Heart Failure with Low Ejection Fraction and In Sinus Rhythm: Should We Anti-coagulate to Reduce Stroke Burden?

Sir, Cardiac failure with reduced ejection fraction (HFrEF) is a rapidly growing problem. Among those hospitalized with heart failure, 46% had ejection fraction less than 40% and carried high morbidity and mortality.[1] Patients with HFrEF who did not have atrial fibrillation (AF) had a stroke incidence of almost twice compared to patients without heart failure and AF.[2] This was mainly attributed to endothelial dysfunction, hypercoagulability, and impaired blood flow leading to the formation of microthrombi.[2] In studies, it was found warfarin compared to antiplatelet has a relative stroke reduction of around 50% when used in HFrEF patients with no AF.[3] However, warfarin could not decrease mortality compared to antiplatelet, and oral anticoagulation is not recommended (as per guideline) in HFrEF with a sinus rhythm. As a cardioembolic stroke itself carries the highest mortality among all stroke types, depriving these patients of oral anticoagulation should receive a second thought! First, warfarin (as used in these studies) is not probably an ideal anticoagulant for this purpose. While some people are genetically hyper- or hypo-responsive to warfarin, many patients have difficulty in maintaining target International normalized ratio (INR) (warfarin has a narrow therapeutic window) due to drug and dietary interactions. It is more problematic for older patients with more comorbidities (like in this population). Second, there is not enough trial using novel oral anticoagulants (NOACS) with a proper dose in these patients (we do not know the ideal dose of NOACS in HFrEF patients with sinus rhythm). Besides, all the above, HFrEF and AF often co-exist (because of common risk factors, structural, and neuro-humoral changes) and we might be missing AF (where oral anticoagulant (OAC) has class I evidence). In a study, it was found almost five percentage of patients with heart failure had AF in future follow-up.[4] The points associated with new-onset AF in these patients were: age of patients over and equal to 65 years, low ejection fraction, history of coronary artery bypass grafting or stenting, low blood pressure, and higher Body Mass Index (BMI).[4] The levels of Atrial Natriuretic Peptide, Brain Natriuretic Peptide, and C-type Natriuretic Peptide (biomarkers of myocardial strain) increase in patients with heart failure and AF.[5] The levels of ST2 and Galectin-3 (biomarkers of myocardial fibrosis); CRP and Interleukin-6 (biomarkers of inflammation) also rise in AF patients.[5] So, we need to identify these high-risk patients with raised biomarkers. Increased D-Dimer, patients with genetic predisposition (KCNE3 and CYP4F2) are also candidates who have a higher chance of developing AF. So, besides using long-term monitoring, we may make a scoring system to identify a group of patients (among HFrEF in sinus rhythm) who would benefit from OAC to prevent stroke burden. Trials, including NOACS in these groups of the population, are required urgently on the Indian subcontinent as stroke is already an epidemic. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.