Publications by authors named "Johann Bauersachs"

455 Publications

Hospitalizations for heart failure: still major differences between East and West Germany 30 years after reunification.

ESC Heart Fail 2021 May 4. Epub 2021 May 4.

Clinic and Policlinic for Cardiology, University Hospital Leipzig, Leipzig, Germany.

Aims: Heart failure (HF) is the most common primary inpatient diagnosis in Germany. We examined temporal trends of HF hospitalization within Germany focusing on regional differences.

Methods And Results: We analysed aggregated data of more than 320 million hospitalizations in Germany from 2000 to 2017. Temporal trends of HF-related parameters were analysed, focusing on regional differences between the federal states. The absolute number of HF-related hospitalizations throughout Germany increased continuously and almost doubled (from 239 694 to 464 724 cases, +94%) with the relative increase being higher in East Germany compared with West Germany (119% vs. 88%). These regional differences persisted after age standardization with 609 and 490 cases per 100 000 population, respectively. The length of stay decreased continuously across Germany (from 14.3 to 10.2 days; -29%), while the total number of HF-related hospital days increased by 51% in East Germany and 35% in West Germany. In 2017, HF remained the leading cause of in-hospital death (8.9% of all cases), with a markedly higher rate in East vs. West Germany (65 vs. 43 deaths per 100 000 population).

Conclusions: Heart failure remains the most common cause of hospitalization and in-hospital death throughout Germany. The increase in HF-related morbidity and mortality was much higher in East Germany compared with West Germany during the observation period. A more detailed understanding of these striking disparities 30 years after the German reunification requires further investigations. There is an urgent need for action with regard to stronger control of risk factors and improvement of both chronic HF management and healthcare structures.
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http://dx.doi.org/10.1002/ehf2.13407DOI Listing
May 2021

High rate of critical coronary stenosis in comatose patients with Non-ST-elevation out-of-hospital cardiac arrest (NSTE-OHCA) undergoing therapeutic hypothermia-Experience from the HAnnover COoling REgistry (HACORE).

PLoS One 2021 4;16(5):e0251178. Epub 2021 May 4.

Department of Cardiology and Angiology, Medizinische Hochschule Hannover, Hannover, Germany.

Background: Myocardial infarction is the most frequent cause for out-of-hospital cardiac arrest (OHCA) in adults. Patients with ST-segment elevations (STE) following return of spontaneous circulation (ROSC) are regularly admitted to the catheterisation laboratory for urgent coronary angiography. Whether patients without obvious STE (NSTE) should receive coronary angiography as part of a standardised diagnostic work-up following OHCA is still debated.

Methods: We analysed a cohort of 517 subsequent OHCA patients admitted at our institution who received a standardised diagnostic work-up including coronary angiography and therapeutic hypothermia. Patients were 63±14 years old, 76% were male. Overall, 180 (35%) had ST-elevation in the post-ROSC ECG, 317 (61%) had shockable rhythm (ventricular fibrillation or tachycardia) at first ECG. ROSC was achieved after 26±21 minutes.

Results: Critical coronary stenosis requiring PCI was present in 83% of shockable and 87% of non-shockable STE-OHCA and in 48% of shockable and 22% of non-shockable NSTE-OHCA patients. In-hospital survival was 61% in shockable and 55% in non-shockable STE-OHCA and 60% in shockable and 28% in non-shockable NSTE-OHCA.

Conclusion: Standardised admission diagnostics in OHCA patients undergoing therapeutic hypothermia with a strict admission protocol incorporating ECG and coronary catheterisation shows a high rate of relevant coronary stenosis in STE-OHCA irrespective of the initial rhythm and in NSTE-OHCA with initial shockable rhythm. Based on the unfavourable outcome and low PCI rate observed in NSTE-OHCA patients with a primary non-shockable ECG rhythm it might be reasonable to restrict routine early coronary angiography to patients with primary shockable rhythms and/or ST-segment elevations after ROSC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251178PLOS
May 2021

Depression Associated with Reduced Heart Rate Variability Predicts Outcome in Adult Congenital Heart Disease.

J Clin Med 2021 Apr 7;10(8). Epub 2021 Apr 7.

Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, D-30625 Hannover, Germany.

In adult congenital heart disease (ACHD), major depressive disorder (MDD) represents a frequent comorbidity. In non-CHD, adverse outcome is predicted by MDD and heart rate variability (HRV), whereas in ACHD their prognostic relevance is unknown. We prospectively evaluated 171 patients (age 35.6 ± 11.4 years; male 42.7%, mean observation time 54.7 ± 14.9 months). Binary regression analysis calculated the association between MDD and HRV. Cox proportional survival analysis estimated their impact on decompensated heart failure and all-cause mortality (HF/death), supraventricular and ventricular tachycardia (SVT/VT), and hospitalization due to unexpected cardiac causes. Exclusively MDD with moderate/severe symptoms showed significantly lower HRV as derived from frequency-domain analysis (Symindex) ( = 0.013). In multivariate Cox regression analysis, patients stratified according to the lower quartile of the Symindex comorbid with MDD (n = 16) exhibited poorer prognosis regarding HF/death (Hazard Ratio (HR): 7.04 (95%CI:(1.87-26.5)), SVT/VT (HR: 4.90 (95%CI:1.74-9.25)) and hospitalization (HR: 3.80 (95%CI:1.36-10.6)). An additional independent predictor was N-terminal pro-B-type natriuretic peptide elevation ( < 0.001), indicating advanced HF and heart disease complexity ( < 0.001). Autonomic nervous system dysfunction measured by altered HRV is considered to be one of the pathways linking MDD and adverse outcomes in cardiac diseases. Our results exceed the existing literature by demonstrating that MDD with decreased HRV is associated with poorer prognosis in ACHD.
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http://dx.doi.org/10.3390/jcm10081554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067842PMC
April 2021

Fibroblast GATA-4 and GATA-6 promote myocardial adaptation to pressure overload by enhancing cardiac angiogenesis.

Basic Res Cardiol 2021 Apr 19;116(1):26. Epub 2021 Apr 19.

Department of Cardiology and Angiology, Hannover Medical School, 30625, Hannover, Germany.

Heart failure due to high blood pressure or ischemic injury remains a major problem for millions of patients worldwide. Despite enormous advances in deciphering the molecular mechanisms underlying heart failure progression, the cell-type specific adaptations and especially intercellular signaling remain poorly understood. Cardiac fibroblasts express high levels of cardiogenic transcription factors such as GATA-4 and GATA-6, but their role in fibroblasts during stress is not known. Here, we show that fibroblast GATA-4 and GATA-6 promote adaptive remodeling in pressure overload induced cardiac hypertrophy. Using a mouse model with specific single or double deletion of Gata4 and Gata6 in stress activated fibroblasts, we found a reduced myocardial capillarization in mice with Gata4/6 double deletion following pressure overload, while single deletion of Gata4 or Gata6 had no effect. Importantly, we confirmed the reduced angiogenic response using an in vitro co-culture system with Gata4/6 deleted cardiac fibroblasts and endothelial cells. A comprehensive RNA-sequencing analysis revealed an upregulation of anti-angiogenic genes upon Gata4/6 deletion in fibroblasts, and siRNA mediated downregulation of these genes restored endothelial cell growth. In conclusion, we identified a novel role for the cardiogenic transcription factors GATA-4 and GATA-6 in heart fibroblasts, where both proteins act in concert to promote myocardial capillarization and heart function by directing intercellular crosstalk.
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http://dx.doi.org/10.1007/s00395-021-00862-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055639PMC
April 2021

ECG and arrhythmias in peripartum cardiomyopathy.

Herzschrittmacherther Elektrophysiol 2021 Mar 31. Epub 2021 Mar 31.

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

Peripartum cardiomyopathy (PPCM) is a rare but life-threatening heart disease, with onset in the last month of pregnancy or in the first months after delivery. Extensive studies on the burden of supraventricular and ventricular arrhythmias are lacking. Patients with PPCM present with electrocardiographic findings typical in acute heart failure. Management of arrhythmias in PPCM depends on the severity and the onset (during pregnancy or after delivery). Studies on the use of the wearable cardioverter-defibrillator in patients with PPCM show a substantial burden of ventricular tachyarrhythmias and sudden death in patients with severely reduced left ventricular function. The aim of the present article is to summarize actual knowledge on electrocardiogram findings, arrhythmias, and sudden cardiac death in patients with PPCM.
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http://dx.doi.org/10.1007/s00399-021-00760-9DOI Listing
March 2021

In Reply.

Dtsch Arztebl Int 2021 01;118(1-2):12-13

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http://dx.doi.org/10.3238/arztebl.m2021.0048DOI Listing
January 2021

The management of secondary mitral regurgitation in patients with heart failure: a joint position statement from the Heart Failure Association (HFA), European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA), and European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Eur Heart J 2021 Mar 18. Epub 2021 Mar 18.

Department of Cardiology, Inselspital, University of Bern, Bern, Switzerland.

Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology-the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)-presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach.
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http://dx.doi.org/10.1093/eurheartj/ehab086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014526PMC
March 2021

Prognostic impact of acute pulmonary triggers in patients with takotsubo syndrome: new insights from the International Takotsubo Registry.

ESC Heart Fail 2021 Mar 13. Epub 2021 Mar 13.

Department of Cardiology, Charité, Campus Rudolf Virchow, Berlin, Germany.

Aims: Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes.

Methods And Results: Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In-hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long-term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long-term mortality (hazard ratio 2.12, 95% confidence interval 1.33-3.38; P = 0.002).

Conclusions: The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in-hospital course and a worse long-term outcome.
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http://dx.doi.org/10.1002/ehf2.13165DOI Listing
March 2021

Genetic ablation of fibroblast activation protein alpha attenuates left ventricular dilation after myocardial infarction.

PLoS One 2021 5;16(3):e0248196. Epub 2021 Mar 5.

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

Introduction: Regulating excessive activation of fibroblasts may be a promising target to optimize extracellular matrix deposition and myocardial stiffness. Fibroblast activation protein alpha (FAP) is upregulated in activated fibroblasts after myocardial infarction (MI), and alters fibroblast migration in vitro. We hypothesized that FAP depletion may have a protective effect on left ventricular (LV) remodeling after MI.

Materials And Methods: We used the model of chronic MI in homozygous FAP deficient mice (FAP-KO, n = 51) and wild type mice (WT, n = 55) to analyze wound healing by monocyte and myofibroblast infiltration. Heart function and remodeling was studied by echocardiography, morphometric analyses including capillary density and myocyte size, collagen content and in vivo cell-proliferation. In non-operated healthy mice up to 6 months of age, morphometric analyses and collagen content was assessed (WT n = 10, FAP-KO n = 19).

Results: Healthy FAP-deficient mice did not show changes in LV structure or differences in collagen content or cardiac morphology. Infarct size, survival and cardiac function were not different between FAP-KO and wildtype mice. FAP-KO animals showed less LV-dilation and a thicker scar, accompanied by a trend towards lower collagen content. Wound healing, assessed by infiltration with inflammatory cells and myofibroblasts were not different between groups.

Conclusion: We show that genetic ablation of FAP does not impair cardiac wound healing, and attenuates LV dilation after MI in mice. FAP seems dispensable for normal cardiac function and homeostasis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248196PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935287PMC
March 2021

[Care of patients with chronic heart failure: an interdisciplinary challenge].

Dtsch Med Wochenschr 2021 Mar 1;146(5):309-316. Epub 2021 Mar 1.

The diverse manifestations of heart failure led to complex treatment guidelines and care scenarios and therefore always require an integrated, multidisciplinary care approach. Patients with chronic heart failure suffer from a large number of cardiac and noncardiac comorbidities. For example, iron deficiency leads to decreased performance and exertional dyspnea and should be diagnosed. Psychological screening questionnaires should be used for the early detection of psychological comorbidities.ARNI and SGLT-inhibitors expand the pharmacotherapeutic possibilities and gain in importance. The constant development of diagnostic possibilities and therapeutic options must be implemented consistently into the care continuum in order to have a lasting effect. The challenge of interdisciplinary coordination can be significantly reduced through jointly agreed process logs (e. g. within the framework of integrated supply contracts or a Heart Failure Unit Network).
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http://dx.doi.org/10.1055/a-1235-0422DOI Listing
March 2021

Standardized secondary prevention in patients with ST-elevation myocardial infarction.

Eur J Prev Cardiol 2020 Oct 7. Epub 2020 Oct 7.

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

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http://dx.doi.org/10.1093/eurjpc/zwaa078DOI Listing
October 2020

Lateral Thoracotomy for Ventricular Assist Device Implantation: A Meta-Analysis of Literature.

ASAIO J 2021 Feb 4. Epub 2021 Feb 4.

From the *Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany †Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany ‡Cardio-Thoracic Surgery Department, Maastricht University Medical Centre (MUMC), Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands.

The use of lateral thoracotomy (LT) for implanting left ventricular assist devices (LVADs) is worldwide increasing, although the available evidence for its positive effects compared with conventional sternotomy (CS) is limited. This systematic review and meta-analysis analyzes the outcomes of LT compared with CS in patients undergoing implantation of a centrifugal continuous-flow LVAD. Four databases and 1,053 publications were screened until December 2019. Articles including patients undergoing implantation of a centrifugal continuous-flow LVAD through LT were included. A meta-analysis to compare LT and CS was performed to summarize evidences from studies including both LT and CS patients extracted from the same population. Primary outcome measure was in-hospital or 30-day mortality. Eight studies reporting on 730 patients undergoing LVAD implantation through LT (n = 242) or CS (n = 488) were included in the meta-analysis. Left thoracotomy showed lower in-hospital/30-day mortality (odds ratio [OR]: 0.520, 95% confidence interval [CI]: 0.27-0.99, p = 0.050), shorter intensive care unit (ICU) stay (mean difference [MD]: 3.29, CI: 1.76-4.82, p < 0.001), lower incidence of severe right heart failure (OR: 0.41; CI: 0.19-0.87, p = 0.020) and postoperative right ventricular assist device (RVAD) implantation (OR: 0.27, CI: 0.10-0.76, p = 0.010), fewer perioperative transfusions (MD: 0.75, CI: 0.36-1.14, p < 0.001), and lower incidence of renal failure (OR: 0.45, CI: 0.20-1.01, p = 0.050) and device-related infections (OR: 0.45, CI: 0.20-1.01, p = 0.050), respectively. This meta-analysis demonstrates that implantation of a centrifugal continuous-flow LVAD system via LT benefits from higher short-term survival, less right heart failure, lower postoperative RVAD need, shorter ICU stay, less transfusions, lower risk of device-related infections and kidney failure. Prospective studies are needed for further proof.
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http://dx.doi.org/10.1097/MAT.0000000000001359DOI Listing
February 2021

Risk stratification and management of women with cardiomyopathy/heart failure planning pregnancy or presenting during/after pregnancy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy.

Eur J Heart Fail 2021 Feb 20. Epub 2021 Feb 20.

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

This position paper focusses on the pathophysiology, diagnosis and management of women diagnosed with a cardiomyopathy, or at risk of heart failure (HF), who are planning to conceive or present with (de novo or previously unknown) HF during or after pregnancy. This includes the heterogeneous group of heart muscle diseases such as hypertrophic, dilated, arrhythmogenic right ventricular and non-classified cardiomyopathies, left ventricular non-compaction, peripartum cardiomyopathy, Takotsubo syndrome, adult congenital heart disease with HF, and patients with right HF. Also, patients with a history of chemo-/radiotherapy for cancer or haematological malignancies need specific pre-, during and post-pregnancy assessment and counselling. We summarize the current knowledge about pathophysiological mechanisms, including gene mutations, clinical presentation, diagnosis, and medical and device management, as well as risk stratification. Women with a known diagnosis of a cardiomyopathy will often require continuation of drug therapy, which has the potential to exert negative effects on the foetus. This position paper assists in balancing benefits and detrimental effects.
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http://dx.doi.org/10.1002/ejhf.2133DOI Listing
February 2021

Five-year outcomes of patients supported with HeartMate 3: a single-centre experience.

Eur J Cardiothorac Surg 2021 Feb 15. Epub 2021 Feb 15.

Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.

Objectives: The HeartMate 3 left ventricular assist device was first implanted in 2014 and received the Conformité Européenne mark in 2015. Since then, several trials demonstrated its high haemocompatibility associated with good survival and low adverse events rates. Herein, we report our institutional experience with patients supported with HeartMate 3 for 5 years.

Methods: This prospective cohort study included patients receiving a HeartMate 3 implantation in 2014 as part of the HeartMate 3 Conformité Européenne Mark clinical trial. Patients had follow-up visits every 3 months while on left ventricular assist device support, and all patients completed the 5-year follow-up. The primary end point was survival at 5 years. Secondary end points included adverse events, health status and quality of life.

Results: Eight patients (men: 75%) aged 59 years (min-max: 52-66 years) were enrolled. At 5 years, survival was 100%. Patients remained on support for a median time of 1825 days (min-max: 101-1825 days); 2 patients successfully received cardiac transplants. No right heart failure, haemolysis, pump thrombosis, pump malfunction or neurological events occurred in any patients. A driveline infection was observed in 6 patients (0.25 events/patient-year). Compared to baseline, a significant improvement in quality of life and in New York Heart Association functional class was noted after the implant and for the whole follow-up time. A slight decline in kidney function and in the 6-min walk test results occurred after 3 years.

Conclusions: This study reports the longest single-centre follow-up of the HeartMate 3, showing excellent haemocompatibility over time with high survival and low complication rates at 5 years.
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http://dx.doi.org/10.1093/ejcts/ezab018DOI Listing
February 2021

Optimized Implementation of cardiac resynchronization therapy - a call for action for referral and optimization of care.

Europace 2021 Feb 5. Epub 2021 Feb 5.

Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.

Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heartfailure hospitalization rates and reduces all-cause mortality. Nevertheless, up to two-thirds ofeligible patients are not referred for CRT. Furthermore, post implantation follow-up is oftenfragmented and suboptimal, hampering the potential maximal treatment effect. This jointposition statement from three ESC Associations, HFA, EHRA and EACVI focuses onoptimized implementation of CRT. We offer theoretical and practical strategies to achievemore comprehensive CRT referral and post-procedural care by focusing on four actionabledomains; (I) overcoming CRT under-utilization, (II) better understanding of pre-implantcharacteristics, (III) abandoning the term 'non-response' and replacing this by the concept ofdisease modification, and (IV) implementing a dedicated post-implant CRT care pathway.
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http://dx.doi.org/10.1093/europace/euab035DOI Listing
February 2021

[Symptom control in heart failure patients - how to handle GFR decrease and hyperkalaemia].

Dtsch Med Wochenschr 2021 Mar 22;146(6):e47-e55. Epub 2021 Jan 22.

Klinik für Nephrologie, Blutreinigung und Rheumatologie, Klinikum Braunschweig.

For heart failure patients with reduced ejection fraction, optimised medication improves symptom control and reduces mortality. Substances influencing the renin-angiotensin-aldosteron-system, so-called RAAS-inhibitors, are the cornerstone of heart failure treatment. This article summarises a consensus between experts in cardiology and in nephrology on a pragmatic approach to manage a drop in glomerular filtration rate and incident hyperkalaemia - the two most common reasons for reducing or discontinuing heart failure medication.
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http://dx.doi.org/10.1055/a-1307-8652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972821PMC
March 2021

Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy.

Sci Rep 2021 Jan 19;11(1):1755. Epub 2021 Jan 19.

Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM have a higher risk for sudden cardiac death compared to a healthy population. In the present study, we investigated the abundancy of selected proteins as potential biomarkers in patients with HCM. We included 60 patients with HCM and 28 healthy controls and quantitatively measured the rate of a set of 92 proteins already known to be associated with cardiometabolic processes via protein screening using the proximity extension assay technology in a subgroup of these patients (20 HCM and 10 healthy controls). After validation of four hits in the whole cohort of patients consisting of 88 individuals (60 HCM patients, 28 healthy controls) we found only one candidate, c-KIT, which was regulated significantly different between HCM patients and healthy controls and thus was chosen for further analyses. c-KIT is a tyrosine-protein kinase acting as receptor for the stem cell factor and activating several pathways essential for cell proliferation and survival, hematopoiesis, gametogenesis and melanogenesis. Serum protein levels of c-KIT were significantly lower in patients with HCM than in healthy controls, even after adjusting for confounding factors age and sex. In addition, c-KIT levels in human cardiac tissue of patients with HOCM were significant higher compared to controls indicating high levels of c-KIT in fibrotic myocardium. Furthermore, c-KIT concentration in serum significantly correlated with left ventricular end-diastolic diameter in HOCM, but not HCM patients. The present data suggest c-KIT as a novel biomarker differentiating between patients with HCM and healthy population and might provide further functional insights into fibrosis-related processes of HOCM.
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http://dx.doi.org/10.1038/s41598-020-80868-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815737PMC
January 2021

Electrocardiographic features and their echocardiographic correlates in peripartum cardiomyopathy: results from the ESC EORP PPCM registry.

ESC Heart Fail 2021 Apr 16;8(2):879-889. Epub 2021 Jan 16.

Division of Cardiology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Aims: In peripartum cardiomyopathy (PPCM), electrocardiography (ECG) and its relationship to echocardiography have not yet been investigated in large multi-centre and multi-ethnic studies. We aimed to identify ECG abnormalities associated with PPCM, including regional and ethnic differences, and their correlation with echocardiographic features.

Methods And Results: We studied 411 patients from the EURObservational PPCM registry. Baseline demographic, clinical, and echocardiographic data were collected. ECGs were analysed for rate, rhythm, QRS width and morphology, and QTc interval. The median age was 31 [interquartile range (IQR) 26-35] years. The ECG was abnormal in > 95% of PPCM patients. Sinus tachycardia (heart rate > 100 b.p.m.) was common (51%), but atrial fibrillation was rare (2.27%). Median QRS width was 82 ms [IQR 80-97]. Left bundle branch block (LBBB) was reported in 9.30%. Left ventricular (LV) hypertrophy (LVH), as per ECG criteria, was more prevalent amongst Africans (59.62%) and Asians (23.17%) than Caucasians (7.63%, P < 0.001) but did not correlate with LVH on echocardiography. Median LV end-diastolic diameter (LVEDD) was 60 mm [IQR 55-65] and LV ejection fraction (LVEF) 32.5% [IQR 25-39], with no significant regional or ethnic differences. Sinus tachycardia was associated with an LVEF < 35% (OR 1.85 [95% CI 1.20-2.85], P = 0.006). ECG features that predicted an LVEDD > 55 mm included a QRS complex > 120 ms (OR 11.32 [95% CI 1.52-84.84], P = 0.018), LBBB (OR 4.35 [95% CI 1.30-14.53], P = 0.017), and LVH (OR 2.03 [95% CI 1.13-3.64], P = 0.017).

Conclusions: PPCM patients often have ECG abnormalities. Sinus tachycardia predicted poor systolic function, whereas wide QRS, LBBB, and LVH were associated with LV dilatation.
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http://dx.doi.org/10.1002/ehf2.13172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006717PMC
April 2021

Heart failure drug treatment: the fantastic four.

Eur Heart J 2021 Feb;42(6):681-683

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

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http://dx.doi.org/10.1093/eurheartj/ehaa1012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878007PMC
February 2021

SCORED and SOLOIST: the next scores for SGLT2 inhibitors.

Cardiovasc Res 2021 Mar;117(4):e49-e51

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

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http://dx.doi.org/10.1093/cvr/cvaa355DOI Listing
March 2021

Circulating cardiovascular microRNAs in critically ill COVID-19 patients.

Eur J Heart Fail 2021 03 5;23(3):468-475. Epub 2021 Mar 5.

Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.

Aims: Coronavirus disease 2019 (COVID-19) is a still growing pandemic, causing many deaths and socio-economic damage. Elevated expression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry receptor angiotensin-converting enzyme 2 on cardiac cells of patients with heart diseases may be related to cardiovascular burden. We have thus analysed cardiovascular and inflammatory microRNAs (miRs), sensitive markers of cardiovascular damage, in critically ill, ventilated patients with COVID-19 or influenza-associated acute respiratory distress syndrome (Influenza-ARDS) admitted to the intensive care unit and healthy controls.

Methods And Results: Circulating miRs (miR-21, miR-126, miR-155, miR-208a, and miR-499) were analysed in a discovery cohort consisting of patients with mechanically-ventilated COVID-19 (n = 18) and healthy controls (n = 15). A validation study was performed in an independent cohort of mechanically-ventilated COVID-19 patients (n = 20), Influenza-ARDS patients (n = 13) and healthy controls (n = 32). In both cohorts, RNA was isolated from serum and cardiovascular disease/inflammatory-relevant miR concentrations were measured by miR-specific TaqMan PCR analyses. In both the discovery and the validation cohort, serum concentration of miR-21, miR-155, miR-208a and miR-499 were significantly increased in COVID-19 patients compared to healthy controls. Calculating the area under the curve using receiver operating characteristic analysis miR-155, miR-208a and miR-499 showed a clear distinction between COVID-19 and Influenza-ARDS patients.

Conclusion: In this exploratory study, inflammation and cardiac myocyte-specific miRs were upregulated in critically ill COVID-19 patients. Importantly, miR profiles were able to differentiate between severely ill, mechanically-ventilated Influenza-ARDS and COVID-19 patients, indicating a rather specific response and cardiac involvement of COVID-19.
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http://dx.doi.org/10.1002/ejhf.2096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014268PMC
March 2021

Neuromarkers and neurological outcome in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia-experience from the HAnnover COoling REgistry (HACORE).

PLoS One 2021 7;16(1):e0245210. Epub 2021 Jan 7.

Cardiac Arrest Centre, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

Background: Neuron-specific enolase (NSE) and S-100b have been used to assess neurological damage following out-of-hospital cardiac arrest (OHCA). Cut-offs were derived from small normothermic cohorts. Whether similar cut-offs apply to patients treated with hypothermia remained undetermined.

Methods: We investigated 251 patients with OHCA treated with hypothermia but without routine prognostication. Neuromarkers were determined at day 3, neurological outcome was assessed after hospital discharge by cerebral performance category (CPC).

Results: Good neurological outcome (CPC≤2) was achieved in 41%. Elevated neuromarkers, older age and absence of ST-segment elevation after ROSC were associated with increased mortality. Poor neurological outcome in survivors was additionally associated with history of cerebrovascular events, sepsis and higher admission lactate. Mean NSE was 33μg/l [16-94] vs. 119μg/l [25-406]; p<0.001, for survivors vs. non-survivors, and 21μg/l [16-29] vs. 40μg/l [23-98], p<0.001 for good vs. poor neurological outcome. S-100b was 0.127μg/l [0.063-0.360] vs. 0.772μg/l [0.121-2.710], p<0.001 and 0.086μg/l [0.061-0.122] vs. 0.138μg/l [0.090-0.271], p = 0.009, respectively. For mortality, thresholds of 36μg/l for NSE and 0.128μg/l for S-100b could be determined; for poor neurological outcome 33μg/l (NSE) and 0.123μg/l (S-100b), respectively. Positive predictive value for NSE was 81% (74-88) and 79% (71-85) for S-100b.

Conclusions: Thresholds for NSE and S-100b predicting mortality and poor neurological outcome are similar in OHCA patients receiving therapeutic hypothermia as in those reported before the era of hypothermia. However, both biomarkers do not have enough specificity to predict mortality or poor neurological outcome on their own and should only be additively used in clinical decision making.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245210PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790428PMC
January 2021

Comparison of anticoagulation strategies for veno-venous ECMO support in acute respiratory failure.

Crit Care 2021 01 4;24(1):701. Epub 2021 Jan 4.

Department of Anaesthesiology and Critical Care Medicine, University Hospital Bonn, Bonn, Germany.

Background: Extracorporeal membrane oxygenation (ECMO) support in acute respiratory failure may be lifesaving, but bleeding and thromboembolic complications are common. The optimal anticoagulation strategy balancing these factors remains to be determined. This retrospective study compared two institutional anticoagulation management strategies focussing on oxygenator changes and both bleeding and thromboembolic events.

Methods: We conducted a retrospective observational cohort study between 04/2015 and 02/2020 in two ECMO referral centres in Germany in patients receiving veno-venous (VV)-ECMO support for acute respiratory failure for > 24 h. One centre routinely applied low-dose heparinization aiming for a partial thromboplastin time (PTT) of 35-40 s and the other routinely used a high-dose therapeutic heparinization strategy aiming for an activated clotting time (ACT) of 140-180 s. We assessed number of and time to ECMO oxygenator changes, 15-day freedom from oxygenator change, major bleeding events, thromboembolic events, 30-day ICU mortality, activated clotting time and partial thromboplastin time and administration of blood products. Primary outcome was the occurrence of oxygenator changes depending on heparinization strategy; main secondary outcomes were the occurrence of severe bleeding events and occurrence of thromboembolic events. The transfusion strategy was more liberal in the low-dose centre.

Results: Of 375 screened patients receiving VV-ECMO support, 218 were included in the analysis (117 high-dose group; 101 low-dose group). Disease severity measured by SAPS II score was 46 (IQR 36-57) versus 47 (IQR 37-55) and ECMO runtime was 8 (IQR 5-12) versus 11 (IQR 7-17) days (P = 0.003). There were 14 oxygenator changes in the high-dose group versus 48 in the low-dose group. Freedom from oxygenator change at 15 days was 73% versus 55% (adjusted HR 3.34 [95% confidence interval 1.2-9.4]; P = 0.023). Severe bleeding events occurred in 23 (19.7%) versus 14 (13.9%) patients (P = 0.256) and thromboembolic events occurred in 8 (6.8%) versus 19 (19%) patients (P = 0.007). Mortality at 30 days was 33.3% versus 30.7% (P = 0.11).

Conclusions: In this retrospective study, ECMO management with high-dose heparinization was associated with lower rates of oxygenator changes and thromboembolic events when compared to a low-dose heparinization strategy. Prospective, randomized trials are needed to determine the optimal anticoagulation strategy in patients receiving ECMO support.
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http://dx.doi.org/10.1186/s13054-020-03348-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780376PMC
January 2021

The year in cardiovascular medicine 2020: heart failure and cardiomyopathies.

Eur Heart J 2021 Feb;42(6):657-670

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

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http://dx.doi.org/10.1093/eurheartj/ehaa1061DOI Listing
February 2021

Separate Origin of Four Major Coronary Arteries.

Cardiovasc Revasc Med 2021 Apr 4;25:86-88. Epub 2020 Dec 4.

Cardiac Arrest Center, Advanced Heart Failure Unit, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.carrev.2020.12.006DOI Listing
April 2021

Sacubitril/valsartan for the management of heart failure: A perspective viewpoint on current evidence.

Int J Cardiol 2021 Mar 8;327:138-145. Epub 2020 Dec 8.

Department of Medicine, Department of Physiology and Pathophysiology, University of Manitoba, St Boniface Hospital, Winnipeg, Manitoba, Canada.

Current international guidelines recommend switching angiotensin converting enzyme inhibitors (ACE-i) or angiotensin receptor blockers (ARBs) to sacubitril/valsartan (S/V) in stable outpatients affected by heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite being on optimal medical therapy. Since these guidelines were published, new data may support further clinical applications and benefits of S/V beyond ambulatory HFrEF patients. The efficacy of S/V seems to be consistent across a wider array of subgroups including age, sex, etiology of HF, comorbidities, EF and estimated cardiovascular risk, with safety and tolerability profiles similar to ACE-I and ARBs. Additional clinical trial data are required to confirm the potential benefits of S/V in patients with mid-range or preserved EF, as suggested by analysis of PARAGON-HF, or in combination with sodium-glucose co-transporter 2 inhibitors or in post-myocardial infarction HF. In this article we summarize the new evidence on the effects and safety profile of S/V in HF and discuss current perspectives and persisting gaps. Currently, available evidence may support S/V as a first-line therapy in outpatient or in-hospital HFrEF patients, and possibly also in HFmrEF patients.
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http://dx.doi.org/10.1016/j.ijcard.2020.11.071DOI Listing
March 2021

Novel antisense therapy targeting microRNA-132 in patients with heart failure: results of a first-in-human Phase 1b randomized, double-blind, placebo-controlled study.

Eur Heart J 2021 01;42(2):178-188

Cardior Pharmaceuticals GmbH, Hannover Medical School Campus, Feodor-Lynen-Straße 15, Hannover 30625, Germany.

Aims: Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models. The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study (NCT04045405).

Methods And Results: Patients had left ventricular ejection fraction between ≥30% and <50% or amino terminal fragment of pro-brain natriuretic peptide (NT-proBNP) >125 ng/L at screening. Twenty-eight patients were randomized to receive CDR132L (0.32, 1, 3, and 10 mg/kg body weight) or placebo (0.9% saline) in two intravenous infusions, 4 weeks apart in four cohorts of seven (five verum and two placebo) patients each. CDR132L was safe and well tolerated, without apparent dose-limiting toxicity. A pharmacokinetic/pharmacodynamic dose modelling approach suggested an effective dose level at ≥1 mg/kg CDR132L. CDR132L treatment resulted in a dose-dependent, sustained miR-132 reduction in plasma. Patients given CDR132L ≥1 mg/kg displayed a median 23.3% NT-proBNP reduction, vs. a 0.9% median increase in the control group. CDR132L treatment induced significant QRS narrowing and encouraging positive trends for relevant cardiac fibrosis biomarkers.

Conclusion: This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. Although this study is limited by the small patient numbers, the indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF.
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http://dx.doi.org/10.1093/eurheartj/ehaa898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954267PMC
January 2021