Atrial Fibrillation
atrial wavelength and a reduction in L-type calcium current and transient outward potassium current. These ionic changes result in shortening of the action potential and a decrease in contractility, resulting in atrial stretch, anisotropy, atrial fibrosis and zig-zag conduction. Thus, this electrical remodelling of the atria was termed ‘the first factor’ by which AF sustains. Histological changes, such as a decrease in connexin-40, increase in atrial myolysis, accumulation of glycogen and mitochondrial swelling, occurred by the first week. These histological changes represent a calcium overload state. The reduction in L-type calcium current is thought to be an adaptive process to limit the calcium overload state in the fibrillating atria. This interplay of electrical, contractile and structural remodelling of the atria, which is self-perpetuating, introduced the concept expressed by Wijffels that ‘atrial fibrillation begets atrial fibrillation’.16
The pathophysiology for HF-related AF was based on a model of high-rate ventricular-pacing-induced HF with development of contractile dysfunction.17
Nattel’s work suggested that anatomical
remodelling may be the primary factor contributing to AF in HF. They found recovery of ionic remodelling and contractile dysfunction in four weeks, but not of the structural remodelling or the ability to maintain AF. Yeh found in dogs that HF-induced AF increased triggered activity due to a calcium-overload state of the atrial myocytes. There were profound changes in calcium handling and regulatory proteins that resulted in a decrease in atrial contraction and an increase in atrial-triggered activity.18
Li reported that HF
increases atrial angiotensin II levels, which promotes arrhythmogenic atrial structural remodelling and conduction abnormalities.19
Several studies have shown that AF produces a deleterious effect on LV function due to poor rate control.20,21
Shinbane demonstrated
that with rapid ventricular pacing in animal models, significant haemodynamic effects occur within 24 hours with progression of LV dysfunction over three to five weeks. Reversal of the haemodynamic effects occurs within 48 hours of pacing cessation, with resolution of LV dysfunction by one to two weeks.20,21
Clark also demonstrated that
despite adequate rate control, irregular ventricular pacing resulted in a decrease in cardiac output, an increase in pulmonary capillary wedge pressure and an increase in right atrial (RA) pressure.22 Pardeans evaluated the haemodynamic effects of AF in chronic HF patients. He reported a worsening of NYHA class, a decline in peak exercise oxygen consumption, a decrease in cardiac index and an increase in mitral and tricuspid regurgitation.23
Therefore, preserved
atrial contraction and sinus rhythm are vital to maintain appropriate cardiac haemodynamics.
Not only are haemodynamics restored after cardioversion of AF to sinus rhythm in HF patients, but there is also evidence of electrical remodelling. Allessie’s instrumented goat studies showed that restoration of sinus rhythm for one week reverses the shortening of atrial refractoriness.15
He also found that during this ‘remodelling
reversal’ phase, the atria are vulnerable and at increased risk of AF recurrence, with the highest incidence of AF recurrence within the first week of cardioversion.24
Hobbs elaborated on the Allessie
research by showing that an increase in AF cycle length, which was used as a surrogate for atrial refractoriness, after cardioversion correlated with the duration of sinus rhythm.25
Dittrich demonstrated
that patients in whom sinus rhythm was restored within three months were more likely to remain in sinus rhythm versus patients in AF for more than 12 months.26
76
Rhythm versus Rate Control
The ‘rhythm versus rate control’ treatment strategy for AF patients has been a source of confusion, excitement and debate for decades in the cardiology community. In the 1990s, trials of AADs, such as the Canadian Trial of Atrial Fibrillation, the CHF-STAT study and the Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA) trial, all demonstrated that amiodarone was superior to sotalol or propafenone in terms of maintaining sinus rhythm.36–38 Amiodarone was approximately 70% effective in maintaining sinus
EUROPEAN CARDIOLOGY
Sinus Rhythm and Survival
Studies have already hinted that restoration of sinus rhythm, without the toxicity of AAD adverse side effects, is associated with increased survival for the HF patient. The Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) study reported that AF patients with LV function <35% who maintained sinus rhythm for one year had a significant reduction in mortality, regardless of whether they were taking the study drug (dofetilide) or placebo.27
In the
Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy (CHF-STAT) study, survival analysis by Kaplan-Meier indicated that patients who converted to sinus rhythm had better survival compared with those who did not convert.28
The Atrial Fibrillation Follow-up
Investigation of Rhythm Management (AFFIRM) study also showed that sinus rhythm, in addition to warfarin, was associated with a lower risk of death (hazard ratio 0.53).29
The AFFIRM study also confirmed
that AADs increased mortality after adjusting for sinus rhythm (hazard ratio 1.49). This study reiterates that the increased mortality due to the deleterious effects of AADs may have been counterbalanced by the beneficial effects of sinus rhythm.
Regardless of the trend towards sinus rhythm and survival, the larger trials such as AFFIRM and the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial, which randomised NYHA II–IV patients with ejection fraction (EF) <35% to AAD or rate control, demonstrated no statistically significant difference in cardiovascular mortality between the two therapies.30,31
Multiple smaller studies,
which will be discussed later, also demonstrated no significant difference in clinical end-points.32–34
Regardless of the multiple
explanations as to why studies keep demonstrating no mortality benefit in rhythm-controlled patients, there is still confusion and debate as to the best treatment strategy for AF patients, especially those with LV dysfunction.
Treatment of Atrial Fibrillation in Congestive Heart Failure Patients
Clinical management of AF in patients with HF requires optimal therapy for both conditions. HF management includes optimisation of HF medications, consisting of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), diuretics, aldosterone antagonists, digoxin, cardiac resynchronisation therapy (CRT) and beta-blockers, as per the American College of Cardiology/ American Heart Association (ACC/AHA) 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult.35
The goal for an AF patient, regardless of EF, involves prevention of thromboembolism and rate versus rhythm control. Regardless of whether a rate or a rhythm control strategy is utilised, prevention of thromboembolism is paramount. Based on ACC/AHA/European Society of Cardiology (ESC) guidelines, all patients should be on warfarin unless contraindicated.1
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