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Background: The AV delay optimization of biventricular pacemakers (cardiac resynchronization therapy) may maximize hemodynamic benefit but consumes specialist time to conduct echocardiographically. Noninvasive BP monitoring is a potentially automatable alternative, but it is unknown whether it gives the same information and similar precision (signal/noise ratio). Moreover, the immediate BP increment on optimization has been reported to decay away: it is unclear whether this is the result of an (undesirable) decrease in stroke volume or a (desirable) compensatory relief of peripheral vasoconstriction.Methods and Results: To discriminate between these alternative mechanisms, we measured simultaneous beat-to-beat stroke volume (flow) using Doppler echocardiography, and BP using finger photoplethysmography, during and after AV delay changes from 40 to 120 ms in 19 subjects with cardiac pacemakers. BP and stroke volume both increased immediately (P<0.001, within 1 heartbeat). BP showed a clear decline a few seconds later (average rate, -0.65 mm Hg/beat; r=0.95 [95% CI, 0.86-0.98]); in contrast, stroke volume did not decline (P=0.87). The immediate BP increment correlated strongly with the stroke volume increment (r=0.74, P<0.001). The signal/noise ratio was 3-fold better for BP than stroke volume (6.8±3.5 versus 2.3±1.4; P<0.001).Conclusions: Improving AV delay immediately increases BP, but the effect begins to decay within a few seconds. Reassuringly, this is because of compensatory vasodilatation rather than reduction in cardiac function. Pacemaker optimization will never be reliable unless there is an adequate signal/noise ratio. Using BP rather than Doppler minimizes noise. The early phase (before vascular compensation) has the richest signal lode. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although higher blood pressures are generally recognised to be an adverse prognostic marker in risk assessment of cardiology patients, its relationship to risk in chronic heart failure (CHF) may be different. OBJECTIVE: To examine systematically published reports on the relationship between blood pressure and mortality in CHF. METHODS: Medline and Embase were used to identify studies that gave a hazard or relative risk ratio for systolic blood pressure in a stable population with CHF. Included studies were analysed to obtain a unified hazard ratio and quantify the degree of confidence. RESULTS: 10 studies met the inclusion criteria, giving a total population of 8088, with 29 222 person-years of follow-up. All studies showed that a higher systolic blood pressure (SBP) was a favourable prognostic marker in CHF, in contrast to the general population where it is an indicator of poorer prognosis. The decrease in mortality rates associated with a 10 mm Hg higher SBP was 13.0% (95% CI 10.6% to 15.4%) in the heart failure population. This was not related to aetiology, ACE inhibitor or beta blocker use. CONCLUSION: SBP is an easily measured, continuous variable that has a remarkably consistent relationship with mortality within the CHF population. The potential of this simple variable in outpatient assessment of patients with CHF should not be neglected. One possible application of this information is in the optimisation of cardiac resynchronisation devices. [ABSTRACT FROM AUTHOR]

Background: Pulse Wave Velocity (PWV) is a measure of arterial stiffness which predicts cardiovascular risk independently of blood pressure. Local PWV can be measured non-invasively in the ascending aorta of adults by means of Ultrasound (US), using successive recordings of Diameter (D) and the velocity (U) [1]. Aim: To test US measurements of local PWV in the ascending aorta of human adults against MRI measurements of local PWV. Methods: PWV in the ascending aorta of 8 healthy volunteers (age 22–34y, 3 females) was measured using a Siemens MAGNETOM Aera 1.5T MRI scanner as per standard protocols with cine and phase contrast imaging (sampling frequency 100 samples/cardiac cycle) and D and U were calculated using validated software [2]. US images were recorded using GE Vivid E95 scanner with a 1.5–4.5 MHz phased array transducer. PLAX was used for diameter recordings and A5CH for velocity. Measurements were recorded for 20s during a breath-hold. D and U waveforms were extracted from each imaging modality to calculate PWV using the ln(D)U-loops technique [3]. Results: Average results are summarised in Table 1. The mean difference in PWV between MRI and US was 2.8 ± 0.3%. Conclusions: PWV measured by US shows excellent agreement with MRI in the ascending aorta of adults. Given US availability, this technique offers an easy, affordable and non-invasive means of determining PWV and mechanical properties of the ascending aorta; thus, providing a tool for screening studies.

The number of patients at the intersection of cancer and cardiovascular disease (CVD) is increasing, reflecting ageing global populations, rising burden of shared cardiometabolic risk factors, and improved cancer survival. Many cancer treatments carry a risk of cardiotoxicity. Baseline cardiovascular risk assessment is recommended in all patients with cancer and requires consideration of individual patient risk and the cardiotoxicity profile of proposed anticancer therapies. Patients with pre-existing CVD are potentially at high or very high risk of cancer-therapy related cardiovascular toxicity. The detection of pre-existing CVD should prompt cardiac optimisation and planning of surveillance during cancer treatment. In patients with severe CVD, the risk of certain cancer therapies may be prohibitively high. Such decisions require multidisciplinary discussion with consideration of alternative anti-cancer therapies, risk-benefit assessment, and patient preference. Current practice is primarily guided by expert opinion and data from select clinical cohorts. There is need for development of a stronger evidence base to guide clinical practice in cardio-oncology. The establishment of multicentre international registries and national-level healthcare data linkage projects are important steps towards facilitating enrichment of cardio-oncology research programmes. In this narrative review, we consider epidemiological trends of cancer and CVD comorbidities and the impact of their co-occurrence on clinical outcomes, current approach to supporting cancer patients with pre-existing CVD and gaps in existing knowledge., Competing Interests: Competing interests: MAM is an International Advisory Board Member of Heart. RKC is an Associate Editor for Heart., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations., Methods and Results: We studied 39 095 (51.5% women, mean age: 63.9 ± 7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals, and P-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control., Conclusion: Hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control., Competing Interests: Conflict of interest: S.E.P. provides consultancy to Cardiovascular Imaging Inc., Calgary, Alberta, Canada. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer., Methods: Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8±1.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics., Results: We studied 18 714 participants (67% women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk., Conclusions: Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors., Competing Interests: Competing interests: SEP provides consultancy to Cardiovascular Imaging Inc, Calgary, Alberta, Canada. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Abstract: Modern cancer therapies have significantly improved survival leading to a growing population of cancer survivors. Similarly, both conventional and newer treatments are associated with a spectrum of cardiovascular disorders with potential long-term sequelae. Prompt detection and treatment of these complications is, therefore, pivotal to enable healthy survivorship and reduce cardiovascular morbidity. Advanced multimodality imaging is a valuable tool for stratifying patient risk, identifying cardiovascular toxicity during and after therapy, and predicting recovery. This review summarizes the potential cardiotoxic complications of anticancer therapies and the multimodality approaches available in each case with special focus on newer techniques and the added value of biomarkers ultimately leading to earlier diagnosis and better prognostication., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Many cardiac pacemakers and defibrillators are not approved by regulators for magnetic resonance imaging (MRI). Even following generator exchange to an approved magnetic resonance (MR)-conditional model, many systems remain classified 'non-MR conditional' due to the leads. This classification makes patient access to MRI challenging, but there is no evidence of increased clinical risk. We compared the effect of MRI on non-MR conditional and MR-conditional pacemaker and defibrillator leads., Methods and Results: Patients undergoing clinical 1.5T MRI with pacemakers and defibrillators in three centres over 5 years were included. Magnetic resonance imaging protocols were similar for MR-conditional and non-MR conditional systems. Devices were interrogated pre- and immediately post-scan, and at follow-up, and adverse clinical events recorded. Lead parameter changes peri-scan were stratified by MR-conditional labelling. A total of 1148 MRI examinations were performed in 970 patients (54% non-MR conditional systems, 39% defibrillators, 15% pacing-dependent) with 2268 leads. There were no lead-related adverse clinical events, and no clinically significant immediate or late lead parameter changes following MRI in either MR-conditional or non-MR conditional leads. Small reductions in atrial and right ventricular sensed amplitudes and impedances were similar between groups, with no difference in the proportion of leads with parameter changes greater than pre-defined thresholds (7.1%, 95% confidence interval: 6.1-8.3)., Conclusions: There was no increased risk of MRI in patients with non-MR conditional pacemaker or defibrillator leads when following recommended protocols. Standardizing MR conditions for all leads would significantly improve access to MRI by enabling patients to be scanned in non-specialist centres, with no discernible incremental risk., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: The aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM)., Background: Left ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD)., Methods: A 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death., Results: MWT analysis was completed by 70 readers (from 6 continents; 91% with >5 years' experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range -59% to 117% [SD ±20%] and -61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk)., Conclusions: Using the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM., Competing Interests: Funding Support and Author Disclosures This program was funded by Barts Charity grant 1107/2356/MRC0140 to Dr Captur. Dr Captur is supported by British Heart Foundation Special Programme Grant MyoFit46 (SP/20/2/34841), the National Institute for Health Research (NIHR) Rare Diseases Translational Research Collaboration, and the NIHR UCL Hospitals Biomedical Research Center. Dr Petersen has received support from the Barts Biomedical Research Centre, funded by the NIHR. Dr Moon is directly and indirectly supported by the UCL Hospitals NIHR BRC and Biomedical Research Unit at Barts Hospital, respectively. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Remodelling of the cardiovascular system (including heart and vasculature) is a dynamic process influenced by multiple physiological and pathological factors. We sought to understand whether remodelling in response to a stimulus, exercise training, altered with healthy ageing., Methods: A total of 237 untrained healthy male and female subjects volunteering for their first time marathon were recruited. At baseline and after 6 months of unsupervised training, race completers underwent tests including 1.5T cardiac magnetic resonance, brachial and non-invasive central blood pressure assessment. For analysis, runners were divided by age into under or over 35 years (U35, O35)., Results: Injury and completion rates were similar among the groups; 138 runners (U35: n = 71, women 49%; O35: n = 67, women 51%) completed the race. On average, U35 were faster by 37 minutes (12%). Training induced a small increase in left ventricular mass in both groups (3 g/m2, P < 0.001), but U35 also increased ventricular cavity sizes (left ventricular end-diastolic volume (EDV)i +3%; left ventricular end-systolic volume (ESV)i +8%; right ventricular end-diastolic volume (EDV)i +4%; right ventricular end-systolic volume (ESV)i +5%; P < 0.01 for all). Systemic aortic compliance fell in the whole sample by 7% (P = 0.020) and, especially in O35, also systemic vascular resistance (-4% in the whole sample, P = 0.04) and blood pressure (systolic/diastolic, whole sample: brachial -4/-3 mmHg, central -4/-2 mmHg, all P < 0.001; O35: brachial -6/-3 mmHg, central -6/-4 mmHg, all P < 0.001)., Conclusion: Medium-term, unsupervised physical training in healthy sedentary individuals induces measurable remodelling of both heart and vasculature. This amount is age dependent, with predominant cardiac remodelling when younger and predominantly vascular remodelling when older., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients., Methods and Results: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms)., Conclusions: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Advances in cancer therapy have led to significantly longer cancer-free survival times over the last 40 years. Improved survivorship coupled with increasing recognition of an expanding range of adverse cardiovascular effects of many established and novel cancer therapies has highlighted the impact of cardiovascular disease in this population. This has led to the emergence of dedicated cardio-oncology services that can provide pre-treatment risk stratification, surveillance, diagnosis, and monitoring of cardiotoxicity during cancer therapies, and late effects screening following completion of treatment. Cardiovascular imaging and the development of imaging biomarkers that can accurately and reliably detect pre-clinical disease and enhance our understanding of the underlying pathophysiology of cancer treatment-related cardiotoxicity are becoming increasingly important. Multi-parametric cardiovascular magnetic resonance (CMR) is able to assess cardiac structure, function, and provide myocardial tissue characterization, and hence can be used to address a variety of important clinical questions in the emerging field of cardio-oncology. In this review, we discuss the current and potential future applications of CMR in the investigation and management of cancer patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Measurement of myocardial T1 is increasingly incorporated into standard cardiovascular magnetic resonance (CMR) protocols, however accuracy may be reduced in patients with metallic cardiovascular implants. Measurement is feasible in segments free from visual artifact, but there may still be off-resonance induced error. Aim: To quantify off-resonance induced T1 error in patients with metallic cardiovascular implants, and validate a method for error correction for a conventional MOLLI pulse sequence. Methods: Twenty-four patients with cardiac implantable electronic devices (CIEDs: 46% permanent pacemakers, PPMs; 33% implantable loop recorders, ILRs; and 21% implantable cardioverter-defibrillators, ICDs); and 31 patients with aortic valve replacement (AVR) (45% metallic) were studied. Paired mid-myocardial short-axis MOLLI and single breath-hold off-resonance field maps were acquired at 1.5 T. T1 values were measured by AHA segment, and segments with visual artifact were excluded. T1 correction was applied using a published relationship between off-resonance and T1. The accuracy of the correction was assessed in 10 healthy volunteers by measuring T1 before and after external placement of an ICD generator next to the chest to generate off-resonance. Results: T1 values in healthy volunteers with an ICD were underestimated compared to without (967 ± 52 vs. 997 ± 26 ms respectively, p = 0.0001), but were similar after correction ( p = 0.57, residual difference 2 ± 27 ms). Artifact was visible in 4 ± 12, 42 ± 31, and 53 ± 27% of AHA segments in patients with ILRs, PPMs, and ICDs, respectively. In segments without artifact, T1 was underestimated by 63 ms (interquartile range: 7-143) per patient. The greatest error for patients with ILRs, PPMs and ICDs were 79, 146, and 191 ms, respectively. The presence of an AVR did not generate T1 error. Conclusion: Even when there is no visual artifact, there is error in T1 in patients with CIEDs, but not AVRs. Off-resonance field map acquisition can detect error in measured T1, and a correction can be applied to quantify T1 MOLLI accurately., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor declared a past co-authorship with several of the authors JM and PK., (Copyright © 2021 Bhuva, Treibel, Seraphim, Scully, Knott, Augusto, Torlasco, Menacho, Lau, Patel, Moon, Kellman and Manisty.)

Aims: To evaluate the repeatability of cardiac magnetic resonance (CMR) radiomics features on test-retest scanning using a multi-centre multi-vendor dataset with a varied case-mix. Methods and Results: The sample included 54 test-retest studies from the VOLUMES resource (thevolumesresource.com). Images were segmented according to a pre-defined protocol to select three regions of interest (ROI) in end-diastole and end-systole: right ventricle, left ventricle (LV), and LV myocardium. We extracted radiomics shape features from all three ROIs and, additionally, first-order and texture features from the LV myocardium. Overall, 280 features were derived per study. For each feature, we calculated intra-class correlation coefficient (ICC), within-subject coefficient of variation, and mean relative difference. We ranked robustness of features according to mean ICC stratified by feature category, ROI, and cardiac phase, demonstrating a wide range of repeatability. There were features with good and excellent repeatability (ICC ≥ 0.75) within all feature categories and ROIs. A high proportion of first-order and texture features had excellent repeatability (ICC ≥ 0.90), however, these categories also contained features with the poorest repeatability (ICC < 0.50). Conclusion: CMR radiomic features have a wide range of repeatability. This paper is intended as a reference for future researchers to guide selection of the most robust features for clinical CMR radiomics models. Further work in larger and richer datasets is needed to further define the technical performance and clinical utility of CMR radiomics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Raisi-Estabragh, Gkontra, Jaggi, Cooper, Augusto, Bhuva, Davies, Manisty, Moon, Munroe, Harvey, Lekadir and Petersen.)

Background: Wave intensity analysis (WIA) in the aorta offers important clinical and mechanistic insight into ventriculo-arterial coupling, but is difficult to measure non-invasively. We performed WIA by combining standard cardiovascular magnetic resonance (CMR) flow-velocity and non-invasive central blood pressure (cBP) waveforms., Methods and Results: Two hundred and six healthy volunteers (age range 21-73 years, 47% male) underwent sequential phase contrast CMR (Siemens Aera 1.5 T, 1.97 × 1.77 mm2, 9.2 ms temporal resolution) and supra-systolic oscillometric cBP measurement (200 Hz). Velocity (U) and central pressure (P) waveforms were aligned using the waveform foot, and local wave speed was calculated both from the PU-loop (c) and the sum of squares method (cSS). These were compared with CMR transit time derived aortic arch pulse wave velocity (PWVtt). Associations were examined using multivariable regression. The peak intensity of the initial compression wave, backward compression wave, and forward decompression wave were 69.5 ± 28, -6.6 ± 4.2, and 6.2 ± 2.5 × 104 W/m2/cycle2, respectively; reflection index was 0.10 ± 0.06. PWVtt correlated with c or cSS (r = 0.60 and 0.68, respectively, P < 0.01 for both). Increasing age decade and female sex were independently associated with decreased forward compression wave (-8.6 and -20.7 W/m2/cycle2, respectively, P < 0.01) and greater wave reflection index (0.02 and 0.03, respectively, P < 0.001)., Conclusion: This novel non-invasive technique permits straightforward measurement of wave intensity at scale. Local wave speed showed good agreement with PWVtt, and correlation was stronger using the cSS than the PU-loop. Ageing and female sex were associated with poorer ventriculo-arterial coupling in healthy individuals., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Convolutional neural network (CNN) based segmentation methods provide an efficient and automated way for clinicians to assess the structure and function of the heart in cardiac MR images. While CNNs can generally perform the segmentation tasks with high accuracy when training and test images come from the same domain (e.g., same scanner or site), their performance often degrades dramatically on images from different scanners or clinical sites. Methods: We propose a simple yet effective way for improving the network generalization ability by carefully designing data normalization and augmentation strategies to accommodate common scenarios in multi-site, multi-scanner clinical imaging data sets. We demonstrate that a neural network trained on a single-site single-scanner dataset from the UK Biobank can be successfully applied to segmenting cardiac MR images across different sites and different scanners without substantial loss of accuracy. Specifically, the method was trained on a large set of 3,975 subjects from the UK Biobank. It was then directly tested on 600 different subjects from the UK Biobank for intra-domain testing and two other sets for cross-domain testing: the ACDC dataset (100 subjects, 1 site, 2 scanners) and the BSCMR-AS dataset (599 subjects, 6 sites, 9 scanners). Results: The proposed method produces promising segmentation results on the UK Biobank test set which are comparable to previously reported values in the literature, while also performing well on cross-domain test sets, achieving a mean Dice metric of 0.90 for the left ventricle, 0.81 for the myocardium, and 0.82 for the right ventricle on the ACDC dataset; and 0.89 for the left ventricle, 0.83 for the myocardium on the BSCMR-AS dataset. Conclusions: The proposed method offers a potential solution to improve CNN-based model generalizability for the cross-scanner and cross-site cardiac MR image segmentation task., (Copyright © 2020 Chen, Bai, Davies, Bhuva, Manisty, Augusto, Moon, Aung, Lee, Sanghvi, Fung, Paiva, Petersen, Lukaschuk, Piechnik, Neubauer and Rueckert.)

Aims: Left ventricular hypertrophy (LVH) in aortic stenosis (AS) varies widely before and after aortic valve replacement (AVR), and deeper phenotyping beyond traditional global measures may improve risk stratification. We hypothesized that machine learning derived 3D LV models may provide a more sensitive assessment of remodelling and sex-related differences in AS than conventional measurements., Methods and Results: One hundred and sixteen patients with severe, symptomatic AS (54% male, 70 ± 10 years) underwent cardiovascular magnetic resonance pre-AVR and 1 year post-AVR. Computational analysis produced co-registered 3D models of wall thickness, which were compared with 40 propensity-matched healthy controls. Preoperative regional wall thickness and post-operative percentage wall thickness regression were analysed, stratified by sex. AS hypertrophy and regression post-AVR was non-uniform-greatest in the septum with more pronounced changes in males than females (wall thickness regression: -13 ± 3.6 vs. -6 ± 1.9%, respectively, P < 0.05). Even patients without LVH (16% with normal indexed LV mass, 79% female) had greater septal and inferior wall thickness compared with controls (8.8 ± 1.6 vs. 6.6 ± 1.2 mm, P < 0.05), which regressed post-AVR. These differences were not detectable by global measures of remodelling. Changes to clinical parameters post-AVR were also greater in males: N-terminal pro-brain natriuretic peptide (NT-proBNP) [-37 (interquartile range -88 to -2) vs. -1 (-24 to 11) ng/L, P = 0.008], and systolic blood pressure (12.9 ± 23 vs. 2.1 ± 17 mmHg, P = 0.009), with changes in NT-proBNP correlating with percentage LV mass regression in males only (ß 0.32, P = 0.02)., Conclusion: In patients with severe AS, including those without overt LVH, LV remodelling is most plastic in the septum, and greater in males, both pre-AVR and post-AVR. Three-dimensional machine learning is more sensitive than conventional analysis to these changes, potentially enhancing risk stratification., Clinical Trial Registration: Regression of myocardial fibrosis after aortic valve replacement (RELIEF-AS); NCT02174471. https://clinicaltrials.gov/ct2/show/NCT02174471., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

More than half of us will need a magnetic resonance imaging (MRI) scan in our lifetimes. MRI is an unmatched diagnostic test for an expanding range of indications including neurological and musculoskeletal disorders, cancer diagnosis, and treatment planning. Unfortunately, patients with cardiac pacemakers or defibrillators have historically been prevented from having MRI because of safety concerns. This results in delayed diagnoses, more invasive investigations, and increased cost. Major developments have addressed this-newer devices are designed to be safe in MRI machines under specific conditions, and older legacy devices can be scanned provided strict protocols are followed. This service however remains difficult to deliver sustainably worldwide: MRI provision remains grossly inadequate because patients are less likely to be referred, and face difficulties accessing services even when referred. Barriers still exist but are no longer technical. These include logistical hurdles (poor cardiology and radiology interaction at physician and technician levels), financial incentives (re-imbursement is either absent or fails to acknowledge the complexity), and education (physicians self-censor MRI requests). This article therefore highlights the recent changes in the clinical, logistical, and regulatory landscape. The aim of the article is to enable and encourage healthcare providers and local champions to build MRI services urgently for cardiac device patients, so that they may benefit from the same access to MRI as everyone else. KEY POINTS: • There is now considerable evidence that MRI can be provided safely to patients with cardiac implantable electronic devices (CIEDs). However, the volume of MRI scans delivered to patients with CIEDs is fifty times lower than that of the estimated need, and patients are approximately fifty times less likely to be referred. • Because scans for this patient group are frequently for cancer diagnosis and treatment planning, MRI services need to develop rapidly, but the barriers are no longer technical. • New services face logistical, educational, and financial hurdles which can be addressed effectively to establish a sustainable service at scale.

Background: Aging increases aortic stiffness, contributing to cardiovascular risk even in healthy individuals. Aortic stiffness is reduced through supervised training programs, but these are not easily generalizable., Objectives: The purpose of this study was to determine whether real-world exercise training for a first-time marathon can reverse age-related aortic stiffening., Methods: Untrained healthy individuals underwent 6 months of training for the London Marathon. Assessment pre-training and 2 weeks post-marathon included central (aortic) blood pressure and aortic stiffness using cardiovascular magnetic resonance distensibility. Biological "aortic age" was calculated from the baseline chronological age-stiffness relationship. Change in stiffness was assessed at the ascending (Ao-A) and descending aorta at the pulmonary artery bifurcation (Ao-P) and diaphragm (Ao-D). Data are mean changes (95% confidence intervals [CIs])., Results: A total of 138 first-time marathon completers (age 21 to 69 years, 49% male) were assessed, with an estimated training schedule of 6 to 13 miles/week. At baseline, a decade of chronological aging correlated with a decrease in Ao-A, Ao-P, and Ao-D distensibility by 2.3, 1.9, and 3.1 × 10 -3 mm Hg -1 , respectively (p < 0.05 for all). Training decreased systolic and diastolic central (aortic) blood pressure by 4 mm Hg (95% CI: 2.8 to 5.5 mm Hg) and 3 mm Hg (95% CI: 1.6 to 3.5 mm Hg). Descending aortic distensibility increased (Ao-P: 9%; p = 0.009; Ao-D: 16%; p = 0.002), while remaining unchanged in the Ao-A. These translated to a reduction in "aortic age" by 3.9 years (95% CI: 1.1 to 7.6 years) and 4.0 years (95% CI: 1.7 to 8.0 years) (Ao-P and Ao-D, respectively). Benefit was greater in older, male participants with slower running times (p < 0.05 for all)., Conclusions: Training for and completing a marathon even at relatively low exercise intensity reduces central blood pressure and aortic stiffness-equivalent to a ∼4-year reduction in vascular age. Greater rejuvenation was observed in older, slower individuals., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patients with cardiac pacemakers and defibrillators are disadvantaged because of poor access to MRI scans, leading to late and misdiagnosis particularly for cancer and neurological disease. New technology allied to tested protocols now allows safe MRI scanning of such patients; however, logistical barriers persist., Aim: To deliver a streamlined sustainable service that provides timely MRI scans to patients with cardiac implantable electronic devices (CIEDs)., Methods: Patients requested a 'one-stop' service for MRI, whereby devices could be reprogrammed and scans acquired at a single location and visit. To provide this 'one-stop' service, we trained a team including administrators, physicians, cardiac physiologists and radiographers. A standard protocol was used to prevent unnecessary request refusals and delays to scheduling. Service volume, waiting time and safety were analysed 6 months before and 2 years after service redesign. Waiting times for internal and external inpatient referrals plus time to treatment for patients on a cancer pathway were analysed., Results: 215 MRI scans were performed over 2 years. After service redesign, MRI provision increased six-fold to 20 times the national average with reduced waiting time from 60 to 15 days and no adverse events. Departmental throughput was maintained. 85 (40%) referrals were external. 41 (19%) inpatients were scanned, reducing bed-stay by 3 days for internal referrals. 24 (11%) scans were for suspected cancer, 83% allowed treatment within the national standard of 62 days. There was no preintervention service for either inpatients or suspected cancer investigation., Conclusion: Implementation of a 'one-stop' service model to provide MRI for patients with CIEDs is safe, streamlined, scalable and has reduced delays making economic and clinical sense. Protocols and checklists are available at mrimypacemaker.com., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Automated analysis of cardiac structure and function using machine learning (ML) has great potential, but is currently hindered by poor generalizability. Comparison is traditionally against clinicians as a reference, ignoring inherent human inter- and intraobserver error, and ensuring that ML cannot demonstrate superiority. Measuring precision (scan:rescan reproducibility) addresses this. We compared precision of ML and humans using a multicenter, multi-disease, scan:rescan cardiovascular magnetic resonance data set., Methods: One hundred ten patients (5 disease categories, 5 institutions, 2 scanner manufacturers, and 2 field strengths) underwent scan:rescan cardiovascular magnetic resonance (96% within one week). After identification of the most precise human technique, left ventricular chamber volumes, mass, and ejection fraction were measured by an expert, a trained junior clinician, and a fully automated convolutional neural network trained on 599 independent multicenter disease cases. Scan:rescan coefficient of variation and 1000 bootstrapped 95% CIs were calculated and compared using mixed linear effects models., Results: Clinicians can be confident in detecting a 9% change in left ventricular ejection fraction, with greater than half of coefficient of variation attributable to intraobserver variation. Expert, trained junior, and automated scan:rescan precision were similar (for left ventricular ejection fraction, coefficient of variation 6.1 [5.2%-7.1%], P =0.2581; 8.3 [5.6%-10.3%], P =0.3653; 8.8 [6.1%-11.1%], P =0.8620). Automated analysis was 186× faster than humans (0.07 versus 13 minutes)., Conclusions: Automated ML analysis is faster with similar precision to the most precise human techniques, even when challenged with real-world scan:rescan data. Assessment of multicenter, multi-vendor, multi-field strength scan:rescan data (available at www.thevolumesresource.com) permits a generalizable assessment of ML precision and may facilitate direct translation of ML to clinical practice.

Opinion Statement: Early detection and treatment of cardiotoxicity from cancer therapies is key to preventing a rise in adverse cardiovascular outcomes in cancer patients. Over-diagnosis of cardiotoxicity in this context is however equally hazardous, leading to patients receiving suboptimal cancer treatment, thereby impacting cancer outcomes. Accurate screening therefore depends on the widespread availability of sensitive and reproducible biomarkers of cardiotoxicity, which can clearly discriminate early disease. Blood biomarkers are limited in cardiovascular disease and clinicians generally still use generic screening with ejection fraction, based on historical local expertise and resources. Recently, however, there has been growing recognition that simple measurement of left ventricular ejection fraction using 2D echocardiography may not be optimal for screening: diagnostic accuracy, reproducibility and feasibility are limited. Modern cancer therapies affect many myocardial pathways: inflammatory, fibrotic, metabolic, vascular and myocyte function, meaning that multiple biomarkers may be needed to track myocardial cardiotoxicity. Advanced imaging modalities including cardiovascular magnetic resonance (CMR), computed tomography (CT) and positron emission tomography (PET) add improved sensitivity and insights into the underlying pathophysiology, as well as the ability to screen for other cardiotoxicities including coronary artery, valve and pericardial diseases resulting from cancer treatment. Delivering screening for cardiotoxicity using advanced imaging modalities will however require a significant change in current clinical pathways, with incorporation of machine learning algorithms into imaging analysis fundamental to improving efficiency and precision. In the future, we should aspire to personalized rather than generic screening, based on a patient's individual risk factors and the pathophysiological mechanisms of the cancer treatment they are receiving. We should aspire that progress in cardiooncology is able to track progress in oncology, and to ensure that the current 'one size fits all' approach to screening be obsolete in the very near future.

Objectives: This paper reports the development, validation, and public availability of a new neural network-based system which attempts to identify the manufacturer and even the model group of a pacemaker or defibrillator from a chest radiograph., Background: Medical staff often need to determine the model of a pacemaker or defibrillator (cardiac rhythm device) quickly and accurately. Current approaches involve comparing a device's radiographic appearance with a manual flow chart., Methods: In this study, radiographic images of 1,676 devices, comprising 45 models from 5 manufacturers were extracted. A convolutional neural network was developed to classify the images, using a training set of 1,451 images. The testing set contained an additional 225 images consisting of 5 examples of each model. The network's ability to identify the manufacturer of a device was compared with that of cardiologists, using a published flowchart., Results: The neural network was 99.6% (95% confidence interval [CI]: 97.5% to 100.0%) accurate in identifying the manufacturer of a device from a radiograph and 96.4% (95% CI: 93.1% to 98.5%) accurate in identifying the model group. Among 5 cardiologists who used the flowchart, median identification of manufacturer accuracy was 72.0% (range 62.2% to 88.9%), and model group identification was not possible. The network's ability to identify the manufacturer of the devices was significantly superior to that of all the cardiologists (p < 0.0001 compared with the median human identification; p < 0.0001 compared with the best human identification)., Conclusions: A neural network can accurately identify the manufacturer and even model group of a cardiac rhythm device from a radiograph and exceeds human performance. This system may speed up the diagnosis and treatment of patients with cardiac rhythm devices, and it is publicly accessible online., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial scar assessment using late gadolinium enhancement Cardiovascular Magnetic Resonance (LGE CMR) is commonly indicated for patients with cardiac implantable electronic devices (CIEDs), however metal artifact can degrade images. We evaluated the clinical impact of LGE CMR incorporating a device-dependent metal artifact reduction strategy in patients with CIEDs., Methods: 136 CMR studies were performed in 133 consecutive patients (age 56 ± 19 years, 69% male) with CIEDs (22% implantable loop recorders [ILRs], 40% permanent pacemakers [PPMs], 38% implantable cardioverter defibrillators [ICDs]; 42% non-MRI conditional) over 2 years, without complication. LGE imaging was tailored to the CIED, using a wideband sequence for left-sided PPMs and ICDs and conventional sequences for ILRs and right-sided PPMs, scoring segmental artifact. Diagnostic utility and impact on clinical management were scored by consensus of experts., Results: CMR provided unexpected diagnoses in 22 (16%) and changed management in 113 (83%) patients. Myocardial scar was present in 92 (68%), with other abnormalities detected in another 13%. Using conventional LGE, 43 (32%) studies were non-diagnostic (79% of defibrillators) compared to 0% using wideband LGE imaging. Wideband LGE results changed clinical management in an additional 39 (75%) defibrillator patients and 10 (19%) pacemaker patients when compared to imaging with conventional LGE sequences., Conclusion: The clinical yield from CMR using optimized LGE sequences in patients with CIEDs is high with no demonstrated clinical risk. A device-dependent LGE imaging strategy using wideband LGE is needed to achieve clinical utility especially in ICD recipients., (Copyright © 2019. Published by Elsevier B.V.)

Rationale: In patients with chronic heart failure, daytime oscillatory breathing at rest is associated with a high risk of mortality. Experimental evidence, including exaggerated ventilatory responses to CO 2 and prolonged circulation time, implicates the ventilatory control system and suggests feedback instability (loop gain > 1) is responsible. However, daytime oscillatory patterns often appear remarkably irregular versus classic instability (Cheyne-Stokes respiration), suggesting our mechanistic understanding is limited., Objectives: We propose that daytime ventilatory oscillations generally result from a chemoreflex resonance, in which spontaneous biological variations in ventilatory drive repeatedly induce temporary and irregular ringing effects. Importantly, the ease with which spontaneous biological variations induce irregular oscillations (resonance "strength") rises profoundly as loop gain rises toward 1. We tested this hypothesis through a comparison of mathematical predictions against actual measurements in patients with heart failure and healthy control subjects., Methods: In 25 patients with chronic heart failure and 25 control subjects, we examined spontaneous oscillations in ventilation and separately quantified loop gain using dynamic inspired CO 2 stimulation., Measurements and Main Results: Resonance was detected in 24 of 25 patients with heart failure and 18 of 25 control subjects. With increased loop gain-consequent to increased chemosensitivity and delay-the strength of spontaneous oscillations increased precipitously as predicted (r = 0.88), yielding larger (r = 0.78) and more regular (interpeak interval SD, r = -0.68) oscillations (P < 0.001 for all, both groups combined)., Conclusions: Our study elucidates the mechanism underlying daytime ventilatory oscillations in heart failure and provides a means to measure and interpret these oscillations to reveal the underlying chemoreflex hypersensitivity and reduced stability that foretells mortality in this population.

MR scanning in patients with cardiac implantable electronic devices (CIEDs) was formerly felt to be contraindicated, but an increasing number of patients have an implanted MR conditional device, allowing them to safely undergo MR scanning, provided the manufacturer's guidance is adhered to. In addition, some patients with non-MR conditional devices may undergo MR scanning if no other imaging modality is deemed suitable and there is a clear clinical indication for scanning which outweighs the potential risk. The following guidance has been formulated by the British Heart Rhythm Society and endorsed by the British Cardiovascular Society and others. It describes protocols that should be followed for patients with CIEDs undergoing MR scanning. The recommendations, principles and conclusions are supported by the Royal College of Radiologists., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aims: Whether adjusting interventricular (VV) delay changes haemodynamic efficacy of cardiac resynchronization therapy (CRT) is controversial, with conflicting results. This study addresses whether the convention for keeping atrioventricular (AV) delay constant during VV optimization might explain these conflicts., Method and Results: Twenty-two patients in sinus rhythm with existing CRT underwent VV optimization using non-invasive systolic blood pressure. Interventricular optimization was performed with four methods for keeping the AV delay constant: (i) atrium and left ventricle delay kept constant, (ii) atrium and right ventricle delay kept constant, (iii) time to the first-activated ventricle kept constant, and (iv) time to the second-activated ventricle kept constant. In 11 patients this was performed with AV delay of 120 ms, and in 11 at AV optimum. At AV 120 ms, time to the first ventricular lead (left or right) was the overwhelming determinant of haemodynamics (13.75 mmHg at ±80 ms, P < 0.001) with no significant effect of time to second lead (0.47 mmHg, P = 0.50), P < 0.001 for difference. At AV optimum, time to first ventricular lead again had a larger effect (5.03 mmHg, P < 0.001) than time to second (2.92 mmHg, P = 0.001), P = 0.02 for difference., Conclusion: Time to first ventricular activation is the overwhelming determinant of circulatory function, regardless of whether this is the left or right ventricular lead. If this is kept constant, the effect of changing time to the second ventricle is small or nil, and is not beneficial. In practice, it may be advisable to leave VV delay at zero. Specifying how AV delay is kept fixed might make future VV delay research more enlightening., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown., Methods and Results: Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1-13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E', and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3-13.1; P<0.05)., Conclusions: There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors., (© 2015 The Authors.)

Background: Biventricular pacing (CRT) shows clear benefits in heart failure with wide QRS, but results in narrow QRS have appeared conflicting. We tested the hypothesis that study design might have influenced findings., Method and Results: We identified all reports of CRT-P/D therapy in subjects with narrow QRS reporting effects on continuous physiological variables. Twelve studies (2074 patients) met these criteria. Studies were stratified by presence of bias-resistance steps: the presence of a randomized control arm over a single arm, and blinded outcome measurement. Change in each endpoint was quantified using a standardized effect size (Cohen's d). We conducted separate meta-analyses for each variable in turn, stratified by trial quality. In non-randomized, non-blinded studies, the majority of variables (10 of 12, 83%) showed significant improvement, ranging from a standardized mean effect size of +1.57 (95%CI +0.43 to +2.7) for ejection fraction to +2.87 (+1.78 to +3.95) for NYHA class. In the randomized, non-blinded study, only 3 out of 6 variables (50%) showed improvement. For the randomized blinded studies, 0 out of 9 variables (0%) showed benefit, ranging from -0.04 (-0.31 to +0.22) for ejection fraction to -0.1 (-0.73 to +0.53) for 6-minute walk test., Conclusions: Differences in degrees of resistance to bias, rather than choice of endpoint, explain the variation between studies of CRT in narrow-QRS heart failure addressing physiological variables. When bias-resistance features are implemented, it becomes clear that these patients do not improve in any tested physiological variable. Guidance from studies without careful planning to resist bias may be far less useful than commonly perceived., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Cardiovascular magnetic resonance is an important tool for patient care and is the best test for myocardial structure and function. Ischemia and scar imaging also provide key insights and focus attention on heart muscle - the site of most cardiac diseases. New ways of measuring abnormal muscle have been developed, including T1 mapping. Abnormal signal can be distinguished either without contrast (native T1), or post-contrast (extracellular volume measurement). Large changes occur in rare diseases (cardiac amyloidosis, Anderson-Fabry disease and iron overload) even at an early stage, while more subtle changes are seen in diffuse fibrosis where a robust test would be of major impact. This review presents the potential future clinical utility of T1 mapping - a technology to watch.

Obtaining a "correct" view in echocardiography is a subjective process in which an operator attempts to obtain images conforming to consensus standard views. Real-time objective quantification of image alignment may assist less experienced operators, but no reliable index yet exists. We present a fully automated algorithm for detecting incorrect medial/lateral translation of an ultrasound probe by image analysis. The ability of the algorithm to distinguish optimal from sub-optimal four-chamber images was compared to that of specialists-the current "gold-standard." The orientation assessments produced by the automated algorithm correlated well with consensus visual assessments of the specialists ([Formula: see text]) and compared favourably with the correlation between individual specialists and the consensus, [Formula: see text]. Each individual specialist's assessments were within the consensus of other specialists, [Formula: see text] of the time, and the algorithm's assessments were within the consensus of specialists 85% of the time. The mean discrepancy in probe translation values between individual specialists and their consensus was [Formula: see text], and between the automated algorithm and specialists' consensus was [Formula: see text]. This technology could be incorporated into hardware to provide real-time guidance for image optimisation-a potentially valuable tool both for training and quality control.

Background: Constant flow and concentration CO2 has previously been efficacious in attenuating ventilatory oscillations in periodic breathing (PB) where oscillations in CO2 drive ventilatory oscillations. However, it has the undesirable effect of increasing end-tidal CO2, and ventilation. We tested, in a model of PB, a dynamic CO2 therapy that aims to attenuate pacemaker-induced ventilatory oscillations while minimising CO2 dose., Methods: First, pacemakers were manipulated in 12 pacemaker recipients, 6 with heart failure (ejection fraction (EF)=23.7±7.3%) and 6 without heart failure, to experimentally induce PB. Second, we applied a real-time algorithm of pre-emptive dynamic exogenous CO2 administration, and tested different timings., Results: We found that cardiac output alternation using pacemakers successfully induced PB. Dynamic CO2 therapy, when delivered coincident with hyperventilation, attenuated 57% of the experimentally induced oscillations in end-tidal CO2: SD/mean 0.06±0.01 untreated versus 0.04±0.01 with treatment (p<0.0001) and 0.02±0.01 in baseline non-modified breathing. This translated to a 56% reduction in induced ventilatory oscillations: SD/mean 0.19±0.09 untreated versus 0.14±0.06 with treatment (p=0.001) and 0.10±0.03 at baseline. Of note, end-tidal CO2 did not significantly rise when dynamic CO2 was applied to the model (4.84±0.47 vs 4.91± 0.45 kPa, p=0.08). Furthermore, mean ventilation was also not significantly increased by dynamic CO2 compared with untreated (7.8±1.2 vs 8.4±1.2 L/min, p=0.17)., Conclusions: Cardiac pacemaker manipulation can be used to induce PB experimentally. In this induced PB, delivering CO2 coincident with hyperventilation, ventilatory oscillations can be substantially attenuated without a significant increase in end-tidal CO2 or ventilation. Dynamic CO2 administration might be developed into a clinical treatment for PB., Trial Registration Number: ISRCTN29344450.

Background: Variability has been described between different echo machines and different modalities when measuring tissue velocities. We assessed the consistency of tissue velocity measurements across different modalities and different manufacturers in an in vitro model and in patients. Furthermore, we present freely available software tools to repeat these evaluations., Methods and Results: We constructed a simple setup to generate reproducible motion and used it to compare velocities measured using three echocardiographic modalities: M-mode, speckle tracking, and tissue Doppler, with a straightforward, non-ultrasound, optical gold standard. In the clinical phase, 25 patients underwent M-mode, speckle tracking, and tissue Doppler measurements of s', e', and a' velocities. In vitro, the M-mode and speckle tracking velocities agreed with optical assessment. Of the three possible tissue Doppler measurement conventions (outer, middle, and inner edge) only the middle agreed with optical assessment (discrepancy -0.20 (95% CI -0.44 to 0.03) cm/s, P = 0.11, outer +5.19 (4.65 to 5.73) cm/s, P < 0.0001, inner -6.26 (-6.87 to -5.65) cm/s, P < 0.0001). A similar pattern occurred across all four studied manufacturers. M-mode was therefore chosen as the in vivo gold standard. Clinical measurements of s' velocities by speckle tracking and the middle line of the tissue Doppler showed concordance with M-mode, while the outer line overestimated significantly (+1.27(0.96 to 1.59) cm/s, P < 0.0001) and the inner line underestimated (-1.82 (-2.11 to -1.52) cm/s, P < 0.0001)., Conclusions: Echocardiographic velocity measurements can be more consistent than previously suspected. The statistically modal velocity, found at the centre of the spectral pulsed wave tissue Doppler envelope, most closely represents true tissue velocity. This article includes downloadable, vendor-independent software enabling calibration of echocardiographic machines using a simple, inexpensive in vitro setup., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Primary prevention guidelines focus on risk, often assuming negligible aversion to medication, yet most patients discontinue primary prevention statins within 3 years. We quantify real-world distribution of medication disutility and separately calculate the average utilities for a range of risk strata., Method and Results: We randomly sampled 360 members of the general public in London. Medication aversion was quantified as the gain in lifespan required by each individual to offset the inconvenience (disutility) of taking an idealized daily preventative tablet. In parallel, we constructed tables of expected gain in lifespan (utility) from initiating statin therapy for each age group, sex, and cardiovascular risk profile in the population. This allowed comparison of the widths of the distributions of medication disutility and of group-average expectation of longevity gain. Observed medication disutility ranged from 1 day to >10 years of life being required by subjects (median, 6 months; interquartile range, 1-36 months) to make daily preventative therapy worthwhile. Average expected longevity benefit from statins at ages ≥50 years ranges from 3.6 months (low-risk women) to 24.3 months (high-risk men)., Conclusion: We can no longer assume that medication disutility is almost zero. Over one-quarter of subjects had disutility exceeding the group-average longevity gain from statins expected even for the highest-risk (ie, highest-gain) group. Future primary prevention studies might explore medication disutility in larger populations. Patients may differ more in disutility than in prospectively definable utility (which provides only group-average estimates). Consultations could be enriched by assessing disutility and exploring its reasons., (© 2014 American Heart Association, Inc.)

Objective: Discussions about statin efficacy in cardiovascular prevention are always based on data from blinded randomized controlled trials (RCTs) comparing statin to placebo; however, discussion of side effects is not. Clinicians often assume symptoms occurring with statins are caused by statins, encouraging discontinuation. We test this assumption and calculate an evidence-based estimate of the probability of a symptom being genuinely attributable to the statin itself., Methods: We identified RCTs comparing statin to placebo for cardiovascular prevention that reported side effects separately in the two arms., Results: Among 14 primary prevention trials (46,262 participants), statin therapy increased diabetes by absolute risk of 0.5% (95% CI 0.1-1%, p = 0.012), meanwhile reducing death by a similar extent: -0.5% (-0.9 to -0.2%, p = 0.003). In the 15 secondary prevention RCTs (37,618 participants), statins decreased death by 1.4% (-2.1 to -0.7%, p < 0.001). There were no other statin-attributable symptoms, although asymptomatic liver transaminase elevation was 0.4% more frequent with statins across all trials. Serious adverse events and withdrawals were similar in both arms., Conclusions: Only a small minority of symptoms reported on statins are genuinely due to the statins: almost all would occur just as frequently on placebo. Only development of new-onset diabetes mellitus was significantly higher on statins than placebo; nevertheless only 1 in 5 of new cases were actually caused by statins. Higher statin doses produce a detectable effect, but even still the proportion attributable to statins is variable: for asymptomatic liver enzyme elevation, the majority are attributable to the higher dose; in contrast for muscle aches, the majority are not.

Aims: Full-disclosure study describing Doppler patterns during iterative atrioventricular delay (AVD) optimization of biventricular pacemakers (cardiac resynchronization therapy, CRT)., Method and Results: Doppler traces of the first 50 eligible patients undergoing iterative Doppler AVD optimization in the BRAVO trial were examined. Three experienced observers classified conformity to guideline-described patterns. Each observer then selected the optimum AVD on two separate occasions: blinded and unblinded to AVD. Four Doppler E-A patterns occurred: A (always merged, 18% of patients), B (incrementally less fusion at short AVDs, 12%), C (full separation at short AVDs, as described by the guidelines, 28%), and D (always separated, 42%). In Groups A and D (60%), the iterative guidelines therefore cannot specify one single AVD. On the kappa scale (0 = chance alone; 1 = perfect agreement), observer agreement for the ideal AVD in Classes B and C was poor (0.32) and appeared worse in Groups A and D (0.22). Blinding caused the scattering of the AVD selected as optimal to widen (standard deviation rising from 37 to 49 ms, P < 0.001). By blinding 28% of the selected optimum AVDs were ≤60 or ≥200 ms. All 50 Doppler datasets are presented, to support future methodological testing., Conclusion: In most patients, the iterative method does not clearly specify one AVD. In all the patients, agreement on the ideal AVD between skilled observers viewing identical images is poor. The iterative protocol may successfully exclude some extremely unsuitable AVDs, but so might simply accepting factory default. Irreproducibility of the gold standard also prevents alternative physiological optimization methods from being validated honestly.

Aims: Prognostic benefit from CRT compared with controls is well established. Symptomatic response rates, however, are controversial and have never been systematically evaluated with standard subtraction of control rates to establish the incremental symptomatic response effect of CRT pacing., Methods and Results: First, we identified 150 consecutive CRT papers and assessed researchers' perceptions of the symptomatic response to CRT. The mean quoted response rate was 66%. Only 26 studies acknowledged the existence of response without the device. Secondly, we examined actual symptomatic response rates in the randomized trials (CARE-HF, COMPANION, CONTAK-CD, MIRACLE, MIRACLE-ICD, MIRACLE-ICD II, MUSTIC, and REVERSE) totalling 3904 patients. The NYHA status improved in 51% of those randomized to CRT vs. 35% of controls (incremental effect 16%). This incremental improvement was significantly greater in open studies (with no device for controls) than in blinded studies (control arm receiving a device but no CRT, such as a defibrillator or a CRT programmed off), 20% vs. 13%, P < 0.001., Conclusions: Quoting CRT responder rates in isolation without recognizing spontaneous 'response' is common but unwise. The incremental symptomatic response rate from CRT pacing is ∼16%, much lower than widely reported. This value is similar to that for drugs in heart failure and should not be considered disappointing: they both exert powerful prognostic benefits. For scientific purposes, e.g. to explore potential improvements, symptomatic benefit from CRT should be quantified, like all other effects, by comparison with a control.

Background: It remains unclear which echocardiographic measure is most suitable for serial measurement in real-world aortic stenosis (AS) follow-up. We determine whether the dimensionless index (DI) between aortic valve and left ventricular outflow tract velocities is measured more consistently using velocity-time-integral (VTI) or peak velocities (V(peak)) in real life., Methods: Serial echocardiograms acquired within 6 months in subjects with AS were analysed with blinding, to compare the variability over time of DI calculated using V(peak), with that of DI calculated using VTI., Results: Paired echocardiograms, acquired on average 72 days apart, were analysed from 70 patients with a range of severities of AS (59% severe). DI, calculated using either V(peak) or VTI, did not significantly change over this short time. Coefficient of variation was significantly better when DI was calculated using V(peak) than VTI (12.6 versus 25.4%, p<0.0001). The variabilities of mean and peak trans-aortic valve 4v(2) and left ventricular outflow tract VTI were no better: 26.9%, 19.1% and 22.1% respectively., Conclusions: Serially-followed variables require minimal noise to maximise detection of genuine change. For AS surveillance, calculating DI--or effective orifice area--from the ratio of V(peak) rather than VTIs would reduce 95% confidence intervals from ± 51% to a still-disappointing ± 25%. Guidelines recommend noisy surveillance measures, causing conscientious echocardiographers to 'peek' at previous values, and impairing clinicians' faith in echocardiographically-observed changes when making clinical decisions. For us in echocardiography to improve our ability to contribute to AS follow-up requires us to first acknowledge and discuss this honestly., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Sympathetic overactivation, is reduced by renal denervation in drug-resistant hypertension. A similar role for renal denervation in heart failure remains unstudied, partly due to the concern about potential concomitant deleterious blood pressure reductions. This pilot study evaluated the safety of renal denervation for heart failure using an intensive follow-up protocol., Method: 7 patients (mean age 69 years) with chronic systolic heart failure (mean BP on referral 112/65 mmHg) on maximal tolerated heart failure therapy underwent bilateral renal denervation May-July 2011. Patients were admitted for pre-procedure baseline assessments and in-patient observation for 5 days following denervation. Follow-up was weekly for 4 weeks, and then monthly for 6 months., Results: No significant haemodynamic disturbances were noted during the acute phase post renal denervation. Over 6 months there was a non-significant trend to blood pressure reduction (Δsystolic -7.1 ± 6.9 mmHg, p=0.35; Δdiastolic -0.6 ± 4.0 mmHg, p=0.88). No hypotensive or syncopal episodes were reported. Renal function remained stable (Δcreatinine -5.7 ± 8.4 μmol/l, p=0.52 and Δurea -1.0 ± 1.0 mmol/l, p=0.33). All 7 patients described themselves as symptomatically improved. The six minute walk distance at six months was significantly increased (Δ=27.1 ± 9.7 m, p=0.03), with each patient showing an increase., Conclusions: This study found no procedural or post procedural complications following renal denervation in patients with chronic systolic heart failure in 6 months of intensive follow-up. Results suggested improvements in both symptoms and exercise capacity, but further randomised, blinded sham-controlled clinical trials are required to determine the impact of renal denervation on morbidity and mortality in systolic heart failure. These data suggest such trials will be safe. ClinicalTrial.gov NCT01584700, (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Aims: Brachial systolic blood pressure (bSBP) exceeds aortic pressure by a variable amount, and estimated central systolic blood pressure (cSBP) may be a better indicator of cardiovascular risk than bSBP. We undertook a systematic review and meta-analysis to compare the effect of single and multiple antihypertensive agents on bSBP, cSBP and augmentation index (AIx)., Methods: A random effects meta-analysis was performed on 24 randomized controlled trials of antihypertensives with measurements of bSBP, cSBP and/or AIx. Separate analyses were performed for drug comparisons with or without placebo, and drug combinations., Results: In the placebo vs. drug meta-analysis, antihypertensive therapy reduced bSBP more than cSBP and there was no statistically significant evidence of heterogeneity by drug class, although the number of individual studies was small. In placebo-adjusted drug vs. drug comparison, treatment with β-blockers, omapatrilat and thiazide diuretics lowered cSBP significantly less than bSBP (i.e. central to brachial amplification decreased), whereas other monotherapies lowered cSBP and bSBP to similar extents. Sample sizes were too small and effect estimates insufficiently precise to allow firm conclusions to be made regarding comparisons between individual drug classes. Antihypertensive combinations that included β-blockers decreased central to brachial amplification. β-Blockers increased AIx, whereas all other antihypertensive agents reduced AIx to similar extents., Conclusions: A reduction in central to brachial amplification by some classes of antihypertensive drug will result in lesser reductions in cSBP despite achievement of target bSBP. This effect could contribute to differences in outcomes in randomized clinical trials when β-blocker- and/or diuretic-based antihypertensive therapy are compared with other regimens., (© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.)