Global constructive work is associated with ventricular arrhythmias after cardiac resynchronization therapy.

AIMS: Non-invasive left ventricular (LV) pressure-strain loops provide a novel method for quantifying myocardial work by incorporating LV pressure in measurements of myocardial deformation. Early studies suggest that myocardial work parameters such as global constructive work (GCW) could be useful and reliable in arrhythmia prediction, particularly in patients undergoing cardiac resynchronization therapy (CRT). The aim of this study was to evaluate whether the magnitude of GCW was associated with the occurrence of ventricular arrhythmias in patients after CRT. METHODS AND RESULTS: Patients on guideline-recommended treatment with a CRT defibrillator (CRT-D) were evaluated by 2D speckle-tracking echocardiography including measurements of GCW at least 6 months after implantation. The primary outcome was a composite of appropriate defibrillator therapy and sustained ventricular arrhythmia under the monitor zone. A total of 162 patients [mean age 66 years (±10), 122 males (75%)] were included. Sixteen (10%) patients experienced the primary outcome during a median follow-up of 18 months (interquartile range: 12-25) after the performance of index echocardiography. Patients with a below-median GCW (<1473 mmHg%) had a hazard ratio (HR) for the outcome of 8.14 [95% confidence interval (CI): 1.83-36.08], P = 0.006 compared with patients above the median in a univariate model and remained an independent predictor after multivariate adjustment for the estimated glomerular filtration rate and QRS duration [HR 4.75 (95% CI: 1.01-22.28), P < 0.05]. CONCLUSION: In patients treated with CRT-D, a GCW below median level was associated with a five-fold increase in the risk of ventricular arrhythmias.

Treatment-induced increase in total body potassium in patients at high risk of ventricular arrhythmias; a randomized POTCAST substudy.

OBJECTIVE: Hypokalemia is associated with increased risk of arrhythmias and it is recommended to monitor plasma potassium (p-K) regularly in at-risk patients with cardiovascular diseases. It is poorly understood if administration of potassium supplements and mineralocorticoid receptor antagonists (MRA) aimed at increasing p-K also increases intracellular potassium. METHODS: Adults aged≥18 years with an implantable cardioverter defibrillator (ICD) were randomized (1:1) to a control group or to an intervention that included guidance on potassium rich diets, potassium supplements, and MRA to increase p-K to target levels of 4.5-5.0 mmol/l for six months. Total-body-potassium (TBK) was measured by a Whole-Body-Counter along with p-K at baseline, after six weeks, and after six months. RESULTS: Fourteen patients (mean age: 59 years (standard deviation 14), 79% men) were included. Mean p-K was 3.8 mmol/l (0.2), and mean TBK was 1.50 g/kg (0.20) at baseline. After six-weeks, p-K had increased by 0.47 mmol/l (95%CI:0.14;0.81), p = 0.008 in the intervention group compared to controls, whereas no significant difference was found in TBK (44 mg/kg (-20;108), p = 0.17). After six-months, no significant difference was found in p-K as compared to baseline (0.16 mmol/l (-0.18;0.51), p = 0.36), but a significant increase in TBK of 82 mg/kg (16;148), p = 0.017 was found in the intervention group compared to controls. CONCLUSIONS: Increased potassium intake and MRAs increased TBK gradually and a significant increase was seen after six months. The differentially regulated p-K and TBK challenges current knowledge on potassium homeostasis and the time required before the full potential of p-K increasing treatment can be anticipated. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03833089).

The effect of increased plasma potassium on myocardial function; a randomized POTCAST substudy.

Plasma potassium (p-K) in the high-normal range has been suggested to reduce risk of cardiovascular arrythmias and mortality through electrophysiological and mechanical effects on the myocardium. In this study, it was to investigated if increasing p-K to high-normal levels improves systolic- and diastolic myocardial function in patients with low-normal to moderately reduced left ventricular ejection fraction (LVEF). The study included 50 patients (mean age 58 years (SD 14), 81% men), with a mean p-K 3.95 mmol/l (SD 0.19), mean LVEF 48% (SD 7), and mean Global Longitudinal Strain (GLS) -14.6% (SD 3.1) patients with LVEF 35-55% from "Targeted potassium levels to decrease arrhythmia burden in high-risk patients with cardiovascular diseases trial" (POTCAST). Patients were given standard therapy and randomized (1:1) to an intervention that included guidance on potassium-rich diets, potassium supplements, and mineralocorticoid receptor antagonists targeting high-normal p-K levels (4.5-5.0 mmol/l). Echocardiography was done at baseline and after a mean follow-up of 44 days (SD 18) and the echocardiograms were analyzed for changes in GLS, mechanical dispersion, E/A, e', and E/e'. At follow-up, mean difference in changes in p-K was 0.52 mmol/l (95%CI 0.35;0.69), P<0.001 in the intervention group compared to controls. GLS was improved with a mean difference in changes of -1.0% (-2;-0.02), P<0.05 and e' and E/e' were improved with a mean difference in changes of 0.9 cm/s (0.02;1.7), P = 0.04 and ? 1.5 (-2.9;-0.14), P = 0.03, respectively. Thus, induced increase in p-K to the high-normal range improved indices of systolic and diastolic function in patients with low-normal to moderately reduced LVEF.

Reduced inferior wall longitudinal strain is associated with malignant arrhythmias in non-ischemic heart failure.

BACKGROUND: Reduced systolic myocardial function in the inferior region of the left ventricle has been suggested to be associated with malignant arrhythmias. We tested this hypothesis in patients with non-ischemic heart failure. METHODS: Patients with non-ischemic heart failure (left ventricular ejection fraction [LVEF] < 35%) were evaluated by 2D-speckle-tracking echocardiography. The regional longitudinal strain was calculated for each of the six left ventricular walls. The reduced regional function was defined as strain below the median. The outcome was a composite of sudden cardiac death, admission with sustained ventricular arrhythmia, resuscitated cardiac arrest, and appropriate therapy from a primary prophylactic implantable cardioverter defibrillator. Time-to-first-event analysis was performed using a Cox model. RESULTS: From two centers, 401 patients were included (median age: 63 years, 72% male) with a median LVEF of 25% (interquartile range [IQR] 20;30), and a median inferior wall strain of -9.0% (-12.5; -5.4). During a median follow-up of 4.0 years, 52 outcomes occurred. After multivariate adjustment for clinical and electrocardiographic parameters, inferior wall strain was independently associated with the outcome (HR 2.50 [1.35; 4.62], p = .003). No independent association was found between the composite outcome and reduced strain in any of the other left ventricular walls, Global Longitudinal Strain (HR 1.66 [0.93; 2.98], p = .09), or LVEF (HR 1.33 [0.75; 2.33], p = .33). CONCLUSIONS: Below median strain in the left ventricular inferior region was independently associated with a 2.5-fold increase in the risk of malignant arrhythmias and sudden cardiac death in patients with non-ischemic heart failure.

Right Ventricular Free Wall Strain and Effect of Defibrillator Implantation in Patients With Nonischemic Systolic Heart Failure.

BACKGROUND: Patients with nonischemic systolic heart failure have an increased risk of malignant ventricular arrhythmias and sudden cardiovascular death. Because the risk is less pronounced than for patients with ischemic cause of heart failure more discriminating tools are needed to identify patients most likely to benefit from implantable cardioverter-defibrillator (ICD) implantation. Right ventricular (RV) dysfunction is associated with a worse prognosis, but whether RV free wall strain (RV-FWS) measured with echocardiography can identify the patients most likely to benefit from ICD implantation is not known. METHODS AND RESULTS: In this extended follow-up analysis of the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial, RV-FWS was measured with echocardiography in 445 patients before randomization. RV dysfunction was defined as an RV-FWS of greater than -20%. The primary end point was all-cause mortality. The median RV-FWS was -18% (quartiles -23% to -14%), and RV dysfunction was measured in 255 patients (57%). During a median follow-up of 5.7 years, 170 patients (38%) died. There was a statistically significant interaction between RV dysfunction and the effect of ICD implantation (P = .003), also after adjusting for known cardiovascular risk factors (P = .01). ICD implantation significantly decreased all-cause mortality in patients with RV dysfunction (hazard ratio 0.54, 95% confidence interval 0.36-0.80, P = .002), but not in patients with normal RV function (hazard ratio 1.34, 95% confidence interval 0.84-2.12, P = .22). CONCLUSIONS: In patients with nonischemic systolic heart failure, RV dysfunction on echocardiography was associated with a greater effect of ICD implantation and could be used to select patients with benefit from ICD treatment.

Targeted potassium levels to decrease arrhythmia burden in high risk patients with cardiovascular diseases (POTCAST): Study protocol for a randomized controlled trial.

BACKGROUND: Low plasma potassium (p-K) is associated with increased risk of malignant arrhythmia and observational studies indicate protective effects of p-K in the upper reference level. However, randomized clinical studies are needed to document whether actively increasing p-K to high-normal levels is possible and safe and improves cardiovascular outcomes. OBJECTIVE: To investigate if increased p-K reduces the risk of malignant arrhythmia and all-cause death in high-risk patients with a cardiovascular disease treated with an implantable cardioverter defibrillator (ICD) for primary or secondary preventive causes. Secondly, to investigate whether high-normal p-K levels can be safely reached and maintained using already available medications and potassium-rich dietary guidance. METHODS: This is a prospective, randomized, and open-labelled study enrolling patient at high-risk of malignant arrhythmias. According to sample size calculations, 1,000 patients will be randomized 1:1 to either an investigational regiment that aims to increase and maintain p-K at high-normal levels (4.5-5.0 mmol/L) or to usual standard of care and followed for an expected four years. The trial will run until a total of 291 events have occurred providing an α = 0.05 and 1-ß = 0.80. The composite primary endpoint includes ventricular tachycardia >125 bpm lasting >30 seconds, any appropriate ICD-therapy, and all-cause mortality. At present, 739 patients have been randomized. CONCLUSIONS: We present the rationale for the design of the POTCAST trial. The inclusion was initiated 2019 and is expected to be finished 2022. The study will show if easily available treatments to increase p-K may be a new treatment modality to protect against malignant arrythmias.

Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers : A Randomized Controlled Trial.

BACKGROUND: Observational evidence suggests that mask wearing mitigates transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is uncertain if this observed association arises through protection of uninfected wearers (protective effect), via reduced transmission from infected mask wearers (source control), or both. OBJECTIVE: To assess whether recommending surgical mask use outside the home reduces wearers' risk for SARS-CoV-2 infection in a setting where masks were uncommon and not among recommended public health measures. DESIGN: Randomized controlled trial (DANMASK-19 [Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection]). (ClinicalTrials.gov: NCT04337541). SETTING: Denmark, April and May 2020. PARTICIPANTS: Adults spending more than 3 hours per day outside the home without occupational mask use. INTERVENTION: Encouragement to follow social distancing measures for coronavirus disease 2019, plus either no mask recommendation or a recommendation to wear a mask when outside the home among other persons together with a supply of 50 surgical masks and instructions for proper use. MEASUREMENTS: The primary outcome was SARS-CoV-2 infection in the mask wearer at 1 month by antibody testing, polymerase chain reaction (PCR), or hospital diagnosis. The secondary outcome was PCR positivity for other respiratory viruses. RESULTS: A total of 3030 participants were randomly assigned to the recommendation to wear masks, and 2994 were assigned to control; 4862 completed the study. Infection with SARS-CoV-2 occurred in 42 participants recommended masks (1.8%) and 53 control participants (2.1%). The between-group difference was -0.3 percentage point (95% CI, -1.2 to 0.4 percentage point; P = 0.38) (odds ratio, 0.82 [CI, 0.54 to 1.23]; P = 0.33). Multiple imputation accounting for loss to follow-up yielded similar results. Although the difference observed was not statistically significant, the 95% CIs are compatible with a 46% reduction to a 23% increase in infection. LIMITATION: Inconclusive results, missing data, variable adherence, patient-reported findings on home tests, no blinding, and no assessment of whether masks could decrease disease transmission from mask wearers to others. CONCLUSION: The recommendation to wear surgical masks to supplement other public health measures did not reduce the SARS-CoV-2 infection rate among wearers by more than 50% in a community with modest infection rates, some degree of social distancing, and uncommon general mask use. The data were compatible with lesser degrees of self-protection. PRIMARY FUNDING SOURCE: The Salling Foundations.

[Amphetamine abuse is a possible cause of pontine haemorrhage].

This is a case report of a 55-year-old male, who was admitted due to right-sided sensorimotor deficits and one-and-a-half syndrome He had snorted 5 g of amphetamine over 24 h two months prior to admission. He was normotensive on admission. A CT brain scan showed left pontine haemorrhage, but a CT angiogram showed no vascular malformations nor vessel beading, and a two-month follow-up MRI showed no vascular malformations nor tumours. To the best of our knowledge, this is the fifth published case of pontine haemorrhage, and the first published case of one-and-a-half syndrome related to amphetamine abuse.

High tobacco consumption lowers body weight: a Mendelian randomization study of the Copenhagen General Population Study.

BACKGROUND: Conflicting evidence has been found regarding the association between high tobacco consumption and body weight among smokers. We tested the hypothesis that high tobacco consumption is causally associated with low body weight. METHODS: We conducted a Mendelian randomization study with a genetic variant in CHRNA3 (rs1051730) as proxy for high tobacco consumption. The cohort consisted of 80,342 participants from the Copenhagen General Population Study, with details on body weight, smoking habits and CHRNA3 genotype, including 15,220 current smokers. RESULTS: In observational analyses, high tobacco consumption was associated with high body weight, body mass index, waist circumference, hip circumference and waist-hip ratio. In multivariable adjusted models a 1-cigarette/day higher tobacco consumption was associated with 0.05 kg (95% confidence interval 0.02; 0.08) higher body weight, 0.02 kg/m(2) (0.01; 0.02) higher body mass index, 0.10 cm (0.07; 0.12) higher waist circumference and 0.02 cm (0.001; 0.03) higher hip circumference. In contrast, the per-allele increase inCHRNA3 rs1051730 associated with high tobacco consumption was associated with 0.59 kg (0.96; 0.22) lower body weight, 0.23 kg/m(2) (0.33; 0.13) lower body mass index, 0.32 cm (0.74; 0.003) lower waist circumference and 0.45 cm (0.66; 0.24) lower hip circumference. No association was found between tobacco consumption and waist-hip ratio in genetic analysis, or among CHRNA3 genotype and any of the outcome variables in former or never smokers. CONCLUSIONS: High tobacco consumption causes lower body weight among current smokers. However, smoking does not seem to affect body shape or fat distribution causally. The lack of association between CHRNA3 genotype and body weight among former smokers and never smokers favours smoking as the causal factor for the observed associations.