Mark Harbinson

Myocardial perfusion scintigraphy: the evidence.

This review summarises the evidence for the role of myocardial perfusion scintigraphy (MPS) in patients with known or suspected coronary artery disease. It is the product of a consensus conference organised by the British Cardiac Society, the British Nuclear Cardiology Society and the British Nuclear Medicine Society and is endorsed by the Royal College of Physicians of London and the Royal College of Radiologists. It was used to inform the UK National Institute of Clinical Excellence in their appraisal of MPS in patients with chest pain and myocardial infarction. MPS is a well-established, non-invasive imaging technique with a large body of evidence to support its effectiveness in the diagnosis and management of angina and myocardial infarction. It is more accurate than the exercise ECG in detecting myocardial ischaemia and it is the single most powerful technique for predicting future coronary events. The high diagnostic accuracy of MPS allows reliable risk stratification and guides the selection of patients for further interventions, such as revascularisation. This in turn allows more appropriate utilisation of resources, with the potential for both improved clinical outcomes and greater cost-effectiveness. Evidence from modelling and observational studies supports the enhanced cost-effectiveness associated with MPS use. In patients presenting with stable or acute chest pain, strategies of investigation involving MPS are more cost-effective than those not using the technique. MPS also has particular advantages over alternative techniques in the management of a number of patient subgroups, including women, the elderly and those with diabetes, and its use will have a favourable impact on cost-effectiveness in these groups. MPS is already an integral part of many clinical guidelines for the investigation and management of angina and myocardial infarction. However, the technique is underutilised in the UK, as judged by the inappropriately long waiting times and by comparison with the numbers of revascularisations and coronary angiograms performed. Furthermore, MPS activity levels in this country fall far short of those in comparable European countries, with about half as many scans being undertaken per year. Currently, the number of MPS studies performed annually in the UK is 1,200/million population/year. We estimate the real need to be 4,000/million/year. The current average waiting time is 20 weeks and we recommend that clinically appropriate upper limits of waiting time are 6 weeks for routine studies and 1 week for urgent studies.

Randomised comparison of electrode positions for cardioversion of atrial fibrillation.

OBJECTIVE To compare the relative efficacy of anteroanterior vanteroposterior 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.

Procedure Guidelines for Radionuclide Myocardial Perfusion Imaging

Radionuclide myocardial perfusion imaging (MPI) is an established and non-invasive imaging technique with diagnostic and prognostic efficacy in the investigation of coronary artery disease. It is the only widely available test for assessing myocardial perfusion directly but there are variations in the way it is performed in different centres. Harmonization of practice, at least at a national level, is therefore essential, and clinical governance now makes it mandatory for practice to be based upon evidence whenever possible [ 1]. This is best achieved by expert analysis of the evidence and to this end the British Nuclear Cardiology Society (BNCS) in association with the British Cardiac Society (BCS) and the British Nuclear Medicine Society (BNMS) have developed procedure guidelines for tomographic myocardial perfusion imaging. A systematic literature search was performed and every effort was made to conform with the AGREE recommendations [ 2]. All recommendations are therefore based on either evidence from clinical studies, previous published guidelines or expert consensus of the writing and advisory groups. The guidelines cover the clinical indications of MPI, the methods used for stress testing, the radiopharmaceuticals and the injected activities and also issues related to acquisition, processing and interpretation of images. They do not cover the benefits or drawbacks of the technique in specific circumstances; neither do they address its cost effectiveness in clinical diagnosis and management nor its potential impact on clinical outcomes. The guidelines aim to assist medical practitioners and other health care professionals in recommending, performing, interpreting and reporting single photon emission computed tomography (SPECT) of myocardial perfusion.

ROUNDED BIPHASIC WAVEFORM REDUCES ENERGY REQUIREMENTS FOR TRANSVENOUS CATHETER CARDIOVERSION OF ATRIAL FIBRILLATION AND FLUTTER

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 AFI, 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 AFI 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.

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.

A comparison of cardiac computerized tomography and exercise stress electrocardiogram test for the investigation of stable chest pain: the clinical results of the CAPP randomized prospective trial.

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.

High-Dose Adenosine Overcomes the Attenuation of Myocardial Perfusion Reserve Caused by Caffeine

OBJECTIVES We studied whether an increase in adenosine dose overcomes caffeine antagonism on adenosine-mediated coronary vasodilation. BACKGROUND Caffeine is a competitive antagonist at the adenosine receptors, but it is unclear whether caffeine in coffee alters the actions of exogenous adenosine, and whether the antagonism can be surmounted by increasing the adenosine dose. METHODS Myocardial perfusion scintigraphy (MPS) was used to assess adenosine-induced hyperemia in 30 patients before (baseline) and after coffee ingestion (caffeine). At baseline, patients received 140 microg/kg/min of adenosine combined with low-level exercise. For the caffeine study, 12 patients received 140 microg/kg/min of adenosine (standard) and 18 patients received 210 microg/kg/min (high dose) after caffeine intake (200 mg). Myocardial perfusion was assessed semiquantitatively and quantitatively, and perfusion defect was characterized according to the presence of reversibility. RESULTS Caffeine reduced the magnitude of perfusion abnormality induced by standard adenosine as measured by the summed difference score (SDS) (12.0 +/- 4.4 at baseline vs. 4.1 +/- 2.1 after caffeine, p < 0.001) as well as defect size (18% [3% to 38%] vs. 8% [0% to 22%], p < 0.01), whereas it had no effect on the abnormalities caused by high-dose adenosine (SDS, 7.7 +/- 4.0 at baseline vs. 7.8 +/- 4.2 after caffeine, p = 0.7). There was good agreement between baseline and caffeine studies for segmental defect category (kappa = 0.72, 95% confidence interval: 0.65 to 0.79) in the high-dose group. An increase in adenosine after caffeine intake was well tolerated. CONCLUSIONS Caffeine in coffee attenuates adenosine-induced coronary hyperemia and, consequently, the detection of perfusion abnormality by adenosine MPS. This can be overcome by increasing the adenosine dose without compromising test tolerability.

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.

Myocardial perfusion scintigraphy in the UK: insights from the British Nuclear Cardiology Society Survey 2000.

Background: The National Institute for Health and Clinical Excellence (NICE) has recently published a very positive technology appraisal of myocardial perfusion scintigraphy (MPS). This has important implications for service provision within the National Health Service, and an accurate knowledge of the current level of MPS activity is necessary. Methods: A postal questionnaire was sent to 207 nuclear medicine departments in the UK, requesting information about nuclear cardiology facilities, activity, and practice. Non-responding departments were sent a second questionnaire, followed where necessary by a telephone call. Results: A response rate of 61% was achieved; 52% of departments performed MPS, and these tended to have more gamma cameras than those which did not (median (25th–75th centile) 2.0, 1.5–2.5 v 1.0, 0.5–1.5; p  =  0.02). The median number of studies performed was 256 (144–460). The estimated rate of MPS in the UK for the year 2000 was 1200 per million population. The median (25th–75th centile) waiting time for MPS was 16 (9–24) weeks. Pharmacological stress was used in 77% of studies, and a technetium-99m based radiopharmaceutical in 60% (two day protocol in 75%). Tomographic rather than planar imaging was performed in 88% of studies, of which 22% were ECG gated. A cardiologist was involved in reporting in 35% of studies. Conclusions: MPS activity in the UK remains low, and it tends to be provided as a low volume service with unacceptably long waiting times and a lack of involvement by cardiologists. The recent NICE appraisal may provide an impetus for further resourcing and development.

Protective effects of intermedin on cardiovascular, pulmonary and renal diseases: comparison with adrenomedullin and CGRP.

Intermedin/adrenomedullin-2 (IMD/AM2) belongs to the calcitonin gene-related peptide (CGRP) / adrenomedullin (AM) family. The biological actions of this family are attributed to their actions at three receptor subtypes comprising the calcitonin receptor-like receptor (CLR) complexed with one of three receptor activity modifying proteins. In contrast to AM and CGRP, IMD binds non-selectively to all three receptor subtypes: CGRP, AM1, AM2. The peptide displays an overlapping but differential and more restricted distribution across the healthy systemic and pulmonary vasculature, heart and kidney relative to CGRP and AM. This, combined with tissue, regional and cell-type specific receptor expression, underpins differences in regard to magnitude, potency and duration of haemodynamic, cardiac and renal effects of IMD relative to those of AM and CGRP, and receptor-subtype involvement. In common with other family members, IMD protects the mammalian vasculature, myocardium and kidney from acute ischaemia-reperfusion injury, chronic oxidative stress and pressure-loading; IMD inhibits apoptosis, attenuates maladaptive tissue remodelling and preserves cardiac and renal function. Robust upregulation of IMD expression in rodent models of cardiovascular and renal disease argues strongly for the pathophysiological relevance of this particular counter-regulatory peptide. Such findings are likely to translate well to the clinic: early reports indicate that IMD is expressed in and protects cultured human vascular and cardiac non-vascular cells from simulated ischaemia-reperfusion injury, primarily via the AM1 receptor, and may have utility as a plasma biomarker in cardiovascular disease. These observations should provide the rationale for short-term administration of the peptide in acute disease, including myocardial infarction, cerebrovascular insult, cardiac and renal failure.