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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

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.

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.

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.

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. 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. 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). 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.

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.

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 mu g/kg bolus and 0.15 mu g/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 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. (Am Heart J 2010;160:1079-84.)

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 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.

Background— The aim of this study was to investigate the clinical outcome 2 years after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). Methods and Results— Using a double-blind, placebo-controlled, multicenter trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone marrow–derived progenitor cells (BMC) or placebo medium into the infarct artery 3 to 7 days after successful infarct reperfusion therapy. At 2 years, the cumulative end point of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (hazard ratio, 0.58; 95% CI, 0.36 to 0.94; P =0.025). Likewise, the combined end point death and recurrence of myocardial infarction and rehospitalization for heart failure, reflecting progression toward heart failure, was significantly reduced in the BMC group (hazard ratio, 0.26; 95% CI, 0.085 to 0.77; P =0.015). Intracoronary administration of BMC remained a significant predictor of a favorable clinical outcome by Cox regression analysis when adjusted for classical predictors of poor outcome after AMI. There was no evidence of increased restenosis or atherosclerotic disease progression after BMC therapy nor any evidence of increased ventricular arrhythmias or neoplasms. In addition, regional left ventricular contractility of infarcted segments, as assessed by MRI in a subgroup of patients at 2-year follow-up, was significantly higher in the BMC group compared with the placebo group ( P Conclusions— Intracoronary administration of BMC is associated with a significant reduction of the occurrence of major adverse cardiovascular events maintained for 2 years after AMI. Moreover, functional improvements after BMC therapy may persist for at least 2 years. Larger studies focusing on clinical event rates are warranted to confirm the effects of BMC administration on mortality and progression of heart failure in patients with AMIs. Clinical Trial Registration— clinicaltrials.gov. Identifier: NCT00279175.

Objectives The purpose of the study was to understand determinants of infarct size in a primary percutaneous intervention (PCI) population treated with pexelizumab compared with placebo. Background In the multicenter APEX-AMI (Pexelizumab in Conjunction With Angioplasty in Acute Myocardial Infarction) trial, pexelizumab did not reduce 90-day mortality. Cardiac magnetic resonance (CMR) with delayed enhancement was used in a substudy evaluating infarct size and left ventricular ejection fraction (LVEF). Methods Consecutive patients undergoing primary PCI for first myocardial infarction (MI) as part of the APEX-AMI trial were enrolled in this substudy at 5 centers. The CMR was completed on days 3 to 5 (n = 99) and day 90 (n = 83) following PCI. Central core lab-masked analyses for quantified LVEF, volumes, and infarct size by planimetry were performed. Results Patients were 60 ± 12 years of age, male (n = 83 [84%]), had similar time from symptom onset to presentation (median 2.6 h vs. 2.5 h; p = 1.0), and similar baseline ST-segment deviation (13.5 mm vs. 14 mm; p = 0.59) in both groups. Pexelizumab-treated patients had smaller infarct size (day 3 LV 10.5% vs. 16.2%, p = 0.022; day 90 LV 5.9% vs. 12.4%, p = 0.015) and higher LVEF (day 3 50.3% vs. 46.2%, p = 0.073; day 90 53.9% vs. 49.3%, p = 0.036) compared with placebo-treated patients. The median peak creatine kinase in the pexelizumab group was also significantly less than placebo (922 mg/dl vs. 1,973 mg/dl; p = 0.03). Notably, the pexelizumab group had lower Thrombolysis In Myocardial Infarction (TIMI) flow grade pre-PCI (46.9% vs. 75.0%; p = 0.018), a difference not seen in the overall APEX-AMI study. A multivariate model including baseline features and pexelizumab treatment found anterior MI location and pre-PCI TIMI flow to be significant independent predictors infarct size (p = 0.001), whereas pexelizumab was not (p = 0.29). No death, heart failure, or shock was noted in either substudy group at 90 days. Conclusions In a CMR substudy of pexelizumab in MI, baseline TIMI flow grade and anterior location were the only predictors of infarct size, with a reduction of pre-PCI TIMI flow grade 0 by 28%, leading to a 35% reduction in infarct size. (The APEX-AMI Trial; NCT00091637 )

Objectives During its German pilot phase, the EuroCMR (European Cardiovascular Magnetic Resonance) registry sought to evaluate indications, image quality, safety, and impact on patient management of routine CMR. Background CMR has a broad range of applications and is increasingly used in clinical practice. Methods This was a multicenter registry with consecutive enrollment of patients in 20 German centers. Results A total of 11,040 consecutive patients were enrolled. Eighty-eight percent of patients received gadolinium-based contrast agents. Twenty-one percent underwent adenosine perfusion, and 11% high-dose dobutamine-stress CMR. The most important indications were workup of myocarditis/cardiomyopathies (32%), risk stratification in suspected coronary artery disease/ischemia (31%), as well as assessment of viability (15%). Image quality was good in 90.1%, moderate in 8.1%, and inadequate in 1.8% of cases. Severe complications occurred in 0.05%, and were all associated with stress testing. No patient died during or due to CMR. In nearly two-thirds of patients, CMR findings impacted patient management. Importantly, in 16% of cases the final diagnosis based on CMR was different from the diagnosis before CMR, leading to a complete change in management. In more than 86% of cases, CMR was capable of satisfying all imaging needs so that no further imaging was required. Conclusions CMR is frequently performed in clinical practice in many participating centers. The most important indications are workup of myocarditis/cardiomyopathies, risk stratification in suspected coronary artery disease/ischemia, and assessment of viability. CMR imaging as used in the centers of the pilot registry is a safe procedure, has diagnostic image quality in 98% of cases, and its results have strong impact on patient management.

Summary. Background: No randomized comparisons are yet available evaluating the effect of pre-hospital high dose tirofiban on the incidence of early stent thrombosis after primary percutaneous coronary intervention (PCI). Objectives: The aim of this analysis was to evaluate whether routine pre-hospital administration of high-dose tirofiban in ST-segment elevation myocardial infarction (STEMI) decreases the incidence of early stent thrombosis after primary PCI. Patients/methods: The Ongoing Tirofiban in Myocardial Evaluation (On-TIME) 2 trial was a prospective multicenter study of consecutive STEMI patients referred for primary PCI in which patients were randomized to pre-hospital no high-dose tirofiban/placebo. We examined the incidence of Academic Research Consortium definite and probable early stent thrombosis and determined predictors and outcome of early stent thrombosis. Results: Primary PCI was performed in 1203 out of 1398 patients (86.1%). In 1073 patients (89.2%) a coronary stent was placed. Early stent thrombosis occurred in 39 patients (3.6%). Pre-hospital initiation of high-dose tirofiban significantly reduced early stent thrombosis (2.1% vs. 5.2%, P = 0.006) and was associated with a lower incidence of urgent repeat PCI (1.9% vs. 5.2%, P = 0.005). Early stent thrombosis, as well as pre-hospital initiation of high-dose tirofiban, was independently associated with 30-day mortality. Conclusions: Pre-hospital initiation of high-dose tirofiban reduces the 30-day incidence of stent thrombosis in STEMI patients treated with primary PCI and stenting. Early stent thrombosis and pre-hospital initiation of high-dose tirofiban were independent predictors of 30-day mortality.

Background: Dual-source CT (DSCT) promises a significant reduction of radiation dose exposure for coronary CT angiography (CTA). Large studies on radiation dose estimates are rare. Objective: To compare radiation dose estimates of DSCT with 16- and 64-slice multidetector CT (MDCT) for non-invasive coronary angiography. Patients and design: Retrospective data analysis was performed on 292 patients: 56 patients were examined with 16-slice MDCT, 38 patients with 64-slice MDCT and 202 patients using DSCT. The effective dose (ED) estimates were calculated for all patients from the dose–length product and the conversion factor k (0.017 mSv/mGy/cm), as recommended by current guidelines. Results: The mean (SD) ED for patients examined by 16-slice MDCT was 9.8 (1.8) mSv, for 64-slice MDCT 8.6 (2.8) mSv and for DSCT 11.4 (7.2) mSv. With a protocol of 100 kV tube voltage and 110 ms ECG pulsing window the mean (SD) ED was 3.8 (1.7) mSv for DSCT scanning. When DSCT with a tube voltage of 100 kV was used, a significant inverse correlation between heart rate and radiation dose exposure was found. Conclusions: When standard protocols for coronary CTA with 16-, 64-slice MDCT and DSCT scanners are used, the radiation dose is still high. However, using optimised and individually adjusted protocols low estimated radiation doses can be achieved.

Despite optimized reperfusion strategies and adjunct pharmacotherapy, ischemic heart failure after myocardial infarction remains a major challenge. Early reports of the use of progenitor cells and their ability to transdifferentiate into myocytes from experimental studies have raised great expectations for new regenerative therapy strategies. However, the results of recent clinical studies have tempered the enthusiasm, and many questions are left unanswered. To better understand the efficacy of stem cell therapy, imaging techniques will help by providing techniques of cell tracking and a comprehensive evaluation of surrogate parameters such as left ventricular function, volumes, and wall motion. The ability of infarct characterization, including infarct size, transmurality, edema, and microvascular obstruction, is unique for MRI. Therefore, MRI has turned out to be the method of choice for cell tracking in experimental settings, as well as the assessment of the clinical effect of stem cell therapy in patients.

Background Computed tomography (CT) enables detection of coronary artery stenoses, but its use is limited by deficient evaluation at elevated heart rates. The accuracy of dual-source CT (DSCT) for the detection of coronary artery disease (CAD) was assessed in 76 patients at high probability of CAD without heart rate control and compared with quantitative coronary angiography (QCA). Methods and Results The 76 patients (47 males, mean age 65.5±10 years) underwent DSCT without preceding heart rate control. Data sets were evaluated by 2 observers in consensus with respect to stenoses >50% decreased diameter. QCA served as the standard of reference. Mean heart rate during scanning was 68±9 beats per min, and the average Agatston score was 337±560. Of 1,160 coronary artery segments, all but 3 were visualized artefact-free; 58 coronary stenoses were correctly detected by CT angiography. In the segment-based analysis, sensitivity was 98.3%, specificity 99.2% and accuracy 99%; patient based analysis revealed a sensitivity of 100%, specificity of 83.3% and overall accuracy of 92.1%. Conclusions Even at elevated heart rates, DSCT can reliably detect coronary artery stenoses and the results correlate well with those for invasive coronary angiography. (Circ J 2009; 73: 316 - 322)

The APEX library was a coordinated and integrated set of ancillary analyses and substudies that were a part of the large APEX-AMI trial. The library included electrocardiogram, angiographic, blood biomarker, genetics, and MRI components. Operationally, the goals and administration of the APEX library were developed concurrently with the design of the parent trial. The goal recruitment in the library was met due to this approach. These data will provide important insights into the pathobiology of acute myocardial infarction and the relationships between inflammation, thrombosis, genetics, and classic clinical markers from angiograms, electrocardiograms, and patient demographics. In conclusion, the APEX library is an example of successful collaboration among academic trial leaders, site investigators, and pharmaceutical sponsors. The operational paradigm of this effort should be considered in future investigations so that important advances in clinical care of disease can be realized efficiently.

Pulmonary Vein Stenting. Introduction: Severe pulmonary vein stenosis (PVS) after catheter ablation of atrial fibrillation (AF) is a well-recognized complication with a further reported incidence of 1.3%. The preferred therapy for symptomatic PVS is pulmonary vein (PV) angioplasty, but this treatment modality is followed by restenosis in 44–70%. Whether there is additional long-term benefit from PVS stenting is uncertain. The aim of this study was the evaluation of the long-term success after PV stenting of severe stenosis. Methods and Results: Ten patients (pts) with 13 PVS were prospectively evaluated. PV stenting was performed with Palmaz Genesis stents. Magnetic resonance imaging (MRI), lung perfusion scans, and CT-scans were performed before, directly after, and every 12 months thereafter. Primary endpoint of the study was the occurrence of restenosis after PV stenting. After a median follow-up of 47.7 (IQRs 25/75 47.2–48.5) months, the primary endpoint was achieved in 3 out of 13 PVs (23% of the treated PVs). We observed two in-stent restenosis 2 and 4 years after PV stenting. These pts experienced onset of dyspnea some weeks before. After an additional balloon angioplasty, the in-stent restenosis was resolved. In one asymptomatic patient, we observed an occlusion of the PV stent 13 months poststenting. Normalization of lung perfusion was noted 4 years after PV stenting versus directly poststenting in all pts without in-stent restenosis (n = 7). Conclusion: PVS stenting with stent sizes ≥10 mm seems to be an adequate therapy modality for treatment of severe acquired PVS. Late in-stent restenosis after PVS stenting can occur. The normalization of the initially disturbed lung perfusion scan is possible and remains stable, even 4 years after PVS stenting. (J Cardiovasc Electrophysiol, Vol. 20, pp. 251-257, March 2009)

The purpose of this study was to evaluate morphological and functional MRI of atrial septal defects (ASD) before and after interventional occlusion by the Amplatzer Septal Occluder (AOC) in comparison to trans-oesophageal echocardiography (TEE), invasive balloon measurement (IVBM) and cardiac catheterisation (QCC). Sixty patients with an ASD type II were enrolled. They underwent TEE, IVBM, QCC and MRI at 1.5T. Cine gradient echo, steady-state free precession sequences and a gradient echo phase contrast sequence were used. In MRI, pulmonary-to-systemic flow ratio (Qp/Qs) was calculated and compared with the QCC Qp/Qs ratio. Qp/Qs ratio in baseline MRI examination was 1.56 +/- 0.29 (range: 1.05-2.2) and in QCC 1.71 +/- 0.30 (range: 1.2-2.4) with a significant correlation (R = 0.65, P0.01). Defect size on MRI was 15.3 +/- 7.4 mm (range: 3-30 mm), in TEE 14.3 +/- 4.9 mm (range: 4-24 mm), and the balloon stretched diameter in IVBM was 23.4 +/- 4.2 mm (range: 14-32 mm). Correlation between defect size in MRI vs. TEE was R = 0.67 (P0.01) and MRI vs. IVBM was R = 0.77 (P0.01). Right ventricular volumes decreased after intervention. MRI is an accurate noninvasive test for diagnosis, planning and follow-up after interventional ASD occlusion using an AOC.

Background Radiation dose exposure is increased in multislice spiral computed tomography (MSCT) compared to conventional coronary angiography (CXA). Methods Retrospective data analysis of 56 patients (66±8 years, 49 males, body surface area 1.98±0.18 m 2 , heart rate 64±11 bpm) who underwent MSCT and CXA was performed (MSCT: 16-slice scanner, rotation time 0.375 s, 120 kV, ECG-pulsing; CXA: current technique system build in 2003). Ten patients with bypass grafts underwent bypass angiography in CXA and MSCT. To compare the radiation doses of both investigations, the effective dose (ED) was chosen as the analysis variable. Results The mean ED for MSCT was 9.76±1.84 mSv ( n =46) for patients without bypass grafts; with calcium scoring the mean ED was 12.46±2.23 mSv ( n =46). In comparison, the mean ED of CXA was 2.60±1.27 mSv ( n =46) for patients without bypass grafts; with bypass grafts ( n =10) the mean ED for MSCT was 12.95±1.75 mSv, for CXA of 6.27±4.04 mSv, respectively. In MSCT heart rates of ≤60 bpm resulted in lower mean ED than heart rates of >60 bpm (8.86±1.24 mSv versus 10.53±1.86 mSv). Conclusions MSCT is still associated with a higher radiation dose exposure than CXA. The radiation dose relation is more favorable for MSCT than for CXA in patients with bypass grafts in comparison to patients without bypass grafts. This study emphasizes the importance of dose reduction techniques.

Tako-Tsubo cardiomyopathy (TTC) is characterized by a transient contractile dysfunction, but its specific pathomechanism remains unknown. Thus, we performed a systematic expression profiling of genes by microarray analysis in the acute phase and after functional recovery. We studied 3 female patients presenting with TTC. Complementary RNA was isolated from left ventricular biopsies taken in the acute phase (group A) and after functional recovery (group B). It was profiled for gene expression using cDNA microarrays. Functionally related genes were determined with the Gene Set Enrichment Analysis (GSEA) bioinformatic tool. Validation of selected genes was performed by means of real-time PCR and immunohistochemistry. In group A, different functional gene sets, such as Nrf2-induced genes , triggered by oxidative stress, and protein biosynthesis were significantly overrepresented among the upregulated targets. Increased transcription of GPX1, CAT, RPS6, and eIF4E was confirmed by RT-PCR. The targets of the Akt/PKB signaling showed significant upregulation in both groups. Immunohistochemistry showed that the downstream targets NF-κB and BcL-X L are upregulated and activated. Gene sets involved in energy metabolism ( oxidative phosphorylation , mitochondrial genes ) showed no differences in group A but were overexpressed in group B. This study demonstrated a significant contribution of oxidative stress to the pathomechanism of TTC; it is possibly triggered by excess catecholamine. Increased protein biosynthesis and an activated cell survival cascade can be interpreted as potential compensatory mechanisms. After functional recovery, processes involved in energy metabolism play a pivotal role, thereby potentially contributing to the normalization of contractile function.

Objectives The aim of this study was to determine the diagnostic accuracy of 16-slice multislice spiral computed tomography (MSCT) of the coronaries and to provide data in a real clinical setting. Previous 16-slice MSCT studies presented data excluding patients with calcification, vessels of < 1.5 or 2 mm, and segments with impaired image quality. By including these data for 16-slice MSCT, a direct comparison with new data from 64-slice MSCT is possible. Methods and results Sixty two patients with suspected or known coronary artery disease (CAD) were prospectively enrolled and underwent computed tomography angiography (CTA) and invasive coronary angiography (ICA). All vessels were evaluated for the presence of a significant coronary artery stenosis (>50%) using the American Heart Association (AHA) 15-segment model. From the evaluation of 917 segments, sensitivity, specificity, and positive and negative predictive value (NPV) (positive predictive value [PPV] and NPV) for the presence of relevant coronary stenosis were 73, 98, and 71 and 98% per segment and 94, 90, and 91 and 93% per patient, respectively. The influence of age, gender, body surface area (BSA), heart rate (HR), stents, and Ca2+-score value was analyzed. High Ca2+-score values were the only statistically significant predictor for impaired diagnostic accuracy. Conclusions In summary, CTA with evaluation of all vessel segments in a broad spectrum of patients allowed accurate and fast noninvasive coronary artery evaluation, including evaluation of stented segments. These data are very similar to those published recently for 64-slice scanners. Copyright © 2007 Wiley Periodicals, Inc.

Aims The purpose of this study was to determine the occurrence of asymptomatic episodes of atrial fibrillation (AF) and wrong AF perception after pulmonary vein isolation (PVI). We evaluated the success of ablation by using the following measurements: (i) clinical symptoms and duration of symptoms noticed by patients and (ii) synchronous event recording (ER). Methods and results Eighty patients with paroxysmal AF underwent PVI and were provided repeatedly with a portable ER upon discharge and every 3 months for a year. The ER automatically detects arrhythmias by a detection algorithm and can also be manually triggered by the patient. In 46/80 patients (57.5%), episodes of AF were documented. Asymptomatic AF was detected in 21.3%. In 9/80 patients (11.3%), who reported clinical AF recurrence, no AF could be shown by ER. We compared patients’ perception to have suffered AF episodes with the ERs and found a sensitivity of 75% and a specificity of 92%. Conclusion Reliance on perception of AF by patients after PVI results in an underestimation of recurrence of the arrhythmia. We observed a maximal occurrence of silent AF or wrong perception of AF in 26/80 (32.6%) patients.

We present gadolinium-enhanced cardiac magnetic resonance imaging (CMRI) in Tako-Tsubo-like left ventricular dysfunction showing the findings in acute phase and in follow-up. Gadolinium-enhanced CMRI allows to distinguish between myocardial infarction and other myocardial alterations, e.g., myocarditis. CMRI may thus permit to non-invasively identify patients with Tako-Tsubo syndrome by ruling out myocardial infarction or myocarditis in the setting of wall motion abnormalities (WMA).

Objective: To determine in an observational study whether N-terminal pro-brain natriuretic peptide (NT-proBNP) is raised in patients with an atrial septal defect (ASD) and whether concentrations change after interventional closure. Methods: 12 patients (6 men, mean (SD) age 44.4 (18.6) years) with a moderate sized ASD type II (23.3 (4.5) mm, pulmonary to systemic flow ratio 2.1 (0.68)) were investigated. In all patients a magnetic resonance imaging (MRI) study was performed and NT-proBNP was assessed at baseline and early (9 (13) days) and late (138 (64) days) after intervention. Results: Concentrations of NT-proBNP were found to be within the normal range at baseline (median 87 pg/ml, interquartile range 65–181 pg/ml) but increased early after the interventional closure (315 pg/ml, 133–384 pg/ml, p = 0.005 versus baseline). The increase of NT-proBNP was associated with an increase in left ventricular dimensions as assessed by MRI (left ventricular end diastolic volume 104 (27) ml to 118 (27) ml, p = 0.003). Late after ASD closure NT-proBNP returned to baseline concentrations (102 pg/ml, 82–188 pg/ml, p = 0.004 versus early follow up). Conclusion: These findings suggest the presence of transitory haemodynamic stress during adaptation of the left ventricle after ASD closure, which may contribute to the understanding of the pathological mechanism of acute heart failure and delayed improvement of exercise capacity after ASD closure.

Introduction: Pulmonary vein stenosis (PVS) is a potential complication of pulmonary vein isolation (PVI) using radiofrequency energy. The aim of our study was the evaluation of the severity and long-term outcome of primary angioplasty and angioplasty with pulmonary vein stenting for PVS. Methods and Results: Twelve patients with 15 PVS (greater than 70% stenosis) were prospectively evaluated. Primary dilation of the stenosis was performed because of clinical symptoms (10 patients) and/or the lung perfusion scans showed a significant perfusion defect (11 patients). Magnetic resonance imaging and lung perfusion scans performed before, directly after, during 3-month, and 6-month follow-up. In the stenting group additional multislice CT-scans directly after, during 6-month, and 12-month follow-up were performed. Within 2 months after primary balloon angioplasty, the PV size parameters were significantly reduced (P < 0.001) with recurrence of PVS in 11 of 15 PVs (73%). Pulmonary vein stenting in 8 patients and 11 PVs resulted in no vein stenosis during 12-month follow-up. Normalization of lung perfusion was noted in 8 of 12 patients. We observed 2 patients with hemoptysis during PV dilation, as severe complications with potential life-threatening character. Conclusion: PVS stenting seems to be superior to balloon angioplasty and effective at least over a period of 12 months in treating acquired PVS after pulmonary vein isolation.

This study evaluated the diagnostic significance of a magnetic resonance imaging (MRI) based scoring model for identification of arrhythmogenic right ventricular cardiomyopathy (ARVC) in patients with MRI evidence of RV abnormalities. Fifty-three patients with RV myocardial abnormalities on MRI were divided into a group with ARVC 1 (n=17) and a group with other RV arrhythmias (n=37). Decision tree learning (DTL) and linear classification (based on a modified ARVC scoring model of major and minor criteria) were used to identify and assess MRI criterion information value, and to induce ARVC diagnostic rules. All major ARVC criteria were more frequent in the ARVC group. Among minor criteria regional RV hypokinesia, mild segmental RV dilatation, and prominent trabeculae were more frequent in the ARVC group while mild global RV dilatation was more frequent in the non-ARVC group. RV aneurysm achieved highest importance in ARVC diagnosis (predictive accuracy 76.8%). Better diagnostic accuracy (sensitivity 93.3%, specificity 89.5%) was achieved when the MRI score for the major and minor criteria reached threshold value of four: two major criteria, or one major and two minor, or four minor criteria. Combinations between major and minor criteria contributed to a statistically valid model for ARVC diagnosis.

B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are elevated in patients with acute coronary syndromes and are closely linked to prognosis. Because there is only a small amount of data available concerning NT-proBNP in patients with stable angina pectoris, we aimed to determine whether NT-proBNP is of additional diagnostic value in these patients.Ninety-four patients with stable angina pectoris were prospectively included. All patients underwent exercise testing and coronary angiography, and 91 patients received thallium-201 single-photon emission computed tomography myocardial scintigraphy. NT-proBNP was analyzed at rest and after exercise testing. NT-proBNP was elevated in patients with inducible myocardial ischemia shown by single-photon emission computed tomography (396 +/- 80 pg/mL vs 160 +/- 101 pg/mL; P.01) closely linked to the extent of coronary artery disease (CAD) (no CAD, 148 +/- 29 pg/mL; 1- or 2-vessel disease, 269 +/- 50 pg/mL; 3-vessel disease 624 +/- 186 pg/mL; P.01). In a multivariate analysis, NT-proBNP was an independent predictor for CAD. The area under the curve of the receiver operating characteristic curve was 0.72 for NT-proBNP to predict CAD. Using an optimized cut off level of 214 pg/mL, CAD can be predicted with high accuracy. The total test efficiency of exercise testing can be improved from 1.46 to 1.52 when combined with NT-proBNP measurement.NT-proBNP is elevated in patients with stable angina pectoris and has a close correlation to disease severity. Combining the measurement of NT-proBNP with exercise testing, the test accuracy for predicting severe CAD can be improved. Our data show an incremental value of NT-proBNP in the diagnostic process of stable angina pectoris.

Study objectives: The functional impact of pulmonary vein (PV) stenosis on pulmonary perfusion after radiofrequency ablation (RFA) for atrial fibrillation (AF) has not been systematically evaluated previously. Therefore, we correlated magnetic resonance (MR) pulmonary perfusion imaging with single-photon emission CT (SPECT) perfusion and with the degree of PV stenosis (PVS) apparent on MR angiography (MRA) after RF ablation. Setting: Joint radiology-cardiology collaborative magnetic resonance unit at the Kerckhoff Heart Center. Design and patients: This was a cohort study of 110 patients who were routinely examined by MRA after RFA for AF, whereby 51 patients with a PV diameter reduction of > 25% or with clinical symptoms (ie, dyspnea and cough) were enrolled into the study. Patients were examined at follow-up by MR perfusion imaging and MRA, and the results were compared to those from patients who underwent SPECT scanning and from a control group of 26 untreated patients. Twelve patients underwent PVS dilatation as well as 22 sequential follow-up examinations. Methods: Pulmonary perfusion was evaluated using a dynamic contrast-enhanced threedimensional MR perfusion sequence (1.5 T, 2.5-s temporal resolution, and 0.05 cm spatial resolution), and high-resolution, contrast-enhanced MRA was performed to measure PV diameter. PV dilatation was performed using an angioplasty catheter that was 8 to 10 mm in diameter. Results: The localization and extent of perfusion defects measured by MRI or SPECT scanning were precisely matched. MR perfusion imaging detected 20 of 21 perfusion defects (sensitivity, 95.2%; specificity, 100%). PVSs and perfusion deficits correlated closely and showed the following threshold: perfusion decreased substantially in PVs 6 mm in diameter. After PVS dilatation, perfusion was restored partially after weeks, and complete normalization was seen in 4 of 12 patients (33%). Conclusions: PVSs caused severe perfusion deficits, which were reliably demonstrated by MR perfusion imaging. Clinical symptoms correlated better with MR perfusion than they did with MRA. The combination with MRA to assess underlying PVS allowed a “one-stop-shopping” MRI procedure to be carried out. The results led to alterations of RFA techniques, and therefore MRA and MR perfusion imaging may be beneficial in patient follow-up and in evaluating new ablation techniques. (CHEST 2004; 126:428 – 437) Abbreviations: AF atrial fibrillation; BW body weight; CE contrast-enhanced; FOV field of view; MPR multiplanar reconstructed; MR magnetic resonance; MRA magnetic resonance angiography; PV pulmonary vein; PVS pulmonary vein stenosis; RFA radiofrequency ablation; SI signal intensity; SPECT single-photon emission CT; 3D three-dimensional

Background— Radiofrequency catheter ablation (RFCA) is a promising intervention to treat atrial fibrillation. However, pulmonary vein (PV) stenosis after RFCA has been reported. The aim of this study was to investigate the incidence and time course of pulmonary vein stenosis after RFCA within a period of 3 months. Contrast-enhanced magnetic resonance angiography (MRA) was used to visualize pulmonary veins and was compared with radiographic angiography. Methods and Results— Forty-six consecutive patients with symptomatic paroxysmal atrial fibrillation had RFCA in the orifice of 138 pulmonary veins. Comparison of diameters measured in 44 untreated vessels either by radiographic angiography or with MRA established the reliability of MRA ( r =0.934). MRA measurements revealed an incidence of relevant diameter reductions of ≥25% or stenosis of ≥50% after RFCA of 25 of 138 (18.1%) treated vessels 1 day and/or 3 months after ablation. A progression of diameter reduction after RFCA was observed in 8.3% (maximum 75%), whereas a regression was observed in 6.3% of treated PVs. Ablation at a radial angle of >180° of a pulmonary vein orifice increased the risk of diameter reduction significantly compared with ablation at a radial angle ≤180° ( P =0.002). Conclusions— The occurrence and progression of PV stenosis is a potential significant complication of RFCA in the orifice of pulmonary veins. These findings may have an impact on the technical performance of this intervention. In addition, long-term studies will be necessary to evaluate lumen reduction over time. MRA is a noninvasive, reproducible imaging modality for this purpose.

Die z. T. unbefriedigenden Ergebnisse nach perkutaner transluminaler koronarer Angioplastie (PTCA) und das Auftreten von Restenosen in bis zu 70% der Falle bei komplexen Koronarstenosen waren der Antrieb fur die Entwicklung alternativer Verfahren. Das Abtragen von Gewebe in der Stenose und die Vermeidung von lokaler Gefasuberdehnung versprachen Vorteile gegenuber der PTCA. Die am haufigsten eingesetzten Verfahren waren die direktionale Atherektomie (DCA), die Laserantioplastie (ELCA) und die Rotationsatherektomie (Rotablation, RA). Fur keines der Verfahren lies sich jedoch ein klarer Vorteil gegenuber der PTCA belegen, sodass einige wenige Nischenindikationen ubrig blieben. Auch in der Behandlung der Instentrestenose konnte die Rotablation in einem randomisierten Vergleich mit der PTCA keinen Vorteil erzielen.

Consumption of natural hallucinogenic substances continues to be a problem. In this case we report from a young male patient presenting with an acute coronary syndrome with significant ST-elevation after the abuse of psychoactive fungi, commonly referred to as "magic mushrooms". Coronary angiography excludes relevant coronary artery disease. In ventriculography contractile dysfunction with hypokinesia in the apical segments could be documented reminiscent to wall motion abnormalities in Tako-Tsubo cardiomyopathy (TTC). Cardiovascular magnetic resonance imaging showed no pathological signal activity in the late-enhancement sequences ruling out myocardial infarction or inflammatory processes. Ventricular function normalized within several days. The active metabolite of psychoactive fungi psilocybin is known to interact with several different dopaminergic, adrenergic and serotonergic receptors. Thus, the pathomechanisms leading to contractile dysfunction after consumption of psychoactive fungi are reminiscent to those documented in TTC.

Severe emotional or physical stress precedes Tako-Tsubo cardiomyopathy (TTC) which is characterized by transient left ventricular impairment in absence of coronary artery disease. In this case we report from a female patient presenting with characteristic features of TTC after examination of upper gastrointestinal. Additionally, severe mitral regurgitation due to acute rupture of the posteromedial papillary muscle was present. Normal left ventricular function was documented before surgical valve repair was performed. TTC is reported to be associated with several complications. This is the first report of TTC accompanied by severe mitral valve regurgitation due to rupture of a papillary muscle.

Tako-Tsubo cardiomyopathy (TTC) which is usually precipitated by profound emotional stress has been widely reported in the past. Recently, several co-morbidities have been found to be associated with this new cardiac entity. In this case we report from a female patient suffering from both, physical and emotional stress. After a persistent episode of severe abdominal pain due to acute cholecystitis and recurrent events of emotional stress, characteristic features of TTC could be documented. Histopathological analysis documented characteristic structural alterations including contraction band necrosis. Thus, this case confirms the hypothesis of an overstimulated sympthatoadrenergic system in TTC resulting from both, severe physical and emotional stress.