No abstract

Background Inflammation and skeletal muscle wasting often coexist in elderly populations, but few studies have examined their relationship in elderly heart failure (HF) patients. This study examined the relationship between inflammation and increased skeletal muscle proteolysis, reduced skeletal mass and strength, and their prognostic implications in elderly HF patients (> 65 years) using a random forest approach. Methods We prospectively enrolled consecutive elderly HF patients (n = 78) and age- and sex-matched control subjects (n = 83). We measured the interleukin (IL)-6, C-reactive protein (CRP), and B-type natriuretic peptide (BNP) levels, lower limb muscle mass and strength, and 6-min walk distance. The amount of muscle proteolysis was determined by urinary 3-methylhystidine, normalized by creatinine (3-MH/Cr). The composite endpoint was defined as all-cause death or hospitalizations due to worsening HF. Results Compared to controls, elderly HF patients had a significantly higher IL-6, CRP, BNP, and 3-MH/Cr, and exhibited a reduced lower limb muscle mass and strength. A correlation analysis demonstrated significant positive correlations between the inflammatory cytokine levels and 3-MH/Cr and BNP, and negative correlations with the lower limb muscle mass and strength, and 6-min walk distance. During a median follow-up of 2.4-years, 24 patients reached the endpoint. A random forest model revealed that inflammatory cytokines, skeletal muscle wasting, and the BNP had greater effects on the risk prediction. The algorithm achieved an area under the receiver operating characteristic curve of 0.887 (95% CI, 0.772–1.000). Conclusion This study provided evidence of the association between inflammation and increased skeletal muscle proteolysis, reduced skeletal mass and strength, and their prognostic roles in elderly HF patients.

BackgroundSince warfarin is primarily bound to serum albumin, hypoalbuminemia is likely to increase the free fraction of warfarin and to increase the risk of bleeding. We prospectively evaluated the impact of serum albumin levels (ALB) on international normalized ratio of prothrombin time (PT-INR) control and hemorrhagic events in atrial fibrillation (AF) patients treated with warfarin.MethodsSeven hundred fifty-five non-valvular AF patients on warfarin were enrolled. PT-INR control and major bleeding events (MB, International Society on Thrombosis and Haemostasis) were prospectively followed and were related to ALB at enrollment.ResultsTwenty-seven patients developed MB during 1-year follow-up. In univariate/multivariate analyses, ALB (OR = 0.49, 95% CI 0.26–0.99, p = 0.04) and hemoglobin levels (OR = 0.78, 95% CI 0.65–0.92, p = < 0.01) were predictive for the annual risk of MB. In Spearman's rank correlation analysis, the baseline ALB was inversely correlated with the percentage of the time in PT-INR > 3.0 (ρ = −0.15, p < 0.0001), but neither 2.0 ≤ PT-INR ≤ 3.0 (ρ = 0.056, p = 0.13) nor PT-INR < 2.0 (ρ = −0.008, p = 0.82) during 1-year follow-up, suggesting that patients with low ALB had a directional tendency to be supratherapeutic control of PT-INR. The ROC curve showed that a cutoff of ALB was 3.6 g/dl to identify MB (AUC = 0.65). In Kaplan-Meier analysis, patients with ALB <3.6 g/dl (23/80, 29%) had more MB than those with ALB ≥3.6 g/dl (87/675, 13%, log-rank = 16.80, p < 0.0001) during long-term follow-up (3.8 ± 2.0 years).ConclusionsHypoalbuminemia increases the likelihood of supratherapeutic PT-INR control and the risk of MB. ALB can be a practical surrogate marker to prevent excessive warfarin control and warfarin-related MB.

Background Ablation index (AI) linearly correlates with lesion depth and may yield better therapeutic performance in pulmonary vein isolation (PVI) when tailored to a patient's wall thickness (WT) in the left atrium (LA). Methods and results First study: In paroxysmal atrial fibrillation patients (PAF; n = 20), the average LA WT (mm) in each anatomical segment for PVI was measured by intracardiac echocardiography (ICE) placed in the LA; the optimal AI for creating 1‐mm transmural lesion (AI/mm) was calculated. Second study: PAF (n = 80) patients were randomly assigned either to a force‐time integral protocol (FTI; 400 g·s, n = 40) or a tailored‐AI protocol (TAI; n = 40). In TAI, the LA WT in each segment was individually measured by ICE before starting ablation; a target AI was adjusted according to the individual WT in each segment (AI/mm × WT). The acute procedure outcomes and the 1‐year AF‐recurrence rate were compared between FTI and TAI. TAI had higher success rate of first‐pass isolation (88% vs. 65%) and had lower incidence of residual PV‐potentials/conduction‐gaps after a circular ablation than FTI (15% vs. 45%). The procedure time to complete PVI decreased in TAI compared to FTI (52 vs. 83 min), being attributed to the increased radiofrequency power and the decreased radiofrequency application time in each point in TAI. TAI had a lower 1‐year AF‐recurrence rate than FTI. Conclusion TAI increased acute procedure success, decreased time for PVI, and reduced the 1‐year AF‐recurrence rate, compared to FTI. Understanding the precise ablation target and tailoring AI would improve the efficacy of PVI.

DOACs still carry a finite risk of LAT in AF patients. Inappropriately reduced DOAC dose should be avoided to minimize the thromboembolic risk. Regular-dose dabigatran may have therapeutic efficacy against LAT.