Cardiotoxic Therapy Research Articles

Evaluation of cardiotoxicity related to cancer treatment in an urban safety-net hospital.

e18804 Background: Improvements in survival of cancer patients has led to an increased awareness of the long-term cardiac effects of chemotherapy. American Society of Clinical Oncology (ASCO) Clinical Practice Guideline emphasizes the needs of identifying patients with higher risk for cardiovascular toxicity prior to treatment initiation. African American (AA) race has been associated with higher incidence of cardiotoxicity and resultant incomplete adjuvant therapy compared to white patients. Here, we investigate the utilization of various imaging modalities to monitor chemotherapy-induced cardiotoxicity in a predominantly AA breast cancer population at the safety-net hospital. Methods: This study was a retrospective analysis of breast cancer patients (n = 33) who received trastuzumab, doxorubicin, and/or paclitaxel between year 2018 and 2020 at the safety-net hospital in Atlanta, Georgia. Patient demographics, clinical characteristics, pathologic variables as well as utilization of echocardiography, echocardiography with global longitudinal strain (GLS), and multigated acquisition scans (MUGA). Results: The majority of patients were AA female (27/33, 81.8%) and the mean age at diagnosis was 52 ± 13.2 years. 11/33 (33%), 24/33 (72.7%), and 20/33 (33.3%) were treated with trastuzumab, paclitaxel, and doxorubicin respectively. Baseline left ventricular ejection fraction (LVEF) was assessed in 32/33 (96.7%) of patients: MUGA 21/32 (65.6%), echocardiography 10/33 (31.3%), and echocardiography with GLS 1/32 (3.1%). 13/32 (40.6%) patients underwent repeated imaging, with the average time between repeat MUGA and echocardiography being 254.3 and 147 days respectively. LVEF decrease of > 10% was noted in 4 patients with repeat MUGA but in none of the repeat echocardiography group. Only 5 patients had echocardiography with GLS over the study period, of which 2/5 (40%) had a drop in GLS in the setting of normal ejection fraction, consistent with occult LV systolic dysfunction. Conclusions: Our study suggests that African American patients at a safety net hospital receive the equivalent level of cardiac surveillance during cancer treatment. However, GLS imaging is underutilized in the detection of subclinical cardiac dysfunction in breast cancer patients receiving chemotherapy. Larger, long terms prospective studies are needed to assess the implications of abnormal GLS and progression to clinical left ventricular systolic dysfunction in the AA breast cancer population.

Spontaneous Non-Sustained Ventricular Tachycardia and Premature Ventricular Contractions and Their Prognostic Relevance in Patients with Cancer in Routine Care.

Simple SummaryIt is largely unknown how frequently cancer patients seen in routine care show ventricular arrhythmias during 24-h electrocardiograms. We have found that non–sustained ventricular tachycardia episodes of ≥3 and ≥4 beats duration were more frequent in cancer patients than controls. Non–sustained ventricular tachycardia with ≥4 beats and ≥20 premature ventricular contractions/day seen in routine 24-h electrocardiograms of patients with cancer carry prognostic relevance.Aims: It is largely unknown whether cancer patients seen in routine care show ventricular arrhythmias in 24 h electrocardiograms (ECGs), and whether when they are detected they carry prognostic relevance. Methods and Results: We included 261 consecutive cancer patients that were referred to the department of cardiology for 24 h ECG examination and 35 healthy controls of similar age and sex in the analysis. To reduce selection bias, cancer patients with known left ventricular ejection fraction <45% were not included in the analysis. Non–sustained ventricular tachycardia (NSVT) episodes of either ≥3 and ≥4 beats duration were more frequent in cancer patients than controls (17% vs. 0%, p = 0.0008; 10% vs. 0%, p = 0.016). Premature ventricular contractions (PVCs)/24 h were not more frequent in cancer patients compared to controls (median (IQR), 26 (2–360) vs. 9 (1–43), p = 0.06; ≥20 PVCs 53% vs. 37%, p = 0.07). During follow-up, (up to 7.2 years, median 15 months) of the cancer patients, 158 (61%) died (1-/3-/5-year mortality rates: 45% [95%CI 39–51%], 66% [95%CI 59–73%], 73% [95%CI 64–82%]). Both non-sustained ventricular tachycardia of ≥4 beats and ≥20 PVCs/24 h independently predicted mortality in univariate and multivariate survival analyses, adjusted for all other univariate predictors of mortality as well as relevant clinical factors, including cancer stage and type, performance status (ECOG), prior potentially cardiotoxic anti-cancer drug therapy, coronary artery disease, potassium concentration, and haemoglobin (multivariate adjusted hazard ratios: NSVT ≥4 beats [HR 1.76, p = 0.022], ≥20 PVCs/24 h [HR 1.63, p < 0.0064]). Conclusions: NSVT ≥4 beats and ≥20 PVCs/day seen in routine 24 h ECGs of patients with cancer carry prognostic relevance.

Effect of Active Cancer on the Cardiac Phenotype: A Cardiac Magnetic Resonance Imaging‐Based Study of Myocardial Tissue Health and Deformation in Patients With Chemotherapy‐Naïve Cancer

BackgroundThe overlap between cancer and cardiovascular care continues to expand, with intersections emerging before, during, and following cancer therapies. To date, emphasis has been placed on how cancer therapeutics influence downstream cardiac health. However, whether active malignancy itself influences chamber volumes, function, or overall myocardial tissue health remains uncertain. We sought to perform a comprehensive cardiovascular magnetic resonance‐based evaluation of cardiac health in patients with chemotherapy‐naïve cancer with comparison with a healthy volunteer population.Methods and ResultsThree‐hundred and eighty‐one patients with active breast cancer or lymphoma before cardiotoxic chemotherapy exposure were recruited in addition to 102 healthy volunteers. Both cohorts underwent standardized cardiovascular magnetic resonance imaging with quantification of chamber volumes, ejection fraction, and native myocardial T1. Left ventricular mechanics were incrementally assessed using three‐dimensional myocardial deformation analysis, providing global longitudinal, circumferential, radial, and principal peak‐systolic strain amplitude and systolic strain rate. The mean age of patients with cancer was 53.8±13.4 years; 79% being women. Despite similar left ventricular ejection fraction, patients with cancer showed smaller chambers, increased strain amplitude, and systolic strain rate in both conventional and principal directions, and elevated native T1 versus sex‐matched healthy volunteers. Adjusting for age, sex, hypertension, and diabetes mellitus, the presence of cancer remained associated with these cardiovascular magnetic resonance parameters.ConclusionsThe presence of cancer is independently associated with alterations in cardiac chamber size, function, and objective markers of tissue health. Dedicated research is warranted to elucidate pathophysiologic mechanisms underlying these findings and to explore their relevance to the management of patients with cancer referred for cardiotoxic therapies.

Highlighting recent treatment advances in metastatic prostate cancer: expanding the treatment arsenal.

Present highlights from recent research examining the treatment of advanced prostate cancer. Although debate remains about the optimal sequencing of docetaxel and novel androgen directed therapies in addition to androgen deprivation therapy (ADT) in the treatment of men with new metastatic prostate cancer, the novel LHRH antagonist relugolix seems poised to become an appealing option in a choice of initial ADT. Novel radioisotopes, genomically selected therapies, and immune therapy combinations show progress in opening up new treatment options for men with castration-resistant prostate cancer. Although no clear consensus has emerged, evolving data continue to refine the selection of systemic therapies in treatment naïve metastatic prostate cancer. With potentially less cardiotoxic androgen deprivation therapies, novel radioisotopes, targeted pharmaceuticals, and immune therapy combinations, progress appears to be on the horizon in improving outcomes for men with advanced prostate cancer.

Management of COVID-19 in cancer patients receiving cardiotoxic anti-cancer therapy. Future recommendations for cardio-oncology

Cardiotoxicity induced by anti-cancer treatment has become a significant threat as the number of cardiotoxic anti-cancer agents is growing. Cancer patients are at an increased risk of contracting coronavirus disease 2019 (COVID-19) because of immune suppression caused by anti-cancer drugs and/or supportive treatment. Deterioration in lung functions due to COVID-19 is responsible for many cardiac events. The presence of COVID-19 and some of its treatment modalities may increase the chance of cardiotoxicity development in cancer patients receiving potentially cardiotoxic agents. This review provides evidence-based information on the cardiotoxicity risk in cancer patients clinically diagnosed with COVID-19 who are receiving potentially cardiotoxic anti-cancer agents. Proposed strategies relating to the management of this patient cohorts are also discussed.

Neurohumoral, cardiac and inflammatory markers in the evaluation of heart failure severity and progression.

Heart failure is common in adult population, accounting for substantial morbidity and mortality worldwide. The main risk factors for heart failure are coronary artery disease, hypertension, obesity, diabetes mellitus, chronic pulmonary diseases, family history of cardiovascular diseases, cardiotoxic therapy. The main factor associated with poor outcome of these patients is constant progression of heart failure. In the current review we present evidence on the role of established and candidate neurohumoral biomarkers for heart failure progression management and diagnostics. A growing number of biomarkers have been proposed as potentially useful in heart failure patients, but not one of them still resembles the characteristics of the “ideal biomarker.” A single marker will hardly perform well for screening, diagnostic, prognostic, and therapeutic management purposes. Moreover, the pathophysiological and clinical significance of biomarkers may depend on the presentation, stage, and severity of the disease. The authors cover main classification of heart failure phenotypes, based on the measurement of left ventricular ejection fraction, including heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, and the recently proposed category heart failure with mid-range ejection fraction. One could envisage specific sets of biomarker with different performances in heart failure progression with different left ventricular ejection fraction especially as concerns prediction of the future course of the disease and of left ventricular adverse/reverse remodeling. This article is intended to provide an overview of basic and additional mechanisms of heart failure progression will contribute to a more comprehensive knowledge of the disease pathogenesis.

Risk Stratification and Management of Arterial Hypertension and Cardiovascular Adverse Events Related to Cancer Treatments: An Oncology Network from Piedmont and Aosta Valley (North-Western Italy) Consensus Document

Cancer patients receiving a potentially cardiotoxic oncologic therapy have an increased risk of cardiovascular adverse events (CVAEs), especially in presence of concomitant arterial hypertension (AH). Therefore, cancer patients should be evaluated before, during and after cardiotoxic treatments, to early identify new-onset or worsening AH or CVAEs. An expert panel of oncology networks from Piedmont and Aosta Valley (North-Western Italy) aimed to provide recommendations to support health professionals in selecting the best management strategies for patients, considering the impact on outcome and the risk–benefit ratio of diagnostic/therapeutic tools. We proposed an useful document for evaluating and managing AH related to cancer treatments. Patients should be divided into 4 cardiovascular (CV) risk groups before starting potentially cardiotoxic therapies: patients with low/moderate risk who should be entirely evaluated by oncologists and patients with high/very high risk who should be referred to a cardiologist or arterial hypertension specialist. According to the CV risk class, every patient should be followed up during cancer treatment to monitor any possible CV complications. Adequate control of AH related to antineoplastic treatments is crucial to prevent severe CVAEs. In the presence of high-profile risk or lack of response to anti-hypertensive therapy, the patients should be managed with a cardiovascular-oncology expert center.

Cardiovascular Family History Increases Risk for Late-Onset Adverse Cardiovascular Outcomes in Childhood Cancer Survivors: A St. Jude Lifetime Cohort Report.

Survivors of childhood cancer have an increased risk of therapy-related cardiovascular disease. It is not known whether family history of cardiovascular disease further increases risk of adverse cardiovascular outcomes among survivors. Family history of cardiovascular disease was collected from 1,260 survivors [median age at diagnosis, 8 years (range, 0-23); age at last follow-up, 35 years (range, 18-66)] of childhood cancer in the St. Jude Lifetime Cohort Study. Multivariable risk models evaluated associations with cardiovascular disease (Common Terminology Criteria for Adverse Events grade 2-4 events) and cardiovascular risk factors. Among survivors exposed to chest-directed radiation and/or anthracycline chemotherapy (n = 824), 7% reported a first-degree family history of heart failure, 19% myocardial infarction, 11% stroke, 26% atherosclerotic disease (myocardial infarction and/or stroke), 62% hypertension, and 31% diabetes mellitus. Eighteen percent of exposed survivors developed heart failure, 9% myocardial infarction, 3% stroke, 11% atherosclerotic disease, 30% hypertension, and 9% diabetes mellitus. Having a first-degree family history of atherosclerotic disease was independently associated with development of treatment-related heart failure [RR, 1.38; 95% confidence interval (CI), 1.01-1.88; P = 0.04] among exposed survivors. Risk for hypertension was increased among exposed survivors with a first-degree family history of hypertension (RR, 1.55; 95% CI, 1.26-1.92; P < 0.0001) or of any cardiovascular disease [myocardial infarction, stroke, or heart failure (RR, 1.30; 95% CI, 1.06-1.59; P = 0.01)]. Family history of cardiovascular disease and cardiovascular risk factors independently increased risk of heart failure and hypertension among survivors of childhood cancer exposed to cardiotoxic therapies. These data show the importance of cardiovascular family history as a risk factor for cardiovascular disease in survivors of childhood cancer.

Genetic Variants Associated with Therapy-Related Cardiomyopathy among Childhood Cancer Survivors of African Ancestry.

Cardiomyopathy occurs at significantly higher rates in survivors of childhood cancer than the general population, but few studies have evaluated racial or ethnic disparities, and none have assessed potential genetic factors contributing to this outcome. In this study, childhood cancer survivors of African ancestry exposed to cardiotoxic therapies (anthracyclines and/or heart radiotherapy; n = 246) were compared with cardiotoxic-exposed survivors of European ancestry (n = 1,645) in the St. Jude Lifetime Cohort. Genetic variants were examined using whole-genome sequencing data among survivors of African ancestry, first based on ejection fraction (EF) as a continuous outcome, followed by clinical history of cardiomyopathy. Survivors of African ancestry showed 1.53- and 2.47-fold risks of CTCAE grade 2-4 and grade 3-4 cardiomyopathy than survivors of European ancestry. A novel locus at 1p13.2 showed significant association with EF (rs6689879*C: EF reduction = 4.2%; P = 2.8 × 10-8) in 246 survivors of African ancestry, which was successfully replicated in 1,645 survivors of European ancestry but with attenuated magnitude (EF reduction = 0.4%; P = 0.042). In survivors of African ancestry, rs6689879*C showed a 5.43-fold risk of cardiomyopathy and 1.31-fold risk in those of European ancestry. Among survivors of African ancestry with rs6689879*C and CTCAE grade 2-4 cardiomyopathy, the PHTF1 promoter region was hypomethylated. Similar results were observed in survivors of European ancestry, albeit with reduced magnitudes of hypomethylation among those with rs6689879*C and CTCAE grade 2-4 cardiomyopathy. PHTF1 was upregulated in human-induced pluripotent stem cell-derived cardiomyocytes from patients with doxorubicin-induced cardiomyopathy. These findings have potential implications for long-term cardiac surveillance and up-front cancer care for patients of African ancestry. SIGNIFICANCE: Childhood cancer survivors of African ancestry are at higher risk of cardiomyopathy than those of European ancestry, and a novel locus at 1p13.2 is associated with therapy-related cardiomyopathy specifically in African-American survivors.See related commentary by Brown and Richard, p. 2272.

Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy

BackgroundIn patients at risk of cancer therapy-related cardiac dysfunction (CTRCD), initiation of cardioprotective therapy (CPT) is constrained by the low sensitivity of ejection fraction (EF) for minor changes in left ventricular (LV) function. Global longitudinal strain (GLS) is a robust and sensitive marker of LV dysfunction, but existing observational data have been insufficient to support a routine GLS-guided strategy for CPT. ObjectivesThis study sought to identify whether GLS-guided CPT prevents reduction in LVEF and development of CTRCD in high-risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care. MethodsIn this international, multicenter, prospective, randomized controlled trial, 331 anthracycline-treated patients with another heart failure risk factor were randomly allocated to CPT initiation guided by either ≥12% relative reduction in GLS (n = 166) or >10% absolute reduction of LVEF (n = 165). Patients were followed for EF and development of CTRCD (symptomatic EF reduction of >5% or >10% asymptomatic to <55%) over 1 year. ResultsOf 331 randomized patients, 2 died, and 22 withdrew consent or were lost to follow-up. Among 307 patients (age: 54 ± 12 years; 94% women; baseline LVEF: 59 ± 6%; GLS: –20.6 ± 2.4%) with a median (interquartile range) follow-up of 1.02 years (0.98 to 1.07 years), most (n = 278) had breast cancer. Heart failure risk factors were prevalent: 29% had hypertension, and 13% had diabetes mellitus. At the 1-year follow-up, although the primary outcome of change in LVEF was not significantly different between the 2 arms, there was significantly greater use of CPT, and fewer patients met CTRCD criteria in the GLS-guided than the EF-guided arm (5.8% vs. 13.7%; p = 0.02), and the 1-year EF was 57 ± 6% versus 55 ± 7% (p = 0.05). Patients who received CPT in the EF-guided arm had a larger reduction in LVEF at follow-up than in the GLS-guided arm (9.1 ± 10.9% vs. 2.9 ± 7.4%; p = 0.03). ConclusionsAlthough the change in LVEF was not different between the 2 arms as a whole, when patients who received CPT were compared, those in the GLS-guided arm had a significantly lower reduction in LVEF at 1 year follow-up. Furthermore, GLS-guided CPT significantly reduced a meaningful fall of LVEF to the abnormal range. The results support the use of GLS in surveillance for CTRCD. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628)

Anthracycline-Induced Cardiotoxicity in Breast Cancer Patients from Southern Sri Lanka: An Echocardiographic Analysis.

Anthracycline-induced cardiotoxicity has never been investigated in Sri Lanka. Therefore, this study was conducted to determine the prevalence of anthracycline-induced cardiotoxicity in breast cancer patients using echocardiographic findings. A prospective cohort study was performed. All newly diagnosed breast cancer patients who were administered with anthracycline and cyclophosphamide (AC schedule) for the first time were enrolled in the study. In the hospital setting, anthracycline is administered only as a combination therapy, and only this combination was selected to limit the effect of other cardiotoxic chemotherapy agents. Records of echocardiography were obtained: one day before anthracycline chemotherapy (baseline), one day after the first chemotherapy dose, one day after the last chemotherapy dose, and six months after the completion of anthracycline chemotherapy. Following parameters were recorded from the echocardiography results: ejection fraction (EF, %), fractioning shortening (FS, %), posterior wall thickness, left ventricle (PWT, mm), the thickness of interventricular septum (IVS, mm), left ventricular end-diastolic diameter (LVEDD, mm), and left ventricular end-systolic diameter (LVESD, mm). Statistical analysis of the echocardiography results was performed using ANOVA at four stages. A p value <0.05 was considered significant. Subclinical cardiac dysfunction was defined as a fall of EF >10% during the follow-up echocardiography. There was no significant change (p > 0.05) between the baseline echocardiographic parameters and one day after the 1st anthracycline dose. However, significant differences (p < 0.05) were observed between the baseline echocardiographic parameters and one day after the last anthracycline dose and six months after the completion of anthracycline therapy with a gradual and progressive deterioration in functional parameters including EF, FS, PWT, and IVS over time. There were 65 patients out of 196 (33.16%) who developed subclinical cardiac dysfunction six months after the completion of anthracycline chemotherapy. The prevalence of subclinical anthracycline-induced cardiotoxicity was relatively higher in these patients. An equation was also developed based on left ventricular ejection fraction (LVEF) to predict the anthracycline-induced cardiotoxicity of a patient six months after the completion of anthracycline chemotherapy. We believe that this will help in the monitoring of patients who undergo anthracycline therapy for cardiotoxicity. It is recommended to carry out a long-term follow-up to detect early-onset chronic progressive cardiotoxicity in all patients who were treated with anthracycline therapy.

SARS-CoV-2 Infection and Cardioncology: From Cardiometabolic Risk Factors to Outcomes in Cancer Patients.

Simple SummaryThe coronavirus disease-2019 (COVID-19) pandemic has significantly changed the management and treatment of some diseases, including cancer, in order to reduce the risk of viral contamination in particularly vulnerable patients. SARS-CoV-2 infection leads to secondary hemophagocytic lymphohistiocytosis (sHLH), which is a multiorgan hyperinflammatory condition based on the hyperactivation of cytotoxic T lymphocytes, macrophages, and natural killer cells, leading to multiorgan failure (including myocarditis, venous thromboembolism, and acute respiratory distress syndrome) and consequently to death. We highlight the major cardiovascular and coagulative complications of COVID-19 with particular reference to cancer patients by analyzing the retrospective clinical studies currently available. Discussions on the harmful or beneficial effects of anticancer therapies as well as on the type of tumor during SARS-CoV-2 infection have been made, with the addition of practical recommendations for the risk reduction of coagulation dysfunctions, myocarditis, venous thromboembolism, and mortality in cancer patients.The coronavirus disease-2019 (COVID-19) is a highly transmissible viral illness caused by SARS-CoV-2, which has been defined by the World Health Organization as a pandemic, considering its remarkable transmission speed worldwide. SARS-CoV-2 interacts with angiotensin-converting enzyme 2 and TMPRSS2, which is a serine protease both expressed in lungs, the gastro-intestinal tract, and cardiac myocytes. Patients with COVID-19 experienced adverse cardiac events (hypertension, venous thromboembolism, arrhythmia, myocardial injury, fulminant myocarditis), and patients with previous cardiovascular disease have a higher risk of death. Cancer patients are extremely vulnerable with a high risk of viral infection and more negative prognosis than healthy people, and the magnitude of effects depends on the type of cancer, recent chemotherapy, radiotherapy, or surgery and other concomitant comorbidities (diabetes, cardiovascular diseases, metabolic syndrome). Patients with active cancer or those treated with cardiotoxic therapies may have heart damages exacerbated by SARS-CoV-2 infection than non-cancer patients. We highlight the cardiovascular side effects of COVID-19 focusing on the main outcomes in cancer patients in updated perspective and retrospective studies. We focus on the main cardio-metabolic risk factors in non-cancer and cancer patients and provide recommendations aimed to reduce cardiovascular events, morbidity, and mortality.

Cardioprotection using strain-guided management of potentially cardiotoxic cancer therapy: 1 year results of the SUCCOUR trial

Abstract Background Conventional criteria for diagnosis of chemotherapy-related cardiac dysfunction (CTRCD) are dependent on the recognition of heart failure (HF) symptoms and/or changes in LVEF. However, the low sensitivity of EF for minor changes in LV function may delay initiation of cardio-protective therapy (CPT). Global longitudinal strain (GLS) is a robust and sensitive marker of LV dysfunction (LVD), but existing observational data are insufficient to justify changing the diagnostic criteria for CTRCD. Purpose To identify whether GLS guidance of CPT would improve cardiac function of at risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care. Methods In this international multicenter prospective randomized controlled trial, 331 pts from 23 international sites taking anthracyclines with another risk factor for HF were randomly allocated into 166 undergoing GLS-guided (CPT for &amp;gt;12% relative reduction in GLS using Echopac software) and 165 EF-guided (CPT for &amp;gt;10% absolute reduction of EF). Pts were followed over 1 year for the primary end-point (ΔEF) with 3D echo (3DE); 2D echo (2DE) was used when 3D images were unsuitable for measurement. Development of CTRCD (EF reduction of 10% to &amp;lt;55%) was a secondary endpoint. Results Of 331 randomized patients, 24 withdrew before follow-up imaging was performed (2 died, and rest withdrew or were lost to follow-up). Among 307 patients (age 54±12 years, 94% women) with follow-up 1.0±0.2 years, 277 had breast cancer, 30 had lymphoma/leukemia. HF risk factors were prevalent: 89 (29%) had hypertension and 39 (13%) had diabetes mellitus. The most common chemotherapy regimen during this study was the combination of anthracycline and trastuzumab. The baseline 3D LVEF was 61±5%, and GLS was −20.8±3.2%. At 1 year follow-up, 31 (10%) met CTRCD and was reduced in the GLS-guided arm (Table 1), although new LV dysfunction (EF&amp;lt;55%) and change of EF were not different. Conclusion In this international multicentre trial, the incidence of CTRCD was reduced by strain-guided cardioprotection. Although the final EF and the number of pts developing EF &amp;lt;55% was not altered by strain-guided therapy, this reduces meaningful reduction of EF to the abnormal range. The results support the use of GLS in surveillance for CTRCD. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): General Electric Medical Systems

Efficacy and safety of catheter ablation for atrial fibrillation in patients with cancer

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia in patients with cancer. Management of AF in patients with cancer poses unique challenges. Long-term use of antiarrhythmic drug (AAD) therapy lacks evidence of efficacy in this population and poses risk of drug interactions. Catheter ablation is a well-established treatment modality for AAD resistant symptomatic AF and in patients with heart failure. Nevertheless, the effectiveness and safety of catheter ablation in patients with cancer is not well established. Method We retrospectively analyzed consecutive patients who underwent catheter ablation for AF, with either history of cancer (other than non-melanoma skin cancer) within 5-years prior or exposure to systemic anthracycline and/or thoracic radiation therapy at any time. Results The study included 162 patients. The mean age was 65.5 (26–84 years) years and 50% were female. Overall 133 (82%) patients had freedom from AF at 12 months following ablation. Of these 74 (54%) required post-ablation AAD, 18 (13.5%) required another ablation within the first 12 months and 9 (6.7%) required both AAD and a second ablation to maintain sinus rhythm. There were 14 adverse events (8.6%); 5 access site and 4 non-access site bleeding, 2 strokes, 2 cardiac tamponade and 1 pulmonary vein stenosis with ≈1% serious complications. Conclusion The success of catheter ablation for AF and the incidence of procedure related complications in patients with a history of recent cancer or prior exposure to cardiotoxic therapies are similar to that reported in patients without a history of cancer and hence if needed, it should be considered in select patients. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Dr. S Ganatra is supported by Lahey Physician Research Stipend Program.

Cardiac biomarkers and association with subsequent cardiomyopathy and mortality among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort.

Survivors of childhood cancer exposed to cardiotoxic therapies are at significant cardiovascular risk. The utility of cardiac biomarkers for identifying the risk of future cardiomyopathy and mortality is unknown. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) were assessed in 1213 adults 10 or more years from a childhood cancer diagnosis; 786 were exposed to anthracycline chemotherapy and/or chest-directed radiation therapy (RT). NT-proBNP values above age- and sex-specific 97.5th percentiles were considered abnormal. Generalized linear models estimated cross-sectional associations between abnormal NT-proBNP and anthracycline or chest RT doses as risk ratios with 95% confidence intervals (CIs). A Poisson distribution estimated rates and a Cox proportional hazards model estimated hazard ratios (HRs) for future cardiac events and death. At a median age of 35.5 years (interquartile range, 29.8-42.5 years), NT-proBNP and cTnT were abnormal in 22.5% and 0.4%, respectively. Exposure to chest RT and exposure to anthracycline chemotherapy were each associated with a dose-dependent increased risk for abnormal NT-proBNP (P for trend <.0001). Among exposed survivors with no history of Common Terminology Criteria for Adverse Events-graded cardiomyopathy and with normal systolic function, survivors with abnormal NT-proBNP had higher rates per 1000 person-years of cardiac mortality (2.93 vs 0.96; P < .0001) and future cardiomyopathy (32.10 vs 15.98; P < .0001) and an increased risk of future cardiomyopathy (HR, 2.28; 95% CI, 1.28-4.08) according to a multivariable assessment. Abnormal NT-proBNP values were prevalent and, among survivors who were exposed to cardiotoxic therapy but did not have a history of cardiomyopathy or current systolic dysfunction, identified those at increased risk for future cardiomyopathy. Further longitudinal studies are needed to confirm this novel finding.

Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: a position statement from the Cardio-Oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology.

Serum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac biomarkers including cardiac troponin and natriuretic peptides can be used to guide initiation of cardioprotective treatments for cancer patients during treatment and to monitor the response to cardioprotective treatments, and they also offer prognostic value. This position statement examines the role of cardiac biomarkers in the management of cancer patients. The Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the Cardio-Oncology Council of the ESC have evaluated the current evidence for the role of cardiovascular biomarkers in cancer patients before, during and after cardiotoxic cancer therapies. The characteristics of the main two biomarkers troponin and natriuretic peptides are discussed, the link to the mechanisms of cardiovascular toxicity, and the evidence for their clinical use in surveillance during and after anthracycline chemotherapy, trastuzumab and HER2-targeted therapies, vascular endothelial growth factor inhibitors, proteasome inhibitors, immune checkpoint inhibitors, cyclophosphamide and radiotherapy. Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio-oncology biomarker research is discussed.

Standardization of cardiac monitoring practices in patients receiving cardiotoxic cancer therapy at an ambulatory oncology center.

251 Background: A significant number of cancer-directed therapies are associated with cardiotoxicity. This adverse effect is well-established in anthracyclines and anti-HER2 agents. At our ambulatory oncology practice, the recent availability of echocardiograms with strain imaging has prompted an evaluation of current practices for cardiotoxicity monitoring. A review of the electronic health record (EHR) in 2019 found that although our institution maintains high rates of baseline monitoring, follow-up monitoring is not standardized and not consistent between different practices. Methods: A multidisciplinary team was formed to conduct a quality improvement project with the aim of increasing the rate of follow-up monitoring in patients who receive anthracyclines or infusional anti-HER2 agents. A survey of providers identified the potential reasons that follow-up cardiac monitoring was not completed. A Pareto chart showed that lack of familiarity with clinical necessity and appropriate timing were the most common barriers to follow-up monitoring. Our first plan-do-study-act focused on addressing these barriers, and a pilot in breast cancer treatment plans was started. Cardiac monitoring orders were added to curative intent protocols containing doxorubicin, trastuzumab, or pertuzumab. Education was provided to physician and nursing teams regarding utility and timing of cardiotoxicity monitoring. Collaboration with the cardiology group ensured timely access and result turnaround time. Results: An initial review of the EHR was conducted to identify current trends in cardiac monitoring. The review showed that there was an increase in the use of echocardiograms with strain imaging for baseline and follow-up monitoring in our patients. From January to April 2020, there was a total of 102 echocardiogram orders which was a 23% increase compared to the same timeframe in the previous year. The majority (61%) of those echocardiogram orders included strain imaging compared to 8% in the previous year. Review of treatment plan utilization and appropriate timing of cardiac monitoring in breast cancer patients is ongoing. Conclusions: This quality improvement project suggests that efforts to standardize cardiac monitoring practices can be achieved through provider education and workflow modifications. Further long-term review of the EHR will be needed to determine whether the timing of follow-up monitoring is appropriate and to identify what changes to the intervention should be made.

Treatment recommendations in cardio-oncology: where are we?

This article provides an overview of current prevention and treatment options for typical cardiovascular side effects of oncological therapies as well as cardiovascular complications of malignant disease. Focus is put on the prevention and treatment of heart failure under potentially cardiotoxic cancer therapies. In addition, current options for the treatment of common venous thromboembolism in cancer patients will be discussed.

Cardiovascular Toxicity Related to Cancer Treatment: A Pragmatic Approach to the American and European Cardio-Oncology Guidelines.

The considerable progress made in the field of cancer treatment has led to a dramatic improvement in the prognosis of patients with cancer. However, toxicities resulting from these treatments represent a cost that can be harmful to short‐ and long‐term outcomes. Adverse events affecting the cardiovascular system are one of the greatest challenges in the overall management of patients with cancer, as they can compromise the success of the optimal treatment against the tumor. Such adverse events are associated not only with older chemotherapy drugs such as anthracyclines but also with many targeted therapies and immunotherapies. Recognizing this concern, several American and European governing societies in oncology and cardiology have published guidelines on the cardiovascular monitoring of patients receiving potentially cardiotoxic cancer therapies, as well as on the management of cardiovascular toxicities. However, the low level of evidence supporting these guidelines has led to numerous discrepancies, leaving clinicians without a consensus strategy to apply. A cardio‐oncology expert panel from the French Working Group of Cardio‐Oncology has undertaken an ambitious effort to analyze and harmonize the most recent American and European guidelines to propose roadmaps and decision algorithms that would be easy for clinicians to use in their daily practice. In this statement, the experts addressed the cardiovascular monitoring strategies for the cancer drugs associated with the highest risk of cardiovascular toxicities, as well as the management of such toxicities.

Abstract IA19: EHR-based tools and algorithms for managing cardiovascular risk among survivors

Abstract During a clinical encounter, providers are often distracted from having conversations with their patients about their health status and disease risk, given the need to document clinical data in the electronic health record (EHR). The promise of the EHR is that the data entered by providers during a clinical encounter can be used for real-time patient monitoring and shared-decision making, and for secondary use by researchers. EHRs have the ability to bring data to life, to make clinical data relevant for patients and providers, and to allow for a more efficient and patient-centered clinical encounter. To do so effectively, we cannot lose sight of the importance of stakeholder engagement when developing EHR-based tools and algorithms. This talk will describe the process for creating an EHR-based tool for addressing cardiovascular health in the primary care setting. The tool was designed to automatically pull data from a variety of clinical sources, and its use resulted in improvements in cardiovascular health among patients. In the context of this project, we demonstrated 1) use of an evidence-based cardiovascular health algorithm at the point of care; 2) usability of the tool by providers; 3) improvements in cardiovascular health among patients with access to the tool; and 4) informatics can be considered an interventional discipline. The result of this work encouraged us to consider other settings in which this tool could be implemented and evaluated. Since cancer survivors are at increased risk for cardiovascular disease due to having poorer cardiovascular health compared to the general population as well as their potential for receipt of cardiotoxic cancer therapies, we refined the aforementioned tool with the input of oncology providers. This talk will enumerate the lessons learned from the process of adapting an existing EHR tool for use among a new population of patients and providers. Next steps for this work will include modifying existing cardiovascular disease risk scores for validation among cancer survivors. Current algorithms tend to underestimate cardiovascular disease risk among survivors since they take into account traditional cardiovascular risk factors but not factors that represent the unique experience of cancer survivors, including receipt of cancer therapies that may increase the risk for cardiovascular disease in this population. It is critical for algorithms to learn from new evidence and evolve to better predict risk among patients. This talk will outline best practices for the creation of algorithms that can complement EHR-based tools and serve as a resource for shared decision-making for disease prevention and management. Citation Format: Randi E. Foraker. EHR-based tools and algorithms for managing cardiovascular risk among survivors [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr IA19.