Pathophysiologie des Renin-Angiotensin-Systems bei Vorhofflimmern

Zusammenfassung

Kardiovaskuläre Erkrankungen, die mit einer Aktivierung des Renin-Angiotensin-Systems einhergehen - Myokardinfarkt, Herzinsuffizienz, Hypertonie - führen häufig zu Vorhofflimmern. An der Auslösung und Aufrechterhaltung von Vorhofflimmern ist nicht nur die mechanische Vorhofdehnung, sondern auch eine verstärkte Expression einzelner Komponenten des Renin-Angiotensin-Systems in den Vorhöfen beteiligt. Diese induziert über eine inflammatorische Signalkaskade und oxidativen Stress eine Myolyse und verstärkte Fibrose. Letztlich ermöglichen eine lokal verlangsamte Erregungsleitung und eine verkürzte Refraktärzeit kreisende Erregungen, die einen grundlegenden Mechanismus von Vorhofflimmern darstellen. Sowohl ACE-Hemmer als auch AT₁-Blocker reduzieren in einer Meta-Analyse das relative Risiko von Vorhofflimmern um ca. 30 %; weitere prospektive, randomisierte, klinische Studien sind notwendig, um diesen Effekt endgültig zu belegen.

Pathophysiology of the renin-angiotensin-system in atrial fibrillation

Cardiovascular diseases which are associated with an activation of the renin-angiotensin-system - myocardial infarction, heart failure, hypertension - often induce atrial fibrillation. The initiation and maintenance of atrial fibrillation is not only initiated by mechanical distension of the atria, but also by increased atrial expression of components of the renin-angiotensin-system, which initiate an inflammatory signal cascade and oxidative stress and in consequence myolysis and interstitial fibrosis. Ultimately, locally decreased conduction velocity and abbreviated refractory period facilitate reentry circuit(s) as an underlying pathomechanism of atrial fibrillation. In a meta-analysis, ACE inhibitors and AT₁ blockers, both reduce the relative risk of atrial fibrillation by about 30 %. Further prospective randomized clinical studies are required to establish final evidence.

Vorhofflimmern - Angiotensin - ACE-Hemmer - AT₁-Blocker - Inflammation - Oxidativer Stress

atrial fibrillation - angiotensin - ACE inhibitor - AT₁-Blocker - inflammation - oxidative stress

Literatur

• 1 Allessie M A, Boyden P A, Camm J. et al . Pathophysiology and prevention of atrial fibrillation.  Circulation. 2001;  103 769-777
• 2 Ausma J, Borgers M. Dedifferentiation of atrial cardiomyocytes: from in vivo to in vitro.  Cardiovasc Res. 2002;  55 9-12
• 3 Bkaily G, Sculptoreanu A, Wang S. et al . Angiotensin II-induced increase of T-type Ca2+ current and decrease of L-type Ca2+ current in heart cells.  Peptides. 2005;  26 1410-1417
• 4 Boldt A, Wetzel U, Weigl J. et al . Expression of angiotensin II receptors in human left and right atrial tissue in atrial fibrillation with and without underlying mitral valve disease.  J Am Coll Cardiol. 2005;  42 1785-1792
• 5 Boos C J, Anderson R A, Lip G YH. Is atrial fibrillation an inflammatory disorder?.  Eur Heart J. 2006;  27(2) 136-149
• 6 Bosch R F, Grammer J B, Kühlkamp V, Seipel L. Elektrisches Remodeling bei Vorhofflimmern. Zelluläre und molekulare Mechanismen.  Z Kardiol. 2000;  89 795-802
• 7 Chen Y J, Chen Y C, Tai C T. et al . Angiotensin II and angiotensin II receptor blocker modulate the arrhythmogenic activity of pulmonary veins.  Br J Pharmacol. 2006;  147 (1) 12-22
• 8 Dernellis J, Panaretou M. Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation.  Eur Heart J. 2004;  25 1100-1107
• 9 Dobrev D, Ravens U. Remodeling of cardiomyocyte ion channels in human atrial fibrillation.  Basic Res Cardiol. 2003;  98 137-148
• 10 Donoghue M, Wakimoto H, Maguire C T. et al . Heart block, ventricular tachycardia, and sudden death in ACE2 transgenic mice with downregulated connexins.  J Mol Cell Cardiol. 2003;  35 1043-1053
• 11 Engelhorn T, Goerike S, Doerfler A. et al . The Angiotensin II type I (AT1)-receptor blocker candesartan increases cerebral blood flow, reduces infarct size and improves neurilogical outcome following transient cerebral ischemia in rats.  J Cereb Blood Flow Metab. 2004;  24 467-474
• 12 Goette A, Arndt M, Röcken C. et al . Regulation of angiotensin II receptor subtypes during atrial fibrillation.  Circulation. 2000;  101 2678-2681
• 13 Goette A, Staack T, Röcken C. et al . Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation.  J Am Coll Cardiol. 2000;  35 1669-1677
• 14 Healey J S, Baranchuk A, Crystal E. et al . Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.  J Am Coll Cardiol. 2005;  45 1832-1839
• 15 Kim Y M, Guzik T J, Zhang Y H. et al . A myocardial Nox2 containing NAD(P)H oxidase contributes to oxidative stress in human atrial fibrillation.  Circ Res. 2005;  97 629-636
• 16 Korantzopoulos P, Kolettis T M, Kountouris E. et al . Oral vitamin C administration reduces early recurrence rates after electrical cardioversion of persistent atrial fibrillation and attenuates associated inflammation.  Int J Cardiol. 2005;  102 321-326
• 17 Kostin S, Klein G, Szalay Z. et al . Structural correlate of atrial fibrillation in human patients.  Cardiovasc Res. 2002;  54 361-379
• 18 L’Allier P L, Ducharme A, Keller P -F. et al . Angiotensin-converting enzyme inhibition in hypertensive patients is associated with a reduction in the occurence of atrial fibrillation.  J Am Coll Cardiol. 2005;  44 159-164
• 19 Li D, Shinagawa K, Pang L. et al . Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure.  Circulation. 2001;  104 2608-2614
• 20 Madrid A H, Bueno M G, Rebollo J MG. et al . Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation. A prospective and randomized study.  Circulation. 2002;  106 331-336
• 21 Mathew J P, Fontes M L, Tudor I C. et al . A multicenter risk index for atrial fibrillation after cardiac surgery.  JAMA. 2004;  291 1720-1729
• 22 Nakashima H, Kumagai K, Urata H. et al . Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation.  Circulation. 2000;  101 2612-2617
• 23 Nattel S. New ideas about atrial fibrillation 50 years on.  Nature. 2002;  415 219-226
• 24 Neuberger H -R, Schotten U, Blaauw Y. et al . Chronic atrial dilation, electrical remodeling, and atrial fibrillation in the goat.  J Am Coll Cardiol. 2006;  47 644-653
• 25 Ogimoto A, Hamada M, Nakura J. et al . Relation between angiotensin-converting enzyme II genotype and atrial fibrillation in Japanese patients with hypertrophic cardiomyopathy.  J Hum Genet. 2004;  47 184-189
• 26 Pedersen O D, Bagger H, Kober L, Torp-Pedersen C. Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction.  Circulation. 1999;  100 376-380
• 27 Schulz R, Heusch G. AT1-receptor blockade in experimental myocardial ischemia/reperfusion.  Clinical Nephrology. 2003;  60 S67-S74
• 28 Sonoyama K, Igawa O, Miake J. et al . Effects of angiotensin II on the action potential durations of atrial myocytes in hypertensive rats.  Hypertens Res. 2005;  28 173-179
• 29 Tsai C -T, Lai L -P, Chiang F -T. et al . Renin-angiotensin system gene polymorphisms and atrial fibrillation.  Circulation. 2004;  109 1640-1646
• 30 Ueng K -C, Tsai T -P, Yu W -C. et al . Use of enalapril to facilitate sinus rhythm maintenance after external cardioversion of long-standing persistent atrial fibrilation. Results of a prospective and controlled study.  Eur Heart J. 2003;  24 2090-2098
• 31 van der Velden H MW, Jongsma H J. Cardiac gap junctions and connexins: their role in atrial fibrillation and potential as therapeutics targets.  Cardiovasc Res. 2002;  54 270-279
• 32 Vermes E, Tardif J -C, Bourassa M G. et al . Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction. Insight from the studies of left ventricular dysfunction (SOLVD) trials.  Circulation. 2003;  107 2926-2931
• 33 Wachtell K, Lehto M, Gerdts E. et al . Angiotensin II receptor blockade reduces new-onset atrial fibrillation ans subsequent stroke compared to atenolol. The losartan intervention for end point reduction in hypertension (LIFE) Study.  J Am Coll Cardiol. 2005;  45 712-719
• 34 Wijffels M CEF, Kirchhof C JHJ, Dorland R, Allessie M A. Atrial fibrillation begets atrial fibrillation: A study in awake chronically instrumented goats.  Circulation. 1995;  92 1954-1968