Extracorporeal Life Support in Infarct-Related Cardiogenic Shock.

BACKGROUND: Extracorporeal life support (ECLS) is increasingly used in the treatment of infarct-related cardiogenic shock despite a lack of evidence regarding its effect on mortality. METHODS: In this multicenter trial, patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization was planned were randomly assigned to receive early ECLS plus usual medical treatment (ECLS group) or usual medical treatment alone (control group). The primary outcome was death from any cause at 30 days. Safety outcomes included bleeding, stroke, and peripheral vascular complications warranting interventional or surgical therapy. RESULTS: A total of 420 patients underwent randomization, and 417 patients were included in final analyses. At 30 days, death from any cause had occurred in 100 of 209 patients (47.8%) in the ECLS group and in 102 of 208 patients (49.0%) in the control group (relative risk, 0.98; 95% confidence interval [CI], 0.80 to 1.19; P = 0.81). The median duration of mechanical ventilation was 7 days (interquartile range, 4 to 12) in the ECLS group and 5 days (interquartile range, 3 to 9) in the control group (median difference, 1 day; 95% CI, 0 to 2). The safety outcome consisting of moderate or severe bleeding occurred in 23.4% of the patients in the ECLS group and in 9.6% of those in the control group (relative risk, 2.44; 95% CI, 1.50 to 3.95); peripheral vascular complications warranting intervention occurred in 11.0% and 3.8%, respectively (relative risk, 2.86; 95% CI, 1.31 to 6.25). CONCLUSIONS: In patients with acute myocardial infarction complicated by cardiogenic shock with planned early revascularization, the risk of death from any cause at the 30-day follow-up was not lower among the patients who received ECLS therapy than among those who received medical therapy alone. (Funded by the Else Kröner Fresenius Foundation and others; ECLS-SHOCK ClinicalTrials.gov number, NCT03637205.).

Comparison of a Pure Plug-Based Versus a Primary Suture-Based Vascular Closure Device Strategy for Transfemoral Transcatheter Aortic Valve Replacement: The CHOICE-CLOSURE Randomized Clinical Trial.

BACKGROUND: Transcatheter aortic valve replacement is an established treatment option for patients with severe symptomatic aortic stenosis and is most commonly performed through the transfemoral access route. Percutaneous access site closure can be achieved using dedicated plug-based or suture-based vascular closure device (VCD) strategies, but randomized comparative studies are scarce. METHODS: The CHOICE-CLOSURE trial (Randomized Comparison of Catheter-based Strategies for Interventional Access Site Closure during Transfemoral Transcatheter Aortic Valve Implantation) is an investigator-initiated, multicenter study, in which patients undergoing transfemoral transcatheter aortic valve replacement were randomly assigned to vascular access site closure using either a pure plug-based technique (MANTA, Teleflex) with no additional VCDs or a primary suture-based technique (ProGlide, Abbott Vascular) potentially complemented by a small plug. The primary end point consisted of access site- or access-related major and minor vascular complications during index hospitalization, defined according to the Valve Academic Research Consortium-2 criteria. Secondary end points included the rate of access site- or access-related bleeding, VCD failure, and time to hemostasis. RESULTS: A total of 516 patients were included and randomly assigned. The mean age of the study population was 80.5±6.1 years, 55.4% were male, 7.6% of patients had peripheral vascular disease, and the mean Society of Thoracic Surgeons score was 4.1±2.9%. The primary end point occurred in 19.4% (50/258) of the pure plug-based group and 12.0% (31/258) of the primary suture-based group (relative risk, 1.61 [95% CI, 1.07-2.44], P=0.029). Access site- or access-related bleeding occurred in 11.6% versus 7.4% (relative risk, 1.58 [95%CI: 0.91-2.73], P=0.133) and device failure in 4.7% versus 5.4% (relative risk, 0.86, [95% CI, 0.40-1.82], P=0.841) in the respective groups. Time to hemostasis was significantly shorter in the pure plug-based group (80 [32-180] versus 240 [174-316] seconds, P<0.001). CONCLUSIONS: Among patients treated with transfemoral transcatheter aortic valve replacement, a pure plug-based vascular closure technique using the MANTA VCD is associated with a higher rate of access site- or access-related vascular complications but a shorter time to hemostasis compared with a primary suture-based technique using the ProGlide VCD. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04459208.

Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes.

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).

Extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock - Design and rationale of the ECLS-SHOCK trial.

BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted. STUDY DESIGN: The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke. CONCLUSIONS: The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.

Influence of excess weight and obesity on performance and outcome of pulmonary vein isolation with the cryoballoon.

Pulmonary vein isolation (PVI) has become a cornerstone therapy in the treatment of atrial fibrillation (AF). Patients with overweight or obesity suffer more often from AF, and studies investigating the safety and feasibility of PVI in these patients have shown varying results. In this study we analyzed PVI performed with the 2nd generation cryoballoon (CB) with regard to safety, procedure and fluoroscopy time in patients with normal weight, overweight and obesity. We analyzed 228 consecutive patients treated with CB PVI in our hospital in 2018 and 2019. Fifty nine (25.88%) patients presented with normal weight (body mass index (BMI) of <25), 115 (50.44%) patients with overweight (BMI between 25 and 29.9) and 54 (23.68%) were obese patients (BMI >30). All pulmonary veins (PV) were isolated successfully. Concerning procedural parameters, neither complications, procedural time, nor fluoroscopy time differed significantly. There was a significant increase of dose area product (DAP) in obese patients compared to normal weight and overweight patients (2035.5 ± 1930.1 µGym2 vs. 975.3 ± 814.9 vs. 1325.1 ± 2081.3, p = 0.001) but no significant difference between overweight and normal weight patients (p = 0.611). Our follow-up data of 168 patients (73.68%) observed for 12 months showed no differences in the recurrence of AF in the three BMI groups [80.9% vs. 83.3% (p = 0.733) vs. 86.55% (p = 0.460)]. In conclusion, CB PVI in overweight and obese patients is safe with similar levels of complications and recurrence of AF as patients of normal weight. However, obese patients and operators are exposed to higher radiation doses.

Reliable Detection of Atrial Fibrillation with a Medical Wearable during Inpatient Conditions.

Atrial fibrillation (AF) is the most common arrhythmia and has a major impact on morbidity and mortality; however, detection of asymptomatic AF is challenging. This study sims to evaluate the sensitivity and specificity of non-invasive AF detection by a medical wearable. In this observational trial, patients with AF admitted to a hospital carried the wearable and an ECG Holter (control) in parallel over a period of 24 h, while not in a physically restricted condition. The wearable with a tight-fit upper armband employs a photoplethysmography technology to determine pulse rates and inter-beat intervals. Different algorithms (including a deep neural network) were applied to five-minute periods photoplethysmography datasets for the detection of AF. A total of 2306 h of parallel recording time could be obtained in 102 patients; 1781 h (77.2%) were automatically interpretable by an algorithm. Sensitivity to detect AF was 95.2% and specificity 92.5% (area under the receiver operating characteristics curve (AUC) 0.97). Usage of deep neural network improved the sensitivity of AF detection by 0.8% (96.0%) and specificity by 6.5% (99.0%) (AUC 0.98). Detection of AF by means of a wearable is feasible in hospitalized but physically active patients. Employing a deep neural network enables reliable and continuous monitoring of AF.

In-hospital mortality of patients with atrial arrhythmias: insights from the German-wide Helios hospital network of 161 502 patients and 34 025 arrhythmia-related procedures.

Aims: Atrial fibrillation (AFib) and atrial flutter (AFlut) are common arrhythmias with increased use of invasive procedures. A steady re-evaluation of relevant safety endpoints is recommended and both quality management and pay-for-performance programs are evolving. Therefore, the aims of this study were (i) to investigate and report overall in-hospital mortality and mortality of invasive arrhythmia-related procedures and (ii) to identify mortality predictors in a German-wide hospital network. Methods and results: Administrative data provided by 78 Helios hospitals between 2010 and 2017 were examined using International Statistical Classification of Diseases and Related Health Problems- and Operations and Procedures-codes to identify patients with AFib or AFlut as main discharge diagnosis or secondary diagnosis combined with invasive arrhythmia-related interventions. In 161 502 patients, in-hospital mortality was 0.6% with a significant decrease from 0.75% to 0.5% (P < 0.01) during the observational period. In multivariable analysis, age [odds ratio (OR) 2.69, 95% confidence interval (CI) 2.36-3.05; P < 0.01], high centre volume (OR 0.57, 95% CI 0.50-0.65; P < 0.01), emergency hospital admission (OR 1.57, 95% CI 1.38-1.79; P < 0.01), and Charlson Comorbidity Index (CCI, OR 4.95, 95% CI 4.50-5.44; P < 0.01) were found as independent predictors of in-hospital mortality. Mortality rates were 0.05% for left atrial catheter ablation (CA, n = 21 744), 0.3% for right atrial CA (n = 9972), and 0.56% for implantation of a left atrial appendage occluder (n = 2309), respectively. Conclusion: We analysed for the first time in-hospital mortality rates of patients with atrial arrhythmias in a German-wide, multi-centre administrative dataset. This allows feasible, comparable, and up-to-date performance measurement of clinically important endpoints in a real-world setting which may contribute to quality management programs and towards value-based healthcare.

Temporarily increased stroke rate after Takotsubo syndrome: need for an anticoagulation?

BACKGROUND: Previous studies have reported slightly higher stroke rates in Takotsubo Syndrome compared to acute myocardial infarction. Our goal was to evaluate the temporal course of stroke rates and left ventricular recovery in patients with Takotsubo Syndrome. METHODS: We retrospectively examined the clinical and imaging data of 72 patients with Takotsubo Syndrome. The data collected came from January 2005 to March 2017. Left ventricular performance was evaluated by cardiovascular magnetic resonance imaging (MRI) in all patients during the acute phase of Takotsubo Syndrome and in a follow-up scan 2 months later. Acute stroke and major adverse clinical events, such as myocardial infarction or recurrence of Takotsubo Syndrome and death, were also determined for each patient at 30 days and 12 months after initial presentation. RESULTS: The MRI scans performed during the acute phase of Takotsubo Syndrome demonstrated apical ballooning with anterior wall motion dysfunction in 65 (90%) patients. Imaging performed 2 months later demonstrated resolution of this in 97% of those patients. Median left ventricular ejection fraction also significantly increased between both scans (49.5% vs. 64.0%, P < 0.001). We observed 9 (12%) events in the study population within 12 months of the initial diagnosis of Takotsubo Syndrome. Stroke had an event rate of 2.8% after 30 days and 4.2% after 12 months. CONCLUSIONS: Apical ballooning was found in the majority of our Takotsubo Syndrome patients on the MRI scans performed at presentation. This finding was subsequently associated with higher than expected stroke rates within 30 days of diagnosis and with rapid recovery of left ventricular function within 2 months of diagnosis. This suggests that rapid improvement in left ventricular morphology and function may facilitate the formation of cardiac emboli and consequently increase stroke rates in Takotsubo Syndrome. Although no guidelines currently exist for the treatment of Takotsubo Syndrome, these results may point to a potential role for temporary oral anticoagulation in high-risk patients. Future studies should examine if stroke rates after Takotsubo Syndrome have been underestimated.

Percutaneous short-term active mechanical support devices in cardiogenic shock: a systematic review and collaborative meta-analysis of randomized trials.

AIMS: Evidence on the impact on clinical outcome of active mechanical circulatory support (MCS) devices in cardiogenic shock (CS) is scarce. This collaborative meta-analysis of randomized trials thus aims to investigate the efficacy and safety of percutanzeous active MCS vs. control in CS. METHODS AND RESULTS: Randomized trials comparing percutaneous active MCS to control in patients with CS were identified through searches of medical literature databases. Risk ratios (RR) and 95% confidence intervals (95% CI) were calculated to analyse the primary endpoint of 30-day mortality and device-related complications including bleeding and leg ischaemia. Mean differences (MD) were calculated for mean arterial pressure (MAP), cardiac index (CI), pulmonary capillary wedge pressure (PCWP), and arterial lactate. Four trials randomizing 148 patients to either TandemHeart™ or Impella® MCS (n = 77) vs. control (n = 71) were identified. In all four trials intra-aortic balloon pumping (IABP) served as control. There was no difference in 30-day mortality (RR 1.01, 95% CI 0.70 to 1.44, P = 0.98, I2 = 0%) for active MCS compared with control. Active MCS significantly increased MAP (MD 11.85 mmHg, 95% CI 3.39 to 20.31, P = 0.02, I2 = 32.7%) and decreased arterial lactate (MD - 1.36 mmol/L, 95% CI - 2.52 to - 0.19, I2 = 0%, P = 0.02) at comparable CI (MD 0.32, 95% CI - 0.24 to 0.87, P = 0.14, I2 = 44.1%) and PCWP (MD - 5.59, 95% -15.59 to 4.40, P = 0.14, I2 = 81.1%). No significant difference was observed in the incidence of leg ischaemia (RR 2.64, 95% CI 0.83 to 8.39, P = 0.10, I2 = 0%), whereas the rate of bleeding was significantly increased in MCS compared to IABP (RR 2.50, 95% CI 1.55 to 4.04, P < 0.001, I2 = 0%). CONCLUSION: Results of this collaborative meta-analysis do not support the unselected use of active MCS in patients with CS complicating AMI.

Evaluation of therapy management and outcome in Takotsubo syndrome.

BACKGROUND: To date there is no validated evidence for standardized treatment of patients with Takotsubo syndrome (TTS). Medication therapy after final TTS diagnosis remains unclear. Previous data on patient outcome is ambivalent. Aim of this study was to evaluate medication therapy in TTS and to analyze patient outcome. METHODS: Within an observational retrospective cohort study we analyzed our medical records and included 72 patients with TTS that underwent cardiovascular magnetic resonance imaging (CMR) after a median of 2 days interquartile range (IQR 1-3.5). We investigated medication therapy at discharge. Medication implementation and major adverse clinical events (MACE) were prospectively evaluated after a median follow-up of 24 months (IQR 6-43). Left ventricular function, myocardial oedema and late gadolinium enhancement were analyzed in a CMR follow-up if available. RESULTS: Antithrombotic therapy was recommended in 69 (96%) patients including different combinations. Antiplatelet monotherapy was prescribed in 28 (39%) patients. Dual antiplatelet therapy was recommended in 29 (40%) patients. Length of therapy duration varied from one to twelve months. Only in one case oral anticoagulation was prescribed due to apical ballooning with a left ventricular ejection fraction <30%. In all other cases oral anticoagulation was recommended due to other indications. ß-adrenoceptor antagonists and ACE inhibitors were recommended in 63 (88%), mineralocorticoid receptor antagonists were prescribed in 31 (43%) patients. After a median of 2 months (IQR 1.3-2.9) left ventricular function significantly recovered (49.1% ± 10.1 vs. 64.1% ± 5.7, P < 0.001) and myocardial oedema significantly decreased (13.5 ± 11.3 vs. 0.6% ± 2.4, P = <0.001) in the CMR follow-up. The 30-day mortality was 1%. MACE rate after 24 months was 12%. CONCLUSION: Although therapy guidelines for TTS currently do not exist, we found that the majority of patients were treated with antithrombotic and heart failure therapy for up to twelve months. Left ventricular function and myocardial oedema recovered rapidly within the first two months. Outcome analysis showed a low bleeding rate and a high short-term survival. Therefore, TTS patients might benefit from antithrombotic and heart failure therapy at least for the first two months.

Applicability of a Novel Formula (Bogossian formula) for Evaluation of the QT-Interval in Heart Failure and Left Bundle Branch Block Due to Right Ventricular Pacing.

BACKGROUND: The presence of left bundle branch block (LBBB) due to right ventricular pacing represents a particular challenge in properly measuring the QTc interval. In 2014, a new formula for the evaluation of QT interval in patients with LBBB was reported. METHODS: 145 patients with implantable cardioverter defibrillator were included in this prospective multicenter observational study. Inclusion criteria were: no permanent right ventricular stimulation, an intrinsic QRS interval of <120 ms, and reduced left ventricular function. 12-lead electrocardiogram recordings during intrinsic rhythm and during right ventricular threshold testing were performed. After LBBB correction using the reported Bogossian formula, the QTc interval was evaluated with Bazett's formula. The corrected QTc interval was compared in each patient with the QTc interval during intrinsic rhythm. All measurements were performed by an experienced electrophysiologist and a trainee who worked independently and in a blinded manner. RESULTS: 74 patients (65 ± 13 years; male n = 42) with apical and 71 patients (68 ± 11 years; male n = 42) with nonapical right ventricular pacing were included in this study. The mean left ventricular ejection fraction was 40 ± 13%. The QTc interval was determined to be 461 ± 34 ms (modified by Bogossian's formula) in paced and 436 ± 34 ms in intrinsic rhythm. The QTc interval was overestimated by ΔQTc of 25 ± 21 ms (mean deviation 5.7%) when using the Bogossian formula. CONCLUSION: The novel Bogossian formula seems to be a reliable tool for QTc interval evaluation in patients with heart failure and right ventricular pacing. However, a slight overestimation of the QT-interval must be respected.

A new experimentally validated formula to calculate the QT interval in the presence of left bundle branch block holds true in the clinical setting.

BACKGROUND: The evaluation of the QT interval in the presence of left bundle branch block (LBBB) is associated with the challenge to discriminate native QT interval from the prolongation due to the increase in QRS duration. The newest formula to evaluate QT interval in the presence of LBBB suggests: modified QT during LBBB = measured QT interval minus 50% of LBBB duration. The purpose of this study is therefore to validate the abovementioned formula in the clinical setting. METHODS: Validation in two separate groups of patients: Patients who alternated between narrow QRS and intermittent LBBB and patients with narrow QRS who developed LBBB after transcatheter aortic valve implantation (TAVI). RESULTS: The acquired mean native QTc intervals and those calculated by the presented formula displayed no significant differences (p > .99 and p > .75). CONCLUSIONS: In this study we proved for the first time the validity and applicability of the experimentally acquired formula for the evaluation of the QT interval in the presence of LBBB in a clinical setting.

Serum insulin-like growth factor-1 and its binding protein-7: potential novel biomarkers for heart failure with preserved ejection fraction.

BACKGROUND: Insulin-like growth factor binding protein-7 (IGFBP-7) modulates the biological activities of insulin-like growth factor-1 (IGF-1). Previous studies demonstrated the prognostic value of IGFBP-7 and IGF-1 among patients with systolic heart failure (HF). This study aimed to evaluate the IGF1/IGFBP-7 axis in HF patients with preserved ejection fraction (HFpEF). METHODS: Serum IGF-1 and IGFBP-7 levels were measured in 300 eligible consecutive patients who underwent comprehensive cardiac assessment. Patients were categorized into 3 groups including controls with normal diastolic function (n = 55), asymptomatic left ventricular diastolic dysfunction (LVDD, n = 168) and HFpEF (n = 77). RESULTS: IGFBP-7 serum levels showed a significant graded increase from controls to LVDD to HFpEF (median 50.30 [43.1-55.3] vs. 54.40 [48.15-63.40] vs. 61.9 [51.6-69.7], respectively, P < 0.001), whereas IGF-1 levels showed a graded decline from controls to LVDD to HFpEF (120.0 [100.8-144.0] vs. 112.3 [88.8-137.1] vs. 99.5 [72.2-124.4], p < 0.001). The IGFBP-7/IGF-1 ratio increased from controls to LVDD to HFpEF (0.43 [0.33-0.56] vs. 0.48 [0.38-0.66] vs. 0.68 [0.55-0.88], p < 0.001). Patents with IGFB-7/IGF1 ratios above the median demonstrated significantly higher left atrial volume index, E/E' ratio, and NT-proBNP levels (all P ≤ 0.02). CONCLUSION: In conclusion, this hypothesis-generating pilot study suggests the IGFBP-7/IGF-1 axis correlates with diastolic function and may serve as a novel biomarker in patients with HFpEF. A rise in IGFBP-7 or the IGFBP-7/IGF-1 ratio may reflect worsening diastolic function, adverse cardiac remodeling, and metabolic derangement.

ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 vs. 12 months of clopidogrel therapy after drug-eluting stenting.

BACKGROUND: In patients receiving aspirin, the optimal duration of clopidogrel therapy after drug-eluting stent (DES) implantation remains unclear. METHODS: This multicentre, randomized, double-blind, placebo-controlled trial tested the hypothesis that in patients undergoing DES implantation, 6 months of clopidogrel is non-inferior to 12 months in terms of clinical outcomes. At 6 months after DES implantation, patients on clopidogrel were randomly assigned to either a 6-month period of placebo or an additional 6-month period of clopidogrel. The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, and thrombolysis in myocardial infarction major bleeding at 9 months after randomization. RESULTS: Owing to slow recruitment and low event rates, the trial was stopped prematurely after enrolment of 4005 of 6000 planned patients. Of 4000 patients included in the final analysis, 1997 received 6 months of clopidogrel and 2003 received 12 months. The primary endpoint occurred in 29 patients (1.5%) assigned to 6 months of clopidogrel and 32 patients (1.6%) assigned to 12 months, observed difference -0.1%, upper limit of one-sided 95% confidence interval (CI) 0.5%, limit of non-inferiority 2%, Pfor noninferiority <0.001. Stent thrombosis was observed in five patients (0.3%) assigned to 6 months of clopidogrel and three patients (0.2%) assigned to 12 months; hazard ratio (HR) 1.66, 95% CI: 0.40-6.96, P = 0.49. Thrombolysis in myocardial infarction major bleeding was observed in 4 patients (0.2%) assigned to 6 months clopidogrel and 5 patients (0.3%) assigned to 12 months; HR 0.80, 95% CI: 0.21-2.98, P = 0.74. CONCLUSIONS: In the present trial, characterized by low event rates, we did not observe a significant difference in net clinical outcome between 6 and 12 months of clopidogrel therapy after DES implantation. However, the results of the trial must be considered in view of its premature termination and lower than expected event rates. The trial is registered with ClinicalTrials.gov, Identifier: NCT00661206.

Intra-aortic balloon pump counterpulsation (IABP) for myocardial infarction complicated by cardiogenic shock.

BACKGROUND: Intra-aortic balloon pump counterpulsation (IABP) is currently the most commonly used mechanical assist device for patients with cardiogenic shock due to acute myocardial infarction. Although there has been only limited evidence from randomised controlled trials, the previous guidelines of the American Heart Association/American College of Cardiology (AHA/ACC) and the European Society of Cardiology (ESC) strongly recommended the use of the IABP in patients with infarction-related cardiogenic shock on the basis of pathophysiological considerations, non-randomised trials and registry data. The recent guidelines downgraded the recommendation based on a meta-analysis which could only include non-randomised trials showing conflicting results. Up to now, there have been no guideline recommendations and no actual meta-analysis including the results of the large randomised multicentre IABP-SHOCK II Trial which showed no survival benefit with IABP support. This systematic review is an update of the review published in 2011. OBJECTIVES: To evaluate, in terms of efficacy and safety, the effect of IABP versus non-IABP or other assist devices guideline compliant standard therapy on mortality and morbidity in patients with acute myocardial infarction complicated by cardiogenic shock. SEARCH METHODS: Searches of CENTRAL, MEDLINE (Ovid) and EMBASE (Ovid), LILACS, IndMed and KoreaMed, registers of ongoing trials and proceedings of conferences were updated in October 2013. Reference lists were scanned and experts in the field contacted to obtain further information. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials on patients with acute myocardial infarction complicated by cardiogenic shock. DATA COLLECTION AND ANALYSIS: Data collection and analysis were performed according to the published protocol. Individual patient data were provided for six trials and merged with aggregate data. Summary statistics for the primary endpoints were hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS: Seven eligible studies were identified from a total of 2314 references. One new study with 600 patients was added to the original review. Four trials compared IABP to standard treatment and three to other percutaneous left assist devices (LVAD). Data from a total of 790 patients with acute myocardial infarction and cardiogenic shock were included in the updated meta-analysis: 406 patients were treated with IABP and 384 patients served as controls; 339 patients were treated without assisting devices and 45 patients with other LVAD. The HR for all-cause 30-day mortality of 0.95 (95% CI 0.76 to 1.19) provided no evidence for a survival benefit. Different non-fatal cardiovascular events were reported in five trials. During hospitalisation, 11 and 4 out of 364 patients from the intervention groups suffered from reinfarction or stroke, respectively. Altogether 5 out of 363 patients from the control group suffered from reinfarction or stroke. Reocclusion was treated with subsequent re-revascularization in 6 out of 352 patients from the intervention group and 13 out of 353 patients of the control group. The high incidence of complications such as moderate and severe bleeding or infection in the control groups has to be attributed to interventions with other LVAD. Possible reasons for bias were more frequent in small studies with high cross-over rates, early stopping and the inclusion of patients with IABP at randomisation. AUTHORS' CONCLUSIONS: Available evidence suggests that IABP may have a beneficial effect on some haemodynamic parameters. However, this did not result in survival benefits so there is no convincing randomised data to support the use of IABP in infarct-related cardiogenic shock.

Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction.

BACKGROUND: The combination of glycoprotein IIb/IIIa inhibitors and heparin has not been compared with bivalirudin in studies specifically involving patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). We compared the two treatments in this patient population. METHODS: Immediately before PCI, we randomly assigned, in a double-blind manner, 1721 patients with acute non-ST-segment elevation myocardial infarction to receive abciximab plus unfractionated heparin (861 patients) or bivalirudin (860 patients). The study tested the hypothesis that abciximab and heparin would be superior to bivalirudin with respect to the primary composite end point of death, large recurrent myocardial infarction, urgent target-vessel revascularization, or major bleeding within 30 days. Secondary end points included the composite of death, any recurrent myocardial infarction, or urgent target-vessel revascularization (efficacy end point) and major bleeding (safety end point) within 30 days. RESULTS: The primary end point occurred in 10.9% of the patients in the abciximab group (94 patients) and in 11.0% in the bivalirudin group (95 patients) (relative risk with abciximab, 0.99; 95% confidence interval [CI], 0.74 to 1.32; P=0.94). Death, any recurrent myocardial infarction, or urgent target-vessel revascularization occurred in 12.8% of the patients in the abciximab group (110 patients) and in 13.4% in the bivalirudin group (115 patients) (relative risk, 0.96; 95% CI, 0.74 to 1.25; P=0.76). Major bleeding occurred in 4.6% of the patients in the abciximab group (40 patients) as compared with 2.6% in the bivalirudin group (22 patients) (relative risk, 1.84; 95% CI, 1.10 to 3.07; P=0.02). CONCLUSIONS: Abciximab and unfractionated heparin, as compared with bivalirudin, failed to reduce the rate of the primary end point and increased the risk of bleeding among patients with non-ST-segment elevation myocardial infarction who were undergoing PCI. (Funded by Nycomed Pharma and others; ISAR-REACT 4 ClinicalTrials.gov number, NCT00373451.).

Novel mitral clipping technique overcoming extreme atrial dilatation.

The mitral clipping technique is emerging as a promising new treatment option for severe mitral regurgitation. The device was designed and assessed in intermediate risk populations, which is in contrast to the real world, where most patients are deemed to be at very high risk for open heart surgery. The cardiac anatomy of these patients often challenges the freedom grades of the current mitral clip device. In this case presentation, we describe a novel technique overcoming extreme atrial dilation in a patient with severe mitral regurgitation despite previous implantation of two mitral clips. Based on a low/anterior trans-septal puncture, this procedure relied on a counter clock-wise 90° turn of the steerable sheath and alignment of the clip delivery system to the mitral valve, thereby gaining additional longitudinal freedom. This resulted in the successful implantation of two additional clips with achievement of a mild to moderate mitral regurgitation without relevant gradient and dramatic and sustained clinical improvement of the patient.

Cephalic Vein Cutdown Is Superior to Subclavian Puncture as Venous Access for Patients with Cardiac Implantable Devices after Long-Term Follow-Up.

BACKGROUND: Cephalic vein cutdown (CVC) and subclavian vein puncture (SVP) are the most commonly used access sites for transvenous lead placement of cardiac implantable electronic devices (CIEDs). Limited knowledge exists about the long-term patency of the vascular lumen housing the leads. METHODS: Among the 2703 patients who underwent CIED procedures between 2005 and 2013, we evaluated the phlebographies of 162 patients scheduled for an elective CIED replacement (median of 6.4 years after the first operation). The phlebographies were divided into four stenosis types: Type I = 0%, Type II = 1-69%, Type III = 70-99%, and Type IV = occlusion. Due to the fact that no standardized stenosis categorization exists, experienced physicians in consensus with the involved team made the applied distribution. The primary endpoint was the occurrence of stenosis Type III or IV in the CVC group and in the SVP group. RESULTS: In total, 162 patients with venography were enrolled in this study. The prevalence of high-degree stenosis was significantly lower in the CVC group (7/89, 7.8%) than in the SVP group (15/73, 20.5%, p = 0.023). In the CVC group, venographies showed a lower median stenosis (33%) than in the SVP group (median 42%). CONCLUSIONS: The present study showed that the long-term patency of the subclavian vein is higher after CVC than after SVP for venous access in patients with CIED.

Patient-specific induced pluripotent stem-cell models for long-QT syndrome.

BACKGROUND: Long-QT syndromes are heritable diseases associated with prolongation of the QT interval on an electrocardiogram and a high risk of sudden cardiac death due to ventricular tachyarrhythmia. In long-QT syndrome type 1, mutations occur in the KCNQ1 gene, which encodes the repolarizing potassium channel mediating the delayed rectifier I(Ks) current. METHODS: We screened a family affected by long-QT syndrome type 1 and identified an autosomal dominant missense mutation (R190Q) in the KCNQ1 gene. We obtained dermal fibroblasts from two family members and two healthy controls and infected them with retroviral vectors encoding the human transcription factors OCT3/4, SOX2, KLF4, and c-MYC to generate pluripotent stem cells. With the use of a specific protocol, these cells were then directed to differentiate into cardiac myocytes. RESULTS: Induced pluripotent stem cells maintained the disease genotype of long-QT syndrome type 1 and generated functional myocytes. Individual cells showed a "ventricular," "atrial," or "nodal" phenotype, as evidenced by the expression of cell-type­specific markers and as seen in recordings of the action potentials in single cells. The duration of the action potential was markedly prolonged in "ventricular" and "atrial" cells derived from patients with long-QT syndrome type 1, as compared with cells from control subjects. Further characterization of the role of the R190Q­KCNQ1 mutation in the pathogenesis of long-QT syndrome type 1 revealed a dominant negative trafficking defect associated with a 70 to 80% reduction in I(Ks) current and altered channel activation and deactivation properties. Moreover, we showed that myocytes derived from patients with long-QT syndrome type 1 had an increased susceptibility to catecholamine-induced tachyarrhythmia and that beta-blockade attenuated this phenotype. CONCLUSIONS: We generated patient-specific pluripotent stem cells from members of a family affected by long-QT syndrome type 1 and induced them to differentiate into functional cardiac myocytes. The patient-derived cells recapitulated the electrophysiological features of the disorder. (Funded by the European Research Council and others.)

Pulsed field ablation for pulmonary vein isolation: real-world experience and characterization of the antral lesion size compared with cryoballoon ablation.

BACKGROUND: Pulsed field ablation (PFA) is a new, non-thermal technology in the treatment of atrial fibrillation (AF). Early investigations have shown a promising safety profile with durable pulmonary vein isolation (PVI) and large antral lesions. However, clinical data remains scarce. METHODS: We investigated a cohort of 43 patients. Twenty-three patients underwent PVI with PFA in our hospital and we analyzed them with regard to procedural characteristics and with regard to the size of acute antral lesion which was estimated by using an electroanatomical map of the left atrium (LA). We compared these data with data of 20 patients who had undergone cryoballon (CB) PVI in our hospital. RESULTS: We could show acute isolation of all veins in all patients (100% PFA, 100% CB). Post-ablation high-density mapping revealed no early reconnection (0%). The acute antral lesion size of PFA was significantly higher compared to the CB (67.03 ± 12.69% vs. 57.39 ± 10.91%, p = 0.01). In the PFA group, we found no acute phrenic nerve injury, no major or minor bleeding, and no tamponade but one (4.34%) patient suffered from a stroke. Transient hypotension was observed frequently as well as transient bradycardia or asystole episodes requiring right ventricular pacing. In the CB group, no complications occurred. Furthermore, we discuss practical issues on PFA procedures. CONCLUSIONS: PFA is a promising technology with high acute PV isolation rate and large antral lesions compared to CB. However, larger trials with more patients and data on long-term freedom of AF but also complications are needed.