Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial.

Importance: There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure. Objective: To compare low-dose digoxin with bisoprolol (a ß-blocker). Design, Setting, and Participants: Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019. Interventions: Digoxin (n = 80; dose range, 62.5-250 µg/d; mean dose, 161 µg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d). Main Outcomes and Measures: The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting. Results: Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, -1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, -2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P < .001). At 12 months, 8 of 20 outcomes were significantly different (all favoring digoxin), with a median NT-proBNP level of 960 pg/mL (interquartile range, 626 to 1531 pg/mL) in the digoxin group vs 1250 pg/mL (interquartile range, 847 to 1890 pg/mL) in the bisoprolol group (ratio of geometric means, 0.77 [95% CI, 0.64 to 0.92]; P = .005). Adverse events were less common with digoxin; 20 patients (25%) in the digoxin group had at least 1 AE vs 51 patients (64%) in the bisoprolol group (P < .001). There were 29 treatment-related AEs and 16 serious AEs in the digoxin group vs 142 and 37, respectively, in the bisoprolol group. Conclusions and Relevance: Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points. Trial Registration: ClinicalTrials.gov Identifier: NCT02391337 and clinicaltrialsregister.eu Identifier: 2015-005043-13.

The effects of vigorous intensity exercise in the third trimester of pregnancy: a systematic review and meta-analysis.

BACKGROUND: Fetal growth is dependent upon utero-placental vascular supply of oxygen and nutrients from the mother and has been proposed to be compromised by vigorous intensity exercise in the third trimester. The aim of this systematic review was to investigate the effects of vigorous intensity exercise performed throughout pregnancy, on infant and maternal outcomes. METHODS: Electronic searching of the PubMed, Medline, EMBASE, Cochrane Library, Web of Science and CINAHL databases was used to conduct the search up to November 2018. Study designs included in the systematic review were randomised control trials, quasi-experimental studies, cohort studies and case-control studies. The studies were required to include an intervention or report of pregnant women performing vigorous exercise during gestation, with a comparator group of either lower intensity exercise or standard care. RESULTS: Ten cohort studies (n = 32,080) and five randomized control trials (n = 623) were included in the systematic review (n = 15), with 13 studies included in the meta-analysis. No significant difference existed in birthweight for infants of mothers who engaged in vigorous physical activity and those who lacked this exposure (mean difference = 8.06 g, n = 8006). Moreover, no significant increase existed in risk of small for gestational age (risk ratio = 0.15, n = 4504), risk of low birth weight (< 2500 g) (risk ratio = 0.44, n = 2454) or maternal weight gain (mean difference = - 0.46 kg, n = 1834). Women who engaged in vigorous physical activity had a small but significant increase in length of gestational age before delivery (mean difference = 0.21 weeks, n = 4281) and a small but significantly reduced risk of prematurity (risk ratio = - 0.20, n = 3025). CONCLUSIONS: Findings from this meta-analysis indicate that vigorous intensity exercise completed into the third trimester appears to be safe for most healthy pregnancies. Further research is needed on the effects of vigorous intensity exercise in the first and second trimester, and of exercise intensity exceeding 90% of maximum heart rate. TRIAL REGISTRATION: PROSPERO trial registration CRD42018102109 .

Exercise capacity and muscle strength in patients with cirrhosis.

Exercise capacity and muscle strength are predictors of outcome in a number of clinical populations. Advanced liver disease is a catabolic state, and patients often have muscle wasting. However, the relationships between exercise capacity, strength, and outcomes for patients undergoing liver transplantation are poorly understood. Thirteen studies have examined the association between these parameters in patients with cirrhosis, and they have found a significant reduction in the exercise capacity and muscle strength of patients with cirrhosis versus healthy controls. These impairments appear to be independent of the etiology of cirrhosis, but the data are equivocal with respect to their association with disease severity. Two studies reported a significant and independent association between pretransplant exercise capacity and posttransplant survival. Another 2 studies found that exercise training was well tolerated in patients with cirrhosis and resulted in improvements in exercise capacity (both studies) and muscle mass (1 study). These data are provocative and suggest that measuring and improving the exercise capacity and muscle strength of patients with cirrhosis who are awaiting liver transplantation could potentially improve outcomes.