Cancer Therapeutics-related Cardiac Dysfunction Research Articles

Artificial intelligence applied to electrocardiographic images for the risk stratification of cancer therapeutics-related cardiac dysfunction

Abstract Background Traditional risk stratification strategies for cancer therapeutics-related cardiac dysfunction (CTRCD) rely on serial monitoring by specialized imaging, limiting their scalability and affordability. Purpose To examine an artificial intelligence (AI)-enhanced electrocardiographic (AI-ECG) surrogate for imaging-based risk biomarkers, and its association with CTRCD. Methods Between 2013-2023, across 5 hospitals of a large U.S.-based health system, we identified patients with breast cancer or non-Hodgkin lymphoma (NHL) who received anthracyclines (AC) and/or trastuzumab (TZM), as well as a (negative) control cohort of patients receiving immune checkpoint inhibitors (ICI). We deployed a validated AI model of left ventricular systolic dysfunction (LVSD) to ECG images (≥0.1=positive screen) (ref 1) and explored the association between the model’s predictions and: i) global longitudinal strain (GLS) measurements within 15 days; ii) future CTRCD (defined as a new cardiomyopathy, heart failure, or left ventricular ejection fraction (LVEF) decrease to <50%), as well as a more specific secondary outcome of LVEF decrease <40%. In a negative control analysis of patients receiving ICI, we correlated baseline AI-ECG LVSD predictions with downstream myocarditis. Results Higher AI-ECG LVSD predictions were associated with progressively worse GLS (-18% [IQR: -20 to -17%] for AI-ECG predictions <0.1, to -12% [-15 to -9%] for ≥0.5, p<0.001, n=7,271) (A). In 1,308 patients receiving AC/TZM (age 59 [IQR 49-67] years, 999 [76.4%] women, 80 [IQR 42-115] follow-up months) a positive baseline AI-ECG LVSD screen was associated with higher incidence of CTRCD (n=404 events, adjusted HR 2.22 [95%CI: 1.63-3.02]) and/or LVEF <40% (n=72 events, adjusted HR 4.76 [95%CI: 2.62-8.66]) (B). In a negative control analysis of 2,056 patients receiving ICI (age 65 [IQR 57-73] years, 913 (44.4%) women, follow-up 63 [IQR 28-99] months) AI-ECG predictions were not associated with downstream myocarditis (adjusted HR 1.36 [0.47-3.93]). Conclusions AI applied directly to baseline ECG images may stratify the risk of CTRCD associated with anthracycline or trastuzumab exposure.

Prognosis After Withdrawal of Cardioprotective Therapy in Patients With Improved Cancer Therapeutics–Related Cardiac Dysfunction

BackgroundThe long-term prognosis after the discontinuation of cardioprotective therapy (CPT) in patients with cancer therapeutics–related cardiac dysfunction (CTRCD) that has shown improvement remains unclear. ObjectivesThis study aims to assess the prognosis after CPT withdrawal in patients exhibiting improved CTRCD. MethodsIn this retrospective analysis of a single-center prospective cohort study, patients with improved CTRCD, defined as an increase in left ventricular ejection fraction (LVEF) ≥10 percentage points from the time of CTRCD diagnosis, were included. We analyzed their clinical outcomes, which included hospitalization for heart failure or a decrease in LVEF ≥10 percentage points within 2 years after CTRCD improvement, alongside echocardiographic changes. ResultsThe cohort comprised 134 patients with improved CTRCD. The median follow-up duration after CTRCD diagnosis was 368.3 days (Q1-Q3: 160-536 days). After improvement, 90 patients continued CPT (continued group [CG]) and 44 withdrew CPT (withdrawn group [WG]). Among patients whose baseline LVEF at CTRCD diagnosis ranged from 45% to 55%, the final mean LVEF was comparable between both groups (CG: 64.9% ± 4.4% vs WG: 62.9% ± 4.2%; P = 0.059). However, for patients with a baseline LVEF <45%, the final mean LVEF was significantly lower in the WG (CG: 53.3% ± 6.4% vs WG: 48.2% ± 6.9%; P < 0.001). The occurrence of composite major clinical events was notably higher in the WG (HR: 3.06; 95% CI: 1.51-7.73; P = 0.002). ConclusionsPatients who withdrew CPT after demonstrating improvement in CTRCD experienced worse clinical outcomes. Notably, a significant decrease in LVEF was observed after CPT withdrawal in patients with a baseline LVEF <45%.

Artificial Intelligence-Enhanced Risk Stratification of Cancer Therapeutics-Related Cardiac Dysfunction Using Electrocardiographic Images.

Background: Risk stratification strategies for cancer therapeutics-related cardiac dysfunction (CTRCD) rely on serial monitoring by specialized imaging, limiting their scalability. We aimed to examine an application of artificial intelligence (AI) to electrocardiographic (ECG) images as a surrogate for imaging risk biomarkers, and its association with early CTRCD. Methods: Across a U.S.-based health system (2013-2023), we identified 1,550 patients (age 60 [IQR:51-69] years, 1223 [78.9%] women) without cardiomyopathy who received anthracyclines and/or trastuzumab for breast cancer or non-Hodgkin lymphoma and had ECG performed ≤12 months before treatment. We deployed a validated AI model of left ventricular systolic dysfunction (LVSD) to baseline ECG images and defined low, intermediate, and high-risk groups based on AI-ECG LVSD probabilities of <0.01, 0.01 to 0.1, and ≥0.1 (positive screen), respectively. We explored the association with early CTRCD (new cardiomyopathy, heart failure, or left ventricular ejection fraction [LVEF]<50%), or LVEF<40%, up to 12 months post-treatment. In a mechanistic analysis, we assessed the association between global longitudinal strain (GLS) and AI-ECG LVSD probabilities in studies performed within 15 days of each other. Results: Among 1,550 patients without known cardiomyopathy (median follow-up: 14.1 [IQR:13.4-17.1] months), 83 (5.4%), 562 (36.3%) and 905 (58.4%) were classified as high, intermediate, and low risk by baseline AI-ECG. A high- vs low-risk AI-ECG screen (≥0.1 vs <0.01) was associated with a 3.4-fold and 13.5-fold higher incidence of CTRCD (adj.HR 3.35 [95%CI:2.25-4.99]) and LVEF<40% (adj.HR 13.52 [95%CI:5.06-36.10]), respectively. Post-hoc analyses supported longitudinal increases in AI-ECG probabilities within 6-to-12 months of a CTRCD event. Among 1,428 temporally-linked echocardiograms and ECGs, AI-ECG LVSD probabilities were associated with worse GLS (GLS -19% [IQR:-21 to -17%] for probabilities <0.1, to -15% [IQR:-15 to -9%] for ≥0.5 [p<0.001]). Conclusions: AI applied to baseline ECG images can stratify the risk of early CTRCD associated with anthracycline or trastuzumab exposure in the setting of breast cancer or non-Hodgkin lymphoma therapy.

Left Ventricular Twist and the "Rigid Body Rotation" Pattern in Patients Treated with Anthracyclines or Anti-HER2.

Background: During the physiological cardiac cycle, the helix orientation of the muscle fibres induces the rotation of the apex relative to the base of the left ventricular (LV). In heart failure, LV torsion is impaired, and rotation at basal and apical levels occurs in the same direction, a phenomenon called rigid body rotation (RBR). We aimed to evaluate whether the RBR pattern and GLS together could improve the diagnosis of cardiotoxicity in patients treated with anthracyclines and/or anti-HER2. Methods: With an observational, retrospective study involving 175 patients (mean age 55 ± 12 years, 94% females), we evaluated the development of cancer therapeutic-related cardiac dysfunction (CTRCD) defined according to ESC guidelines. We characterised LV dysfunction by echocardiographic standard and speckle-tracking (GLS and RBR pattern) measurements. Patients with a previous diagnosis of structural heart disease or atrial fibrillation were excluded. Results: At the time of enrolment, the chemotherapy regimen included trastuzumab (96%), pertuzumab (21%), and anthracyclines (13%). Twenty-two patients (12.5%) developed cardiotoxicity, and thirteen patients developed an RBR within 6 months of follow-up. In all cases, the RBR pattern was associated with cardiotoxicity (p < 0.001), reporting an optimal specificity but poor sensitivity at three and six months. However, the addition of the RBR pattern to the global longitudinal strain (GLS) ≥ -16% increased the odds ratio (OR) from 25.6 to 32.6 at three months and from 32.5 to 49.6 at six months rather than GLS alone. Conclusions: The RBR pattern improves the diagnostic accuracy of GLS for the detection of cardiotoxicity secondary to anthracyclines and anti-HER2-based treatments.

Echocardiographic Assessment of Left Ventricular Systolic Function in Lymphoma Patient After Initial Dose of Chemotherapy in Baghdad Teaching Hospital

Despite cancer therapeutics-related cardiac dysfunction (CTRCD) can be initially asymptomatic, if not detected and properly managed, it may progress to severe and irreversible heart failure. Therefore, identification of high-risk patients and early detection of subclinical myocardial dysfunction are fundamental tasks for the management of cancer patients undergoing chemotherapy, involving both cardiologists and oncologists. LVEF has low sensitivity for the detection of small changes in LV function. LVEF calculated by conventional 2DE often fails to detect small changes in LV contractility because of several factors. These factors include LV geometric assumptions, inadequate visualization of the true LV apex, lack of consideration of subtle regional wall motion abnormalities, and inherent variability of the measurement. Accordingly, strategies using newer echocardiographic technology, such as STE-derived strain imaging for the early detection of subclinical LV systolic dysfunction. GLS being the most robust and reproducible among the myocardial strain parameters, this parameter has raised the interest of the investigators to detect early and subclinical myocardial dysfunction in patients at risk of CTCRD

Left atrial strain is reduced following trastuzumab in breast cancer patients.

The effect of trastuzumab therapy on left atrial (LA) function remains largely unknown. Our aim was to assess the changes in LA strain parameters longitudinally in patients treated with trastuzumab. We retrospectively studied 170 patients with stage I-IV HER2+ breast cancer. All patients had baseline echocardiograms and repeat echocardiograms at 3months and after 1year. We measured LA strain at all three time points. Changes in LA strain and strain rate (sr) parameters were evaluated using repeated-measures mixed-effects models. The cohort was stratified according to development of cancer therapeutics-related cardiac dysfunction (CTRCD) during follow-up. The mean age was 52.7±13.8years, 25.3% had hypertension and 16.0% had metastatic disease. Multiple LA strain parameters (predicted delta value, [95%CI]) showed statistically significant declines in patients who developed CTRCD from baseline to the 3-month follow-up after multivariable adjustment; LA reservoir strain (LAεres ): -4.7%; [-8.1% to -1.3%], p=.007; LA conduit strain (LAεcon ): -2.8%; [-5.3% to -.4%], p=.021); and LAεres sr: -.2/s; [-.3/s to -.09/s], p<.001). In patients who did not develop CTRCD, LA strain parameters declined significantly but to a smaller degree than in the CTRCD group (LAεres : -1.7%; [-3.1% to -.3%], p=.020, LAεcon : -2.2%; [-3.3% to -1.1%], p<.001, and LA booster pump strain : -2.4%; [-3.5% to -1.4%], p<.001). LA strain rates did not decline significantly in the non-CTRCD group. Trastuzumab treatment was associated with declines in LA strain parameters in patients with breast cancer. The largest declines were observed in patients who developed CTRCD during treatment.

Rationale and Design of the Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT): A Pilot Study

Cancer therapeutics-related cardiac dysfunction (CTRCD) is a well-recognised complication of cancer treatment. Treatment of CTRCD involves cardioprotective therapy (CPT) which can lead to a recovery of CTRCD with normalisation of the left ventricular ejection fraction (LVEF). As a result, there are potentially millions of cancer survivors with recovered CTRCD on CPT. Cardioprotective therapy can be associated with an undesirable long-term pill burden, financial costs, and side effects. Cancer survivorship is anticipated to increase significantly by the end of this decade. To date, there is no evidence of the safety of stopping CPT in this setting. This study seeks to evaluate the hypothesis that ceasing cardioprotective medication is a feasible and safe option without significant impact on LVEF in low-risk patients who have recovered from CTRCD. We will perform a multicentre prospective open-label randomised controlled trial with blinded endpoint (PROBE) of supervised CPT cessation compared to continuing CPT (control). The primary study end point is the change in LVEF by cardiac magnetic resonance imaging at 6 months of enrolment between the two groups. Secondary end points include changes in quality-of-life questionnaires, other cardiac imaging parameters, and recurrence of heart failure. Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT) is one of the first studies currently underway to evaluate the safety of ceasing CPT in recovered CTRCD. The results will inform clinical practice in this evidence-free zone.

Abstract 17680: MIBG Myocardial Scintigraphy is Useful for Predicting CTRCD Caused by Trastuzumab

Introduction: Trastuzumab is known to reduce the mortality rate, recurrence rate, and metastasis rate in Human epidermal growth factor receptor type 2 (HER2)-positive breast cancer patients, and it is recommended to administer it for 12 months to all early-stage HER2-positive breast cancer patients. However, trastuzumab administration can lead to Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD). The guidelines suggest that regular echocardiography every 3 months is useful for early detection of CTRCD, but there are no tests available to predict it before its onset.The purpose of this study is to determine whether cardiac sympathetic nerve evaluation using MIBG myocardial scintigraphy before trastuzumab administration can predict the development of CTRCD three months after administration. Methods: MIBG myocardial scintigraphy was performed before trastuzumab administration in 35 HER2-positive breast cancer patients, and cardiac function assessment was conducted using echocardiography before administration, at 1 month, and at 3 months. Simultaneously, NT-proBNP and troponin levels were measured. CTRCD was defined as a decrease in global longitudinal strain (GLS) of 10% or more from before administration at the 3-month follow-up. Results: Anthracycline and trastuzumab regimens were used in 21 patients (60%). CTRCD occurred in 17 patients at the 3-month follow-up. There were no significant differences in age or previous medication between the CTRCD group and the non-CTRCD group, but the early H/M ratio in MIBG myocardial scintigraphy was significantly lower in the CTRCD group (2.77±0.36) compared to the non-CTRCD group (3.10±0.36) (p&lt;0.01). There were no significant differences in the delay H/M ratio or washout rate. None of the echocardiographic parameters, NT-proBNP levels, or troponin levels showed significant differences and did not become predictive factors. Conclusions: MIBG myocardial scintigraphy is useful for predicting CTRCD caused by trastuzumab. Preclinical studies have suggested that HER2 transactivation from β-adrenergic receptors in the myocardium confers cardioprotection. Suppression of HER2 signaling during cardiac sympathetic nerve dysfunction potentially contributes to the development of CTRCD.

MO21-2 High incidence of cancer therapeutics-related cardiac dysfunction in the patients with cardiac sarcoma

MO21-2 High incidence of cancer therapeutics-related cardiac dysfunction in the patients with cardiac sarcoma

Effectiveness of surveillance by echocardiography for cancer therapeutics-related cardiac dysfunction of patients with breast cancer

BackgroundCancer therapeutics-related cardiac dysfunction (CTRCD) affect the prognosis of patients with breast cancer. Echocardiographic surveillance of patients treated with anti-human epidermal growth factor receptor type 2 (HER2) antibodies has been recommended, but few reports have provided evidence on patients with breast cancer only. We aimed to evaluate the effectiveness of echocardiographic surveillance for breast cancer patients. MethodsWe identified 250 patients with breast cancer who were treated with anti-HER2 antibodies from July 2007 to September 2021. We divided 48 patients with echocardiographic surveillance every 3 months into the surveillance group and 202 patients without echocardiographic surveillance into the non-surveillance group. In the surveillance group, patients with a considerable reduction in global longitudinal strain of 15 % were considered for the initiation of cardioprotective drugs. The composite outcome of CTRCD and acute heart failure was the study endpoint. ResultsThe mean age was 59 ± 12 years. During the follow-up period of 15 months (12–17 months), 12 patients reached the endpoint. The surveillance group had significantly lower incidence of the composite outcome (2.1 % vs. 5.5 %, adjusted odds ratio: 0.28, 95 % confidential intervals: 0.09–0.94; p = 0.039) and higher rates of prescriptions of cardioprotective drugs than the non-surveillance group. ConclusionsThe incidence of cardiac complications was significantly lower in the surveillance group than the non-surveillance group, which supports the effectiveness of echocardiographic surveillance in patients with breast cancer.

Status of pediatric echocardiography clinical trials: a cross-sectional study of registered trials in ClinicalTrials.gov.

The objective of this study is to analyze the characteristics of pediatric echocardiography clinical trials registered in ClinicalTrials.gov. A data set including pediatric echocardiography clinical trials was downloaded from ClinicalTrials.gov until May 13, 2022. We searched the PubMed, Medline, Google Scholar, and Embase databases to extract publication data. Pediatric echocardiography trial characteristics, application areas, and publication status were described. The secondary objectives were to evaluate factors associated with trial publication. We identified 410 pediatric echocardiography reporting definite age, of which 246 were interventional and 146 were observational. Drug interventions were the most commonly studied (32.9%). The most applied area of pediatric echocardiography was congenital heart disease, followed by hemodynamics of preterm or neonatal infants, cardiomyopathy, inflammatory heart disease, pulmonary hypertension, and cardio-oncology. According to the primary completion data, 54.9% of the trials were completed before August 2020. 34.2% of the trials had been published within 24 months. Union countries and quadruple masking were more likely to be published. Echocardiography is rapidly evolving in pediatric clinical applications, including anatomic imaging and functional imaging. Novel speckle tracking techniques have also been pivotal in the assessment of cancer therapeutics-related cardiac dysfunction. A small number of clinical trials in pediatric echocardiography are published in a timely fashion. Concerted efforts are needed to promote trial transparency.

Cardiovascular Side Effects of Anthracyclines and HER2 Inhibitors among Patients with Breast Cancer: A Multidisciplinary Stepwise Approach for Prevention, Early Detection, and Treatment.

Cardiovascular (CV) diseases (CVD) are a major cause of long-term morbidity and mortality affecting life expectancy amongst cancer survivors. In recent years, because of the possibility of early diagnosis and the increased efficacy of neo-adjuvant and adjuvant systemic treatments (targeting specific molecular pathways), the high percentage of survival from breast cancer led CVD to become the first cause of death among survivors. Therefore, it is mandatory to adopt cardioprotective strategies to minimize CV side effects and CVD in general in breast cancer patients. Cancer therapeutics-related cardiac dysfunction (CTRCD) is a common group of side effects of chemotherapeutics widely employed in breast cancer (e.g., anthracycline and human epidermal growth factor receptor 2 inhibitors). The aim of the present manuscript is to propose a pragmatic multidisciplinary stepwise approach for prevention, early detection, and treatment of cardiotoxicity in patients with breast cancer.

Prognostic value of left ventricular global longitudinal strain on speckle echocardiography for predicting chemotherapy-induced cardiotoxicity in breast cancer patients: A systematic review and meta-analysis.

Literature suggests that left ventricular global longitudinal strain (LV-GLS) on speckle echocardiography has the potential to predict cardiotoxicity amongst breast cancer patients receiving chemotherapy such as anthracycline, taxane, cyclophosphamide, and trastuzumab. Our study aimed to collect evidence for the prognostic value of LV-GLS for predicting chemotherapy-induced cardiotoxicity in breast cancer patients. A detailed search of the PubMed, Google Scholar, Cochrane Library, and Scopus databases was conducted for published articles up to August 31, 2022. In our meta-analysis, we looked at 13 studies with a total of 1007 breast cancer patients getting chemotherapy that looked at the predictive value of GLS. Absolute GLS change during treatment showed a pooled sensitivity of 84% (95% CI 74% to 91%) and a pooled specificity of 77% (95% CI 68% to 84%). For a relative change in GLS, we observed a pooled sensitivity of 76% (95% CI 56% to 89%) and a pooled specificity of 83% (95% CI 73% to 90%). For an absolute change in GLS, we observed a positive likelihood ratio (LR), and the negative LR was 4 and .21. Summary receiver operating characteristics curve with prediction and confidence intervals represents a promising summary area under the curve (sAUC) of .88, 95% CI ranges from .85 to .91 for absolute change in GLS, as well as for relative change (sAUC, .87, 95% CI .84 to .90). Our results demonstrated an estimation of LV-GLS after the beginning of required chemotherapy, including anthracyclines and trastuzumab, had a promising prognostic value for predicting the likelihood of cancer therapeutics-related cardiac dysfunction. To confirm our findings, well-designed prospective adequately powered diagnostic randomised trials are necessary.

Serial Non-Invasive Myocardial Work Measurements for Patient Risk Stratification and Early Detection of Cancer Therapeutics-Related Cardiac Dysfunction in Breast Cancer Patients: A Single-Centre Observational Study

Serial transthoracic echocardiographic (TTE) assessment of LVEF and GLS are the gold standard in screening Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD). Non-invasive left-ventricle (LV) pressure-strain loop (PSL) emerged as a novel method to quantify Myocardial Work (MW). This study aims to describe the temporal changes and longitudinal trajectories of MW indices during cardiotoxic treatment. We included 50 breast cancer patients with normal LV function referred for anthracycline therapy w/wo Trastuzumab. Medical therapy, clinical and echocardiographic data were recorded before and 3, 6, and 12 months after initiation of the chemotherapy. MW indices were calculated through PSL analysis. According to ESC guidelines, mild and moderated CTRCD was detected in 10 and 9 patients, respectively (20% CTRCDmild, 18% CTRCDmod), while 31 patients remained free of CTRCD (62% CTRCDneg). Prior to chemotherapy MWI, MWE and CW were significantly lower in CTRCDmod than in CTRCDneg and CTRCDmild. Overt cardiac dysfunction in CTRCDmod at 6 months was accompanied by significant worse values in MWI, MWE and WW compared to CTRCDneg and CTRCDmild. MW features such as low baseline CW, especially when associated with a rise in WW at follow-up, may identify patients at risk for CTRCD. Additional studies are needed to explore the role of MW in CRTCD.

Beta-Blockers for Primary Prevention of Anthracycline-Induced Cardiac Toxicity: An Updated Meta-Analysis of Randomized Clinical Trials.

Cardiotoxicity is a well-recognized complication of chemotherapy with Anthracyclines. However, results from trials evaluating beta-blockers for prevention are controversial. Therefore, we performed a meta-analysis to find whether prophylactic administration of beta-blockers can help prevent Anthracyclines-induced cardiotoxicity. We assessed randomized trials and observational studies where a prophylactic intervention was compared with a control arm in patients with a normal left ventricular ejection fraction (LVEF) receiving Anthracyclines. The primary outcome was EF reduction. The secondary outcome was the development of Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD), defined as a decrease in the LVEF of >10% to a value of <53%. We included 17 trials comprising 1291 patients (671 patients in the intervention arm and 620 in the control arm). Carvedilol was administered in eight studies, and others used bisoprolol, metoprolol, or nebivolol. Compared with baseline, LVEF reduced in both intervention and control groups after chemotherapy (MD = -1.93%, 95% CI: -2.94, -0.92, p = 0.001, I2 = 72.1% vs. MD = -4.78%, 95% CI: -6.51, -3.04, p = 0.001, I 2 = 91.6%, respectively). LVEF was less reduced among the beta-blocker receivers (MD = 3.44%, 95% CI: 1.41-5.46, p = 0.001, I2 = 94.0%). Among the eight studies reporting the incidence of CTRCD, 45 out of 370 participants in the intervention arm and 54 out of 341 in the control arm were reported to experience this complication (RR = 0.76; 95% CI: 0.53,1.09; I 2 = 24.4%; p = 0.235). Treatment with beta-blockers prevents dilatation of the left ventricle, development of diastolic dysfunction, and reduction of LVEF. However, these hemodynamic effects do not translate into a significant reduction in CTRCD incidence and prevention of hospitalization for heart failure or cardiac death.

Two-dimensional speckle tracking echocardiography help identify breast cancer therapeutics–related cardiac dysfunction

BackgroundCancer therapeutics–related cardiac dysfunction (CTRCD) from different chemotherapy strategies are underdetermined by echocardiography. As an imaging marker of subclinical cardiac dysfunction, two-dimensional speckle tracking echocardiography (2D-STE) may assist in identifying the impact patterns of different CTRCD.MethodsA total of 67 consecutive patients with invasive ductal breast carcinoma who will undertake neoadjuvant chemotherapy were enrolled and grouped according to their different chemotherapy regimens based on their biopsy results. Group A included 34 patients who received anthracycline without trastuzumab, whereas Group B had 33 patients who received trastuzumab without anthracycline. Echocardiography was performed at three time-points, i.e., baseline (T0), cycle-2 (T2), and cycle-4 (T4) of chemotherapy. Conventional echocardiographic measurements and 2D-STE strain values, and myocardial work (MW) parameters, were compared between different groups at different time-points.ResultsThe mean age had no statistical difference between the two groups. E/e′ was the only conventional echocardiographic parameter that had variation in group A (P < 0.05). Compared with baseline, GLS in group A decreased at T2, and GCS decreased at T4 (P < 0.05). GLS and GCS in group B both decreased at T4 (P < 0.05). More patients in group A had a more than 15% fall of baseline GLS rather than GCS at T2 (P < 0.05), however, there was no difference of either GLS or GCS decline rate at T4 between the two groups. All the MW parameters in group A had variations overtime, whereas only GCW in group B (P < 0.05).ConclusionEarly subclinical myocardial dysfunction can be identified by 2D-STE in breast cancer patients with chemotherapy, and GLS provides profound value in demonstrating the temporal changes in early myocardial damage induced by anthracycline. LV contractility injury in patients with trastuzumab may be mild at first but increases in severity with exposure time as early as cycle-4. Awareness of these differences may help to stratify the prevention of late cardiovascular events caused by different CTRCDs. In addition, GCW may be the most sensitive myocardial work parameter of CTRCD.

Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3-Year Results of the SUCCOUR Trial

BackgroundGlobal longitudinal strain (GLS) can predict cancer therapeutics–related cardiac dysfunction and guide initiation of cardioprotection (CPT). ObjectivesIn 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. MethodsIn 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. ResultsAmong 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. ConclusionsAmong 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)

Abstract 12295: Relation Between Withdrawal of Heart Failure Therapy and Left Ventricular Function After Improvement of Cancer Therapeutics Related Cardiac Dysfunction

Introduction: This study aimed to investigate withdrawal of guideline-directed medical therapy (GDMT) is associated with decline of left ventricular (LV) function after recovery from cancer therapeutics related cardiac dysfunction (CTRCD). Methods: From Mar 2015 to Dec 2021, 126 patients with improving CTRCD [defined as &gt;10% point improvement in LV ejection fraction (LVEF)] were identified. They were divided into 2 groups: patients who continued GDMT (GDMT+) and withdrew GDMT (GDMT-) after improvement of CTRCD. LV functional changes within 1 year and composite clinical outcome which was defined as hospitalization due to heart failure and all-cause death were compared between 2 groups. Results: The most frequent primary cancer was breast cancer [94 (74.6%)], followed by lymphoma [16 (12.7%)] and multiple myeloma [7 (5.6%)]. GDMT was withdrawn in 41 (32.5%) patients after improvement of CTRCD. Mean LVEF and LV global longitudinal strain (GLS) were comparable between 2 groups at the time of CTRCD diagnosis (LVEF: 44.6±8.5% in GDMT+ vs. 45.5±7.7% in GDMT-, p=0.592, LV GLS: 13.3±2.9% in GDMT+ vs. 13.6±2.7% in GDMT-, p=0.553), and when LVEF was improved (LVEF: 57.1±8.0% vs. 58.3±7.4%, p=0.457, LV GLS: 14.1±3.2% vs. 14.6±3.1%, p=0.398). Dividing into 4 groups according to LVEF at the time of CTRCD diagnosis, patients with LVEF 45-55% showed no significant difference of LV function after withdrawal of GDMT (LVEF: 65.4±3.9% vs. 63.5±4.1%, p=0.066, LV GLS: 16.9±2.2% vs. 16.2±1.8%, p=0.205), but patients with LVEF &lt;45% experienced significant decline of LVEF (LVEF: 52.7±6.4% vs. 48.7±7.2%, p=0.041, LV GLS: 11.8±2.7% vs. 11.2±2.4%, p=0.445). Withdrawal of GDMT was associated with poor composite clinical outcome in the multivariable-adjusted model [hazard ratio (95% CI) 1.38 (1.01 - 1.93), p=0.005]. Conclusions: Withdrawal of GDMT was associated with poor clinical outcome and decline of LV function in patients with improving CTRCD, particularly in patients with LVEF &lt;45%.

Abstract 10353: Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3 Year Results of the SUCCOUR Trial

Introduction: Global longitudinal strain (GLS) can predict cancer therapeutics-related cardiac dysfunction (CTRCD) and guide initiation of cardioprotection (CPT) at the time of chemotherapy. No prospective randomized controlled trial (RCT) has identified the impact on LV function in survivors. Hypothesis: GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care. Methods: In this international (28 sites) multicenter prospective RCT, patients (pts) were included if they were administrated anthracyclines and had another risk factor for HF. They were randomly allocated into undergoing GLS-guided CPT for &gt;12% relative reduction in GLS or EF-guided CPT for &gt;10% absolute reduction of EF. Primary endpoint was the change in EF (ΔEF) from baseline to 3 years by 3D echocardiography. Results: Among 331 pts enrolled, 255 (77%, 60±16 years, 95% women) completed 3-year follow-up (123 in EF-guided group and 132 in GLS-guided). Most had breast cancer (236, 93%), 67 (26%) with hypertension and 32 (13%) with diabetes mellitus. A regimen of anthracycline and trastuzumab was the most common chemotherapy regimen (84%). The baseline LVEF was 61±4% with GLS of 20.7±2.3% in the entire population. CPT was administrated in 18 pts (15%) in EF-guided and 41 (31%) in GLS-guided (p=0.02). Most patients showed recovery in EF and GLS after chemotherapy (Figure). ΔEF was -2.0±4.8 in EF-guided and -1.4±5.4 in GLS-guided (p=0.25), but LVEF at 3 years in EF-guided was lower than that of GLS-guided (58.0±5.6% vs 59±4.9%, p=0.043). Ten pts in EF-guided developed CTRCD, and 6 in GLS-guided (p=0.24). Conclusions: Most of the enrolled pts were taking potentially cardiotoxic chemotherapy for breast cancer. Almost all improved LV function over 3 years, and although GLS-guided CPT was associated with higher EF at 3 years, there was no difference in ΔEF compared with EF-guided surveillance.

Iodine-123 β-methyl-P-iodophenyl-pentadecanoic Acid (123I-BMIPP) Myocardial Scintigraphy for Breast Cancer Patients and Possible Early Signs of Cancer-Therapeutics-Related Cardiac Dysfunction (CTRCD).

(1) Background: The mortality of breast cancer has decreased due to the advancement of cancer therapies. However, more patients are suffering from cancer-therapeutics-related cardiac dysfunction (CTRCD). Diagnostic and treatment guidelines for CTRCD have not been fully established yet. Ultrasound cardiogram (UCG) is the gold standard for diagnosis of CTRCD, but many breast cancer patients cannot undergo UCG due to the surgery wounds or anatomical reasons. The purpose of the study is to evaluate the usefulness of myocardial scintigraphy using Iodine-123 β-methyl-P-iodophenyl-pentadecanoic acid (123I-BMIPP) in comparison with UCG. (2) Methods: 100 breast cancer patients who received chemotherapy within 3 years underwent Thallium (201Tl) and 23I-BMIPP myocardial perfusion and metabolism scintigraphy. The images were visually evaluated by doctors and radiological technologists, and the grade of uptake reduction was scored by Heart Risk View-S software (Nihon Medi-Physics). The scores were deployed in a 17-segment model of the heart. The distribution of the scores were analyzed. (3) Results: Nine patients (9%) could not undergo UCG. No correlation was found between left ventricular ejection fraction (LVEF) and Heart Risk View-S scores of 201Tl myocardial perfusion scintigraphy nor those of BMIPP myocardial metabolism scintigraphy. In a 17-segment model of the heart, the scores of the middle rings were higher than for the basal ring. (4) Conclusions: Evaluation by UCG is not possible for some patients. Myocardial scintigraphy cannot serve as a perfect alternative to UCG. However, it will become the preferable second-choice screening test, as it could point out the early stage of CTRCD.