Speeding up beta-blockade prior to coronary CT angiography: can we predict the dose of intravenous metoprolol required to achieve target heart rate in a given patient?

AIM: To evaluate the use and safety of intravenous (IV) metoprolol in a cohort of patients undergoing coronary computed tomographic angiography (CCTA) at a university hospital, and in particular, to establish if the minimum dose required to achieve the target heart rate (HR) in a given patient can be predicted from the baseline HR. MATERIALS AND METHODS: Patients undergoing CCTA at a tertiary centre between January 2015 and May 2018, with baseline HR ≥60 bpm requiring IV metoprolol, were identified retrospectively from the database. Patients with a contraindication to beta-blockade or an indication for CCTA other than coronary disease were excluded. HR at baseline and at the time of scanning were recorded, together with the total dose of IV metoprolol administered. RESULTS: Of 625 patients identified, 330 (52.8%) achieved HR ≤60 with IV metoprolol. Patients who achieved target HR had lower baseline HR. They received a lower radiation exposure due to tight prospective gating and a lower tube voltage. The lower quartile dose of metoprolol administered was 5 mg for patients with baseline HR <65 beats per minute (bpm), but 10 mg for HR 65-74 bpm, and ≥20 mg for higher HRs. There were no cases of symptomatic bradycardia/hypotension. CONCLUSION: Patients with a resting HR of ≥60 bpm can reasonably be given an initial minimum dose of 5-20 mg metoprolol IV before CCTA, with additional doses as required.

A qualitative and quantitative assessment of the impact of three processing algorithms with halving of study count statistics in myocardial perfusion imaging: filtered backprojection, maximal likelihood expectation maximisation and ordered subset expectation maximisation with resolution recovery.

INTRODUCTION: Ordered subset expectation maximisation with depth-dependent resolution recovery (OSEM-RR) is a processing algorithm reported to improve images with halved tracer activity in myocardial perfusion scintigraphy (MPS) compared to filtered backprojection (FBP) using conventional activities. OSEM-RR has not yet been compared with maximal likelihood expectation maximisation (MLEM). METHODS: 39 patients undergoing MPS and two anthropomorphic phantoms (one with, one without an inferior wall insert) had full-time (FT) and half-time (HT) SPECT datasets acquired simultaneously and processed by FBP, MLEM and OSEM-RR. Two experienced reporters scored images of all clinical studies (n=234) for conspicuity of a perfusion defect, with results being compared using Wilcoxon paired and Kappa tests. A quantitative assessment based on mean segmental pixel counts taken from numbers automatically displayed over the 20 segments of Cedars Sinai Autoquant QPS image were compared using Pearson's correlation and Bland Altman analysis. RESULTS: A small but consistent superior concurrence between FT and HT datasets for OSEM-RR compared to FBP and MLEM was observed for both qualitative and quantitative analyses. OSEM-RR resulted in better definition of the inferior wall defect on the phantom study. CONCLUSION: OSEM-RR appears superior to both FBP and MLEM in terms of handling reduced count statistics.

EANM/ESC guidelines for radionuclide imaging of cardiac function.

Radionuclide imaging of cardiac function represents a number of well-validated techniques for accurate determination of right (RV) and left ventricular (LV) ejection fraction (EF) and LV volumes. These first European guidelines give recommendations for how and when to use first-pass and equilibrium radionuclide ventriculography, gated myocardial perfusion scintigraphy, gated PET, and studies with non-imaging devices for the evaluation of cardiac function. The items covered are presented in 11 sections: clinical indications, radiopharmaceuticals and dosimetry, study acquisition, RV EF, LV EF, LV volumes, LV regional function, LV diastolic function, reports and image display and reference values from the literature of RVEF, LVEF and LV volumes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to "prevailing or general consensus". The guidelines are designed to assist in the practice of referral to, performance, interpretation and reporting of nuclear cardiology studies for the evaluation of cardiac performance.

Role of non-invasive imaging in the management of coronary artery disease: an assessment of likely change over the next 10 years. A report from the British Cardiovascular Society Working Group.

Coronary angiography has been the gold standard for determining the severity, extent and prognosis of coronary atheromatous disease for the past 15-20 years. However, established non-invasive testing (such as myocardial perfusion scintigraphy and stress echocardiography) and newer imaging modalities (multi-detector x ray computed tomography and cardiovascular magnetic resonance) now need to be considered increasingly as a challenge to coronary angiography in contemporary practice. An important consideration is the degree to which appropriate use of such techniques impacts on the need for coronary angiography over the next 10-15 years. This review aims to determine the role of the various investigation techniques in the management of coronary artery disease and their resource implications, and should help determine future service provision, accepting that we are in a period of significant technological change.

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.

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.

Transthoracic echocardiography using second harmonic imaging with Valsalva manoeuvre for the detection of right to left shunts.

AIMS: To assess transthoracic echocardiography (TTE) using second harmonic imaging with Valsalva manoeuvre compared to transesophageal echocardiography (TEE) for the diagnosis of right to left cardiac and pulmonary shunts. METHODS AND RESULTS: One hundred and ten patients referred for TEE underwent TTE with bubble contrast. Bubbles in the left atrium within three cardiac cycles were considered diagnostic for a patent foramen ovale (PFO) and later as a pulmonary shunt. Greater than 20 bubbles in the left atrium was considered a large shunt and less than 20 a small shunt. TEE was performed immediately afterwards and read blinded to the TTE results. Pick-up rates were similar with 19 TEE positive (13 PFO) and 18 TTE positive (14 PFO) patients. There were five TEE positive/TTE negative cases who had significantly poorer TTE image quality score (2.7 +/- 0.8 vs 1.9 +/- 0.6, p < 0.05). There were six TEE negative/TTE positive cases, two cases requiring Valsalva manoeuvre to become positive. The Valsalva manoeuvre significantly increased the number of bubbles shunting (10 +/- 11 vs 20 +/- 19, p < 0.005). CONCLUSION: TTE with Valsalva manoeuvre is as good as TEE in diagnosing shunts. Valsalva manoeuvre increases the size of shunt. Both techniques produce false negative results.

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.

Does a selective adenosine A(1) receptor agonist protect against exercise induced ischaemia in patients with coronary artery disease?

BACKGROUND: The "warm up" effect in angina may represent ischaemic preconditioning, which is mediated by adenosine A(1) receptors in most models. OBJECTIVE: To investigate the effect of a selective A(1) agonist, GR79236 (GlaxoSmithKline), on exercise induced angina and ischaemic left ventricular dysfunction in patients with coronary artery disease. DESIGN: A double blind crossover study. PATIENTS: 25 patients with multivessel coronary artery disease. INTERVENTIONS: On mornings one week apart, patients received intravenous GR79236 10 microgram/kg or placebo, and then carried out two supine bicycle exercise tests separated by 30 minutes. Equilibrium radionuclide angiography was done before and during exercise. RESULTS: The onset of chest pain or 1 mm ST depression was delayed and occurred at a higher rate-pressure product during the second exercise test following either placebo or GR79236. Compared with placebo, GR79236 did not affect these indices during equivalent tests. GR79236 reduced resting global ejection fraction from (mean (SD)) 63 (7)% to 61 (5)% (p < 0.05) by a selective reduction in the regional ejection fraction of "ischaemic" left ventricular sectors (those where the ejection fraction fell during the first exercise test following placebo). Ischaemic sectors showed increased function during the second test following placebo (72 (21)% v 66 (20)%; p = 0.0001), or during the first test following GR79236 (69 (21)% v 66 (20)%; p = 0.0001). Sequential exercise further increased the function of ischaemic sectors even after drug administration. CONCLUSIONS: GR79236 failed to mimic the warm up effect, and warm up occurred even in the presence of this agent. This suggests that ischaemic preconditioning is not an important component of this type of protection. The complex actions of the drug on regional left ventricular function at rest and during exercise suggest several competing A(1) mediated actions.

The warm-up effect protects against ischemic left ventricular dysfunction in patients with angina.

OBJECTIVES: The goal of this study was to investigate whether the "warm-up" effect in angina protects against ischemic left ventricular (LV) dysfunction. BACKGROUND: After exercise, patients with coronary disease demonstrate persistent myocardial dysfunction, which may represent stunning, as well as warm-up protection against further angina, which may represent ischemic preconditioning. The effect of warm-up exercise on LV function during subsequent exercise has not been investigated. METHODS: Thirty-two patients with multivessel coronary disease and preserved LV function performed two supine bicycle exercise tests 30 min apart. Equilibrium radionuclide angiography was performed before, during and up to 60 min after each test. Global LV ejection fraction and volume changes and regional ejection fraction for nine LV sectors were calculated for each acquisition. RESULTS: Onset of chest pain or 1 mm ST depression was delayed and occurred at a higher rate-pressure product during the second exercise test. Sectors whose regional ejection fraction fell during the first test showed persistent reduction at 15 min (68 +/- 20 vs. 73 +/- 20%, p < 0.0001). These sectors demonstrated increased function during the second test (71 +/- 20 vs. 63 +/- 20%, p = 0.0005). The reduction at 15 min and the increase during the second test were both in proportion to the reduction during the first test. Effects on global function were only apparent when the initial response to exercise was considered. CONCLUSIONS: The warm-up effect is accompanied by protection against ischemic regional LV dysfunction. The degree of stunning and protection after exercise is related to the severity of dysfunction during exercise, consistent with results from experimental models.

Does cytosine-thymine-guanine (CTG) expansion size predict cardiac events and electrocardiographic progression in myotonic dystrophy?

OBJECTIVE: To assess whether the size of the cytosine-thymine-guanine (CTG) expansion mutation in myotonic dystrophy predicts progression of conduction system disease and cardiac events. DESIGN: Longitudinal study involving ECG and clinical follow up over (mean (SD)) 4.8 (1.8) and 6.2 (1.9) years, respectively, of patients stratified by CTG expansion size (E0 to E4). PATIENTS: 73 adult patients under annual review in a regional myotonic dystrophy clinic. Patients were grouped into E0/E1 (n = 25), E2 (n = 34), and E3/E4 (n = 14). RESULTS: The proportion of patients with a QRS complex > 100 ms at baseline increased with the size of the CTG expansion (EO/E1, 4%; E2, 12%; E3/E4, 36%; p = 0.02). This trend was more pronounced at follow up (E0/E1, 4%; E2, 21%; E3/E4, 57%; p = 0.0004). The rate of widening of the QRS complex (ms/year) was similarly related to the size of the mutation (EO/E1, 0.4 (1.3); E2, 1.4 (2.5); E3/E4, 1.5 (1.6); p = 0.04). First degree atrioventricular block was present in 23% of patients at baseline and 34% at follow up, with no significant relation to expansion size. Seven patients suffered a cardiac event during follow up (sudden death in two, permanent pacemaker insertion in three, chronic atrial arrhythmia in two), of whom six were in CTG expansion group E2 or greater. Patients who experienced a cardiac event during follow up had more rapid rates of PR interval increase (9.9 (11.1) v 1.6 (2.9) ms/year; p = 0.008) and a trend to greater QRS complex widening (3.6 (4.5) v 0.9 (1.5) ms/year; p = 0.06) than those who did not. CONCLUSIONS: Larger CTG expansions are associated with a higher rate of conduction disease progression and a trend to increased risk of cardiac events in myotonic dystrophy.

Quantitative regional analysis of myocardial wall motion.

This paper presents a new technique for semiautomatic quantification of regional heart function from 2-D echocardiography. It uses a novel left ventricular border tracking algorithm based on shape-space ideas that we have recently described. In this paper, we show how to decompose the tracked output into clinically meaningful segmental parameters (wall excursion and thickening), using what we call a computational interpretational space (CIS). This leads to a quantitative and automatic scoring scheme for endocardial excursion and myocardial thickening. The method is illustrated on data from a patient with a myocardial infarct in the apical anterior/inferior region of the heart and is also assessed in a small retrospective dobutamine stress echocardiography clinical case study.

Exercise equilibrium radionuclide angiography predicts long-term cardiac prognosis in patients with abdominal aortic aneurysm being considered for surgery.

BACKGROUND: Patients with an abdominal aortic aneurysm (AAA) have a high prevalence of coronary disease and are at risk for cardiac events. This may offset the prognostic benefit of surgical repair. We investigated whether preoperative exercise equilibrium radionuclide angiography (ERNA) could be used to identify patients at high risk for cardiac events after successful AAA repair. METHODS: Between 1990 and 1995, 173 patients with an AAA were referred for supine bicycle exercise ERNA preoperatively. Follow-up information was obtained from a questionnaire sent to each patient's family physician. Cardiac events were defined as cardiac death or nonfatal myocardial infarction. RESULTS: A total of 139 patients were able to exercise and did not die or suffer myocardial infarction perioperatively. The median follow-up period was 3.8 years. Diabetes mellitus, an exercise ejection fraction (EF) below 0.50, and a fall in EF with exercise were univariable predictors of cardiac risk during the follow-up period (P < .05). On multivariable analysis, diabetes mellitus (risk ratio [RR], 6.9; 95% CI 1.5 to 32.0) and an EF fall (RR, 4.1; 95% CI 1.5 to 11.4) emerged as the most important predictors. CONCLUSIONS: Exercise ERNA predicts long-term cardiac events in patients being considered for elective AAA repair. Such predictive information may influence the decision to operate, for example, on small unthreatening aneurysms, or lead to invasive cardiological management to minimize risk.