Remote ischaemic conditioning (RIC) and postconditioning (PostC) are both potent activators of innate protection against ischaemia-reperfusion injury and have demonstrated cardioprotection in ...experimental and clinical ST-elevation myocardial infarction (STEMI) trials. However, their combined effects have not been studied in detail. The aim of this study was to evaluate if the co-application of intrahospital RIC and PostC has a more powerful effect on myocardial salvage compared with either PostC alone or control.
This prospective, controlled, single-centre study randomized 696 STEMI patients to one of the following three groups: (i) combined intrahospital RIC + PostC in addition to primary percutaneous coronary intervention (PCI); (ii) PostC in addition to PCI; and (iii) conventional PCI (control). The primary endpoint myocardial salvage index was assessed by cardiac magnetic resonance (CMR) imaging within 3 days after infarction. Secondary endpoints included infarct size and microvascular obstruction (MVO) assessed by CMR. The combined clinical endpoint consisted of death, reinfarction, and new congestive heart failure within 6 months. The primary endpoint myocardial salvage index was significantly greater in the combined RIC + PostC group when compared with the control group (49 interquartile range 30-72 vs. 40 interquartile range 16-68, P = 0.02). Postconditioning alone failed to improve myocardial salvage when compared with conventional PCI (P = 0.39). The secondary endpoints, including infarct size and MVO, showed no significant differences between groups. Clinical follow-up at 6 months revealed no differences in the combined clinical endpoint between groups (P = 0.44).
Combined intrahospital RIC + PostC in conjunction with PCI in STEMI significantly improves myocardial salvage in comparison with control and PostC.
NCT02158468.
Background:As adolescents rarely experience cardiovascular events, surrogate markers of atherosclerosis are useful to justify and monitor effects of primary prevention and therapy of risk factors. ...Endothelial function assessed by reactive hyperemic peripheral arterial tonometry (RH-PAT) resulting in a reactive hyperemic index (RHI) is a noninvasive method with limited data for use in children and adolescents.Methods and Results:We performed a total of 931 RHI measurements in 445 high-school students, aged 10–17 years, over a time period of 5 years. Students were randomized by class to 60 min physical exercise (PE) at school daily (intervention group), or 2 units of 45-min PE weekly (control group). To characterize the factors influencing the RHI, anthropometry, cardiopulmonary exercise testing, blood cholesterol and quality of life were assessed and used to build mixed linear models. Main influential factors were age, with an increase of RHI from 1.53±0.42 in the youngest to 1.96±0.59 in the oldest students, sex, with higher values in girls, and physical activity. This increase adjusted by age and sex was estimated as 0.11 0.08, 0.14 per year. RHI was higher in the intervention group by 0.09 −0.05, 0.23 in comparison with the control group.Conclusions:If RH-PAT is used in research or as a clinical tool in adolescents, the shown age- and sex-dependence of RHI have to be taken in account.
The infusion of bone marrow–derived progenitor cells into the infarct-related coronary artery after an acute myocardial infarction was associated with an absolute increase in the ejection fraction of ...5.5%. Determining whether this modest improvement in ventricular function will translate into a long-term clinical benefit will require larger trials with longer follow-up.
The infusion of bone marrow–derived progenitor cells into the infarct-related coronary artery after an acute myocardial infarction was associated with an absolute increase in the ejection fraction of 5.5%.
Prompt reperfusion of the infarct-related coronary artery has considerably improved the clinical outcome in patients with acute myocardial infarction.
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Although contemporary reperfusion strategies using stent implantation and aggressive inhibition of platelet aggregation have been shown to increase myocardial salvage,
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improvements in global left ventricular function are rather modest, despite the use of optimal reperfusion therapy.
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Heart failure that develops after infarction remains a major cause of morbidity and mortality.
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Experimental studies suggested that intravascular or intramyocardial administration of progenitor cells derived from bone marrow (BMC) or blood may contribute to functional regeneration of infarcted myocardium and enhance neovascularization . . .
A reduction in number and function of endothelial progenitor cells (EPCs) occurs in both physiologic aging and chronic heart failure (CHF). We assessed whether disease and aging have additive effects ...on EPCs or whether beneficial effects of exercise training are diminished in old age.
We randomized 60 patients with stable CHF and 60 referent controls to a training or a control group. To detect possible aging effects we included subjects below 55 (young) and above 65 years (older). Subjects in the training group exercised four times daily at 60% to 70% of VO2max for four weeks under supervision. At baseline and after the intervention the number and function of EPCs were assessed.
As compared with young referent controls, older referent controls showed at baseline a reduced EPC number (young: 190 ± 37 CD34/KDR positive cells/ml blood; older: 131 ± 26 CD34/KDR positive cells/ml blood; p < 0.05) and function (young: 230 ± 41 migrated cells/1000 plated cells; older: 185 ± 28 cells/1000 plated cells; p < 0.05). In young and older CHF patients EPC-number (young: 85 ± 21 CD34/KDR positive cells/ml blood; older: 78 ± 20 CD34/KDR positive cells/ml blood) and EPC-function (young: 113 ± 26 cells/1000 plated cells; older: 120 ± 27 cells/1000 plated cells) were impaired. As a result of exercise training, EPC function improved by 24% in older referent controls (p < 0.05), while it remained unchanged in young training referent controls and controls respectively. In young and older patients with CHF four weeks of exercise training resulted in a significant improvement in EPC numbers and EPC function (young: number +66% function +43%; p < 0.05; older: number +69% function +36%; p < 0.05). These results were accompanied by a significant increase in flow mediated dilatation in the training groups of young/older CHF patients and in older referent controls.
Four weeks of exercise training are effective in improving EPC number and EPC function in CHF patients. These training effects were not impaired among older patients, emphasizing the potentials of rehabilitation interventions in a patient group where CHF has a high prevalence.
The objective of the present analysis was to systematically examine the effect of intracoronary bone marrow cell (BMC) therapy on left ventricular (LV) function after ST-segment elevation myocardial ...infarction in various subgroups of patients by performing a collaborative meta-analysis of randomized controlled trials.
We identified all randomized controlled trials comparing intracoronary BMC infusion as treatment for ST-segment elevation myocardial infarction. We contacted the principal investigator for each participating trial to provide summary data with regard to different pre-specified subgroups age, diabetes mellitus, time from symptoms to percutaneous coronary intervention, infarct-related artery, LV end-diastolic volume index (EDVI), LV ejection fraction (EF), infarct size, presence of microvascular obstruction, timing of cell infusion, and injected cell number and three different endpoints change in LVEF, LVEDVI, and LV end-systolic volume index (ESVI). Data from 16 studies were combined including 1641 patients (984 cell therapy, 657 controls). The absolute improvement in LVEF was greater among BMC-treated patients compared with controls: 2.55% increase, 95% confidence interval (CI) 1.83-3.26, P < 0.001. Cell therapy significantly reduced LVEDVI and LVESVI (-3.17 mL/m², 95% CI: -4.86 to -1.47, P < 0.001; -2.60 mL/m², 95% CI -3.84 to -1.35, P < 0.001, respectively). Treatment benefit in terms of LVEF improvement was more pronounced in younger patients (age <55, 3.38%, 95% CI: 2.36-4.39) compared with older patients (age ≥ 55 years, 1.77%, 95% CI: 0.80-2.74, P = 0.03). This heterogeneity in treatment effect was also observed with respect to the reduction in LVEDVI and LVESVI. Moreover, patients with baseline LVEF <40% derived more benefit from intracoronary BMC therapy. LVEF improvement was 5.30%, 95% CI: 4.27-6.33 in patients with LVEF <40% compared with 1.45%, 95% CI: 0.60 to 2.31 in LVEF ≥ 40%, P < 0.001. No clear interaction was observed between other subgroups and outcomes.
Intracoronary BMC infusion is associated with improvement of LV function and remodelling in patients after ST-segment elevation myocardial infarction. Younger patients and patients with a more severely depressed LVEF at baseline derived most benefit from this adjunctive therapy.
Background
In the REPAIR-AMI trial, intracoronary infusion of bone marrow-derived cells (BMCs) was associated with a significantly greater recovery of contractile function in patients with acute ...myocardial infarction (AMI) at 4-month follow-up than placebo infusion. The current analysis investigates clinical outcome and predictors of event-free survival at 5 years.
Methods and results
In the multicentre, placebo-controlled, double-blind REPAIR-AMI trial, 204 patients received intracoronary infusion of BMCs (n = 101) or placebo (n = 103) into the infarct vessel 3–7 days following successful percutaneous coronary intervention. Fifteen patients died in the placebo group compared with seven patients in the BMC group (P = 0.08). Nine placebo-treated patients and five BMC-treated patients required rehospitalization for chronic heart failure (P = 0.23). The combined endpoint cardiac/cardiovascular/unknown death or rehospitalisation for heart failure was more frequent in the placebo compared with the BMC group (18 vs. 10 events; P = 0.10). Univariate predictors of adverse outcomes were age, the CADILLAC risk score, aldosterone antagonist and diuretic treatment, changes in left ventricular ejection fraction, left ventricular end-systolic volume, and N-terminal pro-Brain Natriuretic Peptide (all P < 0.01) at 4 months in the entire cohort and in the placebo group. In contrast, in the BMC group, only the basal (P = 0.02) and the stromal cell-derived factor-1-induced (P = 0.05) migratory capacity of the administered BMC were associated with improved clinical outcome.
Conclusion
In patients of the REPAIR-AMI trial, established clinical parameters are associated with adverse outcome at 5 years exclusively in the placebo group, whereas the migratory capacity of the administered BMC determines event-free survival in the BMC-treated patients. These data disclose a potency–effect relationship between cell therapy and long-term outcome in patients with AMI.
Aims
In late-stage chronic heart failure (CHF), elevated cytokines and cachexia are often observed. Several studies have shown that exercise training exerts beneficial effects on skeletal muscle in ...this setting. Furthermore, it has been shown that the expression of myostatin, a key regulator of skeletal muscle mass, is increased in a variety of cachectic states. This study aimed to investigate the expression of myostatin in CHF, the influence of exercise training on myostatin levels, and regulation of myostatin by tumour necrosis factor-α (TNF-α).
Methods and results
In an animal model of CHF (LAD-ligation model), protein expression of myostatin was elevated 2.4-fold in the skeletal muscle and more than four-times in the myocardium, compared with control (Co). Exercise training on a treadmill over 4 weeks led to a significant reduction in myostatin protein expression in the skeletal muscle and the myocardium of CHF animals, with values returning to baseline levels. In differentiated C2C12 cells, TNF-α induced the expression of myostatin through a p38MAPK-dependent pathway involving nuclear factor kappa-B (NF-κB). The increased TNF-α mRNA levels in the skeletal muscle of CHF animals correlated significantly with myostatin expression.
Conclusion
These alterations in myostatin expression in the skeletal and heart muscle following exercise training could help to explain the beneficial anti-catabolic effects of exercise training in CHF.
In the arterial wall nitric oxide (NO) is the key transmitter for endothelium-dependent regulation of vascular tone. It is produced in intact endothelial cells by endothelial NO synthase (eNOS) as ...the key enzyme from L-arginine. Endothelial NO generation is highly regulated by mechanical, humoral, and metabolic factors. The regulation of NO synthesis occurs at different levels: ENOS gene polymorphisms are related to eNOS expression and activity and may potentially increase coronary event rate, mRNA expression is influenced by estrogen status and shear stress, mRNA stability is enhanced by vascular endothelial growth factor (VEGF), and final enzyme activity is regulated by the phosphorylation status at serine/threonine residues. Released from endothelial cells NO is rapidly transported to the neighboring vascular smooth muscle cells (VSMCs), where it induces the production of cGMP as a second messenger. CGMP in turn increases Ca2+ uptake into intracellular calcium stores thereby lowering Ca2+i and inducing VSMC relaxation and vasodilation. On its way to the VSMCs NO may be prematurely degraded by reactive oxygen species. On the other hand, chronic endurance exercise with regular bouts of increased laminar flow along the endothelium has the potential to increase eNOS mRNA expression and phosphorylation via AKT (protein kinase B) and to reduce oxidative stress by improving antioxidative protection. The growing knowledge about the complex regulation of NO synthesis and degradation in cardiovascular diseases and its response to exercise has led to a new understanding of the protective effects of long-term habitual physical activity against atherosclerotic heart disease and vascular aging.
The aim of this study was to investigate the clinical outcome 2 years after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI).
Using a ...double-blind, placebo-controlled, multicenter trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone marrow-derived progenitor cells (BMC) or placebo medium into the infarct artery 3 to 7 days after successful infarct reperfusion therapy. At 2 years, the cumulative end point of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (hazard ratio, 0.58; 95% CI, 0.36 to 0.94; P=0.025). Likewise, the combined end point death and recurrence of myocardial infarction and rehospitalization for heart failure, reflecting progression toward heart failure, was significantly reduced in the BMC group (hazard ratio, 0.26; 95% CI, 0.085 to 0.77; P=0.015). Intracoronary administration of BMC remained a significant predictor of a favorable clinical outcome by Cox regression analysis when adjusted for classical predictors of poor outcome after AMI. There was no evidence of increased restenosis or atherosclerotic disease progression after BMC therapy nor any evidence of increased ventricular arrhythmias or neoplasms. In addition, regional left ventricular contractility of infarcted segments, as assessed by MRI in a subgroup of patients at 2-year follow-up, was significantly higher in the BMC group compared with the placebo group (P<0.001).
Intracoronary administration of BMC is associated with a significant reduction of the occurrence of major adverse cardiovascular events maintained for 2 years after AMI. Moreover, functional improvements after BMC therapy may persist for at least 2 years. Larger studies focusing on clinical event rates are warranted to confirm the effects of BMC administration on mortality and progression of heart failure in patients with AMIs. Clinical Trial Registration- clinicaltrials.gov. Identifier: NCT00279175.
This study sought to investigate the prevalence of ventricular tachycardia after percutaneous coronary intervention (PCI) of chronic total occlusion (CTO).
PCI of a CTO is associated with improvement ...of the left ventricular ejection fraction and possibly associated with reduced mortality. However, benefits of CTO-PCI must be weighed against a higher risk of procedure-related complications. The incidence of new-onset ventricular tachycardia after a successful CTO-PCI has not been investigated so far. In this retrospective registry we seek to describe characteristics and predictors of occurrence of post-procedural ventricular tachycardias.
Between 2010 and 2015, 485 patients underwent successful CTO-PCI at Heart Center Leipzig. Of them, 342 had complete follow-up and were further analyzed. Ventricular tachycardias were detected in 9 (2.6%) patients. All of them were monomorphic ventricular tachycardias occurring in median 1 day (interquartile range IQR 0.25-4.75 days) after PCI and caused prolongation of the hospital stay. Patients with ventricular tachycardia were older, had worse left ventricular ejection fraction (mean 33.1%, SD 5.9%) and more frequently a CTO of an infarct-related artery. The target vessel was not associated with the occurrence of ventricular arrhythmias. In multivariable analysis, only impaired left ventricular systolic function was an independent predictor for procedure-related ventricular tachycardia. Mortality rates were not different between patients with or without ventricular tachycardia.
Ventricular tachycardia can occur early after CTO-PCI as possible reperfusion arrhythmia and poorer left ventricular ejection fraction is the only independent predictor for onset. Although the occurrence of ventricular tachycardia after CTO-PCI seems not to influence mortality, awareness of this possible complication and longer monitoring may be recommended.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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