Dobutamine Stress Echocardiography Ischemia as a Predictor of the Placebo-Controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Stress Echocardiography-Stratified Analysis of ORBITA.

BACKGROUND: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina). METHODS: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling. RESULTS: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (Pinteraction=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (Pinteraction=0.116), physical limitation (Pinteraction=0.461), quality of life (Pinteraction=0.689), EuroQOL 5 quality-of-life score (Pinteraction=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (Pinteraction=0.693), and treadmill exercise time (Pinteraction=0.426). CONCLUSIONS: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02062593.

Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Single-Vessel Coronary Artery Disease.

BACKGROUND: There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease. METHODS: We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling. RESULTS: Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], -4.0 to 45.5; P=0.100) with no interaction of FFR ( Pinteraction=0.318) or iFR ( Pinteraction=0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70-1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR ( Pinteraction<0.00001) and decreasing iFR ( Pinteraction<0.00001). PCI did not improve angina frequency score significantly more than placebo (odds ratio, 1.64; 95% CI, 0.96-2.80; P=0.072) with no detectable evidence of interaction with FFR ( Pinteraction=0.849) or iFR ( Pinteraction=0.783). However, PCI resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47; 95% CI, 1.30-4.72; P=0.006) but neither FFR ( Pinteraction=0.693) nor iFR ( Pinteraction=0.761) modified this effect. CONCLUSIONS: In patients with stable angina and severe single-vessel disease, the blinded effect of PCI was more clearly seen by stress echocardiography score and freedom from angina than change in treadmill exercise time. Moreover, the lower the FFR or iFR, the greater the magnitude of stress echocardiographic improvement caused by PCI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02062593.

Population-based studies of myocardial hypertrophy: high resolution cardiovascular magnetic resonance atlases improve statistical power.

BACKGROUND: Cardiac phenotypes, such as left ventricular (LV) mass, demonstrate high heritability although most genes associated with these complex traits remain unidentified. Genome-wide association studies (GWAS) have relied on conventional 2D cardiovascular magnetic resonance (CMR) as the gold-standard for phenotyping. However this technique is insensitive to the regional variations in wall thickness which are often associated with left ventricular hypertrophy and require large cohorts to reach significance. Here we test whether automated cardiac phenotyping using high spatial resolution CMR atlases can achieve improved precision for mapping wall thickness in healthy populations and whether smaller sample sizes are required compared to conventional methods. METHODS: LV short-axis cine images were acquired in 138 healthy volunteers using standard 2D imaging and 3D high spatial resolution CMR. A multi-atlas technique was used to segment and co-register each image. The agreement between methods for end-diastolic volume and mass was made using Bland-Altman analysis in 20 subjects. The 3D and 2D segmentations of the LV were compared to manual labeling by the proportion of concordant voxels (Dice coefficient) and the distances separating corresponding points. Parametric and nonparametric data were analysed with paired t-tests and Wilcoxon signed-rank test respectively. Voxelwise power calculations used the interstudy variances of wall thickness. RESULTS: The 3D volumetric measurements showed no bias compared to 2D imaging. The segmented 3D images were more accurate than 2D images for defining the epicardium (Dice: 0.95 vs 0.93, P<0.001; mean error 1.3 mm vs 2.2 mm, P<0.001) and endocardium (Dice 0.95 vs 0.93, P<0.001; mean error 1.1 mm vs 2.0 mm, P<0.001). The 3D technique resulted in significant differences in wall thickness assessment at the base, septum and apex of the LV compared to 2D (P<0.001). Fewer subjects were required for 3D imaging to detect a 1 mm difference in wall thickness (72 vs 56, P<0.001). CONCLUSIONS: High spatial resolution CMR with automated phenotyping provides greater power for mapping wall thickness than conventional 2D imaging and enables a reduction in the sample size required for studies of environmental and genetic determinants of LV wall thickness.

United Kingdom standards for non-invasive cardiac imaging: recommendations from the Imaging Council of the British Cardiovascular Society.

Heart and circulatory diseases affect more than seven million people in the UK. Non-invasive cardiac imaging is a critical element of contemporary cardiology practice. Progressive improvements in technology over the last 20 years have increased diagnostic accuracy in all modalities and led to the incorporation of non-invasive imaging into many standard cardiac clinical care pathways. Cardiac imaging tests are requested by a variety of healthcare practitioners and performed in a range of settings from the most advanced hospitals to local health centres. Imaging is used to detect the presence and consequences of cardiovascular disease, as well as to monitor the response to therapies. The previous UK national imaging strategy statement which brought together all of the non-invasive imaging modalities was published in 2010. The purpose of this document is to collate contemporary standards developed by the modality-specific professional organisations which make up the British Cardiovascular Society Imaging Council, bringing together common and essential recommendations. The development process has been inclusive and iterative. Imaging societies (representing both cardiology and radiology) reviewed and agreed on the initial structure. The final document therefore represents a position, which has been generated inclusively, presents rigorous standards, is applicable to clinical practice and deliverable. This document will be of value to a variety of healthcare professionals including imaging departments, the National Health Service or other organisations, regulatory bodies, commissioners and other purchasers of services, and service users, i.e., patients, and their relatives.

Multiple thromboembolic events associated with bilateral superior vena cava and anomalous drainage into the left atrium.

A 49-year-old female patient presented with acute-on-chronic chest pain. She was diagnosed with multiple systemic thromboemboli, including myocardial infarctions, bilateral chronic pulmonary emboli, ischaemic stroke, deep venous thrombosis and superficial thrombophlebitis. She had a background of sickle cell trait. Cardiac magnetic resonance showed bilateral superior vena cava (SVC). The right-sided SVC (RSVC) was joined by the right upper pulmonary vein and drained anomalously into the left atrium. This caused a small volume right to left shunt. The persistent left SVC drained into the right atrium (RA) via a dilated coronary sinus. The overall clinical impression was recurrent paradoxical emboli due to anomalous venous anatomy with a thrombophilia secondary to sickle cell trait. In the normal embryo, the right common cardinal vein develops to become the RSVC, which drains into the RA by term.

Regional variation in cardiovascular magnetic resonance service delivery across the UK.

OBJECTIVES: To examine service provision in cardiovascular magnetic resonance (CMR) in the UK. Equitable access to diagnostic imaging is important in healthcare. CMR is widely available in the UK, but there may be regional variations. METHODS: An electronic survey was sent by the British Society of CMR to the service leads of all CMR units in the UK in 2019 requesting data from 2017 and 2018. Responses were analysed by region and interpreted alongside population statistics. RESULTS: The survey response rate was 100% (82 units). 100 386 clinical scans were performed in 2017 and 114 967 in 2018 (15% 1-year increase; 5-fold 10-year increase compared with 2008 data). In 2018, there were 1731 CMR scans/million population overall, with significant regional variation, for example, 4256 scans/million in London vs 396 scans/million in Wales. Median number of clinical scans per unit was 780, IQR 373-1951, range 98-10 000, with wide variation in mean waiting times (median 41 days, IQR 30-49, range 5-180); median 25 days in London vs 180 days in Northern Ireland). Twenty-five units (30%) reported mean elective waiting times in excess of 6 weeks, and 8 (10%) ≥3 months. There were 351 consultants reporting CMR, of whom 230 (66%) were cardiologists and 121 (34%) radiologists; 81% of units offered a CMR service for patients with pacemakers and defibrillators. CONCLUSIONS: This survey provides a unique, contemporary insight into national CMR delivery with 100% centre engagement. The 10-year growth in CMR usage at fivefold has been remarkable but heterogeneous across the UK, with some regions still reporting low usage or long waiting times which may be of clinical concern.

Placebo-Controlled Efficacy of Percutaneous Coronary Intervention for Focal and Diffuse Patterns of Stable Coronary Artery Disease.

[Figure: see text].

Measuring the heart in pulmonary arterial hypertension (PAH): implications for trial study size.

PURPOSE: To calculate the sample size for a theoretical pulmonary arterial hypertension (PAH) randomized controlled trial (RCT) by using cardiovascular magnetic resonance (CMR) imaging to determine the repeatability of measures between two scans. MATERIALS AND METHODS: Two same-day examinations from 10 PAH patients were analyzed manually and semiautomatically. Study size was calculated from the standard deviation (SD) of repeatability. Different approaches to right-ventricle (RV) mass were investigated, agreement between methods tested and interobserver reproducibility measured by Bland-Altman analysis to explore how the PAH heart might be best measured. RESULTS: Repeatability was good for almost all manually-measured indices but poor for semiautomated measurement of RV mass and left-ventricle (LV) end-diastolic volume (EDV). Thus, for an RCT (power, 80%; significance level, 5%) analyzing "outcome" indices (RVEDV, LVEDV, RV ejection fraction, and RV mass; anticipated change: 10 mL, 10 mL, 3%, and 10 g, respectively) manually, 34 patients are required compared to 78 if analysis is semiautomated. RV mass was repeatable if the interventricular septum was divided between ventricles or if wholly apportioned to the LV. Limits of agreement between manual and semiautomated analyses were unsatisfactory for RV measures and interobserver reproducibility was worse for semiautomated than manual analysis. CONCLUSION: Manual is more robust than semiautomated analysis and at present should be favored in RCTs in PAH as it leads to lower sample size requirements.

Validation of carotid arterial wall volume measurement by cardiovascular magnetic resonance.

PURPOSE: To validate cardiovascular magnetic resonance (CMR) arterial wall volume measurement using whole arterial specimens ex vivo. MATERIALS AND METHODS: Twenty cadaveric carotid arteries (from 10 patients) were fixed in formaldehyde and imaged with a clinical T1-weighted 2D CMR sequence and, for imaging validation, with a high-resolution 3D sequence. Histological validation was performed by sectioning the arteries and microscopically determining area and volume. RESULTS: Comparison between the clinical 2D CMR sequence and the 3D high-resolution validation sequence showed equivalent luminal volumes (889 vs. 880 mm(3); P = 0.54; R(2) = 0.99), and slightly higher 2D CMR arterial wall volumes (982 vs. 916 mm(3); +7%; P < 0.01; R(2) = 0.96) and adventitial volumes (1901 vs. 1826 mm(3); +4%; P < 0.01; R(2) = 0.99). Comparison between 2D CMR and microscopy, performed over a similar longitudinal extent of vessel, showed slightly higher 2D CMR volumes for the lumen (354 vs. 308 mm(3); +14%; P < 0.01; R(2) = 0.97), arterial wall (388 vs. 351 mm(3); +10%; P < 0.01; R(2) = 0.97) and total volumes (750 vs. 665 mm(3); +12%; P < 0.01; R(2) = 0.95). CONCLUSION: The accuracy of the clinical 2D CMR vessel wall sequence for measuring carotid lumen, adventitial, and wall volumes is good against ex vivo measurements, with minor overestimation. This study validates carotid arterial wall quantification by CMR for atherosclerosis research.

Ultra-short echo time cardiovascular magnetic resonance of atherosclerotic carotid plaque.

BACKGROUND: Multi-contrast weighted cardiovascular magnetic resonance (CMR) allows detailed plaque characterisation and assessment of plaque vulnerability. The aim of this preliminary study was to show the potential of Ultra-short Echo Time (UTE) subtraction MR in detecting calcification. METHODS: 14 ex-vivo human carotid arteries were scanned using CMR and CT, prior to histological slide preparation. Two images were acquired using a double-echo 3D UTE pulse, one with a long TE and the second with an ultra-short TE, with the same TR. An UTE subtraction (DeltaUTE) image containing only ultra-short T2 (and T2*) signals was obtained by post-processing subtraction of the 2 UTE images. The DeltaUTE image was compared to the conventional 3D T1-weighted sequence and CT scan of the carotid arteries. RESULTS: In atheromatous carotid arteries, there was a 71% agreement between the high signal intensity areas on DeltaUTE images and CT scan. The same areas were represented as low signal intensity on T1W and areas of void on histology, indicating focal calcification. However, in 15% of all the scans there were some incongruent regions of high intensity on DeltaUTE that did not correspond with a high intensity signal on CT, and histology confirmed the absence of calcification. CONCLUSIONS: We have demonstrated that the UTE sequence has potential to identify calcified plaque. Further work is needed to fully understand the UTE findings.

Diagnosis of early dysfunction of a tissue mitral valve replacement by three-dimensional transoesophageal echocardiography.

We present the case of a 42-year-old man who underwent tissue mitral valve replacement for symptomatic mitral stenosis. Post-operative course was unremarkable but three-dimensional transoesophageal echocardiography clearly indicated that one cusp had very restricted motion with incomplete opening and premature closure. The cause of this early single cusp failure is unclear. It was not related to flow effects. It is conceivable that cusp failure such as here might contribute towards the degeneration of tissue valve replacements.

Effect of rosiglitazone on progression of atherosclerosis: insights using 3D carotid cardiovascular magnetic resonance.

BACKGROUND: There is recent evidence suggesting that rosiglitazone increases death from cardiovascular causes. We investigated the direct effect of this drug on atheroma using 3D carotid cardiovascular magnetic resonance. RESULTS: A randomized, placebo-controlled, double-blind study was performed to evaluate the effect of rosiglitazone treatment on carotid atherosclerosis in subjects with type 2 diabetes and coexisting vascular disease or hypertension. The primary endpoint of the study was the change from baseline to 52 weeks of carotid arterial wall volume, reflecting plaque burden, as measured by carotid cardiovascular magnetic resonance. Rosiglitazone or placebo was allocated to 28 and 29 patients respectively. Patients were managed to have equivalent glycemic control over the study period, but in fact the rosiglitazone group lowered their HbA1c by 0.88% relative to placebo (P < 0.001). Most patients received a statin or fibrate as lipid control medication (rosiglitazone 78%, controls 83%). Data are presented as mean +/- SD. At baseline, the carotid arterial wall volume in the placebo group was 1146 +/- 550 mm3 and in the rosiglitazone group was 1354 +/- 532 mm3. After 52 weeks, the respective volumes were 1134 +/- 523 mm3 and 1348 +/- 531 mm3. These changes (-12.1 mm3 and -5.7 mm3 in the placebo and rosiglitazone groups, respectively) were not statistically significant between groups (P = 0.57). CONCLUSION: Treatment with rosiglitazone over 1 year had no effect on progression of carotid atheroma in patients with type 2 diabetes mellitus compared to placebo.

The role of computed tomography in cardiovascular imaging: from X-ray department to emergency room.

Computed tomography coronary angiography (CTCA) is widely accepted in the evaluation of patients with stable chest pain. Its use in patients with unstable chest pain is more controversial. CTCA can be performed alone or with a computed tomography pulmonary angiogram and aortogram as a 'triple rule-out' scan. Published trial data show that discharging a patient with low-risk acute chest pain after a normal CTCA is a very safe thing to do. Length of stay is generally reduced, but radiation exposure is higher and there is more downstream testing, so it is broadly cost-neutral. Future studies should evaluate this approach in intermediate- to high-risk patients.

Body fat is associated with reduced aortic stiffness until middle age.

Obesity is a major risk factor for cardiometabolic disease, but the effect of body composition on vascular aging and arterial stiffness remains uncertain. We investigated relationships among body composition, blood pressure, age, and aortic pulse wave velocity in healthy individuals. Pulse wave velocity in the thoracic aorta, an indicator of central arterial stiffness, was measured in 221 volunteers (range, 18-72 years; mean, 40.3±13 years) who had no history of cardiovascular disease using cardiovascular MRI. In univariate analyses, age (r=0.78; P<0.001) and blood pressure (r=0.41; P<0.001) showed a strong positive association with pulse wave velocity. In multivariate analysis, after adjustment for age, sex, and mean arterial blood pressure, elevated body fat% was associated with reduced aortic stiffness until the age of 50 years, thereafter adiposity had an increasingly positive association with aortic stiffness (ß=0.16; P<0.001). Body fat% was positively associated with cardiac output when age, sex, height, and absolute lean mass were adjusted for (ß=0.23; P=0.002). These findings suggest that the cardiovascular system of young adults may be capable of adapting to the state of obesity and that an adverse association between body fat and aortic stiffness is only apparent in later life.

Screening for abdominal aortic aneurysm in coronary care unit patients with acute myocardial infarction using portable transthoracic echocardiography.

AIMS: Patients with acute myocardial infarction (AMI) represent a high-risk population in which screening for abdominal aortic aneurysm (AAA) is recommended but only occasionally performed. Transthoracic echocardiography (TTE) may offer the unique opportunity to evaluate the cardiac function and to screen for AAA during the same examination. We aimed to evaluate the feasibility of AAA screening at bedside using a portable cardiac ultrasound (US) echo machine and to determine the prevalence of AAA in population with AMI. METHODS AND RESULTS: The AA diameter was measured at bedside at the end of a regular TTE performed in consecutive patients admitted for AMI in the coronary care unit using a portable echo machine (Vividi, General Electric). AAA was defined by a transverse diameter of ≥ 30 mm. We prospectively enrolled 193 patients (65 ± 11 years, 77% male). Measurement of the AA diameter was feasible in 93% and the duration was 3 ± 1 min. An AAA was observed in nine patients (4.7%) and the prevalence increased with age (7.7% after 60 years and 9.2% after 65 years). No AAA was observed in patients under 50 years old. Inter-observer variability between cardiologists using the portable US system was excellent (mean difference 1.8 ± 2.0 mm) as well as the accuracy compared with measurements performed by a radiologist using a dedicated vascular US system (mean difference 1.5 ± 1.3 mm). CONCLUSION: Overall, the prevalence of AAA was 4.7%, increased with age, and seems higher than expected in the 'same-aged population'. In regard to the simplicity, accuracy, and feasibility, screening for AAA during TTE (one cardiovascular shot) may be of value after AMI especially in elderly patients.

Aortic root dilatation in young patients with cryptogenic stroke and patent foramen ovale.

BACKGROUND: No previous study has looked for an association between aortic dilatation and the clinical sequelae of patent foramen ovale (PFO), although a possible relationship has been identified in case reports. AIM: To compare aortic dimensions in patients with symptomatic PFO and healthy controls. METHODS: Forty-seven patients were identified who presented with cryptogenic cerebrovascular accident (CVA) assessed as most likely secondary to PFO (confirmed by contrast study), were aged less than 50 years and underwent percutaneous PFO closure. Forty-seven age-, sex- and body surface area-matched healthy controls were also identified. RESULTS: Aortic root diameters were greater in PFO patients. The difference was more marked at the levels of the sinuses of Valsalva (34±4 vs 31±3 mm, P<0.01) and the proximal ascending aorta (32±4 vs 29±3, P<0.01) and more modest at the level of the aortic annulus (23±3 vs 22±2 mm, P=0.20). In addition, patients with massive right-to-left shunting tended to have larger aortic diameters. In contrast, left ventricular end-systolic and end-diastolic diameters were not larger than in controls (30±4 vs 32±5 mm, P=0.10 and 48±5 vs 50±4 mm, P=0.04, respectively). CONCLUSION: The present study shows that aortic diameter is increased in young patients with cryptogenic CVA and PFO compared with in healthy subjects. Our results suggest that aortic dilatation may potentiate the risk of CVA in PFO patients and support further research in this area.

An inter-landmark approach to 4-D shape extraction and interpretation: application to myocardial motion assessment in MRI.

This paper presents a novel approach to shape extraction and interpretation in 4-D cardiac magnetic resonance imaging data. Statistical modeling of spatiotemporal interlandmark relationships is performed to enable the decomposition of global shape constraints and subsequently of the image analysis tasks. The introduced descriptors furthermore provide invariance to similarity transformations and thus eliminate pose estimation errors in the presence of image artifacts or geometrical inconsistencies. A set of algorithms are derived to address key technical issues related to constrained boundary tracking, dynamic model relaxation, automatic initialization, and dysfunction localization. The proposed framework is validated with a relatively large dataset of 50 subjects and compared to existing statistical shape modeling methods. The results indicate increased adaptation to spatiotemporal variations and imaging conditions.