Mark Rosenberg

University Medical Center Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany

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Publications (21)74.99 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We aimed to test, for the first time, the feasibility of intracoronary delivery of an innovative, injectable bioabsorbable scaffold (IK-5001), to prevent or reverse adverse left ventricular remodeling and dysfunction in patients after ST-segment-elevation myocardial infarction.
    Circulation Cardiovascular Interventions 10/2014; · 6.54 Impact Factor
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    ABSTRACT: Abstract Background: Troponin-T (cTnT) and NT-proBNP provide prognostic information in light-chain amyloidosis (AL). Thus, these biomarkers are widely used in clinical routine for risk stratification. Recently, plasma level of osteopontin (OPN), a secreted phosphoglycoprotein expressed by a variety of cell types, has been reported as a risk predictor in various cardiovascular diseases. Methods: OPN was determined retrospectively in 150 consecutive patients newly diagnosed with AL amyloidosis. All patients were evaluated according to a routine protocol including electrocardiography, echocardiography and laboratory testing. Results: Mean OPN was 591 ± 37 ng/mL. Cardiac involvement was established in 83 (55.3%). Median OPN plasma level were associated with number of organs involved, renal function, eligibility for high-dose melphalan chemotherapy and autologous stem cell transplantation, and severity of cardiac amyloidosis. Median follow-up was 19.2 months. 1-year all-cause-survival was 83.4%. The cut-offs discriminating 1-year all-cause-mortality for NT-proBNP, troponin T, and OPN were 2544 ng/L, 0.035 µg/L, and 426.8 ng/mL, respectively. Outcome was worse in patients with biomarkers above the individual ROC derived cut-off. A significant improvement of survival was observed in patients with cTNT >0.035 µg/L or NT-proBNP >2544 ng/L and OPN below ROC-derived cut-off of 426.8 ng/mL as compared to patients with OPN above 426.8 ng/L. No further discrimination was achieved by OPN in the cohorts of low troponin T or low NT-proBNP, respectively. Separate multivariate models identified OPN (cut-off 426.8 ng/mL) and troponin T (cut-off 0.035 µg/L) as independent predictors of all-cause-mortality. Conclusions: These data demonstrated that OPN appears to be a valuable marker in the clinical routine for evaluation of patients with AL amyloidosis, especially if it is used in combination with cTNT and/or NT-proBNP.
    Amyloid. 07/2014;
  • Clinical Research in Cardiology 04/2014; · 3.67 Impact Factor
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    ABSTRACT: Background Heart involvement is the leading cause of death of patients with eosinophilic granulomatosis with polyangiitis (formerly Churg–Strauss syndrome) (EGPA) and is more frequent in antineutrophil cytoplasm antibody (ANCA)-negative patients. Post-transplant outcome has only been reported once. Methods We conducted a retrospective international multicenter study. Patients satisfying the American College of Rheumatology and/or revised Chapel Hill Consensus Conference Nomenclature criteria were identified by collaborating vasculitis and transplant specialists, and the help of the Churg–Strauss Syndrome Association. Results Nine ANCA– patients who received transplants between October 1987 and December 2009 were identified. The vasculitis and cardiomyopathy diagnoses were concomitant for 5 patients and separated by 12–288 months for the remaining 4. Despite ongoing immunosuppression, histologic examination of 7 (78%) patients’ explanted hearts showed histologic patterns suggestive of active vasculitis. The overall 5-year survival rate was low (57%) but rose to 80% when considering only the 6 patients transplanted during the last decade. After survival lasting 3–60 months, 4 (44%) patients died sudden deaths. Conclusions The search for EGPA-related cardiomyopathy is mandatory early during the course of this vasculitis. Indeed, prompt treatment with corticosteroids and cyclophosphamide may achieve recovery of cardiac function. Most patients in this series were undertreated. For patients with refractory EGPA, heart transplantation should be performed and carries a fair prognosis. No optimal immunosuppressive strategy has yet been identified.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 01/2014; · 3.54 Impact Factor
  • International journal of cardiology 09/2013; · 6.18 Impact Factor
  • International journal of cardiology 07/2013; · 6.18 Impact Factor
  • La Presse Médicale 04/2013; 42(4):652–653. · 0.87 Impact Factor
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    ABSTRACT: Asymmetric dimethylarginine (ADMA) is associated with increased mortality in patients with chronic heart failure but it remains unclear if the etiology of heart failure influences the prognostic value of dimethylarginines. L-Arginine, ADMA, and symmetric dimethylarginine (SDMA) were measured by liquid chromatography-tandem mass spectrometry in 341 patients with chronic heart failure due to dilated cardiomyopathy (DCM; n = 226) or ischemic cardiomyopathy (ICM; n = 115). Median (interquartile range [IQR]) ADMA and SDMA plasma levels were higher, L-arginine and the L-arginine-ADMA ratio were lower in patients with severe forms of heart failure (New York Heart Association (NYHA) functional class III or IV) compared with milder forms (NYHA functional class I or II) (ADMA 0.57 (0.14) μmol/L vs 0.54 (0.12) μmol/L [P < .001]; SDMA 0.47 (0.27) μmol/L vs 0.37 (0.13) μmol/L [P < .001]; L-arginine 81.8 (39.1) μmol/L vs 92.6 (39.3) μmol/L [P < .01]), but no significant differences were observed between the different etiologies. The L-arginine-ADMA ratio was associated with outcome only in patients with DCM. In multivariate analysis, the mortality risk of DCM patients was significantly lower for those in the highest quartile compared with the lowest quartile during a median observation time of 3.3 years (hazard ratio 0.31, 95% CI 0.11-0.88; P = .028, adjusted for other risk factors). DCM patients with unfavourable L-arginine-ADMA ratio are at increased risk for death.
    Journal of cardiac failure 12/2012; 18(12):904-11. · 3.25 Impact Factor
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    ABSTRACT: Previous experimental studies concluded that stem cells (SC) may exert their beneficial effects on the ischemic heart by paracrine activation of antiapoptotic pathways. In order to identify potential cardioprotective mediators, we performed a systematic analysis of the differential gene expression of hematopoietic SC after coculture with cardiomyocytes (CM). After 48 h of coculture with neonatal rat ventricular CM (NRVCM), two consecutive cell sorting steps generated a highly purified population of conditioned murine hematopoietic SC (>99%). Next, a genome-wide microarray analysis of cocultured vs. monocultured hematopoietic SC derived from three independent experiments was performed. The analysis of differentially expressed genes was focused on products that are secretable and/or membrane-bound and potentially involved in antiapoptotic signalling. We found CCL-12, Macrophage Inhibitory Factor, Fibronectin and connexin 40 significantly upregulated in our coculture model. An ELISA of cell culture supernatants was performed to confirm secretion of candidate genes and showed that coculture supernatants revealed markedly higher CCL-12 concentrations. Moreover, we stimulated NRVCM with concentrated coculture supernatants which resulted in a significant reduction of apoptosis compared to monoculture-derived supernatant. Mechanistically, NRVCMs stimulated with coculture supernatants showed a higher level of AKT-phosphorylation, consistent with enhanced antiapoptotic signaling. In summary, our results show that the interaction between hematopoietic SC and NRVCM led to a modified gene expression and induction of antiapoptotic pathways. These findings may thus at least in part explain the cardioprotective effects of hematopoietic SC.
    Journal of Translational Medicine 06/2012; 10:115. · 3.46 Impact Factor
  • International journal of cardiology 03/2012; 155(3):504-5. · 6.18 Impact Factor
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    ABSTRACT: Osteopontin (OPN) was found upregulated in several heart failure models and appears to play an important role in myocardial remodelling. As we have previously demonstrated that OPN predicts mortality in patients with pulmonary hypertension (PH), we now evaluated whether OPN also predicts adverse right ventricular (RV) remodelling and dysfunction in PH. We prospectively included 71 patients with PH of different etiology in this study. OPN plasma level were determined by ELISA and assessed for correlation with RV dilatation and dysfunction determined by echocardiography. OPN plasma values significantly correlated with RV end-diastolic diameter, Tricuspid Annular Plane Systolic Excursion (TAPSE) and Tricuspid Annular Systolic Velocity (TASV) (r = 0·43, P = 0·0002; r = -0·46, P = 0·0006; r = -0·31, P = 0·02). Furthermore, stratification of our study population according to RV end-diastolic diameter and RV dysfunction revealed that patients with enlarged and functionally impaired RV's display higher OPN levels (956 ng/mL vs. 628 ng/mL, P = 0·0005; 1108 ng/mL vs. 792 ng/mL; P = 0·02). Next, we determined OPN cut-off values for the detection of RV remodelling and dysfunction by receiver operating curve analyses and further stratified these parameters in a multivariate analysis. Here, OPN emerged as an independent predictor of RV dilatation and dysfunction. Finally, we demonstrate synergism of OPN and NT-proBNP in the prediction of RV dilatation and dysfunction by calculation of the Rothman Synergy Index. In summary, OPN predicts adverse RV remodelling and dysfunction in PH. Together with our previously published data regarding OPN's value for the prognostication of death in PH, we believe that OPN can improve risk stratification in patients with PH beyond current assessment standards.
    European Journal of Clinical Investigation 03/2012; 42(9):933-42. · 3.37 Impact Factor
  • M Rosenberg, N Frey
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    ABSTRACT: The number of patients who develop cardiac problems during pregnancy are increasing and represent to date the major cause of maternal death in western countries. Pregnancy induces several changes which together increase the hemodynamic burden on the cardiovascular system and can also cause a prothrombotic state. Hence, latent or apparent cardiac disease can acutely decompensate during pregnancy. From a cardiovascular perspective, pregnancies are most often complicated by acute coronary syndromes, peripartum cardiomyopathy, arrhythmias, or pulmonary embolism. Due to potential fetal harm conventional diagnostic and therapeutic approaches are limited by the restricted use of radiogenic cardiac imaging and applicable medications. Therefore, knowledge about available therapeutic options is of greatest importance, since guideline recommendations have clearly been demonstrated to reduce morbidity and mortality in acute cardiac emergencies during pregnancy.
    Medizinische Klinik, Intensivmedizin und Notfallmedizin. 02/2012; 107(2):101-9.
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    ABSTRACT: The aim of the present study was to assess potential differences in cardiac autonomic nervous modulation in patients with transient left ventricular apical ballooning syndrome (AB) and the midventricular variant (MB) of this syndrome. We hypothesized that differences in regional distribution of cardiac autonomic innervation in AB and MB may induce alterations in autonomic modulation, and we tested this assumption by using a combination of traditional and novel nonlinear parameters of heart rate variability (HRV). In a prospective single-center study, 49 consecutive patients with transient left ventricular dysfunction syndrome underwent Holter electrocardiographic recording on the third day after admission. A total of 27 recordings of patients with AB and 10 recordings of patients with MB were valid for analysis of HRV, nonlinear dynamic measures of HRV, detrended fluctuation analysis (DFA), and phase-rectified signal averaging (PRSA). There were no significant differences in baseline clinical characteristics between AB and MB patients. Patients with MB showed significantly lower values for mean RR interval (835 ± 104 ms vs. 908 ± 118 ms; P < .05), 1/f power law slope (-1.28 ± 0.2 vs. -1.13 ± 0.2; P < .01), and deceleration capacity (DC) (4.6 ± 1.4 ms vs. 6.0 ± 1.4 ms; P < .01), and significantly higher values for low-frequency (LF) spectral component (5.3 ± 0.5 ln ms(2)/Hz vs. 4.8 ± 0.5 ln ms(2)/Hz), LF/high-frequency (HF) (1.7 ± 0.9 ms vs. 1.3 ± 0.6 ms; P < .05), and DFA α1 (1.09 ± 0.1 vs. 0.99 ± 0.1; P < .01) than patients with AB. There were no significant correlations between parameters of HRV, DFA, 1/f power law slope, and PRSA. There are significant differences in heart rate dynamics between AB and MB syndromes. Patients with MB show stronger fractal correlations of heart rate dynamics. Thus, inhomogeneous efferent bilateral sympathetic coactivation and differences in reflex autonomic regulation may be underlying pathophysiological mechanisms for AB and MB syndromes.
    Heart rhythm: the official journal of the Heart Rhythm Society 12/2010; 7(12):1825-32. · 4.56 Impact Factor
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    M. Rosenberg, N. Frey
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    ABSTRACT: Der Alkoholabusus ist die häufigste Ursache einer sekundären Kardiomyopathie. Man geht davon aus, dass der Konsum von >90g reinem Alkohol pro Tag über einen Zeitraum >5Jahren bei entsprechender Disposition eine alkoholische Kardiomyopathie (ACM) induzieren kann. Die dabei zugrunde liegenden molekularen Mechanismen sind komplex und beeinflussen zahlreiche zelluläre Vorgänge wie die intrazelluläre Energiegewinnung, die Kalziumhomöostase sowie die Funktion des kontraktilen Apparates. Darüber hinaus scheint es interindividuelle Unterschiede in der Sensitivität gegenüber den toxischen Effekten des Alkohols zu geben, was die Bedeutung genetischer und weiterer umweltbedingter Faktoren in der Pathogenese der ACM hervorhebt. Die Diagnosestellung bleibt aufgrund fehlender spezifischer Zeichen schwierig und beruht auf der Koinzidenz eines Alkoholabusus und einer ätiologisch ungeklärten dilatativen Kardiomyopathie. Eine künftige Alkoholabstinenz sowie die Verwendung einer spezifischen Herzinsuffizienztherapie sind für eine Verbesserung der linksventrikulären Pumpfunktion und der individuellen Prognose von größter Bedeutung. Long-term alcohol abuse is the leading cause of a secondary cardiomyopathy. In general, alcoholic patients consuming >90g alcohol per day for more than 5 years are at risk for developing an alcoholic cardiomyopathy (ACM). The underlying pathophysiology is complex and involves many aspects of cardiomyocyte function, such as impaired intracellular energy generation, calcium homeostasis and myofibrillar force generation. Clinical data suggest that there are interindividual differences in the susceptibility to alcohol-induced myocardial damage, which emphasizes the importance of genetic and environmental traits in the pathogenesis of ACM. Since there are no specific signs of ACM, diagnosis remains difficult and basically relies on the coincidence of alcohol abuse and dilated cardiomyopathy. Alcohol abstinence, as well as the use of specific heart failure pharmacotherapies, is critical in improving ventricular function and outcomes in these patients.
    Der Kardiologe 01/2010; 4(1):55-64.
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    ABSTRACT: Tumour necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) is a multifunctional cytokine that has recently been implicated in cardiovascular disease. The aim of this study was to define the plasma levels of sTWEAK in patients with stable chronic heart failure and evaluate the possibility of a prognostic impact of sTWEAK. sTWEAK levels in plasma samples from 364 patients with systolic heart failure were compared with 36 control patients. The median levels of sTWEAK in heart failure patients were significantly lower than those of the control group (217 pg/mL, interquartile range 136-311 vs. 325 pg/mL, interquartile range 250-394 pg/mL). Moreover, sTWEAK levels were lower in patients with ischaemic cardiomyopathy vs. dilated cardiomyopathy and correlated significantly with functional NYHA class. Patients with plasma levels below a ROC-derived cut-off value of 227 pg/mL had a significantly higher mortality rate after 4 years. Upon univariate and multivariate analyses, sTWEAK levels below 227 pg/mL emerged as an independent predictor of subsequent death. In contrast to other cytokines shown to be increased in heart failure patients, plasma levels of sTWEAK are significantly reduced in chronic stable heart failure. In addition, lower plasma levels of sTWEAK predict an adverse prognosis independent of established risk markers such as NT-proBNP.
    European Journal of Heart Failure 11/2009; 11(11):1050-6. · 5.25 Impact Factor
  • Mark Rosenberg, Martin Urbansky, Markus Haass
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    ABSTRACT: Transfer of current treatment guidelines for high blood cholesterol into clinical practice, especially under timely consideration of the last coronary angiography (CA), remains unclear. We therefore tested the efficiency of statin treatment in 209 patients with coronary heart disease and allocated them according to the time of the last CA in 2 groups (<or= />12 months). Median low-density lipoprotein cholesterol (LDL-C) of the study population was 117 mg/dL. Whereas 81% of the patients with CA <or= 12 months received statins, application rate dropped to 67% in patients with angiograms >12 months (P<0.05). Comparison of the median ratio of the applied statin dose to its equivalent dose demonstrated a higher therapy intensity in patients with recent CA (1.0 vs. 0.5; P < 0.05). Therefore, patients with CA <or= 12 months had lower median LDL-C levels (102 vs. 121 mg/dL; P<0.001) and were more likely to have LDL-C levels <100 mg/dL (40% vs. 19%; P<0.01). The results of our study show that in patients with coronary heart disease, application and dose rates of statins are inversely related to the time of the last CA.
    Journal of cardiovascular pharmacology 02/2009; 53(3):215-22. · 2.83 Impact Factor
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    ABSTRACT: Osteopontin, a glycoprotein that can be detected in plasma, was found to be upregulated in several animal models of cardiac failure and may thus represent a new biomarker that facilitates risk stratification in patients with heart failure. We therefore tested whether osteopontin plasma levels are elevated in patients with chronic heart failure and whether they provide independent prognostic information. We analyzed osteopontin plasma levels in 420 patients with chronic heart failure due to significantly impaired left ventricular systolic function and correlated the results with disease stage and prognostic information (median follow-up of 43 months). We found that osteopontin plasma levels were significantly elevated in patients with heart failure as compared with healthy control subjects (532 versus 382 ng/mL, P=0.008), irrespective of heart failure origin (ischemic versus dilated cardiomyopathy). Furthermore, osteopontin levels were higher in patients with moderate to severe heart failure than in patients with no or mild symptoms (672 ng/mL for New York Heart Association class III/IV versus 479 ng/mL for class I/II, P<0.0001). Estimated 4-year death rates in patients with osteopontin levels above or below a cutoff value derived from receiver operating characteristic analyses were 56.5% and 28.4%, respectively (hazard ratio 3.4, 95% confidence interval 2.2 to 5.3, P<0.0001). In a multivariable model that included demographic, clinical, and biochemical parameters such as N-terminal prohormone brain natriuretic peptide, osteopontin emerged as an independent predictor of death (hazard ratio 2.3, 95% confidence interval 1.4 to 3.5, P<0.001). Our findings suggest that osteopontin might be useful as a novel prognostic biomarker in patients with chronic heart failure.
    Circulation Heart Failure 05/2008; 1(1):43-9. · 6.68 Impact Factor
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    ABSTRACT: Recent studies have shown that stem cell therapy may alleviate the detrimental effects of myocardial infarction. Yet, most of these reports observed only modest effects on cardiac function, suggesting that there still is need for improvement before widespread clinical use. One potential approach would be to increase migration of stem cells to the heart. We therefore tested whether local administration of stem cell factor (SCF) improves myocardial homing of intravenously infused lin-/c-kit+ stem cells after myocardial infarction. Myocardial infarction was induced in mice via ligation of the left anterior descending artery and 2.5 microg of SCF were injected into the peri-infarct zone. Sham-operated mice and animals with intramyocardial injection of phosphate-buffered saline (PBS) served as controls. Twenty-four hours after myocardial infarction, lin-/c-kit+ stem cells were separated from murine bone marrow by magnetic cell sorting, labelled with the green fluorescent cell tracker CFDA or 111 Indium, and subsequently 750 000 labelled cells were systemically infused via the tail vein. Another 24 or 72 h later, respectively (i.e. 48 and 96 h after myocardial infarction), hearts were removed and analysed for myocardial homing of stem cells. Green fluorescent stem cells were exclusively detected in the peri-infarct zone of animals having prior SCF treatment. Radioactive measurements revealed that an intramyocardial SCF injection significantly amplified myocardial homing of lin-/c-kit+ stem cells compared to animals with PBS injections (3.58 +/- 0.53 vs. 2.28 +/- 0.23 cpm/mg/10(6)cpm, +60%, P < 0.05) and sham-operated mice without myocardial infarction (3.58 +/- 0.53 vs. 1.95 +/- 0.22 cpm/mg/10(6)cpm, +85%, P < 0.01). Similar results were obtained 72 h after stem cell injection. We demonstrate that intramyocardial administration of SCF sustainably directs more lin-/c-kit+ stem cells to the heart. Future studies will have to show whether higher levels of myocardial SCF (i.e. by virus-mediated gene transfer) can further improve homing of systemically delivered c-kit+ stem cells and thus favourably influence cardiac remodelling following myocardial infarction.
    Cardiovascular Research 01/2008; 77(1):143-50. · 5.81 Impact Factor
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    ABSTRACT: Apical ballooning syndrome, or takotsubo cardiomyopathy, is a syndrome characterized by transient left ventricular dysfunction, frequently presenting with electrocardiographic changes and elevated cardiac biomarkers in the absence of obstructive coronary artery disease. We describe a case where repeated emotional stress caused recurrent ventricular dysfunction in varying regions of the left ventricle.
    Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 04/2007; 20(4):439.e11-2. · 2.98 Impact Factor
  • European Journal of Heart Failure Supplements 01/2007; 6(1):21-21.

Publication Stats

128 Citations
74.99 Total Impact Points

Institutions

  • 2012–2014
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
  • 2013
    • Christian-Albrechts-Universität zu Kiel
      Kiel, Schleswig-Holstein, Germany
  • 2010–2012
    • Universitätsklinikum Schleswig - Holstein
      Kiel, Schleswig-Holstein, Germany
  • 2006–2009
    • Universität Heidelberg
      • • Department of Cardiology
      • • II. Medical Clinic
      Heidelberg, Baden-Wuerttemberg, Germany