Publications by authors named "Klaus Empen"

76 Publications

Reduced-dose intravenous thrombolysis for acute intermediate high-risk pulmonary embolism: Rationale and design of the PEITHO-3 trial.

Thromb Haemost 2021 Sep 24. Epub 2021 Sep 24.

Hopital Europeen Georges Pompidou, Paris, France.

Intermediate high-risk pulmonary embolism (PE) is characterised by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent haemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of haemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion efficacy. The Pulmonary Embolism International Trial (PEITHO)-3 study (EudraCT 2018-000816-96) is a randomised, placebo-controlled, double-blind, multicentre, multinational trial with long-term follow-up. We will compare the efficacy and safety of a reduced-dose alteplase regimen with standard heparin anticoagulation. Patients with intermediate high-risk PE will also fulfil at least one clinical criterion of severity: systolic blood pressure ≤ 110 mmHg, respiratory rate >20 breaths/min, or history of heart failure. The primary efficacy outcome is the composite of all-cause death, haemodynamic decompensation or PE recurrence within 30 days of randomisation. Key secondary outcomes, to be included in hierarchical analysis, are fatal or GUSTO severe or life-threatening bleeding; net clinical benefit (primary efficacy outcome plus severe or life-threatening bleeding); and all-cause death, all within 30 days. All outcomes will be adjudicated by an independent committee. Further outcomes include PE-related death, haemodynamic decompensation, or stroke within 30 days; dyspnoea, functional limitation or RV dysfunction at 6 months and 2 years; and utilisation of healthcare resources within 30 days and 2 years. The study is planned to enrol 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations.
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http://dx.doi.org/10.1055/a-1653-4699DOI Listing
September 2021

Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial.

Lancet Haematol 2021 Sep 4;8(9):e627-e636. Epub 2021 Aug 4.

Internal and Subintensive Medicine Department, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy.

Background: Current guidelines recommend a risk-adjusted treatment strategy for the management of acute pulmonary embolism. This is a particular patient category for whom optimal treatment (anticoagulant treatment, reperfusion strategies, and duration of hospitalisation) is currently unknown. We investigated whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h, followed by a switch to a direct oral anticoagulant (dabigatran), is effective and safe.

Methods: We did a multinational, multicentre, single-arm, phase 4 trial at 42 hospitals in Austria, Belgium, France, Germany, Italy, Netherlands, Romania, Slovenia, and Spain. Adult patients (aged ≥18 years) with symptomatic intermediate-risk pulmonary embolism, with or without deep-vein thrombosis, were enrolled. Patients received parenteral low-molecular-weight or unfractionated heparin for 72 h after diagnosis of pulmonary embolism before switching to oral dabigatran 150 mg twice per day following a standard clinical assessment. The primary outcome was recurrent symptomatic venous thromboembolism or pulmonary embolism-related death within 6 months. The primary and safety outcomes were assessed in the intention-to-treat population. The study was terminated early, as advised by the data safety and monitoring board, following sample size adaptation after the predefined interim analysis on Dec 18, 2018. This trial is registered with the EU Clinical Trials Register (EudraCT 2015-001830-12) and ClinicalTrials.gov (NCT02596555).

Findings: Between Jan 1, 2016, and July 31, 2019, 1418 patients with pulmonary embolism were screened, of whom 402 were enrolled and were included in the intention-to-treat analysis (median age was 69·5 years [IQR 60·0-78·0); 192 [48%] were women and 210 [52%] were men). Median follow-up was 217 days (IQR 210-224) and 370 (92%) patients adhered to the protocol. The primary outcome occurred in seven (2% [upper bound of right-sided 95% CI 3]; p<0·0001 for rejecting the null hypothesis) patients, with all events occurring in those with intermediate-high-risk pulmonary embolism (seven [3%; upper bound of right-sided 95% CI 5] of 283). At 6 months, 11 (3% [95% CI 1-5]) of 402 patients had at least one major bleeding event and 16 (4% [2-6]) had at least one clinically relevant non-major bleeding event; the only fatal haemorrhage occurred in one (<1%) patient before the switch to dabigatran.

Interpretation: A strategy of early switch from heparin to dabigatran following standard clinical assessment was effective and safe in patients with intermediate-risk pulmonary embolism. Our results can help to refine guideline recommendations for the initial treatment of acute intermediate-risk pulmonary embolism, optimising the use of resources and avoiding extended hospitalisation.

Funding: German Federal Ministry of Education and Research, University Medical Center Mainz, and Boehringer Ingelheim.
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http://dx.doi.org/10.1016/S2352-3026(21)00203-9DOI Listing
September 2021

Ethnic comparison in takotsubo syndrome: novel insights from the International Takotsubo Registry.

Clin Res Cardiol 2021 May 19. Epub 2021 May 19.

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

Background: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes.

Methods: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients.

Results: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients.

Conclusion: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers.

Trial Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01947621.
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http://dx.doi.org/10.1007/s00392-021-01857-4DOI Listing
May 2021

Analysis of DCM associated protein alterations of human right and left ventricles.

J Proteomics 2021 01 17;231:104018. Epub 2020 Oct 17.

Department for Internal Medicine B, University Medicine Greifswald, Ferdinand-Sauerbruch-Str., D-17475 Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany. Electronic address:

Dilated cardiomyopathy (DCM) is characterized by ventricular chamber enlargement and impaired myocardial function. Endomyocardial biopsies (EMB) enable immunohistochemical and molecular characterization of this disease. However, knowledge about specific molecular patterns and their relation to cardiac function in both ventricles is rare. Therefore, we performed a mass spectrometric analysis of 28 paired EMBs of left (LV) and right ventricles (RV) of patients with DCM or suspected myocarditis allowing quantitative profiling of 743 proteins. We analysed associations between protein abundance of LV and RV as well as the echocardiographic parameters LVEF, TAPSE, LVEDDI, and RVEDDI by linear regression models. Overall, more LV than RV proteins were associated with LV parameters or with RVEDDI. Most LV and RV proteins increasing in level with impairing of LVEF were annotated to structural components of cardiac tissue. Additionally, a high proportion of LV proteins with metabolic functions decreased in level with decreasing LVEF. Results were validated with LV heart sections of a genetic murine heart failure model. The study shows, that remodelling and systolic dysfunction in DCM is mirrored by distinct alterations in protein composition of both ventricles. Loss of LV systolic function is reflected predominantly by alterations in proteins assigned to metabolic functions in the LV whereas structural remodelling was more obvious in the RV. Alterations related to intermediate filaments were seen in both ventricles and highlight such proteins as early indicators of LV loss of function. SIGNIFICANCE: The present study report protein sets in the RV and the LV being associated with ventricular function and remodelling in DCM. Protein abundances in the LV and the RV emphasize and expand current knowledge on pathophysiological changes in heart failure and DCM. While RV and LV EMBs do not differ concerning diagnostic assessment of inflammatory status and virus persistence, additional information reflecting disease severity associated protein alterations can be gained by EMB protein profiling. RV and LV protein data provided complementary information. The protein pattern of the LV reflects metabolic changes and an impaired energy production, which is associated with the degree of LV systolic dysfunction and remodelling and may yield important information about the disease status in DCM. On the other hand, at this disease stage of DCM with still preserved RV function, RV alterations in structural proteins may reflect myocardial compensatory protective mechanisms for maintenance of structure and cellular function. The study highlight particular proteins being of interest as heart failure biomarkers in both ventricles which seem to reflect the severity of the disease. Further comparative studies between different HF aetiologies have to evaluate those proteins as markers specific for DCM.
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http://dx.doi.org/10.1016/j.jprot.2020.104018DOI Listing
January 2021

Survival and quality of life after early discharge in low-risk pulmonary embolism.

Eur Respir J 2021 02 4;57(2). Epub 2021 Feb 4.

Emergency Dept, Clinico San Carlos Hospital, IdISSC, Madrid, Spain.

Introduction: Early discharge of patients with acute low-risk pulmonary embolism requires validation by prospective trials with clinical and quality-of-life outcomes.

Methods: The multinational Home Treatment of Patients with Low-Risk Pulmonary Embolism with the Oral Factor Xa Inhibitor Rivaroxaban (HoT-PE) single-arm management trial investigated early discharge followed by ambulatory treatment with rivaroxaban. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. The present analysis includes the entire trial population (576 patients). In addition to 3-month recurrence (primary outcome) and 1-year overall mortality, we analysed self-reported disease-specific (Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire) and generic (five-level five-dimension EuroQoL (EQ-5D-5L) scale) quality of life as well as treatment satisfaction (Anti-Clot Treatment Scale (ACTS)) after pulmonary embolism.

Results: The primary efficacy outcome occurred in three (0.5%, one-sided upper 95% CI 1.3%) patients. The 1-year mortality was 2.4%. The mean±sd PEmb-QoL decreased from 28.9±20.6% at 3 weeks to 19.9±15.4% at 3 months, a mean change (improvement) of -9.1% (p<0.0001). Improvement was consistent across all PEmb-QoL dimensions. The EQ-5D-5L was 0.89±0.12 at 3 weeks after enrolment and improved to 0.91±0.12 at 3 months (p<0.0001). Female sex and cardiopulmonary disease were associated with poorer disease-specific and generic quality of life; older age was associated with faster worsening of generic quality of life. The ACTS burden score improved from 40.5±6.6 points at 3 weeks to 42.5±5.9 points at 3 months (p<0.0001).

Conclusions: Our results further support early discharge and ambulatory oral anticoagulation for selected patients with low-risk pulmonary embolism. Targeted strategies may be necessary to further improve quality of life in specific patient subgroups.
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http://dx.doi.org/10.1183/13993003.02368-2020DOI Listing
February 2021

Dual device closure of a bilobar left atrial appendage with a plug (Watchman 2.5™ 30 mm) and a pacifier (Amulet™ 20 mm) device.

Hellenic J Cardiol 2021 Jan-Feb;62(1):81-83. Epub 2020 Apr 15.

Mid-German Heart Center, Department of Internal Medicine III (KIM III), Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06120 Halle (Saale), Germany. Electronic address:

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http://dx.doi.org/10.1016/j.hjc.2020.03.005DOI Listing
August 2021

Impact of aspirin on takotsubo syndrome: a propensity score-based analysis of the InterTAK Registry.

Eur J Heart Fail 2020 02 20;22(2):330-337. Epub 2019 Dec 20.

Department of Internal Medicine III, Heart Center University of Cologne, Cologne, Germany.

Aims: The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS).

Methods And Results: Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50-3.04, P = 0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78-1.58, P = 0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting.

Conclusion: In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621.
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http://dx.doi.org/10.1002/ejhf.1698DOI Listing
February 2020

Adenosine stress perfusion cardiac magnetic resonance imaging in patients undergoing intracoronary bone marrow cell transfer after ST-elevation myocardial infarction: the BOOST-2 perfusion substudy.

Clin Res Cardiol 2020 May 10;109(5):539-548. Epub 2019 Aug 10.

Department of Cardiology, Robert-Bosch-Medical Centre, Stuttgart, Germany.

Aims: In the placebo-controlled, double-blind BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) 2 trial, intracoronary autologous bone marrow cell (BMC) transfer did not improve recovery of left ventricular ejection fraction (LVEF) at 6 months in patients with ST-elevation myocardial infarction (STEMI) and moderately reduced LVEF. Regional myocardial perfusion as determined by adenosine stress perfusion cardiac magnetic resonance imaging (S-CMR) may be more sensitive than global LVEF in detecting BMC treatment effects. Here, we sought to evaluate (i) the changes of myocardial perfusion in the infarct area over time (ii) the effects of BMC therapy on infarct perfusion, and (iii) the relation of infarct perfusion to LVEF recovery at 6 months.

Methods And Results: In 51 patients from BOOST-2 (placebo, n = 10; BMC, n = 41), S-CMR was performed 5.1 ± 2.9 days after PCI (before placebo/BMC treatment) and after 6 months. Infarct perfusion improved from baseline to 6 months in the overall patient cohort as reflected by the semi-quantitative parameters, perfusion defect-infarct size ratio (change from 0.54 ± 0.20 to 0.43 ± 0.22; P = 0.006) and perfusion defect-upslope ratio (0.54 ± 0.23 to 0.68 ± 0.22; P < 0.001), irrespective of randomised treatment. Perfusion defect-upslope ratio at baseline correlated with LVEF recovery (r = 0.62; P < 0.001) after 6 months, with a threshold of 0.54 providing the best sensitivity (79%) and specificity (74%) (area under the curve, 0.79; 95% confidence interval, 0.67-0.92).

Conclusion: Infarct perfusion improves from baseline to 6 months and predicts LVEF recovery in STEMI patients undergoing early PCI. Intracoronary BMC therapy did not enhance infarct perfusion in the BOOST-2 trial.
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http://dx.doi.org/10.1007/s00392-019-01537-4DOI Listing
May 2020

Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial.

Eur Heart J 2020 01;41(4):509-518

Helios Albert-Schweitzer-Klinik, Albert-Schweitzer-Weg 1, 37154 Northeim, Germany.

Aims: To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban.

Methods And Results: We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%).

Conclusion: Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.
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http://dx.doi.org/10.1093/eurheartj/ehz367DOI Listing
January 2020

Cardiac arrest in takotsubo syndrome: results from the InterTAK Registry.

Eur Heart J 2019 07;40(26):2142-2151

Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Leipzig, Germany.

Aims: We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS).

Methods And Results: We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P < 0.001) and 5-year mortality (68.9% vs. 16.7%, P < 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission.

Conclusions: Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.
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http://dx.doi.org/10.1093/eurheartj/ehz170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612368PMC
July 2019

Impella Support for Acute Myocardial Infarction Complicated by Cardiogenic Shock.

Circulation 2019 03;139(10):1249-1258

University Hospital Jena, Department of Internal Medicine I, Germany (S.M-W., P.C.S.).

Background: Percutaneous mechanical circulatory support devices are increasingly used in acute myocardial infarction complicated by cardiogenic shock (AMI-CS), despite limited evidence for their effectiveness. The aim of this study was to evaluate outcomes associated with use of the Impella device compared with intra-aortic balloon pump (IABP) and medical treatment in patients with AMI-CS.

Methods: Data of patients with AMI-CS treated with the Impella device at European tertiary care hospitals were collected retrospectively. All patients underwent early revascularization and received optimal medical treatment. Using IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) trial inclusion and exclusion criteria, 372 patients were identified and included in this analysis. These patients were matched to 600 patients from the IABP-SHOCK II trial. The following baseline criteria were used as matching parameters: age, sex, mechanical ventilation, ejection fraction, prior cardiopulmonary resuscitation, and lactate. Primary end point was 30-day all-cause mortality.

Results: In total, 237 patients treated with an Impella could be matched to 237 patients from the IABP-SHOCK II trial. Baseline parameters were similarly distributed after matching. There was no significant difference in 30-day all-cause mortality (48.5% versus 46.4%, P=0.64). Severe or life-threatening bleeding (8.5% versus 3.0%, P<0.01) and peripheral vascular complications (9.8% versus 3.8%, P=0.01) occurred significantly more often in the Impella group. Limiting the analysis to IABP-treated patients as a control group did not change the results.

Conclusions: In this retrospective analysis of patients with AMI-CS, the use of an Impella device was not associated with lower 30-day mortality compared with matched patients from the IABP-SHOCK II trial treated with an IABP or medical therapy. To further evaluate this, a large randomized trial is warranted to determine the effect of the Impella device on outcome in patients with AMI-CS.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03313687.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.036614DOI Listing
March 2019

Incomplete echocardiographic recovery at 6 months predicts long-term sequelae after intermediate-risk pulmonary embolism. A post-hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial.

Clin Res Cardiol 2019 Jul 18;108(7):772-778. Epub 2018 Dec 18.

Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Introduction: Symptoms and functional limitation are frequently reported by survivors of acute pulmonary embolism (PE). However, current guidelines provide no specific recommendations on which patients should be followed after acute PE, when follow-up should be performed, and which tests it should include. Definition and classification of late PE sequelae are evolving, and their predictors remain to be determined.

Methods: In a post hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial, we focused on 219 survivors of acute intermediate-risk PE with clinical and echocardiographic follow-up 6 months after randomisation as well as over the long term (median, 3 years after acute PE). The primary outcome was a composite of (1) confirmed chronic thromboembolic pulmonary hypertension (CTEPH) or (2) 'post-PE impairment' (PPEI), defined by echocardiographic findings indicating an intermediate or high probability of pulmonary hypertension along with New York Heart Association functional class II-IV.

Results: Confirmed CTEPH or PPEI occurred in 29 (13.2%) patients, (6 with CTEPH and 23 with PPEI). A history of chronic heart failure at baseline and incomplete or absent recovery of echocardiographic parameters at 6 months predicted CTEPH or PPEI at long-term follow-up.

Conclusions: CTEPH or PPEI occurs in almost one out of seven patients after acute intermediate-risk PE. Six-month echocardiographic follow-up may be useful for timely detection of late sequelae.
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http://dx.doi.org/10.1007/s00392-018-1405-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584226PMC
July 2019

Remote ischemic preconditioning of the heart: Combining lower limb ischemia and electronic stimulation of the gastrocnemius muscle.

Clin Hemorheol Microcirc 2018 ;70(4):381-389

Kreiskrankenhaus Wolgast, Department of Internal Medicine, Wolgast, Germany.

Background: Remote ischemic preconditioning (RIPC) has been demonstrated to induce potent cardioprotection in individuals experiencing coronary ischemia. A protocol combining limb ischemia and electronic muscle stimulation of the ischemic skeletal muscle (RIPC+), performed in advance of coronary artery occlusion, was superior in terms of infarct size reduction when compared to RIPC alone.

Methods: This study was performed to evaluate the benefit of RIPC + in humans compared to a standard RIPC protocol and a control group. Patients with a single vessel coronary artery disease undergoing elective PCI were eligible to participate in this study. ST-segment elevations from an intracoronary ECG during 3 brief episodes of coronary artery balloon occlusions/dilatation were used as the primary endpoint.

Results: ST-elevations significantly declined from the first to the third angioplasty in the control but remained at the same level in the RIPC and RIPC+groups. The RIPC group was characterized by the lowest ST-segment shift during coronary ischemia, which was comparable to coronary balloon occlusion number 3 in the control group, indicating successful preconditioning by the conventional RIPC method. In contrast, ST segment elevations were significantly higher in the RIPC + group. Troponin levels taken 24 h after the study procedure were significantly lower in the RIPC when compared to the control and the RIPC + group.

Conclusion: Our results again confirm the feasibility of remote ischemic preconditioning in patients undergoing coronary angioplasty. According to our results ischemia combined with electronic skeletal muscle stimulation was not superior to conventional RIPC cycles (skeletal muscle ischemia alone).
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http://dx.doi.org/10.3233/CH-189303DOI Listing
April 2019

Long-Term Prognosis of Patients With Takotsubo Syndrome.

J Am Coll Cardiol 2018 08;72(8):874-882

Deutsches Herzzentrum München, Technische Universität München, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.

Background: Prognosis of Takotsubo syndrome (TTS) remains controversial due to scarcity of available data. Additionally, the effect of the triggering factors remains elusive.

Objectives: This study compared prognosis between TTS and acute coronary syndrome (ACS) patients and investigated short- and long-term outcomes in TTS based on different triggers.

Methods: Patients with TTS were enrolled from the International Takotsubo Registry. Long-term mortality of patients with TTS was compared to an age- and sex-matched cohort of patients with ACS. In addition, short- and long-term outcomes were compared between different groups according to triggering conditions.

Results: Overall, TTS patients had a comparable long-term mortality risk with ACS patients. Of 1,613 TTS patients, an emotional trigger was detected in 485 patients (30%). Of 630 patients (39%) related to physical triggers, 98 patients (6%) had acute neurologic disorders, while in the other 532 patients (33%), physical activities, medical conditions, or procedures were the triggering conditions. The remaining 498 patients (31%) had no identifiable trigger. TTS patients related to physical stress showed higher mortality rates than ACS patients during long-term follow-up, whereas patients related to emotional stress had better outcomes compared with ACS patients.

Conclusions: Overall, TTS patients had long-term outcomes comparable to age- and sex-matched ACS patients. Also, we demonstrated that TTS can either be benign or a life-threating condition depending on the inciting stress factor. We propose a new classification based on triggers, which can serve as a clinical tool to predict short- and long-term outcomes of TTS. (International Takotsubo Registry [InterTAK Registry]; NCT01947621).
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http://dx.doi.org/10.1016/j.jacc.2018.06.016DOI Listing
August 2018

MD-2 is a new predictive biomarker in dilated cardiomyopathy and exerts direct effects in isolated cardiomyocytes.

Int J Cardiol 2018 Nov 13;270:278-286. Epub 2018 Jun 13.

Department of Cardiology and Internal Medicine B, University Medicine Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Germany.

Background: Myeloid differentiation factor-2 (MD-2) has been shown to be an important modulator of the innate immune system, but its role in cardiac diseases is unknown. We investigated whether MD-2 plays a role as risk predictor and contributor in dilated cardiomyopathy (DCM).

Methods And Results: We included 174 patients with reduced left ventricular (LV) ejection fraction (LVEF <45%) due to DCM. Coronary artery disease and severe valvular diseases were excluded in all patients by angiography or echocardiography. Cardiac inflammation, viral infection and MD-2 expression were analyzed from right ventricular endomyocardial biopsies. MD-2 was quantified by ELISA in serum upon first hospital admission. Myocyte contractility and inflammatory response after stimulation with recombinant MD-2 protein were analyzed in isolated rat cardiomyocytes. Median follow-up of the patients was 3.51 years (2.73; 4.48) with 34 deaths. Absolute mortality risk increases in patients displaying a MD-2 serum concentration greater than the median (302 ng/ml) was 23% (P < 0.0001). Age- and sex-adjusted Cox regression analyses demonstrated that mortality risk was highly related to MD-2 concentrations (P < 0.001), but not to age or sex. An increase of 100 ng/ml in the MD-2 level was associated with an absolute mortality risk increase of 50.4%. Receiver operating characteristic (ROC) analyses showed no difference between MD-2 and nterminal-pro brain natriuretic peptide (NT-pro-BNP), while the combination of both MD-2 and NT-pro-BNP resulted in a significantly increased capability of risk prediction when compared to NT-pro-BNP alone (P = 0.014). In-vitro, recombinant MD-2 decreases cell shortening and modulates cytokine activation in isolated cardiomyocytes.

Conclusion: MD-2 predicts long-term outcome in DCM patients and improves mortality risk prediction capability compared to NT-pro-BNP alone. In addition, MD-2 exerts direct negative inotropic effects on isolated cardiomyocytes in-vitro. Further randomized trials should confirm MD-2 as a diagnostic and therapeutic target.
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http://dx.doi.org/10.1016/j.ijcard.2018.06.025DOI Listing
November 2018

Dabigatran after Short Heparin Anticoagulation for Acute Intermediate-Risk Pulmonary Embolism: Rationale and Design of the Single-Arm PEITHO-2 Study.

Thromb Haemost 2017 12 6;117(12):2425-2434. Epub 2017 Dec 6.

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.

Patients with intermediate-risk pulmonary embolism (PE) may, depending on the method and cut-off values used for definition, account for up to 60% of all patients with PE and have an 8% or higher risk of short-term adverse outcome. Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have been approved for the treatment of venous thromboembolism, their safety and efficacy as well as the optimal anticoagulation regimen using these drugs have not been systematically investigated in intermediate-risk PE. Moreover, it remains unknown how many patients with intermediate-high-risk and intermediate-low-risk PE were included in most of the phase III NOAC trials. The ongoing Pulmonary Embolism International Thrombolysis 2 (PEITHO-2) study is a prospective, multicentre, multinational, single-arm trial investigating whether treatment of acute intermediate-risk PE with parenteral heparin anticoagulation over the first 72 hours, followed by the direct oral thrombin inhibitor dabigatran over 6 months, is effective and safe. The primary efficacy outcome is recurrent symptomatic venous thromboembolism or death related to PE within the first 6 months. The primary safety outcome is major bleeding as defined by the International Society on Thrombosis and Haemostasis. Secondary outcomes include all-cause mortality, the overall duration of hospital stay (index event and repeated hospitalizations) and the temporal pattern of recovery of right ventricular function over the 6-month follow-up period. By applying and evaluating a contemporary risk-tailored treatment strategy for acute PE, PEITHO-2 will implement the recommendations of current guidelines and contribute to their further evolution.
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http://dx.doi.org/10.1160/TH17-06-0434DOI Listing
December 2017

Takayasu's arteritis: a case with relapse after urgent coronary revascularization.

BMC Res Notes 2017 Jul 25;10(1):311. Epub 2017 Jul 25.

Medizinische Klinik B, Universitätsmedizin Greifswald, Sauerbruchstrasse, 17475, Greifswald, Germany.

Background: Vasculitides are commonly unrecognized causes of coronary stenosis and myocardial ischemia. We report on a 24-year old patient with Takayasu's arteritis who underwent urgent percutaneous coronary intervention, suffered from symptomatic restenosis of the left main coronary artery during standard immunosuppressive therapy.

Case Presentation: A 24-year old woman was referred for coronary angiography because of typical progressive angina pectoris. On bicycle ergometry, there were both reproducible symptoms and deep ST segment depressions on precordial leads. Semi-selective angiography of the left coronary artery revealed high-grade ostial stenosis. Because of persistent angina pectoris and electrocardiographic signs of acute myocardial ischemia, immediate percutaneous coronary angioplasty with subsequent implantation of an everolimus-eluting stent was performed. This intervention was performed with excellent angiographic results. Because of several concomitant criteria including hypoechogenicity on postprocedural intravascular ultrasonography, the diagnosis of Takayasu's disease was made. The patient was treated with prednisolone and cyclophosphamide for 5 months. Because of recurrent angina pectoris, another coronary angiography was performed, which revealed high-grade in-stent-restenosis. Immunomodulatory therapy was switched to high-dose prednisolone and the anti-IL-6 receptor antagonist tocilizumab. The high-grade in-stent-restenosis persisted, and aortocoronary bypass graft surgery was performed with two saphenous vein grafts to the left anterior descending and circumflex artery. Since then, the patient has been doing well for 2 years.

Conclusion: In cases of treatment refractoriness during standard immunosuppressive therapy, more recently developed biological compounds may offer an alternative strategy.
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http://dx.doi.org/10.1186/s13104-017-2628-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576295PMC
July 2017

Intracoronary autologous bone marrow cell transfer after myocardial infarction: the BOOST-2 randomised placebo-controlled clinical trial.

Eur Heart J 2017 Oct;38(39):2936-2943

Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.

Aims: Intracoronary infusion of autologous nucleated bone marrow cells (BMCs) enhanced the recovery of left ventricular ejection fraction (LVEF) after ST-segment elevation myocardial infarction (STEMI) in the randomised-controlled, open-label BOOST trial. We reassessed the therapeutic potential of nucleated BMCs in the randomised placebo-controlled, double-blind BOOST-2 trial conducted in 10 centres in Germany and Norway.

Methods And Results: Using a multiple arm design, we investigated the dose-response relationship and explored whether γ-irradiation which eliminates the clonogenic potential of stem and progenitor cells has an impact on BMC efficacy. Between 9 March 2006 and 16 July 2013, 153 patients with large STEMI were randomly assigned to receive a single intracoronary infusion of placebo (control group), high-dose (hi)BMCs, low-dose (lo)BMCs, irradiated hiBMCs, or irradiated loBMCs 8.1 ± 2.6 days after percutaneous coronary intervention (PCI) in addition to guideline-recommended medical treatment. Change in LVEF from baseline (before cell infusion) to 6 months as determined by MRI was the primary endpoint. The trial is registered at Current Controlled Trials (ISRCTN17457407). Baseline LVEF was 45.0 ± 8.5% in the overall population. At 6 months, LVEF had increased by 3.3 percentage points in the control group and 4.3 percentage points in the hiBMC group. The estimated treatment effect was 1.0 percentage points (95% confidence interval, -2.6 to 4.7; P = 0.57). The treatment effect of loBMCs was 0.5 percentage points (-3.0 to 4.1; P = 0.76). Likewise, irradiated BMCs did not have significant treatment effects. BMC transfer was safe and not associated with adverse clinical events.

Conclusion: The BOOST-2 trial does not support the use of nucleated BMCs in patients with STEMI and moderately reduced LVEF treated according to current standards of early PCI and drug therapy.
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http://dx.doi.org/10.1093/eurheartj/ehx188DOI Listing
October 2017

Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism.

J Am Coll Cardiol 2017 Mar;69(12):1536-1544

Pulmonology and Intensive Care Service, Georges Pompidou European Hospital, Assistance Publique Hôpitaux de Paris, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France; INSERM UMR S 970, Paris, France (INNOVTE, France).

Background: The long-term effect of thrombolytic treatment of pulmonary embolism (PE) is unknown.

Objectives: This study investigated the long-term prognosis of patients with intermediate-risk PE and the effect of thrombolytic treatment on the persistence of symptoms or the development of late complications.

Methods: The PEITHO (Pulmonary Embolism Thrombolysis) trial was a randomized (1:1) comparison of thrombolysis with tenecteplase versus placebo in normotensive patients with acute PE, right ventricular (RV) dysfunction on imaging, and a positive cardiac troponin test result. Both treatment arms received standard anticoagulation. Long-term follow-up was included in the third protocol amendment; 28 sites randomizing 709 of the 1,006 patients participated.

Results: Long-term (median 37.8 months) survival was assessed in 353 of 359 (98.3%) patients in the thrombolysis arm and in 343 of 350 (98.0%) in the placebo arm. Overall mortality rates were 20.3% and 18.0%, respectively (p = 0.43). Between day 30 and long-term follow-up, 65 deaths occurred in the thrombolysis arm and 53 occurred in the placebo arm. At follow-up examination of survivors, persistent dyspnea (mostly mild) or functional limitation was reported by 36.0% versus 30.1% of the patients (p = 0.23). Echocardiography (performed in 144 and 146 patients randomized to thrombolysis and placebo, respectively) did not reveal significant differences in residual pulmonary hypertension or RV dysfunction. Chronic thromboembolic pulmonary hypertension (CTEPH) was confirmed in 4 (2.1%) versus 6 (3.2%) cases (p = 0.79).

Conclusions: Approximately 33% of patients report some degree of persistent functional limitation after intermediate-risk PE, but CTEPH is infrequent. Thrombolytic treatment did not affect long-term mortality rates, and it did not appear to reduce residual dyspnea or RV dysfunction in these patients. (Pulmonary Embolism Thrombolysis study [PEITHO]; NCT00639743).
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http://dx.doi.org/10.1016/j.jacc.2016.12.039DOI Listing
March 2017

Endomyocardial proteomic signature corresponding to the response of patients with dilated cardiomyopathy to immunoadsorption therapy.

J Proteomics 2017 01 9;150:121-129. Epub 2016 Sep 9.

Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany. Electronic address:

Dilated cardiomyopathy (DCM) is a disease of the myocardium with reduced left ventricular ejection fraction (LVEF). Cardiac autoantibodies (AAbs) play a causal role in the development and progression of DCM. Removal of AAbs using immunoadsorption (IA/IgG) has been shown as a therapeutic option to improve cardiac function. However, the response to therapy differs significantly among patients. The reasons for this variability are not completely understood. Hitherto, no potential biomarker is available to predict improvement of cardiac function after therapy accurately. This shotgun proteome study aims to disclose the differences in the endomyocardial proteome between patients with improved LVEF after IA/IgG (responders) and those without improvement (non-responders) before therapy start. Comparative analysis revealed 54 differentially abundant proteins that were mostly confined to carbohydrate and lipid metabolism, energy and immune regulation, and cardioprotection. Selected proteins representing various functional categories were further confirmed by multiple reaction monitoring (MRM). Among those, protein S100-A8, perilipin-4, and kininogen-1 were found the most robust candidates differentiating responders and non-responders. Receiver operating characteristic curve (ROC) analysis of these proteins revealed highest potential for protein S100-A8 (AUC 0.92) with high sensitivity and specificity to be developed as a classifier for the prediction of cardiac improvement after IA/IgG therapy.

Significance: We evaluated the differences in the myocardial proteome of responder and non-responder DCM patients before immunoadsorption therapy and identified a number of differentially abundant proteins involved in energy and lipid metabolism, immune system, and cardioprotection. MRM was used for verification of results. Proteins S100-A8, perilipin-4, and kininogen-1 were found to display the largest differences. The results provide a lead for further studies to screen for protein biomarker candidates in plasma that might be helpful to stratify patients for immunoadsorption therapy treatment.
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http://dx.doi.org/10.1016/j.jprot.2016.09.001DOI Listing
January 2017

Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution.

Basic Res Cardiol 2016 09 13;111(5):53. Epub 2016 Jul 13.

Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Friedrich-Ludwig-Jahn-Straße 15a, 17475, Greifswald, Germany.

Immunoadsorption with subsequent immunoglobulin substitution (IA/IgG) represents a therapeutic approach for patients with dilated cardiomyopathy (DCM). Here, we studied which molecular cardiac alterations are initiated after this treatment. Transcription profiling of endomyocardial biopsies with Affymetrix whole genome arrays was performed on 33 paired samples of DCM patients collected before and 6 months after IA/IgG. Therapy-related effects on myocardial protein levels were analysed by label-free proteome profiling for a subset of 23 DCM patients. Data were analysed regarding therapy-associated differences in gene expression and protein levels by comparing responders (defined by improvement of left ventricular ejection fraction ≥20 % relative and ≥5 % absolute) and non-responders. Responders to IA/IgG showed a decrease in serum N-terminal proBNP levels in comparison with baseline which was accompanied by a decreased expression of heart failure markers, such as angiotensin converting enzyme 2 or periostin. However, despite clinical improvement even in responders, IA/IgG did not trigger general inversion of DCM-associated molecular alterations in myocardial tissue. Transcriptome profiling revealed reduced gene expression for connective tissue growth factor, fibronectin, and collagen type I in responders. In contrast, in non-responders after IA/IgG, fibrosis-associated genes and proteins showed elevated levels, whereas values were reduced or maintained in responders. Thus, improvement of LV function after IA/IgG seems to be related to a reduced gene expression of heart failure markers and pro-fibrotic molecules as well as reduced fibrosis progression.
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http://dx.doi.org/10.1007/s00395-016-0569-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101709PMC
September 2016

Culprit lesion location and outcome in patients with cardiogenic shock complicating myocardial infarction: a substudy of the IABP-SHOCK II-trial.

Clin Res Cardiol 2016 Dec 4;105(12):1030-1041. Epub 2016 Jul 4.

Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine), University Heart Center Lübeck, University Hospital Schleswig-Holstein, Ratzeburger Allee 160, Lübeck, 23538, Germany.

Background: In myocardial infarction without cardiogenic shock (CS), the affected coronary vessel has significant influence on the final infarct size and patient prognosis. CS data on this relation are scarce. The objective of this study was to determine the prognostic relevance of the culprit lesion location in patients with CS complicating acute myocardial infarction.

Methods: In the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial patients with CS were randomized to therapy with intraaortic balloon pump or control. Additional CS patients not eligible for the randomized trial were included in a registry. We compared the location of the culprit lesions in these patients with regard to the affected coronary vessel [left main (LM), left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA)] and location within the vessel (proximal, mid or distal) regarding short- and long-term outcome.

Results: Of 758 patients, the majority had the culprit lesion in the LAD (44 %) compared to RCA (27 %), LCX (19 %) or LM (10 %). Proximal lesions were more frequent than mid or distal culprit lesions (60 vs. 27 vs. 13 %, p < 0.001). No differences were observed for mortality with respect to either culprit vessel (log-rank p value = 0.54). In contrast, a higher mortality was observed for patients with distal culprit lesions after 1 year (log-rank p value = 0.04). This difference persisted after multivariable adjustment (hazard ratio for distal lesions 1.40; 95 % confidential interval 1.03-1.90; p = 0.03).

Conclusion: For patients with CS complicating myocardial infarction, the culprit vessel seems to be unrelated with mortality whereas distal culprit lesions may have a worse outcome.
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http://dx.doi.org/10.1007/s00392-016-1017-6DOI Listing
December 2016

Home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban. Rationale and design of the HoT-PE Trial.

Thromb Haemost 2016 07 24;116(1):191-7. Epub 2016 Mar 24.

Stavros V. Konstantinides, MD, FESC, Center for Thrombosis and Hemostasis, University Medical Center Mainz, Langenbeckstrasse 1, Building 403, 55131 Mainz, Germany, Tel.: +49 6131 17 8382, Fax: +49 6131 17 3456, E-mail:

Pulmonary embolism (PE) is a potentially life-threatening acute cardiovascular syndrome. However, more than 95 % of patients are haemodynamically stable at presentation, and among them are patients at truly low risk who may qualify for immediate or early discharge. The Home Treatment of Pulmonary Embolism (HoT-PE) study is a prospective international multicentre single-arm phase 4 management (cohort) trial aiming to determine whether home treatment of acute low-risk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. Patients with confirmed PE, who have no right ventricular dysfunction or free floating thrombi in the right atrium or ventricle, are eligible if they meet none of the exclusion criteria indicating haemodynamic instability, serious comorbidity or any condition mandating hospitalisation, or a familial/social environment unable to support home treatment. The first dose of rivaroxaban is given in hospital, and patients are discharged within 48 hours of presentation. Rivaroxaban is taken for at least three months. The primary outcome is symptomatic recurrent venous thromboembolism or PE-related death within three months of enrolment. Secondary outcomes include quality of life and patient satisfaction, and health care resource utilisation compared to existing data on standard-duration hospital treatment. HoT-PE is planned to analyse 1,050 enrolled patients, providing 80 % power to reject the null hypothesis that the recurrence rate of venous thromboembolism is >3 % with α≤0.05. If the hypothesis of HoT-PE is confirmed, early discharge and out-of-hospital treatment may become an attractive, potentially cost-saving option for a significant proportion of patients with acute PE.
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http://dx.doi.org/10.1160/TH16-01-0004DOI Listing
July 2016

ADP receptor antagonists in patients with acute myocardial infarction complicated by cardiogenic shock: a post hoc IABP-SHOCK II trial subgroup analysis.

EuroIntervention 2016 Dec 10;12(11):e1395-e1403. Epub 2016 Dec 10.

Ludwig-Maximilians-Universität, Munich and German Heart Center Munich, Munich, Germany.

Aims: The aim of this post hoc subgroup analysis of the Intraaortic Balloon Pump in Cardiogenic Shock II trial was to compare the clinical outcome of patients treated with either clopidogrel or the newer, more potent P2Y12 receptor inhibitors prasugrel or ticagrelor.

Methods And Results: The primary endpoint was one-year mortality with respect to different P2Y12 receptor inhibitors. Secondary safety endpoints were GUSTO bleedings until hospital discharge. After exclusion of 117 patients (patients who died before or during PCI, patients with unavailable information on P2Y12 receptor inhibitor treatment, patients not receiving or receiving a combination of different P2Y12 receptor inhibitors as acute antiplatelet therapy), 483 patients were analysed. Of these, 373 patients (77.2%) received clopidogrel and 110 patients (22.8%) either prasugrel or ticagrelor as acute antiplatelet therapy. The adjusted rate of mortality did not differ between prasugrel/ticagrelor and clopidogrel treated patients (HR: 0.83, 95% CI: 0.59-1.19, padj=0.31). GUSTO bleedings did not differ between groups (14.3% for prasugrel/ticagrelor and 16.4% for clopidogrel, HR: 0.91, 95% CI: 0.55-1.5, padj=0.7).

Conclusions: This IABP-SHOCK II trial subgroup analysis shows that the use of potent P2Y12 receptor inhibitors like prasugrel or ticagrelor is feasible and might not be harmful in selected patients with cardiogenic shock complicating acute myocardial infarction. However, the superiority in comparison to clopidogrel remains to be proven.
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http://dx.doi.org/10.4244/EIJY15M12_04DOI Listing
December 2016

Long-term strategies support autonomy in radiation safety in invasive cardiology.

J Cardiol 2016 07 19;68(1):43-8. Epub 2015 Sep 19.

Department of Internal Medicine, Ernst Moritz Arndt University, Greifswald, Germany.

Background And Purpose: Despite comprehensive radiation safety programs, radiation exposure in invasive cardiology remains considerable. According to the 2013 German Registry, median in-hospital dose area products (DAP) amount to 19.8Gycm(2) for invasive coronary angiography (CA). We analyzed long-term radiation-reducing strategies for an experienced interventionalist from 1997 to 2012, for the target intervention of CA.

Methods: Among representative cohorts, we evaluated iterative alterations in collimation, time on beam, pulse rates, detector entrance doses, and angulations on the basis of DAP, radiographic DAP(R) and fluoroscopic DAP(F), the respective times on beam, and the number of frames and runs.

Results: Patients' median overall DAP decreased from 33.8Gycm(2) at baseline to 2.4 and 0.6Gycm(2) for CA in conventional (C) and electrocardiogram-gated (E) modes - one diastolic radiographic frame per heartbeat at 77% of the RR interval. Further median dose parameters for CA at baseline and finally in C/E mode were as follows: effective dose (6.76-0.48/0.13mSv), radiography time (43.8-12.9/21.7s), frames (548-105/25), frames/run (41.3-14.4/3.4), DAP(R)/frame (42.6-16.6/12.6mGycm(2)), DAP(R)/s (532-130/13.8mGycm(2)/s), fluoroscopy time (195-120/119s), DAP(F)/pulse (2.0-1.1/0.8mGycm(2)), and DAP(F)/s (48.9-4.4/3.1mGycm(2)/s).

Conclusions: Our data highlight the efficacy of various radiation-reducing strategies by autonomous control and iterative training in radiation safety toward submillisievert levels for CA, and define realizable benchmarks for comparison with the performance data of any individual.
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http://dx.doi.org/10.1016/j.jjcc.2015.08.012DOI Listing
July 2016

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy.

N Engl J Med 2015 Sep;373(10):929-38

From University Heart Center, Department of Cardiology (C. Templin, J.R.G., J.D., D.R.B., M.J., V.L.C., V.G., C.A.N., M.S., P.E., F.R., T.F.L.), and Department of Psychiatry and Psychotherapy (K. Eisenhardt, J.J.), University Hospital Zurich, and Division of Biostatistics, Epidemiology, Biostatistics, and Prevention Institute, University of Zurich (B.S.), Zurich, Spitalregion Rheintal Werdenberg Sarganserland, Altstätten (J.H.), Department of Cardiology, Kantonsspital Lucerne, Lucerne (F. Cuculi, P.E.), Department of Cardiology, Kantonsspital Winterthur, Winterthur (T.A.F.), and Department of Cardiology, University Hospital Basel, Basel (C.K., S.O.) - all in Switzerland; Department of Cardiology and Angiology, Hannover Medical School, Hannover (L.C.N., J.B.), Department of Cardiology, Heidelberg University Hospital, Heidelberg (J.F., H.A.K.), Deutsches Herzzentrum München, Technische Universität München (C.B., H.S., W.K.), and DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance (H.S., W.K.), Munich, University Heart Center Lübeck, Medical Clinic II, Department of Cardiology, Angiology and Intensive Care Medicine, Lübeck (C.M., H.T.), DZHK, partner site Hamburg/Kiel/Lübeck (C.M., H.T., M.K.), Division of Cardiology, Asklepios Clinics St. Georg Hospital (A.C., K.-H.K.), and Department of General and Interventional Cardiology, University Heart Center Hamburg (M.K.), Hamburg, Department of Cardiology, Charité, Campus Rudolf Virchow, Berlin (C. Tschöpe, H.-P.S.), Department of Internal Medicine III, Heart Center University of Cologne, Cologne (G.M., R.P.), Department of Internal Medicine III, Cardiology, Angiology, and Intensive Care Medicine, Saarland University, Homburg (C.U., M.B.), Department of Cardiology, University Hospital Essen, Essen (R.E.), Clinic for Cardiology and Pneumology, Georg August University Göttingen (C.J., G.H.), and DZHK, partner site Göttingen (C.J., G.H.), Göttingen, Department of Internal Medicine II

Background: The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood.

Methods: The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome.

Results: Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year.

Conclusions: Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).
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http://dx.doi.org/10.1056/NEJMoa1406761DOI Listing
September 2015
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