Heart failure and atrial fibrillation are global epidemics that significantly increase mortality and bring a great burden. How to prevent thromboembolic risk when a patient has both heart failure and atrial fibrillation? Recently, a review published by Heart Failure Clin gives a summary.
Pathophysiology of atrial fibrillation and heart failure1. Atrial fibrillation and heart failure Heart failure is a complex syndrome that the ESC classifies into three categories:< span>✎Heart failure with reduced ejection fraction (HFrEF): LVEF≤40%;✎Heart failure with median ejection fraction (HFmrEF): LVEF 40%–49%; ✎ Heart failure with preserved ejection fraction (HFpEF): LVEF ≥50%. Heart failure and atrial fibrillation interact. Patients with all subtypes of HF had an increased risk of atrial fibrillation, which remained after adjustment for coexisting risk factors (ie, age, body mass index, and hypertension). Atrial fibrillation reduces atrial contractility and left ventricular filling, resulting in approximately a 20% reduction in cardiac output. When the ventricular rate is uncontrolled, rapid atrial fibrillation can worsen left ventricular ejection fraction (LVEF), even in patients with previously normal LVEF. Animal model experiments suggest that possible mechanisms may include energy consumption, intracellular and extracellular matrix remodeling, myocardial ischemia, and abnormal calcium channel activity. HF can lead to increased left atrial pressure, which can ultimately lead to increased left atrial volume, resulting in cellular and molecular changes in the left atrium, which in turn increase atrial depolarization and stress. The automaticity and heterogeneity of repolarization (a recognized predisposing factor for AF), and the prevalence of AF increases with worsening NYHA class. Neurohormones also play a role in the relationship between atrial fibrillation and heart failure. In patients with heart failure, the renin-angiotensin-aldosterone system, harmful hormones, and cytokines are all activated. To a certain extent, this can lead to fibrosis of the adventitial membrane, leading to atrial repolarization heterogeneity. Furthermore, under normal conditions, increased blood volume inhibits renal sympathetic activation, resulting in increased diuresis. In heart failure patients, this reflex is impaired. Defective synthesis of atrial natriuretic peptide (ANP), another mechanism associated with heart failure and atrial fibrillation, is secreted when the left atrium is stretched. It has a certain role in reducing hypertension, volume overload, inhibiting the proliferation of cardiac fibroblasts and fibrosis. Defective synthesis of ANP also increases the risk of atrial fibrillation in patients with heart failure. 2. Thromboembolic risk in patients with atrial fibrillation and heart failure Virchow’s triad is present in both heart failure and atrial fibrillation: hypercoagulable state (activation of platelets and coagulation factors), endothelial dysfunction (atrial dilation and fibrosis), and blood stasis ( Abnormal and/or lack of atrial systolic function). Atrial fibrillation is closely associated with stroke and systemic embolism, and is influenced by other relevant risk factors. Studies show a 5-fold increased risk of stroke in patients with atrial fibrillation across all age groups. Congestive heart failure is an independent risk factor for stroke in patients with atrial fibrillation, and the combination of the two can increase the severity of stroke and all-cause mortality. Even in the absence of atrial fibrillation, patients with heart failure are at increased risk of thromboembolism. Currently, a variety of systematic scores can be used to predict the risk of stroke in patients with atrial fibrillation, and the CHA₂DS₂-VASc and ABC stroke scores have better predictive value for stroke events. In addition, all stroke prevention medications were associated with bleeding risk. In clinical practice, the HAS-BLED score can be applied to assess the bleeding risk of patients. It reminds us of the modifiable bleeding risk and prompts early intervention or more frequent testing in high-risk patients. In view of the history of renal disease, anemia, liver disease and bleeding in some patients with heart failure, it is particularly important to evaluate the bleeding risk and formulate an individualized anticoagulation treatment plan. Atrial fibrillation and subtypes of heart failureAlthough all types of heart failure ( HFpEF, HFmrEF, and HFrEF) all increase the risk of atrial fibrillation, but HFpEF has an even greater risk. This may be associated with increased left atrial stiffness in patients with HFpEF. Prospective cohort study showed that the mean CHA₂DS₂-VASc score of patients in the HFpEF group (4.7 points) was higher than that in the HFrEF group (4.1 points) and HFmrEF group (4.4 points). However, although this group of patients had higher CHA₂DS₂-VASc scores, the patients were at or lower risk of stroke. In addition, the researchers found that a 1% decrease in LVEF was associated with a 0.054% increased risk of stroke; among patients on anticoagulation, a 1% decrease in LVEF was associated with a 0.030% increased risk of stroke. A meta-analysis prior to 2016 showed no significant difference in the risk of atrial fibrillation between the two groups. The heterogeneity of patients with HFpEF may explain the differences in the results of these trials. Heart failure subtype, NYHA class and age were independent predictors of thromboembolic risk in patients with atrial fibrillation and heart failure. The OR for each additional grade in NYHA was 2.92; the OR for each 1-year increase in age was 1.04. There is also a clear relationship between heart failure subtypes and all-cause mortality, with significantly higher all-cause mortality in patients with HFrEF. In addition, hypertrophic cardiomyopathy (HCM) is often classified as HFpEF. Given the significantly increased risk of stroke in patients with HCM, anticoagulation should be considered in all patients with AF and HCM. Antithrombotic strategies for heart failure with atrial fibrillation
all atriums All patients with fibrillation and heart failure should be treated with anticoagulation. Up to now, warfarin and vitamin K antagonists are still the main drugs for antithrombotic treatment of atrial fibrillation. The study showed that compared with placebo, warfarin reduced the risk of ischemic stroke by 65% and the risk of all-cause death by 26%. However, elderly patients often have multiple comorbidities, require multiple drug treatments, interact or increase with warfarin, and inconvenience in routine testing, thus promoting non-vitaminDevelopment of hormone K antagonist oral anticoagulants (NOACs).
NOACs are approved for the antithrombotic treatment of non-valvular atrial fibrillation. The most commonly used NOACs are apixaban, edoxaban, rivaroxaban (factor Xa inhibitor), and dabigatran (direct thrombin inhibitor).
All NOACs were superior or non-inferior to warfarin in stroke prevention; bleeding risk , NOACs also showed some non-inferiority. Therefore, except in patients with contraindications, NOACs are often used as first-line therapy for stroke prevention in atrial fibrillation.
Previous studies have shown that heart failure is a risk factor for bleeding with warfarin anticoagulation, suggesting that NOACs may act as a risk factor for heart failure The preferred anticoagulant in patients with atrial fibrillation. However, there is no evidence that which type of NOACs is more effective in preventing thromboembolic risk in patients with heart failure and atrial fibrillation.
It is worth noting that patients with heart failure often have renal impairment, and the renal function of patients should be considered when NOACs are prescribed. How do the guidelines recommend antithrombotic therapy for heart failure complicated with atrial fibrillation?
For patients with heart failure and atrial fibrillation, the “2021 ESC Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Failure” recommends that all heart failure patients with paroxysmal, persistent or Patients with permanent atrial fibrillation are on long-term anticoagulation unless contraindicated. NOACs are the drug of choice for patients with atrial fibrillation without severe mitral stenosis and/or mechanical valves. In patients with contraindications to oral anticoagulants, left atrial appendage occlusion may be considered. The specific recommendations are as follows:
✎For all heart failure with atrial fibrillation, CHA₂DS₂-VASc≥2 points (male) or ≥3 points (female), long-term oral anticoagulation is recommended (I, A).
✎NOACs are preferred over vitamin K antagonists in patients with atrial fibrillation and heart failure unless the patient has moderate or severe mitral stenosis or a mechanical heart valve (I, A).
✎Long-term oral anticoagulation should be considered for stroke prevention in patients with atrial fibrillation with a CHA₂DS₂-VASc score of ≥1 (men) or ≥2 (women). B).
“2018 Guidelines for Diagnosis and Treatment of Heart Failure in China” pointed out that
The risk of thromboembolism is significantly increased in patients with heart failure complicated with atrial fibrillation. Anticoagulation therapy needs to weigh the benefits against the risk of bleeding. It is recommended to use the CHA₂DS₂-VASc and HAS-BLED scores to assess the risk of thromboembolism and bleeding in patients, respectively (I, B) ;
For patients with HCM complicated with atrial fibrillation, the CHA₂DS₂-VASc score is not required, and oral anticoagulant therapy should be administered directly (I, B). ConclusionHeart failure and atrial fibrillation often coexist, which can lead to thrombosis in patients Increased risk of embolism. Evidence-based evidence suggests that anticoagulation reduces the risk of thromboembolism in patients regardless of HF subtype. NOACs are much better than warfarin in anticoagulation. However, there are no dedicated randomized controlled trials evaluating the efficacy of NOACs in patients with atrial fibrillation and heart failure.
References:
[1]Mohammed Obeidat, Malcolm Burgess, Gregory Y.H. Lip, et al. Atrial Fibrillation in Heart Failure-Focus on Antithrombotic Management. Heart Failure Clin 16 (2020) 107-120. doi.org/10.1016/j.hfc.2019.08.007.
[2]Theresa A McDonagh, Marco Metra, Marianna Adamo, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal, ehab368, 27 August 2021.
[3]Chinese Heart Failure Group of Cardiology Branch of Medical Association, Editorial Board of Chinese Journal of Cardiovascular Diseases, Heart Failure Professional Committee of Chinese Medical Doctor Association. Guidelines for Diagnosis and Treatment of Heart Failure in China 2018. Chinese Journal of Cardiovascular Diseases, 2018, 46(10): 760 -789.