Atrial arrhythmogenicity in aged Scn5a+/∆KPQ mice modeling long QT type 3 syndrome and its relationship to Na+ channel expression and cardiac conduction

Recent studies have reported that human mutations in Nav1.5 predispose to early age onset atrial arrhythmia. The present experiments accordingly assess atrial arrhythmogenicity in aging Scn5a+/∆KPQ mice modeling long QT3 syndrome in relationship to cardiac Na+ channel, Nav1.5, expression. Atrial electrophysiological properties in isolated Langendorff-perfused hearts from 3- and 12-month-old wild type (WT), and Scn5a+/∆KPQ mice were assessed using programmed electrical stimulation and their Nav1.5 expression assessed by Western blot. Cardiac conduction properties were assessed electrocardiographically in intact anesthetized animals. Monophasic action potential recordings demonstrated increased atrial arrhythmogenicity specifically in aged Scn5a+/ΔKPQ hearts. These showed greater action potential duration/refractory period ratios but lower atrial Nav1.5 expression levels than aged WT mice. Atrial Nav1.5 levels were higher in young Scn5a+/ΔKPQ than young WT. These levels increased with age in WT but not Scn5a+/ΔKPQ. Both young and aged Scn5a+/ΔKPQ mice showed lower heart rates and longer PR intervals than their WT counterparts. Young Scn5a+/ΔKPQ mice showed longer QT and QTc intervals than young WT. Aged Scn5a+/ΔKPQ showed longer QRS durations than aged WT. PR intervals were prolonged and QT intervals were shortened in young relative to aged WT. In contrast, ECG parameters were similar between young and aged Scn5a+/ΔKPQ. Aged murine Scn5a+/ΔKPQ hearts thus exhibit an increased atrial arrhythmogenicity. The differing Nav1.5 expression and electrocardiographic indicators of slowed cardiac conduction between Scn5a+/ΔKPQ and WT, which show further variations associated with aging, may contribute toward atrial arrhythmia in aged Scn5a+/ΔKPQ hearts

The survival time of chocolates on hospital wards:covert observational study

Objective To quantify the consumption of chocolates in a hospital ward environment. Design Multicentre, prospective, covert observational study. Setting Four wards at three hospitals (where the authors worked) within the United Kingdom. Participants Boxes of Quality Street (Nestlé) and Roses (Cadbury) on the ward and anyone eating these chocolates. Intervention Observers covertly placed two 350 g boxes of Quality Street and Roses chocolates on each ward (eight boxes were used in the study containing a total of 258 individual chocolates). These boxes were kept under continuous covert surveillance, with the time recorded when each chocolate was eaten. Main outcome measure Median survival time of a chocolate. Results 191 out of 258 (74%) chocolates were observed being eaten. The mean total observation period was 254 minutes (95% confidence interval 179 to 329). The median survival time of a chocolate was 51 minutes (39 to 63). The model of chocolate consumption was non-linear, with an initial rapid rate of consumption that slowed with time. An exponential decay model best fitted these findings (model R(2)=0.844, P<0.001), with a survival half life (time taken for 50% of the chocolates to be eaten) of 99 minutes. The mean time taken to open a box of chocolates from first appearance on the ward was 12 minutes (95% confidence interval 0 to 24). Quality Street chocolates survived longer than Roses chocolates (hazard ratio for survival of Roses v Quality Street 0.70, 95% confidence interval 0.53 to 0.93, P=0.014). The highest percentages of chocolates were consumed by healthcare assistants (28%) and nurses (28%), followed by doctors (15%). Conclusions From our observational study, chocolate survival in a hospital ward was relatively short, and was modelled well by an exponential decay model. Roses chocolates were preferentially consumed to Quality Street chocolates in a ward setting. Chocolates were consumed primarily by healthcare assistants and nurses, followed by doctors. Further practical studies are needed

The survival time of chocolates on hospital wards: covert observational study

Objective To quantify the consumption of chocolates in a hospital ward environment. Design Multicentre, prospective, covert observational study. Setting Four wards at three hospitals (where the authors worked) within the United Kingdom. Participants Boxes of Quality Street (Nestlé) and Roses (Cadbury) on the ward and anyone eating these chocolates. Intervention Observers covertly placed two 350 g boxes of Quality Street and Roses chocolates on each ward (eight boxes were used in the study containing a total of 258 individual chocolates). These boxes were kept under continuous covert surveillance, with the time recorded when each chocolate was eaten. Main outcome measure Median survival time of a chocolate. Results 191 out of 258 (74%) chocolates were observed being eaten. The mean total observation period was 254 minutes (95% confidence interval 179 to 329). The median survival time of a chocolate was 51 minutes (39 to 63). The model of chocolate consumption was non-linear, with an initial rapid rate of consumption that slowed with time. An exponential decay model best fitted these findings (model R(2)=0.844, P<0.001), with a survival half life (time taken for 50% of the chocolates to be eaten) of 99 minutes. The mean time taken to open a box of chocolates from first appearance on the ward was 12 minutes (95% confidence interval 0 to 24). Quality Street chocolates survived longer than Roses chocolates (hazard ratio for survival of Roses v Quality Street 0.70, 95% confidence interval 0.53 to 0.93, P=0.014). The highest percentages of chocolates were consumed by healthcare assistants (28%) and nurses (28%), followed by doctors (15%). Conclusions From our observational study, chocolate survival in a hospital ward was relatively short, and was modelled well by an exponential decay model. Roses chocolates were preferentially consumed to Quality Street chocolates in a ward setting. Chocolates were consumed primarily by healthcare assistants and nurses, followed by doctors. Further practical studies are needed

Long-Term Impact of Body Mass Index on Survival of Patients Undergoing Cardiac Resynchronization Therapy: A Multi-Centre Study

Obesity is a risk factor for heart failure (HF), but its presence among HF patients may be associated with favorable outcomes. We investigated the long-term outcomes across different body mass index (BMI) groups, after cardiac resynchronization therapy (CRT), and whether defibrillator back-up (CRT-D) confers survival benefit. One thousand two-hundred seventy-seven (1,277) consecutive patients (mean age: 67.0 +/- 12.7 years, 44.1% women, and mean BMI: 28.3 +/- 5.6 Kg/m(2)) who underwent CRT implantation in 5 centers between 2000-2014 were followed-up for a median period of 4.9 years (IQR 2.4 to 7.5). More than 10% of patients had follow-up for &gt;10 years. Patients were classified according to BMI as normal: &lt;25.0 Kg/m(2), overweight: 25.0 to 29.9 Kg/m(2) and obese: &gt;= 30.0 Kg/m(2). 364 patients had normal weight, 494 were overweight and 419 were obese. CRT-Ds were implanted in &gt;75% of patients, but were used less frequently in obese individuals. The composite endpoint of all-cause mortality or cardiac transplant/left ventricular assist device (LVAD) occurred in 50.9% of patients. At 10-year follow-up, less than a quarter of patients in the lowest and highest BMI categories were still alive and free from heart transplant/LVAD. After adjustment BMI of 25 to 29.9 Kg/m(2) (HR = 0.73 [95%CI 0.56 to 0.96], p = 0.023) and use of CRT-D (HR = 0.74 [95% CI 0.55 to 0.98], p = 0.039) were independent predictors of survival free from LVAD/heart transplant. BMI of 25 to 29.9 Kg/m(2) at the time of implant was independently associated with favourable long-term 10-year survival. Use of CRT-D was associated with improved survival irrespective of BMI class. (C) 2021 Elsevier Inc. All rights reserved