Individuals with impaired glucose tolerance demonstrate normal cardiac sympathetic innervation using I-123 mIBG scintigraphy.

BACKGROUND: Impaired glucose tolerance (IGT) is associated with an increased risk of type 2 diabetes (T2DM) and cardiovascular disease. Some but not all studies have reported cardiac autonomic dysfunction in subjects with IGT and there is only one direct study of cardiac innervation in subjects with IGT. The purpose of this study was to assess global and regional cardiac sympathetic innervation and cardiac autonomic function in individuals with IGT. METHODS AND RESULTS: We undertook (123)I-mIBG scintigraphy and cardiac autonomic function in 15 subjects with IGT and 15 age and sex-matched healthy controls. Early heart to mediastinum ratio (HMR) (1.71 ± 0.17 vs 1.67 ± 0.13, P = .49), late HMR (1.73 ± 0.18 vs 1.73 ± 0.16, P = .97) and washout rate (WR) (18.6 ± 4.2 vs 19.1 ± 7.6%, P = .84), did not differ between subjects with IGT and control subjects. More detailed regional analysis revealed reduced tracer uptake at the apex, base and inferior wall in all subjects and the anterior wall in a minority of subjects. There were no differences in total score (56.6 ± 4.0 vs 53.3 ± 8.4, P = .193), modified score (48.5 ± 3.3 vs 46.2 ± 6.0, P = .215), anterior wall score (10.2 ± 1.3 vs 10.1 ± 1.6, P = .898), inferior wall score (8.9 ± 1.9 vs 7.7 ± 2.6, P = .163), basal score (18.7 ± 1.9 vs 18.2 ± 3.3, P = .636) and tests of cardiac autonomic function between the groups. CONCLUSION: Global and regional measures of MIBG uptake and washout as well as cardiac autonomic function did not differ between subjects with IGT and healthy controls.

Stress and strain: double trouble or useful tool?

Cardiac deformation imaging is being used more and more routinely in resting echocardiography. The technique can also be applied to stress studies, and may provide additional information to that obtained by standard analysis alone. This review explores its present role, limitations, and potential uses. Although currently not widely used in stress studies, deformation imaging has the capability to provide clinically useful information.

Non-adenomatous non-epithelial carcinoma (hemangiopericytoma) of prostate treated with conservative surgery followed by adjuvant chemoradiation.

Hemangiopericytoma is a malignant vascular tumour of soft tissue. Microscopically, the tumour shows tightly packed cellular areas surrounding thin-walled branching blood vessels. Traditionally these tumours are treated using wide surgical excision. Only a very few cases of hemangiopericytoma of the prostate have been described worldwide. The feasibility of managing such a case with a combination of conservative surgery and adjuvant anti-malignancy treatment is unexplored. Here, we report a case of hemangiopericytoma of the prostate treated with local excision, with preservation of prostate, followed by adjuvant radiotherapy (40 Gy in 20 fractions to pelvis followed by 24 Gy in 12 fractions as boost to prostate) and chemotherapy (doxorubicin and iphosphamide). Post-treatment computed tomography scan after 4 weeks showed regression of pelvic lymph nodes and a normal-appearing prostate. Levels of serum prostate-specific and carcinogenic embryonic antigen were normal throughout the period of treatment. To date, followup has been uneventful, except for occasional bouts of diarrhea.We conclude that conservative surgery followed by adjuvant radiation and chemotherapy, with subsequent close follow-up, may adequately control localized disease in selected cases of hemangiopericytoma of the prostate. The role of conservative surgery in tumours located at other sites has yet to be defined.

Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): randomised controlled trial.

BACKGROUND: The improvement in left-ventricular ejection fraction (LVEF) in response to beta blockers is heterogeneous in patients with heart failure due to ischaemic heart disease, possibly indicating variations in the myocardial substrate underlying left-ventricular dysfunction. We investigated whether improvement in LVEF was associated with the volume of hibernating myocardium (viable myocardium with contractile failure). METHODS: We did a double-blind, randomised trial to compare placebo and carvedilol for 6 months in individuals with stable, chronic heart failure due to ischaemic left-ventricular systolic dysfunction. We enrolled 489 patients, of whom 387 were randomised. Patients were designated hibernators or non-hibernators according to the volume of hibernating myocardium. The primary endpoint was change in LVEF, measured by radionuclide ventriculography, in hibernators versus non-hibernators, on carvedilol compared with placebo. Analysis was by intention to treat. RESULTS: 82 patients dropped out of the study because of adverse events, withdrawal of consent, or failure to complete the investigation. Thus, 305 (79%) were analysed. LVEF was unchanged with placebo (mean change -0.4 [SE 0.9] and -0.4 [0.8] for non-hibernators and hibernators, respectively) but increased with carvedilol (2.5 [0.9] and 3.2 [0.8], respectively; p<0.0001 compared with baseline). Mean placebo-subtracted change in LVEF was 3.2% (95% CI 1.8-4.7; p=0.0001) overall, and 2.9% (0.7-5.1; p=0.011) and 3.6% (1.7-5.4; p=0.0002) in non-hibernators and hibernators, respectively. Effect of hibernator status on response of LVEF to carvedilol was not significant (0.7 [-2.2 to 3.5]; p=0.644). However, patients with more myocardium affected by hibernation or by hibernation and ischaemia had a greater increase in LVEF on carvedilol (p=0.0002 and p=0.009, respectively). INTERPRETATION: Some of the effect of carvedilol on LVEF might be mediated by improved function of hibernating or ischaemic myocardium, or both. Medical treatment might be an important adjunct or alternative to revascularisation for patients with hibernating myocardium.

Organization-induced charge redistribution in self-assembled organic monolayers on gold.

The charge redistribution that occurs within dipolar molecules as they self-assemble into organized organic monolayer films has been studied. The extent of charge transfer is probed by work function measurements, using low-energy photoelectron spectroscopy (LEPS), contact potential difference (CPD), and X-ray photoelectron spectroscopy (XPS), with the latter providing fine details about the internal charge distribution along the molecule. In addition, two-photon photoelectron spectroscopy is applied to investigate the electronic structure of the adsorbed layers. We show that charge transfer acts to reduce the dipole-dipole interaction between the molecules but may either decrease or increase the molecule-to-surface dipole moment.

Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction.

In a double-blind study, 99 patients (82 men, age range 40 to 75 years) with acute myocardial infarction (AMI) were randomly assigned to receive captopril or placebo. Treatment began within 24 hours of admission. Serial echocardiographic measurements of endocardial segment lengths and left ventricular (LV) volumes, and ejection fractions were obtained. The 2 groups were matched at baseline except for an excess of previous AMI in the placebo group (13 of 50 vs 2 of 49 patients, p = 0.002). The increase in anterior segment length, from baseline to 2 months, was significantly less in the captopril than in the placebo group (2.8 +/- 1.6 vs 10.4 +/- 2.4mm, 95% confidence interval [CI] -13.5 to -1.7, p = 0.01). The increase in posterior segment length was also less in the captopril group, but the difference was not significant (3.2 +/- 1.2 vs 7.0 +/- 1.8mm, 95% CI -8.0 to 0.5, p = 0.08). Fewer patients in the captopril group demonstrated increases in segment length greater than 2 standard deviations of the measurement error (14 of 70 [20%] vs 29 of 72 [40%] patients, p = 0.009). In patients with anterior AMI, the infarct-containing anterior segment length increased by 4.5 +/- 2.3 mm in the captopril versus 12.4 +/- 3.1 mm in the placebo group (95% CI -15.7 to -0.2, p = 0.046), and fewer patients in the captopril group demonstrated infarct expansion (6 of 20 [30%] vs 13 of 21 [62%] patients, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Legionella pneumonia complicating Wegener's granulomatosis.

We describe a previously healthy man who presented with features consistent with Wegener's granulomatosis. While undergoing investigation, he developed acute respiratory failure, thought to represent progression of his vasculitis. Open lung and sinus biopsies were performed to obtain the diagnosis. Vasculitis was confirmed on the paranasasl biopsy, and the lung biopsy showed pneumonia due to Legionella pneumophila, an association not previously reported in Wegener's granulomatosis. If immunosuppressive therapy had been started without making the diagnosis of Legionella pneumonia on lung biopsy, the patient might well have succumbed to the infection.

Circulating endothelin is not extracted by the pulmonary circulation in man.

To determine whether endothelin is extracted from plasma during passage through the pulmonary circulation, we measured its concentration at several points, including the pulmonary artery and the left superior pulmonary vein in seven patients undergoing cardiac surgery. Endothelin concentrations were very similar at all sites sampled. In patients undergoing coronary artery bypass grafting, there is no net pulmonary clearance of endothelin.

Validation of an echocardiographic wall motion index in heart failure due to ischaemic heart disease.

AIMS: The echocardiographic assessment of left ventricular ejection fraction (LVEF) by geometric methods is limited in many patients because of inadequate views and also in the presence of regional wall motion abnormalities due to ischaemic heart disease (IHD). This study aimed to examine the application of a wall motion index (WMI) method, using a nine-segment LV model in patients with chronic heart failure (CHF) due to IHD. METHODS AND RESULTS: Echocardiography was performed in 71 consecutive subjects with CHF due to IHD. WMI could be derived in 70 subjects (99%). The inter-observer variability (repeatability coefficient) of WMI was 0.66, i.e. LVEF+/-20%. In 66 subjects, LVEF was measured, within 4 weeks, using radionuclide ventriculography (RNV-EF). The inter-observer variability of RNV-EF was +/-3.1%. Using the mean of two observations for each method, the Bland-Altman range of agreement for LVEF was 26% (+/-13%). CONCLUSION: WMI is a widely applicable echocardiographic method for assessing LV systolic function and has moderate agreement with RNV-EF. Unlike RNV-EF, however, WMI is not likely to be a suitable method for the measurement of small, but prognostically important, changes in LV function that may occur in CHF.

Trends in pacemaker mode prescription 1984-1994: a single centre study of 3710 patients.

OBJECTIVE: To evaluate trends in pacemaker mode prescription from 1984 to 1994 with particular reference to the changes in pacemaker mode prescription for patients aged 80 years and older at implant. DESIGN: Prospective evaluation of indications for pacing and pacemaker mode prescription in all patients undergoing new pacemaker implantation from 1992 to 1994. Comparison with retrospectively obtained data for patients paced from 1984 to 1991. SETTING: Tertiary referral cardiothoracic centre. PATIENTS: Group 1: 2622 patients paced at one centre and entered into the national pacing database from 1984 to 1991. Group 2: 1088 consecutive patients paced from 1992 to 1994. RESULTS: Use of atrial (AAI) and dual chamber (DDD) pacemakers increased progressively in patients of all ages from 1984 to 1994. There was an increase in the proportion of patients aged 80 years and older from 25.4% (group 1) to 40.5% (group 2). Patients of all ages in group 2 were more likely to receive DDD units for atrioventricular block (odds ratio (95% confidence interval) (CI) 9.0 (7.0 to 11.5)) and AAI or DDD units for sinus node disease (odds ratio (95% CI) 11.0 (7.7 to 15.8)) than those in group 1. Elderly patients (age > or = 80 at implant) with atrioventricular block or sinus node disease and a suitable atrial rhythm were less likely to receive DDD or AAI pacemakers than younger patients in both groups. CONCLUSIONS: Use of atrial and dual chamber pacing modes has increased substantially in patients of all ages over the last decade. Although elderly patients represent an increasing proportion of the paced population, they remain less likely to receive atrial or dual chamber pacemakers than younger patients.

Impact of stenting on coronary angioplasty procedures.

OBJECTIVE: To compare patient selection and outcome of coronary angioplasty procedures before and after the widespread availability and use of stents. SUBJECTS AND METHODS: Group 1 consisted of 252 consecutive patients and group 2 comprised 389 patients who underwent angioplasty between April 1993 and March 1994, and April 1995 and March 1996, respectively, in a tertiary cardiothoracic centre. Clinical variables were collected before the procedures. Endpoints included in-hospital death, the need for repeat coronary angiography, repeat angioplasty, and coronary artery bypass surgery. Lesions were classified under American Heart Association/American College of Cardiology criteria in 100 randomly selected patients from each group. RESULTS: 311 and 482 angioplasty procedures were performed in patients from groups 1 and 2, respectively. One or more stents were deployed in nine (4%) and 179 (46%, p < 0.01) patients, respectively. The success rate was higher in group 2 than in group 1 patients (483/523 (92%) v 274/372 (88%), respectively, p < 0.05). There were significantly more single vessel angioplasty procedures (198/252 (79%) v 272/389 (70%), p < 0.05), type A lesions (30/116 (26%) v 19/130 (15%), p < 0.05), patients with stable angina (220/252 (87%) v 311/389 (80%), p < 0.05), and fewer acute myocardial infarction patients (1/252 (0%) v 12/389 (3%), p < 0.05) treated in group 1 than in group 2, respectively. Similar numbers of angioplasty were performed in the left anterior descending, left circumflex, and right coronary arteries. There were no significant differences in the in-hospital mortality or the need for repeat coronary angiography, angioplasty, or bypass surgery at 24 hours or six months after the initial procedure. CONCLUSION: Patients undergoing angioplasty in the stenting era had features associated with an increased risk of complication. Despite this, the primary success rate was higher, and the complication rate and the need for subsequent revascularisation were similar in the two groups, supporting the widely held clinical impression that stenting has made a valuable impact on the practice of angioplasty.

The effects of angiotensin-converting enzyme inhibition on coronary blood flow and infarct size limitation.

A number of theoretical and practical aspects of acute myocardial infarction suggest a potential role for ACE inhibition in enhancing coronary blood flow and limitation of infarct size. Indeed, the use of ACE inhibitors in acute myocardial infarction could be viewed as a logical intervention in the face of the neuroendocrine response which accompanies the acute phase. During the first 24 h post-infarction, very high plasma concentrations of arginine-vasopressin and catecholamines occur. This is followed by a sharp rise in the concentration of angiotensin II (ANG II) over the next few days. The neuroendocrine response is most marked in those patients with larger infarcts, who frequently develop left ventricular failure. The extent to which these factors influence coronary flow in acute myocardial infarction is unknown, although in chronic heart failure ACE inhibition does not reduce coronary blood flow despite a reduction in rate-pressure product, suggesting a coronary vasodilator effect. However, in the presence of fixed coronary stenoses, the fall in blood pressure and, therefore, of coronary perfusion pressure must be taken into account. Whether or not the use of ACE inhibitors can limit infarct size in man also remains to be determined, although it has been clearly demonstrated that concentrations of ANG II similar to those observed in the early phase of myocardial infarction can cause myocardial cell damage in experimental animals. Post-infarction ventricular enlargement can be reduced by ACE inhibitors. Additionally, ACE inhibitors, through their balanced vasodilator effect, maintain cardiac output whilst reducing filling pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

The carvedilol hibernation reversible ischaemia trial, marker of success (CHRISTMAS) study. Methodology of a randomised, placebo controlled, multicentre study of carvedilol in hibernation and heart failure.

BACKGROUND: Carvedilol reduces mortality and improves symptoms and ejection fraction in ischemic heart failure, but its mode of action is not well defined and not all patients respond to treatment. The aim of the CHRISTMAS (Carvedilol Hibernation Reversible Ischaemia Trial, Marker of Success) study is to examine whether hibernation may be a significant factor determining this response. This paper describes the methodology and the rationale for the choice of the nuclear cardiology and echocardiography imaging techniques used in the study. METHODS AND RESULTS: The CHRISTMAS study is a double-blind, randomised, parallel group, multinational study of oral carvedilol versus placebo in patients with chronic stable heart failure due to left ventricular systolic dysfunction from coronary artery disease. The study aims to randomise 400 patients who are on optimal treatment. Two parallel groups will be randomised to carvedilol or placebo, namely 200 with hibernating myocardium at baseline and 200 matched patients without. The presence of hibernation is defined from a mismatch between regional contractile function and regional viability, measured by echocardiography (severe segmental asynergy) and nitrate prepared resting Tc99m-MIBI myocardial perfusion imaging (segmental activity >60%). The primary treatment-related end-point of the study is the comparison of the mean change, from baseline to the final visit, in radionuclide-determined left ventricular ejection fraction in patients on placebo with those on carvedilol, between the groups designated as hibernating and non-hibernating. Other end-points being examined include the prevalence of hibernation in heart failure, the relationship between the volume of hibernating myocardium and the ejection fraction response, the prevalence of reversible ischemia in heart failure, and the comparison of echo with gated SPECT. To date, 303 patients have been screened and 251 patients randomised in the study. The study aims to report in 2000. CONCLUSIONS: The CHRISTMAS study addresses the issue of whether the presence of hibernation is a predictor of the ejection fraction response to carvedilol in heart failure. It also examines the potential role of medical therapy in hibernation as well as a number of other end-points. The study may potentially lead to an important new role for nuclear cardiology in heart failure, and demonstrates important synergy between cardiac imaging and the pharmaceutical industry.

Cerebral embolisation during modern cardiopulmonary bypass.

OBJECTIVES: Cerebral microembolisation still occurs during cardiopulmonary bypass and may cause both stroke and postoperative cognitive impairment. We investigated the frequency of cerebral embolisation during coronary artery bypass surgery with modern cardiopulmonary bypass and related these to ascending aortic atherosclerosis. METHODS: Transcranial Doppler monitoring for cerebral embolisation to both middle cerebral arteries was performed in 65 patients undergoing coronary artery surgery with non-pulsatile alpha-stat hypothermic bypass. Epicardial ultrasound imaging of ascending aortic atherosclerosis was performed in 14 patients. RESULTS: Thirty patients (56.9%) had more than 200 emboli entering the middle cerebral artery territories during surgery; most at the start of bypass and during defibrillation. Readjustment of aortic clamps and aortic cannulation also caused a large number of emboli which were probably particulate. Aortic disease was mild (mean plaque thickness 1 mm, interquartile range 0.9-1.2 mm) and did not relate to the number of cerebral emboli produced by aortic manipulation. CONCLUSIONS: Cerebral embolisation remains common during coronary surgery despite advances in filter and bypass pump technology. Aortic manipulation and clamping was associated with emboli but epicardial ultrasound imaging was of little help in its prediction.

Importance of RAA system and the treatment of patients with ACE inhibition after myocardial infarction.

There is activation of the renin angiotensin system after both complicated and uncomplicated myocardial infarction. Angiotensin II increases myocardial oxygen consumption whilst reducing coronary flow and is also directly toxic to the myocardium. Angiotensin converting enzyme inhibitors produce beneficial haemodynamic and neuroendocrine changes in patients with acute left ventricular failure, and may have a role in selected patients with cardiogenic shock. There is evidence to suggest that they might prevent the development of late cardiac failure by limiting the extent of post infarction ventricular dilation. Further research is necessary to define their role in the treatment of acute myocardial infarction.

Right ventricular involvement in acute myocardial infarction.

The presence of right ventricular dysfunction in patients with acute myocardial infarction has important implications. It is a marker for in-hospital mortality and failure to recognize it may lead to inappropriate treatment with serious consequences for the patient. Patients surviving the acute event do, however, have a relatively good long-term prognosis.

What is the impact of providing a transcatheter aortic valve implantation service on conventional aortic valve surgical activity: patient risk factors and outcomes in the first 2 years.

OBJECTIVES: To assess the impact of introducing a transcatheter aortic valve implantation (TAVI) service on aortic valve surgical activity and outcomes. DESIGN: A retrospective analysis of prospectively collected data. SETTING: University hospital of south Manchester. PATIENTS: 815 consecutive patients undergoing isolated aortic valve replacement (AVR) or coronary artery bypass grafting plus AVR from January 2006 to December 2009. Fifty consecutive patients who underwent TAVI from January 2008 to December 2009. MAIN OUTCOME MEASURES: Aortic valve surgical activity in the 2years before the introduction of a TAVI service and in the 2years following. Outcomes following conventional aortic valve surgery and TAVI. RESULTS: In the 2years following the introduction of TAVI at this centre, conventional AVR activity has increased by 37% compared with an 8% increase nationally (p<0.001). Compared with the 2years before TAVI there was no change in the mean logistic EuroSCORE (7.4 vs 7.9 p=0.16) or crude mortality rate (2.9% vs 2.1% p=0.48). Fifty high-risk patients underwent TAVI with a 30-day mortality rate of 0%. The mean logistic EuroSCORE of the TAVI patients was 25.3. CONCLUSIONS: TAVI is an emerging alternative to AVR in high-risk patients. Since the introduction of a TAVI service at this centre, conventional AVR activity has increased. Despite a trend of increasing mean logistic EuroSCORE indicating that more complex cases are being undertaken, there has been a non-significant reduction in the crude mortality rate. Offering a TAVI service has a positive impact on the volume of conventional AVR surgical activity.

Cardiac involvement in muscular dystrophies.

The muscular dystrophies are a heterogeneous group of conditions with a variable distribution and prognosis. Cardiac complications are common and may significantly alter both quality and quantity of life. Whilst complications are disease specific, many patients will require long-term cardiology follow-up looking for the development of a cardiomyopathic process or conduction problems. Improvements in diagnostic techniques now allow mutation-specific diagnosis to be made in some patients so adequate counselling, management and screening can be put in place for individuals and their families.

Left ventricular torsion in primary chronic mitral regurgitation.

BACKGROUND: Torsion is essential for normal systolic and diastolic function of the left ventricle (LV), and is known to be abnormal in animal models of mitral regurgitation (MR). There are no comparable data in humans. OBJECTIVES: To study LV torsion in humans with chronic primary MR using speckle-tracking echocardiography. METHODS: Rotation and rotation rate were measured from two-dimensional (2D) greyscale LV base and apex short-axis images by speckle-tracking echocardiography in 38 patients and 30 controls. Using custom software, plots of torsion against time were constructed by deducting base rotation from apex rotation. Loops of torsion against LV radial/longitudinal displacement and volume were automatically plotted. RESULTS: Peak systolic torsion, systolic torsional velocity and untwisting velocity were similar in the two groups. In controls, untwisting started 23 ms before aortic valve closure but was delayed in MR to 15 ms after aortic valve closure, p<0.001. In normal subjects there was rapid untwisting during isovolumic relaxation, with minimal expansion of the LV radial and longitudinal axes. In MR, early untwisting rate was decreased, with less untwisting for a given volume increase. Extensive LV remodelling and worsening MR were associated with progressive reductions in systolic torsion and untwisting velocity, and progressive delay in the onset of untwisting. CONCLUSIONS: Chronic MR results in significant delay and slowing of LV untwisting, such that early untwisting is coupled with chamber expansion. Correlations between disease severity and torsional parameters suggest a potential role of these variables in assessing early signs of ventricular dysfunction.