The long term effects of uncoupling interventions as a therapy for dementia in humans.

In this paper we use simulation methods to study a hypothetical uncoupling agent as a therapy for dementia. We simulate the proliferation of mitochondrial deletion mutants amongst a population of wild-type in human neurons. Mitochondria play a key role in ATP generation. Clonal expansion can lead to the wild-type being overwhelmed by deletions such that a diminished population can no longer fulfil a cell's energy requirement, eventually leading to its demise. The intention of uncoupling is to reduce the formation of deletion mutants by reducing mutation rate. However, a consequence of uncoupling is that the energy production efficacy is also reduced which in turn increases wild-type copy number in order to compensate for the energy deficit. The results of this paper showed that uncoupling reduced the severity of dementia, however, there was some increase in cognitive dysfunction pre-onset of dementia. The effectiveness of uncoupling was dependent upon the timing of intervention relative to the onset of dementia and would necessitate predicting its onset many years in advance.

A comparison of mtDNA deletion mutant proliferation mechanisms.

In this paper we use simulation methods to investigate the proliferation of deletion mutations of mitochondrial DNA in neurons. We simulate three mtDNA proliferation mechanisms, namely, random drift, replicative advantage and vicious cycle. For each mechanism, we investigated the effect mutation rates have on neuron loss within a human host. We also compare heteroplasmy of each mechanism at mutation rates that yield the levels neuron loss that would be associated with dementia. Both random drift and vicious cycle predicted high levels of heteroplasmy, while replicative advantage showed a small number of dominant clones with a low background of heteroplasmy.

A comparison of clinical outcomes following atrial fibrillation ablation for heart failure patients with preserved or reduced left ventricular function: A systematic review and meta-analysis.

BACKGROUND: This review aims to determine if patients who undergo atrial fibrillation (AF) ablation with heart failure with preserved ejection fraction (HFpEF) do better, or worse or the same compared to patients with heart failure with reduced ejection fraction (HFrEF). METHODS: A search of MEDLINE and EMBASE was performed using the search terms: "atrial fibrillation", "ablation" and terms related to HFpEF and HFrEF in order to identify studies that evaluated one or more of i) AF recurrence, ii) periprocedural complications and iii) adverse outcomes at follow up for patients with HFpEF and HFrEF who underwent AF ablation. Data was extracted from included studies and statistically pooled to evaluate adverse events and AF recurrence. RESULTS: 5 studies were included in this review and the sample size of the studies ranged from 91 to 521 patients with heart failure. There was no significant difference in the pooled rate for no AF or symptom recurrence after AF ablation comparing patients with HFpEF vs HFrEF (RR 1.07 95%CI 0.86-1.33, p = 0.15). The most common complications were access site complications/haematoma/bleeding which occurred in similar proportion in each group; HFpEF (3.1%) and HFrEF (3.1%). In terms of repeat ablations, two studies were pooled to yield a rate of 78/455 (17.1%) for HFpEF vs 24/279 (8.6%) for HFrEF (p = 0.001. CONCLUSIONS: Heart failure patients with preserved or reduced ejection fraction have similar risk of AF or symptom recurrence after AF ablation but two studies suggest that patients with HFpEF are more likely to have repeat ablations.

The Effect of Mitochondrial DNA Half-Life on Deletion Mutation Proliferation in Long Lived Cells.

The proliferation of mitochondrial DNA (mtDNA) with deletion mutations has been linked to aging and age related neurodegenerative conditions. In this study we model the effect of mtDNA half-life on mtDNA competition and selection. It has been proposed that mutation deletions ([Formula: see text]) have a replicative advantage over wild-type ([Formula: see text]) and that this is detrimental to the host cell, especially in post-mitotic cells. An individual cell can be viewed as forming a closed ecosystem containing a large population of independently replicating mtDNA. Within this enclosed environment a selfishly replicating [Formula: see text] would compete with the [Formula: see text] for space and resources to the detriment of the host cell. In this paper, we use a computer simulation to model cell survival in an environment where [Formula: see text] compete with [Formula: see text] such that the cell expires upon [Formula: see text] extinction. We focus on the survival time for long lived post-mitotic cells, such as neurons. We confirm previous observations that [Formula: see text] do have a replicative advantage over [Formula: see text]. As expected, cell survival times diminished with increased mutation probabilities, however, the relationship between survival time and mutation rate was non-linear, that is, a ten-fold increase in mutation probability only halved the survival time. The results of our model also showed that a modest increase in half-life had a profound affect on extending cell survival time, thereby, mitigating the replicative advantage of [Formula: see text]. Given the relevance of mitochondrial dysfunction to various neurodegenerative conditions, we propose that therapies to increase mtDNA half-life could significantly delay their onset.

Why antioxidant therapies have failed in clinical trials.

In spite of considerable research, and many clinical trials involving thousands of patients, there is a conspicuous lack of antioxidant therapies available. In this paper we present results for the interaction and neutralization of a free radical species. We adopt two modeling techniques, one based upon Gillespieâ;;s Stochastic Simulation Algorithm and one based upon a discrete Markov chain. An advantage of these models is that they incorporate the number of molecules present per unit volume, and with the Markov chain model, the relative dimensions of these molecules. By means of these models we question the basis of antioxidant therapies based on trapping or scavenging of reactive species. We demonstrate the extraordinary capacity of the enzymatic antioxidant defenses relative to non-enzymatic defenses. We conclude that, if the concentration of an non-enzymatic antioxidant is too low there is little chance of collision and interaction with a free radical species. Furthermore, if the rate of reaction between the free radical and the non-enzymatic antioxidant is below a necessary threshold then the effect of an antioxidant will be dwarfed by the free radical defense systems naturally present. As such we suggest that failure of most antioxidant therapies in clinical trials is to be expected.

Extracellular purines in lung endothelial permeability and pulmonary diseases.

The purinergic signaling system is an evolutionarily conserved and critical regulatory circuit that maintains homeostatic balance across various organ systems and cell types by providing compensatory responses to diverse pathologies. Despite cardiovascular diseases taking a leading position in human morbidity and mortality worldwide, pulmonary diseases represent significant health concerns as well. The endothelium of both pulmonary and systemic circulation (bronchial vessels) plays a pivotal role in maintaining lung tissue homeostasis by providing an active barrier and modulating adhesion and infiltration of inflammatory cells. However, investigations into purinergic regulation of lung endothelium have remained limited, despite widespread recognition of the role of extracellular nucleotides and adenosine in hypoxic, inflammatory, and immune responses within the pulmonary microenvironment. In this review, we provide an overview of the basic aspects of purinergic signaling in vascular endothelium and highlight recent studies focusing on pulmonary microvascular endothelial cells and endothelial cells from the pulmonary artery vasa vasorum. Through this compilation of research findings, we aim to shed light on the emerging insights into the purinergic modulation of pulmonary endothelial function and its implications for lung health and disease.

Influence of tumor histology on preoperative staging accuracy of breast metastases to the axilla.

Histologic confirmation of axillary nodal metastases preoperatively avoids a sentinel node biopsy and enables a one step surgical procedure. The aim of this study was to establish the local positive predictive value of axillary ultrasound (AUS) and guided needle core biopsy (NCB) in axillary staging of breast cancer, and to identify factors influencing yield. A prospective audit of 142 consecutive patients (screening and symptomatic) presenting from 1st December 2008-31st May 2009 with breast lesions categorized R4-R5, who underwent a preoperative AUS, and proceeded to surgery was undertaken. Ultrasound-guided NCB was performed on nodes radiologically classified R3-R5. Lymph node size, number, and morphological features were documented. Yield was correlated with tumor size, grade, and histologic type. AUS/NCB was correlated with post surgical pathologic findings to determine sensitivity, specificity, positive and negative predictive value of AUS and NCB. A total of 142 patients underwent surgery, of whom 52 (37%) had lymph node metastases on histology. All had a preoperative AUS, 51 (36%) had abnormal ultrasound findings. 46 (90%) underwent axillary node NCB of which 24 (52%) were positive. The smallest tumor size associated with positive nodes at surgery was 11.5 mm. The sensitivity of AUS was 65%. Specificity was 81%, with a positive predictive value (PPV) of 67% and negative predictive (NPV) value of 80%. Sensitivity of U/S-guided NCB was 75%, with a specificity of 100%, PPV 100% and NPV 64%. Sensitivity of AUS for lobular carcinoma was 36% versus 76% for all other histologies. Sensitivity of NCB for lobular cancer was 33% versus 79% for all other histologies. The most significant factor producing discordance between preoperative AUS and definitive histologic evidence of lymph node metastasis was tumor type. Accurate preoperative lymph node staging was prejudiced by lobular histology (p < 0.0019).

The prevalence of dementia in humans could be the result of a functional adaptation.

In this paper we propose that high copy number of the mitochondrial genome in neurons is a functional adaptation. We simulated the proliferation of deletion mutants of the human mitochondrial genome in a virtual mitochondrion and recorded the cell loss rates due to deletions overwhelming the wild-type. Our results showed that cell loss increased with mtDNA copy number. Given that neuron loss equates to cognitive dysfunction, it would seem counterintuitive that there would be a selective pressure for high copy number over low. However, for a low copy number, the onset of cognitive decline, while mild, started early in life. Whereas, for high copy number, it did not start until middle age but progressed rapidly. There could have been an advantage to high copy number in the brain if it delayed the onset of cognitive decline until after reproductive age. The prevalence of dementia in our aged population is a consequence of this functional adaptation.

What Are the Causes of Death among Patients Admitted to a Contemporary Tertiary-Level Cardiology Department? An Analysis of 10 Years of Morbidity and Mortality Meetings.

Despite the efforts to deliver the best evidence-based care, in-hospital death is an inevitable event among some patients hospitalized in cardiology departments. We conducted a retrospective evaluation of mortality events from inpatient admissions to the cardiology department between 2010 and 2019. Data were collected from morbidity and mortality meeting presentations that evaluated comorbidities, medical history, treatments, and causes of death for the overall cohort and according to age group and sex. There were 1182 registered deaths. The most common causes of death among patients were acute myocardial infarction (AMI, 53.0%), heart failure (HF, 11.7%), cardiac arrest (CA, 6.6%), HF with complication/defined cardiomyopathy (6.3%), and sepsis (4.4%). We observed a decline in deaths from AMI from 61.9% in 2010 to 46.7% in 2019, while there was a clear increase in deaths from HF (11.1% in 2010 to 25.9% in 2019). Compared to patients ≥65 years, younger patients were more likely to have died from CA (15.7% vs. 4.3%, p < 0.001) and other cardiac reasons (3.0% vs. 0.4%, p < 0.001). The majority of deaths were due to AMI, HF, and CA. We observed a significant declining trend in the proportion of deaths due to AMI in recent years, with an increase in deaths due to HF.

Bivariate phase-rectified signal averaging for assessment of spontaneous baroreflex sensitivity: normalization of the results.

BACKGROUND: Previously proposed technique for assessment of spontaneous baroreflex sensitivity (BRS) based on bivariate phase-rectified signal averaging measures averaged R-R interval (RRI) changes triggered by beat-to-beat increases in systolic blood pressure (SBP). In this study, we investigate a normalized version of the method that relates the averaged RRI changes to the triggering blood pressure changes, thus providing the results in measurement units comparable with existing literature. METHODS: Data of previously reported prospective observational study were used. In each of 146 heart failure patients presenting with sinus rhythm, 10-minute recordings of electrocardiogram and arterial and blood pressures were obtained in the supine resting position. The averaged RRI increases initiated by beat-to-beat SBP increases were measured (original BRS result in milliseconds) and normalized for the averaged beat-to-beat SBP increases (normalized BRS result in milliseconds per millimeters of mercury). Both results were compared in terms of predicting all-cause mortality during a mean follow-up of 2.7 ± 1.1 years when 42 patients (28.8%) died. RESULTS: Both types of results were highly correlated (r = 0.938, P < .001) and led to similarly strong separation of high- and low-risk groups. The receiver operator characteristics of both indices were well within the 95% confidence intervals of each other, and the areas under the characteristics were practically identical: 71.1% (95% confidence interval, 60.7%-80.9%) for original BRS and 69.7% (58.9%-79.2%) for normalized BRS. CONCLUSION: The results might question the concept of a linear relationship between the SBP changes and RRI changes. The phase-rectified signal averaging-based assessment of BRS may be used with equal legitimacy in the nonnormalized and normalized forms; the normalized form provides results in conventional measurement units.

Cardiac care of children with dystrophinopathy and females carrying DMD-gene variations.

OBJECTIVE: We provide succinct, evidence-based and/or consensus-based best practice guidance for the cardiac care of children living with Duchenne muscular dystrophy (DMD) as well as recommendations for screening and management of female carriers of mutations in the DMD-gene. METHODS: Initiated by an expert working group of UK-based cardiologists, neuromuscular clinicians and DMD-patient representatives, draft guidelines were created based on published evidence, current practice and expert opinion. After wider consultation with UK-cardiologists, consensus was reached on these best-practice recommendations for cardiac care in DMD. RESULTS: The resulting recommendations are presented in the form of a succinct care pathway flow chart with brief justification. The guidance signposts evidence on which they are based and acknowledges where there have been differences in opinion. Guidelines for cardiac care of patients with more advanced cardiac dystrophinopathy at any age have also been considered, based on the previous published work of Quinlivan et al and are presented here in a similar format. The recommendations have been endorsed by the British Cardiovascular Society. CONCLUSION: These guidelines provide succinct, reasoned recommendations for all those managing paediatric patients with early or advanced stages of cardiomyopathy as well as females with cardiac dystrophinopathy. The hope is that this will result in more uniform delivery of high standards of care for children with cardiac dystrophinopathy, so improving heart health into adulthood through timely earlier interventions across the UK.

Metabolism and pharmacokinetics of naronapride (ATI-7505), a serotonin 5-HT(4) receptor agonist for gastrointestinal motility disorders.

The absorption and disposition of the serotonin 5-HT(4) receptor agonist, naronapride (6-[(3S,4R)-4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-1-yl]-hexanoic acid 1-aza-bicyclo[2,2,2]oct-(R)-3-yl ester dihydrochloride; ATI-7505), were evaluated in healthy males given a single 120-mg oral dose of (14)C-labeled compound. Serial blood samples and complete urine and feces were collected up to 552 h postdose. Naronapride was extensively metabolized, undergoing rapid hydrolysis to 6-[(3S,4R)-4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-1-yl]-hexanoic acid (ATI-7500) with stoichiometric loss of quinuclidinol. ATI-7500 was either N-glucuronidated on the phenyl ring or its hexanoic acid side chain underwent two-carbon cleavage, probably through a ß-oxidation metabolic pathway, to form 4-[(3S,4R)-4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-1-yl]-butanoic acid (ATI-7400). ATI-7400 underwent further side-chain oxidation to form 2-[(3S,4R)-4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-1-yl]-acetic acid (ATI-7100). Quinuclidinol, ATI-7500, ATI-7400, and ATI-7100 were the major metabolites, with plasma area under the curve values approximately 72-, 17-, 8-, and 2.6-fold that of naronapride. Naronapride, ATI-7500, ATI-7400, and ATI-7100 accounted for 32.32, 36.56, 16.28, and 1.58%, respectively, of the dose recovered in urine and feces. ATI-7400 was the most abundant radioactive urinary metabolite (7.77%), and ATI-7500 was the most abundant metabolite in feces (35.62%). Fecal excretion was the major route of elimination. Approximately 32% of the dose was excreted unchanged in feces. Naronapride, ATI-7500, and quinuclidinol reached peak plasma levels within 1 h postdose. Peak ATI-7400 and ATI-7100 concentrations were reached within 1.7 h, suggesting rapid ATI-7500 metabolism. Naronapride plasma terminal half-life was 5.36 h, and half-lives of the major metabolites ranged from 17.69 to 33.03 h. Naronapride plasma protein binding was 30 to 40%. The mean blood/plasma radioactivity ratio indicated minimal partitioning of (14)C into red blood cells.

Bivariate phase-rectified signal averaging for assessment of spontaneous baroreflex sensitivity: pilot study of the technology.

BACKGROUND: Assessment of spontaneous baroreflex sensitivity (BRS), an index of autonomic function, poses practical challenges. In this pilot study, we propose a novel technique for assessment of spontaneous BRS based on bivariate phase-rectified signal averaging (PRSA). This is an extension of the monovariate PRSA technology used for calculation of deceleration capacity. METHODS: A prospective, observational study was conducted in a training cohort of 146 patients with heart failure (New York Heart Association class 2.7 ± 0.8, left ventricular ejection fraction 23.6% ± 9.0%) presenting with sinus rhythm. In all patients, 10-minute recordings of ECG and arterial and blood pressure were obtained in the supine resting position. The algorithm for BRS assessment based on bivariate PRSA (BRS(PRSA)) included (1) identification of heartbeat intervals occurring at the time of systolic pressure increases, (2) selection of heartbeat adjacent interval sections, (3) alignment and (4) averaging of these segments, and (5) quantification of the average heart beat interval change by Haar wavelet analysis. Primary end point was death of any cause. During mean follow-up of 2.7 ± 1.1 years, 42 patients (28.8%) died. RESULTS: BRS(PRSA) was significantly associated with the primary end point (3.7 ± 5.3 ms vs -0.33 ± 6.6 ms in survivors and nonsurvivors, respectively). BRS(PRSA) yielded an area under the receiver operating characteristics curve of 69.8% (95% confidence interval, 59.9-79.7), which was comparable to the area under the curve of left ventricular ejection fraction (70.4%; 95% confidence interval, 61.3-79.5). Using the optimum dichotomy for BRS(PRSA) of 1.14 milliseconds, 52 (36%) patients had an abnormal BRS(PRSA). The 3-year mortality risk of these patients was 45.3% compared to 19.0% in patients with normal BRS(PRSA). On multivariate analysis, abnormal BRS(PRSA) was an independent risk factor from left ventricular ejection fraction ≤ 30% and New York Heart Association class > II. CONCLUSION: BRS(PRSA) is an independent and strong predictor of mortality in patients with heart failure. Prospective validation and comparisons with standard measures of BRS are needed.

MAGNETO cardiography parameters to predict future Sudden Cardiac Death (MAGNETO-SCD) or ventricular events from implantable cardioverter defibrillators: study protocol, design and rationale.

INTRODUCTION: Predicting sudden cardiac death (SCD) is challenging as current risk predictors have significant limitations. Evaluating magnetocardiogram (MCG) parameters could be of great value and we plan to assess the capability of a new mobile unshielded MCG device in predicting SCD and ventricular arrhythmias (VA) in patients undergoing implantable cardioverter defibrillator (ICD) implantation. METHODS AND ANALYSIS: A prospective multicentre (University Hospitals Coventry and Warwickshire (UHCW) National Health Service (NHS) Trust/University Hospital North Midlands NHS Trust, UK) observational study evaluating the VitalScan MCG (Creavo Medical Technologies, UK) to predict future VA risk; 270 patients meeting criteria for primary or secondary prevention ICDs (ischaemic or non-ischaemic aetiology) are being recruited. The first patient was recruited September 2019 and the study will be completed at final participant follow-up. The primary endpoint is appropriate ICD therapy for VA, secondary endpoint is SCD. Previous trials using MCG identified late QRS signals/QRS fragmentation as potential indicators of SCD in small samples using large shielded expensive MCG devices that were difficult to use clinically. It is hoped the MAGNETO-SCD trial will show this new MCG device can provide real world risk stratification for SCD/VA risk. The trial has recruited 25 patients (13 with secondary prevention indication) from a single site (UHCW) with recruitment starting at the second site in March 2020. ETHICS AND DISSEMINATION: Research Ethics Committee, Yorkshire and Humber Sheffield Research Ethics Committee UK (Ref: 19/YH/0143) and Health Research Authority (IRAS reference 254466, EDGE ID: 123146) approval received on 17/07/2019. The Medicines and Healthcare products Regulatory Agency approval received 11/07/2019. Results will be disseminated via a peer-reviewed publication and presentation at international conferences. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov Registry (NCT04352816) and EU Clinical Trials Registry (EudraCT2019-002994-78).

Twiddler's syndrome in a patient with a biventricular-defibrillator device.

A 69-year-old man with previous myocardial infarction and proximal three-vessel coronary artery disease underwent coronary bypass grafting, with an epicardial lead placed on the lateral left ventricular wall during surgery. A cardiac resynchronization therapy-defibrillator (CRT-D) device was subsequently implanted using active right atrial and right ventricular leads, with the pulse generator placed in a pre-pectoral pocket. Four weeks later, the right atrial lead was failing to sense or capture, and chest X-ray revealed it had pulled out of the myocardium and coiled up behind the device; a diagnosis of Twiddler's syndrome was made. Twiddler's syndrome is unusual in patients with CRT-D devices and may cause symptoms such as inappropriate shocks and hiccups. Placement of the pulse generator in a sub-pectoral position may help prevent it.

Temporary pacing wire in the coronary sinus: a novel treatment of acute heart failure?

Treatment of acute heart failure relies initially on medical therapy. Patients can be considered for cardiac resynchronization therapy once they are able to lie flat for several hours. However, placement of a temporary pacing wire (TPW) into the coronary sinus may allow the patient to receive resynchronization therapy in the acute phase. We report a case of a patient who had a dramatic improvement of symptoms and blood pressure after a TPW was placed in the coronary sinus.

Early invasive versus conservative treatment in patients with failed fibrinolysis--no late survival benefit: the final analysis of the Middlesbrough Early Revascularisation to Limit Infarction (MERLIN) randomized trial.

BACKGROUND: Early (30 days) and midterm (6 months) clinical outcomes in trials comparing rescue angioplasty (rescue percutaneous coronary intervention [rPCI]) with conservative treatment of failed fibrinolysis complicating ST-segment elevation myocardial infarction have shown variable results. Whether early rPCI confers late (up to 3 years) clinical benefits is not known. METHODS: The MERLIN trial compared rPCI and a conservative strategy in patients with failed fibrinolysis complicating ST-segment elevation myocardial infarction. Three hundred seven patients with electrocardiographic evidence of failure to reperfuse at 60 minutes were included. Patients in cardiogenic shock were excluded. Thirty-day and 1-year results have been reported. Results of 3 years of follow-up are presented. RESULTS: Three-year mortality in the conservative arm and rPCI, respectively, was 16.9% versus 17.6% (P = .9, relative difference [RD] -0.8, 95% CI [-9.3 to 7.8]). Death rates were similar (3.9% vs 3.2%) between 1- and 3-year follow-up, respectively. The incidence of the composite secondary end point of death, reinfarction, stroke, unplanned revascularization, or heart failure was significantly higher in the conservative arm (64.3% vs 49%, P = .01, RD 15.3, 95% CI [4.2-26]). There was no significant difference in the rate of reinfarction (0.7% vs 0.7%) or heart failure (1.3% vs 2.7%) between 1 and 3 years between the conservative and rPCI arms, respectively. The incidence of subsequent unplanned revascularization at 3 years was significantly higher in the conservative arm (33.8% vs 14.4%, P < .01, RD 19.4, 95% CI [10-28.7]), most of which occurred within 1 year; the rates between 1 and 3 years were 3.9% in the conservative arm versus 2% in the rPCI arm. There was a trend toward fewer strokes in the conservative arm at 3 years (conservative arm 2.6% vs rPCI 6.5%, P = .1, RD -3.9%, 95% CI [-9.4 to 0.8]), with similar stroke rates (1.3% vs 1.3%) between 1- and 3-year follow-up. CONCLUSIONS: Rescue angioplasty did not confer a late survival advantage at 3 years. The composite end point occurred less often in the rPCI arm mainly because of fewer unplanned revascularization procedures in the early phase of follow-up. The highest risk of clinical events in patients with failed reperfusion is in the first year, beyond which the rate of clinical events is low.

A prospective randomised controlled trial to determine the early and late reactions after the use of iopamidol 340 (Niopam) and iomeprol 350 (Iomeron) in cardiac catheterisation.

UNLABELLED: A new generation of intravascular contrast agents, the non-ionic monomers have safety profiles that are superior to those of older ionic compounds. There are, however, significant differences between these agents. AIM: The aim of this study was to determine the incidence of early (<24h) and late (>24h to 7 days) reactions to two non-ionic contrast agents currently used during cardiac catheterisation: iopamidol 340 (Niopam Bracco UK Ltd.) and iomeprol 350 (Iomeron Bracco UK Ltd.). METHODS: This was a prospective, randomised, double blinded trial. One thousand nine hundred and eighty-five patients undergoing cardiac catheterisation received one of the following contrast agents on a weekly basis: iopamidol 340 (Niopam) and iomeprol 350 (Iomeron). Reactions that were possibly related to the contrast agents were recorded on predefined data collection forms during the first 24h of the procedure (early reaction) and after 24h to 7 days (late reaction) by means of a questionnaire. RESULTS: The baseline characteristics were matched in both the groups. There was no significant difference in the incidence of heat sensation experienced between the two groups (p=0.1). Early non-heat reactions occurred in 2.7% of patients receiving iopamidol 340 (Niopam) and 4% of those receiving iomeprol 350 (Iomeron) (p=0.1). Significant electrocardiographic changes were recorded in 1.7% of patients who received iopamidol 340 (Niopam), and 1% of those who received iomeprol 350 (Iomeron) (p=0.2). Bradycardia occurred more frequently in the iopamidol 350 group (0.8%) compared to the iomeprol 350 group (0.1%) p=0.02. Late reactions occurred in 16.2% of those receiving iopamidol 340 (Niopam) and 21.7% of those receiving iomeprol 350 (Iomeron) (p=0.02). A total of 23 (3.7%) patients in the iopamidol group and 39 (6.2%) patients in the iomeprol group reported nausea, p=0.01. CONCLUSIONS: The incidence of early adverse reactions was similar with the two non-ionic contrast agents. Although bradycardia was slightly more frequent using iopamidol 340, nausea was reported more commonly 24h after the procedure in patients receiving Iomeron 350 (Iomeron). We conclude that there were only minor clinical differences between these agents; both are safe and well tolerated.

A randomized trial of prophylactic antiarrhythmic agents (amiodarone and sotalol) in patients with atrial fibrillation for whom direct current cardioversion is planned.

UNLABELLED: Antiarrhythmic agents enhance maintenance of sinus rhythm (SR) after direct current cardioversion (DCC) for atrial fibrillation but there are few comparative trials. BACKGROUND: The aims of the study were (1) to establish whether patients successfully cardioverted to SR are more likely to stay in SR over 6 months if taking amiodarone or sotalol, and if so, to establish whether one agent is better than the other; (2) to establish whether taking amiodarone or sotalol is better at achieving chemical cardioversion within the 6 weeks before DCC; and (3) to establish whether DCC is more likely to be successful on a drug. METHODS: Randomized, prospective, nonblinded, controlled study of treatment with either amiodarone (n = 27), sotalol (n = 36), or no antiarrhythmic agent (n = 31). RESULTS: Chemical cardioversion occurred in 7 patients in the amiodarone group (A), 7 patients in the sotalol group (S), but none in the no-antiarrhythmic group (N). A total of 33 (92%) patients in the sotalol group, 22 (81%) patients in the amiodarone group, and 23 (74%) patients in the no-antiarrhythmic group were in SR after cardioversion. Of the original cohort of patients, 17 (63%) patients in the amiodarone group remained in SR at 6-month follow-up, compared with 14 (39%) in the sotalol group and 5 (16%) in the no-antiarrhythmic group (A vs N, P < .0002, P < .0006B [after Bonferroni correction]; A vs S, P = .05, P = .15B; and S vs N, P = .03, P = .09B). CONCLUSIONS: Amiodarone and sotalol achieved chemical cardioversion before planned electrical cardioversion in 26% and 19% of patients, respectively. After successful cardioversion, amiodarone appears better than sotalol at maintaining SR at 6 months.