[show abstract][hide abstract] ABSTRACT: Acute myocardial infarction (AMI) remains a major cause of mortality and morbidity worldwide despite the latest therapeutic advances designed to decrease myocardial injury. Preclinical and emerging clinical evidence show that the intracoronary injection of autologous bone marrow mononuclear cells (BMCs) following AMI leads to improvement in left ventricular ejection function (LVEF). In this clinical trial we will for the first time assess the effect of early (<24 h) infusion of autologous BMCs following AMI on cardiac function.
REGENERATE-AMI is a double-blind, randomised, multicentre, placebo-controlled trial to determine whether early (<24 h) intracoronary infusion of BMCs improves LVEF after AMI. The study will enrol 100 patients presenting with an anterior AMI demonstrating anterior regional wall motion abnormality. Patients will be randomised to receive intracoronary infusion of BMCs or placebo (0.9% saline). Primary endpoint will be change in LVEF at 1 year compared to baseline, measured by cardiac MRI. Secondary endpoints at 6 months include the change in global LVEF relative to baseline measured by quantitative left ventriculography and echocardiography, as well as major adverse cardiac events which is also measured at 1 year.
The study will be performed in agreement with the Declaration of Helsinki and is approved by local ethics committee (NRES Committee London West London: 07/Q0603/76).
http://clincialtrials.gov (NCT00765453). The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals.
BMJ Open 01/2014; 4(2):e004258. · 1.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to investigate the effects of baseline anaemia on the outcome in patients treated by primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction.
This study was a retrospective cohort study of 2418 patients with ST-elevation myocardial infarction treated by PPCI between January 2004 and August 2010 at a single centre. We investigated the outcome in patients with anaemia compared with that in patients with a normal haemoglobin (Hb) level. Anaemia was defined according to the WHO definition as an Hb level less than 12 g/dl for female individuals and less than 13 g/dl for male individuals. We also calculated hazard ratios using a stratified model according to the Hb level.
A total of 471 (19%) patients were anaemic at presentation. The anaemic cohort was older (72.2 vs. 62.4 years, P<0.0001) and had a higher incidence of diabetes (28 vs. 16%, P<0.0001), hypertension (57 vs. 43%, P=0.01), hypercholesterolaemia (48 vs. 40%, P=0.007), previous PCI (15 vs. 9%, P<0.0001), previous myocardial infarction (23 vs. 12%, P=0.002), and cardiogenic shock (12 vs. 5%, P<0.0001). Over a mean follow-up period of 3 years there was significantly higher all-cause mortality in the anaemic group compared with the normal Hb group (20.4 vs. 13.5%, P<0.0001). However, after adjustment for all variables using multivariate analysis, anaemia (on the basis of the WHO definitions) was found not to be an independent predictor of mortality or major adverse cardiac events over the follow-up period. Further, when we used a model stratified by g/dl, we found that there was an increased risk for adverse outcomes among men with low Hb levels. There appeared to be a threshold value of Hb (13 g/dl) associated with increased risk. Although a similar trend was observed among women, no significant difference was observed.
Patients with anaemia undergoing PPCI are at a higher risk of an adverse outcome. Anaemia is a simple and powerful marker of poor prognosis. Although anaemia (based on the WHO definitions) does not appear to be an independent predictor of all-cause mortality or major adverse cardiac events after PPCI on multivariate analysis, there appears to be a threshold value of Hb among men, below which there is an associated increased risk for PPCI.
[show abstract][hide abstract] ABSTRACT: There are limited data about the effectiveness of primary percutaneous coronary intervention (PPCI) for stent thrombosis treatment. We aimed to evaluate the prevalence and outcomes of PPCI in patients with ST elevation acute myocardial infarction (STEMI) due to stent thrombosis, and comparing the outcomes with patients treated for de novo coronary thrombosis. This was an observational cohort study of 2,935 patients who underwent PPCI from 2003 to 2011 with follow-up for a median of 3.0 years (interquartile range 1.2 to 4.6). The primary end point was the first major adverse cardiac event (MACE) defined as death, nonfatal myocardial infarction, stroke, or target vessel revascularization. Stent thrombosis overall accounted for 6.6% (194 of 2,935) of all STEMIs with a proportion that increased over time (3.3% in 2004 to 9.4% in 2011). A total of 34.5% were early, 30.9% late stent thrombosis, and 34.5% were very late stent thrombosis. Indications for the original intervention were elective in 27.8%, after acute coronary syndrome (non-STEMI or unstable angina) in 21.1%, and after PPCI in 51.1%. Patients with stent thrombosis had higher rates of hypertension, hypercholesterolemia, diabetes, renal dysfunction, and previous myocardial infarction or coronary artery bypass surgery compared with patients with native artery occlusion. MACE rates were higher in patients with stent thrombosis compared with patients with native artery occlusions (40.9%, 95% confidence interval [CI] 31.1 to 50.6 vs 15.1%, 95% CI 12.5 to 18.3; p <0.0001). The poor outcome of stent thrombosis was particularly associated with early and late stent thromboses. Very late stent thrombosis appears to be a relatively less serious event, with similar outcomes to native vessel thromboses (MACE very late stent thrombosis 16.5%, 95% CI 8.2 to 28.6 vs native 15.1%, 95% CI 12.5 to 18.3, p = 0.245). In conclusion, stent thrombosis accounts for an increasing proportion of STEMI and is associated with worse outcomes compared with native artery occlusion.
The American journal of cardiology 09/2013; · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: The severity of coronary artery narrowing is a poor predictor of functional significance, in particular in intermediate coronary lesions (30-70% diameter narrowing). The aim of this work was to compare the performance of a quantitative hyperaemic myocardial blood flow (MBF) index derived from adenosine dynamic computed tomography perfusion (CTP) imaging with that of visual CT coronary angiography (CTCA) and semi-automatic quantitative CT (QCT) in the detection of functionally significant coronary lesions in patients with stable chest pain.
CTCA and CTP were performed in 80 patients (210 analysable coronary vessels) referred to invasive coronary angiography (ICA). The MBF index (mL/100 mL/min) was computed using a model-based parametric deconvolution method. The diagnostic performance of the MBF index in detecting functionally significant coronary lesions was compared with visual CTCA and QCT. Coronary lesions with invasive fractional flow reserve of ≤0.75 were defined as functionally significant. The optimal cut-off value of the MBF index to detect functionally significant coronary lesions was 78 mL/100 mL/min. On a vessel-territory level, the MBF index had a larger area under the curve (0.95; 95% confidence interval [95% CI]: 0.92-0.98) compared with visual CTCA (0.85; 95% CI: 0.79-0.91) and QCT (0.89; 95% CI: 0.84-0.93) (both P-values <0.001). In the analysis restricted to intermediate coronary lesions, the specificity of visual CTCA (69%) and QCT (77%) could be improved by the subsequent use of the MBF index (89%).
In this proof-of-principle study, the MBF index performed better than visual CTCA and QCT in the identification of functionally significant coronary lesions. The MBF index had additional value beyond CTCA anatomy in intermediate coronary lesions. This may have a potential to support patient management.
European heart journal cardiovascular Imaging. 08/2013;
[show abstract][hide abstract] ABSTRACT: AIMS: Myocardial revascularization by either coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI) carries the risk of serious complications. Observational data suggest that outcomes may be improved by experienced operators, but there are few studies that have analysed the relationship between mortality and primary operator grade. The aim of this study was to investigate the effect of operator grade (trainee vs. consultant) upon outcomes of revascularization procedures. METHODS AND RESULTS: This was an observational study at a tertiary cardiology centre with accredited training programmes, between 2003 and 2011. A total of 22 697 consecutive patients undergoing either CABG or PCI were included. Associations between operator grade and mortality were assessed by hazard ratios, estimated by Cox regression analyses; 6689 patients underwent CABG, whereas 16 008 underwent PCI. Trainees performed 1968 (29.4%) CABG procedures and 8502 (53.1%) PCI procedures. The proportion of procedures performed by trainees declined over time for both CABG (30.2% in 2003 vs. 26.0% in 2010) and for PCI (58.1% in 2003 vs. 44.5% in 2010). In the unadjusted Cox analysis, consultant operator grade was associated with an increased 5-year mortality after both CABG [HR: 1.26 (95% CI: 1.07-1.47)] and PCI procedures [HR: 1.34 (95% CI: 1.22-1.47)] compared with a trainee operator. However, following multiple adjustment, consultant grade was no longer associated with mortality after either procedure [CABG: HR: 1.02 (95% CI: 0.87-1.20), PCI: HR: 1.08 (95% CI: 0.98-1.20)]. CONCLUSION: There was no observed detrimental effect on patient outcomes arising from procedures undertaken by trainees working in a structured training environment compared with consultants.
European Heart Journal 05/2013; · 14.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: AIM: Female sex has been associated with worse outcome after percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). We assessed the influence of female sex on the long-term outcome of patients undergoing PCI for ACS. This included an unadjusted analysis and a fully-adjusted multivariate analysis including a propensity score. METHODS: This was an observational cohort study involving 7304 patients who had PCI for ACS [ST-elevation myocardial infarction (STEMI), non-ST elevation (NSTE) ACS] between October 2003 and September 2010. We analysed the effect of female sex on outcome. RESULTS: The primary end point was all-cause mortality, which was obtained from the UK Office of National Statistics at a median follow-up of 3.2 years (IQR: 1.5-4.6). Women were significantly older and had higher rates of diabetes mellitus compared with men. Over long-term follow-up, mortality was significantly higher in women with ACS compared with men; as a whole [all ACS: odds ratio (OR) 1.351, P<0.001] or when analysed by ACS type (NSTE ACS: OR 1.260, P=0.009; STEMI: OR 1.625, P<0.001). However, after adjustment using multivariate analysis, female sex was not an independent predictor of mortality in any ACS group (all ACS: OR 0.978, P=0.772; NSTE ACS: OR 0.954, P=0.603; STEMI: OR 1.081, P=0.567). This observation remained after the incorporation of a propensity score into the multivariate analysis [OR 0.95, 95% confidence interval 0.82-1.10]. CONCLUSION: Women presenting with ACS were older and had more baseline comorbidities. Female sex, however, does not appear to be an independent risk factor for mortality in our cohort.
[show abstract][hide abstract] ABSTRACT: INTRODUCTION: Acute myocardial infarction (AMI) is a major cause of death and disability in the UK and worldwide. Presently, timely and effective reperfusion with primary percutaneous coronary intervention (PPCI) remains the most effective treatment strategy for limiting infarct size, preserving left ventricular ejection fraction (LVEF) and improving clinical outcomes. However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is currently no effective therapy. Extensive preclinical evidence exists to suggest that sodium nitrite (as a source of endogenous nitric oxide) is an effective therapeutic strategy for preventing myocardial reperfusion injury. The purpose of NITRITE-AMI is to test whether sodium nitrite reduces reperfusion injury and subsequent infarct size in patients undergoing PPCI for MI. METHODS AND DESIGN: NITRITE-AMI is a double-blind, randomised, single-centre, placebo-controlled trial to determine whether intracoronary nitrite injection reduces infarct size in patients with myocardial infarction undergoing primary angioplasty. The study will enrol 80 patients presenting with ST-elevation myocardial infarction. Patients will be randomised to receive either a bolus of intracoronary sodium nitrite or placebo (sodium chloride) at the time of PPCI. The primary outcome is infarct size assessed by creatine kinase area under the curve (AUC) over 48 h. Secondary endpoints include troponin T AUC and infarct size, LV dimensions and myocardial salvage index assessed by cardiac MR (CMR), markers of platelet reactivity and inflammation, the safety and tolerability of intracoronary nitrite, and 1 year major adverse cardiac events. ETHICS AND DISSEMINATION: The study is approved by the local ethics committee (NRES Committee London West London: 11/LO/1500) and by the Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT nr. 2010-022460-12). The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals. TRIAL REGISTRATION: United Kingdom Clinical Research Network (Study ID 12117), http://clinicaltrials.gov (NCT01584453) and Current Controlled Trials (ISRCTN:38736987).
[show abstract][hide abstract] ABSTRACT: Timely delivery of primary percutaneous coronary intervention (PPCI) is the treatment of choice for ST-segment elevation myocardial infarction (STEMI). Optimum delivery of PPCI requires an integrated network of hospitals, following a multidisciplinary, consultant-led, protocol-driven approach. We investigated whether such a strategy was effective in providing equally effective in-hospital and long-term outcomes for STEMI patients treated by PPCI within normal working hours compared with those treated out-of-hours (OOHs).
Large PPCI centre in London.
3347 STEMI patients were treated with PPCI between 2004 and 2012. The follow-up median was 3.3 years (IQR: 1.2-4.6 years).
The primary endpoint was long-term major adverse cardiac events (MACE) with all-cause mortality a secondary endpoint.
Of the 3347 STEMI patients, 1299 patients (38.8%) underwent PPCI during a weekday between 08:00 and 18:00 (routine-hours group) and 2048 (61.2%) underwent PPCI on a weekday between 18:00 and 08:00 or a weekend (OOHs group). There were no differences in baseline characteristics between the two groups with comparable door-to-balloon times (in-hours (IHs) 67.8 min vs OOHs 69.6 min, p=0.709), call-to-balloon times (IHs 116.63 vs OOHs 127.15 min, p=0.60) and procedural success. In hospital mortality rates were comparable between the two groups (IHs 3.6% vs OOHs 3.2%) with timing of presentation not predictive of outcome (HR 1.25 (95% CI 0.74 to 2.11). Over the follow-up period there were no significant differences in rates of mortality (IHs 7.4% vs OFHs 7.2%, p=0.442) or MACE (IHs 15.4% vs OFHs 14.1%, p=0.192) between the two groups. After adjustment for confounding variables using multivariate analysis, timing of presentation was not an independent predictor of mortality (HR 1.04 95% CI 0.78 to 1.39).
This large registry study demonstrates that the delivery of PPCI with a multidisciplinary, consultant-led, protocol-driven approach provides safe and effective treatment for patients regardless of the time of presentation.
[show abstract][hide abstract] ABSTRACT: Cell-based regenerative therapy treatment of cardiovascular diseases considered as irreversible, as acute myocardial infarction, chronic ischemic heart failure, non-ischemic dilated cardiomyopathy and refractory angina pectoris. Large randomized clinical trials with hard clinical endpoints are still necessary before considering cell-based regenerative therapy as a valuable alternative therapeutic option in cardiology.
[show abstract][hide abstract] ABSTRACT: AIM: Primary percutaneous coronary intervention (PPCI) produces more effective coronary reperfusion and allows immediate risk stratification compared with fibrinolysis. We investigated the safety and feasibility of very early discharge at 2 days following PPCI in selected low-risk cases. METHODS: This was a prospective observational cohort study of 2779 patients who underwent PPCI between 2004 and 2011. Patients meeting the following criteria were deemed suitable for very early discharge; TIMI III flow, left ventricle (LF) ejection fraction >40%, and rhythmic and haemodynamic stability out to 48 h. Higher-risk patients who did not fulfil these criteria were discharged later according to physician preference. All patients were offered outpatient review by a multidisciplinary team. Endpoints included 30 day readmission rates and major adverse cardiac events (MACE) out to a median of 2.8 years (IQR range: 1.3-4.4 years). RESULTS: 1309 (49.3%) PPCI patients met very early discharge criteria, of whom 1117 (85.3%) were actually discharged at 2 days. 620 (23.4%) were discharged at 3 days, and 916 (34.5%) >3 days after admission (median 5, IQR: 4-8) days). Patients discharged at 2 days were younger, and had lower rates of diabetes, renal dysfunction, multivessel coronary artery disease, previous myocardial infarction, and previous coronary artery bypass surgery, compared with patients discharged later. 30-day readmission rates for non-MACE events were 4.8%, 4.9% and 4.6% for patients discharged 2 days, 3 days and >3 days after admission, respectively. MACE rates were lowest in patients discharged at 2 days (9.6%, 95% CI 4.7% to 16.6%) compared with patients discharged at 3 days (12.3% 95% CI 6.0% to 19.2%) and >3 days (28.6% 95% CI 22.9% to 34.7%, p<0.0001) after admission. CONCLUSIONS: Our data suggest that discharge of low-risk patients 2 days after successful PPCI is feasible and safe. Over 40% of all patients with ST-elevation myocardial infarction may be suitable for early discharge with important implications for healthcare costs.
[show abstract][hide abstract] ABSTRACT: Platelets are causally involved in coronary artery obstruction in acute coronary syndromes (ACS). This cell type is unique to mammals and its production, which is unlike that of any other mammalian cell, involves polyploid nuclear change in the mother cell (megakaryocyte) and the production of anucleate cells with a log Gaussian distribution of volume. Platelets vary more in cellular volume than any other circulating blood element in mammals. Larger platelets are denser, contain more secretory granules, and are more reactive than their smaller counterparts. A causal relationship between the presence of large, dense, reactive platelets in the circulation and ACS is supported by many clinical studies. Furthermore, the results of two large, prospective, epidemiological studies have demonstrated that mean platelet volume was the strongest independent predictor of outcome in patients with acute myocardial infarction. Notably, evidence indicates that an increase in mean platelet volume in the pathogenesis of ACS can potentially overwhelm current therapeutics. The control system for the physiological and pathophysiological production of large platelets should, therefore, be researched. An understanding of this system might give rise to new therapeutics that could control platelet reactivity and thereby comprehensively prevent ACS.
[show abstract][hide abstract] ABSTRACT: The rapid translation from bench to bedside that has been seen in the application of regenerative medicine to cardiology has led to exciting new advances in our understanding of some of the fundamental mechanisms related to human biology. The first generation of cells used in phase l-ll trials (mainly bone marrow mononuclear cells) are now entering phase III clinical trials with the goal of producing a cell-based therapeutic that can change the outcome of cardiac disease. First generation cell therapy appears to have addressed safety concerns as well as showing "activity" in numerous published meta-analyses. With the knowledge gained to date, the field is moving towards the next generation of cells-the "engineered" cell-that have been developed to display a phenotype that will further enhance the myocardial repair/salvage process. This almanac review covers the latest basic research that may soon have application to humans as well as the results of the latest clinical trials.
[show abstract][hide abstract] ABSTRACT: The potential of autologous bone marrow (BM)-derived progenitor/stem cell (BMSC) therapy for cardiac repair maybe limited by patient-related factors, such as age and the disease process itself. In this exploratory analysis, we assessed the impact of age, different disease states, and granulocyte colony-stimulating factor (G-CSF) therapy on progenitor cell concentration and function in patients recruited to our clinical trials of BMSC therapy for ischaemic heart failure (IHD), dilated cardiomyopathy (DCM), and acute myocardial infarction (AMI). The concentrations of CD34+ cells and endothelial progenitor cells (EPCs) were measured in the peripheral blood (PB) and BM of 201 patients. Additionally, cell mobilization following G-CSF and the functional capability of CD34+ cells (using a colony-forming unit assay) were assessed. We found that older age was associated with a lower PB CD34+ cell concentration in the whole study group as well as blunting the effect of G-CSF on BMSC mobilization in IHD patients. Nonischaemic heart failure (DCM) was associated with a significantly higher baseline PB CD34+ and EPC concentration compared to IHD. Following G-CSF treatment, the CD34+ cell concentration was greater in the BM compared to PB, however, the PB CD34+ cells appeared to have a greater and improved (compared to baseline) functional potential. Our results suggest treatment with G-CSF improves the functional potential of mobilized circulating progenitor cells compared to those in the BM. Further work is required to determine which source of cells is best for the purposes of cardiac repair following G-CSF therapy.
Stem cells and development 07/2012; · 4.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study investigated the impact of procedural success on mortality following chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in a large cohort of patients in the drug-eluting stent era.
Despite advances in expertise and technologies, many patients with CTO are not offered PCI.
A total of 6,996 patients underwent elective PCI for stable angina at a single center (2003 to 2010), 836 (11.9%) for CTO. All-cause mortality was obtained to 5 years (median: 3.8 years; interquartile range: 2.0 to 5.4 years) and stratified according to successful chronic total occlusion (sCTO) or unsuccessful chronic total occlusion (uCTO) recanalization. Major adverse cardiac events (MACE) included myocardial infarction (MI), urgent revascularization, stroke, or death.
A total of 582 (69.6%) procedures were successful. Stents were implanted in 97.0% of successful procedures (mean: 2.3 ± 0.1 stents per patient, 73% drug-eluting). Prior revascularization was more frequent among uCTO patients: coronary artery bypass grafting (CABG) (16.5% vs. 7.4%; p < 0.0001), PCI (36.0% vs. 21.2%; p < 0.0001). Baseline characteristics were otherwise similar. Intraprocedural complications, including coronary dissection, were more frequent in unsuccessful cases (20.5% vs. 4.9%; p < 0.0001), but did not affect in-hospital MACE (3% vs. 2.1%; p = NS). All-cause mortality was 17.2% for uCTO and 4.5% for sCTO at 5 years (p < 0.0001). The need for CABG was reduced following sCTO (3.1% vs. 22.1%; p < 0.0001). Multivariate analysis demonstrated that procedural success was independently predictive of mortality (hazard ratio [HR]: 0.32 [95% confidence interval (CI): 0.18 to 0.58]), which persisted when incorporating a propensity score (HR: 0.28 [95% CI: 0.15 to 0.52]).
Successful CTO PCI is associated with improved survival out to 5 years. Adoption of techniques and technologies to improve procedural success may have an impact on prognosis.
[show abstract][hide abstract] ABSTRACT: Stem cell transplantation is emerging as a potential therapy to treat heart diseases. Promising results from early animal studies led to an explosion of small, non-controlled clinical trials that created even further excitement by showing that stem cell transplantation improved left ventricular systolic function and enhanced remodelling. However, the specific mechanisms by which these cells improve heart function remain largely unknown. A large variety of cell types have been considered to possess the regenerative ability needed to repair the damaged heart. One of the most studied cell types is the bone marrow-derived mononuclear cells and these form the focus of this review. This review article aims to provide an overview of their use in the setting of acute myocardial infarction, the challenges it faces and the future of stem cell therapy in heart disease.
[show abstract][hide abstract] ABSTRACT: To compare short and medium-term prognosis in South Asian and Caucasian patients undergoing percutaneous coronary intervention (PCI) to determine if there are ethnic differences in case death rates.
Retrospective cohort study.
A cardiology referral centre in east London.
9771 patients who underwent PCI from October 2003 to December 2007 of whom 7966 (81.5%) were Caucasian and 1805 (18.5%) were South Asian.
In-hospital major adverse cardiac events (MACE; death, myocardial infarction, stroke and target vessel revascularisation), subsequent revascularisation rates (PCI and coronary artery bypass grafting; CABG) and all-cause mortality during a median follow-up of 2.5 years (range 1.5-3.6 years).
South Asian patients were younger than Caucasian patients (59.69±0.27 vs 64.69±0.13 years, p<0.0001), and more burdened by cardiovascular risk factors, particularly type II diabetes mellitus (45.9%±1.2% vs 15.7%±0.4%, p<0.0001). The in-hospital rates of MACE were similar for South Asians and Caucasians (3.5% vs 2.8%, p=0.40). South Asians had higher rates of clinically driven PCI for restenosis and subsequent CABG, although Kaplan-Meier estimates of all-cause mortality showed no significant differences; this was regardless of whether PCI was performed post-acute coronary syndrome or as an elective procedure. The adjusted hazard of death for South Asians compared with Caucasians was 1.00 (95% CI 0.81 to 1.23).
In this large PCI cohort, the in-hospital and longer-term mortality of South Asians appeared no worse than that of Caucasians. South Asians had higher rates of restenosis and CABG during follow-up. Data suggest that the excess coronary mortality for South Asians compared with Caucasians is not explained by differences in case-fatality rates.