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01.05.2015 | Original Contribution

Soluble Flt-1 links microvascular disease with heart failure in CKD

verfasst von: Giovana S. Di Marco, Dominik Kentrup, Stefan Reuter, Anna B. Mayer, Lina Golle, Klaus Tiemann, Manfred Fobker, Christiane Engelbertz, Günter Breithardt, Eva Brand, Holger Reinecke, Hermann Pavenstädt, Marcus Brand

Erschienen in: Basic Research in Cardiology | Ausgabe 3/2015

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Abstract

Chronic kidney disease (CKD) is associated with an increased risk of heart failure (HF). Elevated plasma concentrations of soluble Flt-1 (sFlt-1) have been linked to cardiovascular disease in CKD patients, but whether sFlt-1 contributes to HF in CKD is still unknown. To provide evidence that concludes a pathophysiological role of sFlt-1 in CKD-associated HF, we measured plasma sFlt-1 concentrations in 586 patients with angiographically documented coronary artery disease and renal function classified according to estimated glomerular filtration rate (eGFR). sFlt-1 concentrations correlated negatively with eGFR and were associated with signs of heart failure, based on New York Heart Association functional class and reduced left ventricular ejection fraction (LVEF), and early mortality. Additionally, rats treated with recombinant sFlt-1 showed a 15 % reduction in LVEF and a 29 % reduction in cardiac output compared with control rats. High sFlt-1 concentrations were associated with a 15 % reduction in heart capillary density (number of vessels/cardiomyocyte) and a 24 % reduction in myocardial blood volume. Electron microscopy and histological analysis revealed mitochondrial damage and interstitial fibrosis in the hearts of sFlt-1-treated, but not control rats. In 5/6-nephrectomised rats, an animal model of CKD, sFlt-1 antagonism with recombinant VEGF121 preserved heart microvasculature and significantly improved heart function. Overall, these findings suggest that a component of cardiovascular risk in CKD patients could be directly attributed to sFlt-1. Assessment of patients with CKD confirmed that sFlt-1 concentrations were inversely correlated with renal function, while studies in rats suggested that sFlt-1 may link microvascular disease with HF in CKD.

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Amann K, Ritz E (2000) Microvascular disease—the Cinderella of uraemic heart disease. Nephrol Dial Transplant 15:1493–1503. doi:10.1093/ndt/15.10.1493 CrossRefPubMed

Bellamy L, Casas JP, Hingorani AD, Williams DJ (2007) Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ 335:974. doi:10.1136/bmj.39335.385301.BE CrossRefPubMedCentralPubMed

Bencini PL, Montagnino G, Citterio A, Graziani G, Crosti C, Ponticelli C (1985) Cutaneous abnormalities in uremic patients. Nephron 40:316–321CrossRefPubMed

Bergmann A, Ahmad S, Cudmore M, Gruber AD, Wittschen P, Lindenmaier W, Christofori G, Gross V, Gonzalves AC, Grone HJ, Ahmed A, Weich HA (2010) Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model. J Cell Mol Med 14:1857–1867. doi:10.1111/j.1582-4934.2009.00820.x CrossRefPubMedCentralPubMed

Brand E, Pavenstadt H, Schmieder RE, Engelbertz C, Fobker M, Pinnschmidt HO, Wegscheider K, Breithardt G, Reinecke H (2013) The Coronary Artery Disease and Renal Failure (CAD-REF) registry: trial design, methods, and aims. Am Heart J 166:449–456. doi:10.1016/j.ahj.2013.06.010 CrossRefPubMed

Bridges JP, Gilbert JS, Colson D, Gilbert SA, Dukes MP, Ryan MJ, Granger JP (2009) Oxidative stress contributes to soluble fms-like tyrosine kinase-1 induced vascular dysfunction in pregnant rats. Am J Hypertens 22:564–568. doi:10.1038/ajh.2009.24 CrossRefPubMedCentralPubMed

Cabiati M, Campan M, Caselli C, Prescimone T, Giannessi D, Del RS (2010) Sequencing and cardiac expression of natriuretic peptide receptors A and C in normal and heart failure pigs. Regul Pept 162:12–17. doi:10.1016/j.regpep.2010.02.004 CrossRefPubMed

Cindrova-Davies T, Sanders DA, Burton GJ, Charnock-Jones DS (2011) Soluble FLT1 sensitizes endothelial cells to inflammatory cytokines by antagonizing VEGF receptor-mediated signalling. Cardiovasc Res 89:671–679. doi:10.1093/cvr/cvq346 CrossRefPubMedCentralPubMed

Currie G, Delles C (2013) Proteinuria and its relation to cardiovascular disease. Int J Nephrol Renovasc Dis 7:13–24. doi:10.2147/IJNRD.S40522 PubMedCentralPubMed

10.

De Boer RA, Pinto YM, Van Veldhuisen DJ (2003) The imbalance between oxygen demand and supply as a potential mechanism in the pathophysiology of heart failure: the role of microvascular growth and abnormalities. Microcirculation 10:113–126. doi:10.1038/sj.mn.7800188 CrossRefPubMed

11.

Del RS, Andreassi MG, Clerico A, Biagini A, Giannessi D (2001) Endothelin-1, endothelin-1 receptors and cardiac natriuretic peptides in failing human heart. Life Sci 68:2715–2730CrossRef

12.

Di Marco GS, Reuter S, Hillebrand U, Amler S, Konig M, Larger E, Oberleithner H, Brand E, Pavenstadt H, Brand M (2009) The soluble VEGF receptor sFlt1 contributes to endothelial dysfunction in CKD. J Am Soc Nephrol 20:2235–2245. doi:10.1681/ASN.2009010061 CrossRefPubMedCentralPubMed

13.

Di Marco GS, Reuter S, Kentrup D, Ting L, Ting L, Grabner A, Jacobi AM, Pavenstadt H, Baba HA, Tiemann K, Brand M (2011) Cardioprotective effect of calcineurin inhibition in an animal model of renal disease. Eur Heart J 32:1935–1945. doi:10.1093/eurheartj/ehq436 CrossRefPubMed

14.

Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, Matsushita K, Wen CP (2013) Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet 382:339–352. doi:10.1016/S0140-6736(13)60595-4 CrossRefPubMed

15.

Gavin JB, Maxwell L, Edgar SG (1998) Microvascular involvement in cardiac pathology. J Mol Cell Cardiol 30:2531–2540. doi:10.1006/jmcc.1998.0824 CrossRefPubMed

16.

Giordano FJ, Gerber HP, Williams SP, VanBruggen N, Bunting S, Ruiz-Lozano P, Gu Y, Nath AK, Huang Y, Hickey R, Dalton N, Peterson KL, Ross J Jr, Chien KR, Ferrara N (2001) A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function. Proc Natl Acad Sci USA 98:5780–5785. doi:10.1073/pnas.091415198 CrossRefPubMedCentralPubMed

17.

Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY (2004) Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351:1296–1305. doi:10.1056/NEJMoa041031 CrossRefPubMed

18.

Gordon O, Gilon D, He Z, May D, Lazarus A, Oppenheim A, Keshet E (2012) Vascular endothelial growth factor-induced neovascularization rescues cardiac function but not adverse remodeling at advanced ischemic heart disease. Arterioscler Thromb Vasc Biol 32:1642–1651. doi:10.1161/ATVBAHA.112.248674 CrossRefPubMed

19.

Guo Q, Carrero JJ, Yu X, Barany P, Qureshi AR, Eriksson M, Anderstam B, Chmielewski M, Heimburger O, Stenvinkel P, Lindholm B, Axelsson J (2009) Associations of VEGF and its receptors sVEGFR-1 and -2 with cardiovascular disease and survival in prevalent haemodialysis patients. Nephrol Dial Transplant 24:3468–3473. doi:10.1093/ndt/gfp315 CrossRefPubMed

20.

Hara A, Wada T, Furuichi K, Sakai N, Kawachi H, Shimizu F, Shibuya M, Matsushima K, Yokoyama H, Egashira K, Kaneko S (2006) Blockade of VEGF accelerates proteinuria, via decrease in nephrin expression in rat crescentic glomerulonephritis. Kidney Int 69:1986–1995. doi:10.1038/sj.ki.5000439 CrossRefPubMed

21.

Heineke J, Molkentin JD (2006) Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol 7:589–600. doi:10.1038/nrm1983 CrossRefPubMed

22.

Hilfiker-Kleiner D, Limbourg A, Drexler H (2005) STAT3-mediated activation of myocardial capillary growth. Trends Cardiovasc Med 15:152–157. doi:10.1016/j.tcm.2005.05.002 CrossRefPubMed

23.

Hochholzer W, Reichlin T, Stelzig C, Hochholzer K, Meissner J, Breidthardt T, Reiter M, Duehsler B, Freidank H, Winkler K, Twerenbold R, Mueller C (2011) Impact of soluble fms-like tyrosine kinase-1 and placental growth factor serum levels for risk stratification and early diagnosis in patients with suspected acute myocardial infarction. Eur Heart J 32:326–335. doi:10.1093/eurheartj/ehq429 CrossRefPubMed

24.

Jacobi J, Porst M, Cordasic N, Namer B, Schmieder RE, Eckardt KU, Hilgers KF (2006) Subtotal nephrectomy impairs ischemia-induced angiogenesis and hindlimb re-perfusion in rats. Kidney Int 69:2013–2021. doi:10.1038/sj.ki.5000448 CrossRefPubMed

25.

Kendall RL, Wang G, Thomas KA (1996) Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR. Biochem Biophys Res Commun 226:324–328. doi:10.1006/bbrc.1996.1355 CrossRefPubMed

26.

Kendrick J, Chonchol MB (2008) Nontraditional risk factors for cardiovascular disease in patients with chronic kidney disease. Nat Clin Pract Nephrol 4:672–681. doi:10.1038/ncpneph0954 CrossRefPubMed

27.

Kim SY, Lee SH, Park S, Kang SM, Chung N, Shim WH, Cho SY, Sun HJ, Manabe I, Jang Y (2011) Vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, and the severity of coronary artery disease. Angiology 62:176–183. doi:10.1177/0003319710370963 CrossRefPubMed

28.

Kitzman DW, Upadhya B, Vasu S (2015) What the dead can teach the living: systemic nature of heart failure with preserved ejection fraction. Circulation 131:522–524. doi:10.1161/CIRCULATIONAHA.114.014420 CrossRefPubMed

29.

Kottgen A, Russell SD, Loehr LR, Crainiceanu CM, Rosamond WD, Chang PP, Chambless LE, Coresh J (2007) Reduced kidney function as a risk factor for incident heart failure: the atherosclerosis risk in communities (ARIC) study. J Am Soc Nephrol 18:1307–1315. doi:10.1681/ASN.2006101159 CrossRefPubMed

30.

Ky B, French B, Ruparel K, Sweitzer NK, Fang JC, Levy WC, Sawyer DB, Cappola TP (2011) The vascular marker soluble fms-like tyrosine kinase 1 is associated with disease severity and adverse outcomes in chronic heart failure. J Am Coll Cardiol 58:386–394. doi:10.1016/j.jacc.2011.03.032 CrossRefPubMedCentralPubMed

31.

Lavainne F, Meffray E, Pepper RJ, Neel M, Delcroix C, Salama AD, Fakhouri F (2014) Heparin use during dialysis sessions induces an increase in the antiangiogenic factor soluble Flt1. Nephrol Dial Transplant 29:1225–1231. doi:10.1093/ndt/gft517 CrossRefPubMed

32.

Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA (2004) Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 350:672–683. doi:10.1056/NEJMoa031884 CrossRefPubMed

33.

Levy AP (1999) A cellular paradigm for the failure to increase vascular endothelial growth factor in chronically hypoxic states. Coron Artery Dis 10:427–430CrossRefPubMed

34.

Li F, Hagaman JR, Kim HS, Maeda N, Jennette JC, Faber JE, Karumanchi SA, Smithies O, Takahashi N (2012) eNOS deficiency acts through endothelin to aggravate sFlt-1-induced pre-eclampsia-like phenotype. J Am Soc Nephrol 23:652–660. doi:10.1681/ASN.2011040369 CrossRefPubMedCentralPubMed

35.

Luttun A, Carmeliet P (2003) Soluble VEGF receptor Flt1: the elusive preeclampsia factor discovered? J Clin Invest 111:600–602CrossRefPubMedCentralPubMed

36.

Matsui M, Takeda Y, Uemura S, Matsumoto T, Seno A, Onoue K, Tsushima H, Morimoto K, Soeda T, Okayama S, Somekawa S, Samejima KI, Kawata H, Kawakami R, Nakatani K, Iwano M, Saito Y (2013) Suppressed soluble Fms-like tyrosine kinase-1 production aggravates atherosclerosis in chronic kidney disease. Kidney Int 85:393–403. doi:10.1038/ki.2013.339 CrossRefPubMed

37.

May D, Gilon D, Djonov V, Itin A, Lazarus A, Gordon O, Rosenberger C, Keshet E (2008) Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation. Proc Natl Acad Sci USA 105:282–287. doi:10.1073/pnas.0707778105 CrossRefPubMedCentralPubMed

38.

Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, Libermann TA, Morgan JP, Sellke FW, Stillman IE, Epstein FH, Sukhatme VP, Karumanchi SA (2003) Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 111:649–658. doi:10.1172/JCI17189 CrossRefPubMedCentralPubMed

39.

Murphy SR, LaMarca B, Cockrell K, Arany M, Granger JP (2012) L-arginine supplementation abolishes the blood pressure and endothelin response to chronic increases in plasma sFlt-1 in pregnant rats. Am J Physiol Regul Integr Comp Physiol 302:R259–R263. doi:10.1152/ajpregu.00319.2011 CrossRefPubMedCentralPubMed

40.

Muttukrishna S, Swer M, Suri S, Jamil A, Calleja-Agius J, Gangooly S, Ludlow H, Jurkovic D, Jauniaux E (2011) Soluble Flt-1 and PlGF: new markers of early pregnancy loss? PLoS One 6:e18041. doi:10.1371/journal.pone.0018041 CrossRefPubMedCentralPubMed

41.

Neubauer S (2007) The failing heart—an engine out of fuel. N Engl J Med 356:1140–1151. doi:10.1056/NEJMra063052 CrossRefPubMed

42.

Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13:9–22PubMed

43.

O’Riordan E, Chen J, Brodsky SV, Smirnova I, Li H, Goligorsky MS (2005) Endothelial cell dysfunction: the syndrome in making. Kidney Int 67:1654–1658. doi:10.1111/j.1523-1755.2005.00256.x CrossRefPubMed

44.

Onoue K, Uemura S, Takeda Y, Somekawa S, Iwama H, Nishida T, Morikawa Y, Nakagawa H, Tsutsumi T, Sung JH, Takemoto Y, Soeda T, Okayama S, Ishigami K, Kawata H, Horii M, Nakajima T, Saito Y (2009) Usefulness of soluble Fms-like tyrosine kinase-1 as a biomarker of acute severe heart failure in patients with acute myocardial infarction. Am J Cardiol 104:1478–1483. doi:10.1016/j.amjcard.2009.07.016 CrossRefPubMed

45.

Parodi EM, Kuhn B (2014) Signalling between microvascular endothelium and cardiomyocytes through neuregulin. Cardiovasc Res 102:194–204. doi:10.1093/cvr/cvu021 CrossRefPubMedCentralPubMed

46.

Patten IS, Rana S, Shahul S, Rowe GC, Jang C, Liu L, Hacker MR, Rhee JS, Mitchell J, Mahmood F, Hess P, Farrell C, Koulisis N, Khankin EV, Burke SD, Tudorache I, Bauersachs J, del MF, Hilfiker-Kleiner D, Karumanchi SA, Arany Z (2012) Cardiac angiogenic imbalance leads to peripartum cardiomyopathy. Nature 485:333–338. doi:10.1038/nature11040 CrossRefPubMedCentralPubMed

47.

Rajakumar A, Michael HM, Rajakumar PA, Shibata E, Hubel CA, Karumanchi SA, Thadhani R, Wolf M, Harger G, Markovic N (2005) Extra-placental expression of vascular endothelial growth factor receptor-1, (Flt-1) and soluble Flt-1 (sFlt-1), by peripheral blood mononuclear cells (PBMCs) in normotensive and preeclamptic pregnant women. Placenta 26:563–573. doi:10.1016/j.placenta.2004.09.001 CrossRefPubMed

48.

Ramaciotti C, Sharkey A, McClellan G, Winegrad S (1992) Endothelial cells regulate cardiac contractility. Proc Natl Acad Sci USA 89:4033–4036CrossRefPubMedCentralPubMed

49.

Sattar N, Greer IA (2002) Pregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening? BMJ 325:157–160. doi:10.1136/bmj.325.7356.157 CrossRefPubMedCentralPubMed

50.

Searle J, Slagman A, Gwosc S, Vollert JO, Holert F, Muller C, Muller R, Mockel M (2012) Soluble fms-like tyrosine kinase-1 (sFLT-1) predicts post-percutaneous coronary intervention (PCI) myocardial infarction (MI type 4a). Biomarkers 17:730–737. doi:10.3109/1354750X.2012.725428 CrossRefPubMed

51.

Smith DH, Thorp ML, Gurwitz JH, McManus DD, Goldberg RJ, Allen LA, Hsu G, Sung SH, Magid DJ, Go AS (2013) Chronic kidney disease and outcomes in heart failure with preserved versus reduced ejection fraction: the Cardiovascular Research Network PRESERVE Study. Circ Cardiovasc Qual Outcomes 6:333–342. doi:10.1161/CIRCOUTCOMES.113.000221 CrossRefPubMedCentralPubMed

52.

Thang OH, Serne EH, Grooteman MP, Smulders YM, ter Wee PM, Tangelder GJ, Nube MJ (2011) Capillary rarefaction in advanced chronic kidney disease is associated with high phosphorus and bicarbonate levels. Nephrol Dial Transplant 26:3529–3536. doi:10.1093/ndt/gfr089 CrossRefPubMed

53.

Ventura-Clapier R, Garnier A, Veksler V, Joubert F (2011) Bioenergetics of the failing heart. Biochim Biophys Acta 1813:1360–1372. doi:10.1016/j.bbamcr.2010.09.006 CrossRefPubMed

54.

Vorovich E, French B, Ky B, Goldberg L, Fang JC, Sweitzer NK, Cappola TP (2014) Biomarker predictors of cardiac hospitalization in chronic heart failure: a recurrent event analysis. J Card Fail 20:569–576. doi:10.1016/j.cardfail.2014.05.013 CrossRefPubMed

55.

Widyantoro B, Emoto N, Nakayama K, Anggrahini DW, Adiarto S, Iwasa N, Yagi K, Miyagawa K, Rikitake Y, Suzuki T, Kisanuki YY, Yanagisawa M, Hirata K (2010) Endothelial cell-derived endothelin-1 promotes cardiac fibrosis in diabetic hearts through stimulation of endothelial-to-mesenchymal transition. Circulation 121:2407–2418. doi:10.1161/CIRCULATIONAHA.110.938217 CrossRefPubMed

Titel: Soluble Flt-1 links microvascular disease with heart failure in CKD
verfasst von: Giovana S. Di Marco
Dominik Kentrup
Stefan Reuter
Anna B. Mayer
Lina Golle
Klaus Tiemann
Manfred Fobker
Christiane Engelbertz
Günter Breithardt
Eva Brand
Holger Reinecke
Hermann Pavenstädt
Marcus Brand
Publikationsdatum: 01.05.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Basic Research in Cardiology / Ausgabe 3/2015
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-015-0487-4

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Soluble Flt-1 links microvascular disease with heart failure in CKD

Abstract

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