the Other?
G. BORIANI, M. BIFFI, C. MARTIGNANI, C. VALZANIA, I. DIEMBERGER, M. ZIACCHI, D. SAPORITO, P. ARTALE, G. DOMENICHINI, L. FRABETTI, A. BRANZI
The Epidemiology of Atrial Fibrillation and Heart Failure
Atrial fibrillation (AF) and chronic heart failure (HF) are two common car- diac diseases, affecting 1–2% of the population [1–3] with a prevalence that rises steeply with age. AF and HF are conditioned by common risk factors and frequently coexist [3].
AF is the most common sustained arrhythmia, and the need for treat- ment constitutes an important burden on health care systems. It is estimated that 2.3 million Americans and probably a similar number of Europeans are affected by AF. Projected data from the ATRIA study indicate that the num- ber of people in the United States affected by AF will increase to more than 5.6 million in the coming decades, corresponding to a 2.5-fold increase [4].
HF is also a very frequent cardiovascular disorder, and it is estimated that it affects 15–20 million people worldwide. HF represents the most important risk factor for AF in developed countries where the prevalence of rheumatic heart disease has declined and a large amount of patients affected by various heart diseases survive to old age. Approximately two thirds of patients with HF are older than 65 years of age and thus have a high probability of AF pre- senting as a comorbidity [3]. In the Framingham study, HF was associated with a five- to six-fold increased risk of AF, which was higher than the risk related to valvular heart disease [5].
The most impressive data on the risk of developing AF or HF during life come from two studies from the Framingham cohort, where the cumulative, lifetime risk of developing AF [6] or HF [7] was evaluated in more than 8000
Institute of Cardiology, University of Bologna, Azienda Ospedaliera S.Orsola-Malpighi, Bologna, Italy
patients followed from 1968 through 1999. In these studies, the lifetime risk of developing AF and HF, for subjects aged 40 years or more, was 1 in 4 and 1 in 5, respectively.
The true epidemiological burden of AF–HF comorbidity in the ‘real world’ is only partially known and is surely underestimated by any analysis based on randomised clinical trials examining HF, where AF is often one of the exclusion criteria. Indeed, as shown in Fig. 1, the prevalence of AF is higher in hospitalised HF patients or in community HF patients than in HF patients participating in randomised clinical trials [8].
The Euro Heart Failure survey, conducted in 24 countries in Europe, showed that up to 45% patients with HF presented with AF, in the intermit- tent or chronic form. According to the Euro Heart Failure survey, the overall prevalence of new onset AF in patients with HF requiring hospitalisation was 13%, ranging from 8% to 36% [9]. The prevalence of AF was related to the severity of HF, varying between 10% and 20% in mild to moderate HF to 50% in patients with more advanced HF [3, 9–11].
0 10 20 30 40 50 60 70 80 90 100
% chronic AF
Trial patients
Community patients
Hospitalized patients
31%
12%
22%
Fig. 1.Prevalence of chronic atrial fibrillation (AF) in various settings of heart-failure patients, according to the literature
Hospitalised patients
The Interplay Between Atrial Fibrillation and Heart Failure
A temporal sequence of AF preceding HF gains further support from a prospective epidemiologic investigation. The Manitoba Follow-Up Study examined the relationship of AF to the development of HF in a cohort of men fit for pilot training in the Canadian Air Force [2]. Adjusting for other cardiovascular conditions and risk factors, the investigators found that sub- jects with AF had an independent 3-fold increase in the risk for developing congestive heart failure during follow-up. Since HF is a well known risk fac- tor for AF, the extent to which AF causes HF, as opposed to HF causing AF, remains unclear. In many instances, the conditions are interdependent.
In clinical practice, the relationship between AF and HF, or left ventricu- lar dysfunction, is intriguing. Indeed, AF may cause HF, particularly when there is a fast uncontrolled ventricular response. This form of HF may be reversible after rhythm or rate-control and is called tachycardiomiopathy [12–14]. At the initial patient observation, it may be quite difficult to distin- guish it from the most common phenomenon of AF facilitated by the mechanical, electrophysiological, and neurohormonal derangements caused by HF in a background of primary ventricular dilation and ipokinaesia.
The haemodynamic consequences of AF are related to the loss of atrial contribution to cardiac output, to an increase in heart rate with shortening in the duration of diastole, and to irregularity in the diastolic intervals. The loss of atrial contribution to ventricular filling may be well-tolerated in a healthy heart but may have adverse consequences in the presence of left ven- tricular dysfunction. Loss of atrial transport is particularly significant if there is impairment in left ventricular filling due to reduced diastolic com- pliance or to mitral stenosis. In this kind of patient, a high heart rate or an irregular heart rate with frequent short diastolic intervals will be poorly tol- erated. Over the long term, a sustained uncontrolled tachycardia with heart rate higher than 120 beats/min gives rise to an impairment of left ventricu- lar function with various degrees of ventricular dysfunction. This may result in an important worsening of the patient’s condition, unless heart rate can be controlled or sinus rhythm restored. This clinical condition is known as
‘tachycardiomyopathy’ or ‘tachycardia-induced cardiomyopathy’ [12–14].
The Relationship Between Atrial Fibrillation and Heart Failure: A Chicken–Egg Dilemma?
In clinical practice, the diagnosis of tachycardiomyopathy remains a difficult issue, since characterisation of patients with pure reversible tachycardia- induced cardiomyopathy and differentiation from other patients with dilated
cardiomyopathy is very difficult ‘a priori’ and constitutes a ‘chicken–egg type of dilemma’ [12–16]. Tachycardiomyopathy may be suspected by the coexis- tence of chronic AF and of left ventricular dysfunction with improvement in cardiac performance following rate control or rhythm control. However, even the absence of improvement does not demonstrate that a tachycardiomyopa- thy component was not present, since it may reflect an advanced stage of irreversible tachycardia-related myocardial injury [12–16]. Indeed, the degree of regression of ventricular dysfunction with rate control depends on several factors and may be total, partial, or absent.
Apart from clear cases of tachycardiomyopathy secondary to AF, there is also the possibility that AF may have a subtle long term deleterious effect on left ventricular function [14]. Indeed, a subtle form of cardiomyopathy sec- ondary to chronic AF may be related to a series of factors including: (1) con- trolled heart rate at rest but with disproportionately high rates (> 120 beats/min) during minor exercises and normal daily activity [16], (2) lack of physiological rate-response during daily activity, and (3) irregularity of the ventricular cycle during AF. Patients with already impaired left ventricular function and excessive sympathetic activation may be particularly prone to this possibility. The real prevalence of these forms of occult or latent tachy- cardiomyopathy among patients with chronic persistent AF is unknown, but a series of observations suggests its relevance [14–16].
Clinical Significance of Atrial Fibrillation in Heart Failure
In the Framingham Study, the development of AF in patients with HF was associated with a 2.7-fold increased risk of death in women and a 1.6-fold risk in men [17]. Middlekauff et al. analysed a series of 390 patients with advanced HF and found that AF was associated with a higher risk of all- cause and sudden death mortality compared with sinus rhythm [10]. In the SOLVD trials, a 1.3-fold greater risk of all-cause death related to AF was found [18]. This increase was probably linked to an increase risk of death from progressive pump failure. In the DIAMOND trial, the presence of AF in HF patients was associated with significantly lower survival compared with patients in sinus rhythm [19].
Costs of Atrial Fibrillation and Heart Failure
The cost of hospitalising patients with AF in the United States has been esti- mated to be approximately $1 billion annually. According to Medicare data, the relative hospital costs in 1991 of 12 625 elderly Medicare patients with
recent-onset AF compared to matched patients without AF ranged from
$1442 in 75- to 84-year-old women, to $3250 in 65- to 74-year-old women. In both men and women, and across the two decades of age studied, patients with AF had significantly higher annual hospital costs than subjects without AF [20]. Similarly, and even more impressively, the costs of HF are becoming a major threat to health care systems, especially in relationship with increas- ing costs for hospitalisation [21]. According to data reported by the American Heart Association, the treatment of HF in the United States in 2004 accounted for an overall cost of 26.8 billion dollars.
Therapeutic Implications of Atrial Fibrillation and Heart Failure Comorbidity
The multiple relationships between AF an HF make the therapeutic approach extremely complex and multifactorial. Indeed, for both AF and HF a wide variety of therapeutic endpoints can be considered, ranging from symptom relief to mortality prevention, and including the prevention of major events, an improvement in quality of life, and a reduction in hospitalisation. Even limiting this analysis of potential therapeutic endpoints to AF, a complex pic- ture emerges, as shown in Table 1. The complexity of any therapeutic approach to AF–HF comorbidity is magnified by the wide range of potential treatment options for AF, including atrial cardioversion and rhythm control [3, 22, 23], pharmacological or non-pharmacological rate control [3, 15], ablation directed on the atrial substrate with the aim to suppress AF [25], and algorithms for atrial pacing combined with cardiac resynchronisation therapy [26]. With regard to the treatment of HF, a favourable effect on AF has been documented for a ser ies of dr ugs used in HF t reat ment (angiotensin converting enzyme inhibitors and AT-1 receptor blockers) [11].
Conclusions
The interplay between AF and HF is complex, and the clinical implications of this relationship are currently enhanced by the epidemiological relevance of both HF and AF. Until more precise clinical data are available, from prospec- tive controlled evaluations, rate control and rhythm control should be pur- sued in all patients with a clinical picture of unrecognised and unexplained HF/ventricular dysfunction coupled with AF at relatively fast ventricular response. This may allow interruption of the vicious cycle existing between AF and HF, in which each disease facilitates, promotes, and worsens the other. A wide range of pharmacological and non-pharmacological treat-
ments is currently available, and, in view of the variable clinical picture of the patients and the clinical priorities, tailoring of medical decisions appears to be mandatory.
Table 1.Potential therapeutic endpoints in the treatment of atrial fibrillation (AF) Symptoms
• Palpitations
• Dyspnoea
• Fatigue
• Dizziness/syncope
• Others Clinical events
• Stroke/ thromboembolism
• Haemorrhagic complications
• Onset/ worsening of heart failure
• Death
• Others
Medical interventions
• Hospitalisation
• Hospitalisation for heart failure
• Electrical cardioversion Rhythm endpoints
• Measures of rhythm control
• Measures of rate control
• Days spent in AF
• AF burden
• Others
Other clinical measures
• Functional capacity
• Quality of life
• Ventricular function
• Cognitive function
• Other
Economic endpoints
• Cost
• Cost-effectiveness
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