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Background Cardiorespiratory fitness (CRF) is reduced in cancer survivors and predicts cardiovascular disease (CVD)–related and all-cause mortality. However, routine measurement of CRF is not always feasible. Objectives The purpose of this study was to identify clinical, cardiac biomarker, and imaging measures associated with reduced peak oxygen consumption (VO2peak) (measure of CRF) early post–breast cancer therapy to help inform CVD risk. Methods Consecutive women with early-stage HER2+ breast cancer receiving anthracyclines and trastuzumab were recruited prospectively. Within 6 ± 2 weeks of trastuzumab completion, we collected clinical information, systolic/diastolic echocardiographic measures, high-sensitivity troponin I, B-type natriuretic peptide, and VO2peak using a cycle ergometer. Regression models were used to examine the association between VO2peak and clinical, imaging, and cardiac biomarkers individually and in combination. Results Among 147 patients (age 52.2 ± 9.3 years), the mean VO2peak was 19.1 ± 5.0 mL O2·kg−1·min−1 (84.2% ± 18.7% of predicted); 44% had a VO2peak below threshold for functional independence (, Central Illustration

Background Radiation therapy (RT) results in myocardial changes consisting of diffuse fibrosis, which may result in changes in diastolic function. Objectives The aim of this study was to explore RT-associated changes in left ventricular (LV) diastolic function. Methods Sixty chemotherapy-naive patients with left-sided, early-stage breast cancer were studied with speckle tracking echocardiography at 3 time points: prior to, immediately after, and 3 years after RT. Global and regional early diastolic strain rate (SRe) were quantified, as were parameters of systolic function. Results Regional changes in SRe, particularly the apical and anteroseptal segments, were observed over time and were more evident than global changes. The apical SRe declined from a median of 1.24 (interquartile range: 1.01 to 1.39) s-1 at baseline to 1.02 (interquartile range: 0.79 to 1.15) s-1 at 3 years of follow-up (p < 0.001). This decline was associated with the left ventricular maximal radiation dose (β = 0.36, p = 0.007). The global SRe was, Central Illustration

A 34-year-old man presented with fever, palpitations, maculopapular rash, pharyngitis, left cheilitis, and bilateral gonalgia. High-sensitivity troponin I concentration was 4,900 ng/l. Transthoracic echocardiogram revealed reduced global longitudinal strain. Cardiac magnetic resonance imaging showed acute myocarditis. Adult-onset Still’s disease was diagnosed, and treatment with intravenous corticosteroids and tocilizumab was initiated. (Level of Difficulty: Beginner.), Central Illustration

Cell therapy is a promising tool to prevent and treat heart failure in congenital heart disease. We report the first case of intramyocardial injection of allogeneic mesenchymal stromal cells as rescue therapy in a neonate with ischemic heart failure following arterial switch procedure for isolated transposition of the great arteries. (Level of Difficulty: Advanced.), Central Illustration

Background The vascular endothelium is a novel target for the detection, management, and prevention of doxorubicin (DOX)-induced cardiotoxicity. Objectives The study aimed to: 1) develop a methodology by computed tomography angiography (CTA) to evaluate stress-induced changes in epicardial coronary diameter; and 2) apply this to a chronic canine model of DOX-induced cardiotoxicity to assess vascular toxicity. Methods To develop and validate quantitative methods, sequential retrospectively gated coronary CTAs were performed in 16 canines. Coronary diameters were measured at prespecified distances during rest, adenosine (ADE) (280 μg/kg/min), rest 30 min post-ADE, and dobutamine (DOB) (5 μg/kg/min). A subgroup of 8 canines received weekly intravenous DOX (1 mg/kg) for 12 to 15 weeks, followed by rest-stress CTA at cumulative doses of ∼4-mg/kg (3 to 5 mg/kg), ∼8-mg/kg (7 to 9 mg/kg), and ∼12-mg/kg (12 to 15 mg/kg) of DOX. Echocardiograms were performed at these timepoints to assess left ventricular ejection fraction and global longitudinal strain. Results Under normal conditions, epicardial coronary arteries reproducibly dilated in response to ADE (left anterior descending coronary artery [LAD]: 12 ± 2%, left circumflex coronary artery [LCx]: 13 ± 2%, right coronary artery [RCA]: 14 ± 2%) and DOB (LAD: 17 ± 3%, LCx: 18 ± 2%, RCA: 15 ± 3%). With DOX, ADE vasodilator responses were impaired after ∼4-mg/kg (LAD: –3 ± 1%, LCx: 0 ± 2%, RCA: –5 ± 2%) and ∼8-mg/kg (LAD: –3 ± 1%, LCx: 0 ± 1%, RCA: –2 ± 2%). The DOB dilation response was preserved at ∼4-mg/kg of DOX (LAD: 18 ± 4%, LCx: 11 ± 3%, RCA: 11 ± 2%) but tended to decrease at ∼8-mg/kg of DOX (LAD: 4 ± 2%, LCx: 8 ± 3%, RCA: 3 ± 2%). A significant left ventricular ejection fraction reduction was observed only at 12 to 15 mg/kg DOX (baseline: 63 ± 2%, 12-mg/kg: 45 ± 3%). Global longitudinal strain was abnormal at ∼4-mg/kg of DOX (p = 0.011). Conclusions CTA can reliably assess epicardial coronary diameter in response to pharmacological stressors, providing a noninvasive functional index of coronary vasoreactivity. Impaired epicardial vasodilation occurs early in DOX-induced cardiotoxicity., Central Illustration

Progressive conduction system disease affects patients with transthyretin cardiac amyloidosis, often requiring permanent pacing as the His-Purkinje system is affected. We present a case of left bundle branch pacing in a patient with transthyretin cardiac amyloidosis and infra-Hisian conduction disease with a favorable improvement in cardiac function and stable pacing thresholds. (Level of Difficulty: Intermediate.), Graphical abstract, Progressive conduction system disease affects patients with transthyretin cardiac amyloidosis, often requiring permanent pacing as the His-Purkinje…

We present a patient with hypertrophic obstructive cardiomyopathy and accompanying aortic valve stenosis who had a myocardial infarction with a significant proximal left anterior descending coronary artery stenosis. The primary percutaneous coronary intervention resulted in a notable improvement in the left ventricular outflow tract gradient and global longitudinal strain. (Level of Difficulty: Beginner.), Graphical abstract, The authors present a patient with hypertrophic obstructive cardiomyopathy and accompanying aortic valve stenosis who had a myocardial infarction with…

The discipline of cardio-oncology has expanded at a remarkable pace. Recent developments and challenges to clinicians who practice cardio-oncology were presented at the Global Cardio-Oncology Summit on October 3 to 4, 2019, in São Paulo, Brazil. Here, we present the top 10 priorities for our field that were discussed at the meeting, and also detail a potential path forward to address these challenges. Defining robust predictors of cardiotoxicity, clarifying the role of cardioprotection, managing and preventing thromboembolism, improving hematopoietic stem cell transplant outcomes, personalizing cardiac interventions, building the cardio-oncology community, detecting and treating cardiovascular events associated with immunotherapy, understanding tyrosine kinase inhibitor cardiotoxicity, and enhancing survivorship care are all priorities for the field. The path forward requires a commitment to research, education, and excellence in clinical care to improve our patients' lives., Central Illustration, Highlights • The discipline of cardio-oncology has enjoyed extensive and complex development at a breathtaking pace. • Extensive ongoing clinical and basic research continue to shape and formulate the practice of cardio-oncology. • The path forward for the field needs to be centered on excellence in clinical care, transformative research, and broad education principles.

Objectives The objective of this study was to determine the relationship between heart rate and relapse among patients in the TRED-HF (Therapy withdrawal in REcovered Dilated cardiomyopathy trial). Background Understanding markers and mechanisms of relapse among patients with recovered dilated cardiomyopathy (DCM) may enable personalized management. Methods The relationship between serial heart rate measurements and relapse was examined among patients in the TRED-HF trial, a randomized trial which examined the safety and feasibility of withdrawing heart failure therapy from 51 patients with recovered DCM over 6 months. In total, 25 patients were randomized to therapy withdrawal and 26 to continue therapy, of whom 25 subsequently began therapy withdrawal in a single arm crossover phase. Results The mean ± SD heart rate for those who had therapy withdrawn and did not relapse was 64.6 ± 10.7 beats/min at baseline and 74.7 ± 10.4 beats/min at follow-up, compared to 68.3 ± 11.3 beats/min at baseline and 86.1 ± 11.8 beats/min at follow-up for those who relapsed. After adjusting for differences in heart rate at baseline, patients who had therapy withdrawn and relapsed had a 10.4 beats/min (95% CI: 4.0–16.8) greater rise in heart rate than patients who had therapy withdrawn and did not relapse (P = 0.002). After data were adjusted for age, log N-terminal pro–B-type natriuretic peptide, and left ventricular ejection fraction (LVEF), heart rate (per 10 beats/min; hazard ratio [HR]: 1.65; 95% CI: 1.10-2.57; P = 0.01) and change in heart rate from baseline (per 10 beats/min; HR: 1.70; 95% CI: 1.12–2.57; p = 0.01) were associated with relapse. The results remained qualitatively the same after adjusting for beta-blocker dose. Conclusions For patients with DCM and improved LVEF, the rise in heart rate after treatment is withdrawn treatment identifies patients who are more likely to relapse. Whether the increase in heart rate is a marker or a mediator of relapse requires investigation. (Therapy withdrawal in REcovered Dilated cardiomyopathy trial [TRED]; NCT02859311), Central Illustration

Background Coronavirus disease 2019 (COVID-19) can cause cardiac injury resulting in abnormal right or left ventricular function (RV/LV) with worse outcomes. We hypothesized that two-dimensional (2D) speckle-tracking assessment of LV global longitudinal strain (GLS) and RV free wall strain (FWS) by transthoracic echocardiography can assist as markers for subclinical cardiac injury predicting increased mortality. Methods We performed 2D strain analysis via proprietary software in 48 patients hospitalized with COVID-19. Clinical information, demographics, comorbidities, and lab values were collected via retrospective chart review. The primary outcome was in-hospital mortality based on an optimized abnormal LV GLS value via ROC analysis and RV FWS. Results The optimal LV GLS cutoff to predict death was −13.8%, with a sensitivity of 85% (95% CI 55–98%) and specificity of 54% (95% CI 36–71%). Abnormal LV GLS > −13.8% was associated with a higher risk of death [unadjusted hazard ratio 5.15 (95% CI 1.13–23.45), p = 0.034], which persisted after adjustment for clinical variables. Among patients with LV ejection fraction (LVEF) >50%, those with LV GLS > −13.8% had higher mortality compared to those with LV GLS −13.8% (−13.7 ± 5.9 vs. −19.6 ± 6.7, p = 0.003), but not associated with decreased survival. Conclusion Abnormal LV strain with a cutoff of >−13.8% in patients with COVID-19 is associated with significantly higher risk of death. Despite normal LVEF, abnormal LV GLS predicted worse outcomes in patients hospitalized with COVID-19. There was no mortality difference based on RV strain.

Highlights • Early systolic lengthening (ESL) is a paradoxical lengthening of myocardial fibers. • Speckle tracking echocardiography is a common imaging tool for assessment of ESL. • ESL was a predictor of cardiovascular and all-cause death in CABG patients. • Specifically, the prognostic value of ESL was enhanced in women undergoing CABG., Background Early systolic lengthening (ESL), a paradoxical stretch of myocardial fibers, has been linked to loss of myocardial viability and contractile dysfunction. We assessed the long-term prognostic potential of ESL in coronary artery bypass graft (CABG) patients. Methods We retrospectively included patients (n = 709; mean age 68 years; 85% men) who underwent speckle tracking echocardiography (median 15 days) prior to CABG. Endpoints were cardiovascular death (CVD) and all-cause mortality. We assessed amplitude of ESL (%), defined as peak positive strain, and duration of ESL (ms), determined as time from Q-wave on the ECG to peak positive strain. We applied Cox models adjusted for clinical risk assessed as EuroSCORE II. Results During median follow-up of 3.8 years [IQR 2.7–4.9 years], 45 (6%) experienced CVD and 80 (11%) died. In survival analyses adjusted for EuroSCORE II, each 1% increase in amplitude of ESL was associated with CVD (HR 1.35 [95%CI 1.09–1.68], P = 0.006) and all-cause mortality (HR 1.29 [95%CI 1.08–1.54], P = 0.004). Similar findings applied to duration of ESL (per 10ms increase) and CVD (HR 1.12 [95%CI 1.02–1.23], P = 0.016) and all-cause mortality (HR 1.09 [95%CI 1.01––1.17], P = 0.031). The prognostic value of ESL amplitude was modified by sex (P interaction

Highlights • Cardiac amyloidosis has high associated morbidity and, until recently, limited treatment options. • This review discusses the mechanism and clinical trial performance of multiple emerging therapies. • Additional studies should identify optimal treatment paradigms and biomarker strategies for cardiac response to therapy., Summary Cardiac amyloidosis is a restrictive cardiomyopathy that results from the deposition of misfolded light chain or transthyretin proteins, most commonly, in cardiac tissue. Traditionally, treatment options for light chain (AL) and transthyretin (ATTR) amyloidosis have been limited. However, there are now multiple novel therapeutics in development and several therapeutics recently approved that promise to revolutionize clinical management of AL and ATTR. Most of these agents disrupt specific stages of amyloidogenesis such as light chain or transthyretin protein production, formation of amyloidogenic intermediates, or amyloid fibril aggregation. Others aim to remove existing amyloid tissue deposits using monoclonal antibody technology. Although these advances represent an important step forward in the care of cardiac amyloidosis patients, additional studies are needed to define the optimal treatment paradigms for AL and ATTR and to validate clinical, imaging, or serum biomarker strategies that may confirm a cardiac response to therapy., Central Illustration

Background Heterozygous familial hypercholesterolemia (heFH) is a genetic disorder leading to premature coronary artery disease (CAD). We hypothesized that the subclinical pathophysiologic consequences of hypercholesterolemia may be detected before the occurrence of clinically overt CAD by stress testing and myocardial strain imaging. Patients-methods We evaluated the treadmill tests (ETTs) of 46 heFH men without known arterial hypertension/diabetes mellitus/vasculopathy like CAD and of 39 healthy men matched for age, baseline systolic/diastolic blood pressure (BP) and heart rate (HR), using Bruce protocol. Global longitudinal strain (GLS) of the left ventricle (LV) additionally to ejection fraction was obtained. Results heFH men reached a significantly higher peak systolic and diastolic BP compared to controls (p = 0.002 and p, Highlights • Stress testing and myocardial strain imaging may detect subclinical consequences of heterozygous familial hypercholesterolemia. • Male patients with heFH underwent exercise treadmill testing and speckle-tracking echocardiography. • Male heFH patients showed a higher rise in systolic/diastolic blood pressure during exercise treadmill testing than healthy controls. • Global longitudinal strain of heFH males is slightly impaired compared with healthy subjects.

Objectives This study sought to explore the spectrum of cardiac abnormalities in student athletes who returned to university campus in July 2020 with uncomplicated coronavirus disease 2019 (COVID-19). Background There is limited information on cardiovascular involvement in young individuals with mild or asymptomatic COVID-19. Methods Screening echocardiograms were performed in 54 consecutive student athletes (mean age 19 years; 85% male) who had positive results of reverse transcription polymerase chain reaction nasal swab testing of the upper respiratory tract or immunoglobulin G antibodies against severe acute respiratory syndrome coronavirus type 2. Sequential cardiac magnetic resonance imaging was performed in 48 (89%) subjects. Results A total of 16 (30%) athletes were asymptomatic, whereas 36 (66%) and 2 (4%) athletes reported mild and moderate COVID-19 related symptoms, respectively. For the 48 athletes completing both imaging studies, abnormal findings were identified in 27 (56.3%) individuals. This included 19 (39.5%) athletes with pericardial late enhancements with associated pericardial effusion. Of the individuals with pericardial enhancements, 6 (12.5%) had reduced global longitudinal strain and/or an increased native T1. One patient showed myocardial enhancement, and reduced left ventricular ejection fraction or reduced global longitudinal strain with or without increased native T1 values was also identified in an additional 7 (14.6%) individuals. Native T2 findings were normal in all subjects, and no specific imaging features of myocardial inflammation were identified. Hierarchical clustering of left ventricular regional strain identified 3 unique myopericardial phenotypes that showed significant association with the cardiac magnetic resonance findings (p = 0.03). Conclusions More than 1 in 3 previously healthy college athletes recovering from COVID-19 infection showed imaging features of a resolving pericardial inflammation. Although subtle changes in myocardial structure and function were identified, no athlete showed specific imaging features to suggest an ongoing myocarditis. Further studies are needed to understand the clinical implications and long-term evolution of these abnormalities in uncomplicated COVID-19., Central Illustration

International audience; Purpose: Coronavirus disease 2019 (COVID-19) infection may trigger a multi-systemic disease involving different organs. There has been growing interest regarding the harmful effects of COVID-19 on the cardiovascular system. This systematic review aims to systematically analyze papers reporting echocardiographic findings in hospitalized COVID-19 subjects. Materials and methods: We included prospective and retrospective studies reporting echocardiography data in >10 hospitalized adult subjects with COVID-19; from 1st February 2020 to 15th January 2021. Results: The primary electronic search identified 1120 articles. Twenty-nine studies were finally included, enrolling 3944 subjects. Overall the studies included a median of 68.0% (45.5–100.0) of patients admitted to ICU. Ten studies (34.4%) were retrospective, and 20 (68.9%) single-centred. Overall enrolling 1367 subjects, three studies reported normal echocardiographic findings in 49 ± 18% of cases. Seven studies (24.1%) analyzed the association between echocardiographic findings and mortality, mostly related to right ventricular (RV) dysfunction. Conclusions: Data regarding the use of echocardiography on hospitalized, predominantly ICU, COVID-19 patients were retrieved from studies with heterogeneous designs, variable sample sizes, and severity scores. Normal echocardiographic findings were reported in about 50% of subjects, with LVEF usually not affected. Overall, RV dysfunction seems more likely associated with increased mortality. Trial Registration: CRD42020218439.

Objective To characterize the clinical and transthoracic echocardiographic features and 30-day outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19). Methods Retrospective cohort study that included consecutive inpatients with COVID-19 infection who underwent clinically indicated transthoracic echocardiography at 10 sites in the Mayo Clinic Health System between March 10 and August 5, 2020. Echocardiography was performed at bedside by cardiac sonographers according to an abbreviated protocol. Echocardiographic results, demographic characteristics, laboratory findings, and clinical outcomes were analyzed. Results There were 179 patients, aged 59.8±16.9 years and 111 (62%) men; events within 30 days occurred in 70 (39%) patients, including prolonged hospitalization in 43 (24%) and death in 27 (15%). Echocardiographic abnormalities included left ventricular ejection fraction less than 50% in 29 (16%), regional wall motion abnormalities in 26 (15%), and right ventricular systolic pressure (RVSP) of 35 or greater mm Hg in 44 (44%) of 101 in whom it was measured. Myocardial injury, defined as the presence of significant troponin level elevation accompanied by new ventricular dysfunction or electrocardiographic abnormalities, was present in 13 (7%). Prior echocardiography was available in 36 (20%) patients and pre-existing abnormalities were seen in 28 (78%) of these. In a multivariable age-adjusted model, area under the curve of 0.81, prior cardiovascular disease, troponin level, D-dimer level, and RVSP were related to events at 30 days. Conclusion Bedside Doppler assessment of RVSP appears promising for short-term risk stratification in hospitalized patients with COVID-19 infection undergoing clinically indicated echocardiography. Pre-existing echocardiographic abnormalities were common; caution should be exercised in attributing such abnormalities to the COVID-19 infection in this comorbid patient population.

Echocardiographic imaging is crucial for patient management during cardiotoxic cancer therapy. Left ventricular ejection fraction is the most commonly used parameter for identifying left ventricular dysfunction. However, it lacks sensitivity to detect subclinical changes in cardiac function due to cardiotoxic treatment. Global longitudinal strain (GLS) is the best studied strain parameter with established diagnostic and prognostic value. Multiple studies have demonstrated changes in GLS as an early marker of cardiotoxicity. This document serves as a primer to help clinicians in the acquisition and interpretation of strain in cardio-oncology. Cases with embedded videos illustrate a step-by-step approach to obtaining GLS measurements and common pitfalls to avoid. The document includes a concise summary of the indications of GLS in cardio-oncology and its role in guiding oncological therapy. Practical approaches on how to implement strain in the echo laboratory with guidance on training and quality assurance are also discussed., Central Illustration, Highlights • Compared with LVEF, GLS is a more sensitive and reproducible measure of LV systolic function and has emerged as an early marker of cardiotoxicity. • Despite evidence supporting the clinical utility of GLS imaging, familiarity with the practical process of strain imaging among clinicians is lacking. • Although each vendor has its own proprietary software for strain imaging, the basic steps of measuring GLS are similar. • Education is needed to enhance the performance, analysis, and interpretation of GLS for the management of cardio-oncology patients.

Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT), a potentially curative therapy for malignant and nonmalignant diseases, is being increasingly used in younger patients. Although allo-HSCT survivors have an established increased risk of cardiovascular disease, there is limited knowledge of the long-term effects on cardiac function in survivors. Objectives The purpose of this study was to describe left ventricular (LV) systolic function in long-term allo-HSCT survivors treated in childhood, adolescence, or early adulthood. Methods Our cross-sectional cohort study included 104 patients (56% women), age 18 ± 10 years at time allo-HSCT with 17 ± 6 years of follow-up. Echocardiography included 2-dimensional (2D) and 3-dimensional (3D) analyses and speckle tracking imaging. In total, 55 healthy control subjects with a similar age, sex, and body mass index were used for comparison. Left ventricular systolic dysfunction (LVSD) was defined as reduced 2D left ventricular ejection fraction (LVEF) of, Central Illustration

Introduction Left ventricular (LV) systolic dysfunction is the most frequent initial presentation of patient with LV noncompaction (NC). Our objectives were to evaluate myocardial contraction properties in patients with LVNC and the relationship of non-compacted segments with the degree of global and regional systolic deformation. Methods We included 50 LVNC with an echocardiography and speckle imaging calculation of peak longitudinal strain (PLS). Each of the 16 LV myocardial segments was defined as NC (ratio NC/compacted layer > 2), borderline (NC/C 0–2) and compacted (NC/C = 0). Basal, median and apical strain values were calculated as the average of segmental strain values. For comparison a group of 50 patients with dilated cardiomyopathy (DCM) underwent the same measurements. Results There was no statistical difference between the 2 groups for any conventional LV systolic parameters. A characteristic deformation pattern was observed in LVNC with higher strain values in the LV apical segments (− 12.8 ± 5.9 vs − 10.7 ± 5.7) and an apical–basal ratio (1.52 ± 0.73 vs 1.12 ± 0.42; p, Highlights • We observed a base–apex gradient with relatively preserved deformation values in the apical region in LVNC. • We find lower regional deformation values in compacted segments. • We illustrate the role of deformation echocardiography to evaluate the degree and extent of LV segmental dysfunction. • We define a new tool to help classification of patient with similar dilated cardiomyopathy phenotype. • We confirmed the concept that LVNC is a phenotypic marker of an underlying diffuse cardiomyopathy.

The subspecialty of cardio-oncology aims to reduce cardiovascular morbidity and mortality in patients with cancer or following cancer treatment. Cancer therapy can lead to a variety of cardiovascular complications, including left ventricular systolic dysfunction, pericardial disease, and valvular heart disease. Echocardiography is a key diagnostic imaging tool in the diagnosis and surveillance for many of these complications. The baseline assessment and subsequent surveillance of patients undergoing treatment with anthracyclines and/or human epidermal growth factor receptor (HER) 2-positive targeted treatment (e.g., trastuzumab and pertuzumab) form a significant proportion of cardio-oncology patients undergoing echocardiography. This guideline from the British Society of Echocardiography and British Cardio-Oncology Society outlines a protocol for baseline and surveillance echocardiography of patients undergoing treatment with anthracyclines and/or trastuzumab. The methodology for acquisition of images and the advantages and disadvantages of techniques are discussed. Echocardiographic definitions for considering cancer therapeutics-related cardiac dysfunction are also presented., Central Illustration, Highlights • Cardio-oncology patients account for an increasing proportion of echocardiography requests. • Accurate assessment of LV systolic function is critical to decision-making in this patient group. • 2D LVEF, 3D LVEF, GLS, and RV assessment should be used in the echocardiographic assessment of these patients. • The clinical implications of a significant decline in GLS with potentially cardiotoxic cancer therapy require further investigation.