Continuous infusion versus bolus injection of loop diuretics for acute heart failure.

BACKGROUND: Acute heart failure (AHF) is new onset of, or a sudden worsening of, chronic heart failure characterised by congestion in about 95% of cases or end-organ hypoperfusion in 5% of cases. Treatment often requires urgent escalation of diuretic therapy, mainly through hospitalisation. This Cochrane review evaluated the efficacy of intravenous loop diuretics strategies in treating AHF in individuals with New York Heart Association (NYHA) classification III or IV and fluid overload. OBJECTIVES: To assess the effects of intravenous continuous infusion versus bolus injection of loop diuretics for the initial treatment of acute heart failure in adults. SEARCH METHODS: We identified trials through systematic searches of bibliographic databases and in clinical trials registers including CENTRAL, MEDLINE, Embase, CPCI-S on the Web of Science, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry platform (ICTRP), and the European Union Trials register. We conducted reference checking and citation searching, and contacted study authors to identify additional studies. The latest search was performed on 29 February 2024. SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving adults with AHF, NYHA classification III or IV, regardless of aetiology or ejection fraction, where trials compared intravenous continuous infusion of loop diuretics with intermittent bolus injection in AHF. We excluded trials with chronic stable heart failure, cardiogenic shock, renal artery stenosis, or end-stage renal disease. Additionally, we excluded studies combining loop diuretics with hypertonic saline, inotropes, vasoactive medications, or renal replacement therapy and trials where diuretic dosing was protocol-driven to achieve a target urine output, due to confounding factors. DATA COLLECTION AND ANALYSIS: Two review authors independently screened papers for inclusion and reviewed full-texts. Outcomes included weight loss, all-cause mortality, length of hospital stay, readmission following discharge, and occurrence of acute kidney injury. We performed risk of bias assessment and meta-analysis where data permitted and assessed certainty of the evidence. MAIN RESULTS: The review included seven RCTs, spanning 32 hospitals in seven countries in North America, Europe, and Asia. Data collection ranged from eight months to six years. Following exclusion of participants in subgroups with confounding treatments and different clinical settings, 681 participants were eligible for review. These additional study characteristics, coupled with our strict inclusion and exclusion criteria, improve the applicability of the body of the evidence as they reflect real-world clinical practice. Meta-analysis was feasible for net weight loss, all-cause mortality, length of hospital stay, readmission, and acute kidney injury. Literature review and narrative analysis explored daily fluid balance; cardiovascular mortality; B-type natriuretic peptide (BNP) change; N-terminal-proBNP change; and adverse incidents such as ototoxicity, hypotension, and electrolyte imbalances. Risk of bias assessment revealed two studies with low overall risk, four with some concerns, and one with high risk. All sensitivity analyses excluded trials at high risk of bias. Only narrative analysis was conducted for 'daily fluid balance' due to diverse data presentation methods across two studies (169 participants, the evidence was very uncertain about the effect). Results of narrative analysis varied. For instance, one study reported higher daily fluid balance within the first 24 hours in the continuous infusion group compared to the bolus injection group, whereas there was no difference in fluid balance beyond this time point. Continuous intravenous infusion of loop diuretics may result in mean net weight loss of 0.86 kg more than bolus injection of loop diuretics, but the evidence is very uncertain (mean difference (MD) 0.86 kg, 95% confidence interval (CI) 0.44 to 1.28; 5 trials, 497 participants; P < 0.001, I2 = 21%; very low-certainty evidence). Importantly, sensitivity analysis excluding trials with high risk of bias showed there was insufficient evidence for a difference in bodyweight loss between groups (MD 0.70 kg, 95% CI -0.06 to 1.46; 3 trials, 378 participants; P = 0.07, I2 = 0%). There may be little to no difference in all-cause mortality between continuous infusion and bolus injection (risk ratio (RR) 1.53, 95% CI 0.81 to 2.90; 5 trials, 530 participants; P = 0.19, I2 = 4%; low-certainty evidence). Despite sensitivity analysis, the direction of the evidence remained unchanged. No trials measured cardiovascular mortality. There may be little to no difference in the length of hospital stay between continuous infusion and bolus injection of loop diuretics, but the evidence is very uncertain (MD -1.10 days, 95% CI -4.84 to 2.64; 4 trials, 211 participants; P = 0.57, I2 = 88%; very low-certainty evidence). Sensitivity analysis improved heterogeneity; however, the direction of the evidence remained unchanged. There may be little to no difference in the readmission to hospital between continuous infusion and bolus injection of loop diuretics (RR 0.85, 95% CI 0.63 to 1.16; 3 trials, 400 participants; P = 0.31, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show insufficient evidence for a difference in the readmission to hospital between groups. There may be little to no difference in the occurrence of acute kidney injury as an adverse event between continuous infusion and bolus injection of intravenous loop diuretics (RR 1.02, 95% CI 0.70 to 1.49; 3 trials, 491 participants; P = 0.92, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show that continuous infusion may make little to no difference on the occurrence of acute kidney injury as an adverse events compared to the bolus injection of intravenous loop diuretics. AUTHORS' CONCLUSIONS: Analysis of available data comparing two delivery methods of diuretics in acute heart failure found that the current data are insufficient to show superiority of one strategy intervention over the other. Our findings were based on trials meeting stringent inclusion and exclusion criteria to ensure validity. Despite previous reviews suggesting advantages of continuous infusion over bolus injections, our review found insufficient evidence to support or refute this. However, our review, which excluded trials with clinical confounders and RCTs with high risk of bias, offers the most robust conclusion to date.

Kidney health in the COVID-19 pandemic: An umbrella review of meta-analyses and systematic reviews.

Background: This umbrella review aims to consolidate evidence from systematic reviews and meta-analyses investigating the impact of the coronavirus disease-2019 (COVID-19) on kidney health, and the associations between kidney diseases and clinical outcomes in COVID-19 patients. Methods: Five databases, namely, EMBASE, PubMed, Web of Science, the Cochrane Database of Systematic Reviews and Ovid Medline, were searched for meta-analyses and systematic reviews from January 1, 2020 to June 2, 2022. Two reviewers independently selected reviews, identified reviews for inclusion and extracted data. Disagreements were resolved by group discussions. Two reviewers independently assessed the methodological quality of all included reviews using ROBIS tool. A narrative synthesis was conducted. The characteristics and major findings of the included reviews are presented using tables and forest plots. The included meta-analyses were updated when necessary. The review protocol was prospectively registered in PROSPERO (CRD42021266300). Results: A total of 103 reviews were identified. Using ROBIS, 30 reviews were rated as low risk of bias. Data from these 30 reviews were included in the narrative synthesis. Ten meta-analyses were updated by incorporating 119 newly available cohort studies. Hospitalized COVID-19 patients had a notable acute kidney injury (AKI) incidence of 27.17%. AKI was significantly associated with mortality (pooled OR: 5.24) and severe conditions in COVID-19 patients (OR: 14.94). The pooled prevalence of CKD in COVID-19 patients was 5.7%. Pre-existing CKD was associated with a higher risk of death (pooled OR: 2.21) and disease severity (pooled OR: 1.87). Kidney transplant recipients were susceptible to SARS-CoV-2 infection (incidence: 23 per 10,000 person-weeks) with a pooled mortality of 18%. Conclusion: Kidney disease such as CKD or recipients of kidney transplants were at increased risk of contracting COVID-19. Persons with COVID-19 also had a notable AKI incidence. AKI, the need for RRT, pre-existing CKD and a history of kidney transplantation are associated with adverse outcomes in COVID-19. Systematic review registration: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021266300, identifier: CRD42021266300.

Effectiveness and Safety of Apixaban in over 3.9 Million People with Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND: There is a plethora of real-world data on the safety and effectiveness of direct-acting oral anticoagulants (DOACs); however, study heterogeneity has contributed to inconsistent findings. We compared the effectiveness and safety of apixaban with those of other direct-acting oral anticoagulants (DOACs) and vitamin K antagonists (VKA e.g., warfarin). METHODS: A systematic review and meta-analysis was conducted retrieving data from PubMed, SCOPUS and Web of Science from January 2009 to December 2021. Studies that evaluated apixaban (intervention) prescribed for adults (aged 18 years or older) with AF for stroke prevention compared to other DOACs or VKAs were identified. Primary outcomes included stroke/systemic embolism (SE), all-cause mortality, and major bleeding. Secondary outcomes were intracranial haemorrhage (ICH) and ischaemic stroke. Randomised controlled trials and non-randomised trials were considered for inclusion. RESULTS: In total, 67 studies were included, and 38 studies were meta-analysed. Participants taking apixaban had significantly lower stroke/SE compared to patients taking VKAs (relative risk (RR) 0.77, 95% confidence interval (CI) 0.64-0.93, I2 = 94%) and dabigatran (RR 0.84, 95% CI 0.74-0.95, I2 = 66%), but not to patients administered rivaroxaban. There was no statistical difference in mortality between apixaban and VKAs or apixaban and dabigatran. Compared to patients administered rivaroxaban, participants taking apixaban had lower mortality rates (RR 0.83, 95% CI 0.71-0.96, I2 = 96%). Apixaban was associated with a significantly lower risk of major bleeding compared to VKAs (RR 0.58, 95% CI 0.52-0.65, I2 = 90%), dabigatran (RR 0.79, 95% CI 0.70-0.88, I2 = 78%) and rivaroxaban (RR 0.61, 95% CI 0.53-0.70, I2 = 87%). CONCLUSIONS: Apixaban was associated with a better overall safety and effectiveness profile compared to VKAs and other DOACs.

Yearly Incidence of Stroke and Bleeding in Atrial Fibrillation with Concomitant Hyperthyroidism: A National Discharge Database Study.

Background: Hyperthyroidism is associated with atrial fibrillation (AF), and the latter is a major risk factor for stroke. Aim: We aimed to investigate the yearly incidence of stroke and bleeding in AF patients with and without concomitant hyperthyroidism from the French National Hospital Discharge Database. Methods: Admissions with AF between January 2010 and December 2019 were retrospectively identified and retrieved from the French national database. Incidence rates of ischaemic stroke and bleeding were compared in AF patients with and without concomitant hyperthyroidism. The associations of risk factors with ischaemic stroke were assessed by Cox regression. Results: Overall 2,421,087 AF patients, among whom 32,400 had concomitant hyperthyroidism were included in the study. During the follow-up (mean: 2.0 years, standard deviation SD: 2.2 years), the yearly incidence of ischaemic stroke was noted to be 2.6 (95% confidence interval CI: 2.5−2.8) in AF patients with concomitant hyperthyroidism, and 2.3 (95%CI: 2.3−2.4) in non-thyroid AF patients. Hyperthyroidism was noted as an independent risk factor for ischaemic stroke (adjusted hazard ratio aHR: 1.133, 95%CI: 1.080−1.189) overall, particularly within the first year of hyperthyroidism diagnosis (aHR 1.203, 95%CI 1.120−1.291), however, the association became non-significant in subsequent years (aHR 1.047, 95%CI 0.980−1.118). Major bleeding incidence was lower in the hyperthyroid AF group in comparison to the non-thyroid AF group (incidence ratio: 5.1 vs. 5.4%/year, p < 0.001). The predictive value of CHA2DS2VASc and HAS-BLED scores for ischaemic stroke and bleeding events, respectively, did not differ significantly between AF patients with or without concomitant hyperthyroidism. Conclusions: Hyperthyroidism seems to be an independent risk factor of ischaemic stroke in AF patients, particularly within the first year of hyperthyroidism diagnosis.

Stroke prevention in atrial fibrillation.

Atrial fibrillation (AF) is the commonest sustained cardiac rhythm disorder associated with an increased risk of stroke and systemic embolic events. The prevention of stroke using oral anticoagulants has been a pivotal component of AF management. The purpose of this review is to summarize recent advances in the treatment and prevention of stroke in AF over the last 5 years. We performed a comprehensive structured literature search using MEDLINE for publications from 11th March 2015 through to 31st December 2020. We focused mainly on primarily published research articles and systematic reviews including updates in different international guidelines. We found that improved awareness and detection of AF and use of clinical risk stratification are central to the identification of patients at risk of stroke who would benefit from oral anticoagulation. The recommendation of non-vitamin K antagonist oral anticoagulants over warfarin in both efficacy and safety perspective is represented in all international guidelines. Beyond stroke prevention, there is a move to more holistic or integrated care management of AF, which has been shown to improve outcomes. We conclude that stroke prevention remains a dominant part of the management of patients with AF. Not all stroke risk factors carry equal weight, and many require additional scrutiny (e.g. severity of CAD, type of diabetes, duration of hypertension). The utilization of clinical risk scores to help decision-making should take into account that these scores are mere simplification tools to aid decision-making and the additional clinical benefit with more complex risk scores and addition of biomarkers is limited. Also, stroke and bleeding risks are dynamic and require regular review. Instead of arbitrarily categorizing patients into (artificial) low, moderate, and high stroke risk strata, anticoagulation should be offered to all patients with AF unless they are low risk with no risk factors for stroke. Stroke prevention is also part of the proactive, integrated care approach to holistic management of patients with AF, which can be simplified in the ABC (Atrial fibrillation Better Care) pathway: 'A' Avoid stroke/Anticoagulation; 'B' Better symptom management emphasising patient-centred symptom directed decisions on rate or rhythm control strategies; and 'C' refers to Cardiovascular risk and comorbidity optimization, including lifestyle changes and attention to patient values and preferences, as well as the psychological morbidity associated with AF.

The Prognosis of Baseline Mitral Regurgitation in Patients with Transcatheter Aortic Valve Implantation.

Mitral regurgitation (MR) is the most common valvular lesion in transcatheter aortic valve implantation (TAVI) recipients. This study aims to assess the long-term prognostic impact of baseline MR in TAVI patients. METHODS: Adult patients who underwent TAVI were identified in the French National Hospital Discharge Database. All-cause and cardiovascular mortality, stroke, and rehospitalization with heart failure (HF) were compared in TAVI patients with and without baseline MR and tricuspid regurgitation (TR), respectively; the associations of MR and TR with the outcomes were assessed by Cox regression. RESULTS: Baseline MR was identified in 8240 TAVI patients. Patients with baseline MR have higher yearly incidence of all-cause mortality (HR: 1.192, 95% confidence interval CI: 1.125-1.263), cardiovascular mortality (HR: 1.313, 95%CI: 1.210-1.425), and rehospitalization for heart failure (HF) (HR: 1.411, 95%CI: 1.340-1.486) compared to those without, except for stroke rate (HR: 0.988, 95%CI: 0.868-1.124). Neither baseline MR nor TR was an independent risk predictor for all-cause mortality or cardiovascular mortality in TAVI patients. Baseline MR was independently associated with rehospitalization for HF in TAVI patients. CONCLUSIONS: Baseline MR and TR were associated with increased all-cause and cardiovascular mortality post-TAVI, however, neither of them was independent predictor for all-cause or cardiovascular mortality.

Catheter ablation as first-line treatment for paroxysmal atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of catheter ablation (CA) compared with antiarrhythmic drugs (AADs) as first-line treatment for symptomatic paroxysmal atrial fibrillation (AF). METHODS: Systematic review and meta-analysis of randomised controlled trials identified using MEDLINE, Cochrane Library and Embase published between 01/01/2000 and 19/03/2021. The primary efficacy endpoint was the first documented recurrence of atrial arrhythmias following the blanking period. The primary safety endpoint was a composite of all serious adverse events (SAEs). RESULTS: From 441 records, 6 studies met the inclusion criteria. 609 patients received CA, while 603 received AAD therapy. 212/609 patients in the CA group had a recurrence of atrial arrhythmias as compared with 318/603 in the AADs group resulting in a 36% relative risk reduction (risk ratio: 0.64, 95% CI 0.51 to 0.80, p<0.01). The risk of all SAEs was not statistically different between CA and AAD (0.87, 0.58 to 1.30, p=0.49); 107/609 SAE in the CA group vs 126/603 in the AAD group. Both recurrence of symptomatic atrial arrhythmias (109/505 vs 186/504) and healthcare utilisation (126/397 vs 185/394) were significantly lower in the CA group (0.53, 0.35 to 0.79 and 0.65, 0.48 to 0.89, respectively). There was a 79% reduction in the crossover rate during follow-up among patients randomised to CA compared with AAD (0.21, 0.13 to 0.32, p<0.01). CONCLUSIONS: First-line treatment with CA is superior to AAD therapy in patients with symptomatic paroxysmal AF, as it significantly reduces the recurrence of any atrial arrhythmias and symptomatic atrial arrhythmias, and healthcare resource utilisation with comparable safety profile.

Cardiovascular risk factors, cardiovascular disease, and COVID-19: an umbrella review of systematic reviews.

AIMS: To consolidate evidence to determine (i) the association between cardiovascular risk factors and health outcomes with coronavirus 2019 (COVID-19); and (ii) the impact of COVID-19 on cardiovascular health. METHODS AND RESULTS: An umbrella review of systematic reviews was conducted. Fourteen medical databases and pre-print servers were searched from 1 January 2020 to 5 November 2020. The review focused on reviews rated as moderate or high-quality using the AMSTAR 2 tool. Eighty-four reviews were identified; 31 reviews were assessed as moderate quality and one was high-quality. The following risk factors were associated with higher mortality and severe COVID-19: renal disease [odds ratio (OR) (95% confidence interval) for mortality 3.07 (2.43-3.88)], diabetes mellitus [OR 2.09 (1.80-2.42)], hypertension [OR 2.50 (2.02-3.11)], smoking history [risk ratio (RR) 1.26 (1.20-1.32)], cerebrovascular disease [RR 2.75 (1.54-4.89)], and cardiovascular disease [OR 2.65 (1.86-3.78)]. Liver disease was associated with higher odds of mortality [OR 2.81 (1.31-6.01)], but not severe COVID-19. Current smoking was associated with a higher risk of severe COVID-19 [RR 1.80 (1.14-2.85)], but not mortality. Obesity associated with higher odds of mortality [OR 2.18 (1.10-4.34)], but there was an absence of evidence for severe COVID-19. In patients hospitalized with COVID-19, the following incident cardiovascular complications were identified: acute heart failure (2%), myocardial infarction (4%), deep vein thrombosis (7%), myocardial injury (10%), angina (10%), arrhythmias (18%), pulmonary embolism (19%), and venous thromboembolism (25%). CONCLUSION: Many of the risk factors identified as associated with adverse outcomes with COVID-19 are potentially modifiable. Primary and secondary prevention strategies that target cardiovascular risk factors may improve outcomes for people following COVID-19.

The interpretation of CHA2DS2-VASc score components in clinical practice: a joint survey by the European Heart Rhythm Association (EHRA) Scientific Initiatives Committee, the EHRA Young Electrophysiologists, the Association of Cardiovascular Nursing and Allied Professionals, and the European Society of Cardiology Council on Stroke.

This European Heart Rhythm Association (EHRA) Scientific Initiatives Committee, EHRA Young Electrophysiologists, Association of Cardiovascular Nursing and Allied Professionals, and European Society of Cardiology (ESC) Council on Stroke joint survey aimed to assess the interpretation of the CHA2DS2-VASc score components and preferred resources for calculating the score. Of 439 respondents, most were general cardiologists (46.7%) or electrophysiologists (EPs) (42.1%). The overall adherence to the ESC-defined scoring criteria was good. Most variation was observed in the interpretation of the significance of left ventricular ejection fraction and brain natriuretic peptide in the scoring for the 'C' component, as well as the 'one-off high reading of blood pressure' to score on the 'H' component. Greater confidence was expressed in scoring the 'H' component (72.3%) compared with the 'C' (46.2%) and 'V' (45.9%) components. Respondents mainly relied on their recall for the scoring of CHA2DS2-VASc score (64.2%). The three most favoured referencing resources varied among different professionals, with pharmacists and physicians relying mainly on memory or web/mobile app, whereas nurses favoured using a web/mobile app followed by memory or guidelines/protocol. In conclusion, this survey revealed overall good adherence to the correct definition of each component in scoring of the 'C', 'H', and 'V' elements of the CHA2DS2-VASc score, although the variation in their interpretations warrants further clarifications. The preferred referencing resources to calculate the score varied among different healthcare professionals. Guideline education to healthcare professionals and updated and unified online/mobile scoring tools are suggested to improve the accuracy in scoring the CHA2DS2-VASc score.

Epidemiology of Atrial Fibrillation: Geographic/Ecological Risk Factors, Age, Sex, Genetics.

Atrial fibrillation is the most common arrhythmia globally. The global prevalence of atrial fibrillation is positively correlated with the sociodemographic index of different regions. Advancing age, male sex, and Caucasian race are risk factors; female sex is correlated with higher atrial fibrillation mortality worldwide likely owing to thromboembolic risk. African American ethnicity is associated with lower atrial fibrillation risk, same as Asian and Hispanic/Latino ethnicities compared with Caucasians. Atrial fibrillation may be heritable, and more than 100 genetic loci have been identified. A polygenic risk score and clinical risk factors are feasible and effective in risk stratification of incident disease.

Distinct Regulatory Effects of Myeloid Cell and Endothelial Cell NAPDH Oxidase 2 on Blood Pressure.

BACKGROUND: Hypertension caused by increased renin-angiotensin system activation is associated with elevated reactive oxygen species production. Previous studies implicate NADPH oxidase (Nox) proteins as important reactive oxygen species sources during renin-angiotensin system activation, with different Nox isoforms being potentially involved. Among these, Nox2 is expressed in multiple cell types, including endothelial cells, fibroblasts, immune cells, and microglia. Blood pressure (BP) is regulated at the central nervous system, renal, and vascular levels, but the cell-specific role of Nox2 in BP regulation is unknown. METHODS: We generated a novel mouse model with a floxed Nox2 gene and used Tie2-Cre, LysM Cre, or Cdh5-CreERT2 driver lines to develop cell-specific models of Nox2 perturbation to investigate its role in BP regulation. RESULTS: Unexpectedly, Nox2 deletion in myeloid but not endothelial cells resulted in a significant reduction in basal BP. Both Tie2-CreNox2 knockout (KO) mice (in which Nox2 was deficient in both endothelial cells and myeloid cells) and LysM CreNox2KO mice (in which Nox2 was deficient in myeloid cells) had significantly lower BP than littermate controls, whereas basal BP was unaltered in Cdh5-CreERT2 Nox2KO mice (in which Nox2 is deficient only in endothelial cells). The lower BP was attributable to an increased NO bioavailability that dynamically dilated resistance vessels in vivo under basal conditions without a change in renal function. Myeloid-specific Nox2 deletion had no effect on angiotensin II-induced hypertension, which, however, was blunted in Tie2-CreNox2KO mice, along with preservation of endothelium-dependent relaxation during angiotensin II stimulation. CONCLUSIONS: We identify a hitherto unrecognized modulation of basal BP by myeloid cell Nox2, whereas endothelial cell Nox2 regulates angiotensin II-induced hypertension. These results identify distinct cell-specific roles for Nox2 in BP regulation.

High-frequency speckle tracking echocardiography in the assessment of left ventricular function and remodeling after murine myocardial infarction.

The objectives of this study were to assess the feasibility and accuracy of high-frequency speckle tracking echocardiography (STE) in a murine model of myocardial infarction (MI). STE is used clinically to quantify global and regional cardiac function, but its application in mice is challenging because of the small cardiac size and rapid heart rates. A high-frequency micro-ultrasound system with STE (Visualsonics Vevo 2100) was compared against magnetic resonance imaging (MRI) for the assessment of global left ventricular (LV) size and function after murine MI. Animals subjected to coronary ligation (n = 46) or sham ligation (n = 27) were studied 4 wk postoperatively. Regional and global deformation were also assessed. STE-derived LV ejection fraction (EF) and mass correlated well with MRI indexes (r = 0.93, 0.77, respectively; P < 0.001), as did STE-derived mass with postmortem values (r = 0.80, P < 0.001). Higher STE-derived volumes correlated positively with MRI-derived infarct size (P < 0.01). Global strain parameters were significantly reduced after MI (all P < 0.001) and strongly correlated with LV mass and MRI-derived infarct size as promising surrogates for the extent of remodeling and infarction, respectively (both P < 0.05). Regional strain analyses showed that radial strain and strain rate were relatively preserved in anterior basal segments after MI compared with more apical segments (P < 0.001); however, longitudinal strain and strain rate were significantly impaired both basally and distally (P < 0.001). Strain-derived parameters of dyssynchrony were significantly increased in the MI group (P < 0.01). Analysis time for STE was 210 ± 45 s with acceptable inter- and intraobserver variability. In conclusion, high-frequency STE enables quantitative assessment of regional and global function in the remodeling murine LV after MI.

Ionizing radiation regulates cardiac Ca handling via increased ROS and activated CaMKII.

Ionizing radiation (IR) is an integral part of modern multimodal anti-cancer therapies. IR involves the formation of reactive oxygen species (ROS) in targeted tissues. This is associated with subsequent cardiac dysfunction when applied during chest radiotherapy. We hypothesized that IR (i.e., ROS)-dependently impaired cardiac myocytes' Ca handling might contribute to IR-dependent cardiocellular dysfunction. Isolated ventricular mouse myocytes and the mediastinal area of anaesthetized mice (that included the heart) were exposed to graded doses of irradiation (sham 4 and 20 Gy) and investigated acutely (after ~1 h) as well as chronically (after ~1 week). IR induced a dose-dependent effect on myocytes' systolic function with acutely increased, but chronically decreased Ca transient amplitudes, which was associated with an acutely unaltered but chronically decreased sarcoplasmic reticulum (SR) Ca load. Likewise, in vivo echocardiography of anaesthetized mice revealed acutely enhanced left ventricular contractility (strain analysis) that declined after 1 week. Irradiated myocytes showed persistently increased diastolic SR Ca leakage, which was acutely compensated by an increase in SR Ca reuptake. This was reversed in the chronic setting in the face of slowed relaxation kinetics. As underlying cause, acutely increased ROS levels were identified to activate Ca/calmodulin-dependent protein kinase II (CaMKII). Accordingly, CaMKII-, but not PKA-dependent phosphorylation sites of the SR Ca release channels (RyR2, at Ser-2814) and phospholamban (at Thr-17) were found to be hyperphosphorylated following IR. Conversely, ROS-scavenging as well as CaMKII-inhibition significantly attenuated CaMKII-activation, disturbed Ca handling, and subsequent cellular dysfunction upon irradiation. Targeted cardiac irradiation induces a biphasic effect on cardiac myocytes Ca handling that is associated with chronic cardiocellular dysfunction. This appears to be mediated by increased oxidative stress and persistently activated CaMKII. Our findings suggest impaired cardiac myocytes Ca handling as a so far unknown mediator of IR-dependent cardiac damage that might be of relevance for radiation-induced cardiac dysfunction.

Nutritional support for acute kidney injury.

BACKGROUND: Treatment for acute kidney Injury (AKI) primarily relies on treating the underlying cause and maintaining the patient until kidney function has recovered. Enteral and parenteral nutrition are commonly used to treat nutritional disorders in AKI patients, however their efficacy in treating AKI are still debated. This review was first published in 2010. OBJECTIVES: To evaluate the effectiveness and safety of nutritional support for patients with AKI. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Chinese Biomedical Disc, VIP and China National Knowledge Infrastructure (CNKI).Date of last search: 4 July 2012 SELECTION CRITERIA: All randomised controlled trials (RCTs) reported for AKI and nutrition were included. DATA COLLECTION AND ANALYSIS: Authors independently assessed study quality and extracted data. Results were expressed as risk ratio (RR) with 95% confidence intervals (CI) or mean difference (MD). MAIN RESULTS: Eight studies (257 participants) were included. An overall pooled analysis was not performed due to the different interventions used and different outcomes measured. Selection bias was not reported (unclear) in six studies and was adequately reported (low) for random sequence generation in two studies. Participant/personnel blinding was adequately reported in one study and unclear in seven. Incomplete outcome reporting bias was low in six studies and high in two. Selective reporting was low in six studies, unclear in one study, and high in one study. No other biases were detected. There was a significant increase in recovery rate for AKI (RR 1.70, 95% CI 1.70 to 2.79) and survival in dialysed patients (RR 3.56, 95% CI 0.97 to 13.08) for intravenous essential L-amino acids (EAA) compared to hypertonic glucose alone. Compared to lower calorie-total parenteral nutrition (TPN), higher calorie-TPN did not improve estimated nitrogen balance, protein catabolic rate, or urea generation rate; but increased serum triglycerides, glucose, insulin need and nutritional fluid administration. There was no difference between groups in estimated nitrogen balance, but there were differences between urea nitrogen appearance (MD 0.98, 95% CI 0.25 to 1.71) and net protein utilisation (MD 21.50%, 95% CI 0.39 to 42.61). Urea nitrogen appearance was lower in the low nitrogen intake group than in the high nitrogen intake group. There was no significant difference in death between EAA and general amino acids (GAA) (RR 1.52, 95% CI 0.63 to 3.68). High dose amino acids did not improve cumulative water excretion, furosemide requirement, nitrogen balance or death compared to normal dose amino acids. Glucose+EAA+histidin had better nitrogen balance than glucose+GAA; glucose+nitrogen+fat significantly increased serum creatinine compared with glucose+GAA; glucose+EAA+histidin significantly improved nitrogen balance, U/P urea and serum creatinine, but increased plasma urea compared to glucose+nitrogen+fat. AUTHORS' CONCLUSIONS: There was insufficient evidence found to support the effectiveness of nutritional support for AKI. Further high quality studies are required to provide reliable evidence of the effect and safety of nutritional support.

[Visualization of right atrial flow patterns and quantification of pulmonary to systemic flow ratio in patients with atrial septal defect by vector flow mapping].

OBJECTIVE: To evaluate the ability of vector flow mapping (VFM) in visualizing right atrial flow and quantifying pulmonary to systemic flow ratio in patients with atrial septal defect (ASD). METHODS: VFM was performed on 30 patients with ASD and 50 healthy volunteers. The pulmonary to systemic flow ratio (Qp/Qs) was calculated using VFM and spectral doppler compared with that obtained through oximetric data derived from cardiac catheterization. RESULTS: Blood streams from superior and inferior caval veins did not collide but turned forward, contributing to a forward clockwise vortex during systole on the subcostal bi-atrial plane in the healthy volunteers. The vortex was disrupted continuously by a left to right shunt in the patients with ASD during the hole cardiac cycle. The Qp/Qs measured by VFM was less angle-dependent in all the cases than the other methods. The mean value of Qp/Qs of the healthy volunteers calculated by apical three-chamber view and apical five-chamber view ranged from 0.84:1 to 1.15:1, which is consistent with the theoretical value 1 of no left to right shunts. The values of Qp/Qs of patients with ASD measured by VFM and spectral doppler showed no significant differences with those obtained through oximetric data [(2.18 +/- 0.48) vs. (2.29 +/- 0.76), P = 0.29; (2.30 +/- 0.91) vs. (2.29 +/- 0.76), P = 0.86]. However, the Qp/Qs value measured by VFM had a better correlation with the oximetric data than that measured by spectral doppler (r = 0.71, P < 0.001 vs. r = 0.38, P < 0.05). The inter-observer and intraobserver variability of Qp/Qs measured by VFM was 9.84% and 9.86% respectively. CONCLUSION: VFM can visualize right atrial flow field in patients with ASD and quantify Qp/Qs in a more accurate way than spectral dopler.

[Evaluation of papillary muscle function of patients with chronic ischemic mitral regurgitation using two-dimensional speckle tracking imaging].

OBJECTIVE: To evaluate the papillary muscle function of patients with chronic ischemic mitral regurgitation (IMR) using two-dimensional speckle tracking imaging. METHODS: 119 patients with chronic IMR and 94 normal controls were enrolled in this study. The peak systolic strain (PSS) and peak systolic strain rate (PSSR) of the papillary muscle were assessed with two-dimensional strain software. The PSS and PSSR were compared between the patients with anterior myocardial infarct (AMI) and those with inferior myocardial infarct (IMI). The correlation between the degree of IMR and the position of MI was analysed. RESULTS: The patients with chronic IMR had significantly lower PSS and PSSR than the normal controls. The IMI patients had significantly lower PSS and PSSR than the AMI patients. The IMI patients had significantly higher degree of MR than the AMI patients. CONCLUSION: Two-dimensional speckle tracking imaging is a reliable method for assessing papillary muscle function.