Guideline adherence in the use of coronary angiography in patients presenting at the emergency department without myocardial infarction - Results from the German ENLIGHT-KHK project.

Background: For patients with acute myocardial infarction (AMI), direct coronary angiography (CA) is recommended, while for non-AMI patients, the diagnostic work-up depends on clinical criteria. This analysis provides initial prospective German data for the degree of guideline-adherence (GL) in the use of CA on non-AMI patients presenting at the emergency department (ED) with suspected acute coronary syndrome (ACS) according to the 2015 ESC-ACS-GL. Furthermore the implications of the application of the 2020 ESC-ACS-GL recommendations were evaluated. Methods: Patient symptoms were identified using a standardized questionnaire; medical history and diagnostic work-up were acquired from health records. In accordance with the 2015 ESC-ACS-GL, CA was considered GL-adherent if intermediate risk criteria (IRC) were present or non-invasive, image-guided testing (NIGT) was pathological. Results: Between January 2019 and August 2021, 229 patients were recruited across seven centers. Patients presented with chest pain, dyspnea, and other symptoms in 66.7%, 16.2% and 17.1%, respectively, were in mean 66.3 ± 10.5 years old, and 36.3% were female. In accordance with the 2015 ESC-ACS-GL, the use of CA was GL-adherent for 64.0% of the patients. GL-adherent compared to non-adherent use of CA resulted in revascularization more often (44.5% vs. 17.1%, p < 0.001). Applying the 2020 ESC-ACS-GL, 20.4% of CA would remain GL-adherent. Conclusions: In the majority of cases, the use of CA was adherent to the 2015 ESC-ACS-GL. With regard to the 2020 and 2023 ESC-ACS-GL, efforts to expand the utilization of NIGT are crucial, especially as GL-adherent use of CA is more likely to result in revascularization.(German Clinical Trials Register DRKS00015638; https://drks.de/search/de/trial/DRKS00015638; (registration date: 19 February 2019)).

Evaluation of the guideline-adherence of coronary angiography in patients with suspected chronic coronary syndrome - Results from the German prospective multicentre ENLIGHT-KHK project.

Background: With 900'000 coronary angiographies (CA) per year, Germany has the highest annual per capita volume in Europe. Until now there are no prospective clinical data on the degree of guideline-adherence in the use of CA in patients with suspected chronic coronary syndrome (CCS) in Germany. Methods: Between January 2019 and August 2021, 458 patients with suspected CCS were recruited in nine German centres. Guideline-adherence was evaluated according to the current European Society of Cardiology and German guidelines. Pre-test probability (PTP) for CAD was determined using age, gender, and a standardized patient questionnaire to identify symptoms. Data on the diagnostic work-up were obtained from health records. Results: Patients were in mean 66.6 years old, male in 57.3 %, had known CAD in 48.4 % and presented with typical, atypical, non-anginal chest pain or dyspnoea in 35.7 %, 41.3 %, 23.0 % and 25.4 %, respectively. PTP according to the European guidelines was in mean 24.2 % (11.9 %-36.5 % 95 % CI). 20.9 % of the patients received guideline-recommended preceding non-invasive image guided testing. The use of CA was adherent to the European and German guideline recommendations in 20.4 % and 25.4 %, respectively. In multivariate-analysis, arterial hypertension and prior revascularization were predictors of guideline non-adherence. Conclusion: These are the first prospective clinical data which demonstrated an overall low degree of guideline-adherence in the use of CA in patients with suspected CCS in the German health care setting. To improve adherence rates, the availability of and access to non-invasive image guided testing needs to be strengthened. (German Clinical Trials Registry DRKS00015638 - Registration Date: 19.02.2019).

Distal Transradial Access for Coronary Angiography and Interventions in Everyday Practice: Data From the TRIANGLE Registry (TwitteR Initiated registry for coronary ANgiography in Germany via distaL radial accEss).

INTRODUCTION: Transradial access (TRA) has become the primary route for coronary angiography (CAG) and percutaneous coronary interventions (PCI). Recently a new puncture site more distally in the area of the anatomical snuffbox has been described. With this multicenter registry, we wish to demonstrate the feasibility and safety of the distal radial access (dRA). METHODS: Between December 2018 and May 2019 all patients with a planned CAG or PCI via dRA in three cardiology centers in Germany were entered into this registry. Procedural data, puncture success, crossover rate and complications were registered. Proximal and distal radial artery patency were examined by ultrasound within 48 h. RESULTS: A total of 327 patients were enrolled (mean age: 69 ± 12 years, 69% male gender, 49% PCI), in 5 cases bilateral distal puncture was performed. Puncture success, defined as completed sheath placement was high (N = 316/332, 95%) and the crossover rate was low (27/332, 8%). The rate of proximal radial artery occlusion after 1-48 h was low (2/332 1%), the rate of occlusion at the distal puncture site was also very low (3/332, 1%). Major complications were not encountered. CONCLUSION: Coronary angiography and interventions via the distal transradial access in the area of the anatomical snuffbox can be performed with a high rate of success and safety. This data suggests a reduced rate of radial artery occlusion compared to previously reported data after cannulation via the standard forearm radial artery puncture site. Randomized studies are needed to further investigate these results. TRIAL REGISTRATION: This study was registered in the German registry for clinical trials: DRKS00017110, retrospectively on 07.May 2019.

Left Ventricular Hypertrabeculation Is Not Associated With Cardiovascular Morbity or Mortality: Insights From the Eurocmr Registry.

Aim: Left ventricular non-compaction (LVNC) is perceived as a rare high-risk cardiomyopathy characterized by excess left ventricular (LV) trabeculation. However, there is increasing evidence contesting the clinical significance of LV hyper-trabeculation and the existence of LVNC as a distinct cardiomyopathy. The aim of this study is to assess the association of LV trabeculation extent with cardiovascular morbidity and all-cause mortality in patients undergoing clinical cardiac magnetic resonance (CMR) scans across 57 European centers from the EuroCMR registry. Methods and Results: We studied 822 randomly selected cases from the EuroCMR registry. Image acquisition was according to international guidelines. We manually segmented images for LV chamber quantification and measurement of LV trabeculation (as per Petersen criteria). We report the association between LV trabeculation extent and important cardiovascular morbidities (stroke, atrial fibrillation, heart failure) and all-cause mortality prospectively recorded over 404 ± 82 days of follow-up. Maximal non-compaction to compaction ratio (NC/C) was mean (standard deviation) 1.81 ± 0.67, from these, 17% were above the threshold for hyper-trabeculation (NC/C > 2.3). LV trabeculation extent was not associated with increased risk of the defined outcomes (morbidities, mortality, LV CMR indices) in the whole cohort, or in sub-analyses of individuals without ischaemic heart disease, or those with NC/C > 2.3. Conclusion: Among 882 patients undergoing clinical CMR, excess LV trabeculation was not associated with a range of important cardiovascular morbidities or all-cause mortality over ~12 months of prospective follow-up. These findings suggest that LV hyper-trabeculation alone is not an indicator for worse cardiovascular prognosis.

Coronary computed tomography angiography (CCTA) in patients with suspected stable coronary artery disease (CAD): diagnostic impact and clinical consequences in the German Cardiac CT Registry depending on stress test results.

To evaluate diagnostic impact of clinical use of coronary computed tomography angiography (CCTA) in patients with suspected stable coronary artery disease (CAD) and its consequences in daily practice for patient management, depending on stress test results in daily practice. Between 2009 and 2014 of a total population of 1352 patients of the German Cardiac Computed Tomography (CT) Registry who had previously undergone stress tests, CCTA visualizations were carried out on the coronary arteries with suspected stable CAD. Patients were divided into three groups according to stress test results: Group 1 with inconclusive (n = 178, 13.2%), Group 2 with ischemia in stress test (n = 372, 27.5%) and Group 3 without ischemia in stress test (n = 802, 59.3%). The test of preference was the stress electrocardiogram (ECG), which was performed more frequently in patients without ischemia in stress test as compared to those with ischemia (96.3% vs. 93.0%, p = 0.015). The incidence of detected obstructive CAD was lower in patients with suggested ischemia in stress test as compared to patients with inconclusive results (14.1% vs. 21.1%, p = 0.037). There was no difference in the incidence of an obstructive CAD in patients with and without ischemia in stress test (14.1% vs. 15.8%, p = 0.440). CCTA is a reliable, non-invasive option for ruling-out obstructive CAD irrespective of the stress test result.

Long-term clinical outcome after intracoronary application of bone marrow-derived mononuclear cells for acute myocardial infarction: migratory capacity of administered cells determines event-free survival.

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.

European Cardiovascular Magnetic Resonance (EuroCMR) registry--multi national results from 57 centers in 15 countries.

BACKGROUND: The EuroCMR registry sought to evaluate indications, image quality, safety and impact on patient management of clinical routine CMR in a multi-national European setting. Furthermore, interim analysis of the specific protocols should underscore the prognostic potential of CMR. METHODS: Multi-center registry with consecutive enrolment of patients in 57 centers in 15 countries. More than 27000 consecutive patients were enrolled. RESULTS: The most important indications were risk stratification in suspected CAD/Ischemia (34.2%), workup of myocarditis/cardiomyopathies (32.2%), as well as assessment of viability (14.6%). Image quality was diagnostic in more than 98% of cases. Severe complications occurred in 0.026%, always associated with stress testing. No patient died during or due to CMR. In 61.8% CMR findings impacted on patient management. Importantly, in nearly 8.7% the final diagnosis based on CMR was different to the diagnosis before CMR, leading to a complete change in management. Interim analysis of suspected CAD and risk stratification in HCM specific protocols revealed a low rate of adverse events for suspected CAD patients with normal stress CMR (1.0% per year), and for HCM patients without LGE (2.7% per year). CONCLUSION: The most important indications in Europe are risk stratification in suspected CAD/Ischemia, work-up of myocarditis and cardiomyopathies, as well as assessment of viability. CMR imaging is a safe procedure, has diagnostic image quality in more than 98% of cases, and its results have strong impact on patient management. Interim analyses of the specific protocols underscore the prognostic value of clinical routine CMR in CAD and HCM.

MR-IMPACT II: Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary artery disease Trial: perfusion-cardiac magnetic resonance vs. single-photon emission computed tomography for the detection of coronary artery disease: a comparative multicentre, multivendor trial.

AIMS: Perfusion-cardiac magnetic resonance (CMR) has emerged as a potential alternative to single-photon emission computed tomography (SPECT) to assess myocardial ischaemia non-invasively. The goal was to compare the diagnostic performance of perfusion-CMR and SPECT for the detection of coronary artery disease (CAD) using conventional X-ray coronary angiography (CXA) as the reference standard. METHODS AND RESULTS: In this multivendor trial, 533 patients, eligible for CXA or SPECT, were enrolled in 33 centres (USA and Europe) with 515 patients receiving MR contrast medium. Single-photon emission computed tomography and CXA were performed within 4 weeks before or after CMR in all patients. The prevalence of CAD in the sample was 49%. Drop-out rates for CMR and SPECT were 5.6 and 3.7%, respectively (P = 0.21). The primary endpoint was non-inferiority of CMR vs. SPECT for both sensitivity and specificity for the detection of CAD. Readers were blinded vs. clinical data, CXA, and imaging results. As a secondary endpoint, the safety profile of the CMR examination was evaluated. For CMR and SPECT, the sensitivity scores were 0.67 and 0.59, respectively, with the lower confidence level for the difference of +0.02, indicating superiority of CMR over SPECT. The specificity scores for CMR and SPECT were 0.61 and 0.72, respectively (lower confidence level for the difference: -0.17), indicating inferiority of CMR vs. SPECT. No severe adverse events occurred in the 515 patients. CONCLUSION: In this large multicentre, multivendor study, the sensitivity of perfusion-CMR to detect CAD was superior to SPECT, while its specificity was inferior to SPECT. Cardiac magnetic resonance is a safe alternative to SPECT to detect perfusion deficits in CAD.

Superior diagnostic performance of perfusion-cardiovascular magnetic resonance versus SPECT to detect coronary artery disease: The secondary endpoints of the multicenter multivendor MR-IMPACT II (Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary Artery Disease Trial).

BACKGROUND: Perfusion-cardiovascular magnetic resonance (CMR) is generally accepted as an alternative to SPECT to assess myocardial ischemia non-invasively. However its performance vs gated-SPECT and in sub-populations is not fully established. The goal was to compare in a multicenter setting the diagnostic performance of perfusion-CMR and gated-SPECT for the detection of CAD in various populations using conventional x-ray coronary angiography (CXA) as the standard of reference. METHODS: In 33 centers (in US and Europe) 533 patients, eligible for CXA or SPECT, were enrolled in this multivendor trial. SPECT and CXA were performed within 4 weeks before or after CMR in all patients. Prevalence of CAD in the sample was 49% and 515 patients received MR contrast medium. Drop-out rates for CMR and SPECT were 5.6% and 3.7%, respectively (ns). The study was powered for the primary endpoint of non-inferiority of CMR vs SPECT for both, sensitivity and specificity for the detection of CAD (using a single-threshold reading), the results for the primary endpoint were reported elsewhere. In this article secondary endpoints are presented, i.e. the diagnostic performance of CMR versus SPECT in subpopulations such as multi-vessel disease (MVD), in men, in women, and in patients without prior myocardial infarction (MI). For diagnostic performance assessment the area under the receiver-operator-characteristics-curve (AUC) was calculated. Readers were blinded versus clinical data, CXA, and imaging results. RESULTS: The diagnostic performance (= area under ROC = AUC) of CMR was superior to SPECT (p = 0.0004, n = 425) and to gated-SPECT (p = 0.018, n = 253). CMR performed better than SPECT in MVD (p = 0.003 vs all SPECT, p = 0.04 vs gated-SPECT), in men (p = 0.004, n = 313) and in women (p = 0.03, n = 112) as well as in the non-infarct patients (p = 0.005, n = 186 in 1-3 vessel disease and p = 0.015, n = 140 in MVD). CONCLUSION: In this large multicenter, multivendor study the diagnostic performance of perfusion-CMR to detect CAD was superior to perfusion SPECT in the entire population and in sub-groups. Perfusion-CMR can be recommended as an alternative for SPECT imaging. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT00977093.

Risk of bleeding after prehospital administration of high dose tirofiban for ST elevation myocardial infarction.

BACKGROUND: In most patients with ST-elevation myocardial infarction (STEMI), antiplatelet drugs are already administrated in the ambulance, before hospital admission. We investigated the safety of prehospital initiation of a high dose of the glycoprotein IIb/IIIa inhibitor tirofiban on top of aspirin, clopidogrel and heparin. METHODS: It concerns a sub-analysis of the On-TIME 2 trial. 1398 patients were enrolled and 1275 patients (91.2%) had clinical follow up. Non CABG-related bleeding was defined according to the TIMI criteria. Logistic regression was used to determine predictors of 30-day bleeding. The independent association between bleeding and mortality (30-day and 1-year) was evaluated using Cox proportional Hazard models. RESULTS: Bleeding (major or minor) was observed in 47 patients (3.7%), with only 13 patients (1%) with major bleeding. The strongest independent determinants of bleeding were age (OR 1.05, 95% CI 1.01-1.08, p=0.011), Killip class >1 at admission (OR 2.5, 95% CI 1.2-5.3, p=0.020) and intra aortic balloon pump (IABP) use (OR 4.2, 95% CI 1.6-11.1, p=0.003). High dose tirofiban was not an independent predictor of bleeding (OR 1.7, 95% CI 0.9-3.2, p=0.116). Bleeding was associated with an increased risk of 30-day mortality (HR 5.5, 95% CI 1.6-7.8, p<0.001) and one-year mortality (HR 3.2, 95% CI 1.4-7.2, p=0.005). CONCLUSION: Prehospital use of high dose tirofiban is safe and associated with a low risk of bleeding. Age, Killip class >1, IABP use, but not high dose tirofiban are independent determinants of bleeding in STEMI patients. Bleeding is independently associated with 30-day and 1-year mortality.

Efficacy and safety of a high loading dose of clopidogrel administered prehospitally to improve primary percutaneous coronary intervention in acute myocardial infarction: the randomized CIPAMI trial.

OBJECTIVES: To compare a loading dose of 600 mg clopidogrel given in the prehospital phase versus clopidogrel administered only after the diagnostic angiogram in patients with STEMI scheduled for primary PCI. BACKGROUND: The optimal time and dose for the initiation of clopidogrel therapy in patients with STEMI scheduled for primary PCI has not been studied in prospective randomized trials. METHODS: The primary efficacy endpoint was the TIMI 2/3 patency of the infarct-related artery in the diagnostic angiography immediately prior to PCI. RESULTS: We randomized 337 patients to prehospital (n = 166) loading dose versus standard therapy (n = 171). The time interval between initiation of clopidogrel therapy and diagnostic angiography was 47 min. TIMI 2/3 patency before PCI was not different between the groups (49.3 vs. 45.1%, P = 0.5). We observed a trend towards a reduction of the combined endpoint death, re-infarction, and urgent target vessel revascularization in the prehospital-treated patients (3.0 vs. 7.0%, P = 0.09), this difference was significant if patients were classified as treated (4/161 vs. 13/174; 2.5 vs. 7.5%, P < 0.05). There was no difference in TIMI major bleeding complications (9.1 vs. 8.2%, P = 0.8). CONCLUSIONS: Early inhibition of the platelet ADP-receptor with a high loading dose of 600 mg clopidogrel given in the prehospital phase in patients with STEMI scheduled for primary PCI is safe, did not increase pre-PCI patency of the infarct vessel, but was associated with a trend towards a reduction in clinical events.

Acute adverse reactions to gadolinium-based contrast agents in CMR: multicenter experience with 17,767 patients from the EuroCMR Registry.

OBJECTIVES: The purpose of this study was to assess the frequency, manifestation, and severity of acute adverse reactions associated with administration of several gadolinium-based contrast agents to patients who underwent cardiac magnetic resonance (CMR) imaging in the EuroCMR (European Cardiovascular Magnetic Resonance) Registry multinational and multicenter setting. BACKGROUND: The frequency, manifestations, and severity of acute adverse reactions associated with gadolinium-based contrast agents in the specific setting of cardiovascular magnetic resonance have not been systematically evaluated yet. METHODS: This is a multicenter and multinational registry with consecutive enrollment of patients in 45 European centers. During the current observation, 17,767 doses of gadolinium-based contrast agent were administered to 17,767 patients. The mean dose was 25.6 ml (range 5 to 80 ml), which is equivalent to 0.128 mmol/kg (range 0.012 to 0.3 mmol/kg). RESULTS: Thirty acute adverse reactions due to contrast administration occurred (0.17%). All reactions were classified as mild according to the American College of Radiology definition. The most frequent complaints following contrast administration were rashes and hives (9 of 30), followed by nausea (7 of 30), and anxiety (6 of 30). The event rate ranged from 0.06% (linear nonionic agent gadodiamide) to 0.47% (linear ionic agent gadobenate dimeglumine). Interestingly, we also found different event rates between the three main indications for CMR imaging, ranging from 0.1% (risk stratification in suspected coronary artery disease) to 0.42% (viability in known coronary artery disease). CONCLUSIONS: The incidence of acute adverse reactions after administration of gadolinium-based contrast in the "off-label" setting of CMR in our population was not different from the incidence in the U.S. Food and Drug Administration-approved general radiology setting. Thus, the off-label use of gadolinium-based contrast in CMR should be regarded as safe concerning the frequency, manifestation, and severity of acute events.

The impact of age on effects of pre-hospital initiation of high bolus dose of tirofiban before primary angioplasty for ST-elevation myocardial infarction.

PURPOSE: Glycoprotein IIb/IIIa inhibitors are favourable in ST-elevation myocardial infarction (STEMI) patients, and the additional value of early pre-hospital high bolus dose tirofiban has recently been established. The aim of this study was to determine the impact of age on myocardial reperfusion and clinical outcomes of pre-hospital administration of high bolus dose tirofiban. METHODS: This is a pre-specified sub-analysis of the multicentre, double-blind, placebo-controlled, randomised On-TIME 2 trial and it's open label phase. The primary endpoint was mean residual ST segment deviation 1 h after primary PCI and was evaluated in three age groups. RESULTS: Of the 466 patients in the highest tertile (≥68 years), median age was 74.4 years (IQR 71.3-78.6 years) and 231 (50%) were randomised to tirofiban. Mean residual ST segment deviation 1 h after PCI was significantly lower in elderly patients pre-treated with tirofiban compared to elderly patients without tirofiban pre-treatment (4.2 ± 5.2 mm vs 6.4 ± 7.5 mm, p = 0.001). Furthermore, elderly patients pre-treated with tirofiban had a non-significantly higher rate of 30-day major or minor bleeding compared to elderly patients without tirofiban pre-treatment (14.2% vs 9.0%, p = 0.088). 30-day net adverse clinical events in elderly patients with- or without tirofiban was not significantly different (11.9% vs 15.2%, p = 0.300). CONCLUSION: The effect of pre-hospital initiation of high bolus dose tirofiban on myocardial reperfusion, as determined by ST-segment resolution is highest in the elderly patients. However, this was associated with a trend towards more bleeding complications, resulting in a balanced clinical effect after 30-day follow-up. Future studies should evaluate whether the elderly STEMI patient may benefit from highly effective and safer antiplatelet therapy.

Maladaptive hypertrophy after acute myocardial infarction positive effect of bone marrow-derived stem cell therapy on regional remodeling measured by cardiac MRI.

OBJECTIVE: In the aftermath of myocardial infarction, increased loading conditions will trigger hypertrophy of viable myocardium. This in turn causes deterioration of regional contractility. Cardiac magnetic resonance imaging (cMRI) allows the exact differentiation of viable and infarcted myocardium and therefore the measurement of regional wall thickness and function. Bone marrow-derived stem cell (BMC) transfer has been shown to improve global function and remodeling. The present study examines the effect of BMC transfer on regional remodeling and function after myocardial infarction by cMRI. DESIGN: Fifty-four patients of the MR substudy of the REPAIR-AMI trial have been studied at baseline and 12-month follow-up. Enddiastolic wall thickness (EDWT) and wall thickening (WT%) have been measured on SSFP cine sequences. RESULTS: Enddiastolic wall thickness decreased in both placebo and BMC groups in viable as well as infarcted segments. The effect was largest in the pre-specified subgroup of patients below the median EF of 48.9% (infarcted segments -1.14 mm Placebo vs. -1.91 mm BMC, p for interaction 0.01, remote segments -0.19 mm Placebo vs. -0.94 mm BMC, p for interaction 0.00001). Corrected for baseline values BMC therapy yielded smaller EDWT at 12 months in infarcted and remote segments (infarcted 7.58 mm Placebo vs. 6.13 mm BMC p = 0.0001, remote 8.76 mm Placebo vs. 7.32 mm BMC, p = 0.0001). This was associated with better contractility within the infarcted segments among BMC patients (WT% 24.17% Placebo vs. 49.31% BMC, p = 0.0001). The WT% was inversely correlated with EDWT (r = -0.37, p = 0.0001). CONCLUSION: Bone marrow-derived stem cell therapy yields smaller EDWT when compared with placebo patients suggesting a positive effect on maladaptive hypertrophy of viable myocardium. This notion is supported by the enhanced regional contractility within the BMC group which is inversely correlated with EDWT.

MEDAFI-Trial (Micro-embolization during ablation of atrial fibrillation): comparison of pulmonary vein isolation using cryoballoon technique vs. radiofrequency energy.

AIMS: Cerebral embolism is a possible serious complication during catheter ablation of atrial fibrillation (AF). The purpose of this prospective pilot study was to analyse the incidence and possible impact of cryo ablation on cerebral lesions and possible differences to radiofrequency (RF) ablation during pulmonary vein isolation (PVI). METHODS AND RESULTS: Pulmonary vein isolation was performed in 89 patients, either with the cryoballoon technique (n = 45) or with RF ablation (n = 44). Phenprocoumon was stopped 3 days before intervention and replaced by subcutaneous low-molecular-weight heparin. During the catheter procedure, an infusion of unfractionated heparin was maintained to achieve an activated clotting time (ACT) of > 300 s. Cerebral magnetic resonance imaging scans were performed 1 day before and after PVI, and at 3-month follow-up. Chronic lesions were observed in 11 patients (12.3%) before PVI without statistically significant difference between the two groups. None of the patients had neurological symptoms during or following the procedure. Seven patients (7.9%) developed acute lesions 1 day after PVI, without statistically significant difference between the group treated by cryoenergy (8.9%) and RF ablation (6.8%). Patients with acute lesions were significantly older compared with those without acute cerebral lesions. No additional cerebral lesions during follow-up were observed. CONCLUSION: A considerable portion of patients with AF but without any neurological symptoms had chronic cerebral lesions before PVI. Additional acute lesions could be added after the procedure. Both ablation techniques showed additional cerebral acute lesions with no neurological symptoms after PVI.

Facilitated reperfusion with prehospital glycoprotein IIb/IIIa inhibition: predictors of complete ST-segment resolution before primary percutaneous coronary intervention in the On-TIME 2 trial: correlates of reperfusion before primary PCI.

OBJECTIVE: The objective of this study is to evaluate the incidence, predictors, and outcome of complete ST-segment resolution (STR) during transportation after pretreatment with dual or triple antiplatelet therapy in the Ongoing Tirofiban in Myocardial Infarction Evaluation (On-TIME) 2 trial. METHODS: Patients with ST-segment elevation myocardial infarction were randomized in the ambulance to pretreatment with high-dose tirofiban (HDT) or to a control pretreatment (placebo or no HDT) on top of 600-mg clopidogrel, 500-mg aspirin, and 5000-IU unfractionated heparin. Complete STR was defined as ≥70% STR on the electrocardiogram obtained before percutaneous coronary intervention (PCI) as compared with the inclusion electrocardiogram. RESULTS: Complete STR before PCI occurred in 16.8% (n = 188/1121) and more frequently in the HDT group (19.0% vs 14.6%, P = .05). Independent predictors for complete STR before PCI were younger age (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.70-0.96, P = .01 per 10 year increase), fast diagnosis (OR, 0.97; 95% CI, 0.97-1.0, P = .004 per 15-minute increase time from symptom onset to diagnosis), longer pretreatment time (OR, 1.09; 95% CI, 1.03-1.16, P = .003 per 15-minute increase time start study medication to angiography), and randomization to HDT (OR, 1.39; 95% CI, 1.0-1.9, P = .05). Complete STR before PCI was associated with very low 30-day (0.5% vs 2.8%, P = .07) and 1-year (1.1% vs 5.0%, P = .019) mortality. CONCLUSIONS: Dual or triple antiplatelet pretreatment in the ambulance results in complete STR before PCI in 17% of patients. Fast ST-segment elevation myocardial infarction diagnosis, prehospital initiation of pretreatment early after symptom onset, and HDT independently predicted STR before PCI. Complete STR is associated with improved clinical outcome.

The golden hour of prehospital reperfusion with triple antiplatelet therapy: a sub-analysis from the Ongoing Tirofiban in Myocardial Evaluation 2 (On-TIME 2) trial early initiation of triple antiplatelet therapy.

BACKGROUND: It is known that the efficacy of thrombolytic therapy in ST-segment elevation myocardial infarction (STEMI) is highly time dependent with the best efficacy when given within the so-called golden hour. This analysis from the On-TIME 2 trial evaluated the efficacy of triple antiplatelet therapy on initial patency and ST-segment resolution (STR) in relation to time from symptom onset to first medical contact. METHODS: The On-TIME 2 trial included 1,398 consecutive STEMI patients referred for primary percutaneous coronary intervention (PCI). Patients were randomized to dual (500 mg aspirin and 600 mg clopidogrel) or triple antiplatelet (500 mg aspirin, 600 mg clopidogrel, and tirofiban 25 µg/kg bolus and 0.15 µg/kg per minute maintenance infusion for 18 hours) pretreatment in the ambulance. Primary outcome of this sub-analysis was initial patency of the infarct-related vessel and STR before PCI according to time from symptom onset to first medical contact in quartiles. In addition, the incidence of aborted myocardial infarction, defined as the absence of a rise in creatinine kinase, was assessed. RESULTS: Initial patency, STR before PCI, and the incidence of aborted myocardial infarction gradually increased with shorter time from symptom onset to first medical contact. Initial Thrombolysis in Myocardial Infarction flow was present in 21.2% in the total population and 26.2%, 21.5%, 18.1%, and 18.8% in the time quartiles, respectively (P for trend=.01). The incidence of complete STR pre-angiography was 16.6% in the total population and 23.4%, 18.2%, 14.7%, and 9.9% in the 4 quartiles, respectively (P for trend<.001). This was largely driven by the effect of triple antiplatelet therapy, which further improved initial patency and STR and led to a significantly higher incidence of aborted myocardial infarction (13.2% vs 8.7%, P=.011), especially in the patients with short duration of symptoms. CONCLUSION: Antiplatelet pretreatment before primary PCI, including a glycoprotein IIb/IIIa blocker, seems to be most effective when given shortly after symptom onset. Further studies should be performed to test this hypothesis.

Safety, efficacy, and indications of beta-adrenergic receptor blockade to reduce heart rate prior to coronary CT angiography.

For selected indications, coronary computed tomographic (CT) angiography is an established clinical technology for evaluation in patients suspected of having or known to have coronary artery disease. In coronary CT angiography, image quality is highly dependent on heart rate, with heart rate reduction to less than 60 beats per minute being important for both image quality and radiation dose reduction, especially when single-source CT scanners are used. ß-Blockers are the first-line option for short-term reduction of heart rate prior to coronary CT angiography. In recent years, multiple ß-blocker administration protocols with oral and/or intravenous application have been proposed. This review article provides an overview of the indications, efficacy, and safety of ß-blockade protocols prior to coronary CT angiography with respect to different scanner techniques. Moreover, implications for radiation exposure and left ventricular function analysis are discussed.

Prehospital triple antiplatelet therapy in patients with acute ST elevation myocardial infarction leads to better platelet aggregation inhibition and clinical outcome than dual antiplatelet therapy.

OBJECTIVE: To assess whether prehospital initiation of high-dose tirofiban in addition to high-dose clopidogrel results in more adequate inhibition of platelet aggregation (IPA) and better clinical outcome after primary percutaneous coronary intervention (PCI). METHODS: Prespecified two-centre substudy of the prospective, international, multicentre, placebo controlled Ongoing Tirofiban in Myocardial Infarction Evaluation trial 2 (On-TIME-2 trial). 648 of 964 (67%) patients in the On-TIME-2 trial with ST elevation myocardial infarction undergoing primary PCI were studied. Pre-PCI IPA after early prehospital initiation of high-bolus dose (25 µg/kg) tirofiban was compared to placebo in addition to acetylsalicylic acid, unfractionated heparin and 600 mg clopidogrel. RESULTS: IPA was measured at a median of 60 min after study medication administration. In all four tests: Fe induced platelet aggregation, ADP induced platelet aggregation, platelet function analyser (PFA)-100 (collagen-epinephrine and collagen-ADP cartridge) IPA was higher in patients pretreated with high-dose tirofiban (p<0.001 for all tests), even after >74 min of pretreatment. Patients in the highest quartile of IPA had less residual ST segment deviation 1 h post-PCI (p value for trend: p=0.001, 0.004, 0.001, 0.002 respectively). There was a significant relationship between PFA-100 (both cartridges) and major adverse cardiovascular events (MACE, p=0.028, p=0.035) and early thrombosis (p=0.009, p=0.007). CONCLUSIONS: 60 min of prehospital initiated antiplatelet treatment including high-dose tirofiban resulted in higher levels of IPA compared to pretreatment with acetylsalicylic acid and high-dose clopidogrel alone, even after longer pretreatment times. Levels of IPA were significantly related to ST resolution and MACE, including stent thrombosis. This substudy confirms the main findings of the On-TIME2 trial that clopidogrel alone is suboptimal, even at high dose and administered well in advance of primary PCI.

Pre-hospital administration of tirofiban in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: a sub-analysis of the On-Time 2 trial.

AIMS: Glycoprotein IIb/IIIa blocking agents seem to improve percutaneous coronary intervention (PCI) results in patients with ST-elevation myocardial infarction (STEMI). We aimed to compare the effect of pre-hospital administration of tirofiban in STEMI patients with and without diabetes mellitus (DM) treated with primary PCI. METHODS AND RESULTS: We performed a pre-specified sub-analysis of the randomised On-Time II trial (n=984) and it's open label run-in phase (n=414), which investigated pre-hospital administration of high dose tirofiban in STEMI patients treated with primary PCI. Two-hundred and twenty (16%) diabetic patients (known DM or Hba1C ≥6.2%) were included, 101 in the placebo group and 119 in the tirofiban group. In patients with DM, randomisation to tirofiban resulted in a lower residual ST deviation (5.1±8.5 mm vs. 6.2±5.6 mm, p=0.003), a reduced infarct size (CK 1694±1925 U/L vs. CK 2040±1829 U/L, p=0.02) and a trend towards lower one-year mortality (4.6% vs. 11.6%, p=0.07). The beneficial effects of tirofiban were more pronounced in diabetic patients compared to patients without diabetes. CONCLUSIONS: Pre-hospital administration of tirofiban in diabetic STEMI patients treated with primary PCI improves ST resolution and reduces myocardial infarct size. Tirofiban seems particularly beneficial in patients with diabetes.