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

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

Prevalenza di fibrillazione atriale per età e sesso nello Studio ATRIA 2 4 6 8 10 12 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 Uomini Donne Prevalenza (%) <55 55-64 60-64 70-74 65-69 80-84 75-79 >85 Gruppi di età (anni) Go AS et al, JAMA 2001 3

AF in the general population 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)

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

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

“Lone” Atrial Fibrillation The Olmsted County Study “Lone” Atrial Fibrillation The 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

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

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

ACID REFLUX DISEASE 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

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

The potential mechanism of GERD-induced AF

REFLUX DISEASE ATRIAL FIBRILLATION INFLAMMATION AUTOIMMUNE Afferent-efferent reflux mechanism with cerebral representation of cardiac rhythm Local pericarditis myocarditis Vagal nerves, peripheral nerves Inflammatory mediators-cytokines and interleukins Autoantibodies against myosin chains Sympatho-vagal imbalance ATRIAL FIBRILLATION

INFLAMMATION

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)

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.

INFLAMMATION AND ATRIAL FIBRILLATION

The human esophagus produces IL-6 and other inflammatory citokines

Sympatho-vagal imbalance

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.

AUTONOMIC SYSTEM AND ATRIAL FIBRILLATION

Autoimmune GERD Autoantibodies

Hiatal Hernia

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

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

The Current Literature on AF & GERD

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

Thirty-two patients (13 women and 19 men, age 20-69 years) with a combination of dysrhytmias and GERD, and 9 patients (5 women and 4 men, age 43-58 years) with GERD only underwent simultaneous 24-hours pH and ECG monitoring Power spectrum analysis of heart rate variability was obtained woth both low-frequency (LF) (symptathetic modulation) and high-frequency (HF) (vagal modulation) components. Hourly mean esophageal pH and LF/HF ratio (esophagus-heart) were correlated. A 3-month regimen of esomeprazole 40 mg/day was prescrived. In 18 patients with dysrhythmias and in none with GERD only, a significant correlation between esophageal pH and LF/HF ratio was observed. A significatn reduction of cardiac symptoms after PPI therapy was observed only in these patients (13/16 vs 4/11, p<0.01)

The study concluded that there could be a subgroup of patients with heart dysrhythmias in whom esophageal acid stimulus elicited cardiac autonomic reflexes, and acid suppression in this subgroup may improve both GERD and cardiac symptoms. Although this study demonstrated a reduction or disappearance of the dysrhythmias in patients with a cardiac response to esophageal acid exposure, it had some limitations.

N° of patients

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

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

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

40% 37% 29%

87% 81% 63%

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

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.

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.