Functional Tricuspid Regurgitation and Right Atrial Remodeling in Heart Failure With Preserved Ejection Fraction.

Tricuspid regurgitation (TR) is common in patients with heart failure with preserved ejection fraction (HFpEF), but it has not been well characterized. We hypothesized that right atrial (RA) remodeling would be associated with TR in HFpEF, forming a type of atrial functional TR (AFTR). Echocardiography was performed in 328 patients with HFpEF. TR severity was defined using a guidelines-based approach. Ventricular functional TR was defined as the presence of right ventricular (RV) systolic pressure >50 mm Hg or RV dilation, and the remaining patients were classified as having AFTR if they had RA dilation or tricuspid annular enlargement. RA dilation was common (78%) in the significant TR group (more than mild), exceeding the prevalence of RV dilation (32%), and RA dilation was correlated with tricuspid annular diameter and TR vena contracta width (r = 0.67 and r = 0.70, both p <0.0001). Despite the absence of RV dilation and pulmonary hypertension, 38% of patients with significant TR had AFTR. Patients with AFTR and those with ventricular functional TR displayed higher heart failure hospitalization rates than those with nonsignificant TR (adjusted hazard ratios, 2.45 and 4.31; 95% confidence interval 1.12 to 5.35 and 2.44 to 7.62, p = 0.02 and p <0.0001, respectively). In conclusion, TR in HFpEF is related to RA remodeling, and the presence of AFTR was associated with poor clinical outcomes. The current data highlight the importance of RA remodeling in the pathophysiology of TR in HFpEF.

Lumbar Roll Usage While Sitting Reduces the Forward Head Posture in Healthy Individuals: A Systematic Review with Meta-Analysis.

This systematic review and meta-analysis investigated whether the use of a lumbar roll reduced forward head posture (FHP) while sitting among individuals with or without musculoskeletal disorders. EMBASE, MEDLINE, and the Cochrane Library were systematically searched from their inception to August 2020. The quality of evidence for variables used in the meta-analysis was determined using the GRADE system. Five studies satisfied the criteria for data analysis. All studies included individuals without any spinal symptoms. Data from five studies on neck angle showed a statistically significant (p = 0.02) overall effect (standardized mean difference (SMD) = 0.77), indicating a lesser neck flexion angle while sitting with a lumbar roll than without it. Data from two studies on head angle showed a statistically significant (p = 0.04) overall effect (SMD = 0.47), indicating a lesser head extension angle while sitting with a lumbar roll than without it. In each meta-analysis, the quality of evidence was very low in the GRADE system. The use of a lumbar roll while sitting reduced FHP among individuals without spinal symptoms.

Impact of Right Atrial Remodeling in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Few studies have investigated right atrial (RA) remodeling in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to characterize the RA remodeling in HFpEF and to determine its prognostic significance. METHODS AND RESULTS: Patients with HFpEF were classified based on the presence of RA enlargement (RA volume index >39 mL/m2 in men and >33 mL/m2 in women). Compared with patients with normal RA size (n = 234), patients with RA dilation (n = 67) showed a higher prevalence of atrial fibrillation (AF), worse right ventricular systolic function, more severe pulmonary hypertension, and a greater prevalence of mild tricuspid regurgitation, as well as impaired RA reservoir function, with increased hepatobiliary enzyme levels. AF was strongly associated with the presence of RA dilation (odds ratio [OR] 10.2, 95% confidence interval [CI] 4.00-26.1 in current AF vs no AF and odds ratio 3.38, 95% CI 1.26-9.07, earlier AF vs no AF). Patients with RA dilation had more than a two-fold increased risk of composite outcomes of all-cause mortality or HF hospitalization (adjusted hazard ratio 2.01, 95% CI 1.09-3.70, P = .02). The presence of RA dilation also displayed an additive prognostic value over left atrial dilation alone. CONCLUSIONS: These data demonstrate that HFpEF with RA remodeling is associated with distinct echocardiographic features characterizing advanced right heart dysfunction with an increased risk of adverse outcomes.

Independent and incremental prognostic value of semiquantitative measures of tricuspid regurgitation severity in heart failure with preserved ejection fraction.

AIMS: This study sought to determine the independent and incremental prognostic value of semiquantitative measures of tricuspid regurgitation (TR) severity over right heart remodelling and pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Echocardiography was performed on 311 HFpEF patients. TR severity was defined by the semiquantitative measures [i.e. vena contracta width (VCW) and jet area] and by the guideline-based integrated qualitative approach (absent, mild, moderate, or severe). All-cause mortality or heart failure hospitalization occurred in 101 patients over a 2.1-year median follow-up. There was a continuous association between TR severity and the composite outcome with a hazard ratio (HR) of 1.17 per 1 mm increase of VCW [95% confidence interval (CI) 1.08-1.26, P < 0.0001]. Compared with patients with the lowest VCW category (≤1 mm), RV-adjusted HRs for the outcome were 1.99 (95% CI 1.05-3.77), 2.63 (95% CI 1.16-5.95), and 5.00 (95% CI 1.60-15.7) for 1-3, 3-7, and ≥7 mm VCW categories, respectively. TR severity as defined by the guideline-based approach showed a similarly graded association, but it was no longer significant in models including PH. In contrast, VCW remained independently and incrementally associated with the outcome after adjusting for established prognostic factors, as well as RV diameter and PH (fully adjusted HR 1.14 per 1 mm, 95% CI 1.02-1.27, P = 0.02; χ2 58.8 vs. 51.5, P = 0.03). CONCLUSION: The current data highlight the potential value of the semiquantitative measures of TR severity for the risk stratification in patients with HFpEF.

Post-marketing surveillance study of the long-term use of mizoribine for the treatment of lupus nephritis: 2-Year results.

OBJECTIVES: To understand the status of mizoribine use in patients with lupus nephritis (LN) and to collect safety- and efficacy-related data on 2-year treatment with mizoribine. METHODS: A continuous survey was conducted between March 2010 and July 2015. RESULTS: The analysis set included 559 patients (mean age 39.5 years, females 82.6%, mean duration of systemic lupus erythematosus (SLE) 8.4 years, mean duration of LN 5.9 years). Renal function was satisfactory for 6 months, but worsened from 12 months, with significant worsening at 24 months. By the ACR 2006 remission criteria (eGFR >60), at 24 months, 26.5% of patients achieved complete remission, and 63.3% achieved complete or partial remission. The urine protein to creatinine ratio decreased significantly. The SLE Disease Activity Index 2000 score decreased significantly at 12 and 24 months. Overall, 98 (17.5%) patients experienced 124 adverse drug reactions (ADRs); 3.6% experienced serious ADRs. Mizoribine was used with a steroid in 99.3% and an immunosuppressant in 51.2%; tacrolimus was used in 43.8%. The oral steroid dosage decreased from baseline to 24 months. The incidence of ADRs was not significantly different with concomitant tacrolimus use. CONCLUSIONS: The results suggest that long-term mizoribine is safe and effective, even when used with tacrolimus.

Long-term post-marketing surveillance of mizoribine for the treatment of lupus nephritis: Safety and efficacy during a 3-year follow-up.

OBJECTIVE: To determine the safety and efficacy of long-term use of mizoribine by undertaking a 3-year post-marketing surveillance study. METHODS: Subjects were all lupus nephritis patients newly treated with mizoribine between 1 October 2003 and 30 September 2005 at contracted study sites. RESULTS: Mizoribine was administered to 881 lupus nephritis patients in the safety analysis set consisting of 946 patients recruited from 281 contracted study sites after satisfying the eligibility criteria. There were 301 events of adverse drug reactions that were observed in 196 (20.7%) of the 946 subjects. There were 34 events of serious adverse drug reactions in 31 patients (3.2%). No deterioration in hematological and biochemical test values was observed, but immunological testing showed significant improvements in C3, CH50, and anti-DNA antibody titers. The negative rate of proteinuria also increased over time. The median steroid dosage was 15 mg/day at the commencement of treatment, but was reduced to 10 mg/day at 12 months and 8 mg/day at 36 months. CONCLUSION: The findings of the 3-year long-term drug use surveillance study indicated that mizoribine can be used over the long term with relatively few adverse drug reactions, suggesting its suitability for use in maintenance drug therapy.