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Background and Aims: Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD). We aimed to assess whether statins prevent decline in left ventricular ejection fraction (LVEF) in anthracycline-treated patients at increased risk for CTRCD., Methods: In this multicenter double-blinded, placebo-controlled trial, patients with cancer at increased risk of anthracycline-related CTRCD (per ASCO guidelines) were randomly assigned to atorvastatin 40 mg or placebo once-daily. Cardiovascular magnetic resonance (CMR) imaging was performed before and within 4 weeks after anthracyclines. Blood biomarkers were measured at every cycle. The primary outcome was post-anthracycline LVEF, adjusted for baseline. CTRCD was defined as a fall in LVEF by >10% to <53%. Secondary endpoints included left ventricular (LV) volumes, CTRCD, CMR tissue characterization, high sensitivity troponin I (hsTnI), and B-type natriuretic peptide (BNP)., Results: We randomized 112 patients (56.9 ± 13.6 years, 87 female, and 73 with breast cancer): 54 to atorvastatin and 58 to placebo. Post-anthracycline CMR was performed 22 (13-27) days from last anthracycline dose. Post-anthracycline LVEF did not differ between the atorvastatin and placebo groups (57.3 ± 5.8% and 55.9 ± 7.4%, respectively) when adjusted for baseline LVEF (P = 0.34). There were no significant between-group differences in post-anthracycline LV end-diastolic (P = 0.20) or end-systolic volume (P = 0.12), CMR myocardial edema and/or fibrosis (P = 0.06-0.47), or peak hsTnI (P ≥ 0.99) and BNP (P = 0.23). CTRCD incidence was similar (4% versus 4%, P ≥ 0.99). There was no difference in adverse events., Conclusions: In patients at increased risk of CTRCD, primary prevention with atorvastatin during anthracycline therapy did not ameliorate early LVEF decline, LV remodeling, CTRCD, change in serum cardiac biomarkers, or CMR myocardial tissue changes., Trial Registration: NCT03186404., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Global longitudinal strain (GLS) can predict cancer therapeutics-related cardiac dysfunction and guide initiation of cardioprotection (CPT)., Objectives: In this study, the authors sought to determine whether echocardiography GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care at 3 years., Methods: In this international multicenter prospective randomized controlled trial, patients were enrolled from 28 international sites. All patients treated with anthracyclines with another risk factor for heart failure were randomly allocated to GLS-guided (>12% relative reduction in GLS) or ejection fraction (EF)-guided (>10% absolute reduction of EF to <55%) CPT. The primary end point was the change in 3-dimensional (3D) EF (ΔEF) from baseline to 3 years., Results: Among 331 patients enrolled, 255 (77%, age 54 ± 12 years, 95% women) completed 3-year follow-up (123 in the EF-guided group and 132 in the GLS-guided group). Most had breast cancer (n = 236; 93%), and anthracycline followed by trastuzumab was the most common chemotherapy regimen (84%). Although 67 (26%) had hypertension and 32 (13%) had diabetes mellitus, left ventricular function was normal at baseline (EF: 59% ± 6%, GLS: 20.7% ± 2.3%). CPT was administered in 18 patients (14.6%) in the EF-guided group and 41 (31%) in the GLS-guided group (P = 0.03). Most patients showed recovery in EF and GLS after chemotherapy; 3-year ΔEF was -0.03% ± 7.9% in the EF-guided group and -0.02% ± 6.5% in the GLS-guided (P = 0.99) group; respective 3-year EFs were 58% ± 6% and 59% ± 5% (P = 0.06). At 3 years, 17 patients (5%) had cancer therapeutics-related cardiac dysfunction (11 in the EF-guided group and 6 in the GLS guided group; P = 0.16); 1 patient in each group was admitted for heart failure., Conclusions: Among patients taking potentially cardiotoxic chemotherapy for cancer, the 3-year data showed improvement of LV dysfunction compared with 1 year, with no difference in ΔEF between GLS- and EF-guided CPT. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628)., Competing Interests: Funding Support and Author Disclosures This study was supported in part by a project grant (1119955) from the National Health and Medical Research Council, Canberra, Australia, and an unrestricted grant from General Electric Healthcare, Horten, Norway. At the CHU de Québec site, the study was funded by the Fondation du CHU de Québec. Dr Marwick is supported by an investigator grant (2008129) from the National Health and Medical Research Council, Canberra, Australia. Dr Thavendiranathan is supported by a Canadian Institutes of Health Research New Investigator Award (147814), an Ontario Early Research Award, and a Canada Research Chair in Cardio-oncology. Dr K. Negishi is supported by a fellowship (award reference no. 101868) from the National Heart Foundation of Australia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Echocardiographic global longitudinal strain (GLS) is a useful measure for detection of cancer treatment-related cardiac dysfunction (CTRCD) but is influenced by blood pressure changes. This limitation may be overcome by assessment of myocardial work (MW), which incorporates blood pressure into the calculation., Objectives: This work aims to determine whether myocardial work indices (MWIs) can help diagnose or prognosticate CTRCD., Methods: In this prospective cohort study, 136 women undergoing anthracycline and trastuzumab treatment for HER2+ breast cancer, underwent serial echocardiograms and cardiac magnetic resonance pre- and post-anthracycline and every 3 months during trastuzumab. GLS, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency were measured. CTRCD was defined with cardiac magnetic resonance. Generalized estimating equations quantified the association between changes in GLS and MWIs and CTRCD at the current (diagnosis) and subsequent visit (prognosis). Regression tree analysis was used to explore the combined use of GLS and MW for the diagnostic/prognostic assessment of CTRCD., Results: Baseline left ventricular ejection fraction (LVEF) was 63.2 ± 4.0%. Thirty-seven (27.2%) patients developed CTRCD. An absolute change in GLS (standardized odds ratio [sOR]: 1.97 [95% CI: 1.07-3.66]; P = 0.031) and GWI (sOR: 1.73 [95% CI: 1.04-2.85]; P = 0.033) were associated with concurrent CTRCD. An absolute change in GLS (sOR: 1.79 [95% CI: 1.22-2.62]; P = 0.003), GWI (sOR: 1.67 [95% CI: 1.20-2.32]; P = 0.003), and GCW (sOR: 1.65 [95% CI: 1.17-2.34]; P = 0.005) were associated with subsequent CTRCD. Change in GWI and GCW demonstrated incremental value over GLS and clinical factors for the diagnosis of concurrent CTRCD. In a small group with a GLS change <3.3% (absolute), and a >21 mm Hg reduction in systolic blood pressure, worsening of GWI identified patients with higher probability of concurrent CTRCD (24.0% vs 5.2%). MWIs did not improve identification of subsequent CTRCD beyond knowledge of GLS change., Conclusions: GLS can be used to diagnose and prognosticate cardiac magnetic resonance (CMR) defined CTRCD, with additional value from MWIs in selected cases. (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538)., Competing Interests: Funding Support and Author Disclosures This study was funded by an operating grant from the Canadian Institutes of Health Research (137132 and 142456) and the Ontario Early Research Award to Dr Thavendiranathan. University Health Network has a Master Research Agreement with Siemens Healthineers. Dr Amir has received fees for expert testimony from Genentech/Roche; and has received honoraria from Amgen. Dr Abdel-Qadir has received support from a National New Investigator Award from the Heart and Stroke Foundation of Canada. Dr Marwick has been supported in part by a Project Grant (1119955) from the National Health and Medical Research Council, Canberra, Australia; and has received an unrestricted grant from General Electric Healthcare, Horten, Norway, for the support of the SUCCOUR trial. Dr Thavendiranathan (147814) has been supported by the Canadian Institutes of Health Research New Investigator Award and a Canada Research Chair in Cardio-oncology; and has received speaker honorarium from Amgen, Boehringer Ingelheim, and Takeda. Dr Wintersperger has received research support and speaker honorarium from Siemens Healthineers; and provides consultation to Bayer AG., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose of the Review: Anthracycline chemotherapy carries a risk of myocardial dysfunction and heart failure even at relatively low doses, and the clinical prediction of cancer treatment-related cardiac dysfunction (CTRCD) is inexact. Careful imaging or biomarker surveillance during chemotherapy can identify CTRCD before the development of heart failure. Currently, this surveillance is performed using ejection fraction (EF). While this is a reliable and reproducible test with three-dimensional techniques, the most widely used imaging technique is two-dimensional echocardiography, for which EF measurements have broad confidence intervals., Recent Findings: The use of global myocardial strain (GLS) provides a more reliable and reproducible means of assessing global cardiac function and shows meaningful changes before a significant change of EF. Observational studies have shown that although absolute measurements of GLS, both at baseline and during therapy, are predictive of CTRCD risk, the most reliable approach is to assess the change of GLS with therapy - a meaningful relative change of 10-15% being significant. A clinical trial comparing GLS to EF surveillance did not show a significant change of EF in the overall study group, but did show that patients managed with a the GLS-guided approach were less likely to develop a meaningful change of cardiac function to an abnormal level. In at-risk patients, there is good evidence for the protective value of neurohormonal antagonists and statins: the use of GLS enables these benefits to be directed to those most likely to benefit, while minimizing their use in the majority of people, who do not need them. Although GLS requires an element of training and efforts to ensure uniformity, it has proven to be a feasible, robust, and reproducible technique, ready for wide adoption., (© 2022. The Author(s).)

Importance: Diagnosis of cancer therapy-related cardiac dysfunction (CTRCD) remains a challenge. Cardiovascular magnetic resonance (CMR) provides accurate measurement of left ventricular ejection fraction (LVEF), but access to repeated scans is limited., Objective: To develop a diagnostic model for CTRCD using echocardiographic LVEF and strain and biomarkers, with CMR as the reference standard., Design, Setting, and Participants: In this prospective cohort study, patients were recruited from University of Toronto-affiliated hospitals from November 2013 to January 2019 with all cardiac imaging performed at a single tertiary care center. Women with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer were included. The main exclusion criterion was contraindication to CMR. A total of 160 patients were recruited, 136 of whom completed the study., Exposures: Sequential therapy with anthracyclines and trastuzumab., Main Outcomes and Measures: Patients underwent echocardiography, high-sensitivity troponin I (hsTnI), B-type natriuretic peptide (BNP), and CMR studies preanthracycline and postanthracycline every 3 months during and after trastuzumab therapy. Echocardiographic measures included 2-dimensional (2-D) LVEF, 3-D LVEF, peak systolic global longitudinal strain (GLS), and global circumferential strain (GCS). LVEF CTRCD was defined using the Cardiac Review and Evaluation Committee Criteria, GLS or GCS CTRCD as a greater than 15% relative change, and abnormal hsTnI and BNP as greater than 26 pg/mL and ≥ 35 pg/mL, respectively, at any follow-up point. Combinations of echocardiographic measures and biomarkers were examined to diagnose CMR CTRCD using conditional inference tree models., Results: Among 136 women (mean [SD] age, 51.1 [9.2] years), CMR-identified CTRCD occurred in 37 (27%), and among those with analyzable images, in 30 of 131 (23%) by 2-D LVEF, 27 of 124 (22%) by 3-D LVEF, 53 of 126 (42%) by GLS, 61 of 123 (50%) by GCS, 32 of 136 (24%) by BNP, and 14 of 136 (10%) by hsTnI. In isolation, 3-D LVEF had greater sensitivity and specificity than 2-D LVEF for CMR CTRCD while GLS had greater sensitivity than 2-D or 3-D LVEF. Regression tree analysis identified a sequential algorithm using 3-D LVEF, GLS, and GCS for the optimal diagnosis of CTRCD (area under the receiver operating characteristic curve, 89.3%). The probability of CTRCD when results for all 3 tests were negative was 1.0%. When 3-D LVEF was replaced by 2-D LVEF in the model, the algorithm still performed well; however, its primary value was to rule out CTRCD. Biomarkers did not improve the ability to diagnose CTRCD., Conclusions and Relevance: Using CMR CTRCD as the reference standard, these data suggest that a sequential approach combining echocardiographic 3-D LVEF with 2-D GLS and 2-D GCS may provide a timely diagnosis of CTRCD during routine CTRCD surveillance with greater accuracy than using these measures individually., Trial Registration: ClinicalTrials.gov Identifier: NCT02306538.

Atrial enlargement in response to pathological stimuli (e.g., hypertension, mitral valve disease) and physiological stimuli (exercise, pregnancy) can be comparable in magnitude, but the diseased enlarged atria is associated with complications such as atrial fibrillation (AF), whereas physiological atrial enlargement is not. Pathological atrial enlargement and AF is also observed in a small percentage of athletes undergoing extreme/intense endurance sport and pregnant women with preeclampsia. Differences between physiological and pathological atrial enlargement and underlying mechanisms are poorly understood. This review describes human and animal studies characterizing atrial enlargement under physiological and pathological conditions and highlights key knowledge gaps and clinical challenges, including: 1) the limited ability of atria to reverse remodel; and 2) distinguishing physiological and pathological enlargement via imaging/biomarkers. Finally, this review discusses how targeting distinct molecular mechanisms underlying physiological and pathological atrial enlargement could provide new therapeutic and diagnostic strategies for preventing or reversing atrial enlargement and AF., Competing Interests: Funding Support and Author Disclosures Drs. Voskoboinik and La Gerche are supported by fellowships from the National Heart Foundation of Australia (102122, 102206). Dr. McMullen is supported by a National Health and Medical Research Council Fellowship (ID APP1078985). 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.)

Objectives: The purpose of this study was to investigate the effect of the temporal and observer variability of cardiac magnetic resonance (CMR)-measured native T 1 , T 2 , and extracellular volume fraction (ECV) and serum biomarkers for the detection of cancer-therapeutics-related cardiac dysfunction (CTRCD)., Background: Biomarkers and serial quantitative CMR tissue characterization may help identify early myocardial changes of CTRCD, but these parameters require both accuracy and reliability., Methods: A total of 50 participants (age 48.9 ± 12.1 years) underwent 3 CMR studies (1.5-T) and biomarker measurements (high-sensitivity troponin-I and B-type natriuretic peptide) at 3-month intervals: 20 with HER2-positive breast cancer (10 with and 10 without CTRCD), and 30 prospectively recruited healthy participants. T 1 and T 2 maps were obtained at 3 left ventricular short-axis locations. Temporal and observer variability were calculated as the coefficient of variation and as the standard error of the measurement (SEM) using repeated measures and 2-way analysis of variance. Minimal detected difference was defined as 2 × SEM., Results: Compared with the patients without CTRCD, those with CTRCD had larger temporal change in native T 1 (27.2 ms [95% confidence interval (CI): 20.8 to 39.3 ms] vs. 12.4 ms [95% CI: 9.5 to 17.9 ms]), T 2 (2.0 ms [95% CI: 1.5 to 2.9 ms] vs. 1.0 ms [95% CI: 0.74 to 1.4 ms]), and ECV (2.1% [95% CI: 1.5% to 3.1%] vs. 1.0% [95% CI: 0.8% to 1.5%]). However, the temporal changes in biomarkers overlapped. The minimal detected difference for T 1 (29 ms), T 2 (3.0 ms), and ECV (2.2%) in healthy participants approached the mean temporal changes in patients with CTRCD. For individual patients with CTRCD, there was overlap in the temporal changes of all 3 parameters, and the variability in healthy participants with the least overlap for native T 1 . The interobserver/intraobserver variabilities for the CMR parameters were low (coefficient of variation 0.5% to 4.3%)., Conclusions: The temporal changes in both biomarkers and tissue characterization measures in individual patients overlap with the temporal variability in healthy participants and approach the minimal detectable temporal differences. While the accuracy of the parameters awaits further study, the temporal variability of these methods may pose challenges to routine clinical application in individual patients receiving cancer therapy., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate the hypothesis that global longitudinal strain (GLS) guidance of cardioprotective therapy would improve cardiac function of at-risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care., Background: The conventional criteria for diagnosis of chemotherapy-related cardiac dysfunction (CTRCD) are dependent on the recognition of heart failure symptoms and/or changes in left ventricular ejection fraction. However, the measurement variability of left ventricular ejection fraction necessitates broad diagnostic ranges, with the consequence of low sensitivity for CTRCD. Observational data have shown GLS to be a robust and sensitive marker to predict CTRCD and thereby guide the initiation of cardioprotective therapy, but these data are insufficient to justify changing the diagnostic criteria for CTRCD., Methods: The SUCCOUR (Strain sUrveillance of Chemotherapy for improving Cardiovascular Outcomes) trial is an international multicenter prospective randomized controlled trial. Patients who are taking cardiotoxic chemotherapy (n = 320) with at least 1 risk factor will be randomly allocated into GLS- and ejection fraction-guided strategies. All participants will be followed over 3 years for the primary endpoint (change in 3-dimensional ejection fraction) and other secondary endpoints., Results: Among the first 185 patients (age 54 ± 13 years; 93% women) from 23 international sites, 88% had breast cancer, 9% had lymphoma, and 3% had other cancers. Heart failure risk factors were prevalent: 34% had hypertension and 10% had diabetes mellitus. The most common chemotherapy regimen during this study was the combination of anthracycline and trastuzumab. The baseline 3-dimensional left ventricular ejection fraction was 61 ± 4%, and GLS was 20.3 ± 2.5%. Of 93 patients followed up in the first year of the study, 10 had to withdraw for noncardiac reasons. Of 40 patients randomized to the GLS-guided arm, 15 have been started on cardioprotective therapy, whereas 4 of 46 patients in the ejection fraction-guided arm have been started on therapy., Conclusions: The SUCCOUR trial will be the first randomized controlled trial of GLS and will provide evidence to inform guidelines regarding the place of GLS for surveillance for CTRCD. (Strain sUrveillance of Chemotherapy for improving Cardiovascular Outcomes [SUCCOUR]; ANZ Clinical Trials ACTRN12614000341628)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to show the degree to which experience and training affect the precision and validity of global longitudinal strain (GLS) measurement and to evaluate the variability of strain measurement after feedback., Background: The application of GLS for the detection of subclinical dysfunction has been recommended in an expert consensus document and is being used with increasing frequency. The role of experience in the precision and validity of GLS measurement is unknown, as is the efficacy of training., Methods: Fifty-eight readers, divided into 4 groups on the basis of their experience with GLS, calculated GLS from speckle strain analysis of 9 cases with various degrees of image quality. Intraclass correlation coefficients (ICCs), mean difference, SD, and coefficient of variation (CV) were compared against the measurements of a reference group that had experience with >1,000 cases of strain measurement. Individualized feedback was distributed, and repeat measurements were performed by 40 readers. Comparisons with the baseline variation provided information about whether feedback was effective., Results: The ICC for GLS was significantly greater than that for ejection fraction regardless of image quality. Experience with strain measurement affected the concordance in strain values among the readers; the group with the highest level of experience showed significantly better ICC than those with no experience, although the ICC of the inexperienced readers was still very good (0.996 vs. 0.975; p = 0.0002). As experience increased, the mean difference, SD, and CV became significantly smaller. The CV of segmental strain analysis showed significant improvement after training, regardless of experience., Conclusions: The favorable interobserver agreement of GLS makes it more attractive than ejection fraction for follow-up of left ventricular function by multiple observers. Although experience is important, the precision of GLS was high for all groups. Training appears to be of most value for the assessment of segmental strain., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The increasing cost of healthcare is a widespread international problem to which the cost of imaging has been an important contributor. Some imaging tests are ordered inappropriately and contribute to wasted use of resources. Appropriate use criteria have been developed in the USA in order to guide test selection, but there are a number of problems, including the evidence base for these criteria and the steps that can be taken to change physician practice. A restrictive approach to test ordering is difficult to fit to the nuances of clinical presentation and may compromise patient care. We propose an alternative approach to physician guidance based on the most common markers of inappropriate testing.

Background: Thoracic radiation results in radiation-associated heart disease (RAHD), often requiring cardiothoracic surgery (CTS). We sought to measure long-term survival in RAHD patients undergoing CTS, to compare them with a matched control population undergoing similar surgical procedures, and to identify potential predictors of long-term survival., Methods and Results: In this retrospective observational cohort study of patients undergoing CTS, matched on the basis of age, sex, and type/time of CTS, 173 RAHD patients (75% women; age, 63±14 years) and 305 comparison patients (74% women; age, 63±4 years) were included. The vast majority of RAHD patients had prior breast cancer (53%) and Hodgkin lymphoma (27%), and the mean time from radiation was 18±12 years. Clinical and surgical parameters were recorded. The preoperative EuroSCORE and all-cause mortality were recorded. The mean EuroSCOREs were similar in the RAHD and comparison groups (7.8±3 versus 7.4±3, respectively; P=0.1). Proximal coronary artery disease was higher in patients with RAHD versus the comparison patients (45% versus 38%; P=0.09), whereas redo CTS was lower in the RACD versus the comparison group (20% versus 29%; P=0.02). About two thirds of patients in either group had combination surgical procedures. During a mean follow-up of 7.6±3 years, a significantly higher proportion of patients died in the RAHD group than in the comparison group (55% versus 28%; P<0.001). On multivariable Cox proportional hazard analysis, RAHD (2.47; 95% confidence interval, 1.82-3.36), increasing EuroSCORE (1.22; 95% confidence interval, 1.16-1.29), and lack of β-blockers (0.66; 95% confidence interval, 0.47-0.93) were associated with increased mortality (all P<0.01)., Conclusions: In patients undergoing CTS, RAHD portends increased long-term mortality. Alternative treatment strategies may be required in RAHD to improve long-term survival.

The reservoir, conduit, and contractile functions of the left atrium are integral to overall cardiac performance. Recent advances in cardiac imaging offer the accurate assessment of LA phasic functions and structure, using techniques such as 3-dimensional echocardiography, color tissue Doppler imaging, and speckle tracking, as well as cardiac computed tomography and magnetic resonance imaging. These new developments are particularly important in view of the increasing use of intervention involving the left atrium. This review article highlights and contrasts the imaging of the size, mechanics, and structure of the left atrium using multiple modalities. The authors discuss recent studies on the clinical applications of the various techniques in disease conditions., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The combination of high energy expenditure and the borderline adequacy of perfusion make the subendocardium uniquely vulnerable to injury. Selective subendocardial involvement is usually a marker of subclinical disease. Technical advances in new noninvasive imaging modalities, especially in spatial resolution, now permit qualitative and quantitative assessment of subendocardial structure, function, and perfusion. Many newer techniques have the potential to provide superior prognostic information to current standard assessment methods. This review describes the contemporary capabilities of multiple imaging modalities for assessment of the subendocardium, and seeks to guide the clinician regarding the information and technical deficiencies of each modality.

For over 30 of its 50-year history, echocardiography has provided noninvasive, widely available and inexpensive imaging. This technique now has a huge evidence base that is incorporated in the guidelines for many cardiac diseases, to the extent that echocardiography (2DE) has a central position in modern cardiac diagnosis and management. The paradox is that in contributing the lion's share of cardiac imaging, echocardiography has become removed from the province of the imaging specialist and its role as an interesting and worthwhile source of investigation and training has been superseded by the newer methodologies including cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR). However, the clinical contribution of potential advances are likely to be realised only if "advanced echocardiography" - including deformation, contrast and three-dimensional imaging - are differentiated from the "plain vanilla" of routine echocardiography. Successful translation of these advances into clinical practice will show that these new techniques are complimentary and in some cases competitive with the new imaging methodologies. This review seeks to provide a perspective of how echocardiography will integrate with the new imaging methodologies for the most common indications for cardiac imaging, with specific attention to the contribution of new methodologies including three-dimensional echocardiography (3DE) and deformation imaging.

Echocardiography has become an integral part of modern cardiology, and parameters measured by echocardiography are enshrined in guidelines as components of clinical decision-making in the management of heart failure, valve disease and arrhythmias. This review will explore four modalities which will underpin the future of echocardiography - the hand-held machine, quantification, three-dimensional imaging, and contrast. Finally, we will explore the implications of the new financial milieu for the selection of cardiac imaging modalities.

Background: Although guidelines recommend the use of beta-adrenoceptor blocking drugs to reduce cardiac events (CEs) after major noncardiac surgery, trial results have varied between showing benefit, ineffectiveness, and harm. We sought whether optimizing beta-blockade (BB) delivery could make them more effective., Methods: Intermediate risk patients undergoing major noncardiac surgery (n = 400) were randomized to 2 strategies of BB therapy: universal BB (UBB; n = 197) comprising an algorithm-based, nurse-led strategy to optimize dosing and adherence to bisoprolol titration over > or =1 week preoperatively versus usual care (UC; n = 203), whereby BB are continued in those already taking them or prescribed for patients identified as high risk based on ischemia (new or inducible wall motion abnormalities) at dobutamine echocardiography (DbE). Daily electrocardiogram and troponin levels were obtained on 3 postoperative days. The primary end point was a major CE (cardiac death or myocardial infarction) within 30 days., Results: There were 25 major CEs (6.3%), occurring in 13 (6.6%) of 197 UBB and 12 (5.9%) of 203 UC patients (OR 1.12, 95% CI 0.52-2.39). Independent predictors of CEs were baseline systolic blood pressure (beta 1.02, P = .005) and postoperative hypotension (beta 1.02, P = .03) but not treatment strategy. Those randomized to UBB had significantly better heart rate control perioperatively, at the cost of bradycardia and hypotension. The negative predictive value of DbE in this study was 95%., Conclusions: These data confirm a persistent CE rate after major noncardiac surgery despite nurse-led dose titration of bisoprolol. Cardiac events were equivalent to a UC strategy based on DbE results.

Background: Three-dimensional echocardiography (3DE) appears to show incremental benefit over two-dimensional echocardiography (2DE), but it's uptake has been slow. We tested attendees before and after an intensive interactive training course to identify its efficacy., Methods: Attendees (n = 35, 23 cardiologists, 12 sonographers) were shown how to use 3DE review software and asked to identify the pathology of five patients (wall motion abnormality, peri-prosthetic mitral regurgitation, subaortic membrane, small ventricular septal defect, submitral stenosis) on 2D and 3D images. In the following one and a half-day interactive teaching course, brief presentations on application of 3DE for assessment of wall motion, valve and congenital abnormalities were followed by review of 3D datasets, during which the attendees made their own interpretations before being shown the optimal viewing strategy. Test cases were not discussed and the test was repeated at the end of the course., Results: Most attendees (57%) had access but with little or no use of a 3DE system. Three-dimensional echocardiography had no incremental value before training. After training, overall correct responses significantly improved compared with baseline interpretation, although improvement was not the same for all diagnoses. All groups (cardiologists vs. sonographers, inexperienced vs. moderately experienced reviewers) improved similarly., Conclusions: Incorporation of 3DE into standard practice may be limited by inexperience. An interactive teaching course with rehearsal and direct mentoring appears to overcome this limitation and may improve the uptake of this technique.

Heart failure and diabetes mellitus are frequently associated, with diabetes potentiating the development of heart failure after other myocardial insults. This review documents the evidence in support of a specific primary myocardial disease in diabetes. The strongest clinical evidence relates to the detection of otherwise unexplained diastolic dysfunction in apparently healthy diabetic subjects, but recent studies with sensitive echocardiographic markers have shown systolic disturbances as well. The mechanism of this myocardial disease is multifactorial, with contributions from metabolic effects on the myocyte, structural changes in the myocardium and interstitium, autonomic neuropathy, and perhaps coronary vascular disease. The common pathway appears to be related to glycemic control and new evidence suggests better metabolic control to be beneficial, as well as angiotensin-converting enzyme inhibition and cross-link breakers.

Cardiovascular magnetic resonance (CMR) imaging has become an essential technique for the assessment of cardiac function and morphology, and is now routinely used to monitor disease progression and intervention efficacy in the clinic. Cardiac fibrosis is a common characteristic of numerous cardiovascular diseases and often precedes cardiac dysfunction and heart failure. Hence, the detection of cardiac fibrosis is important for both early diagnosis and the provision of guidance for interventions/therapies. Experimental mouse models with genetically and/or surgically induced disease have been widely used to understand mechanisms underlying cardiac fibrosis and to assess new treatment strategies. Improving the appropriate applications of CMR to mouse studies of cardiac fibrosis has the potential to generate new knowledge, and more accurately examine the safety and efficacy of antifibrotic therapies. In this review, we provide 1) a brief overview of different types of cardiac fibrosis, 2) general background on magnetic resonance imaging (MRI), 3) a summary of different CMR techniques used in mice for the assessment of cardiac fibrosis including experimental and technical considerations (contrast agents and pulse sequences), and 4) provide an overview of mouse studies that have serially monitored cardiac fibrosis during disease progression and/or therapeutic interventions. Clinically established CMR protocols have advanced mouse CMR for the detection of cardiac fibrosis, and there is hope that discovery studies in mice will identify new antifibrotic therapies for patients, highlighting the value of both reverse translation and bench-to-bedside research. [ABSTRACT FROM AUTHOR]

Arterial hypertension remains the most frequent cardiovascular (CV) risk factor, and is responsible for a huge global burden of disease. Echocardiography is the first-line imaging method for the evaluation of cardiac damage in hypertensive patients and novel techniques, such as 2D and D speckle tracking and myocardial work, provide insight in subclinical left ventricular (LV) impairment that would not be possible to detect with conventional echocardiography. The structural, functional, and mechanical cardiac remodelling that are detected with imaging are intermediate stages in the genesis of CV events, and initiation or intensification of antihypertensive therapy in response to these findings may prevent or delay progressive remodelling and CV events. However, LV remodelling—especially LV hypertrophy—is not specific to hypertensive heart disease (HHD) and there are circumstances when other causes of hypertrophy such as athlete heart, aortic stenosis, or different cardiomyopathies need exclusion. Tissue characterization obtained by LV strain, cardiac magnetic resonance, or computed tomography might significantly help in the distinction of different LV phenotypes, as well as being sensitive to subclinical disease. Selective use of multimodality imaging may therefore improve the detection of HHD and guide treatment to avoid disease progression. The current review summarizes the advanced imaging tests that provide morphological and functional data about the hypertensive cardiac injury. [ABSTRACT FROM AUTHOR]

Objective Autonomic dysfunction may contribute to the etiology and exercise intolerance of subclinical diabetic heart disease. This study sought the efficacy of exercise training for improvement of peak oxygen uptake (VO2peak) and cardiac autonomic function in type 2 diabetic patients with non-ischemic subclinical left-ventricular (LV) dysfunction. Materials/Methods Forty-nine type 2 diabetic patients with early diastolic tissue Doppler velocity > 1 standard deviation below the age-based mean entered an exercise intervention (n = 24) or usual care (n = 25) for 6-months (controlled, pre-/post- design). Co-primary endpoints were treadmill VO2peak and 5-min heart-rate variability (by the coefficient of variation of normal RR intervals [CVNN]). Autonomic function was additionally assessed by resting heart-rate (for sympathovagal balance estimation), baroreflex sensitivity, cardiac reflexes, and exercise/recovery heart-rate profiles. Echocardiography was performed for LV function (systolic/diastolic tissue velocities, myocardial deformation) and myocardial fibrosis (calibrated integrated backscatter). Results VO2peak increased by 11% during the exercise intervention (p = 0.001 vs.--1% in controls), but CVNN did not change (p = 0.23). Reduction of resting heart-rate in the intervention group (p < 0.05) was associated with an improvement in the secondary endpoint of heart-rate variability total spectral power (p < 0.05). However, baroreflex sensitivity, cardiac reflexes, and exercise/recovery heart-rate profiles showed no significant benefit. No effects on LV function were observed despite favorable reduction of calibrated integrated backscatter in the intervention group (p < 0.05). Conclusions The exercise intolerance of subclinical diabetic heart disease was amenable to improvement by exercise training. Despite a reduction in resting heart-rate and potential attenuation of myocardial fibrosis, no other cardiac autonomic or LV functional adaptations were detected. [ABSTRACT FROM AUTHOR]

The article discusses the burden and management of chronic heart failure (CHF). Topics discussed include the $1 billion estimated annual cost of CHF in Australia, the expert panel assembled by the National Health Foundation of Australia for the improvement of quality of care for CHF patients, and the consideration of the patient-centered care as the best-practice management for CHF.

Objectives: We sought the impact of recent recommendations on observer concordance on interpretation of diastolic stage and assessment of filling pressure. Background: Worsening stages of diastolic dysfunction are associated with worsening outcome. However, the echocardiographic classification of diastolic function is complex, and parameters may be discordant. The interobserver agreement of diastolic assessment is undefined. Methods: A complete diastolic evaluation (transmitral flow, left atrial volume, tissue Doppler, pulmonary venous flow, mitral flow propagation, and left ventricular images) was obtained in 20 patients and interpreted by 14 experts in 8 countries (280 case reads). Each investigator was asked to interpret diastolic class and left ventricular filling pressure. Brain natriuretic peptide level was drawn on the same day of the echocardiogram to corroborate filling pressures obtained by the echocardiogram. Concordance was assessed as kappa, and accuracy was compared with specific application of the recommendations by 2 investigators. Results: For recognition of raised filling pressure, the sensitivity and specificity of readers for raised filling pressure defined by the reference read were 66 ± 37% and 88 ± 26%, respectively. Complete agreement among all readers was obtained in 10 of 20 cases. Diagnosis of normal and categories of abnormal filling was correct in 71% to 95%, with the lowest values obtained for normal and pseudonormal filling. There was no difference between U.S. and international readers. Not all patients in each diastolic stage showed all of the changes that are typical of that stage, and variations appeared to be attributable to differences in weighting of conflicting observations. Overall, kappa values for filling pressure and diastolic class were 0.71 (range 0.60 to 0.80) and 0.68 (range 0.54 to 0.86). Conclusions: Correct results for estimation of filling pressure were obtained by a high proportion of readers. Classification of diastolic stages continues to be variable and might be addressed by provision of a uniform hierarchy of observations. [Copyright &y& Elsevier]

The load dependence of global longitudinal strain (GLS) means that changes in systolic blood pressure (BP) between visits may confound the diagnosis of cancer-treatment-related cardiac dysfunction (CTRCD). We sought to determine whether the estimation of myocardial work, which incorporates SBP, could overcome this limitation. In this case–control study, 44 asymptomatic patients at risk of CTRCD underwent echocardiography at baseline and after oncologic treatment. CTRCD was defined on the basis of the change in the ejection fraction. Those with CTRCD were divided into subsets with and without a follow-up SBP increment >20 mmHg (CTRCD+BP+ and CTRCD+BP−), and matched with patients without CTRCD (CTRCD−BP+ and CTRCD−BP−). The work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were assessed in addition to the GLS. The largest increases in the GWI and GCW at follow-up were found in CTRCD−BP+ patients. The CTRCD+BP− patients demonstrated significantly larger decreases in GWI and GCW than their CTRCD+BP+ and CTRCD−BP− peers. ROC analysis for the discrimination of LV functional changes in response to increased afterload in the absence of cardiotoxicity revealed higher AUCs for GCW (AUC = 0.97) and GWI (AUC = 0.93) than GLS (AUC = 0.73), GWW (AUC = 0.51), or GWE (AUC = 0.63, all p-values < 0.001). GCW (OR: 1.021; 95% CI: 1.001–1.042; p < 0.04) was the only feature independently associated with CTRCD−BP+. Myocardial work is superior to GLS in the serial assessments in patients receiving cardiotoxic chemotherapy. The impairment of GLS in the presence of an increase in GWI and GCW indicates the impact of elevated afterload on LV performance in the absence of actual myocardial impairment. [ABSTRACT FROM AUTHOR]

Objective: The outcome of patients with chronic kidney disease (CKD) is influenced by overt left ventricular (LV) abnormalities. We sought the predictive value and treatment response of subclinical LV dysfunction in CKD. Method: Resting and dobutamine stress echocardiography were used to identify LV enlargement, dysfunction, or ischemia in 176 patients with CKD. In 129 patients who had normal dobutamine stress echocardiography, myocardial tissue characterization was performed using tissue Doppler imaging and integrated backscatter. Clinical, biochemical, and echocardiographic parameters were recorded at baseline, and patients were followed up for cardiac events and all-cause mortality over 2.4 years. Follow-up echocardiographic and tissue characterization parameters were performed in 80 patients. Results: Previous cardiac history (HR 5.2, P = .002) and serum phosphate (HR 6.2, P = .001) were independent clinical predictors of events (model χ2 = 20.9). Diastolic tissue velocity (HR 0.8, P = .05) was an independent predictor of outcome, and its addition to clinical assessment added incremental prognostic information (model χ2 = 24.8, P < .001). Patients who underwent transplantation (n = 45) showed reduction of wall thickness (P < .001) and LV volumes (P < .001) and increases in diastolic tissue velocity (P = .007) and strain (P = .001), whereas these measurements worsened in those who remained on dialysis. Conclusion: In patients with CKD, subclinical LV dysfunction is associated with adverse outcome. Subclinical disease can be improved by transplantation but progresses in patients who continue on dialysis. [Copyright &y& Elsevier]

Background: Exercise training improves functional capacity in patients with systolic dysfunction (SD), but the role of exercise training in diastolic dysfunction (DD) is unclear. We compared the responses of patients with exercise intolerance and SD or DD to 16 weeks of exercise training. Methods: Fifty-one patients with SD and DD were enrolled in exercise training, which was completed in 24 patients with SD (22 men, 62 ± 8 years old, ejection fraction <35%) and 18 patients with DD (9 men, 65 ± 5 years old, ejection fraction >45%). Peak VO 2 , quality of life (Minnesota Living with Heart Failure and Hare-Davis questionnaires), and echocardiographic measures (ejection fraction, systolic and diastolic tissue velocity, and filling pressure) were performed at baseline and after 16 weeks of training. Results: Patients with SD and those with DD showed similar baseline peak VO 2 (11.9 ± 2.5 vs 12.5 ± 4.1 mL/[kg min], P = .55) and E/E′ ratio (21 ± 13 vs 14.4 ± 15, P = .07), but different systolic velocity (3.4 ± 1.0 vs 5.5 ± 1.7 cm/s, P < .001), diastolic velocity (3.9 ± 1.5 vs 5.1 ± 1.8 cm/s, P = .05), and ejection fraction (26 ± 8% vs 55 ± 9%, P < .001). Baseline quality of life scores were worse in patients with SD. There was a similar increment in peak VO 2 in SD (24%, P = .001) and DD (30%, P < .001) after exercise training, but this did not correlate with improved diastolic parameters. Quality of life scores improved in both SD and DD, although SD scores remained significantly worse. Conclusions: In patients with exercise limitation attributed to DD, the improvement in peak VO 2 and quality of life with exercise training is similar to those with SD, but unrelated to changes in diastolic function. [Copyright &y& Elsevier]

The improvement of exercise capacity due to exercise training in heart failure has been associated with peripheral adaptation, but the contribution of cardiac responses is less clear. We sought the extent to which the improvement of functional capacity in patients undergoing exercise training for heart failure was related to myocardial performance. Thirty-seven patients (35 men, age 64 ± 11) with symptomatic heart failure and left ventricular ejection fraction ≤35% (29 ± 9%) were studied during a 16-week exercise training program. LV function was assessed by resting and exercise 2D-echocardiography, tissue Doppler derived myocardial strain, and strain rate. Peak oxygen consumption (VO2) and LV function were measured at baseline and follow-up, and the contribution of LV function at baseline and its response to training to the change of each parameter was sought. Baseline peak VO2 (12.4 ± 4.6) increased by 9% at 8 weeks (13.5 ± 4.2, P = 0.26), and by 21% at 16 weeks (15.0 ± 4.9, P < 0.001). Although there were no overall changes in myocardial parameters in this study, change in peak VO2 at 16 weeks was significantly correlated with baseline strain (r = 0.51, P = 0.003) and the improvement of strain at 8 weeks (r = 0.44, P = 0.01), independent of baseline functional capacity and clinical variables. Thus, change in peak VO2 following 16 weeks exercise training is related to myocardial function at baseline. [ABSTRACT FROM AUTHOR]

Background: Exercise training (ExT) improves exercise capacity in chronic heart failure, but the results of home-based training have been variable. We sought the predictors of favorable outcome using a telemonitoring approach. Methods: Exercise capacity and quality of life (QOL) were assessed in 30 patients (28 men, age 64 ± 8 years) with symptomatic chronic heart failure and left ventricular ejection fraction ≤35% (28% ± 9%) undergoing 8 months of home ExT. Patients were provided with heart rate monitors and exercise diaries after undergoing 4 months of hospital-based ExT. Weekly telephone contact was established and heart rate data were downloaded bimonthly. Changes in peak oxygen consumption per unit time (V˙o 2) and QOL were compared between the 15 most and 15 least adherent patients defined by the number of hours per week at >60% maximum heart rate, observed during heart-rate monitoring. Results: Peak V˙o 2 increased by 26% (P < .001) after 4 months of hospital ExT, but this increase had fallen to 8% (P = .07) at 12 months; only adherent patients (n = 15) showed persistent improvement of peak V˙o 2 at 12 months (P = .02). Improvement in peak V˙o 2 at 12 months was associated with baseline peak V˙o 2 (r = −0.61, P < .001) and hours logged on the heart rate monitor (r = 0.47, P = .01). Quality of life improvements were sustained at 12 months for the Minnesota Living with Heart Failure Questionnaire and Hare-Davis Depression Questionnaire. Nevertheless, QOL improvements achieved during the outpatient program were lost or attenuated at 12 months in nonadherent patients but were maintained in adherent patients. Conclusions: Telemonitoring is feasible for following adherence to home ExT. Ongoing adherence is critical in obtaining sustained benefit from ExT in heart failure. [Copyright &y& Elsevier]

Objective: Screening for coronary artery disease is constrained by its low prevalence in unselected patients. We compared the ability of clinical scores to identify a high-risk group with diabetes mellitus and investigated a Bayesian strategy by combination with exercise echocardiography (ExE). Methods: The Framingham risk score (FRS), a score based on the American Diabetes Association (ADA) screening guidelines, the United Kingdom Prospective Diabetes Study (UKPDS) risk engine, and a disease-specific diabetic cardiac risk score (DCRS) were calculated in 199 asymptomatic patients with type 2 diabetes mellitus undergoing ExE. The frequency of abnormal ExE and the proportion of these with coronary stenoses were sought in groups designated as high risk on the basis of optimal cutoffs for each score. All patients were followed up for 1 year. Results: High risk was identified in fewer patients with the DCRS (27%) than FRS (38%, P = .02), ADA (41%, P = .004), and UKPDS (43%, P = .001). Exercise echocardiography was positive in 27 (14%); 11 of 23 proceeding to angiography showed significant stenoses. Areas under the receiver operator characteristic curves for prediction of a positive ExE were similar for DCRS, UKPDS, and FRS but less for ADA (P = .04). Positive ExE was uncommon in low-risk patients (8%-11%) and most were false positives (58%-80%). Cardiovascular events (n = 9) were more likely in the high-risk compared with the low-risk UKPDS (9% vs 2%, P = .03) and DCRS (12% vs 2%, P = .01). Conclusion: Combination of the UKPDS or DCRS with ExE may optimize detection of coronary artery disease and cardiac events in asymptomatic patients, while minimizing the numbers of ExE and false-positive rate. [ABSTRACT FROM AUTHOR]

Contrast echocardiography has an established role for enhancement of the right heart Doppler signals, the detection of intra-cardiac shunts, and most recently for left ventricular cavity opacification (LVO). The use of intravenously administered micro-bubbles to traverse the myocardial microcirculation in order to outline myocardial viability and perfusion has been the source of research studies for a number of years. Despite the enthusiasm of investigators, myocardial contrast echocardiography (MCE) has not attained routine clinical use and LV opacification during stress has been less widely adopted than the data would support. The purpose of this review is to facilitate an understanding of the involved imaging technologies that have made this technique more feasible for clinical practice, and to guide its introduction into the practice of the non-expert user. [ABSTRACT FROM AUTHOR]

Discusses how the succuss of fibrinolytic and other therapies has reduced the mortality of myocardial infarction, although many survivors develop congestive heart failure. Appraisal of the treatment of myocardial infarction; Pathogenesis and epidemiology of viable myocardium; Techniques for detection of myocardial viability; Who should be revascularized; Future directions.

Consistent epidemiological data demonstrate that patients with heart failure with preserved ejection fraction (HFpEF) are more likely to be women than men. Exploring mechanisms behind this sex difference in heart failure epidemiology may enrich the understanding of underlying HFpEF pathophysiology and phenotypes, with the ultimate goal of identifying therapeutic approaches for the broader HFpEF population. In this review we evaluate the influence of sex on the key domains of cardiac structure and function, the systemic and pulmonary circulation, as well as extracardiac factors and comorbidities that may explain the predisposition of women to HFpEF. We highlight the potential role of factors exclusive to or more prevalent in women such as pregnancy, preeclampsia, and iron deficiency. Finally, we discuss existing controversies and gaps in knowledge, as well as the clinical importance of known sex differences in the context of the potential need for sex-specific diagnostic criteria, improved risk stratification models, and targeted therapies. [ABSTRACT FROM AUTHOR]

Different patterns of abnormal left ventricular (LV) geometry are associated with variations in prognosis, but the mechanisms of these effects remain undefined. We investigated the association of myocardial deformation with these findings and their evolution. Two-dimensional echocardiography was performed in 85 hypertensive patients referred for serial evaluation (age 58 ± 13 years, 48% male). LV mass index and regional wall thickness were used to assign patients into groups with normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Septal strain and strain rate were measured using velocity vector imaging. The evolution of morphological changes was followed over 2.7 ± 1.3 years. Analysis of LV geometry revealed normal geometry in 13 patients (15%), concentric remodeling in 20 (24%), concentric hypertrophy in 42 (49%), and eccentric hypertrophy in 10 (12%). Overall strain was −13.6 ± 4.5%, and strain rate was −0.65 ± 0.24/second. Strain was significantly lower in patients with concentric remodeling (−12.8 ± 4.2%) or concentric hypertrophy (−12.5 ± 4.1%) compared with patients with normal geometry (−17.5 ± 5.5%, p ≤0.05), and these associations were independent of blood pressure. Strain rate was also significantly reduced in patients with concentric hypertrophy (p ≤0.01). There were no significant differences in baseline strain, wall stress, blood pressure, or age between patients who changed LV geometric class and those who did not. In conclusion, baseline myocardial tissue deformation, but not evolution, is associated with LV geometry in treated hypertensive patients. [Copyright &y& Elsevier]

Tissue Doppler imaging (TDI) is evolving as a useful echocardiographic tool for quantitative assessment of left ventricular (LV) systolic and diastolic function. Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as heart failure, acute myocardial infarction, and hypertension. In these conditions, myocardial mitral annular or basal segmental (Sm) systolic and early diastolic (Ea or Em) velocities have been shown to predict mortality or cardiovascular events. In particular, those with reduced Sm or Em values of <3 cm/s have a very poor prognosis. In heart failure and after myocardial infarction, noninvasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/Ea or E/Em) is a strong prognosticator, especially when E/Ea is ≥15. In addition, systolic intraventricular dyssynchrony measured by segmental analysis of myocardial velocities is another independent predictor of adverse clinical outcome in heart failure subjects, even when the QRS duration is normal. In heart failure patients who received cardiac resynchronization therapy, the presence of systolic dyssynchrony at baseline is associated with favorable LV remodeling, which in turn predicts a favorable long-term clinical outcome. Finally, TDI and derived deformation parameters improve prognostic assessment during dobutamine stress echocardiography. A high mean Sm value in the basal segments of patients with suspected coronary artery disease is associated with lower mortality rate or myocardial infarction and is superior to the wall motion score. [Copyright &y& Elsevier]