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Objective: To compare the relative efficacy of anteroanterior v anteroposterior electrode pad positions for external cardioversion of atrial fibrillation.Design: Prospective randomised trial.Setting: Tertiary referral cardiology centre in the United Kingdom.Patients: 90 patients undergoing elective cardioversion for atrial fibrillation.Interventions: Cardioversion was attempted with self adhesive electrode pads with an area of 106 cm2 placed either in the anteroanterior (AA) or anteroposterior (AP) positions. Initial shock was 100 J which, if unsuccessful, was followed by 200 J, 300 J, and 360 J if required. Peak current and transthoracic impedance were measured.Main Outcome Measures: Cardioversion success rate and energy requirements.Results: Cardioversion was successful in 81% of the patients (73/90). There was no statistically significant difference in the cardioversion success rate (AA 84%, 38/45 patients; AP 78%, 35/45 patients; p = 0.42) or mean (SD) energy requirement for all patients (AA 223 (96.1) J; AP 232 (110) J) or for patients who were successfully cardioverted (AA 197.9 (82.4) J; AP 195.4 (97.2) J; p = 0.9) between the two pad positions. The mean transthoracic impedance (TTI) for the first shock (AA 77.5 (18.4) ohms; AP 73.7 (18.7) ohms; p = 0.34) was not significantly different between the two groups. TTI correlated significantly with body mass index, percentage body fat, and chest AP diameter. There was a progressive decrease in TTI with serial shocks. While aetiology and TTI were the two independent significant predictive factors for energy requirement, duration of atrial fibrillation was the only independent predictor of cardioversion success in a multivariate analysis.Conclusions: Electrode pad position is not a determinant of cardioversion success rate or energy requirement. [ABSTRACT FROM AUTHOR]

Background: Androgen deprivation therapy (ADT), with a proven role in prostate cancer management, has been associated with various cardiovascular diseases. However, few studies have investigated these associations by type of ADT, particularly for newer ADTs such as the gonadotropin-releasing hormone (GnRH) antagonist degarelix. We investigated the risk of cardiovascular disease by type of ADT in a real-world setting., Methods: We identified men newly diagnosed with prostate cancer, from 2009 to 2015, from the Scottish Cancer Registry and ADTs from the nationwide Prescribing Information System. Cardiovascular events were based upon hospitalization (from hospital records) or death from cardiovascular disease (from death records). We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular events with time-varying ADT exposure, comparing ADT users with untreated patients, after adjusting for potential confounders, including prior cardiovascular disease., Results: The cohort contained 20,216 prostate cancer patients, followed for 73,570 person-years, during which there were 3,853 cardiovascular events. ADT was associated with a 30% increase in cardiovascular events (adjusted HR = 1.3; 95% CI = 1.2, 1.4). This reflected increases in cardiovascular events associated with GnRH agonists (adjusted HR = 1.3; 95% CI = 1.2, 1.4), degarelix (adjusted HR = 1.5; 95% CI = 1.2, 1.9), but not bicalutamide monotherapy (adjusted HR = 1.0; 95% CI = 0.82, 1.3)., Conclusions: There were increased risks of cardiovascular disease with the use of GnRH agonists and degarelix, but not with bicalutamide monotherapy. This is the first study to observe increased cardiovascular risks with degarelix, but the cause of this association is unclear and merits further investigation.

Background Left circumflex culprit is often missed by the standard 12-lead ECG . Extended lead systems (body surface potential map [ BSPM ]) should improve the diagnosis of culprit left circumflex stenosis with myocardial infarction. Methods and Results Retrospective analysis of a hospital research registry (August 2000-August 2010) comprising consecutive patients with (1) ischemic-type chest pain at rest; (2) 12-lead ECG and 80-lead BSPM at first medical contact; and (3) cardiac troponin-T 12 hours after symptom onset and/or creatine kinase MB fraction, were undertaken. Enrolled in the cohort were patients with culprit left circumflex stenosis (thrombolysis in myocardial infarction flow grade 0/1) at angiography. Acute myocardial infarction AMI was defined as cardiac troponin-T ≥0.1 μg/L and/or creatine kinase MB fraction >2 upper limits of normal. Enrolled were 482 patients: 168 had exclusion criteria. Of the remaining 314 (age 64±11 years; 62% male), 254 (81%) had AMI : of these, 231 had BSPM STE -sensitivity 0.91, specificity 0.72, positive predictive value 0.93, negative predictive value 0.65, and c-statistic 0.803 for AMI ( P<0.001). Of those with BSPM STE and AMI (n=231), STE was most frequently detected in the posterior (n=111, 48%), lateral (n=53, 23%), inferior (n=39, 17%), and right ventricular (n=21, 9%) territories. Conclusions Among patients with 12-lead ECG non-ST-segment-elevation myocardial infarction and culprit left circumflex stenosis, initial BSPM identifies ST-segment elevation beyond the territory of the 12-lead ECG . Greater use of the BSPM may result in earlier identification of AMI , which may lead to more rapid reperfusion.

Introduction: Epicardial potentials (EPs) derived from the body surface potential map (BSPM) improve acute myocardial infarction (AMI) diagnosis. In this study, we compared EPs derived from the 80-lead BSPM using a standard thoracic volume conductor model (TVCM) with those derived using a patient-specific torso model (PSTM) based on body mass index (BMI)., Methods: Consecutive patients presenting to both the emergency department and pre-hospital coronary care unit between August 2009 and August 2011 with acute ischaemic-type chest pain at rest were enrolled. At first medical contact, 12-lead electrocardiograms and BSPMs were recorded. The BMI for each patient was calculated. Cardiac troponin T (cTnT) was sampled 12 hours after symptom onset. Patients were excluded from analysis if they had any ECG confounders to interpretation of the ST-segment. A cardiologist assessed the 12-lead ECG for ST-segment elevation myocardial infarction by Minnesota criteria and the BSPM. BSPM ST-elevation (STE) was ⩾0.2 mV in anterior, ⩾0.1 mV in lateral, inferior, right ventricular or high right anterior and ⩾0.05 mV in posterior territories. To derive EPs, the BSPM data were interpolated to yield values at 352 nodes of a Dalhousie torso. Using an inverse solution based on the boundary element method, EPs at 98 cardiac nodes positioned within a standard TVCM were derived. The TVCM was then scaled to produce a PSTM using a model developed from computed tomography in 48 patients of varying BMIs, and EPs were recalculated. EPs >0.3 mV defined STE. A cardiologist blinded to both the 12-lead ECG and BSPM interpreted the EP map. AMI was defined as cTnT ⩾0.1 µg/L., Results: Enrolled were 400 patients (age 62 ± 13 years; 57% male); 80 patients had exclusion criteria. Of the remaining 320 patients, the BMI was an average of 27.8 ± 5.6 kg/m 2 . Of these, 180 (56%) had AMI. Overall, 132 had Minnesota STE on ECG (sensitivity 65%, specificity 89%) and 160 had BSPM STE (sensitivity 81%, specificity 90%). EP STE occurred in 165 patients using TVCM (sensitivity 88%, specificity 95%; p < 0.001) and in 206 patients using PSTM (sensitivity 98%, specificity 79%; p < 0.001). Of those with AMI by cTnT and EPs ⩽0.3 mV using TVCM ( n = 22), 18 (82%) patients had EPs >0.3 mV when an individualised PSTM was used., Conclusion: Among patients presenting with ischaemic-type chest pain at rest, EPs derived from BSPM using a novel PSTM significantly improve sensitivity for AMI diagnosis.

Background: Observational studies suggest that patients with heart failure have a tendency to a reduced status of a number of micronutrients and that this may be associated with an adverse prognosis. A small number of studies also suggest that patients with heart failure may have reduced dietary intake of micronutrients, a possible mechanism for reduced status., Objective: The aims of this study were to assess dietary micronutrient intake and micronutrient status in a group of patients with heart failure., Methods: Dietary intake was assessed in 79 outpatients with chronic stable heart failure with a reduced ejection fraction using a validated food frequency questionnaire. Blood concentrations of a number of micronutrients, including vitamin D, were measured in fasting blood samples, drawn at the time of food frequency questionnaire completion., Results: More than 20% of patients reported intakes less than the reference nutrient intake or recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, and iodine. More than 5% of patients reported intakes less than the lower reference nutrient intake or minimum recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, selenium, and iodine. Vitamin D deficiency (plasma total 25-hydroxy-vitamin D concentration <50 nmol/L) was observed in 75.6% of patients., Conclusions: Vitamin D deficiency was common in this group of patients with heart failure. Based on self-reported dietary intake, a substantial number of individuals may not have been consuming enough vitamin D and a modest number of individuals may not have been consuming enough riboflavin, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, or iodine to meet their dietary needs.

More than half of those born after 1960 will develop cancer during their lifetime. Fortunately, owing to improved diagnosis and treatment, cure rates have risen steadily over the last three decades. With an increased survivorship, more will experience adverse effects of cancer therapeutics on the heart. As the oncologist's focus begins to encompass the issues of cancer survivorship, awareness of the management of cardiac toxicity would be prudent for all physicians looking after patients with cancer.

Objective: To assess the cost-effectiveness of cardiac CT compared with exercise stress testing (EST) in improving the health-related quality of life of patients with stable chest pain., Methods: A cost-utility analysis alongside a single-centre randomised controlled trial carried out in Northern Ireland. Patients with stable chest pain were randomised to undergo either cardiac CT assessment or EST (standard care). The main outcome measure was cost per quality adjusted life year (QALY) gained at 1 year., Results: Of the 500 patients recruited, 250 were randomised to cardiac CT and 250 were randomised to EST. Cardiac CT was the dominant strategy as it was both less costly (incremental total costs -£50.45; 95% CI -£672.26 to £571.36) and more effective (incremental QALYs 0.02; 95% CI -0.02 to 0.05) than EST. At a willingness-to-pay threshold of £20 000 per QALY the probability of cardiac CT being cost-effective was 83%. Subgroup analyses indicated that cardiac CT appears to be most cost-effective in patients with a likelihood of coronary artery disease (CAD) of <30%, followed by 30%-60% and then >60%., Conclusions: Cardiac CT is cost-effective compared with EST and cost-effectiveness was observed to vary with likelihood of CAD. This finding could have major implications for how patients with chest pain in the UK are assessed, however it would need to be validated in other healthcare systems., Trial Registration Number: (ISRCTN52480460); results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Application of intermedin/adrenomedullin-2 (IMD/AM-2) protects cultured human cardiac vascular cells and fibroblasts from oxidative stress and simulated ischaemia-reoxygenation injury (I-R), predominantly via adrenomedullin AM1 receptor involvement; similar protection had not been investigated previously in human cardiomyocytes (HCM). Expression of IMD, AM and their receptor components was studied in HCM. Receptor subtype involvement in protection by exogenous IMD against injury by simulated I-R was investigated using receptor component-specific siRNAs. Direct protection by endogenous IMD against HCM injury, both as an autocrine factor produced in HCM themselves and as a paracrine factor released from HCMEC co-cultured with HCM, was investigated using peptide-specific siRNA for IMD. IMD, AM and their receptor components (CLR, RAMPs1-3) were expressed in HCM. IMD 1nmol L(-1), applied either throughout ischaemia (3h) and re-oxygenation (1h) or during re-oxygenation (1h) alone, attenuated HCM injury (P<0.05); cell viabilities were 59% and 61% respectively vs. 39% in absence of IMD. Cytoskeletal disruption, protein carbonyl formation and caspase activity followed similar patterns. Pre-treatment (4 days) of HCM with CLR and RAMP2 siRNAs attenuated (P<0.05) protection by exogenous IMD. Pre-treatment of HCMEC with IMD (and AM) siRNA augmented (P<0.05) I-R injury: cell viabilities were 22% (and 32%) vs. 39% untreated HCMEC. Pre-treatment of HCM with IMD (and AM) siRNA did not augment HCM injury: cell viabilities were 37% (and 39%) vs. 39% untreated HCM. Co-culture with HCMEC conferred protection from injury on HCM; such protection was attenuated when HCMEC were pre-treated with IMD (but not AM) siRNA before co-culture. Although IMD is present in HCM, IMD derived from HCMEC and acting in a paracrine manner, predominantly via AM1 receptors, makes a marked contribution to cardiomyocyte protection by the endogenous peptide against acute I-R injury., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Intermedin/adrenomedullin-2 (IMD) is a member of the adrenomedullin/CGRP peptide family. Less is known about the distribution of IMD than for other family members within the mammalian cardiovascular system, particularly in humans. The aim was to evaluate plasma IMD levels in healthy subjects and patients with chronic heart failure. IMD and its precursor fragments, preproIMD(25-56) and preproIMD(57-92), were measured by radioimmunoassay in 75 healthy subjects and levels of IMD were also compared to those of adrenomedullin (AM) and mid-region proadrenomedullin(45-92) (MRproAM(45-92)) in 19 patients with systolic heart failure (LVEF<45%). In healthy subjects, plasma levels (mean+SE) of IMD (6.3+0.6 pg ml(-1)) were lower than, but correlated with those of AM (25.8+1.8 pg ml(-1); r=0.49, p<0.001). Plasma preproIMD(25-56) (39.6+3.1 pg ml(-1)), preproIMD(57-92) (25.9+3.8 pg ml(-1)) and MRproAM(45-92) (200.2+6.7 pg ml(-1)) were greater than their respective bioactive peptides. IMD levels correlated positively with BMI but not age, and were elevated in heart failure (9.8+1.3 pg ml(-1), p<0.05), similarly to MRproAM(45-92) (329.5+41.9 pg ml(-1), p<0.001) and AM (56.8+10.9 pg ml(-1), p<0.01). IMD levels were greater in heart failure patients with concomitant renal impairment (11.3+1.8 pg ml(-1)) than those without (6.5+1.0 pg ml(-1); p<0.05). IMD and AM were greater in patients receiving submaximal compared with maximal heart failure drug therapy and were decreased after 6 months of cardiac resynchronization therapy. In conclusion, IMD is present in the plasma of healthy subjects less abundantly than AM, but is similarly correlated weakly with BMI. IMD levels are elevated in heart failure, especially with concomitant renal impairment, and tend to be reduced by high intensity drug or pacing therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cardiac computerized tomography (CT) has evolved from a research tool to an important diagnostic investigation in cardiology, and is now recommended in European, US, and UK guidelines. This review is designed to give the reader an overview of the current state of cardiac CT. The role of cardiac CT is multifaceted, and includes risk stratification, disease detection, coronary plaque quantification, defining congenital heart disease, planning for structural intervention, and, more recently, assessment of ischemia. This paper addresses basic principles as well as newer evidence.

Background: Although the General Medical Council recommends that United Kingdom medical students are taught 'whole person medicine', spiritual care is variably recognised within the curriculum. Data on teaching delivery and attainment of learning outcomes is lacking. This study ascertained views of Faculty and students about spiritual care and how to teach and assess competence in delivering such care., Methods: A questionnaire comprising 28 questions exploring attitudes to whole person medicine, spirituality and illness, and training of healthcare staff in providing spiritual care was designed using a five-point Likert scale. Free text comments were studied by thematic analysis. The questionnaire was distributed to 1300 students and 106 Faculty at Queen's University Belfast Medical School., Results: 351 responses (54 staff, 287 students; 25 %) were obtained. >90 % agreed that whole person medicine included physical, psychological and social components; 60 % supported inclusion of a spiritual component within the definition. Most supported availability of spiritual interventions for patients, including access to chaplains (71 %), counsellors (62 %), or members of the patient's faith community (59 %). 90 % felt that personal faith/spirituality was important to some patients and 60 % agreed that this influenced health. However 80 % felt that doctors should never/rarely share their own spiritual beliefs with patients and 67 % felt they should only do so when specifically invited. Most supported including training on provision of spiritual care within the curriculum; 40-50 % felt this should be optional and 40 % mandatory. Small group teaching was the favoured delivery method. 64 % felt that teaching should not be assessed, but among assessment methods, reflective portfolios were most favoured (30 %). Students tended to hold more polarised viewpoints but generally were more favourably disposed towards spiritual care than Faculty. Respecting patients' values and beliefs and the need for guidance in provision of spiritual care were identified in the free-text comments., Conclusions: Students and Faculty generally recognise a spiritual dimension to health and support provision of spiritual care to appropriate patients. There is lack of consensus whether this should be delivered by doctors or left to others. Spiritual issues impacting patient management should be included in the curriculum; agreement is lacking about how to deliver and assess.

Aims: To determine the symptomatic and prognostic differences resulting from a novel diagnostic pathway based on cardiac computerized tomography (CT) compared with the traditional exercise stress electrocardiography test (EST) in stable chest pain patients., Methods and Results: A prospective randomized controlled trial compared selected patient outcomes in EST and cardiac CT coronary angiography groups. Five hundred patients with troponin-negative stable chest pain and without known coronary artery disease were recruited. Patients completed the Seattle Angina Questionnaires (SAQ) at baseline, 3, and 12 months to assess angina symptoms. Patients were also followed for management strategies and clinical events. Over the year 12 patients withdrew, resulting in 245 in the EST cohort and 243 in the CT cohort. There was no significant difference in baseline demographics. The CT arm had a statistical difference in angina stability and quality-of-life domains of the SAQ at 3 and12 months, suggesting less angina compared with the EST arm. In the CT arm, there was more significant disease identified and more revascularizations. Significantly, more inconclusive results were seen in the EST arm with a higher number of additional investigations ordered. There was also a longer mean time to management. There were no differences in major adverse cardiac events between the cohorts. At 1 year in the EST arm, there were more Accident and Emergency (A&E) attendances and cardiac admission., Conclusion: Cardiac CT as an index investigation for stable chest pain improved angina symptoms and resulted in fewer investigations and re-hospitalizations compared with EST., Clinical Trial Registration: http://www.controlled-trials.com/ISRCTN52480460., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Structural and functional changes in the microcirculation in type 1 diabetes mellitus predict future end-organ damage and macrovascular events. We explored the utility of novel signal processing techniques to detect and track changes in ocular hemodynamics in patients with this disease. Twenty-four patients with uncomplicated type 1 diabetes mellitus and eighteen age- and sex-matched control subjects were studied. Doppler ultrasound was used to interrogate the carotid and ophthalmic arteries, and digital photography was used to image the retinal vasculature. Frequency analysis algorithms were applied to quantify velocity waveform structure and retinal photographic data at baseline and after inhalation of 100% O2. Frequency data were compared between groups. No significant differences were found in the resistive index between groups at baseline or after inhaled O2. Frequency analysis of Doppler flow velocity waveforms identified significant differences in bands 3-7 between patients and control subjects in data captured from the ophthalmic artery (P < 0.01 for each band). In response to inhaled O2, changes in frequency band amplitudes were significantly greater in control subjects compared with patients (P < 0.05). Only control subjects demonstrated a positive correlation (R = 0.61) between changes in retinal vessel diameter and frequency band amplitudes derived from ophthalmic artery waveform data. The use of multimodal signal processing techniques applied to Doppler flow velocity waveforms and retinal photographic data identified preclinical changes in the ocular microcirculation in patients with uncomplicated diabetes mellitus. An impaired autoregulatory response of the retinal microvasculature may contribute to the future development of retinopathy in such patients., (Copyright © 2014 the American Physiological Society.)

Objectives: This study sought to investigate the effect of a multiple micronutrient supplement on left ventricular ejection fraction (LVEF) in patients with heart failure., Background: Observational studies suggest that patients with heart failure have reduced intake and lower concentrations of a number of micronutrients. However, there have been very few intervention studies investigating the effect of micronutrient supplementation in patients with heart failure., Methods: This was a randomized, double-blind, placebo-controlled, parallel-group study involving 74 patients with chronic stable heart failure that compared multiple micronutrient supplementation taken once daily versus placebo for 12 months. The primary endpoint was LVEF assessed by cardiovascular magnetic resonance imaging or 3-dimensional echocardiography. Secondary endpoints were Minnesota Living With Heart Failure Questionnaire score, 6-min walk test distance, blood concentrations of N-terminal prohormone of brain natriuretic peptide, C-reactive protein, tumor necrosis factor alpha, interleukin-6, interleukin-10, and urinary levels of 8-iso-prostaglandin F2 alpha., Results: Blood concentrations of a number of micronutrients increased significantly in the micronutrient supplement group, indicating excellent compliance with the intervention. There was no significant difference in mean LVEF at 12 months between treatment groups after adjusting for baseline (mean difference: 1.6%, 95% confidence interval: -2.6 to 5.8, p = 0.441). There was also no significant difference in any of the secondary endpoints at 12 months between treatment groups., Conclusions: This study provides no evidence to support the routine treatment of patients with chronic stable heart failure with a multiple micronutrient supplement. (Micronutrient Supplementation in Patients With Heart Failure [MINT-HF]; NCT01005303)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

To determine if calcium scores (CS) could act as a more effective gatekeeper than Diamond Forrester (DF) in the assessment of patients with suspected coronary artery disease (CAD). A sub-study of the Cardiac CT for the Assessment of Chest Pain and Plaque (CAPP) study, a randomised control trial evaluating the cost-effectiveness of cardiac CT in symptomatic patients with stable chest pain. Stable pain was defined as troponin negative pain without symptoms of unstable angina. 250 patients undergoing cardiac CT had both DF scores and CS calculated, with the accuracy of both evaluated against CT coronary angiogram. Criteria given in UK national guidelines were compared. Of the 250 patients, 4 withdrew. 140 (57 %) patients were male. The mean DF was 47.8 and mean CS 172.5. Of the 144 patients with non-anginal pain 19.4 % had significant disease (>50 % stenosis). In general the DF over estimated the presence of CAD whereas the CS reclassified patients to lower risk groups, with 91 in the high risk DF category compared to 26 in the CS. Both receiver operating curve and McNemar Bowker test analysis suggested the DF was less accurate in the prediction of CAD compared to CS [Formula: see text] Projected downstream investigations were also calculated, with the cost per number of significant stenoses identified cheaper with the CS criteria. Patients with suspected stable CAD are more accurately risk stratified by CS compared to the traditional DF. CS was more successful in the prediction of significant stenosis and appears to be more effective at targeting clinical resources to those patients that are in need of them.

Aims: To determine whether 80-lead body surface potential mapping (BSPM) improves detection of acute coronary artery occlusion in patients presenting with out-of-hospital cardiac arrest (OHCA) due to ventricular fibrillation (VF) and who survived to reach hospital., Methods and Results: Of 645 consecutive patients with OHCA who were attended by the mobile coronary care unit, VF was the initial rhythm in 168 patients. Eighty patients survived initial resuscitation, 59 of these having had BSPM and 12-lead ECG post-return of spontaneous circulation (ROSC) and in 35 patients (age 69±13 yrs; 60% male) coronary angiography performed within 24 h post-ROSC. Of these, 26 (74%) patients had an acutely occluded coronary artery (TIMI flow grade [TFG] 0/1) at angiography. Twelve-lead ECG criteria showed ST-segment elevation (STE) myocardial infarction (STEMI) using Minnesota 9-2 criteria--sensitivity 19%, specificity 100%; ST-segment depression (STD) ≥0.05 mV in ≥2 contiguous leads--sensitivity 23%, specificity 89%; and, combination of STEMI or STD criteria--sensitivity 46%, specificity 100%. BSPM STE occurred in 23 (66%) patients. For the diagnosis of TFG 0/1 in a main coronary artery, BSPM STE had sensitivity 88% and specificity 100% (c-statistic 0.94), with STE occurring most commonly in either the posterior, right ventricular or high right anterior territories., Conclusion: Among OHCA patients presenting with VF and who survived resuscitation to reach hospital, post-resuscitation BSPM STE identifies acute coronary occlusion with sensitivity 88% and specificity 100% (c-statistic 0.94)., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Heart failure is a common condition in the Western world, particularly among elderly persons and with an ever-aging population, the incidence is expected to increase. Diet in the setting of heart failure is important--patients with this condition are advised to consume a low-salt diet and monitor their weight closely. Nutritional status of patients with heart failure also is important--those with poor nutritional status tend to have a poor long-term prognosis. A growing body of evidence suggests an association between heart failure and micronutrient status. Reversible heart failure has been described as a consequence of severe thiamine and selenium deficiency. However, contemporary studies suggest that a more subtle relationship may exist between micronutrients and heart failure. This article reviews the existing literature linking heart failure and micronutrients, examining studies that investigated micronutrient intake, micronutrient status, and the effect of micronutrient supplementation in patients with heart failure, and focusing particularly on vitamin A, vitamin C, vitamin E, thiamine, other B vitamins, vitamin D, selenium, zinc, and copper., (Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: Non-invasive diagnosis of acute myocardial infarction (AMI) associated with significant left main stem (LMS) stenosis remains challenging., Methods: Consecutive patients presenting with acute ischaemic-type chest pain from 2000 to 2010 were analysed. Entry criteria: 12-lead ECG and Body Surface Potential Map (BSPM) at presentation, cardiac troponin T (cTnT) ≥12 h and coronary angiography during admission. cTnT ≥0.03 µg/l defined AMI. ECG abnormalities assessed: STEMI by Minnesota criteria; ST elevation (STE) aVR ≥0.5 mm; ST depression (STD) ≥0.5 mm in ≥2 contiguous leads (CL); T-wave inversion (TWI) ≥1 mm in ≥2 CL. BSPM STE was ≥2 mm in anterior, ≥1 mm in lateral, inferior, right ventricular or high right anterior and ≥0.5 mm in posterior territories. Significant LMS stenosis was ≥70%., Results: Enrolled were 2810 patients (aged 60 ± 12 years; 71% male). Of these, 116 (4.1%) had significant LMS stenosis with AMI occurring in 92 (79%). STEMI by Minnesota criteria occurred in 13 (11%) (sensitivity 12%, specificity 92%), STE in lead aVR in 23 (20%) (sensitivity 23%, specificity 92%), TWI in 38 (33%) (sensitivity 34%, specificity 71%) and STD in 51 (44%) (sensitivity 49%, specificity 75%). BSPM STE occurred in 85 (73%): sensitivity 88%, specificity 83%, positive predictive value 95% and negative predictive value 65%. Of those with AMI, 74% had STE in either the high right anterior or right ventricular territories not identified by the 12-lead ECG. C-Statistic for AMI diagnosis using BSPM STE was 0.800 (P < 0.001)., Conclusion: In patients with significant LMS stenosis presenting with chest pain, BSPM STE has improved sensitivity (88%), with specificity 83%, over 12-lead ECG in the diagnosis of AMI.

Objective: Waveform analysis has been used to assess vascular resistance and predict cardiovascular events. We aimed to identify microvascular abnormalities in patients with IGT using ocular waveform analysis. The effects of pioglitazone were also assessed., Methods: Forty patients with IGT and 24 controls were studied. Doppler velocity recordings were obtained from the central retinal, ophthalmic, and common carotid arteries, and sampled at 200 Hz. A discrete wavelet-based analysis method was employed to quantify waveforms. The RI was also determined. Patients with IGT were randomized to pioglitazone or placebo, and measurements were repeated after 12-week treatment., Results: In the ocular waveforms, significant differences in power spectra were observed in frequency band 4 (corresponding to frequencies between 6.25 and 12.50 Hz) between groups (p < 0.05). No differences in RI occurred. No association was observed between waveform parameters and fasting glucose or insulin resistance. Pioglitazone had no effect on waveform structure, despite significantly reducing insulin resistance, fasting glucose, and triglycerides (p < 0.05)., Conclusions: Analysis of ocular Doppler flow waveforms using the discrete wavelet transform identified microvascular abnormalities that were not apparent using RI. Pioglitazone improved glucose, insulin sensitivity, and triglycerides without influencing the contour of the waveforms., (© 2011 John Wiley & Sons Ltd.)

Impaired FMD (flow-mediated dilatation) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as DM (diabetes mellitus). Endothelium-dependent FMD is a homoeostatic response to short-term increases in local shear stress. Microvascular dysfunction in DM influences blood flow velocity patterns. We explored the determinants of the FMD response in relation to evoked DSS (diastolic shear stress) and forearm microcirculation haemodynamics by quantifying changes in Doppler flow velocity waveforms between groups. Forty patients with uncomplicated Type 1 DM and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Postischaemic Doppler velocity spectral envelopes were recorded and a wavelet-based time-frequency spectral analysis method was employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 compared with 3.94 mm, P=0.23). FMD was significantly impaired in patients with Type 1 DM (3.95 compared with 7.75%, P<0.001). Endothelium-independent dilatation in response to GTN (glyceryl trinitrate) was also significantly impaired (12.07 compared with 18.77%, P<0.001). DSS (dyn/cm2) was significantly reduced in the patient group (mean 20.19 compared with 29.5, P=0.001). Wavelet interrogation of postischaemic flow velocity waveforms identified significant differences between groups. In conclusion, DSS, microcirculatory function and endothelium-independent vasodilatation in response to GTN are important determinants that impact on the magnitude of FMD response and are impaired in patients with Type 1 DM. Impaired FMD response is multifactorial in origin and cannot be attributed solely to a diminished NO bioavailability.

Background: Flow-mediated dilatation (FMD) of the brachial artery is commonly measured as a surrogate marker of endothelial function. Its measurement is, however, technically demanding and reports regarding its reproducibility have not always been favourable., Aim: Two Type I diabetes and control group comparator studies were conducted to assess the reproducibility of FMD and to analyse blood flow data normally discarded during FMD measurement., Design: The studies were sequential and differed only with regard to operator and ultrasound machine. Seventy-two subjects with diabetes and 71 controls were studied in total., Methods: Subjects had FMD measured conventionally. Blood velocity waveforms were averaged over 10 pulses post forearm ischaemia and their component frequencies analysed using the wavelet transform, a mathematical tool for waveform analysis. The component frequencies were grouped into 11 bands to facilitate analysis., Results: Subjects were well-matched between studies. In Study 1, FMD was significantly impaired in subjects with Type I diabetes vs. controls (median 4.35%, interquartile range 3.10-4.80 vs. 6.50, 4.79-9.42, P < 0.001). No differences were detected between groups in Study 2, however. However, analysis of blood velocity waveforms yielded significant differences between groups in two frequency bands in each study., Conclusion: This report highlights concerns over the reproducibility of FMD measures. Further work is required to fully elucidate the role of analysing velocity waveforms after forearm ischaemia.

Objective: Quantification of Doppler flow velocity waveforms has been shown to predict adverse cardiovascular outcomes and identify altered downstream haemodynamics and vascular damage in a number of organ beds. We employed novel techniques to quantify Doppler flow velocity waveforms from the retro bulbar circulation., Methods and Results: In total, 39 patients with uncomplicated Type 1 diabetes mellitus, and no other significant cardiovascular risk factors were compared with 30 control subjects. Flow velocity waveforms were captured from the ophthalmic artery (OA), central retinal artery (CRA) and the common carotid artery. The flow velocity profiles were analysed in the time domain to calculate the resistive index (RI), and time-frequency domain using novel discrete wavelet transform methods for comparison. Analysis of flow waveforms from the OA and CRA identified specific frequency band differences between groups, occurring independently of potential haemodynamic or metabolic confounding influences. No changes were identified in the calculated RI from any arterial site., Conclusion: Novel analysis of the arterial flow velocity waveforms recorded from the retro bulbar circulation identified quantifiable differences in Doppler flow velocity waveform morphology in patients with diabetes prior to the development of overt retinopathy. The technique may be useful as an additional marker of cardiovascular risk.

HMG Co-A reductase inhibitors (statins) are a group of drugs which lower cholesterol by inhibiting the conversion of HMG Co-A to mevalonate early in the cholesterol synthetic pathway. They are used in the primary and secondary prevention of cardiovascular events in patients deemed to be at increased risk and their benefit in patients with ischaemic heart disease is well supported. Their use in patients with heart failure (HF) however, is controversial. Evidence from observational and mechanistic studies suggests that statins should benefit patients with HF. However, larger randomised controlled trials have failed to demonstrate these expected benefits. The aim of this review article is to summarise the data from trials of statin use in patients with HF and attempt to explain the apparent conflict between recent placebo controlled trials and earlier observational and mechanistic studies.

Chronic constrictive pericarditis (CCP) is a clinical syndrome caused by compression of the heart due to a thickened or rigid pericardium. In the affluent West, the majority of cases of CCP are neither tuberculous nor calcific. In an American cohort undergoing pericardectomy for the condition, only 27% had calcification and under 10% had TB [1]. As a result, pericardial calcification (PC) as a marker of CCP has become neglected. We present a 48-year-old male admitted with atrial flutter, acute chest infection and signs of right heart congestion. PC was documented one year previously on a non-contrast CT chest. On this occasion, cardiac catheterisation confirmed hemodynamically significant CCP and cardiac magnetic resonance (cMR) study showed contiguous mass lesions in the pericardium, compression of the right ventricle, enlargement of the right atrium, hepatic enlargement and a pneumonic process in the left lung. He was commenced on antibiotics and anti-tuberculous therapy with a diagnosis of bacterial super-infection of tuberculous CCP. This was confirmed at pericardectomy along with an infected fistula into the left lung. Any finding of PC should be followed up with a thorough haemodynamic and anatomical assessment using any of a wide range of non-invasive imaging modalities.

We describe a case of pericardial constriction following viral pericarditis and illustrate the use of cardiac magnetic resonance imaging in the diagnostic process. The advantages of cardiac magnetic resonance in the investigation of pericardial disease are briefly explained.

Background: We present two clinical cases from a single institution where a final diagnosis of cardiac failure was made following the initial finding of ascites and an elevated CA 125 level. In both cases gynaecological malignancy was initially suspected., Methods: Following negative confirmatory tests for gynaecological malignancy, echocardiography was undertaken., Results: Patient 1 had severe right ventricular dilatation and dysfunction. Patient 2 had biventricular dysfunction with pulmonary hypertension. Both patients responded to standard therapy for heart failure, including loop diuretics.

Quantitative analysis of the arterial pressure pulse waveform recorded by applanation tonometry of the radial artery can track NO (nitric oxide)-mediated modulation of arterial smooth muscle tone. The changes in pressure pulse waveform morphology result from pulse wave reflection arising predominantly from smaller arteries and arterioles. Employing Doppler ultrasound to record the spectral flow velocity waveform in the ophthalmic artery, we studied the effects of NO modulation on waveforms recorded in the proximity of the terminal ocular microcirculatory bed. In healthy young men (n=10; age 18-26 years), recordings were made at baseline, following 300 mug of sublingual GTN (glyceryl trinitrate) and during the intravenous infusion of 0.25 and 0.5 mg/kg of L-NAME (N(G)-nitro-L-arginine methyl ester). Peaks (P1, P2 and P3) and nodes (N1, N2 and N3) on the arterial flow velocity waveform were identified during the cardiac cycle and employed to quantify wave shape change in response to the haemodynamic actions of the pharmacological interventions. The administration of GTN resulted in a significant (P<0.05) increase in heart rate without significant alteration in blood pressure. At the doses employed, L-NAME did not significantly alter systemic haemodynamics. With the exception of peak Doppler systolic velocity, all other peaks and nodes decreased significantly in response to GTN (P<0.05 for all points compared with baseline). In response to the administration of L-NAME, all peaks and nodes decreased significantly (P<0.05 for all points compared with baseline). The resistive index, a ratio calculated from the peak and trough flow velocities employed to assess change in flow resistance, increased significantly in response to GTN (0.77 at baseline compared with 0.85; P<0.05). Quantification of changes in the flow velocity spectral waveform during the cardiac cycle sensitively identified NO modulation of smooth muscle tone prior to alteration in systemic haemodynamics. Focusing on the resistive index, which identifies isolated points on the waveform describing the excursions of flow, may provide misleading information in relation to the haemodynamic effects of drug interventions.

Aims: To compare the success rate for transthoracic direct current cardioversion (DCC) of atrial fibrillation (AF) with antero-posterior (AP) and antero-apical (AA) electrode positions using an impedance compensated biphasic (ICB) waveform., Methods and Results: Three-hundred and seven patients [mean age 66 (SD+/-13), 195 male] with AF were recruited in three centres. Patients were randomized to an AA (n=150) or AP (n=144) pad position. Thirteen patients with implanted pacemakers were defaulted to the AP pad position. Cardioversion was performed using an ICB waveform with a 70, 100, 150, and 200 J energy selection protocol. If the fourth shock was unsuccessful, the pads were crossed over to the alternative position for a final 200 J shock. Shock 1 was successful in 54/150 (36%) AA and 45/144 (31%) AP patients, whereas success was achieved by shock 2 in 99/150 (66%) AA and 74/144 (51%) AP, by shock 3 in 123/150 (82%) AA and 109/144 (76%) AP, and by shock 4 in 143/150 (95%) AA and 127/144 (88%) AP and after cross-over in 144/150 (96%) AA and 135/144 (94%) AP. Overall success rate was higher than expected at 95%. Pad position was not associated significantly with success. There was a trend towards an improved outcome with the AA configuration (P=0.05)., Conclusion: The influence of pad position for DCC of AF may be less pertinent with ICB waveforms than with monophasic waveforms.

This is a case report of allergic reaction to Gadolinium-DTPA on first exposure, with a brief review of safety of MR contrast agents.

The aim of this study was to compare the efficacy of internal atrial defibrillation by conventional truncated exponential biphasic waveforms with and without waveform rounding (1-2 phases) and to determine optimal duration for this novel double rounded waveform. Atrial fibrillation, induced by rapid electrical stimulation, was converted by internal shocks through defibrillation catheters (lateral right atrium and coronary sinus) in anesthetised sheep. Rounding the leading edges of the conventional biphasic waveform (Ventritex HVS-02; settings 100/-50 V, 150/-70 V, and 200/-100 V; n = 8) reduced delivered peak and trough voltages, currents, and energy (by > or = 21 %, P < 0.001; for double (both phases) rounded) without decreasing cardioversion success. At 100/-50 V the efficacy of single (first phase) rounded (53 +/- 13%; mean +/- SEM) and double rounded (59 +/- 11%) shocks was similar to the conventional waveform (56 +/- 14%). Double rounded waveform (phase durations 1-20 ms) efficacy was optimum at 6-10 ms phase duration (100% success at 10-ms phase duration; 1.52 +/- 0.04 J delivered energy; n = 6). Successful cardioversion by conventional, single rounded, and double rounded biphasic waveforms (duration 6 ms each phase), conventional monophasic, rounded monophasic (duration 12 ms), and a damped sine waveform correlated strongly with peak-to-trough voltage swing within the waveform (r = 0.882; P < 0.01; n = 8). For internal atrial defibrillation, rounding both phases of the conventional biphasic waveforms, the double rounded waveform, permits similar efficacy to the conventional truncated exponential biphasic waveform at reduced peak voltage, current, and delivered energy. Optimum phase duration is 6-10 ms (tested range 1-20 ms).

Background: Drugs acting on the cardiac ATP-sensitive potassium (K-ATP) channels may modulate responses to ischaemia and arrhythmogenesis. We investigated the effects of K-ATP channel modulation on frequency patterns of ventricular fibrillation (VF) and on defibrillation threshold (DFT)., Methods and Results: Each group of 24 pigs randomly received intravenous levcromakalim (LKM) 40 microgram/kg (K-ATP agonist), glibenclamide (Glib) 20 mg/kg (K-ATP antagonist), saline or vehicle. Firstly, QTc interval was measured before and after drug. VF was then induced by endocardial stimulation and its power spectra and dominant frequencies over 15 min determined by fast Fourier transformation. Secondly, transthoracic DFT was determined (step-up/step-down protocol) before and after each drug. LKM reduced QTc interval (e.g., lead II, 354-321 ms, P<0.05) and increased the dominant VF frequency between 6 and 8 min (9.5+/-0.5 Hz at 6.5 min compared with 7.2+/-0.6 Hz (saline), 7.4+/-0.8 Hz (vehicle), 6.8+/-0.5 Hz (Glib), P=0.03). LKM reduced (to 57.2+/-2.1 mmHg) and Glib increased (to 107.8+/-6.1) mean arterial BP compared with saline (80.3+/-5.6) and vehicle (87. 6+/-7.1; P<0.01). There was no significant difference in defibrillation threshold energy, current or voltage, after any drug., Conclusions: Activation of K-ATP channels reduced blood pressure and QTc interval. The lack of major effect on VF dominant frequency and DFT of either LKM or Glib suggests that prior administration of similar drugs to patients should not prejudice outcome from VF cardiac arrest.

Since the introduction of percutaneous transluminal coronary angioplasty (PTCA), percutaneous intervention with balloon catheters, stents, and atherectomy devices has become a widely accepted practice. The persistent complication of non-Q-wave myocardial infarction (MI), as evidenced by increased cardiac enzyme levels after intervention, has aroused only moderate concern because its incidence was perceived to be small and not clinically relevant. With more systematic assessments of cardiac enzymes--specifically, creatine kinase (CK) and its MB isoform--evidence has begun to clarify both the incidence and the prognosis of periprocedural non-Q-wave MI: It appears to occur nearly three times more often than is clinically evident across all device types (8 to 9% of all interventions) and is directly and continuously associated with adverse outcomes, including late death. Although directional and rotational atherectomy improve angiographic outcome compared with PTCA, periprocedural infarction occurs at least twice as often with these newer technologies; the incidence associated with stent placement is comparable to and possibly higher than that of PTCA. Factors that may cause elevated CK-MB levels include distal embolization, side branch occlusion, thrombus, and coronary spasm. Analyses of the major trials of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors, a class of potent antiplatelet agents, show striking effectiveness of these drugs in reducing the incidence of "enzyme-only" or "silent" MI and in improving long-term clinical outcomes. The findings implicate platelet mediation in the occurrence of periprocedural infarction and suggest an important role for antiplatelet therapy, particularly GP IIb/IIIa receptor inhibition, in protecting patients undergoing percutaneous intervention.

We postulated that reducing peak leading edge shock voltage and its rate of rise (waveform rounding) would reduce energy requirements for cardioversion of AF and AFl, and may therefore reduce patient discomfort. Transvenous defibrillating catheters (In-Control Inc.) were placed in the RAA (active fixation) and the CS of six anesthetized sheep. AF or AFl was induced by electrical stimulation (100 Hz, 2 V; Grass stimulator). A standard trapezoidal biphasic (S) waveform (3-ms duration each phase) was compared with a similar waveform that had the first phase rounded (R). Cardioversion was attempted after 30 seconds of arrhythmia, using a Ventritex HVS-O2 defibrillator modified to allow waveform rounding. Each waveform was randomly tested several times at 100-, 150-, and 200-V leading edges, and percentage cardioversion success calculated. Shock energy was calculated from delivered current and voltage using Flukeview (Fluke, Inc.) software. At 100-V leading edge R (64% success) and S (59%), shocks were similarly efficacious (P = 0.37). However, R delivered less current, voltage, and energy than the comparable S shock (means 1.30 A, 65.0 V, 0.33 J R vs 1.92 A, 94.2 V, 0.47 J S; P = 0.0001). Both waveforms were equally successful at 150 V (88% vs 100%; P = NS) and 200 V (100% vs 100%), but again R delivered less current, voltage, and energy (2.05 A, 102.5 V, 0.82 J R vs 2.78 A, 142.3 V, 1.11 J S at 150 V; 2.76 A, 141.2 V, 1.58 J R vs 3.77 A, 189.4 V, 2.03 J S at 200 V; both P = 0.0001). No arrhythmic or other complications occurred in the 174 shocks delivered. Waveform rounding reduces delivered peak voltage, current, and energy without reducing defibrillation efficacy. To determine if these changes are associated with a reduction in discomfort, patients with AF are currently being cardioverted with these waveforms during electrophysiological studies.