higher NYHA class, NT-proBNP levels and use of diuretics, longer HF duration) but less likely to be followed-up in specialty vs. primary care. Concomitant history of ischemic heart disease was more likely in patients with vs. without CKD and/or T2DM but less likely in those with vs without AF. Patients with vs. without T2DM and/or CKD and/or AF had worse prognosis. In particular, risk of HF hospitalization and composite of HF hospitalization/CV death was highest in patients with HFrEF and concomitant comorbidities, whereas the risk of all-cause hospitalization was highest in those with HFpEF or HFmrEF and concomitant comorbidities. Prognostic predictors of CV death/HF hospitalization were consistent in patients with T2DM, CKD or AF, regardless of EF (e.g. male sex, older age, lower EF category, more severe HF, ischemic heart disease, anemia, COPD). Comorbidities burden Conclusion HF patients show a high burden of concomitant diseases, specifically T2DM, CKD and AF. CKD and AF are more prevalent in HFpEF vs. HFmrEF vs. HFrEF, whereas T2DM prevalence is consistent across the EF spectrum. Presence of comorbidities identifies patients with more severe HF regardless of EF category. Presence of comorbidities may identify patients at higher risk of CV outcomes in HFrEF and those at higher risk of non-CV events in HFpEF. Acknowledgement/Funding This study has been supported by funding from Boehringer Ingelheim


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Tetsuari Onishi ◽  
Yasue Tsukishiro ◽  
Hiroya Kawai

Background: Both Left ventricular (LV) global longitudinal strain (GLS) and LV ejection fraction (LVEF) are useful parameters for assessment of LV function. The aim of this study is to confirm the prognostic value of them in patients with non-ischemic and ischemic heart disease. Methods: We studied 179 patients (DCM group: Age 61±15 years, 70 females, LVEF 33±9%) with non-ischemic dilated cardiomyopathy and heart failure symptom, and 97 patients (MI group: Age 66±13 years, 18 females, LVEF 45±7%) who were successfully treated with percutaneous coronary intervention for acute anteroseptal myocardial infarction. Echocardiography was used for LV GLS derived from 2D speckle-tracking method and LVEF with modified Simpson’s method. Outcome was assessed according to death and re-hospitalization with heart failure in the follow-up period. Results: 40 patients in DCM group and 10 patients in MI group experienced at least one event. In these 2 groups, significant differences in GLS and LVEF were found between patients with and without cardiac events (p<0.05). Kaplan-Meier analysis showed patients with worse GLS had an unfavorable outcome in both DCM and MI groups (p<0.05), but LVEF did not associated with outcome. Conclusion: LV GLS has the potential to predict the outcome with higher sensitivity than LVEF in patients with heart disease regardless of ischemic etiology.


2016 ◽  
Vol 2 ◽  
pp. 326-333 ◽  
Author(s):  
Joanna M. Moryś ◽  
Jerzy Bellwon ◽  
Stefan Höfer ◽  
Andrzej Rynkiewicz ◽  
Marcin Gruchała

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Liu ◽  
C Wagner ◽  
K Hu ◽  
B Lengenfelder ◽  
G Ertl ◽  
...  

Abstract Background Mitral annular plane systolic excursion (MAPSE) derived from M-mode echocardiography is a classical risk factor of clinical outcome in heart failure patients. Two-dimensional-echocardiography (2DE) derived global longitudinal strain (GLS) is also related to outcome in patients with heart failure. This study aimed to compare the prognostic performance between GLS and MAPSE in ischemic heart failure patients with reduced ejection fraction. We sought to test the hypothesis that GLS might be superior to MAPSE as a risk stratification marker in these patients. Methods In total, 1277 ischemic heart failure patients with reduced left ventricular ejection fraction (LVEF&lt;50%), referred to our department between 2009 and 2017, were included in this retrospective study. Offline standard echocardiographic measurements including MAPSE and GLS were performed. Average MAPSE of septal and lateral walls (MAPSE_Avg) was calculated. GLS was derived from the segmental averaging (18-segment) of the three apical views. All patients completed at least one-year clinical follow-up by telephone interview or clinical visit. The primary endpoint was defined as all-cause mortality or heart transplantation (HTx). Results At baseline visit, mean age was 70±11 years and 79.6% were men. NYHA class III-IV were identified in 33.5% of patients. Coronary artery disease was confirmed by coronary angiography. 63.0% patients had a history of myocardial infarction, 32.1% underwent PCI, and 16.8% underwent coronary artery bypass grafting. Over a median follow-up period of 26 (14–39) months, 369 (28.9%) patients died and 5 (0.4%) underwent HTx. Median LVEF was 39% (32–45%), and there were 48.0% patients with LVEF between 40–49%, 32.3% patients with LVEF between 30–49% and 19.7% patients with LVEF &lt;30%. MAPSE_Avg was 8.0 (6.5–10.0) mm and median GLS was −9.9% (−7.7 to −12.3%). Clinical covariates significantly associated with all-cause mortality in this cohort included age (HR=1.048), NYHA class III-IV (HR=1.800), AF (HR=1.567), diabetes (HR=1.262), dyslipidemia (HR=0.657), hyperuricemia (HR=1.861), peripheral vascular disease (HR 1.858), chronic respiratory diseases (HR=1.680), and renal dysfunction (HR=2.705). Multivariable Cox regression analysis showed that reduced MAPSE_Avg (&lt;7mm, HR=1.431, 95% CI 1.146–1.786) and reduced GLS (&lt;8.3%, HR=1.519, 95% CI 1.230–1.875) were independent predictors of all-cause mortality after adjustment of above-mentioned clinical confounders. ROC curves demonstrated that the predictive performance of all-cause mortality among LVEF, MAPSE_Avg, and GLS were similar (AUC=0.608, 0.601, and 0.616, respectively, all P&lt;0.001). Conclusions Both 2DE-guided GLS and MAPSE could provide additional prognostic information in ischemic heart failure patients with reduced LVEF. Prognostic performance of GLS, MAPSE, and LVEF is similar in ischemic heart failure patients with reduced LVEF. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The German Federal Ministry of Education and Research


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