Reflusso e Aritmie
Dr. Paolo Pieragnoli
SOD Aritmologia
Firenze
Epidemiologia
• Incidenza e prevalenza della fibrillazione atriale
(FA) aumentano con l’aumentare dell’età
Framingham study
Incidenza (n • 103/2 anni)
80
Uomini
60
Donne
40
20
0
55-64
65-74
75-84
Età (anni)
Benjamin EJ, et al. JAMA 1994
85-94
Prevalenza di fibrillazione atriale per età
e sesso nello Studio ATRIA
12
Prevalenza (%)
10
11,1
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
10,3
9,1
8
7,3
Donne
Uomini
6
5
4
3
1,7
2
0,9
0,1 0,2
0
7,2
<55
5
3,4
1,7
1
0,4
55-64
60-64
65-69
70-74
Gruppi di età (anni)
75-79
80-84
>85
Go AS et al, JAMA 2001
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
(N, milioni)
16
Stima NON conservativa – Continuo
aumento di incidenza
12
8
Stima conservativa – Nessun
ulteriore aumento di incidenza
4
0
2000
2010
2020
2030
2040
2050
Anno
Miyasaka Y. Circulation, 2006
Fibrillazione atriale: cause
• Cardiaca
• Non cardiaca
• “Lone” atrial fibrillation
“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)
• Ageing
• Obesity
•Hypertension
•Diabetes mellitus
•Symptomatic heart failure
•Chronic obstructive pulmonary disease (COPD)
•Tachycardiomyopathy
•Sleep apnea
•Valvular heart disease
•Chronic renal disease
•Cardiomyopathies
•Alcohol abuse
•Atrial septal defect
•Exercise
•Other congenital heart disease
•Local or systemic inflammation
•Thyroid dysfunction
• 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
INFLAMMATION
Afferent-efferent
reflux mechanism
with cerebral
representation of
cardiac rhythm
Local
pericarditis
myocarditis
Vagal nerves,
peripheral
nerves
AUTOIMMUNE
Inflammatory
mediatorscytokines and
interleukins
Sympatho-vagal imbalance
ATRIAL FIBRILLATION
Autoantibodies
against myosin
chains
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
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
GERD
Autoantibodies
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
Reflux esophagitis in the pathogenesis of paroxysmal
atrial fibrillation: results of a pilot study
N° of patients
Methodology
Results
Conclusion
Weilg et al, 2003
N° of patients
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.