Risks of Ventricular Arrhythmia and Heart Failure in Carriers of RBM20 Variants.

BACKGROUND: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes. METHODS: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction. RESULTS: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank P<0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF >35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P<0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point. CONCLUSIONS: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF.

Hypoalgesia after bicycling at lactate threshold is reliable between sessions.

PURPOSE: Exercise decreases pain sensitivity known as exercise-induced hypoalgesia (EIH). However, the consistency of EIH after an acute exercise protocol based on subjective ratings of perceived exertion has been questioned. Objectives were to compare the effect on pressure pain thresholds (PPTs) after bicycling with work-rate at the lactate threshold compared with quiet rest, and investigate between-session reliability of EIH. METHODS: Thirty-four healthy subjects completed three sessions with 7 days in-between. In session 1, the lactate threshold was determined via blood samples (finger-tip pinprick, > 2 mmol/l increase from warm-up) during a graded bicycling task. In session 2 and 3, all subjects performed (1) 15 min quiet-rest, and (2) 15 min bicycling (work-rate corresponding to the lactate threshold) in the two identical sessions. PPTs at the quadriceps and trapezius muscles were assessed before and after both conditions. Reliability was assessed by intraclass correlations (ICCs). RESULTS: Bicycling increased quadriceps PPT compared with quiet-rest in both sessions [mean difference: 45 kPa (95% CI 19-72 kPa), P = 0.002]; however, the increase in trapezius PPT was not significant after exercise. The EIH responses demonstrated fair between-session test-retest reliability (quadriceps: ICC = 0.45; trapezius: ICC = 0.57, P < 0.05), and agreement in EIH responders and non-responders between sessions was significant (quadriceps: κ = 0.46 and trapezius: κ = 0.43, P < 0.05). CONCLUSIONS: In conclusion, bicycling at the lactate threshold increased PPT at the exercising muscle with fair reliability of the local EIH response. The results have implications for future EIH studies in subjects with and without pain and for clinicians who design exercise programs for pain relief.

The rate of invasive testing for trisomy 21 is reduced after implementation of NIPT.

INTRODUCTION: The non-invasive prenatal test (NIPT) was introduced in the North Denmark Region in March 2013. NIPT is offered as an alternative to invasive tests if the combined first trimester risk of trisomy 21 (T21) is ≥ 1:300. The purpose of this study was to investigate the effect of NIPT implementation among high-risk pregnancies in a region with existing first-trimester combined screening for T21. The primary objective was to examine the effect on the invasive testing rate. METHODS: This was a retrospective observational study including high-risk singleton pregnancies in the North Denmark Region. The women were included in two periods, i.e. before and after the implementation of NIPT, respectively. Group 1 (before NIPT): n = 253 and Group 2 (after NIPT): n = 302. RESULTS: After NIPT implementation, the invasive testing rate fell from 70% to 48% (p < 0.01), and the number of high-risk women refusing further testing dropped from 26% to 3% (p < 0.01). NIPT successfully detected four cases of T21; however, two out of three sex-chromosomal abnormalities were false positives. No false negative NIPT results were revealed in this study. CONCLUSIONS: In the North Denmark Region, the implementation of NIPT in high-risk pregnancies significantly reduced the rate of invasive testing. However, the proportion of high-risk women who opted for prenatal tests increased as the majority of women who previously refused further testing now opted for the NIPT. FUNDING: none. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (No. 2015-104).