Reflusso e Aritmie Dr. Paolo Pieragnoli SOD Aritmologia Firenze

1. Lo sport come mezzo di prevenzione 14 Settembre 2013 Reflusso e Aritmie Dr. Paolo Pieragnoli SOD Aritmologia Firenze

2. 80 Framingham study 60 Uomini 40 Donne 20 Incidenza (n • 103/2 anni) 0 55-64 65-74 75-84 85-94 Età(anni) Benjamin EJ, et al. JAMA 1994 Epidemiologia • Incidenza e prevalenza della fibrillazione atriale (FA) aumentano con l’aumentare dell’età

3. Prevalenza di fibrillazione atriale per età e sesso nello Studio ATRIA 12 Donne 10 Uomini 8 6 4 2 0 <55 55-64 60-64 65-69 70-74 75-79 80-84 >85 17,974 soggetti con FA (0.95%) in una popolazione USA (California) di 1.89 milioni di persone Rif. 1.7.1996-31.12.1997 Prevalenza (%) Gruppi di età (anni) Go AS et al, JAMA 2001

4. AF in the generalpopulation • 1.6% prevalence of AF in general population • (Framingham study, AHJ 1983) • 3.2% people aged 30-62 yrs develop AF during the subsequent 24 years (Framingham study, AHJ 1983) • 5.5% people >65 yrs have AF (Furberg, AJC 1994) • 41% paroxysmal, 59% chronic (Framingham study, AHJ 1983)

5. Stima NON conservativa – Continuo aumento di incidenza 16 12 Stima dei soggetti con FA (N, milioni) 8 Stima conservativa – Nessun ulteriore aumento di incidenza 4 0 2000 2010 2020 2030 2040 2050 Anno Miyasaka Y. Circulation, 2006

6. Fibrillazione atriale: cause • Cardiaca • Non cardiaca • “Lone” atrial fibrillation

7. “Lone” Atrial FibrillationThe Olmsted County Study.N Engl J Med 1987; 317: 669-674 • Absence of identifiable cardiovascular, pulmonary, or precipitating illness, age <60 yrs • 2.7% of patients with atrial fibrillation • Mean 15 yrs follow-up • 1.3% incidence of stroke • 94% survival

8. Fibrillazione atriale: cause cardiache • Malattia cardiaca ipertensiva • Malattia cardiaca ischemica • Malattia cardiaca valvolare • Reumatica: stenosi della mitrale • Non reumatica: stenosi dell’aorta, rigurgito mitrale • Pericardite • Tumori cardiaci • Sick sinus syndrome • Cardiomiopatia • Ipertrofica • Idiopatica dilatativa • Chirurgia post bypass coronarico

9. Fibrillazione atriale: cause non cardiache • Polmonare • Metabolica • Ipertiroidismo • Disordine elettrolitico • Tossica: alcol (‘holiday heart’ syndrome)

10. Ageing • Hypertension • Symptomatic heart failure • Tachycardiomyopathy • Valvular heart disease • Cardiomyopathies • Atrial septal defect • Other congenital heart disease • Thyroid dysfunction • Obesity • Diabetes mellitus • Chronic obstructive pulmonary disease (COPD) • Sleep apnea • Chronic renal disease • Alcohol abuse • Exercise • Local or systemic inflammation • ACID REFLUX DISEASE

12. Gastroesophageal reflux disease or acid reflux disease is the most common gastrointestinal diagnosis recorded during visits to outpatien clinics

14. The potential mechanism of GERD-induced AF

15. REFLUX DISEASE INFLAMMATION AUTOIMMUNE Afferent-efferentrefluxmechanismwithcerebralrepresentationofcardiacrhythm Localpericarditismyocarditis Vagalnerves, peripheralnerves Inflammatorymediators-cytokines and interleukins Autoantibodiesagainstmyosinchains Sympatho-vagalimbalance ATRIAL FIBRILLATION

16. INFLAMMATION

17. Relationship between the esophagus and the left atrium. A: posterior-anterior aspect of the left atrium. B: Right anterior oblique view Circulation 112(4), 459–464 (2005)

19. Recurrent acid secretion induces mucosal inflammation and secretion of interleukin IL-1b and IL-6 These inflammatory cytokines play a pivotal role in the pathogenesis of AF.

20. INFLAMMATION AND ATRIAL FIBRILLATION

21. The human esophagus produces IL-6 and other inflammatory citokines

22. Sympatho-vagalimbalance

23. Acid reflux causes a local inflammatory process that may alter the autonomic innervations of the esophageal mucosa, and may also penetrate the esophageal wall and affect the adjacent vagal nerves due to the close juxtaposition of the esophagus and atria, especially the left atrium, where most triggers associated with atrial fibrillation have been described, affecting myelination and thus propagation of stimuli. Inflammation of the esophagegal mucosa affects local receptors that may induce afferent-efferent reflex mechanisms of the cardiac rhythm which can lead to secondary stimulation of the vagal nerves inducing AF.

24. AUTONOMIC SYSTEM AND ATRIAL FIBRILLATION

25. Autoimmune GERD Autoantibodies

26. HiatalHernia

27. Hiatal hernia is a condition in which parts of the abdominal contents, mainly the GEJ and the stomach, are proximally displaced above the diaphram through the esophageal hiatus into the mediastinum. Hiatal hernia (10% in patients younger than 40 years to 70% in patients older than 70 years) may predispose to GERD or worsen existing GERD in a few individuals

29. Possible mechanisms are : • Atrial arrhythmias may be induced by a mechanical effect on the left atrial wall that is related to the passage of food • A large hiatal hernia may also cause compression of the left atrium and may result in an area of relative ischemia and anatomical block resulting in reentry and arrhythmias

30. The CurrentLiterature on AF & GERD

31. Reflux esophagitis in the pathogenesis of paroxysmal atrial fibrillation: results of a pilot study N° of patients Methodology Results Conclusion Weilg et al, 2003

32. N° of patients

33. Relationship between atrial fibrillation and gastroesophageal reflux disease: multicenter questionnaire survey N° of patients Methodology Results Conclusion Shimazu et al, 2011

34. Pulmonary veins isolation: pathophysiology M. Gulizia et al “Diagnosi e terapia del Flutter e della Fibrillazione atriale” 2009

35. Choice between ablation and antiarrhythmic drug therapy for patients with and without structural heart disease European Heart Journal (2010) 31, 2369–2429

40. 40% 37% 29%

41. 87% 81% 63%

42. Major Complications of Catheter Ablation for Atrial Fibrillation Circ J 2010; 74: 1972 – 1977

48. CONCLUSION 1 The association between AF and GERD is still debated, predominantly because of shared confounding factors such as obesity, diabetes and sleep apnea. However, there is a mounting body of evidence that suggests an association between the two; therefore, a large randomized clinical trial is warranted. Currently, the most likely potential mechanism for GERD-induced AF is local release of cytokines secondary to esophageal injury, which creates a proarrhythmogenic environment. Perhaps the most compelling evidence that supports this association is that proton pump inhibitors seem to reduce the incidence and the duration of AF.

49. CONCLUSION 2 At present, few clinicians outside the field of cardiac electrophysiology and gastroenterology are aware of the possible association of GERD, hiatal hernia and AF. As more patients with these disorders are treated and studied, our insights into the pathogenesis will be elucidated. It will be interesting to see whether AF causes GERD reciprocally, thus creating a cycle. Increasing awareness that GERD and/or hiatal hernia may be independent risk factors for AF may result in physicians being more aggressive in treating patients with proton pump inhibitors and hiatal hernia repair, since both of these therapies have shown a reduction in the incidence and duration of AF.