Acceptability of a Novel Smartphone Application for Rhythm Evaluation in Patients with Atrial Fibrillation

Background: Investigators at UMass Medical School and WPI co-developed a novel smartphone application (app), PULSESMART, that detects atrial fibrillation (AF). AF is the world’s most common, serious heart rhythm problem. In its early stages, most cases of AF are paroxysmal (pAF), making them difficult to identify early in the course of disease. Long-term cardiac monitoring is frequently needed to diagnose and prevent complications from AF, such as stroke. Home monitoring for AF can be clinically impactful but existing technologies have cost or methodological limitations. Data are needed on the potential acceptability and usability of heart rhythm monitoring applications. Aim: Our aim was to examine patient acceptability of using a pAF detection app. Methods: 52 patients with pAF underwent rhythm assessment using the app and completed a standardized questionnaire. We looked specifically at responses to 3 questions: 1) how easy was it to use? 2) How important could it be for you? And 3) to what extent does it fit into your daily life? Results: The mean age was 68.5 years and 69% female. The majority of patients reported the app was easy to use (73%), could be important to them and their health (84%), and would fit into their daily lives (78%). Conclusions: After use of the pAF detection app, most patients reported positively. The results suggest that older persons with, or at risk for, pAF may benefit from smartphone-based arrhythmia detection platforms. Further work is needed to assess the feasibility of at-home or in-clinic app use

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Addition of B-Type Natriuretic Peptide to Existing Clinical Risk Scores Enhances Identification of Patients at Risk for Atrial Fibrillation Recurrence After Pulmonary Vein Isolation

INTRODUCTION: Predicting which patients will be free from atrial fibrillation (AF) after pulmonary vein isolation (PVI) remains challenging. Clinical risk prediction scores show modest ability to identify patients at risk for AF recurrence after PVI. B-type natriuretic peptide (BNP) is associated with risk for incident and recurrent AF but is not currently included in existing AF risk scores. We sought to evaluate the incremental benefit of adding preoperative BNP to existing risk scores for predicting AF recurrence during the 6 months after PVI. METHODS: One hundred sixty-one patients with paroxysmal or persistent AF underwent an index PVI procedure between 2010 and 2013; 77 patients (48%) had late AF recurrence after PVI ( \u3e 3 months post-PVI) over the 6-month follow-up period. RESULTS: A BNP greater than or equal to 100 pg/dL (P = 0.01) and AF recurrence within 3 months after PVI (P \u3c 0.001) were associated with late AF recurrence in multivariate analyses. Addition of BNP to existing clinical risk scores significantly improved the areas under the curve for each score, with an integrated discrimination improvement of 0.08 (P = 0.001) and a net reclassification improvement of 60% (P = 0.001) for all risk scores. CONCLUSIONS: Circulating BNP levels are independently associated with late AF recurrence after PVI. Inclusion of BNP significantly improves the discriminative ability of CHADS2, CHA2DS2-VASc, R2CHADS2, and the HATCH score in predicting clinically significant, late AF recurrence after PVI and should be incorporated in decision-making algorithms for management of AF. B-R2CHADS2 is the best score model for prediction of late AF recurrence

Deferoxamine mesylate in patients with intracerebral haemorrhage (i-DEF): a multicentre, randomised, placebo-controlled, double-blind phase 2 trial

BackgroundIron from haemolysed blood is implicated in secondary injury after intracerebral haemorrhage. We aimed to assess the safety of the iron chelator deferoxamine mesylate in patients with intracerebral haemorrhage and to establish whether the drug merits investigation in a phase 3 trial.MethodsWe did a multicentre, futility-design, randomised, placebo-controlled, double-blind, phase 2 trial at 40 hospitals in Canada and the USA. Adults aged 18-80 years with primary, spontaneous, supratentorial intracerebral haemorrhage were randomly assigned (1:1) to receive deferoxamine mesylate (32 mg/kg per day) or placebo (saline) infusions for 3 consecutive days within 24 h of haemorrhage onset. Randomisation was done via a web-based trial-management system centrally in real time, and treatment allocation was concealed from both participants and investigators. The primary outcome was good clinical outcome, which was defined as a modified Rankin Scale score of 0-2 at day 90. We did a futility analysis: if the 90% upper confidence bound of the absolute risk difference between the two groups in the proportion of participants with a good clinical outcome was less than 12% in favour of deferoxamine mesylate, then to move to a phase 3 efficacy trial would be futile. Primary outcome and safety data were analysed in the modified intention-to-treat population, comprising only participants in whom the study infusions were initiated. This trial is registered with ClinicalTrials.gov, number NCT02175225, and is completed.FindingsWe recruited 294 participants between Nov 23, 2014, and Nov 10, 2017. The modified intention-to-treat population consisted of 144 patients assigned to the deferoxamine mesylate group and 147 assigned to the placebo group. At day 90, among patients with available data for the primary outcome, 48 (34%) of 140 participants in the deferoxamine mesylate group, and 47 (33%) of 143 patients in the placebo group, had modified Rankin Scale scores of 0-2 (adjusted absolute risk difference 0·6% [90% upper confidence bound 6·8%]). By day 90, 70 serious adverse events were reported in 39 (27%) of 144 patients in the deferoxamine mesylate group, and 78 serious adverse events were reported in 49 (33%) of 147 patients in the placebo group. Ten (7%) participants in the deferoxamine mesylate and 11 (7%) in the placebo group died. None of the deaths were judged to be treatment related.InterpretationDeferoxamine mesylate was safe. However, the primary result showed that further study of the efficacy of deferoxamine mesylate with anticipation that the drug would significantly improve the chance of good clinical outcome (ie, mRS score of 0-2) at day 90 would be futile.FundingUS National Institutes of Health and US National Institute of Neurological Disorders and Stroke

Deep observations of Kepler's SNR with H.E.S.S.

Kepler’s supernova remnant (SNR) which is produced by the most recent naked-eye supernova in our Galaxy is one of the best studied SNRs, but its gamma-ray detection has eluded us so far. Observations with modern imaging atmospheric Cherenkov telescopes (IACT) have enlarged the knowledge about nearby SNRs with ages younger than 500 years by establishing Cassiopeia A and Tycho’s SNRs as very high energy (VHE) gamma-ray sources and setting a lower limit on the distance to Kepler’s SNR. This SNR is significantly more distant than the other two and expected to be one of the faintest gamma-ray sources within reach of the IACT arrays of this generation. We report strong evidence for a VHE signal from Kepler’s SNR based on deep observations of the High Energy Stereoscopic System (H.E.S.S.) with an exposure of 152 hours, including 122 hours accumulated in 2017-2020. We further discuss implications of this result for cosmic-ray acceleration in young SNRs

Observation of burst activity from SGR1935+2154 associated to first galactic FRB with H.E.S.S.

Fast radio bursts (FRB) are enigmatic powerful single radio pulses with durations of several milliseconds and high brightness temperatures suggesting coherent emission mechanism. For the time being a number of extragalactic FRBs have been detected in the high-frequency radio band including repeating ones. The most plausible explanation for these phenomena is magnetar hyperflares. The first observational evidence of this scenario was obtained in April 2020 when an FRB was detected from the direction of the Galactic magnetar and soft gamma repeater SGR1935+2154. The FRB was preceded with a number of soft gamma-ray bursts observed by Swift-BAT satellite, which triggered the follow-up program of the H.E.S.S. imaging atmospheric Cherenkov telescopes (IACTs). H.E.S.S. has observed SGR1935+2154 over a 2 hour window few hours prior to the FRB detection by STARE2 and CHIME. The observations overlapped with other X-ray bursts from the magnetar detected by INTEGRAL and Swift-BAT, thus providing first observations of a magnetar in a flaring state in the very-high energy domain. We present the analysis of these observations, discuss the obtained results and prospects of the H.E.S.S. follow-up program for soft gamma repeaters and anomalous X-ray pulsars

Observation of burst activity from SGR1935+2154 associated to first galactic FRB with H.E.S.S.

Fast radio bursts (FRB) are enigmatic powerful single radio pulses with durations of several milliseconds and high brightness temperatures suggesting coherent emission mechanism. For the time being a number of extragalactic FRBs have been detected in the high-frequency radio band including repeating ones. The most plausible explanation for these phenomena is magnetar hyperflares. The first observational evidence of this scenario was obtained in April 2020 when an FRB was detected from the direction of the Galactic magnetar and soft gamma repeater SGR1935+2154. The FRB was preceded with a number of soft gamma-ray bursts observed by Swift-BAT satellite, which triggered the follow-up program of the H.E.S.S. imaging atmospheric Cherenkov telescopes (IACTs). H.E.S.S. has observed SGR1935+2154 over a 2 hour window few hours prior to the FRB detection by STARE2 and CHIME. The observations overlapped with other X-ray bursts from the magnetar detected by INTEGRAL and Swift-BAT, thus providing first observations of a magnetar in a flaring state in the very-high energy domain. We present the analysis of these observations, discuss the obtained results and prospects of the H.E.S.S. follow-up program for soft gamma repeaters and anomalous X-ray pulsars