Heart failure (HF) and atrial fibrillation (AF) have emerged as two new cardiovascular epidemics1. They share predisposing risk factors such as hypertension, diabetes mellitus, ischemic heart disease, and valve heart disease and are also linked by structural abnormalities1. The development of AF in a patient with HF leads to symptomatic deterioration, increased risk of thromboembolic episodes, and impaired long-term 2-4. From a clinical perspective, the following issues need to be considered for management of these patients:
(1) Identify and, if and when possible, deal efficiently with the precipitating factors for AF.
(2) Optimize HF treatment
The challenge, however, lies in the fact that different forms of HF (i.e. heart failure and preserved EF versus HF with abnormal EF) may require different approaches. Retrospective analyses of large randomized HF trials involving patients with reduced ejection fraction have reported a lower incidence of new-onset AF in patients treated with ACEIs and ARBs, compared with placebo. It is estimated that ACEI and ARB treatment reduces significantly (30% to 48% reduction) the risk of AF5-8. This beneficial effect of ACEIs and ARBs is, however, less evident in patients with heart failure and preserved EF9.
A recent study which assessed the temporal association of new-onset AF and HF with preserved versus reduced ejection fraction in participants of the Framingham Heart Study10, has found that:
- There is a high incidence of AF in HF patients (around 50%) and, viceversa, a high incidence of HF in AF patients (over 30%) and a temporal association between AF and HF.
- AF is strongly associated with incident HF with preserved ejection fraction.
- Clinical outcome is worse when both AF and HF coexist in a given patient compared with these conditions separately.
- Outcomes are worse in subjects with HF and reduced ejection fraction.
Better therapeutic strategies are needed to address this comorbidity more efficiently.
1.-Colilla S, Crow A, Petkun W, Singer DE, Simon T, Liu X. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. Am J Cardiol. 2013;112:1142–1147.
2.- McManus DD, Hsu G, Sung SH, Saczynski JS, Smith DH, Magid DJ, Gurwitz JH, Goldberg RJ, Go AS; Cardiovascular Research Network PRESERVE Study. Atrial fibrillation and outcomes in heart failure with preserved versus reduced left ventricular ejection fraction. J Am Heart Assoc. 2013;2:e005694.
3.- Dries DL, Exner DV, Gersh BJ, Domanski MJ, Waclawiw MA, Stevenson LW. Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials: Studies of Left Ventricular Dysfunction. J Am Coll Cardiol. 1998;32:695–703.
4.- Wang TJ, Larson MG, Levy D, Vasan RS, Leip EP, Wolf PA, D’Agostino RB, Murabito JM, Kannel WB, Benjamin EJ. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation. 2003;107:2920–2925.
5.- Schneider MP, Hua TA, Bohm M, Wachtell K, Kjeldsen SE, Schmieder RE. Prevention of atrial fibrillation by renin–angiotensin system inhibition a meta-analysis. J Am Coll Cardiol 2010;55:2299–2307.
6.- Healey JS, Baranchuk A, Crystal E, Morillo CA, Garfinkle M, Yusuf S, Connolly SJ. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis. J Am Coll Cardiol 2005;45: 1832–1839.
7.-Jibrini MB, Molnar J, Arora RR. Prevention of atrial fibrillation by way of abrogation of the renin–angiotensin system: a systematic review and meta-analysis. Am J Ther 2008;15:36–43.
8.- Anand K, Mooss AN, Hee TT, Mohiuddin SM. Meta-analysis: inhibition of renin– angiotensin system prevents new-onset atrial fibrillation. Am Heart J 2006;152: 217–222.
9.-Ducharme A, Swedberg K, Pfeffer MA, Cohen-Solal A, Granger CB, Maggioni AP, Michelson EL, McMurray JJ, Olsson L, Rouleau JL, Young JB, Yusuf S. Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: assessment of Reduction in Mortality and morbidity (CHARM) program. Am Heart J 2006; 151:985–991.
10.- Santhanakrishnan R, Wang N, Larson MG, Magnani JW, McManus DD, Lubitz SA, et al. Atrial Fibrillation Begets Heart Failure and Vice Versa: Temporal Associations and Differences in Preserved Versus Reduced Ejection Fraction. Circulation. 2016;133(5):484-92
The results of the study by Santhanakrishnan R et al in Circulation do not come as a surprise; they were intuitively expected by most physicians dealing with patients in whom atrial fibrillation (AF) and heart failure (HF) co-exist; still they raise many novel questions: Does their co-existence tilt the scales in the dilemma of rate vs rhythm control? It is known that low heart rates are not very desirable when AF co-exist, while levels below 70/min are required in HF and sinus rhythm. How many efforts towards re-establishing sinus rhythm should be directed in a patient with HF developing AF? Should medications change? Should dronedarone in view of the findings in the PALLAS trial, and class Ic antiarrhythmics be abandoned when a patient with paroxysmal AF develops HF2. Conversely, when a patient with HF starts manifesting paroxysms of AF should amiodarone be considered? Finally, is the comparison between warfarin and NOACs tilted either way when HF co-exists with AF? It is evident that in the brittle category of patients all our art and all our science is needed for best results.
The combined effects of heart failure and atrial fibrillation
Heart failure (HF) and atrial fibrillation (AF) are a dangerous combination. Not only is AF a risk factor for HF but it is also marker of worse outcome in HF patients. AF increases mortality in both HFrEF (OR 1.49) and HFpEF (OR 2.00) . The risk is even higher in elderly patients. New onset AF doubles mortality in HF patients and is a predictor for in-hospital mortality, longer ICU stay and longer hospital stay . The mnemonic CAN-TREAT HFrEF + AF algorithm can help in management of patients with concomitant AF and HF . The mnemonic stands for: urgent cardioversion if hemodynamic compromise (C), anticoagulation (A), diuretic therapy to normalize fluid balance (N), target initial rate below 110bpm (T), inhibition of RAAS – with ACEI or ARB and antialdosteronic drugs (R), early consideration of rhythm control with amiodarone, cardioversion or ablation (E), advanced HF therapies including resynchronization therapy, defibrillator or mechanical support (A) and aggressive treatment of hypertension, ischemia and other comorbidities (T).
Specific management in patients with concomitant AF and HFpEF is less clear and in everyday clinical practice it does not differ from that implemented in HFpEF patients in sinus rhythm. Controversy regarding the use of digoxin for rate control in patients with concomitant HF and AF is ongoing, as while some studies have demonstrated an increase in mortality, others have failed to demonstrate a negative outcome with this treatment. This controversy has been addressed in a previous cardionote in Cardio Debate.
Atrial fibrillation is one of the so-called new cardiovascular epidemics together with obesity, diabetes and heart failure. The findings described in Cardio Debate are interesting in that they show that there is a close association between AF and HF, but with some distinct differences in timing between HF with preserved left ventricle ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).
Compared with previous analyses of the Framingham cohort, a greater proportion of individuals nowadays have AF without HF, and AF more commonly precedes the development of HF. These findings may be due to a better detection of AF in the general population and HF patients and to a better management of AF patients that may decrease mortality and therefore increase both the prevalence and duration of AF, and in turn increase the prevalence of HF.
An important issue raised by Cardio Debate is that as over 50% of patients with AF will develop HF, we should have to consider patients with AF as probable candidates to develop HF. It is therefore most important to intensify treatment of these patients in order to decrease the incidence of new HF. As it is commonly mentioned, adherence to prevention measures is most important, because the incidence of cardiovascular risk factors has to be reduced if we are to succeed in reducing the epidemics mentioned above. If cardiovascular risk factors are already present, they must be treated accordingly as per European Society of Cardiology (ESC) and other major International guidelines. Although it may seem obvious, results of the surveys of the ESC reveal a significant gap between the goals that we would have to attain and the results that we are actually getting. It is likely that if we are able to achieve targets as proposed by the guidelines, the incidence of both heart failure and atrial fibrillation will decrease significantly.