Clinical Characteristics and Prognostic Factors of Myocarditis in New Zealand Patients.

BACKGROUND: Myocarditis is an inflammation of the heart muscle and an important cause of dilated cardiomyopathy. Its presentation is heterogeneous, and there are limited studies describing the clinical characteristics of these patients, or which factors predict adverse clinical outcomes. We performed a single-centre retrospective study to explore the clinical characteristics of patients with myocarditis. METHOD: Patients >15 years of age admitted to our centre with an ICD-10 diagnosis of myocarditis on their electronic discharge record between 2007 and 2016 were included. Clinical, biochemical and imaging factors were collected. The primary endpoint was combined major adverse cardiac events (MACE) consisting of all-cause mortality, decompensated heart failure leading to hospital admission, documented ventricular arrhythmia, recurrent myocarditis and heart transplantation. RESULTS: During this period, 178 patients were found to have a diagnosis of myocarditis (71% men, median age 39 years). Men were significantly younger than women (36 vs 53 years, U=4,543, p<0.001). ST-elevation on electrocardiogram was recorded in 59% of patients, and these patients were more likely to be male (85% vs 66%, p=0.012), younger (median age 32 vs 44 years, U=4,129, p=0.001) and to have chest pain (94% vs 65%, p<0.001). At a maximal follow-up of 8 years (mean 4.5 years), MACE occurred in 26 patients. MACE was associated with the presence of dyspnoea (26% vs 9%; hazard ratio [HR] 3.33, 95% confidence interval [CI] 1.53-7.28; p=0.003), pulmonary congestion on chest X-ray (54% vs 11%; HR 5.51; 95% CI 2.3-13.23; p<0.001), and left ventricular ejection fraction <50% on transthoracic echocardiography (24% vs 8%; HR 3.22; 95% CI 1.28-8.12; p=0.013). CONCLUSIONS: Myocarditis was more common in young men in our study. Factors associated with adverse outcomes in acute coronary syndromes were not seen in our younger population. Left ventricular dysfunction appears to be more important in predicting adverse outcomes in myocarditis.

ICare-ACS (Improving Care Processes for Patients With Suspected Acute Coronary Syndrome): A Study of Cross-System Implementation of a National Clinical Pathway.

BACKGROUND: Efforts to safely reduce length of stay for emergency department patients with symptoms suggestive of acute coronary syndrome (ACS) have had mixed success. Few system-wide efforts affecting multiple hospital emergency departments have ever been evaluated. We evaluated the effectiveness of a nationwide implementation of clinical pathways for potential ACS in disparate hospitals. METHODS: This was a multicenter pragmatic stepped-wedge before-and-after trial in 7 New Zealand acute care hospitals with 31 332 patients investigated for suspected ACS with serial troponin measurements. The implementation was a clinical pathway for the assessment of patients with suspected ACS that included a clinical pathway document in paper or electronic format, structured risk stratification, specified time points for electrocardiographic and serial troponin testing within 3 hours of arrival, and directions for combining risk stratification and electrocardiographic and troponin testing in an accelerated diagnostic protocol. Implementation was monitored for >4 months and compared with usual care over the preceding 6 months. The main outcome measure was the odds of discharge within 6 hours of presentation RESULTS: There were 11 529 participants in the preimplementation phase (range, 284-3465) and 19 803 in the postimplementation phase (range, 395-5039). Overall, the mean 6-hour discharge rate increased from 8.3% (range, 2.7%-37.7%) to 18.4% (6.8%-43.8%). The odds of being discharged within 6 hours increased after clinical pathway implementation. The odds ratio was 2.4 (95% confidence interval, 2.3-2.6). In patients without ACS, the median length of hospital stays decreased by 2.9 hours (95% confidence interval, 2.4-3.4). For patients discharged within 6 hours, there was no change in 30-day major adverse cardiac event rates (0.52% versus 0.44%; P=0.96). In these patients, no adverse event occurred when clinical pathways were correctly followed. CONCLUSIONS: Implementation of clinical pathways for suspected ACS reduced the length of stay and increased the proportions of patients safely discharged within 6 hours. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au/ (Australian and New Zealand Clinical Trials Registry). Unique identifier: ACTRN12617000381381.

Educational renewal of physician training in Australia and New Zealand: Multiple educational innovations in a complex environment.

AIM: The Royal Australasian College of Physicians is renewing its specialty training programs and shifting towards competency-based medical education. Our aim is to improve the quality and rigor of training and graduate outcomes, and promote high standards of physician practice to serve the health of patients, families, and communities in a changing healthcare environment. METHODS: We are progressing holistic change and multiple educational innovations in a complex environment. Numerous stakeholders, a disparate training landscape and a largely volunteer supervisor workforce pose challenges in supporting effective implementation. This paper describes our progress and experience with three key components of our education renewal program: curricular renewal, a new selection process and faculty development. It offers reflections on the practical challenges, lessons learned and factors critical for success. CONCLUSIONS: Our experience highlights opportunities for training organizations to maximize their influence over workplace training experiences and outcomes by taking a systems approach to the design, delivery and evaluation of the components of education renewal. We found that design, development and delivery of our multiple educational innovations have benefited from co-design approaches, progressive and concurrent development, continual exploration of new strategies, and implementation as soon as viable with a commitment to iterative improvements over time.

Determination of Clinical Outcome in Mitral Regurgitation With Cardiovascular Magnetic Resonance Quantification.

BACKGROUND: Surgery for severe mitral regurgitation is indicated if symptoms or left ventricular dilation or dysfunction occur. However, prognosis is already reduced by this stage, and earlier surgery on asymptomatic patients has been advocated if valve repair is likely, but identifying suitable patients for early surgery is difficult. Quantifying the regurgitation may help, but evidence for its link with outcome is limited. Cardiovascular magnetic resonance (CMR) can accurately quantify mitral regurgitation, and we examined whether this was associated with the future need for surgery. METHODS AND RESULTS: One hundred nine asymptomatic patients with echocardiographic moderate or severe mitral regurgitation had baseline CMR scans and were followed up for up to 8 years (mean, 2.5±1.9 years). CMR quantification accurately identified patients who progressed to symptoms or other indications for surgery: 91% of subjects with regurgitant volume ≤55 mL survived to 5 years without surgery compared with only 21% with regurgitant volume >55 mL (P<0.0001). A similar separation was observed for regurgitant fraction ≤40% and >40%. CMR-derived end-diastolic volume index showed a weaker association with outcome (proportions surviving without surgery at 5 years, 90% for left ventricular end-diastolic volume index <100 mL/m(2) versus 48% for ≥100 mL/m(2)) and added little to the discriminatory power of regurgitant fraction/volume alone. CONCLUSIONS: CMR quantification of mitral regurgitation was associated with the development of symptoms or other indications for surgery and showed better discriminatory ability than the reference-standard CMR-derived ventricular volumes. CMR may be able to identify appropriate patients for early surgery, with the potential to change clinical practice, although the clinical benefits of early surgery require confirmation in a clinical trial.

Aortic regurgitation quantification using cardiovascular magnetic resonance: association with clinical outcome.

BACKGROUND: Current indications for surgery in patients with significant aortic regurgitation (AR) focus on symptoms and left ventricular dilation/dysfunction. However, prognosis is already reduced by this stage, and earlier identification of patients for surgery could be beneficial. Quantifying the regurgitation may help, but there are limited data on its link with outcome. Cardiovascular magnetic resonance (CMR) can accurately quantify AR, and we examined whether this was associated with the future need for surgery. METHODS AND RESULTS: One hundred thirteen patients with echocardiographic moderate or severe AR were monitored for up to 9 years (mean 2.6 ± 2.1 years) following a CMR scan, and the progression to symptoms or other indications for surgery was monitored. AR quantification identified outcome with high accuracy: 85% of the 39 subjects with regurgitant fraction >33% progressed to surgery (mostly within 3 years) in comparison with 8% of 74 subjects with regurgitant fraction ≤ 33% (P<0.0001); the area under the curve on receiver operating characteristic analysis was 0.93 (P<0.0001). This ability remained strong on time-dependent Kaplan-Meier survival curves. CMR-derived left ventricular end-diastolic volume >246 mL had good, although lower, discriminatory ability (area under the curve 0.88), but the combination of this measure with regurgitant fraction provided the best discriminatory power. CONCLUSIONS: High degrees of CMR-quantified AR were associated with the development of symptoms or other indications for surgery. Quantifying AR showed slightly better discriminatory ability than "gold standard" CMR ventricular volume assessment. This could provide a new paradigm for the timing of surgical intervention but requires confirmation in a clinical trial.

New Echocardiography Reference Ranges for Aotearoa (NewERA) Study: the application of international echocardiographic reference values to linear measurements of the hearts of healthy, young Maori and Pacific adults may not detect cardiac enlargement.

AIMS: To develop ethnic-specific echocardiography reference ranges for Aotearoa, and to investigate the impact of indexation to body surface area (BSA). Current reference international ranges are derived from people of mostly NZ European ethnicity and may not be appropriate for Maori and New Zealanders of Pacific ethnicity, who both experience high rates of cardiovascular disease. METHODS: Echocardiography was performed in a cross-sectional study of 263 healthy adults (18-50 years): Maori (N=71, 43 female), Pacific (N=53, 28 female), European (N=139, 74 female). Linear measurements of the left heart are reported and indexed to BSA. The upper/lower limit of normal (ULN/LLN) by ethnicity and sex were derived (quantile regression). Ethnic- and sex-specific differences were examined using ANOVA. RESULTS: The ULN was higher for all un-indexed dimensions in men compared to women, and for most indices the ULN was smallest in NZ Europeans and largest in Maori and Pacific peoples. Indexation reversed these relationships: NZ Europeans had higher ULN for many measurements. CONCLUSIONS: Indexing to BSA introduced bias that preferences the NZ European ethnicity by creating an upper limit reference threshold that far exceeds this sample's upper range. As a result, this may lead to under-recognition of cardiac enlargement in Maori and Pacific patients, and in particular for women. Unique reference ranges for all ethnic groups and sexes are required to optimally detect and manage cardiovascular diseases (CVD) in Aotearoa.

Assessment of valvular heart disease by cardiovascular magnetic resonance imaging: a review.

CMR is a comprehensive non-invasive tool capable of evaluating all aspects of valvular heart disease. It has advantages over echo including direct quantification of regurgitant lesions, highly accurate assessment of ventricular size and function, visualisation myocardial scar, and interrogation of extracardiac abnormalities. Although these gains can be realised with current scanning techniques, CMR's full potential has yet to be realised, and further studies of clinical outcomes are needed before CMR data can be integrated into the management algorithms for patients with significant valvular lesions.

An uncommon cause of myocardial infarction.

A 73 year-old lady with hypertension and chronic atrial fibrillation (AF) developed chest pain followed by ventricular fibrillation (VF) cardiac arrest. Her electrocardiogram post-cardioversion revealed inferior ST-elevation myocardial infarction (MI). Her coronary arteries were angiographically normal. Contrast-enhanced cardiac magnetic resonance(CE-CMR) demonstrated both an inferior subendocardial infarction and left atrial (LA) appendage thrombus suggesting cardioembolism as the most likely cause of her presentation.

Stress perfusion imaging using cardiovascular magnetic resonance: a review.

Stress perfusion CMR can provide both excellent diagnostic and important prognostic information in the context of a comprehensive assessment of cardiac anatomy and function. This coupled with the high spatial resolution, and the lack of both attenuation artefacts and ionising radiation, make CMR stress perfusion imaging a highly attractive stress imaging modality. It is now in routine use in many centres, and shows promise in evaluating patients with clinical problems beyond those of epicardial coronary disease.

Causal Link between Ventricular Ectopy and Concussion.

We present a unique case study report of a male individual with a history of mild nonischaemic cardiomyopathy, with no ventricular ectopy, that at the age of 76 years sustained multiple concussions (i.e., mild traumatic brain injury) within a week of each other. Concussion symptoms included cognitive difficulties, "not feeling well," lethargy, fatigue, and signs of depression. He was later medically diagnosed with postconcussion syndrome. The patient, WJT, was referred for cardiac and neurological assessment. Structural neuroimaging of the brain (MRI) was unremarkable, but electrocardiography (ECG) assessments using a 24-hour Holter monitor revealed significant incidence of ventricular ectopy (9.4%; 9,350/99,836 beats) over a period of 5-6 months after injury and then a further increase in ventricular ectopy to 18% (15,968/88,189 beats) during the subsequent 3 months. The patient was then prescribed Amiodarone 200 mg, and his ventricular ectopy and concussion symptoms completely resolved simultaneously within days. To the authors' knowledge, our study is the first to show a direct link between observable and documented cardiac dysregulation and concussion symptomology. Our study has important implications for both cardiac patients and the patients that sustain a concussion, and if medically managed with appropriate pharmacological intervention, it can reverse ventricular ectopy and concussion symptomology. More research is warranted to investigate the mechanisms for this dramatic and remarkable change in cardiac and cerebral functions and to further explore the brain-heart interaction and the intricate autonomic interaction that exists between the extrinsic and intracardiac nervous systems.

Myocardial scar detected by contrast-enhanced cardiac magnetic resonance imaging is associated with ventricular tachycardia in hypertrophic cardiomyopathy patients.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is associated with myocardial scarring and ventricular tachycardia (VT). Contrast-enhanced cardiac magnetic resonance imaging (CE-CMR) can quantify myocardial scar, and scar imaging has been documented in patients with HCM. We investigated the assessment of myocardial scar in HCM patients using CE-CMR, and its correlation with proven VT. METHODS: Twenty-five patients (mean age 54 +/- 8) with HCM who underwent CE-CMR were identified, and clinical data obtained from chart review. Parameters of LV function were calculated from cine imaging, and myocardial scar was assessed using delayed enhancement imaging following gadolinium administration. RESULTS: Myocardial scar was detected in 16 (64%) patients with a mean mass 9 +/- 15 g. Scar was patchy, mid-myocardial and located in the basal anteroseptum, and RV insertion sites. Scar was seen in septal, apical and concentric variants of HCM. Scar mass correlated with both LV Mass (r2 = 0.74) and maximal LV wall thickness (r2 = 0.42). VT occurred in 32% of patients, and was associated with both increased scar mass and wall thickness compared to non-VT patients (21 +/- 22 g vs. 4 +/- 6 g, and 2.4 +/- 0.5 cm vs. 1.8 +/- 0.5 cm, p < 0.05). LV size and function were similar in patients with and without VT. A scar mass of >7 g predicted the presence of VT with a sensitivity of 75% and specificity 82%. CONCLUSIONS: Myocardial scar imaged by CE-CMR is common in patients with HCM, and is predictive of VT. Scar is seen in all HCM variants, and is associated with maximal wall thickness. There may be a role for CE-CMR in improved risk stratification for individual patients with HCM.

Effects of nitroglycerin on erythrocyte rheology and oxygen unloading: novel role of S-nitrosohemoglobin in relieving myocardial ischemia.

BACKGROUND: We hypothesized that nitroglycerin improves O2 delivery to ischemic tissue by altering erythrocyte rheology and O2 unloading through an increase in bioactive nitric oxide (NO) content. METHODS AND RESULTS: Twelve dogs with resting flow-reducing single-vessel stenosis were studied at rest and during intracoronary infusion of nitroglycerin (0.3 to 0.6 microg.kg(-1).min(-1)). Half the dogs also had occlusion of the remote coronary artery to remove any collateral effects. Systemic and coronary hemodynamics, myocardial blood flow (MBF), whole blood viscosity (WBeta), erythrocyte charge (EC) and mobility (EM), regional myocardial O2 delivery and consumption, and tissue O2 pressure (Po2) were measured. No changes in systemic hemodynamics were seen with nitroglycerin. Despite flow-limiting stenosis, MBF increased significantly in the central 25% of the ischemic bed, which was associated with an approximately 19% decrease in WBeta. There was a good correlation (r=0.87) between the two. The decrease in WBeta was associated with a decrease in EC and an increase in EM (r=0.83). The nitroglycerin-induced increase in tissue Po2 was disproportionate to the increase in MBF, indicating enhanced O2 unloading. Erythrocyte S-nitrosothiol content (reflecting mainly S-nitrosohemoglobin) was significantly higher for blood exposed in vitro to 0.1 micromol/L nitroglycerin or the NO donor SNAP, as compared with control (18.9+/-8.8 and 10.5+/-6.5 versus 2.6+/-0.5x10(-5), P<0.05). CONCLUSIONS: The augmented MBF in the ischemic microcirculation during nitroglycerin administration occurs in tandem with increased erythrocyte S-nitrosothiol content, EM, and O2 unloading. These additional microvascular mechanisms may contribute to the powerful antiischemic effects of nitroglycerin, especially during low-flow states.

ECG-derived spatial QRS-T angle is associated with ICD implantation, mortality and heart failure admissions in patients with LV systolic dysfunction.

BACKGROUND: Increased spatial QRS-T angle has been shown to predict appropriate implantable cardioverter defibrilIator (ICD) therapy in patients with left ventricular systolic dysfunction (LVSD). We performed a retrospective cohort study in patients with left ventricular ejection fraction (LVEF) 31-40% to assess the relationship between the spatial QRS-T angle and other advanced ECG (A-ECG) as well as echocardiographic metadata, with all-cause mortality or ICD implantation for secondary prevention. METHODS: 534 patients ≤75 years of age with LVEF 31-40% were identified through an echocardiography reporting database. Digital 12-lead ECGs were retrospectively matched to 295 of these patients, for whom echocardiographic and A-ECG metadata were then generated. Data mining was applied to discover novel ECG and echocardiographic markers of risk. Machine learning was used to develop a model to predict possible outcomes. RESULTS: 49 patients (17%) had events, defined as either mortality (n = 16) or ICD implantation for secondary prevention (n = 33). 72 parameters (58 A-ECG, 14 echocardiographic) were univariately different (p<0.05) in those with vs. without events. After adjustment for multiplicity, 24 A-ECG parameters and 3 echocardiographic parameters remained different (p<2x10-3). These included the posterior-to-leftward QRS loop ratio from the derived vectorcardiographic horizontal plane (previously associated with pulmonary artery pressure, p = 2x10-6); spatial mean QRS-T angle (134 vs. 112°, p = 1.6x10-4); various repolarisation vectors; and a previously described 5-parameter A-ECG score for LVSD (p = 4x10-6) that also correlated with echocardiographic global longitudinal strain (R2 = - 0.51, P < 0.0001). A spatial QRS-T angle >110° had an adjusted HR of 3.4 (95% CI 1.6 to 7.4) for secondary ICD implantation or all-cause death and adjusted HR of 4.1 (95% CI 1.2 to 13.9) for future heart failure admission. There was a loss of complexity between A-ECG and echocardiographic variables with an increasing degree of disease. CONCLUSION: Spatial QRS-T angle >110° was strongly associated with arrhythmic events and all-cause death. Deep analysis of global ECG and echocardiographic metadata revealed underlying relationships, which otherwise would not have been appreciated. Delivered at scale such techniques may prove useful in clinical decision making in the future.

Assessment of endogenous and therapeutic arteriogenesis by contrast ultrasound molecular imaging of integrin expression.

BACKGROUND: We hypothesized that molecular imaging with contrast-enhanced ultrasound (CEU) and microbubbles targeted to endothelial integrins could be used to noninvasively assess early angiogenic responses to ischemia and growth factor therapy. METHODS AND RESULTS: Hindlimb ischemia was produced in 48 rats by ligation of an iliac artery. Half of the animals received intramuscular sustained-release fibroblast growth factor-2 (FGF-2). Immediately after ligation and at subsequent intervals from 4 to 28 days, blood flow and oxygen tension in the proximal adductor muscles were measured by CEU perfusion imaging and phosphor quenching, respectively. Targeted CEU imaging of alpha(v)- and alpha5beta1-integrin expression was performed with microbubbles bearing the disintegrin echistatin. Iliac artery ligation produced a 65% to 70% reduction in blood flow and oxygen tension. In untreated ischemic muscle, muscle flow and oxygen tension partially recovered by days 14 to 28. In these animals, signal from integrin-targeted microbubbles was intense and peaked before flow increase (days 4 to 7). In comparison to untreated animals, FGF-2-treated muscle had a greater rate and extent of blood flow recovery and greater signal intensity from integrin-targeted microbubbles, which peaked before maximal recovery of flow. On immunohistology, arteriolar but not capillary density increased in the ischemic limb after ligation, the rate and degree of which were greater in FGF-2-treated rats. Immunofluorescence demonstrated intense staining for alpha(v) in arterioles, the temporal course of which correlated with targeted imaging. CONCLUSIONS: Targeted CEU can be used to assess endogenous and therapeutic arteriogenesis before recovery of tissue perfusion. These results suggest that molecular imaging of integrin expression may be useful for evaluating proangiogenic therapies.

Detection of myocardial scar by contrast-enhanced cardiac magnetic resonance imaging in patients with troponin-positive chest pain and minimal angiographic coronary artery disease.

Patients who present with chest pain and elevated serum troponin levels may have minimal angiographic coronary artery disease, leading to diagnostic confusion. We investigated patients with troponin-positive acute coronary syndromes and minimal coronary artery disease (CAD) using contrast-enhanced cardiac magnetic resonance imaging to assess for myocardial scar. Twenty-three patients (54 +/- 8 years of age) who presented with chest pain, high troponin I level, and minimal angiographic CAD were included. Patients with a clinical pericarditis/myocarditis, tachyarrhythmia at presentation, previous myocardial infarction, or an alternative explanation for increased troponin I level were excluded. Myocardial scar was assessed with delayed-enhancement inversion-recovery imaging after administration of gadolinium. Hyperenhancement consistent with myocardial scar was seen in 7 of 23 patients (30%) and was located primarily in the right coronary artery distribution. Peak troponin level, clinical characteristics, and volumetric parameters were similar in patients with or without hyperenhancement. One patient had mid-myocardial enhancement that suggested undiagnosed myocarditis. There was a linear relation between the mass of myocardial scar and peak serum troponin level. In follow-up, subsequent cardiac events were more frequent in patients with hyperenhancement (43% vs 12.5%). In conclusion, patients with troponin-positive acute coronary syndromes may have significant myocardial scar even when minimal CAD is found on angiography.

Bias associated with left ventricular quantification by multimodality imaging: a systematic review and meta-analysis.

PURPOSE: Cardiac MR (CMR) is the gold standard for left ventricular (LV) quantification. However, two-dimensional echocardiography (2DE) is the most common approach, and both three-dimensional echocardiography (3DE) and multidetector CT (MDCT) are increasingly available. The clinical significance and interchangeability of these modalities remains under-investigated. Therefore, we undertook a systemic review to evaluate the accuracy and absolute bias in LV quantification of all the commonly available non-invasive imaging modalities (2DE, CE-2DE, 3DE, MDCT) compared to cardiac MR (CMR). METHODS: Studies were included that reported LV echocardiographic (2DE, CE-2DE, 3DE) and/or MDCT measurements compared to CMR. Only modern CMR (SSFP sequences) was considered. Studies involving small sample size (<10 patients) and unusual cardiac geometry (ie, congenital heart diseases) were excluded. We evaluated LV end-diastolic volume (LVEDV), end-systolic volume (LVESV) and ejection fraction (LVEF). RESULTS: 1604 articles were initially considered: 65 studies were included (total of 4032 scans (echo, CT, MRI) performed in 2888 patients). Compared to CMR, significant biased underestimation of LV volumes with 2DE was seen (LVEDV-33.30 mL, LVESV -16.20 mL, p<0.0001). This difference was reduced but remained significant with CE-2DE (LVEDV -18.05, p<0.0001) and 3DE (LVEDV -14.41, p<0.001), while MDCT values were similar to CMR (LVEDV -1.20, p=0.43; LVESV -0.13, p=0.91). However, excellent agreement for echocardiographic LVEF evaluation (2DE LVEF 0.78-1.01%, p=0.37) was observed, especially with 3DE (LVEF 0.14%, p=0.88). CONCLUSIONS: Comparing imaging modalities to CMR as reference standard, 3DE had the highest accuracy in LVEF estimation: 2DE and 3DE-derived LV volumes were significantly underestimated. Newer generation CT showed excellent accuracy for LV volumes.

The value of CT cardiac angiography and CT calcium score testing in a modern cardiology service in New Zealand: a report of a single centre eight-year experience from 5,237 outpatient procedures.

BACKGROUND: Computed tomographic (CT) cardiac angiography is of increasing value in several areas of patient management in cardiology. We assessed the ability of CT cardiac angiography to effectively 'rule out' severe coronary stenoses in patients presenting with 'atypical' symptoms and/or an equivocal stress test, which offers a new approach to the management of coronary artery disease. We also examined the use of the CT calcium score test in cardiovascular (CVS) risk assessment. METHODS: From a large single centre (Mercy Hospital) in Auckland, using a prospectively acquired, comprehensive database, we audited the entire eight-year experience of 5,169 patients (7/8/06 to 31/1/14) who underwent 5,237 64-slice computed tomographic (CT) cardiac angiogram or CT calcium score tests (GE Lightspeed scanner). RESULTS: From 5,169 patients there were 5,237 CT procedures. The mean patient age was 57 (SD 10) years; 42% patients were female. Of the 3,603 (69%) full CT cardiac angiogram scans, 3,509 (67%) included a calcium score test. One thousand four hundred and eighty-three (28%) of scans were a calcium score test only. Of the 3,603 (69%) full CT cardiac angiogram scans, it was possible to 'rule out' significant coronary atheroma (stenosis ≥50%) in 2,947 (82%) of these procedures. Of the 4,903 (94%) patients who had a CT calcium score test, in whom we could calculate the NZ Framingham-based CVS risk, it was possible to reassign 532 (22%) of these patients who were previously thought to be at 'low risk' to be at a higher CVS risk. CONCLUSION: CT cardiac angiography has become established in the modern management of cardiology patients. It has particular value as a tool to 'rule out' severe coronary stenoses, and as a tool to give a more accurate assessment of CVS risk. It adds significant value to the care of many patients within an established cardiology practice.

Noninvasive assessment of angiogenesis by ultrasound and microbubbles targeted to alpha(v)-integrins.

BACKGROUND: Noninvasive methods for characterizing neovessel formation during angiogenesis are currently lacking. We hypothesized that angiogenesis could be imaged with the use of contrast-enhanced ultrasound (CEU) with microbubbles targeted to alpha(v)-integrins. METHODS AND RESULTS: Microbubbles targeted to alpha(v)-integrins were prepared by conjugating echistatin (MB(E)) or monoclonal antibody against murine alpha(v) (MB(alpha)) to their surface. Control microbubbles (MB(c)) were also prepared. The microvascular behavior of these microbubbles was assessed by intravital microscopy of the cremaster muscle in mice treated for 4 days with sustained-release FGF-2. Microvascular retention was much greater (P<0.01) for MB(E) (11+/-6 mm(-3)) and MB(alpha) (10+/-7 mm(-3)) than that for MB(c) (1+/-1 mm(-3)). Retained MB(E) and MB(alpha) attached directly to the microvascular endothelial surface. Microbubble retention in 4 control mice was minimal. Subcutaneous matrigel plugs enriched with FGF-2 were created in 12 mice and studied 10 days later. Neovessels within the matrigel stained positive for alpha(v)-integrins. CEU demonstrated greater (P<0.01) acoustic intensity for MB(E) (16.0+/-5.9 U) and MB(alpha) (17.0+/-5.5 U) compared with MB(c) (5.8+/-2.6 U). The signal from targeted microbubbles (MB(E) and MB(alpha)) correlated well (r=0.90) with the matrigel blood volume determined by CEU perfusion imaging. CONCLUSIONS: CEU with microbubbles targeted for alpha(v)-integrins may provide a noninvasive method for assessing therapeutic angiogenesis.