The Risk of Cardiovascular Disease in Prostate Cancer Patients Receiving Androgen Deprivation Therapies.

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.

Improving the Diagnosis of Culprit Left Circumflex Occlusion With Acute Myocardial Infarction in Patients With a Nondiagnostic 12-Lead ECG at Presentation: A Retrospective Cohort Study.

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.

Dietary Micronutrient Intake and Micronutrient Status in Patients With Chronic Stable Heart Failure: An Observational Study.

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.

Epicardial potentials computed from the body surface potential map using inverse electrocardiography and an individualised torso model improve sensitivity for acute myocardial infarction diagnosis.

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/m2. 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.

Plasma levels of intermedin (adrenomedullin-2) in healthy human volunteers and patients with heart failure.

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.

Endothelium-derived intermedin/adrenomedullin-2 protects human ventricular cardiomyocytes from ischaemia-reoxygenation injury predominantly via the AM1 receptor.

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.

The Essentials of Cardiac Computerized Tomography.

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.

How should teaching on whole person medicine, including spiritual issues, be delivered in the undergraduate medical curriculum in the United Kingdom?

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.

The effect of multiple micronutrient supplementation on left ventricular ejection fraction in patients with chronic stable heart failure: a randomized, placebo-controlled trial.

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).

A comparison of Diamond Forrester and coronary calcium scores as gatekeepers for investigations of stable chest pain.

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.

The role of micronutrients in heart failure.

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.

Impaired microvascular properties in uncomplicated type 1 diabetes identified by Doppler ultrasound of the ocular circulation.

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.

Heart fatty acid-binding protein in combination with the 80-lead body surface potential map improves early detection of acute myocardial infarction in patients who are cardiac troponin T-negative at presentation.

UNLABELLED: Of patients who present with ischemic-type chest pain and a negative cardiac troponin T (cTnT) at first medical contact, there are patients at a very early stage of infarction. The aim of this research was to assess heart fatty acid-binding protein (H-FABP), a novel marker of myocyte necrosis, in combination with the 80-lead body surface potential map (BSPM) in the early diagnosis of acute myocardial infarction (AMI). METHODS: In this prospective study, consecutive patients presenting with acute ischemic-type chest pain between 2003 and 2006 were enrolled. At first medical contact, blood was sampled for cTnT and H-FABP; in addition, a 12-lead electrocardiogram (ECG) and BSPM were recorded. A second cTnT was sampled 12 hours or more after presentation. Peak cTnT 0.03 µg/L or higher diagnosed AMI. Elevated H-FABP was 5 ng/mL or higher. A cardiologist blinded to both the clinical details and 12-lead ECG interpreted the BSPM. RESULTS: Enrolled were 407 patients (age 62 ± 13 years; 70% men). Of these 407, 180 had cTnT less than 0.03 µg/L at presentation. Acute myocardial infarction occurred in 52 (29%) of 180 patients. Of these 180 patients, 27 had ST-segment elevation (STE) on ECG, 104 had STE on BSPM (sensitivity, 88%; specificity, 55%), and 95 (53%) had H-FABP elevation. The proportion with elevated H-FABP was higher in the AMI group compared with non-AMI group (P < .001). Body surface potential map STE was significantly associated with H-FABP elevation (P < .001). Of those with initial cTnT less than 0.03 µg/L, the c-statistic for the receiver operating characteristic curve distinguishing AMI from non-AMI using H-FABP alone was 0.644 (95% confidence interval [CI], 0.521-0.771), using BSPM alone was 0.716 (95% CI, 0.638-0.793), and using the combination of BSPM and H-FABP was 0.812 (95% CI, 0.747-0.876; P < .001). CONCLUSION: In patients with acute ischemic-type chest pain who have a normal cTnT at presentation, the combination of H-FABP and BSPM at first assessment identifies those with early AMI (c-statistic, 0.812; P < .001), thus allowing earlier triage to reperfusion therapy and secondary prevention.

Ocular blood flow analysis detects microvascular abnormalities in impaired glucose tolerance.

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.

Impaired flow-mediated dilatation response in uncomplicated Type 1 diabetes mellitus: influence of shear stress and microvascular reactivity.

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.

Statins in heart failure-where do we stand?

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.

A classic diagnosis with a new 'spin'.

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.

Nitric oxide modulation of ophthalmic artery blood flow velocity waveform morphology in healthy volunteers.

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.

Acute allergic reaction upon first exposure to gadolinium-DTPA: a case report.

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