Multimodality Cardiac Imaging, Cardiac Symptoms, and Clinical Outcomes in Patients Who Recovered from Mild COVID-19.

Background Many patients have persistent cardiac symptoms after mild COVID-19. However, studies assessing the relationship between symptoms and cardiac imaging are limited. Purpose To assess the relationship between multi-modality cardiac imaging parameters, symptoms, and clinical outcomes in patients recovered from mild COVID-19 compared to COVID-19 negative controls. Materials and Methods Patients who underwent PCR testing for SARS-CoV-2 between August 2020 and January 2022 were invited to participate in this prospective, single-center study. Participants underwent cardiac MRI, echocardiography, and assessment of cardiac symptoms at 3-6 months after SARS-CoV-2 testing. Cardiac symptoms and outcomes were also evaluated at 12-18 months. Statistical analysis included Fisher's exact test and logistic regression. Results This study included 122 participants who recovered from COVID-19 ([COVID+] mean age, 42 years ± 13 [SD]; 73 females) and 22 COVID-19 negative controls (mean age, 46 years ± 16 [SD]; 13 females). At 3-6 months, 20% (24/122) and 44% (54/122) of COVID+ participants had at least one abnormality on echocardiography and cardiac MRI, respectively, which did not differ compared to controls (23% [5/22]; P = .77 and 41% [9/22]; P = .82, respectively). However, COVID+ participants more frequently reported cardiac symptoms at 3-6 months compared to controls (48% [58/122] vs. 23% [4/22]; P = .04). An increase in native T1 (10 ms) was associated with increased odds of cardiac symptoms at 3-6 months (OR, 1.09 [95% CI: 1.00, 1.19]; P = .046) and 12-18 months (OR, 1.14 [95% CI: 1.01, 1.28]; P = .028). No major adverse cardiac events occurred during follow-up. Conclusion Patients recovered from mild COVID-19 reported increased cardiac symptoms 3-6 months after diagnosis compared to controls, but the prevalence of abnormalities on echocardiography and cardiac MRI did not differ between groups. Elevated native T1 was associated with cardiac symptoms 3-6 months and 12-18 months after mild COVID-19.

Self-Reported Physical Activity, QoL, Cardiac Function, and Cardiorespiratory Fitness in Women With HER2+ Breast Cancer.

Background: Women treated for breast cancer are at risk for worsening health-related quality of life (QoL), cardiac function, and cardiorespiratory fitness. Objectives: The aim of this study was to assess the associations of self-reported moderate to vigorous intensity physical activity (MVPA) during cancer treatment with concurrent measures of QoL and cardiac function and with post-treatment cardiorespiratory fitness in women with human epidermal growth factor receptor 2-positive breast cancer receiving sequential anthracyclines and trastuzumab. Methods: EMBRACE-MRI 1 (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI) study participants who completed questionnaires for MVPA (modified Godin Leisure Time Physical Activity Questionnaire) and QoL (EQ-5D-3L, Minnesota Living With Heart Failure Questionnaire) and cardiac imaging every 3 months during treatment and post-treatment cardiopulmonary exercise testing were included. Participants engaging in ≥90 minutes of MVPA each week were labeled "active." Generalized estimation equations and linear regression analyses were used to assess concurrent and post-treatment associations with MVPA and activity status, respectively. Results: Eighty-eight participants were included (mean age 51.4 ± 8.9 years). Mean MVPA minutes, QoL, and cardiac function (left ventricular ejection fraction, global longitudinal strain, E/A ratio, and E/e' ratio) worsened by 6 months into trastuzumab therapy. Higher MVPA (per 30 minutes) during treatment was associated with better concurrent overall (ß = -0.42) and physical (ß = -0.24) Minnesota Living With Heart Failure Questionnaire scores, EQ-5D-3L index (ß = 0.003), visual analogue scale score (ß = 0.43), diastolic function (E/A ratio; ß = 0.01), and global longitudinal strain (ß = 0.04) at each time point (P ≤ 0.01 for all). Greater cumulative MVPA over the treatment period was associated with higher post-treatment cardiorespiratory fitness (peak oxygen consumption; ß = 0.06 per 30 minutes; P < 0.001). Conclusions: Higher self-reported MVPA during treatment for human epidermal growth factor receptor 2-positive breast cancer was associated with better QoL and diastolic and systolic left ventricular function measures during treatment and better post-treatment cardiorespiratory fitness.

Diagnostic and Prognostic Value of Myocardial Work Indices for Identification of Cancer Therapy-Related Cardiotoxicity.

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).

A Combined Echocardiography Approach for the Diagnosis of Cancer Therapy-Related Cardiac Dysfunction in Women With Early-Stage Breast Cancer.

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.

Clinical, Echocardiographic, and Biomarker Associations With Impaired Cardiorespiratory Fitness Early After HER2-Targeted Breast Cancer Therapy.

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 (<18 mL O2·kg-1·min-1). In multivariable analysis, absolute global longitudinal strain (GLS) (ß = 0.58; P = 0.007), age per 10 years (ß: -1.61; P = 0.001), and E/e' (measure of diastolic filling pressures) (ß = -0.45; P = 0.038) were associated with VO2peak. GLS added incremental value in explaining the variability in VO2peak. The combination of age ≥50 years, E/e' ≥7.8, and GLS <18% identified a high probability (85.7%) of compromised functional independence, whereas age <50 years, E/e' <7.8, and GLS ≥18% identified a low probability (0%). High-sensitivity troponin I and B-type natriuretic peptide were not associated with VO2peak. CONCLUSIONS: Readily available clinical measures were associated with VO2peak early post-breast cancer therapy. A combination of these parameters had good discrimination to identify patients with compromised functional independence and potentially increased future CVD risk.

Variability in echocardiography and MRI for detection of cancer therapy cardiotoxicity.

OBJECTIVES: To compare variability of echocardiographic and cardiovascular magnetic resonance (CMR) measured left ventricular (LV) function parameters and their relationship to cancer therapeutics-related cardiac dysfunction (CTRCD). METHODS: We prospectively recruited 60 participants (age: 49.8±11.6 years), 30 women with human epidermal growth factor receptor 2-positive breast cancer (15 with CTRCD and 15 without CTRCD) and 30 healthy volunteers. Patients were treated with anthracyclines and trastuzumab. Participants underwent three serial CMR (1.5T) and echocardiography studies at ~3-month intervals. Cine-CMR for LV ejection fraction (LVEF), myocardial tagging for global longitudinal strain (GLS) and global circumferential strain (GCS), two-dimensional (2D) echocardiography for strain and LVEF and three-dimensional (3D) echocardiography for LVEF measurements were obtained. Temporal, interobserver and intraobserver variability were calculated as the coefficient of variation and as the SE of the measurement (SEM). Minimal detected difference (MDD) was defined as 2xSEM. RESULTS: Patients with CTRCD demonstrated larger mean temporal changes in all parameters compared with those without: 2D-LVEF: 4.6% versus 2.8%; 3D-LVEF: 5.2% vs 2.3%; CMR-LVEF: 6.6% versus 2.7%; 2D-GLS: 1.9% versus 0.7%, 2D-GCS: 2.5% versus 2.2%; CMR-GCS: 2.7% versus 1.6%; and CMR-GLS: 2.1% versus 1.4%, with overlap in 95% CI for 2D-LVEF, 2D-GCS, CMR-GLS and CMR-GCS. The respective mean temporal variability/MDD in healthy volunteers were 3.3%/6.5%, 1.8%/3.7%, 2.2%/4.4%, 0.8%/1.5%, 1.9%/3.7%, 1.8%/3.6% and 1.4%/2.8%. Although the mean temporal variability in healthy volunteers was lower than the mean temporal changes in CTRCD, at the individual level, 2D-GLS, 3D-LVEF and CMR-LVEF had the least overlap. 2D-GLS and CMR-LVEF had the lowest interobserver/intraobserver variabilities. CONCLUSION: Temporal changes in 3D-LVEF, 2D-GLS and CMR LVEF in patients with CTRCD had the least overlap with the variability in healthy volunteers; however, 2D-GLS appears to be the most suitable for clinical application in individual patients.

Imaging-Specific Cardiomyopathies: A Practical Guide.

Heart failure is a clinical syndrome with a broad spectrum of presentations. Cardiovascular imaging techniques such as echocardiography, cardiovascular magnetic resonance, computed tomography, and nuclear imaging play a crucial role in diagnosis, guiding management, and providing prognostic information. Each of these imaging modalities has their own respective strengths and weaknesses. Cardiac imaging can help differentiate between ischemic and nonischemic cardiomyopathies. Additionally, imaging techniques can display disease-specific findings, aiding in diagnosis of nonischemic cardiomyopathies and can provide a means to monitor response to therapy. The choice of imaging modality in the workup of cardiomyopathy should be based on the specific clinical question and the knowledge of the strengths and limitations of each imaging modality.

Aortic root changes before and after surgery for chronic aortic dilatation: A 3D echocardiographic study.

BACKGROUND: Quantitative 3D assessment of the aortic root may improve planning and success of aortic valve (AV)-sparing operations. AIMS: To use 3D transesophageal echocardiography (TEE) to assess the effect of chronic aortic dilatation on aortic root shape and aortic regurgitation (AR) severity and to examine the effects of AV-sparing operations. METHODS AND RESULTS: To determine the changes with chronic aortic dilatation, we studied 48 patients, 23 with aortic dilatation (Group 1 ≤ mild AR, n = 13; Group 2 ≥ moderate AR, n = 10) and 25 Controls. To determine the changes in AV-sparing operations, a subgroup of 15 patients were examined pre- and post surgery. 3D-TEE images were analyzed using multiplanar reconstruction (QLAB, Philips, Philips Medical Systems, Andover, MA, USA) to obtain aortic root areas, diameters, and lengths. We also calculated a novel parameter called total coaptation surface area (TCoapSA), which sums the contact surface area of all the AV cusps. Compared to Controls, Groups 1 and 2 had significantly larger aortic root areas, inter-commissural distances, and cusp heights. Compared to Group 1 and Controls, Group 2 had significantly smaller TCoapSA when adjusted for aortic annular area (P = 0.001) with shorter coaptation height (P < 0.001). In patients undergoing AV-sparing surgery, TCoapSA was significantly larger post surgery (P = 0.001) with greater coaptation height (P < 0.001) and smaller inter-commissural distances (P < 0.001). CONCLUSIONS: The aortic valve is a dynamic structure that remodels in response to aortic dilatation. Successful valve-sparing surgery corrects these changes. Quantitative modeling of the aortic valve and root could potentially improve the repair to the individual patients and modify outcomes.