Myocardial fibrosis in stroke survivors

Stroke survivors are most likely to die of cardiac death, yet few undergo comprehensive cardiac assessment to look for reversible causes. Myocardial fibrosis (MF) is not only the hallmark of cardiomyopathy, but also a substrate for sudden cardiac death, ventricular tachyarrhythmia and heart failure. Procollagen carboxyl-terminal telopeptide (PICP) was found to be a marker of MF. The relationship between PICP and cardiac abnormalities in stroke survivors is unknown. We recently showed that MF in stroke survivors can be treated by spironolactone and amiloride in a randomised placebo-controlled cross-over study with reduction in PICP levels and QTc [1]

Effect of allopurinol on phosphocreatine recovery and muscle function in older people with impaired physical function:a randomised controlled trial

Background: Allopurinol has vascular antioxidant effects and participates in purinergic signalling within muscle. We tested whether allopurinol could improve skeletal muscle energetics and physical function in older people with impaired physical performance. Methods: We conducted a randomised, double blind, parallel group, placebo-controlled trial, comparing 20 weeks of allopurinol 600 mg once daily versus placebo. We recruited community-dwelling participants aged 65 and over with baseline 6-min walk distance of &lt;400 m and no contraindications to magnetic resonance imaging scanning. Outcomes were measured at baseline and 20 weeks. The primary outcome was post-exercise phosphocreatine (PCr) recovery rate measured using 31P magnetic resonance spectroscopy of the calf. Secondary outcomes included 6-min walk distance, short physical performance battery (SPPB), lean body mass measured by bioimpedance, endothelial function and quality of life. Results: In total, 124 participants were randomised, mean age 80 (SD 6) years. A total of 59 (48%) were female, baseline 6-min walk distance was 293 m (SD 80 m) and baseline SPPB was 8.5 (SD 2.0). Allopurinol did not significantly improve PCr recovery rate (treatment effect 0.10 units [95% CI, −0.07 to 0.27], P = 0.25). No significant changes were seen in endothelial function, quality of life, lean body mass or SPPB. Allopurinol improved 6-min walk distance (treatment effect 25 m [95% 4–46, P = 0.02]). This was more pronounced in those with high baseline oxidative stress and urate. Conclusion: Allopurinol improved 6-min walk distance but not PCr recovery rate in older people with impaired physical function. Antioxidant strategies to improve muscle function for older people may need to be targeted at subgroups with high baseline oxidative stress. </p

Additive Intensity Regression Models in Corporate Default Analysis

We consider additive intensity (Aalen) models as an alternative to the multiplicative intensity (Cox) models for analyzing the default risk of a sample of rated, nonfinancial U.S. firms. The setting allows for estimating and testing the significance of time-varying effects. We use a variety of model checking techniques to identify misspecifications. In our final model, we find evidence of time-variation in the effects of distance-to-default and short-to-long term debt. Also we identify interactions between distance-to-default and other covariates, and the quick ratio covariate is significant. None of our macroeconomic covariates are significant

Pretreatment with beta-blockers and the frequency of hypokalemia in patients with acute chest pain

Plasma potassium concentration was measured at admission in 1234 patients who presented with acute chest pain. One hundred and ninety five patients were on P blockers before admission. The potassium concentrations of patients admitted early (within four hours of onsetof symptoms) were compared with those admitted later (4-18 hours after onset of symptoms). There was a transient fall in plasma potassium concentrations in patients not pre-treated with , B blockers. This was not seen in patients who had been on P blockers before admission. Nonselective, B blockers were more effective than cardioselective agents in maintaining concentrationsof plasma potassium. These findings suggest a mechanism for the beneficial effects of ,B blockers on morbidity and mortality in acute myocardial infarction

Patients' inability to perform a preoperative cardiopulmonary exercise test or demonstrate an anaerobic threshold is associated with inferior outcomes after major colorectal surgery.

BACKGROUND: Surgical patients with poor functional capacity, determined by oxygen consumption at anaerobic threshold (AT) during cardiopulmonary exercise testing (CPET), experience longer hospital stays and worse short- and medium-term survival. However, previous studies excluded patients who were unable to perform a CPET or who failed to demonstrate an AT. We hypothesized that such patients are at risk of inferior outcomes after elective surgery. METHODS: All patients undergoing major colorectal surgery attempted CPET to assist in the planning of care. Patients were stratified by their test results into Fit (AT ≥ 11.0 ml O2 kg(-1) min(-1)), Unfit (AT < 11.0 ml O2 kg(-1) min(-1)), or Unable to CPET groups (failed to pedal or demonstrate an AT). For each group, we determined hospital stay and mortality. RESULTS: Between March 2009 and April 2010, 269 consecutive patients were screened, and proceeded to bowel resection. Median hospital stay was 8 days (IQR 5.1-13.4) and there were 44 deaths (16%) at 2 yr; 26 (9.7%) patients were categorized as Unable to CPET, 69 (25.7%) Unfit and 174 (64.7%) Fit. There were statistically significant differences between the three groups in hospital stay [median (IQR) 14.0 (10.5-23.8) vs 9.9 (5.5-15) vs 7.1 (4.9-10.8) days, P < 0.01] and mortality at 2 yr [11/26 (42%) vs 14/69 (20%) vs 19/174 (11%), respectively (P < 0.01)] although the differences between Unable and Unfit were not statistically different. CONCLUSIONS: Patients' inability to perform CPET is associated with inferior outcomes after major colorectal surgery. Future studies evaluating CPET in risk assessment for major surgery should report outcomes for this subgroup

QT peak prolongation predicts cardiac death following stroke

Cardiac death has been linked in many populations to prolongation of the QT interval (QTe). However, basic science research suggested that the best estimate of the time point when repolarisation begins is near the T-wave peak. We found QT peak (QTp) was longer in hypertensive subjects with LVH. A prolonged “depolarisation” phase, rather than “repolarisation” (T peak to T end) might therefore account for the higher incidence of cardiac death linked to long QT. Hypothesis: We have tested the hypothesis that QT peak (QTp) prolongation predicts cardiac death in stroke survivors. Methods and Results: ECGs were recorded from 296 stroke survivors (152 male), mean age 67.2 (SD 11.6) approximately 1 year after the event. Their mean blood pressure was 152/88 mmHg (SD 29/15mmHg). These ECGs were digitised by one observer who was blinded to patient outcome. The patients were followed up for a median of 3.3 years. The primary endpoint was cardiac death. A prolonged heart rate corrected QT peak (QTpc) of lead I carried the highest relative risk of death from all cause as well as cardiac death, when compared with the other more conventional QT indices. In multivariate analyses, when adjusted for conventional risk factors of atherosclerosis, a prolonged QTpc of lead I was still associated with a 3-fold increased risk of cardiac death. (adjusted relative risk 3.0 [95% CI 1.1 - 8.5], p=0.037). Conclusion: QT peak prolongation in lead I predicts cardiac death after strok

Towards understanding the clinical significance of QT peak prolongation: a novel marker of myocardial ischemia independently demonstrated in two prospective studies

Background: QT peak prolongation identified patients at risk of death or non-fatal MI. We tested the hypothesis that QT peak prolongation might be associated with significant myocardial ischaemia in two separate cohorts to see how widely applicable the concept was. Methods and Results: In the first study, 134 stroke survivors were prospectively recruited and had 12-lead ECGs and Nuclear myocardial perfusion scanning. QT peak was measured in lead I of a 12-lead ECG and heart rate corrected by Bazett’s formula (QTpc). QTpc prolongation to 360ms or more was 92% specific at diagnosing severe myocardial ischaemia. This hypothesis-generating study led us to perform a second prospective study in a different cohort of patients who were referred for dobutamine stress echocardiography. 13 of 102 patients had significant myocardial ischaemia. Significant myocardial ischaemia was associated with QT peak prolongation at rest (mean 354ms, 95% CI 341-367ms, compared with mean 332ms, 95% CI 327-337ms in those without significant ischaemia; p=0.002). QT peak prolongation to 360ms or more was 88% specific at diagnosing significant myocardial ischaemia in the stress echocardiography study. QT peak prolongation to 360ms or more was associated with over 4-fold increase odds ratio of significant myocardial ischaemia. The Mantel- Haenszel Common Odds Ratio Estimate=4.4, 95% CI=1.2-16.0, p=0.023. Conclusion: QT peak (QTpc) prolongation to 360ms or more should make us suspect the presence of significant myocardial ischaemia. Such patients merit further investigations for potentially treatable ischaemic heart disease to reduce their risk of subsequent death or non-fatal MI

Global emissions of terpenoid VOCs from terrestrial vegetation in the last millennium

Peer reviewe

Renal and Cardiovascular Effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF):protocol for a randomised controlled double-blind cross-over trial

Introduction: Type 2 diabetes (T2D) and heart failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium-glucose co-transporter 2 (SGLT2) inhibitors and their use in patients with HF. Data on the effect of SGLT2 inhibitor use with diuretics is limited. We hypothesise that SGLT2 inhibition may augment the effects of loop diuretics. We hypothesise that the benefits of SGLT2 inhibitors extend beyond those of their metabolic (glycaemic parameters and weight loss) and haemodynamic parameters; that the effects of SGLT2 inhibitors as an osmotic diuretic and on natriuresis may underlie the cardiovascular and renal benefits demonstrated in the recent EMPA-REG study.Methods and Analysis: To assess the effect of SGLT2 inhibitors when used in combination with a loop diuretic, the RECEDE-CHF trial is a single centre, randomised double-blind, placebo-controlled, crossover trial conducted in a secondary care setting within NHS Tayside, Scotland. 34 eligible participants, aged between 18 to 80 years, with stable T2D and CHF will be recruited. Renal physiological testing will be performed at two points (week 1 and week 6) on each arm to assess the effect of 25 mg empagliflozin, on the primary and secondary outcomes. Participants will be enrolled in the trial for a total period between 14 to 16 weeks. The primary outcome will assess the effect of empagliflozin versus placebo on urine output. The secondary outcomes are to assess the effect of empagliflozin on glomerular filtration rate, cystatin C, urinary sodium excretion, urinary protein/creatinine ratio, and urinary albumin/creatinine ratio when compared to placebo.Ethics and Dissemination: Ethics approval was obtained by the East of Scotland Research Ethics Service. Results of the trial will be submitted for publication in a peer-reviewed journal.Registration Details: clinicaltrials.gov: NCT03226457. Registered: July 17, 2017