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Aims Despite its high incidence and mortality risk, there is no evidence-based treatment for non-ischaemic cardiogenic shock (CS). The aim of this study was to evaluate the use of mechanical circulatory support (MCS) for non-ischaemic CS treatment.Methods and results In this multicentre, international, retrospective study, data from 890 patients with non-ischaemic CS, defined as CS due to severe de-novo or acute-on-chronic heart failure with no need for urgent revascularization, treated with or without active MCS, were collected. The association between active MCS use and the primary endpoint of 30-day mortality was assessed in a 1:1 propensity-matched cohort. MCS was used in 386 (43%) patients. Patients treated with MCS presented with more severe CS (37% vs. 23% deteriorating CS, 30% vs. 25% in extremis CS) and had a lower left ventricular ejection fraction at baseline (21% vs. 25%). After matching, 267 patients treated with MCS were compared with 267 patients treated without MCS. In the matched cohort, MCS use was associated with a lower 30-day mortality (hazard ratio 0.76, 95% confidence interval 0.59-0.97). This finding was consistent through all tested subgroups except when CS severity was considered, indicating risk reduction especially in patients with deteriorating CS. However, complications occurred more frequently in patients with MCS; e.g. severe bleeding (16.5% vs. 6.4%) and access-site related ischaemia (6.7% vs. 0%).Conclusion In patients with non-ischaemic CS, MCS use was associated with lower 30-day mortality as compared to medical therapy only, but also with more complications. Randomized trials are needed to validate these findings. [GRAPHICS] Open Access funding enabled and organized by Projekt DEAL. Conflict of interest: B.S. reports speaker fees from Abiomed and AstraZeneca, outside of the submitted work. B.N.B. reports honoraria from Siemens Healthineers, outside of the submitted work. S.B. reports grants and personal fees from Abbott Diagnostics, Bayer, Siemens, Thermo Fisher, grants from Singulex, personal fees from Abbott, AstraZeneca, Amgen, Medtronic, Pfizer, Roche, Siemens Diagnostics, Novartis, outside of the submitted work. D.E. reports speaker fees from Abiomed, Bayer, Daiichi Sankyo, outside of the submitted work. P.H. reports travel compensation from Abiomed, outside of the submitted work. P.K. reports research support for basic, translational, and clinical research projects from European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK) and German Centre for Cardiovascular Research, from several drug and device companies active in atrial fibrillation, and has received honoraria from several such companies in the past, but not in the last 3 years. He is listed as inventor on two patents held by University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783; unrelated to the submitted work). S.K. reports research support from Cytosorbents and Daiichi Sankyo. He also received lecture fees from Astra, Bard, Baxter, Biotest, Cytosorbents, Daiichi Sankyo, Fresenius Medical Care, Gilead, Mitsubishi Tanabe Pharma, MSD, Pfizer, Philips and Zoll. He received consultant fees from Fresenius, Gilead, MSD and Pfizer, outside of the submitted work. P.L. reports speaker fees from AstraZeneca, Bayer, EdwardsLifesciences, Medtronic and Pfizer outside the submitted work. N.M. reports lecture fees Pfizer/Bristol-Myers Squibb and grant research from Getinge Global USA and Italfarmaco, outside of the submitted work. M.O. reports speaker honoraria from Abbott Medical, AstraZeneca, Abiomed, Bayer vital, Biotronik, Bristol-Myers Squibb, CytoSorbents, Daiichi Sankyo Deutschland, Edwards Lifesciences Services, Sedana Medical, outside of the submitted work. A.P. reports an unrestricted educational grant from Abbott Vascular, outside of the submitted work. T.R. reports speaker fees from AstraZeneca, Daiichy, Bayer, Novartis, Abiomed outside the submitted work. D.W. reports speaker fees from Abiomed, AstraZeneca, Bayer, Berlin-Chemie, Boehringer Ingelheim, Novartis and Medtronic, outside of the submitted work. All other authors have nothing to disclose.

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.

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality. Methods: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score–matched cohort. Results: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63–0.98]; P =0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site–related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%). Conclusions: In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial.

We describe a new mechanism for reopening a patent foramen ovale (PFO) after pulmonary embolism despite normal atrial filling pressures.

The concept of percutaneous extracorporeal life support (ECLS) is based on immediate cardiovascular stabilization allowing for sufficient end-organ perfusion, thus improving the outcome in patients with circulatory arrest. Lifebridge® (Zoll Medical GmbH, Germany) is a portable ECLS device designed for rapid application due to its automated set-up. A total of 60 tertiary cardiovascular centers were interrogated with regard to application and short-term results after use of Lifebridge ECLS system. Detailed data were collected by standardized case report forms in all centers consented to participate in the study. Demographic and clinical baseline characteristics of the patient population, procedural and follow-up data were recorded and analyzed. In total, 444 patients were analyzed regarding mortality. The detailed study cohort consisted of 112 patients. A total of 80% of the study subjects represented patients post cardiopulmonary resuscitation, 43% were in cardiogenic shock and 50% suffered from acute myocardial infarction. The survival rates were 36% immediately after device implementation and 16% after 30 days. Multivariable analysis revealed that only serum lactate concentration at admission could be proven as independent predictor of patients’ outcome. Patients with lactate concentrations above 10 mmol/L exhibited > 95% mortality (p

Background Intravenous morphine administration can adversely affect platelet inhibition induced by P2Y 12 receptor inhibitors after acute myocardial infarction. In contrast, some evidence suggests that opioid agonists may have cardioprotective effects on the myocardium. The aim of this prospective, randomized MonAMI (Impact of Morphine Treatment With and Without Metoclopramide Coadministration on Platelet Inhibition in Acute Myocardial Infarction) trial was, therefore, to investigate the impact of morphine with or without metoclopramide coadministration on myocardial and microvascular injury. Methods and Results Patients with acute myocardial infarction (n=138) were assigned in a 1:1:1 ratio to ticagrelor 180 mg plus: (1) intravenous morphine 5 mg (morphine group); (2) intravenous morphine 5 mg and metoclopramide 10 mg (morphine+metoclopramide group); or (3) intravenous placebo (control group) administered before primary percutaneous coronary intervention. Cardiac magnetic resonance imaging was performed in 104 patients on day 1 to 4 after the index event. Infarct size was significantly smaller in the morphine only group as compared with controls (percentage of left ventricular mass, 15.5 versus 17.9; P =0.047). Furthermore, the number of patients with microvascular obstruction was significantly lower after morphine administration (28% versus 54%; P =0.022) and the extent of microvascular obstruction was smaller (percentage of left ventricular mass, 0 versus 0.74; P =0.037). In multivariable regression analysis, morphine administration was independently associated with a reduced risk for the occurrence of microvascular obstruction (odds ratio, 0.37; 95% CI, 0.14–0.93 [ P =0.035]). There was no significant difference in infarct size ( P =0.491) and extent ( P =0.753) or presence ( P =0.914) of microvascular obstruction when comparing the morphine+metoclopramide group with the control group. Conclusions In this randomized study, intravenous administration of morphine before primary percutaneous coronary intervention resulted in a significant reduction of myocardial and microvascular damage following acute myocardial infarction. This effect was not observed in the morphine plus metoclopramide group. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02627950.

Background: The coronavirus disease (COVID-19) pandemic imposed diverse challenges on the health care system. Morbidity and mortality of non-COVID-19 emergencies might also have changed because hospitals may not be able to provide optimal care due to restructured resources and uncertainties how to deal with potentially infected patients. It has been recommended to stratify treatment of cardiovascular emergencies according to cardiovascular risk. However, data on the prevalence of asymptomatic SARS-CoV-2 infection in patients presenting with cardiac emergencies remain scarce.Methods: We retrospectively analyzed patients' data from a tertiary cardiology department between April 15 and May 31, 2020. All patients were screened on admission for COVID-19 symptoms using a questionnaire and body temperature measurements. All hospitalized patients were routinely screened using nasopharyngeal swab testing.Results: In total, we counted 710 urgent and emergency admissions. Nasopharyngeal swab tests were available in 689 (97%) patients, 409 and 280 of which presented as urgent and emergency admissions, respectively. Among 280 emergency admissions, none tested positive for SARS-CoV-2.Conclusion: In cardiac emergency patients which were screened negative for COVID-19 symptoms, the prevalence of SARS-CoV-2 infection in regions with a modest overall prevalence is low. This finding might be helpful to better determine timing of emergency procedures and reasonable usage of protective equipment during the COVID-19 crisis and the future.

Background Potential predictors of clinical complications of Takotsubo syndrome (TTS) are poorly known. Persistent ST-segment elevation (PSTE) may have an impact on outcome similar as previously reported in acute coronary syndrome. The aim of this study was to assess the prevalence and prognostic relevance of PSTE in patients with TTS. Methods Two-hundred-sixty-nine consecutive patients were enrolled in an international multicenter registry. PSTE was defined as the documentation of ST-elevation at least for the first 48h of hospitalization. Long-term mortality was evaluated in median 1.9years after the acute event. Results PSTE was found in 52 TTS patients (19%). Patients with PSTE were characterized by higher admission levels of troponin-I (23±12 vs 8±49ng/L, p p =0.02) and a higher rate of in-hospital complications (31% vs 17% p =0.03). At multivariate analysis including PSTE, age, male sex, admission ejection fraction, PSTE (odds ratio [OR] 4.2; 95% confidence interval [CI] 1.4–13; p =0.01), age (OR 1.05; 95%CI 1.00–1.10; p =0.03) and admission ejection fraction (OR 0.93; 95%CI 0.87–0.99; p =0.02) were independent predictors of in-hospital complications. At long-term follow-up no significant differences in terms of mortality were observed between patients with and without PSTE (19% vs 15%; p =0.5). However, PSTE was a predictor of major cardiac adverse events (MACE) at follow-up (HR 2.32, 95% CI 1.02–5.31, p 0.045). Conclusions In TTS patients, PSTE is a common finding, represents an independent predictor of in-hospital complications and could be associated with MACE at follow-up.

Background The detailed pathomechanism of Takotsubo syndrome (TS) is still elusive. Due to the predominance of postmenopausal females, a potential role of sex hormones has been suggested. However, the limited available data are contradictory. The aim of this study was to comprehensively assess the role of sex hormone levels in a large cohort of TS patients. Methods Serum samples of 57 female TS patients and 57 female patients with myocardial infarction (MI), matched for age (±2years) and repolarization disturbances were analyzed for estradiol (E2), estrone (E1), testosterone and androstenedione using liquid chromatography-tandem mass spectrometry. Results There was no difference concerning the concentrations of E1 [pmol/l (IQR): 89.1 (62.5, 132.0) vs. 98.8 (63.3, 156.0), p =0,441], testosterone [nmol/l (IQR): 0.67 (0.46, 1.00) vs. 0.80 (0.49, 1.08), p =0.382] and androstenedione [nmol/l (IQR): 2.03 (1.57, 3.11) vs. 2.98 (1.48, 5.27), p =0.244] between female TS and MI patients. Regarding E2, the majority of patients demonstrated concentrations below the detection limit of 30pmol/l (TS: n =41/54, 75.9%; MI: n =32/53, 60.4%; p =0.078). The remaining individuals with detectable E2 concentrations did not show a significant difference between TS and MI patients [pmol/l (IQR): 40.5 (33.0, 53.3) vs. 54.1 (37.9, 60.9); p =0.20]. Conclusions Altered sex hormone levels, especially an estradiol deficiency, could not be identified as a risk factor for TS.

The current study presents data from a real-world cohort of patients with refractory cardiogenic shock (CS) undergoing extracorporeal life support (ECLS) focusing on the comparison of elderly versus younger patients. One hundred consecutive patients with refractory CS underwent percutaneous ECLS implantation performed by interventional cardiologists. Follow-up was performed at hospital discharge as well as at a median of 18 months [interquartile range 15–36]. Patients were grouped according to median age (≤60 versus >60 years). ECLS could be weaned in more than half of the cohort (n = 56, 56%) with no differences between the age groups (p = 1.00). Despite similar rates of initial haemodynamic stabilisation, in-hospital mortality was higher in patients >60 years (82% versus 58%, p = 0.02). At mid-term follow-up, only three patients were alive in the group of patients >60 years. This resulted in a mortality rate of 94% in the elderly in comparison with 68% in patients aged ≤60 years (p = 0.001). Despite a high rate of initial successful ECLS weaning, mid-term prognosis of patients with CS undergoing ECLS above the age of 60 years is poor with superior results in patients aged ≤60 years.

Background Depression is frequent in heart failure (HF) and associated with adverse clinical outcomes. The randomized MOOD-HF trial showed that in depressed patients with systolic heart failure (HF) the selective serotonin reuptake inhibitor escitalopram (E) improved neither survival nor depression compared to placebo (P). The hypothalamic-pituitary-adrenocortical axis is known to be altered in depression or HF. This MOOD-HF substudy aimed to clarify whether circadian salivary cortisol levels (SCL) were predictive of adverse events in depressed MOOD-HF participants and whether outcomes differed according to treatment with E. Methods MOOD-HF participants (all suffering from symptomatic systolic HF with left ventricular ejection fraction (LVEF) Results In the total study cohort (146 patients on E, 147 on P) median morning SCL at BL was 0.210 μg/dL (IQR 0.141–0.338 μg/dL) and median evening (pm) SCL 0.067 μg/dL (0.036–0.128 μg/dL, p During 12 months follow-up the composite endpoint (all-cause death or rehospitalization) occurred least in E-treated patients with low pm-SCL and most often in E-treated patients with high pm-SCL (HR 2.02, 95% CI 1.12–3.65, p=0.010); patients on P had comparable event rates irrespective of BL pm-SCL (Figure A). Thus, numerically patients on E with low BL pm-SCL had lower event rates compared with corresponding P-treated patients (HR 0.76 (0.41–1.40, p=0.796)), while patients with high BL pm-SCL had higher event rates (HR 1.29 (0.74–2.24, p=0.799)) than corresponding P-treated patients. Patients with circadian SCL changes above the median receiving P experienced the composite primary endpoint least, while both subgroups with circadian SCL changes below the median and also patients with circadian SCL changes above the median on E had higher event rates (HR 0.66 (0.45–0.97, p=0.039), Figure B). Conclusion In depressed patients with systolic HF high pm-SCL are associated with more severe disease (depression and cardiac dysfunction). Extending primary MOOD-HF results indicating unfavourable outcomes related to E, the current findings suggest a SCL x treatment interaction with higher event rates in (sicker) patients with high pm-SCL and lower event rates in (less sick) patients with low pm-SCL when treated with the antidepressant. Low circadian changes of SCL were always associated with higher event rates. Acknowledgement/Funding BMBF (Grant 01 KG0702) and Lundbeck A/S Denmark

BACKGROUND Second-generation cryoballoon (CB2)-based pulmonary vein isolation (PVI) has demonstrated encouraging results in the treatment of atrial fibrillation (AF). This study sought to assess data on the safety, efficacy and clinical success of CB2-based PVI in patients with heart failure (HF) and reduced ejection fraction (HFrEF).Methods and Results:CB2-based PVI was performed in 551 consecutive patients in 3 highly experienced EP centers. Patients with HF and LVEF ≤40% were included (HFrEF group, n=50/551, 9.1%). Data were compared with propensity score-matched patients without HF and preserved left ventricular EF (LVEF) (n=50, control group). The median LVEF was HFrEF: 37% (35, 40) and control: 55% (55, 55), P

First-generation radiofrequency renal denervation devices may have had limited efficacy due to incomplete circumferential ablation and dependence on individual operator technique. This study evaluated a next-generation catheter-based technology using ultrasound designed to maximize nerve coverage using circumferential ultrasound energy.This was a prospective, multicenter, nonrandomized, postmarket study evaluating the safety and efficacy of an endovascular ultrasound renal denervation system (Paradise) in patients who met the European Society of Hypertension/European Society of Cardiology definition of resistant hypertension. Major exclusion criteria included renal artery stenosis and renal insufficiency. Patients were followed for 12 months. Safety and efficacy endpoints included procedural safety and renal artery patency, as well as changes in systolic office and 24-h ambulatory bllod pressure (BP) measurement.A total of 96 patients from eight European sites were included. Mean age was 63.9 years and 41% of patients were female. At baseline, mean 24-h ambulatory BP was 156.2/88.4 ± 15.4/12.7 mmHg, and mean office BP was 176.2/95.0 ± 20.6/16.0 mmHg. Patients were on average on 5.1 ± 2.5 antihypertensive agents. At 12 months, the average 24-h ambulatory BP change was -7.5/-3.8 ± 18.3/10.6 mmHg (P = 0.0007; P = 0.0024) with an average office BP change of -15.0/-7.0 ± 27.0/12.3 mmHg (P 0.0001 for both). At 12 months, there was a single patient death unrelated to the device or procedure.This single-arm study represents the largest cohort of patients treated with endovascular ultrasound renal denervation to date. Within this trial, the therapy appeared safe and resulted in sustained reductions in both office BP and 24-h ambulatory BP through 12 months.

Background Arrhythmias are frequent in Takotsubo cardiomyopathy (TTC) and a major determinant of outcome. Objective The purpose of this study was to provide a rationale for management strategies, particularly for permanent device implantation given the reversible nature of TTC. Methods Treatment strategies of arrhythmias including ventricular fibrillation (VF), ventricular tachycardia (VT), asystole, pulseless electrical activity, and complete atrioventricular (AV) or sinoatrial block were assessed in a bicentric cohort of consecutive patients with TTC (n = 286) with a mean follow-up period of 3.3 ± 2.4 years. Results The prevalence of arrhythmias during the acute phase of TTC was 12.2% (n = 35), consisting predominantly of VT (n = 16 [5.6%]), VF (n = 7 [2.4%]), and complete AV block (n = 8 [2.8%]). Seven patients received a permanent pacemaker because of complete AV (n = 6) or sinoatrial (n = 1) block. Regular device checkups were available in 2 patients and demonstrated ongoing high-degree AV block despite recovery of left ventricular function. Three patients with transient bradyarrhythmias who did not receive devices died shortly after hospital discharge from unknown causes. One patient received an implantable cardioverter-defibrillator after resuscitation for VF and did not require device interventions during 2-year follow-up. Patients with polymorphic VT (n = 7), monomorphic VT (n = 6), or VF (n = 2) who were discharged from hospital survived or died of noncardiac reasons, with the cause of death remaining unclear in 1 patient with monomorphic sustained VT. Conclusion Our data suggest that bradyarrhythmias in the acute setting of TTC may require permanent pacemaker implantation. In contrast, polymorphic ventricular arrhythmias might be managed with a temporary approach (eg, wearable cardioverter-defibrillators) until recovery of repolarization time and left ventricular function.

Aims Despite increasing research efforts, the prognostic consequences of takotsubo cardiomyopathy (TTC) remain largely unknown. The aim of this study was therefore to compare the long-term mortality rate of TTC patients with high-risk patients presenting with ST-segment elevation myocardial infarction (STEMI). Methods and results A total of 286 patients with TTC were matched for age and gender with 286 STEMI patients. Outcome was obtained with a standardized telephone follow-up. The primary analysis determined long-term mortality. A secondary analysis was performed evaluating 28-day and 1-year mortality. Follow-up was available for 96% of patients after a mean of 3.8 ± 2.5 years. In TTC patients, long-term mortality was significantly higher compared with the matched STEMI cohort [24.7% vs. 15.1%, hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.07-2.33; P = 0.02]. There was no significant difference in the rates of 28-day (5.5% vs. 5.7%, HR 0.96, 95% CI 0.47-1.94; P = 0.91) and 1-year mortality (12.5% vs. 9%, HR 1.42, 95% CI 0.85-2.38; P = 0.18). In multivariable regression analysis, male sex, a high Killip class on admission, and diabetes mellitus were identified as independent predictors of mortality in TTC patients. A risk score consisting of these factors showed a higher mortality with an increasing number of risk factors. Conclusion Mortality rates in TTC patients are higher than previously expected and long-term mortality exceeded that of patients with STEMI. A simple risk score may provide an approach to identify high-risk patients and predict clinical prognosis.

Background: Catheter-based percutaneous renal denervation therapy (RDN) is a controversially discussed treatment-strategy for patients with resistant arterial hypertension. Home blood pressure monitoring (HBPM) is superior to office blood pressure (OBP) measurements documenting effects of drug or interventional therapy and for predicting cardiovascular morbidity and mortality. We therefore aimed at comparing effects of RDN on OBP and HBPM. Methods: 28 patients with resistant hypertension were studied; 21 patients (29–85 years, median 67 years, 5.4 ± 1.3 antihypertensive drugs) were included into the treatment arm and 7 patients (37–70 years, median 68 years, 5.1 ± 2.2 antihypertensive drugs) served as controls. RDN was performed with a Medtronic™ radiofrequency catheter-ablation-system. For OBP and HBPM measurements patients were followed up to 6 months. For controls, a mean of approximately 378 measurements in 167 ± 13.5 days was included into analysis. In RDN patients follow-up was 157.7 ± 61.8 days with a mean of approximately 323 ambulatory measurements. A mean for each week was calculated. Results: In controls, no significant change of OBP was observed (baseline: systolic 162.2 ± 11.6 mm Hg vs. 6 months: systolic 162.8 ± 22.9 mm Hg; p > 0.05). Accordingly, HBPM values didn't change (baseline: systolic 161.2 ± 15.1 mm Hg vs. 6 months: systolic 155.8 ± 24.6 mm Hg, p > 0.05). In RDN patients a significant reduction of OBP (baseline: systolic 169 ± 12.5 mm Hg vs. 6 months: systolic 150.6 ± 19.2 mm Hg, p

Patients experiencing out-of-hospital cardiac arrest (OHCA) without ST-segment elevation are a heterogenic group with a variety of underlying causes. Up to one-third of patients display a significant coronary lesion compatible with myocardial infarction as OHCA trigger. There are no randomized data on patient selection and timing of invasive coronary angiography after admission. METHODS AND RESULTS: The TOMAHAWK trial randomly assigns 558 patients with return of spontaneous circulation after OHCA with no obvious extracardiac origin of cardiac arrest and no ST-segment elevation/left bundle-branch block on postresuscitation electrocardiogram to either immediate coronary angiography or initial intensive care assessment with delayed/selective angiography in a 1:1 ratio. The primary end point is 30-day all-cause mortality. Secondary analyses will be performed with respect to initial rhythm, electrocardiographic patterns, myocardial infarction as underlying cause, neurological outcome, as well as clinical and laboratory markers. Clinical follow-up will be performed at 6 and 12 months. Safety end points include bleeding and stroke. CONCLUSION: The TOMAHAWK trial will address the unresolved issue of timing and general indication of angiography after OHCA without ST-segment elevation.

Background Left ventricular ( LV ) thrombi during Takotsubo syndrome represent a potential complication and can be associated with cerebrovascular embolic events. The aim of this study was to evaluate the exact incidence, predictors, and management strategies of LV thrombi in patients with Takotsubo syndrome. Methods and Results We enrolled 541 consecutive patients in a multicenter international registry. Clinical features and echocardiographic data at admission, during hospitalization, and after 3 months were evaluated. Survival rates for long‐term follow‐up (mean 984±908 days) were recorded. Twelve Takotsubo syndrome patients (2.2%) developed LV thrombi (all female presenting with apical ballooning pattern). All patients with LV thrombi were treated with oral anticoagulation therapy; however, 2 (17%) had a stroke before treatment initiation. These patients were characterized by a higher prevalence of ST ‐elevation (56% versus 16%; P P =0.001) as compared with those without LV thrombi. At multivariate analysis including age, sex, LV ejection fraction, ST ‐elevation at admission, and apical ballooning pattern, troponin I level >10 ng/mL was the only predictor for LV thrombosis (hazard ratio 6.6, confidence interval, 1.01–40.0; P =0.04). After 3 months all LV thrombi disappeared. Oral anticoagulation therapy was interrupted in all patients except 1. At long‐term follow‐up, the survival rate was not different between patients with and without LV thrombi (84% versus 85%; P =0.99). Conclusions LV thrombi have a relatively low incidence among patients with Takotsubo syndrome and were detected in female patients with apical ballooning pattern and increased troponin levels. Oral anticoagulation therapy for 3 months seems reasonable in these high‐risk patients.

Takotsubo syndrome (TTS), a form of acute transient heart failure, has been associated with severe complications and considerable mortality rates. N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) might serve as a marker to identify high-risk patients but has not yet been investigated regarding prognostic implications in TTS. Aim of this study was to determine the short- and long-term prognostic utility of NT-proBNP in patients with TTS. The predictive value of admission NT-proBNP was assessed in an international, multicenter study including 177 consecutive TTS patients. Predefined endpoints were 30-day major adverse cardiac events (MACE) consisting of all-cause death, cardiogenic shock, and pulmonary edema as well as long-term mortality in median 2.3 years after the acute event. Stratification according to median admission NT-proBNP (4511 pg/ml) resulted in significantly higher 30-day MACE [22.5 versus 9.1%; odds ratio (OR) 2.90, 95% confidence interval (CI) 1.20–6.99 p = 0.015] and long-term mortality rates [16.3 versus 9.4%; hazard ratio (HR) 2.72, 95% CI 1.13–6.56 p = 0.021] in patients > median. The best admission NT-proBNP cutoffs to predict 30-day MACE and long-term mortality were determined at 5560 and 8178 pg/ml respectively, with subsequent improved risk stratification for short-term MACE (OR 3.61, 95% CI 1.49–8.72; p = 0.003) and long-term mortality (HR 4.40; 95% CI 1.85–10.44, p

Ambulatory blood pressure (BP) and central BP are better predictors for overall cardiovascular risk and mortality than brachial BP. Renal denervation (RDN) has been shown to reduce office brachial and central BP as well as brachial ambulatory BP, but data on central ambulatory BP are limited. Patients (N = 94) with treatment resistant hypertension (TRH) who underwent RDN were included. Ambulatory BP, including central pressures, hemodynamics, and arterial stiffness were measured at baseline and 3, 6, 12 months after RDN by an oscillometric device (MobiloGraph(™)). At 3, 6, and 12‐month follow‐ups, brachial ambulatory BP was reduced (P for all

Takotsubo syndrome (TTS) is associated with a considerable risk of complications during the acute phase and substantial long-term mortality rates. Concomitant atrial fibrillation may have an impact on outcome in these patients. Aim of this study was to assess the prevalence and prognostic relevance of atrial fibrillation in TTS.We performed an international, multicenter study including 387 TTS patients consecutively enrolled at 3 centers. Atrial fibrillation was defined as known history before admission or documented episodes during hospital stay. Long-term mortality was evaluated in median 2.9years after the acute event.Atrial fibrillation was found in 97 TTS patients (25.1%) and was associated with older age (p0.01), less emotional triggers (p=0.03), higher incidence of cardiogenic shock (p0.01), lower left ventricular ejection fraction (p0.01), and a prolonged hospital stay (p0.01). Determinants of atrial fibrillation at admission (n=34 patients; 9.0%) in multivariate logistic regression analysis were age (p=0.001) and cardiogenic shock (p=0.013). Long-term mortality was significantly higher in TTS patients with as compared to patients without atrial fibrillation (35.2% versus 15.3%; hazard ratio 3.02, 95% confidence interval 1.90-4.78; p0.001). In multivariate Cox regression analysis atrial fibrillation was identified as an independent determinant of outcome even after adjustment for clinical variables, left ventricular functional parameters (ballooning pattern, ejection fraction), and cardiogenic shock.In TTS patients, atrial fibrillation is frequent and associated with increased long-term mortality rates. Furthermore, our study identifies atrial fibrillation as an independent predictor of outcome and a potential tool for risk stratification in TTS.

Background Takotsubo syndrome (TTS) is characterized by a transient left and/or right ventricular dysfunction as a consequence of a distinctive pattern of regional wall motion abnormalities. However, a systematic evaluation of the left atrial (LA) function in patients with TTS is lacking. The aim of the present study was therefore to comprehensively assess LA performance indexes and function in patients with TTS. Methods We compared LA function assessed by volumetric indexes derived from fractional volume changes in cardiovascular magnetic resonance (CMR) between 125 TTS patients and 125 patients with anterior ST-segment elevation myocardial infarction (STEMI). Furthermore, recovery of LA performance was evaluated in a subgroup of 20 TTS patients with follow-up CMR data. Results Patients with TTS demonstrated a significantly lower total LA emptying fraction (EF) [44% (interquartile range (IQR) 34–53%) versus 51% (IQR 42–56%); p

Background Disrupted atherosclerotic plaques in the left anterior descending coronary artery are discussed controversially as a potential pathophysiological mechanism in Takotsubo syndrome ( TTS ). Therefore, the aim of the present study was to assess plaque burden and morphology by using optical coherence tomography in patients with TTS . Methods and Results A total of 23 consecutive TTS patients were included in this single‐center study and underwent optical coherence tomography imaging of the left main coronary artery and the left anterior descending coronary artery at acute presentation. All patients fulfilled the established diagnostic criteria for TTS and the diagnosis was confirmed with a multimodality imaging approach including cardiac magnetic resonance in 16 patients (69.6%). Atherosclerotic plaques located in the left anterior descending coronary artery or both the left anterior descending coronary artery and the left main coronary artery were detected in 16 TTS patients (69.6%), with 6 patients exhibiting multiple plaque types. In addition to the predominant fibrocalcific (52.2%) and lipid‐rich plaques (30.4%), thin‐cap fibroatheromas were also found in 6 patients (26.1%). However, ruptured plaques or intracoronary thrombi were not observed. Vessel stenosis >50% was found in 3 patients (13.0%) by analyzing cross‐sectional areas. Clinical characteristics and cardiac magnetic resonance findings did not differ significantly between TTS patients with and without atherosclerotic plaques. Conclusions Using optical coherence tomography, the present study revealed a high prevalence of atherosclerotic plaques in patients with TTS , including a considerable number of highly vulnerable thin‐cap fibroatheromas. However, ruptured plaques or intracoronary thrombi were not observed and are therefore most likely not the underlying mechanism of TTS .

The aim of the present analysis was to evaluate the prognostic impact of different ballooning patterns in patients with Takotsubo cardiomyopathy (TTC). A total of 285 consecutive patients with TTC were included. Clinical characteristics and short- and long-term outcomes were compared between patients with typical apical ballooning (n = 204) and patients with an atypical ballooning pattern including midventricular and basal ballooning (n = 81). Patients with typical apical ballooning were significantly older (73.3 ± 10.2 vs 68.4 ± 10.3 years; p0.01) and had a higher prevalence of diabetes mellitus (25.5% vs 12.3%; p = 0.02). The initial left ventricular (LV) ejection fraction was significantly lower in case of apical ballooning (41.5 ± 10.4% vs 46.9 ± 10.9%; p0.01) but recovered to normal values in both groups (58.4 ± 8.0 vs 59.7 ± 7.0; p = 0.25). Although 28-day mortality did not differ significantly (p = 0.10), typical apical ballooning was associated with an increased 6-month (13.4% vs 1.3%; hazard ratio [HR] 10.81, 95% confidence interval [CI] 1.47 to 79.66; p = 0.02) and long-term mortality rates (28.9% vs 14.5%; HR 2.24, 95% CI 1.17 to 4.71; p = 0.02). A landmark analysis which included only patients who survived the first 6 months after the initial event demonstrated similar mortality rates in patients with typical (17.9%) and atypical (13.3%) ballooning (HR 1.36, 95% CI 0.67 to 2.79; p = 0.40). In conclusion, in patients with TTC, typical apical ballooning is associated with more severe LV dysfunction at acute presentation and higher mortality rates within the first 6 months after the initial event. After complete recovery of LV function, prognosis is similar in patients with typical and atypical ballooning patterns.

The efficacy of first-generation radiofrequency renal denervation devices may have been limited due to incomplete circumferential denervation and dependence on individual operator technique. The Paradise Renal Denervation System (ReCor Medical, Palo Alto, CA) was designed to maximize nerve coverage

Cardiogenic shock (CS) is still the predominant cause of in-hospital death in patients with acute myocardial infarction, although mortality has been reduced in recent years. Early percutaneous coronary intervention and coronary artery bypass grafting are causal therapies implemented in CS, supported by catecholamines, fluids, intra-aortic balloon pumping, and also active percutaneous assist devices. There is only limited evidence from randomized studies of any of these treatments in CS, except for early revascularization and the relative ineffectiveness of intra-aortic balloon pumping. This review will present treatment pathways of CS complicating acute myocardial infarction, with a major focus on revascularization, intensive care unit treatment, and mechanical support devices.

AIM: Experimental and clinical studies have demonstrated that matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) are upregulated in dilated failing hearts and involved in the development and progression of myocardial remodelling. However, changes in MMP and TIMP protein levels or activity in the diabetic heart has not yet been described. METHODS: Untreated male Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats were sacrificed at the age of 6 (prediabetic), 22 (diabetic) and 42 (late diabetes) weeks (wks) and body weight, total heart weight and plasma glucose were measured (n=7, each group). MMP-2, MMP-9 and TIMP-1 were quantified by Western blot analysis of total protein isolated from left ventricular tissue. Expression of MMP/TIMP mRNA was determined by quantitative PCR (Taqman ® ). Additionally paraffin sections of the left ventricular myocardium were stained with Sirius Red to quantify cardiac fibrosis in percent of visual field. RESULTS: (see table1 ) In summary, expression of myocardial MMP-2 and MMP-9 increased, whereas TIMP-1 decreased throughout life in diabetic and non-diabetic animals. However, expression of MMP-2 and MMP-9 was significantly diminished in ZDF compared to ZL rats during various stages of diabetes. TIMP-1 expression was lower in diabetic animals only in the prediabetic stage. Similar results were found in quantitative RT-PCR. The relative amount of fibrosis in left ventricular myocardium was markedly enhanced in late stage of diabetes (ZDF 41% fibrosis/visual field vs. ZL 18%). CONCLUSION: The observed results may play a distinctive role in the remodelling processes in late stages of disease. The regulation of expression of MMPs may, therefore, be a useful therapeutic strategy to manage diabetic cardiomyopathy. Table 1 )

In arterial hypertension risk factor evaluation, including LV mass measurements and risk stratification using risk different charts and scores is usual practice. In chronic heart failure NT-proBNP has been shown to be a marker of wall stress and prognosis. Renal denervation (RDN) is a therapeutic

Backround: Patients (pts.) with resistant hypertension have been characterized by increased sympathetic nerve activity when compared to normotensive subjects. Before the introduction of modern antihypertensive drugs patients have been treated with surgical lumbal sympathectomy. However, this procedure was linked with severe side effects such as severe orthostatic dysregulation. Recently, catheter-based bilateral renal denervation (RDN) of sympathetic nerve fibres has been shown to significantly lower blood pressure (BP). However, the effect of RDN on orthostatic blood pressure regulation is not known. Methods: 9 pts. were selected according to the SIMPLICITY criteria and treated with RDN. Follow-up included baseline values and measurements at 3 and 6 months. Office BP was measured with OmeronTM. A Schellong test was performed at baseline, 3 and 6 month after RDN. After being in relaxed supine position for 10 min. BP and heart rate (HR) was measured every 2 minutes. BP and HR were then measured in an upright position over ten min. and after returning into a supine positon. Results: The baseline mean office SBP/DBP was 176/89 mmHg (SEM 5/6 mmHg), after 6 month 141/80 mmHg (SEM 6/4). Pts. were treated with 5.3 antihypertensives mean. As shown by the Schellong test there was no significant difference in the overall orthostatic regulation of the BP, the level of BP was lower 6 month after RDN as compared to baseline. HR did not differ between the two groups. ![Figure][1] Figure 1. SBP at 3 and 6 month Conclusion: (i) In patients with resistant hypertension RDN resulted in a significant blood pressure reduction after 3 and 6 month. (ii) No orthostatic dysregulation or syncope were be identified after RDN using the Schellong-test, indicating that RDN has no effect on venous tone and venous capacity when tilting into an upright position. [1]: pending:yes

Background: Percutaneous renal denervation (RDN) is established as a novel treatment strategy for patients with resistant arterial hypertension. Central aortic blood pressures and aortic stiffness are better predictors for cardiovascular risk than standard peripheral blood pressures. The present study aimed therefore to evaluate the effects of RDN on central pressures and arterial stiffness derived from 24h ambulatory monitoring. Methods: 26 resistant arterial hypertension patients (31–85 years, mean age 66±9 years) with a mean 24h ambulatory systolic blood pressure (ABP) of more than 135 mmHg and an office systolic peripheral blood pressure of more than 150 mmHg were included. Patients were treated with an Ardian/Medtronic™ PRD radiofrequency ablation catheter system. ABP, central pressure and arterial stiffness were measured with an I.E.M. device (MobiloGraph™). Results: In all patients [5.7±1.9 antihypertensive drugs] RDN was technically successful. Peripheral systolic blood pressure (pSBP) declined significantly in the therapy group from 153±13 mmHg to 145±14 mmHg [p=0.002] after three month and to 144±16 mmHg after six months [p