Atrial fibrillation (AF) and heart failure (HF) are two common conditions that often coexist and predispose each to one another. AF increases hospitalization rates and overall mortality in patients with HF. The current available therapeutic options for AF in patients with HF are diverse and guidelines do not provide a clear consensus regarding the best management approach. To determine if catheter ablation for AF is superior to medical therapy alone in patients with coexisting HF, we conducted this systematic review and meta-analysis. The primary outcomes evaluated are left ventricular ejection fraction (LVEF), Minnesota Living with Heart Failure Questionnaire (MLWHFQ) scores, 6-minute walk test (6MWT) distance, heart failure hospitalizations, and mortality. The results are presented as a mean difference for continuous outcome measures and odds ratios for dichotomous outcomes (using Mantel-Haenszel random effects model). 7 full texts met inclusion criteria, including 856 patients. AF catheter ablation was associated with a significant increase in LVEF (mean difference 6.8%; 95% CI: 3.5 – 10.1; P<0.001) and 6MWT (mean difference 29.3; 95% CI: 11.8 – 46.8; P = 0.001), and improvement in MLWHFQ (mean difference -12.1; 95% CI: -20.9 – -3.3; P = 0.007). The risk of all-cause mortality was significantly lower in the AF ablation arm (OR 0.49; 95% CI: 0.31 – 0.77; P = 0.002). In conclusion, atrial fibrillation ablation in patients with systolic heart failure is associated with significant improvement in LVEF, quality of life, 6MWT, and overall mortality.

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Current anticoagulants target coagulation Factors upstream from fibrin assembly and polymerization (i.e. formation of fibrin clot). While effective, this approach requires constant patient monitoring since pharmacokinetics and pharmacodynamics vary from patient to patient. To address these limitations, we developed an alternative anticoagulant that effectively inhibits fibrin polymerization. Specifically, we investigated PEGylated fibrin knob `A' peptides, evaluating the effect of both PEG chain length (0, 2, 5, 10, 20, and 30 kDa) and knob peptide sequence (GPRPAAC, GPRPFPAC, and GPRPPERC) on inhibiting fibrin polymerization (i.e. clot formation). Thrombin-initiated clotting assays with purified fibrinogen were performed to compare clot formation with each peptide-PEG conjugate. Results indicated a biphasic effect of PEG chain length whereby active-PEG conjugates demonstrated increasingly enhanced inhibition of fibrin polymerization from 0 to 5 kDa PEG. However, the anticoagulant activity diminished to control levels for PEG chains above 5 kDa. Ultimately, we observed a 10-fold enhancement of anticoagulant activity with active peptides PEGylated with 5 kDa PEG compared to non-PEGylated knob peptides. The sequence of the active peptide significantly influenced the anticoagulant properties only at the highest 1:100 molar ratio where GPRPFPAC-5 kDa PEG and GPRPPERC-5 kDa PEG demonstrated significantly lower percent clottable protein than GPRPAAC-5 kDa PEG. Moreover, human plasma treated with the active 5 kDa PEG conjugate exhibited delayed the prothrombin time to within the therapeutic range specified for oral anticoagulants. Collectively, this study demonstrated the utility of PEGylated fibrin knob peptides as potential anticoagulant therapeutics.