Cardiotoxic Cancer Therapy Research Articles

Cardiac health in breast cancer (CHiB): protocol for a single-centre, randomised controlled trial.

The incidence of breast cancer has increased from 900 000 to 2.3 million new annual cases over the last 25 years. The 5-year survival rate has markedly risen to over 90% worldwide due to significant therapeutic advancements. Longer survival in patients with breast cancer means more patients may experience long-term effects of their treatments, including cancer therapy-related cardiac dysfunction (CTRCD). To date, there is no established primary prevention to minimise CTRCD. The Cardiac Health in Breast Cancer study is a two-arm, single-centre, randomised controlled trial investigating the impact of an exercise programme on cardiac changes in patients with breast cancer undergoing cardiotoxic cancer therapy. 48 females with breast cancer will be randomised to either a 12-month intervention group (IG) or a control group (CG). The IG will receive a combination of supervised high-intensity interval training (HIIT) and high-intensity resistance training (HIRT) for 6 months, while the CG will follow WHO guidelines for physical activity independently. All participants will undergo transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging and cardiopulmonary exercise testing at baseline, after 6 months and after 12 months. The primary endpoint is the occurrence of symptomatic or asymptomatic CTRCD at the time points of examination, detected by cardiac imaging, which may be mitigated by structured physical exercise. Secondary endpoints include assessments of cardiac inflammation as detected by CMR, mitochondrial dysfunction, health-related quality of life, the occurrence of fatigue, depression and anxiety, as well as exercise capacity, average heart rate, heart rate variability and daily physical activity.

Long term risk of heart failure in adult cancer survivors: a systematic review and meta-analysis

Abstract Background Evaluation of the cardiotoxic effects from cancer is most commonly evaluated at the time of chemotherapy. Although cancer survivorship populations are rapidly expanding, there is a paucity of evidence regarding the frequency and causes of heart failure (HF) >5 years after cardiotoxic therapy. Objectives This systematic review sought to investigate the relationship between cardiotoxic cancer therapies and late-onset HF. Methods We searched the EMBASE and MEDLINE databases for studies reporting HF in adult survivors (≥50 years old), who were ≥5 years post-breast/lymphoma cancer therapy. A random effects model was used to examine the associations of HF. A meta-regression analysis was implemented to determine causes of heterogeneity. Results Thirteen papers were included in the review and meta-analysis (Figure 1), comprising 190,259 participants (mean age 53.5 years, 93% female). The risk of HF was increased (overall log risk-ratio 0.39 (95%CI (0.16-0.62)), (Figure 2). Cardiotoxic treatment, compared with cancer alone, provided a similar risk (log risk ratio of 0.38 [95% CI 0.02-0.77]). In the breast cancer population ratio (11 studies) the overall heart failure log risk was 0.41 [95% CI 0.13-0.69]). Although heterogeneity was significant (I²=77.17), this was explained by differences in patient characteristics; once multivariable analysis accounted for follow up (0.99, 95%CI (0.97-0.99), p=0.047), age (1.14, 95%CI (1.04-1.25), p=0.003) and hypertension (0.95, 95%CI (0.92-0.98), p<0.001), residual heterogeneity was low (I²=28.73). Conclusions HF is increased in adult cancer survivors, associated with cardiotoxic cancer therapy and standard risk factors. Consideration should be given for selective screening for HF in this at-risk population.Fig 1:Literature Search Flow DiagramFig 2:Incident HF in Cancer Survivors

Utility of mobile phone app-assisted screening for heart failure and heart stress in primary care

Abstract Background As heart failure (HF) still has a similar prognosis to some of the most common cancers, a timely diagnosis of HF is of paramount importance. We sought to determine whether a mobile phone app can facilitate screening for HF in primary care. Material and methods The national echocardiographic society conducted a multicenter screening programme for HF in which general practitioners from 13 primary care centres used a mobile phone app to decide whether patients without a prior HF diagnosis should be referred to one of the 6 university hospitals for transthoracic echocardiography (TTE) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing. The app would recommend further testing (TTE and NT-proBNP) to patients with symptoms potentially associated with HF, atrial fibrillation, pathologic electrocardiogram (ECG), previous myocardial infarction or exposure to cardiotoxic cancer therapies, or at least two other risk factors listed in Figure (left panel). Patients with signs of HF were not eligible for the programme. The algorithms proposed in the 2021 ESC guidelines were used to diagnose HF across the entire spectrum of left ventricular ejection fraction (EF). Results Of the 930 screened outpatients (mean age 66±11 years, age range 21-91 years, 61% female), 318 symptomatic patients (34.2%) were diagnosed with new HF (Figure). HF with preserved (HFpEF) was diagnosed more frequently than HF with mildy reduced (HFmrEF) and reduced EF (HFrEF). Heart stress, defined as elevated plasma NT-proBNP in asymptomatic individuals with risk factors irrespective of the presence or absence of structural heart disease or cardiac dysfunction, was found in 22.3% (Figure, right panel). In multivariate regression analysis, advanced age, atrial fibrillation, pathological ECG, long-standing history of arterial hypertension and chronic kidney disease were independently associated with HF, while other risk factors were not (Figure, middle panel). Conclusions Screening in primary care based on symptoms and risk factors, facilitated by a mobile phone app, resulted in a new HF diagnosis in approximately one third of screened patients, with the majority of them having HFpEF. Recalibration of the referral criteria might further improve the performance of the app for screening purposes.

Long-term risk of heart failure in adult cancer survivors: a systematic review and meta-analysis

BackgroundCancer survivors are at increased risk of heart failure (HF). While cardiotoxicity is commonly sought at the time of cancer chemotherapy, HF develops as a result of multiple ‘hits’ over...

The burden of cardiovascular disease and risk for subsequent major adverse cardiovascular events in survivors of childhood cancer: a prospective, longitudinal analysis from the St Jude Lifetime Cohort Study

The effect of the increasing lifetime burden of non-major cardiovascular conditions on risk for a subsequent major adverse cardiovascular event among survivors of childhood cancer has not been assessed. We aimed to characterise the prevalence of major adverse cardiovascular events and their association with the cumulative burden of non-major adverse cardiovascular events in childhood cancer survivors. This is a longitudinal cohort study with participant data obtained from an ongoing cohort study at St Jude Children's Research Hospital: the St Jude Lifetime Cohort Study (SJLIFE). Prospective clinical follow-up was of 5-year survivors of childhood cancer who were diagnosed when aged younger than 25 years from 1962 to 2012. Age-frequency, sex-frequency, and race-frequency matched community-control participants completed a similar one-time clinical assessment. 22 cardiovascular events were graded using a St Jude Children's Research Hospital-modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Cumulative incidence and burden of the primary outcome of major adverse cardiovascular events (cardiomyopathy, myocardial infarction, stroke, and other cardiovascular-related mortality) were estimated. Rate ratios (RR) of the association of major adverse cardiovascular events with 22 non-major adverse cardiovascular events were estimated using multivariable piecewise-exponential regression adjusting for attained age, age at diagnosis, sex, race and ethnicity, treatment era, diagnosis of diabetes, and exposure to cardiotoxic cancer therapies. The St Jude Lifetime Cohort study is registered with ClinicalTrials.gov, NCT00760656, and is ongoing. 9602 5-year survivors of childhood cancer, and 737 community controls were included in the longitudinal follow-up (from Sept 13, 2007, to Dec 17, 2021). The median follow-up was 20·3 years (IQR 12·0-31·4) from the date of primary cancer diagnosis (4311 [44.9%] were females). By the age of 50 years (analysis stopped at age 50 years due to the low number of participants older than that age), the cumulative incidence of major adverse cardiovascular events among survivors was 17·7% (95% CI 15·9-19·5) compared with 0·9% (0·0-2·1) in the community controls. The cumulative burden of major adverse cardiovascular events in survivors was 0·26 (95% CI 0·23-0·29) events per survivor compared with 0·009 (0·000-0·021) events per community control participant. Increasing cumulative burden of grade 1-4 non-major adverse cardiovascular events was associated with an increased future risk of major adverse cardiovascular events (one condition: RR 4·3, 95% CI 3·1-6·0; p<0·0001; two conditions: 6·6, 4·6-9·5; p<0·0001; and three conditions: 7·7, 5·1-11·4; p<0·0001). Increased risk for major adverse cardiovascular events was observed with specific subclinical conditions (eg, grade 1 arrhythmias [RR 1·5, 95% CI 1·2-2·0; p=0·0017]), grade 2 left ventricular systolic dysfunction (2·2, 1·6-3·1; p<0·0001), grade 2 valvular disorders (2·2, 1·2-4·0; p=0·013), but not grade 1 hypercholesterolaemia, grade 1-2 hypertriglyceridaemia, or grade 1-2 vascular stenosis. Among an ageing cohort of survivors of childhood cancer, the accumulation of non-major adverse cardiovascular events, including subclinical conditions, increased the risk of major adverse cardiovascular events and should be the focus of interventions for early detection and prevention of major adverse cardiovascular events. The US National Cancer Institute and the American Lebanese Syrian Associated Charities.

Abstract PO2-12-08: Increased burden of genetic variants in idiopathic cardiomyopathy genes is associated with cancer therapy-related cardiomyopathy

Abstract Background: Breast cancer (BC) patients are at significant risk of therapy-related cardiotoxicity, but prediction of which patients will experience cardiotoxicity and the severity of the outcome are lacking. We hypothesized that germline genetic variants are potential risk factors for cancer treatment-related cardiomyopathy (CTRC) and in this study, we focused on rare non-synonymous variants within 57 genes deemed causative of familial and sporadic forms of idiopathic cardiomyopathies. Methods: We developed a clinical database and biorepository for patients receiving any potentially cardiotoxic cancer therapy at Mayo Clinic Florida. Enrollment is ongoing and includes consent to access external records. Patient data is extracted from records at baseline, completion of treatment and then once per year. The clinical database includes the following datasets: demographics, pathology, chemotherapy, radiation, echocardiography, cardiac MRI, PET/CT scan, blood pressure, BMI, labs, treatment complications. Treatment complications includes pre-existing conditions (smoking, alcohol and drug use history, hypertension, diabetes, coronary artery disease, hyperlipidemia, prior stroke or myocardial infarction, peripheral vascular disease, renal failure); cardiac medications at baseline; cardiac side-effects; time to cardiotoxicity; cardiotoxicity interventions and outcomes. Exome sequencing was performed by the Mayo Clinic NGS core on the first 86 patients in the registry, average of ~120x read depth following Illumina’s standard protocol for the NovaSeq 6000 and S4 flow cell. Genomic variants were extracted for 57 genes known to be causative of dilated, hypertrophic and arrhythmogenic right ventricular cardiomyopathies and channelopathies. Putative risk variants in known cardiomyopathy genes were defined as non-synonymous variants with a frequency of &amp;lt; 0.0004 in the GnomAD database. We compared the number of patients with putative risk variants in those groups with and without CTRC. Results: 84/86 patients had BC diagnosis. Key characteristics are described in the table below. 60/86 (70%) patients had at least one putative risk variant in one of 31 genes (there were no risk variants identified in 27/57 genes). The average number of putative risk variants per patient within the CTRC group was higher than that observed in patients without CTRC (2.06 vs 1.62). Post-hoc analysis suggested this difference is largely from patients with &amp;gt;2 risk variants in the group who experienced CTRC (N=7/17, 41%) compared to those who did not (N=14/69, 20%), p=0.023. Conclusions: Rare missense variants in the causative genes of idiopathic cardiomyopathies are potential risk factors for CTRC and risk may be increased in patients with a higher burden of variants. Analysis of the genetic data from patients that continue to be accrued in this study, including effects of additional clinical risk factors will be undertaken to improve prediction of cardiotoxicity. Table 1 Distribution of putative cardiomyopathy genetic variants in 86 cancer patients with and without treatment-related cardiomyopathy, separated by treatment regimen Citation Format: Nadine Norton, Thien Nguyen, Joseph Reddy, Jinky Harvey, Morgan Weidner, Amanda Arnold, Lily Evans, Laura Vallow, Pooja Advani. Increased burden of genetic variants in idiopathic cardiomyopathy genes is associated with cancer therapy-related cardiomyopathy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-08.

Macrotroponin interference in patients receiving cardiotoxic breast cancer therapy: A pilot study

Macrotroponin interference in patients receiving cardiotoxic breast cancer therapy: A pilot study

Ways to increase the effectiveness of hypertension correction during antitumor therapy with the use of VEGF inhibitors

In recent years, cardioncology has rapidly become responsible for comprehensive decision-making appropriate cancer patients receiving cardiotoxic cancer therapy. Currently, the implementation of a multidisciplinary approach in the correction of adverse events using various drug antitumor therapy regimens is becoming increasingly relevant. In particular, given the widespread use of vascular-endothelial growth factor inhibitors, both at the heart of complex schemes and in mono-supportive modes. It is important to timely identify and correct such a clinically significant adverse event as an increase in blood pressure at the time of administration and in the early follow-up period. Adherence to standard drug regimens for hypertension, which usually provide satisfactory blood pressure control between cycles of administration of vascular-endothelial growth factor inhibitors, in a number of patients did not allow the same effective retention of blood pressure in the planned intervals with the administration of bevacizumab. The intensification of drug therapy for hypertension, both at the pre-infusion stage and at the time of an increase in blood pressure, was of a multidirectional nature. Search and summarize information on the availability and development of physiotherapeutic treatment methods for the correction of hypertension during antitumor therapy in cancer patients using vascular-endothelial growth factor inhibitors. 35 literature sources were analyzed. There are no data on the development of physiotherapeutic methods for the treatment of bevacizumab-induced hypertension. Domestic sources ― 25 articles. Foreign sources ― 10 articles. An analysis of the literature concluded that there is a lack of research on the development of physiotherapeutic methods for the treatment of bevacizumab-induced hypertension. In order to reduce the cardiotoxicity of humanized recombined monoclonal antibodies, maintain the dose interval period, improve survival and eliminate the need for dose adjustment of antihypertensive drugs, it is proposed to consider the use of preformed physical factors in the treatment of bevacizumab-induced hypertension.

Abstract 18584: Predictive Accuracy Of The Pooled Cohort Equations For Estimating Atherosclerotic Cardiovascular Disease Risk Among Women Exposed To Potentially Cardiotoxic Breast Cancer Therapies

Introduction: Risk estimation is a critical component in clinical decision making for preventive cardiovascular care. Suboptimal identification and management of cardiovascular disease (CVD) risk, may contribute to excess CVD morbidity and mortality among breast cancer (BC) patients and survivors. This study aimed to assess the performance of the Pooled Cohort Equations (PCEs) in predicting atherosclerotic cardiovascular disease (ASCVD) events among a real-world population of adult women treated for BC. Methods: Using electronic medical record data collected between Jan. 1, 2011 and Jan. 31, 2023, this external validation study retrospectively identified a cohort of BC women, age 40-79, without history of ASCVD in the one year prior to initiation of a potentially cardiotoxic BC therapy. For all cohort members with cholesterol and blood pressure measurements recorded within one year prior to the index cancer therapy exposure (n=1,239), a 5-year ASCVD risk estimate was calculated. Predictive accuracy of the risk estimate was assessed using a Poisson model-based framework for calibration, including evaluation of calibration-in-the-large, the calibration slope, and calibration plots. To account for potential biases related to informative censoring, calibration was assessed among an inverse probability of censoring weighted (IPCW) pseudopopulation with stabilized and unstabilized weights, and a complete case cohort (n=306). Results: Among the IPCW pseudopopulation, calibration-in-the-large, expressed as a standardized incidence ratio, was 1.85 (95% CI: 1.73, 1.98), indicating that, on average, women in this subpopulation experience a significantly higher number of ASCVD events than expected from baseline PCE risk estimates. The calibration slope, estimated at 0.55 (95% CI: 0.45, 0.66), and evaluation of calibration plots, further indicate particularly poor performance of the PCEs at low and high levels of estimated risk. Findings were consistent across the assessed populations. Conclusions: When calculated prior to initiation of a potentially cardiotoxic BC therapy, the PCEs significantly underestimate 5-year ASCVD risk for BC women, indicating this commonly used ASCVD risk estimate is poorly calibrated for this subpopulation.

MRI-derived extracellular volume as a biomarker of cancer therapy cardiotoxicity: systematic review and meta-analysis

ObjectivesMRI-derived extracellular volume (ECV) allows characterization of myocardial changes before the onset of overt pathology, which may be caused by cancer therapy cardiotoxicity. Our purpose was to review studies exploring the role of MRI-derived ECV as an early cardiotoxicity biomarker to guide timely intervention.Materials and methodsIn April 2022, we performed a systematic search on EMBASE and PubMed for articles on MRI-derived ECV as a biomarker of cancer therapy cardiotoxicity. Two blinded researchers screened the retrieved articles, including those reporting ECV values at least 3 months from cardiotoxic treatment. Data extraction was performed for each article, including clinical and technical data, and ECV values. Pooled ECV was calculated using the random effects model and compared among different treatment regimens and among those who did or did not experience overt cardiac dysfunction. Meta-regression analyses were conducted to appraise which clinical or technical variables yielded a significant impact on ECV.ResultsOverall, 19 studies were included. Study populations ranged from 9 to 236 patients, for a total of 1123 individuals, with an average age ranging from 12.5 to 74 years. Most studies included patients with breast or esophageal cancer, treated with anthracyclines and chest radiotherapy. Pooled ECV was 28.44% (95% confidence interval, CI, 26.85−30.03%) among subjects who had undergone cardiotoxic cancer therapy, versus 25.23% (95%CI 23.31−27.14%) among those who had not (p = .003).ConclusionA higher ECV in patients who underwent cardiotoxic treatment could imply subclinical changes in the myocardium, present even before overt cardiac pathology is detectable.Clinical relevance statementThe ability to detect subclinical changes in the myocardium displayed by ECV suggests its use as an early biomarker of cancer therapy–related cardiotoxicity.Key Points• Cardiotoxicity is a common adverse effect of cancer therapy; therefore, its prompt detection could improve patient outcomes.• Pooled MRI-derived myocardial extracellular volume was higher in patients who underwent cardiotoxic cancer therapy than in those who did not (28.44% versus 25.23%, p = .003).• MRI-derived myocardial extracellular volume represents a potential early biomarker of cancer therapy cardiotoxicity.

Risk of Cardiovascular Events Among Patients With Head and Neck Cancer

Cardiovascular (CV) disease is a substantial cause of morbidity and mortality in cancer due to shared risk factors and exposure to potentially cardiotoxic cancer therapy. However, our understanding of CV risk in patients with head and neck squamous cell carcinoma (HNSCC) is limited. To define CV risk profiles, incident stroke, myocardial infarction (MI), and mortality in patients with HNSCC. This retrospective, population-based cohort study included 35 897 US veterans with newly diagnosed HNSCC from January 1, 2000, to December 31, 2020. Data were analyzed from May 2022 to January 2023. Demographic, cancer-specific, and treatment characteristics. Prevalence of CV risk factors, medication use, and control at HNSCC diagnosis; cumulative incidence of stroke and MI; and all-cause death. Of 35 857 US veterans with HNSCC (median [IQR] age, 63 [58-69] years; 176 [0.5%] American Indian or Alaska Native, 57 [0.2%] Asian, 5321 [16.6%] Black, 207 [0.6%] Native Hawaiian or Other Pacific Islander, and 26 277 [82.0%] White individuals), there were high rates of former or current smoking (16 341 [83%]), hypertension (24 023 [67%]), diabetes (7988 [22%]), and hyperlipidemia (18 421 [51%]). Although most patients were taking risk-lowering medications, 15 941 (47%) had at least 1 uncontrolled CV risk factor. Black race was associated with increased risk of having uncontrolled CV risk factor(s) (relative risk, 1.06; 95% CI, 1.03-1.09), and patients with larynx cancer had higher rates of prevalent and uncontrolled risk factors compared with other cancer subsites. Considering death as a competing risk, the 10-year cumulative incidence of stroke and MI was 12.5% and 8.3%, respectively. In cause-specific hazards models, hypertension, diabetes, carotid artery stenosis, coronary artery disease, and presence of uncontrolled CV risk factor(s) were significantly associated with stroke and MI. In extended Cox models, incident stroke and MI were associated with a 47% (95% CI, 41%-54%) and 71% (95% CI, 63%-81%) increased risk of all-cause death, respectively. The results of this cohort study suggest that in HNSCC, the burden of suboptimally controlled CV risk factors and incident risk of stroke and MI are substantial. Modifiable CV risk factors are associated with risk of adverse CV events, and these events are associated with a higher risk of death. These findings identify populations at risk and potentially underscore the importance of modifiable CV risk factor control and motivate strategies to reduce CV risk in HNSCC survivorship care.

Comparing Renin-Angiotensin-Aldosterone Blockade Regimens for Long-Term Chemotherapy-Related Cardiac Dysfunction: A Network Meta-Analysis.

Cancer therapies including trastuzumab and anthracyclines are cardiotoxic and cause cardiac dysfunction. To prevent cardiotoxicity, pharmacological agents used in heart failure have been administered concomitantly with cardiotoxic cancer therapy, but few studies to date have performed a head-to-head comparison of these different agents. This systematic review and network meta-analysis of randomized-controlled trials aims to evaluate the efficacy of renin-angiotensin-aldosterone system (RAAS) blockers, namely angiotensin-converting enzyme inhibitors (ACE-Is), aldosterone receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs), in primary prevention against chemotherapy-related cardiac dysfunction in patients receiving anthracyclines and/or trastuzumab. A systematic search was performed in major web databases for studies from inception to 15 September 2022. A Bayesian network meta-analysis model was used to assess the relative effects of competing treatments on the primary outcomes of risk of significant decline in left ventricular ejection fraction (LVEF) and mean LVEF decline. Secondary outcomes included left ventricular diastolic function, global longitudinal strain, and cardiac biomarkers. This study is registered with PROSPERO, CRD42022357980. Nineteen studies reported the effects of 13 interventions (N = 1905 patients). Only enalapril (RR 0.05, 95% CI 0.00-0.20) was associated with reduced risk of patients developing significant decline in LVEF relative to placebo. Subgroup analysis showed that the beneficial effect of enalapril was driven by protection against anthracycline-associated toxicity. In addition, no RAAS-inhibiting agents showed efficacy in protection against treatment with both anthracycline and trastuzumab. The use of RAAS inhibition therapy did not conclusively impact on other markers of cardiac function, including left ventricular diastolic function and cardiac biomarkers.

Cardio-Oncology for the Primary Care Provider.

Cardiovascular disease is a major cause of mortality among oncologic patients. As cancer therapies continue to evolve and advance, cancer survival rates have been increasing and so has the burden of cardiovascular disease within this population. For this reason, cardio-oncology plays an important role in promoting multidisciplinary care with the primary care provider, oncology, and cardiology. In this review, we discuss the roles of different providers, strategies to monitor patients receiving cardiotoxic therapies, and summarize cancer therapy class-specific toxicities. Continued collaboration among providers and ongoing research related to cardiotoxic cancer therapies will enable patients to receive maximal, evidence-based, comprehensive care.

Cellular Mechanisms Mediating Exercise-Induced Protection against Cardiotoxic Anthracycline Cancer Therapy.

Anthracyclines such as doxorubicin are widely used chemotherapy drugs. A common side effect of anthracycline therapy is cardiotoxicity, which can compromise heart function and lead to dilated cardiomyopathy and heart failure. Dexrazoxane and heart failure medications (i.e., beta blockers and drugs targeting the renin-angiotensin system) are prescribed for the primary prevention of cancer therapy-related cardiotoxicity and for the management of cardiac dysfunction and symptoms if they arise during chemotherapy. However, there is a clear need for new therapies to combat the cardiotoxic effects of cancer drugs. Exercise is a cardioprotective stimulus that has recently been shown to improve heart function and prevent functional disability in breast cancer patients undergoing anthracycline chemotherapy. Evidence from preclinical studies supports the use of exercise training to prevent or attenuate the damaging effects of anthracyclines on the cardiovascular system. In this review, we summarise findings from experimental models which provide insight into cellular mechanisms by which exercise may protect the heart from anthracycline-mediated damage, and identify knowledge gaps that require further investigation. Improved understanding of the mechanisms by which exercise protects the heart from anthracyclines may lead to the development of novel therapies to treat cancer therapy-related cardiotoxicity.

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 14602: Does Cancer Treatment Break Your Heart? A Linked Health Data Analysis of Thecharacteristics and Survival of Patients Who Have Developed Cardiovascular Disease Post Cancer Treatment

Background: Cancer treatment induced cardiotoxicity, can be a devastating outcome of cancer therapy. It is possible that a patient can survive cancer but develop cardiovascular disease (CVD). Aim: to determine whether there are differences in the characteristics of cancer patients who received potentially cardiotoxic cancer therapy and subsequently developed CVD and those who did not. Methods: This epidemiological study will comprise a retrospective analysis of de-identified linked health data sets, including the Integrated Activity Collection (ISAAC) of Hospital Separations, South Australian Cancer Registry (SACR), Northern Territory Cancer Registry (NTCR) and mortality (Births Deaths and Marriage Registry Data) and NT Hospital Separation data. The total population will be segregated in two distinct groups namely ‘Cancer with no HF’ and ‘Cancer with HF’ to compare the between group differences by demographic factors and medical history. Results: Of the (n=17,389) patients who received chemotherapy cancer treatment between July 2001-June 2017, 49% (8,530) were diagnosed with HF post cancer treatment( median age at cancer diagnosis 65 years; 58% male); crude mortality was 73% within the HF and cancer group; cause of death within this group was HF related 14%; cancer related 63%; other 22% compared to the non HF and cancer group ( median age at cancer diagnosis 58 years; 53% male) who had a mortality rate of 46%; 6.2% CVD related; 68.8% cancer related and 25% other. Conclusion: After adjusting for age, sex, tumour grade, cancer site and CVD admissions prior to cancer diagnosis patients with CVD and cancer had poorer outcomes.

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.

Nuclear medicine in the assessment and prevention of cancer therapy-related cardiotoxicity: prospects and proposal of use by the European Association of Nuclear Medicine (EANM)

Cardiotoxicity may present as (pulmonary) hypertension, acute and chronic coronary syndromes, venous thromboembolism, cardiomyopathies/heart failure, arrhythmia, valvular heart disease, peripheral arterial disease, and myocarditis. Many of these disease entities can be diagnosed by established cardiovascular diagnostic pathways. Nuclear medicine, however, has proven promising in the diagnosis of cardiomyopathies/heart failure, and peri- and myocarditis as well as arterial inflammation. This article first outlines the spectrum of cardiotoxic cancer therapies and the potential side effects. This will be complemented by the definition of cardiotoxicity using non-nuclear cardiovascular imaging (echocardiography, CMR) and biomarkers. Available nuclear imaging techniques are then presented and specific suggestions are made for their application and potential role in the diagnosis of cardiotoxicity.

HFA-ICOS cardiovascular toxicity risk score validation in CARDIOTOX registry

Abstract Background Cancer therapy-related cardiovascular toxicity (CTox) is a growing medical problem and baseline cardiovascular (CV) risk assessment is recommended in all patients scheduled to receive potentially cardiotoxic cancer therapy. Based on literature review, the Heart Failure Association (HFA) Cardio-Oncology working group and the International Cardio-Oncology Society (ICOS) proposed a risk score to predict CTox but, it has not been validated. Purpose To validate the HFA-ICOS anthracycline risk assessment score in the CARDIOTOX registry cohort (NCT02039622). Methods The CARDIOTOX registry is a prospective multicenter study aiming at identifying factors related with CTox and assessing the utility of clinical, biochemical, and echo parameters for the early detection of CV disease during and after cancer therapy. A total of 1324 adult patients were prospectively included from April 2012 to October 2017. Data was collected at baseline, 3 weeks and 3, 6, 12, 18 and 24 months after initiation of treatment. Clinical follow-up was extended until January 2020. All patients receiving anthracycline chemotherapy were stratified according to HFA-ICOS risk score and Kaplan-Meier survival curves were analyzed to estimate the risk of all-cause mortality and anthracycline chemotherapy-related CV complications defined by HFA-ICOS risk score (left ventricular dysfunction (LVD), heart failure (HF) and arrhythmias). Results A total of 1066 patients were included in the analysis. Baseline characteristics are summarized in table 1. 571 patients (53.6%) meet low, 333 (31.2%) medium, 152 (14.3%) high and 10 (0.9%) very-high HFA-ICOS CTox risk criteria. 197 patients (18.4%) died of any cause during follow-up. CV death occurred in 4 patients (2%), all caused by HF. Any degree of CTox was identified in 519 (48.7%) patients during the 110 months follow-up (73 (6.8%) developed clinical HF/HF hospitalization, 29 (2.7%) asymptomatic LVEF &amp;lt;50%; 27 (2.5%) clinically relevant arrhythmias and 390 (36.6%) an asymptomatic increase in cardiac biomarkers or a relative decrease in GLS&amp;gt;15%). Figures 1A and 1B showed the cumulative mortality rate and CTox rate during follow-up. CTox and all-cause mortality rates increased significantly according to the estimated baseline HFA-ICOS score. Conclusions HFA-ICOS risk score categorizes patients according to their risk of developing anthracycline chemotherapy-related CTox, showing a good ability to predict both all-cause mortality and CTox. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III (PI13/00559).

Abstract 204: Evaluation Of Impact Of Cardio-oncology Department On Cardiovascular Outcomes And Oncology Treatment: A Single Center Cross -sectional Retrospective Chart Review

Introduction: Cardiotoxicity secondary to cancer therapy can lead to alterations or discontinuation of therapy regimens and potentially impact patient outcomes. We examined overall cardiovascular and oncology treatment outcomes among cancer patients in an urban center with an established cardio-oncology department. Hypothesis: We hypothesized that in adult cancer patients receiving cardiotoxic treatments, the rates of occurrences of major adverse cardiovascular events (MACE) and the rates of emergency room (ER) visits due to cardiovascular (CV) complications would differ when managed by a cardio-oncologist compared with a general cardiologist. Method: We performed a retrospective chart review of 127 patients managed by a general cardiologist and 254 patients managed by a cardio-oncologist for MACE, CV-related ER visits and oncology treatment modifications. Inclusion criteria included ≥18 years of age, a diagnosis of breast cancer (36.48%, 139 of 381), lung cancer (23.1%, 88 of 381), multiple myeloma (13.65%, 52 of 381) or lymphoma (26.77%, 102 of 381); and history of treatment with a known cardiotoxic agent or chest radiation therapy. A two-tailed chi-square analysis was used to compare differences. Welch’s T test analysis was used to compare the rate of ER visits. Result: There was significantly higher MACE among patients managed by a general cardiologist (46.46%, 59 of 127) compared with a cardio-oncologist (22.83%, 58 of 254). The rate of ER visits due to cardiovascular complications was significantly lower among those managed by a cardio-oncologist (21.26%, 54 of 254) compared with a general cardiologist (59.84%, 76 of 127). Less patients had treatment modifications, delays and discontinuations in patients managed by a cardio-oncologist (with p&lt;0.01 for all). Conclusion: We found lower occurrences of MACE and CV-related ER visits in patients on cardiotoxic cancer therapy managed by a cardio-oncologist compared with a general cardiologist.