Pre-hospital management,procedural performance and outcomes for primary percutaneous coronary intervention in ST-elevation myocardial infarction in the Netherlands: Insights from the Dutch cohort of the APPOSITION-III trial

Aim

The aim of this study was to achieve useful insights into pre-hospital management and procedural performance for ST-elevation myocardial infarction (STEMI) in the Netherlands by extrapolating patient characteristics, and procedural and clinical outcomes of the Dutch patient cohort from the APPOSITION-III trial.

Methods

This is a retrospective analysis from the APPOSITION-III trial with respect to the geographical borders of STEMI management. The APPOSITION-III trial was a European registry for the use of the STENTYS self-expandable stent in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). 965 Patients were enrolled mainly in the Netherlands (n = 420, 43.5?% of the overall study population), Germany (n = 165) and France (n = 131). The data from the Dutch cohort were compared with both the overall study population, and the French and German cohorts, respectively, as well as the European Society of Cardiology (ESC) STEMI guidelines.

Results

In this trial there was a wide inter-country variation on symptom-to-balloon time, 165 minutes (120–318) in the Netherlands, 270 minutes (180–650) in Germany and 360 minutes (120–480) in France, respectively. In general, a preload of dual antiplatelet therapy (DAPT) combined with heparin was more often performed in the Dutch and French cohort than in the German cohort. DAPT at discharge was high across the whole APPOSITION-III population. No important differences were seen between the different groups according to the endpoints major adverse cardiac event and stent thrombosis.

Conclusion

In the Dutch cohort of an European multicentre STEMI study (APPOSITION-III trial), the performance in terms of symptom-to-balloon time, and pre-, peri- and post-procedural medical treatment is in line with the recommendations of ESC STEMI guidelines.

     

e-Transmission of ECGs for expert consultation results in improved triage and treatment of patients with acute ischaemic chest pain by ambulance paramedics

Aims

In pre-hospital settings handled by paramedics, identification of patients with myocardial infarction (MI) remains challenging when automated electrocardiogram (ECG) interpretation is inconclusive. We aimed to identify those patients and to get them on the right track to primary percutaneous coronary intervention (PCI).

Methods and results

In the Rotterdam-Rijnmond region, automated ECG devices on all ambulances were supplemented with a modem, enabling transmission of ECGs for online expert interpretation. The diagnostic protocol for acute chest pain was modified and monitored for 1 year.Patients with an ECG that met the criteria for ST-elevation myocardial infarction (STEMI) were immediately transported to a PCI hospital. ECGs that did not meet the STEMI criteria, but showed total ST deviation ≥800?µv were transmitted for online interpretation by the ECG expert. Online supervision was offered as a service if ECGs showed conduction disorders, or had an otherwise ‘suspicious’ pattern according to the ambulance paramedics.We enrolled 1,076 patients with acute ischaemic chest pain who did not meet the automated STEMI criteria. Their mean age was 63 years; 64% were men. After online consultation, 735 (68%) patients were directly transported to a PCI hospital for further treatment. PCI within 90?min was performed in 115 patients.

Conclusion

During a 1-year evaluation of the modified pre-hospital triage protocol for patients with acute ischaemic chest pain, over 100 acute MI patients with an initially inconclusive ECG received primary PCI within 90?min. Because of these results, we decided to continue the operation of the modified protocol.

     

One-year health status outcomes of unstable angina versus myocardial infarction: a prospective, observational cohort study of ACS survivors

Background

Unstable angina (UA) patients have lower mortality and reinfarction risks than ST-elevation (STEMI) or non-ST elevation myocardial infarction (NSTEMI) patients and, accordingly, receive less aggressive treatment. Little is known, however, about the health status outcomes (angina, physical function, and quality of life) of UA versus MI patients among survivors of an ACS hospitalization.

Methods

In a cohort of 1,192 consecutively enrolled ACS survivors from two Kansas City hospitals, we evaluated the associations between ACS presentation (UA, NSTEMI, and STEMI) and one-year health status (angina, physical functioning and quality of life), one-year cardiac rehospitalization rates, and two-year mortality outcomes, using multivariable regression modeling.

Results

After multivariable adjustment for demographic, hospital, co-morbidity, baseline health status, and treatment characteristics, UA patients had a greater prevalence of angina at 1 year than STEMI patients (adjusted relative risk [RR] = 1.42; 95% CI [1.06, 1.90]) and similar rates as NSTEMI patients (adjusted RR = 1.1; 95% CI [0.85, 1.42]). In addition, UA patients fared no better than MI patients in Short Form-12 physical component scores (UA vs. STEMI score difference -0.05 points; 95% CI [-2.41, 2.3]; UA vs. NSTEMI score difference -1.91 points; 95% CI [-4.01, 0.18]) or Seattle Angina Questionnaire quality of life scores (UA vs. STEMI score difference -1.39 points; 95% CI [-5.63, 2.85]; UA vs. NSTEMI score difference -0.24 points 95% CI [-4.01, 3.54]). Finally, UA patients had similar rehospitalization rates as MI patients (UA vs. STEMI adjusted hazard ratio [HR] = 1.31; 95% CI [0.86, 1.99]; UA vs. NSTEMI adjusted HR = 1.03; 95% CI [0.73, 1.47]), despite better 2-year survival (UA vs. STEMI adjusted HR = 0.51; 95% confidence interval (CI) [0.28, 0.95]; UA vs. NSTEMI adjusted HR = 0.40; 95% CI [0.24, 0.65]).

Conclusion

Although UA patients have better survival rates, they have similar or worse one-year health status outcomes and cardiac rehospitalization rates as compared with MI patients. Clinicians should be aware of the adverse health status outcome risks for UA patients and consider close monitoring for the opportunity to improve their health status and minimize the need for subsequent rehospitalization.     

Soluble ST2 and Interleukin-33 Levels in Coronary Artery Disease: Relation to Disease Activity and Adverse Outcome

Objectives

ST2 is a receptor for interleukin (IL)-33. We investigated an association of soluble ST2 (sST2) and IL-33 serum levels with different clinical stages of coronary artery disease. We assessed the predictive value of sST2 and IL-33 in patients with stable angina, non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI).

Methods

We included 373 patients of whom 178 had stable angina, 97 had NSTEMI, and 98 had STEMI. Patients were followed for a mean of 43 months. The control group consisted of 65 individuals without significant stenosis on coronary angiography. Serum levels of sST2 and IL-33 were measured by ELISAs.

Results

sST2 levels were significantly increased in patients with STEMI as compared to patients with NSTEMI and stable angina as well as with controls. IL-33 levels did not differ between the four groups. During follow-up, 37 (10%) patients died and the combined endpoint (all cause death, MI and rehospitalisation for cardiac causes) occurred in 66 (17.6%) patients. sST2 serum levels significantly predicted mortality in the total cohort. When patients were stratified according to their clinical presentation, the highest quintile of sST2 significantly predicted mortality in patients with STEMI, but not with NSTEMI or stable coronary artery disease. sST2 was a significant predictor for the combined endpoint in STEMI patients and in patients with stable angina. Serum levels of IL-33 were not associated with clinical outcome in the total cohort, but the highest quintile of IL-33 predicted mortality in patients with STEMI.

Conclusions

Serum levels of sST2 are increased in patients with acute coronary syndromes as compared to levels in patients with stable coronary artery disease and in individuals without coronary artery disease. sST2 and IL-33 were associated with mortality in patients with STEMI but not in patients with NSTEMI or stable angina.     

Glucose challenge increases circulating progenitor cells in Asian Indian male subjects with normal glucose tolerance which is compromised in subjects with pre-diabetes: A pilot study

Background

Patients with acute myocardial infarction and newly detected abnormal glucose regulation have been shown to have a less favourable prognosis compared to patients with normal glucose regulation. The importance and timing of oral glucose tolerance testing (OGTT) in patients with acute myocardial infarction without known diabetes is uncertain. The aim of the present study was to evaluate the impact of abnormal glucose regulation classified by an OGTT in-hospital and at three-month follow-up on clinical outcome in patients with acute ST elevation myocardial infarction (STEMI) without known diabetes.

Methods

Patients (n = 224, age 58 years) with a primary percutanous coronary intervention (PCI) treated STEMI were followed for clinical events (all-cause mortality, non-fatal myocardial re-infarction, recurrent ischemia causing hospital admission, and stroke). The patients were classified by a standardised 75 g OGTT at two time points, first, at a median time of 16.5 hours after hospital admission, then at three-month follow-up. Based on the OGTT results, the patients were categorised according to the WHO criteria and the term abnormal glucose regulation was defined as the sum of impaired fasting glucose, impaired glucose tolerance and type 2-diabetes.

Results

The number of patients diagnosed with abnormal glucose regulation in-hospital and at three-month was 105 (47%) and 50 (25%), respectively. During the follow up time of (median) 33 (27, 39) months, 58 (25.9%) patients experienced a new clinical event. There were six deaths, 15 non-fatal re-infarction, 33 recurrent ischemia, and four strokes. Kaplan-Meier analysis of survival free of composite end-points showed similar results in patients with abnormal and normal glucose regulation, both when classified in-hospital (p = 0.4) and re-classified three months later (p = 0.3).

Conclusions

Patients with a primary PCI treated STEMI, without previously known diabetes, appear to have an excellent long-term prognosis, independent of the glucometabolic state classified by an OGTT in-hospital or at three-month follow-up.

Trial registration

The trial is registered at http://www.clinicaltrials.gov, NCT00926133.     

Veno-arterial extracorporeal membrane oxygenation in addition to primary PCI in patients presenting with ST-elevation myocardial infarction

Introduction

Primary percutaneous coronary intervention (pPCI) in ST-elevation myocardial infarction (STEMI) can cause great haemodynamic instability. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide haemodynamic support in patients with STEMI but data on outcome and complications are scarce.

Methods

An in-hospital registry was conducted enrolling all patients receiving VA-ECMO. Patients were analysed for medical history, mortality, neurological outcome, complications and coronary artery disease.

Results

Between 2011 and 2016, 12 patients underwent pPCI for STEMI and received VA-ECMO for haemodynamic support. The majority of the patients were male (10/12) with a median age of 63 (47–75) years and 4 of the 12 patients had a history of coronary artery disease. A cardiac arrest was witnessed in 11 patients. The left coronary artery was compromised in 8 patients and 4 had right coronary artery disease. All patients were in Killip class IV. Survival to discharge was 67% (8/12), 1?year survival was 42% (5/12), 2 patients have not yet reached the 1?year survival point but are still alive and 1 patient died within a year after discharge. All-cause mortality was 42% (5/12) of which mortality on ECMO was 33% (4/12). Patient-related complications occurred in 6 of the 12 patients: 1 patient suffered major neurological impairment, 2 patients suffered haemorrhage at the cannula site, 2 patients had limb ischaemia and 1 patient had a haemorrhage elsewhere. There were no VA-ECMO hardware malfunctions.

Conclusion

VA-ECMO in pPCI for STEMI has a high survival rate and neurological outcome is good, even when the patient is admitted with a cardiac arrest.

     

Comparison between the STENTYS self-apposing bare metal and paclitaxel-eluting coronary stents for the treatment of saphenous vein grafts (ADEPT trial)

Aims

To describe the safety and performance of STENTYS self-expandable bare metal stents (BMS) versus paclitaxel-eluting stents (PES) in saphenous vein grafts (SVGs).

Methods and Results

A randomised controlled trial was performed in four hospitals in three European countries between December 2011 and December 2013. Patients with de novo lesions (>50% stenosis) in an SVG with a diameter between 2.5–6?mm were included. Primary endpoint was late lumen loss at 6 months. Secondary endpoints included procedural success and the occurrence of major adverse cardiac events (MACE) at 12 months. A total of 57 patients were randomised to STENTYS self-apposing BMS (n = 27) or PES (n = 30). Procedural success was obtained in 89.5%. No significant differences in late lumen loss were found between BMS and PES at 6 months (0.53?mm vs 0.47; p = 0.86). MACE rates at 12 months were comparable in both groups (BMS 22.2% vs. PES 26.7%; p = 0.70).

Conclusions

Treatment of SVGs with STENTYS self-expandable stents is safe and effective. No significant differences were found in late lumen loss and MACE between BMS and PES.

     

Study protocol to investigate the effects of testosterone therapy as an adjunct to exercise rehabilitation in hypogonadal males with chronic heart failure

Background

Most studies on risk factors for development of coronary heart disease (CHD) have been based on the clinical outcome of CHD. Our aim was to identify factors that could predict the development of ECG markers of CHD, such as abnormal Q/QS patterns, ST segment depression and T wave abnormalities, in 70-year-old men, irrespective of clinical outcome.

Methods

Predictors for development of different ECG abnormalities were identified in a population-based study using stepwise logistic regression. Anthropometrical and metabolic factors, ECG abnormalities and vital signs from a health survey of men at age 50 were related to ECG abnormalities identified in the same cohort 20 years later.

Results

At the age of 70, 9% had developed a major abnormal Q/QS pattern, but 63% of these subjects had not been previously hospitalized due to MI, while 57% with symptomatic MI between age 50 and 70 had no major Q/QS pattern at age 70. T wave abnormalities (Odds ratio 3.11, 95% CI 1.18–8.17), high lipoprotein (a) levels, high body mass index (BMI) and smoking were identified as significant independent predictors for the development of abnormal major Q/QS patterns. T wave abnormalities and high fasting glucose levels were significant independent predictors for the development of ST segment depression without abnormal Q/QS pattern.

Conclusion

T wave abnormalities on resting ECG should be given special attention and correlated with clinical information. Risk factors for major Q/QS patterns need not be the same as traditional risk factors for clinically recognized CHD. High lipoprotein (a) levels may be a stronger risk factor for silent myocardial infarction (MI) compared to clinically recognized MI.     

A multi-peptide, dual-adjuvant telomerase vaccine (GX301) is highly immunogenic in patients with prostate and renal cancer

Background

Anti-tumor vaccination is a new frontier in cancer treatment applicable to immunogenic neoplasms such as prostate and renal cancers. GX301 is a vaccine constituted by four telomerase peptides and two adjuvants, Montanide ISA-51 and Imiquimod.

Objective

The aim of this study was to analyze safety and tolerability of GX301 in an open-label, phase I/II trial. Immunological and clinical responses were also evaluated as secondary endpoints.

Experimental design

GX301 was administered by intradermally injecting 500 μg of each peptide (dissolved in Montanide ISA-51) in the skin of the abdomen. Imiquimod was applied as a cream at the injection sites. The protocol included 8 administrations at days 1, 3, 5, 7, 14, 21, 35, 63. Eligible patients were affected with stage IV prostate or renal cancer resistant to conventional treatments. Patients were clinically and immunologically monitored up to 6 months from the first immunization.

Results

No grade 3–4 adverse events were observed. Evidence of vaccine-specific immunological responses was detected in 100 % of patients. Disease stabilization occurred in 4 patients. Prolonged progression-free survival and overall survival were observed in patients showing a full pattern of vaccine-specific immunological responses.

Conclusion

GX301 demonstrated to be safe and highly immunogenic. Further studies are needed to determine its clinical efficacy.     

Schwangerschaftsverlauf und geburtshilfliche Risiken bei 178 Frauen mit hereditären neuromuskulären Erkrankungen

Background

Information about pregnancy with hereditary neuromuscular disorders (NMD) is largely restricted to small case series and case reports.

Purpose

The questions whether there are increased obstetric risks and a possible influence of pregnancy on the disease are important for clinical care and genetic counseling.

Methods

We reviewed the obstetric histories of patients with myotonic dystrophy type 1 (DM1) and type 2 (DM2), Charcot–Marie–Tooth disease (CMT), proximal spinal muscular atrophy (SMA), limb girdle muscular dystrophy (LGMD), facioscapulohumeral muscular dystrophy (FSHD), and congenital myopathy (CM). A total of 380 pregnancies with 315 live births by 178 patients were documented.

Results and conclusion

The number of miscarriages was not increased. Preterm births, vaginal operations, and cesarean sections were increased in DM1 and SMA, while abnormal fetal presentation was observed significantly more frequently in DM1, LGMD, and chair-bound patients. Neonatal outcome was favorable in all NMD, but DM1 with congenitally affected infants. A marked worsening of pregnancy on the disease course was reported mainly by LGMD patients.     

Safety and efficacy of thrombectomy in patients undergoing primary percutaneous coronary intervention for Acute ST elevation MI: A Meta-Analysis of Randomized Controlled Trials

Background

Clinical trials comparing thrombectomy devices with conventional percutaneous coronary interventions (PCI) in patients with acute ST elevation myocardial infarction (STEMI) have produced conflicting results. The objective of our study was to systematically evaluate currently available data comparing thrombectomy followed by PCI with conventional PCI alone in patients with acute STEMI.

Methods

Seventeen randomized trials (n = 3,909 patients) of thrombectomy versus PCI were included in this meta-analysis. We calculated the summary odds ratios for mortality, stroke, post procedural myocardial blush grade (MBG), thrombolysis in myocardial infarction (TIMI) grade flow, and post procedural ST segment resolution (STR) using random-effects and fixed-effects models.

Results

There was no difference in risk of 30-day mortality (44/1914 vs. 50/1907, OR 0.84, 95% CI 0.54-1.29, P = 0.42) among patients randomized to thrombectomy, compared with conventional PCI. Thrombectomy was associated with a significantly greater likelihood of TIMI 3 flow (1616/1826 vs. 1533/1806, OR 1.41, P = 0.007), MBG 3 (730/1526 vs. 486/1513, OR 2.42, P < 0.001), STR (923/1500 vs. 715/1494, OR 2.30, P < 0.001), and with a higher risk of stroke (14/1403 vs. 3/1413, OR 2.88, 95% CI 1.06-7.85, P = 0.04). Outcomes differed significantly between different device classes with a trend towards lower mortality with manual aspiration thrombectomy (MAT) (21/949 vs.36/953, OR 0.59, 95% CI 0.35-1.01, P = 0.05), whereas mechanical devices showed a trend towards higher mortality (20/416 vs.10/418, OR 2.07, 95% CI 0.95-4.48, P = 0.07).

Conclusions

Thrombectomy devices appear to improve markers of myocardial perfusion in patients undergoing primary PCI, with no difference in overall 30-day mortality but an increased likelihood of stroke. The clinical benefits of thrombectomy appear to be influenced by the device type with a trend towards survival benefit with MAT and worsening outcome with mechanical devices.     

Takotsubo cardiomyopathy: serious early complications and two-year mortality – a 101 case study

Background

Takotsubo cardiomyopathy (TTC) is characterised by transient contractility disturbances of the apex of the left ventricle.

Methods

We enrolled 101 patients from the northern-eastern part of Poland in the years 2008–2012 who were hospitalised for TCC. The control group consisted of female patients diagnosed with anterior myocardial infarction with ST-segment elevation (anterior STEMI) (n = 101).

Results

89?% of the study group were women. Patients with TTC had diabetes (12.6?% vs 29.7?%; p = 0.002) and hyperlipidaemia (36.8?% vs 64.4?%; p = 0.0001) significantly less frequently, and better kidney function assessed by estimated glomerular filtration rate versus patients with anterior STEMI (74.52?% vs 64.30?%; p = 0.004). In the TTC group there were more patients with chronic obstructive pulmonary disease (11.6?% vs 1.0?%; p = 0.002) and thyroid disturbances, especially hyperthyroidism (23.4?% vs 11.0?%; p = 0.021). In patients with TTC sudden cardiac arrest, pulmonary oedema and cardiogenic shock were observed less frequently than in the control group (14.7?% vs 30.7?%; p = 0.0078). Hospitalisations in TTC patients were less frequently complicated by pneumonia (20.0?% vs 35.6?%; p = 0.0148) and urinary infection (4.2?% vs 21.8?%; p = 0.0003). Cardiac rupture occurred in 3 patients with TTC and in 1 with anterior STEMI. In-hospital mortality was significantly lower in the group with TTC. Also, mortality at 30 days, 3 months, 1 year and 2.5 years was significantly lower in patients with TTC than in patients with MI (p = 0.035; p = 0.0226; p = 0.0075; p = 0.009).

Conclusions

Previously considered to be a benign syndrome, TTC should be reconsidered as a clinical condition at risk for serious complications such as cardiac arrest, cardiogenic shock, pulmonary oedema and cardiac rupture leading to death and causing substantial early hazard. The prognosis in TTC is significantly better than in patients with anterior STEMI.

     

Association of admission testosterone level with ST-segment resolution in male patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

Background

Low level of testosterone may be associated with cardiovascular diseases in men, as some evidence suggests a protective role for testosterone in cardiovascular system. Little is known about the possible role of serum testosterone in response to reperfusion therapy in ST-elevation myocardial infarction (STEMI) and its relationship with ST-segment recovery. The present study was conducted to evaluate the association of serum testosterone levels with ST-segment resolution following primary percutaneous coronary intervention (PPCI) in male patients with acute STEMI.

Methods

Forty-eight men (mean age 54.55 ± 12.20) with STEMI undergoing PPCI were enrolled prospectively. Single-lead ST segment resolution in the lead with maximum baseline ST-elevation was measured and patients were divided into two groups according to the degree of ST-segment resolution: complete (> or =50%) or incomplete (<50%). The basic and demographic data of all patients, their left ventricular ejection fraction (LVEF) and laboratory findings including serum levels of free testosterone and cardiac enzymes were recorded along with angiographic finding and baseline TIMI (Thrombolysis in Myocardial Infarction) flow and also in-hospital complications and then these variables were compared between two groups.

Results

A complete ST-resolution (≥50%) was observed in 72.9% of the patients. The serum levels of free testosterone (P = 0.04), peak cardiac troponin (P = 0.03) were significantly higher and hs-CRP (P = 0.02) were lower in patients with complete ST-resolution compared to those with incomplete ST-resolution. In-hospital complications were observed in 31.2% of patients. The patients with a lower baseline TIMI flow (P = 0.03) and those who developed complications (P = 0.04) had lower levels of free testosterone. A significant positive correlation was observed between the left ventricular function and serum levels of free testosterone (P = 0.01 and r = +0.362).

Conclusion

This study suggests that in men with STEMI undergoing PPCI, higher serum levels of testosterone are associated with a better reperfusion response, fewer complications and a better left ventricular function.

     

Systematic adjudication of myocardial infarction end-points in an international clinical trial

Background

Clinical events committees (CEC) are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected end-point (post-enrolment) myocardial infarction (MI) in the large Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial.

Methods

The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. A central adjudication process was established prospectively to identify all suspected MIs and adjudicate events based on protocol definitions of MI. Suspected MIs were identified by systematic review of data collection forms, cardiac enzyme results, and electrocardiograms. Two physicians independently reviewed all suspected events. If they disagreed whether a MI had occurred, a committee of cardiologists adjudicated the case.

Results

The CEC identified 5005 patients with suspected infarction (46%), of which 1415 (28%) were adjudicated as end-point infarctions. As expected, the process identified more end-point events than did the site investigators. Absolute and relative treatment effects of eptifibatide were smaller when using CEC-determined MI rates rather than site investigator-determined rates. The site-investigator reporting of MI and the CEC assessment of MI disagreed in 20% of the cases reviewed by the CEC.

Conclusions

End-point adjudication by a CEC is important, to provide standardised, systematic, independent, and unbiased assessment of end-points, particularly in trials that span geographic regions and clinical practice settings. Understanding the CEC process used is important in the interpretation of trial results and event rates.     

Rationale and design of the Edwards SAPIEN-3 periprosthetic leakage evaluation versus Medtronic CoreValve in transfemoral aortic valve implantation (ELECT) trial

Background and objectives

Periprosthetic aortic regurgitation (PPR) after transcatheter aortic valve implantation (TAVI) remains an important issue associated with impaired long-term outcomes. The current randomised study aims to evaluate potential differences between the balloon-expandable Edwards SAPIEN-3 and the self-expanding Medtronic CoreValve system with the main focus on post-TAVI PPR by means of novel imaging endpoints, and an additional focus on other clinical endpoints.

Endpoints

The primary endpoint of this study is quantitative assessment of the severity of post-procedural PPR using cardiac magnetic resonance imaging. Several other novel imaging modalities (X-ray contrast angiography, echocardiography) are used as secondary imaging modalities for the assessment of PPR following TAVI. Secondary objectives of the study include clinical outcomes such as cerebral and kidney injury related to TAVI, and quality of life.

Methods and design

The ELECT study is a single-centre, prospective, two-armed randomised controlled trial. For the purpose of this study, 108 consecutive adult patients suitable for transfemoral TAVI will be randomly allocated to receive the SAPIEN-3 (n = 54) or the CoreValve system (n = 54).

Discussion

The ELECT trial is the first randomised controlled trial to quantitatively compare the extent of post-TAVI PPR between the SAPIEN-3 and CoreValve. Furthermore, it will evaluate potential differences between the two prostheses with regard to mid-term clinical outcome and quality of life.

     

Effect of Metformin Treatment on Lipoprotein Subfractions in Non-Diabetic Patients with Acute Myocardial Infarction: A Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) Trial

Objective

Metformin affects low density lipoprotein (LDL) and high density (HDL) subfractions in the context of impaired glucose tolerance, but its effects in the setting of acute myocardial infarction (MI) are unknown. We determined whether metformin administration affects lipoprotein subfractions 4 months after ST-segment elevation MI (STEMI). Second, we assessed associations of lipoprotein subfractions with left ventricular ejection fraction (LVEF) and infarct size 4 months after STEMI.

Methods

371 participants without known diabetes participating in the GIPS-III trial, a placebo controlled, double-blind randomized trial studying the effect of metformin (500 mg bid) during 4 months after primary percutaneous coronary intervention for STEMI were included of whom 317 completed follow-up (clinicaltrial.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01217307","term_id":"NCT01217307"}}NCT01217307). Lipoprotein subfractions were measured using nuclear magnetic resonance spectroscopy at presentation, 24 hours and 4 months after STEMI. (Apo)lipoprotein measures were obtained during acute STEMI and 4 months post-STEMI. LVEF and infarct size were measured by cardiac magnetic resonance imaging.

Results

Metformin treatment slightly decreased LDL cholesterol levels (adjusted P = 0.01), whereas apoB remained unchanged. Large LDL particles and LDL size were also decreased after metformin treatment (adjusted P<0.001). After adjustment for covariates, increased small HDL particles at 24 hours after STEMI predicted higher LVEF (P = 0.005). In addition, increased medium-sized VLDL particles at the same time point predicted a smaller infarct size (P<0.001).

Conclusion

LDL cholesterol and large LDL particles were decreased during 4 months treatment with metformin started early after MI. Higher small HDL and medium VLDL particle concentrations are associated with favorable LVEF and infarct size.     

Comparison of embedded and added motor imagery training in patients after stroke: results of a randomised controlled pilot trial

Background

Motor imagery (MI) when combined with physiotherapy can offer functional benefits after stroke. Two MI integration strategies exist: added and embedded MI. Both approaches were compared when learning a complex motor task (MT): 'Going down, laying on the floor, and getting up again'.

Methods

Outpatients after first stroke participated in a single-blinded, randomised controlled trial with MI embedded into physiotherapy (EG1), MI added to physiotherapy (EG2), and a control group (CG). All groups participated in six physiotherapy sessions. Primary study outcome was time (sec) to perform the motor task at pre and post-intervention. Secondary outcomes: level of help needed, stages of MT-completion, independence, balance, fear of falling (FOF), MI ability. Data were collected four times: twice during one week baseline phase (BL, T0), following the two week intervention (T1), after a two week follow-up (FU). Analysis of variance was performed.

Results

Thirty nine outpatients were included (12 females, age: 63.4 ± 10 years; time since stroke: 3.5 ± 2 years; 29 with an ischemic event). All were able to complete the motor task using the standardised 7-step procedure and reduced FOF at T0, T1, and FU. Times to perform the MT at baseline were 44.2 ± 22s, 64.6 ± 50s, and 118.3 ± 93s for EG1 (N = 13), EG2 (N = 12), and CG (N = 14). All groups showed significant improvement in time to complete the MT (p < 0.001) and degree of help needed to perform the task: minimal assistance to supervision (CG) and independent performance (EG1+2). No between group differences were found. Only EG1 demonstrated changes in MI ability over time with the visual indicator increasing from T0 to T1 and decreasing from T1 to FU. The kinaesthetic indicator increased from T1 to FU. Patients indicated to value the MI training and continued using MI for other difficult-to-perform tasks.

Conclusions

Embedded or added MI training combined with physiotherapy seem to be feasible and benefi-cial to learn the MT with emphasis on getting up independently. Based on their baseline level CG had the highest potential to improve outcomes. A patient study with 35 patients per group could give a conclusive answer of a superior MI integration strategy.

Trial Registration

ClinicalTrials.gov: NCT00858910     

A comparison of clinical outcomes of Chinese sirolimus-eluting stents versus foreign sirolimus-eluting stents for the treatment of coronary artery disease

Background

Chinese sirolimus-eluting stents (SES) have been widely used in recent years. However, the comparison of clinical outcomes between Chinese and foreign SES remains unknown.

Objectives

To compare the outcomes of Chinese SES (Firebird) with foreign SES (Cypher Select) in the treatment of patients undergoing percutaneous coronary intervention (PCI).

Methods

4000 consecutive patients treated with SESs from January 2008 to December 2009 were included in this study. Based on the differences of the stents, the patients were divided into a Chinese SES group (Firebird; n = 2008) and a foreign SES group (Cypher Select; n = 1992). Outcomes were monitored for 1 year. The primary clinical endpoint was major adverse cardiac events (MACE): a composite of death, non-fatal myocardial infarction (MI) and target-vessel revascularisation (TVR).

Results

No differences were observed in the incidence of MACE (17.8% vs. 18.6%, p = 0.514) and TVR rate (9.0% vs. 8.6%, p = 0.632) during 1-year follow-up.

Conclusions

Chinese SES and foreign SES have similar effects on 1-year clinical outcomes and safety.     

Randomized placebo-controlled trial on azithromycin to reduce the morbidity of bronchiolitis in Indigenous Australian infants: rationale and protocol

Background

Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux.

Methods/design

The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study.

Discussion

The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol.

Trial registration number

ClinicalTrials (NCT): NCT01031667     

A benefit-finding intervention for family caregivers of persons with Alzheimer disease: study protocol of a randomized controlled trial

Background

Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarct-area is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA).

Methods

Patients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded.

Results

The primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18-0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051).

Conclusion

We demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability.

Trial registration

ClinicalTrials.gov: NCT00149591.