Smartphone-based screening for atrial fibrillation: a pragmatic randomized clinical trial.

Digital smart devices have the capability of detecting atrial fibrillation (AF), but the efficacy of this type of digital screening has not been directly compared to usual care for detection of treatment-relevant AF. In the eBRAVE-AF trial ( NCT04250220 ), we randomly assigned 5,551 policyholders of a German health insurance company who were free of AF at baseline (age 65 years (median; interquartile range (11) years, 31% females)) to digital screening (n = 2,860) or usual care (n = 2,691). In this siteless trial, for digital screening, participants used a certified app on their own smartphones to screen for irregularities in their pulse waves. Abnormal findings were evaluated by 14-day external electrocardiogram (ECG) loop recorders. The primary endpoint was newly diagnosed AF within 6 months treated with oral anti-coagulation by an independent physician not involved in the study. After 6 months, participants were invited to cross-over for a second study phase with reverse assignment for secondary analyses. The primary endpoint of the trial was met, as digital screening more than doubled the detection rate of treatment-relevant AF in both phases of the trial, with odds ratios of 2.12 (95% confidence interval (CI), 1.19-3.76; P = 0.010) and 2.75 (95% CI, 1.42-5.34; P = 0.003) in the first and second phases, respectively. This digital screening technology provides substantial benefits in detecting AF compared to usual care and has the potential for broad applicability due to its wide availability on ordinary smartphones. Future studies are needed to test whether digital screening for AF leads to better treatment outcomes.

Early molecular imaging response assessment based on determination of total viable tumor burden in [68Ga]Ga-PSMA-11 PET/CT independently predicts overall survival in [177Lu]Lu-PSMA-617 radioligand therapy.

PURPOSE: In patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT), the predictive value of PSMA PET/CT-derived response is still under investigation. Early molecular imaging response based on total viable tumor burden and its association with overall survival (OS) was explored in this study. METHODS: Sixty-six mCRPC patients who received [177Lu]Lu-PSMA-617 RLT within a prospective patient registry (REALITY Study, NCT04833517) were analyzed. Patients received a [68Ga]Ga-PSMA-11 PET/CT scan before the first and after the second cycle of PSMA-RLT. Total lesion PSMA (TLP) was determined by semiautomatic whole-body tumor segmentation. Molecular imaging response was assessed by change in TLP and modified PERCIST criteria. Biochemical response was assessed using standard serum PSA and PCWG3 criteria. Both response assessment methods and additional baseline parameters were analyzed regarding their association with OS by univariate and multivariable analysis. RESULTS: By molecular imaging, 40/66 (60.6%) patients showed partial remission (PR), 19/66 (28.7%) stable disease (SD), and 7/66 (10.6%) progressive disease (PD). Biochemical response assessment revealed PR in 34/66 (51.5%) patients, SD in 20/66 (30.3%), and PD in 12/66 (18.2%). Response assessments were concordant in 49/66 (74.3%) cases. On univariate analysis, both molecular and biochemical response (p = 0.001 and 0.008, respectively) as well as two baseline characteristics (ALP and ECOG) were each significantly associated with OS. The median OS of patients showing molecular PR was 24.6 versus 10.7 months in the remaining patients (with SD or PD). On multivariable analysis molecular imaging response remained an independent predictor of OS (p = 0.002), eliminating biochemical response as insignificant (p = 0.515). CONCLUSION: The new whole-body molecular imaging-derived biomarker, early change of total lesion PSMA (TLP), independently predicts overall survival in [177Lu]Lu-PSMA-617 RLT in mCRPC, outperforming conventional PSA-based response assessment. TLP might be considered a more distinguished and advanced biomarker for monitoring PSMA-RLT over commonly used serum PSA.

Large potassium shifts during dialysis enhance cardiac repolarization instability.

BACKGROUND: Patients with end-stage kidney disease are at high risk for the development of arrhythmias and sudden cardiac death (SCD). This has been especially attributed to large potassium shifts during hemodialysis (HD), and malignant arrhythmias are closely linked to dysfunction of the autonomic nervous system. Nevertheless, there is still a lack of methods for risk stratification in these patients. METHODS: In the present pilot study we investigated changes of the novel ECG-based biomarker periodic repolarization dynamics (PRD) mirroring the effect of efferent sympathetic nervous activity on the ventricular myocardium in 18 patients undergoing routine hemodialysis. High-resolution ECGs were recorded throughout the dialysis and PRD values were calculated out of 30 min intervals at the start and the end of dialysis. RESULTS: We detected a clear correlation between the intradialytic potassium shift and the increase in PRD levels (Spearman correlation coefficient R = 0.62, p = 0.006). Patients with a potassium shift > 1 mmol/l showed significantly increased levels of PRD at the end of dialysis when compared to patients with potassium shifts ≤ 1.0 mmol/l [delta PRD 2.82 (IQR 2.13) vs. - 2.08 (IQR 3.60), p = 0.006]. Spearman analysis showed no significant correlation between PRD changes and fluid removal (R = - 0.23, p = 0.36). CONCLUSIONS: We provide evidence that large potassium shifts during HD enhance sympathetic activity-associated repolarization instability. This could facilitate the occurrence of malignant arrhythmias, and PRD measurements might serve as a non-invasive monitoring tool in HD patients in future.