Introduction

The cardio-oncology subspecialty continues to advance at a remarkable pace, with extensive clinical and basic research moving the field forward. In this article, we summarize and highlight the key findings of the abstracts presented at the American Heart Association Scientific Sessions 2020 related to cardio-oncology topics. The abstracts are categorized as follows:

1. Risk Prediction
2. Interventional and Structural Cardiology
3. Primary and Metastatic Cardiovascular Tumors
4. Echocardiography
5. Immune Checkpoint Inhibitors
6. Multimodality Imaging
7. Focus on Epidemiology
8. Pharmacotherapies
9. Basic Science

We hope this will provide an overview of ongoing research in the field and serve as a quick guide to direct the readers to further readings on topics that interest them.

I. Risk Prediction

D-dimer is a Predictor of Cancer Therapeutics-related Cardiac Dysfunction in Patients Treated With Cardiotoxic Chemotherapy
By Masayoshi Oikawa

• The authors evaluated the associations between baseline D-dimer and changes in left ventricular ejection fraction (LVEF) among 202 patients planned for cardiotoxic chemotherapy (anthracyclines, monoclonal antibodies, tyrosine kinase inhibitors, and proteasome inhibitors) in a prospective cohort study with biomarkers and echocardiograms at baseline, 3 months, 6 months, and 12 months. Among the 52 individuals with an elevated D-dimer of >1.5 mcg/ml, there was a time-dependent decrease in LVEF (baseline: 66 ± 5%; 3 months: 63 ± 7%; 6 months: 62 ± 7%; 12 months: 62 ± 6%; p = 0.05), but not in the low D-dimer group. Baseline D-dimer predicted decrease in LVEF of more than 10% with cardiotoxic chemotherapy in multivariable analysis (odds ratio [OR] 1.21; 95% confidence interval [CI], 1.02-1.44; p = 0.025). At a baseline D-dimer level of 1.56 mcg/ml, sensitivity was 50%, specificity was 77%, and area under the curve was 0.679 to predict reduction in LVEF of more than 10%.

The Performance of the American College of Cardiology/American Heart Association 2013 Pooled Cohort Equations in Cancer Survivors
By Elizabeth Polter

• The authors evaluated the calibration and discrimination of the American College of Cardiology/American Heart Association pooled cohort equation in cancer survivors and non-cancer participants in the Atherosclerosis Risk in Communities study who were free of atherosclerotic cardiovascular disease at baseline and did not use statins. Cancer survivors were matched with up to 5 controls by age, race, sex, and study center with follow-up starting within 1 year after the diagnosis date of the cancer survivor (1-17 years after the diagnosis). Discrimination was worse in cancer survivors (c = 0.73) than in non-cancer controls (c = 0.77), and the pooled cohort equation overestimated risk in both cancer survivors and controls.

Assessing a Clinical Risk Score and the Impact of Race in Breast Cancer Patients at Risk of Cardiotoxicity
By Zachary Brumberger

• The authors report an external validation of the Ezaz et al. clinical risk score to predict cardiomyopathy or heart failure (HF) with breast cancer in a retrospective cohort study of 118 patients with stage I-IV breast cancer treated with anthracyclines and/or trastuzumab. The authors compared model performance of the original risk score (age, adjuvant chemotherapy, coronary artery disease, atrial fibrillation [AF], diabetes mellitus, hypertension, and renal failure) and the original score with the addition of race to predict cardiotoxicity (defined as a decline in LVEF of 10% or more to <53%). The c-statistic of the original model was 0.61 (95% CI, 0.49-0.8) and increased to 0.64 (95% CI, 0.49-0.8) with the addition of the race variable (p = 0.56).

External Validation of a Risk Score for Heart Failure in Acute Myeloid Leukemia
By Gregory Cascino

• The authors report an external validation of a risk score to predict hospitalization for HF in a cohort study of 204 consecutive patients treated with anthracyclines for acute myeloid leukemia (mean age 54; 55% male). The prediction model included the following variables: baseline global longitudinal strain (GLS) >-15% (6 points), baseline LVEF <50% (4 points), preexisting cardiovascular disease (4 points), anthracycline dose ≥250 mg/m2 (2 points), and age >60 years (1 point). In total, 44 (21%) experienced a HF hospitalization over a median follow-up of 18 months. The incidence of HF hospitalization by time to event survival analysis was 14% among those at low predicted risk (0-2 points), 31% among those at medium predicted risk (3-9 points), and 54% among those at high predicted risk (10-17 points), p = 0.05.

Phenotyping Risk Profiles for Heart Failure With Preserved and Reduced Ejection Fraction Among Breast Cancer Survivors
By Alexi Vasbinder

• In this retrospective study utilizing the Medical Records Cohort, the authors evaluated the incidence and phenotypes of HF with preserved ejection fraction (HFpEF) among breast cancer survivors. Among 2250 patients, the cumulative incidence was 7.3% for HF with reduced ejection fraction (HFrEF) and 4.6% for HFpEF. The authors found that smoking, obesity, and hypertension were associated with incident HFpEF, whereas anthracycline use was associated with HFrEF but not HFpEF.

Risk of Preserved versus Reduced Ejection Fraction in Women With and Without History of Breast Cancer: The Pathways Heart Study
By Jamal S Rana

• In this retrospective study utilizing a regional health system database, the author evaluated relative incidence of HFrEF and HFpEF in breast cancer survivors compared to matched controls (n = 14,804 breast cancer survivors, n = 74,034 controls). Total cohort breast cancer survivors had an increased risk of HFrEF (hazard ratio [HR] 1.5 [1.18-1.98]) but not of HFpEF. Those receiving chemotherapy and left-sided radiotherapy had increased risk of HFrEF, whereas only those receiving chemotherapy had an increased risk of HFpEF. Endocrine therapy was not found to be associated with risk of development of HF.

Novel Risk Model for Predicting Cardiovascular Outcome in Breast Cancer Survivors
By Do Young Kim

• The authors developed a model for predicting risk of a composite of cardiovascular mortality, myocardial infarction (MI), congestive HF, and transient ischemic attack or stroke among breast cancer survivors utilizing a multi-center cohort (n = 1256) split into derivation and validation groups. The model (CHEMO-RADIAT) used congestive HF, age >60, prior MI or peripheral artery disease, obesity, glomerular filtration rate <60 mL/min, body mass index >29.9, abnormal lipids, diabetes mellitus, left-sided breast irradiation, cumulative anthracycline dose, and prior transient ischemic attack or stroke to generate a score and risk. The time-dependent C-index of the model for the validation group was 0.85 (95% CI, 0.72-0.98), suggesting it may be useful for cardiovascular risk stratification in breast cancer survivors.

Risk Factors of Fluoropyrimidine Induced Cardiotoxicity Among Cancer Patients: A Systematic Review and Meta-analysis
By Chao Li

• In this systematic review and meta-analysis, from 690 abstracts reviewed, 20 studies that reported predictors of cardiotoxicity with 5-fluorouracil, capecitabine, or floxuridine were included. Pre-existing cardiac disease (pooled risk ratio [RR] 3.01; 95% CI, 2.02-4.49), hypertension (pooled RR 1.52; 95% CI, 1.2-1.9), and smoking (pooled RR 2.2; 95% CI, 1.03-4.8) were associated with higher risk of cardiotoxicity among fluoropyrimidine-treated patients. Capecitabine-based combination therapy had a higher risk of cardiotoxicity than capecitabine monotherapy (pooled RR 1.61; 95% CI, 1.01-2.55).

II. Interventional and Structural Cardiology

Effect of Angiovac on Right Ventricular Function Following Removal of Right Atrial Masses in Patients With and Without Malignancy
By Daniel P Obrien

• In this retrospective single-center study, the authors analyzed changes in right ventricular function assessed by echocardiogram before and after right atrial thrombus removal using the AngioVac (AngioDynamics, Inc.; Latham, NY) thrombectomy and compared patients with (n = 10) and without (n = 18) active malignancy. There was no significant difference in mean right ventricular fractional area change before and after AngioVac clot removal in the entire cohort (mean change 1.6%; p = 0.327) or in those with a history of malignancy (mean change -0.8%; p = 0.683). Similarly, there was no significant difference in mean tricuspid annular plane systolic excursion before and after AngioVac in the entire cohort (difference -0.07 mm; p = 0.48) or in those with a history of malignancy.

Mortality in Cancer Patients Undergoing Percutaneous Coronary Intervention: Insights From a Hospital-based Cross-sectional Study
By Anusha Reddy Gaddam

• This cross-sectional study of the Nationwide Inpatient Sample (2012-2014) examined the association between co-morbid cancer and post-percutaneous coronary intervention (PCI) mortality in 1,131,415 adults. They found that co-morbid cancer was associated with increased risk of death post-PCI (adjusted OR 1.88; 95% CI, 1.69-2.09).

Improved Outcomes in Patients With Anthracycline-Induced Cardiomyopathy Undergoing Left Ventricular Assist Devices: 10-Year Longitudinal INTERMACS Study
By Avirup Guha

• The investigators leveraged the Interagency Registry for Mechanically Assisted Circulatory Support to identify adults with anthracycline-induced cardiomyopathy (n = 248) who underwent continuous flow left ventricular assist device (LVAD) implantation and compared their 12-month mortality to that of patients with idiopathic dilated cardiomyopathy and dilated cardiomyopathy. They found no difference in survival rate at 12 months post-LVAD among all 3 groups (80-85%). Patients with anthracycline-induced cardiomyopathy on guideline-directed medical therapy had improved survival compared to those not on guideline-directed medical therapy prior to LVAD implantation (HR 0.44; 95% CI, 0.19-0.99).

Differential Risk Factor Profiles and Management of Acute Coronary Syndrome in Us Women With or Without Active Breast Cancer
By Robert Weidling

• The authors used the US National Readmissions Database (2016-2017) to report on differences in the clinical characteristics, treatment, and outcomes between women with and without breast cancer admitted for acute coronary syndrome. Among 544,698 cases, 2,782 (0.52%) had breast cancer. Women with breast cancer were younger and had a lower prevalence of cardiovascular risk factors. Despite a similar incidence of ST-segment elevation myocardial infarction (STEMI), women with breast cancer were less likely to undergo PCI or coronary artery bypass grafting, or cardiopulmonary resuscitation in case of cardiac arrest. Mortality rates were otherwise similar.

Utilization of Cardiovascular Procedures in Cardiac Amyloidosis
By Benjamin Buck

• The authors queried the National Inpatient Sample database (2003-2014) to determine whether the procedural management of arrhythmias differed in patients with cardiac amyloidosis. They matched 10,519 admissions with HF and cardiac amyloidosis to 52,295 admissions for HF without cardiac amyloidosis. The rates of cardioversion and implantable cardioverter defibrillator implantation were lower in patients with cardiac amyloidosis compared to those without cardiac amyloidosis, and rates of pacemaker implantation were higher. Patients with HF and cardiac amyloidosis had higher in-hospital mortality and longer length of stay compared to those without. Overall hospitalization charges were similar between both groups.

In-hospital Outcomes of Transcatheter Aortic Valve Replacement (TAVR) in Patients With a History of Malignancy
By Jelani Grant

• The authors queried the National Inpatient Sample database to identify patients with cancer who underwent transcatheter aortic valve replacement (TAVR) (n = 4,735) and compared their in-hospital outcomes to patients who underwent TAVR with no known malignancies (n = 19,880). Overall, a history of malignancy conferred decreased odds of in-hospital death (OR 0.69; 95% CI, 0.53-0.90). Otherwise, there were no differences in post-TAVR complications.

Index Admission and Thirty-day Readmission Outcomes of Cancer Patients Presenting With STEMI
By Mohammed Osman

• The authors queried the US National Readmission Database to identify patients with breast, colorectal, lung, and prostate cancer who were admitted for a STEMI (n = 5,956) and compared their 30-day unplanned re-admission rates to those of patients without cancer who suffered from STEMI (n = 17,931) using propensity-score matching. Patients with cancer had more frequent 30-day readmissions (19% vs. 14%) and higher odds of death during first readmission (OR 1.5; 95% CI, 1.2-1.6). Non-cardiac causes represented 38% of re-admission causes.

Stent Type and Outcomes in Patients With Malignancy Undergoing Percutaneous Coronary Intervention
By Muhammad Mohsin Munawar

• In this retrospective study utilizing the Nationwide Inpatient Sample, the authors used propensity-score matching to compare outcomes in patients with cancer who had received bare-metal stents to those who had received drug-eluting stents (DES) (n = 4,313 per group). They found that patients receiving DES had a higher incidence of stent thrombosis (4.26% vs. 3.01%; p = 0.02), as did those with liver and pancreatic cancer. Otherwise, no differences between bare-metal stents and DES were reported for mortality, acute kidney injury, bleeding complications, or length of stay.

III. Primary and Metastatic Cardiovascular Tumors

Malignant Neoplasms of the Heart in the United States
By Neiberg A Lima

• In this retrospective study using the National Inpatient Sample (2002-2014), the authors evaluated incidence and complications of malignant cardiac neoplasms. They found roughly 0.001% of discharges had malignant cardiac neoplasms, with 80% being metastatic tumors involving the heart and 20% being primary cardiac neoplasms. Of the cohort, 10.12% of patients died during admissions. Atrial arrhythmias (19.95%) and stroke (3.42%) were frequent complications.

A National Level Analysis of Long-term Outcomes in Patients With Carotid Body Tumors
By Edgar Aranda-Michel

• In this retrospective study utilizing the National Cancer Database, the authors evaluated the association between treatment modalities and outcomes among patients with carotid body tumors (n = 130). The cohort's 10-year overall survival was 81.5%, with patients undergoing surgery and radiation having the longest survival. Multivariable analysis found that only radiation therapy was associated with survival (HR 0.25; p = 0.008), and metastatic disease was associated with mortality (HR 4.45; p = 0.03).

Benign Cardiac Neoplasms in the United States - A Thirteen-year Review
By Neiberg Lima

• In this retrospective study utilizing the National Inpatient Sample (2002-2014), the authors described the characteristics and trends of benign cardiac neoplasms. They found benign cardiac neoplasms in <0.01% of discharges. Benign cardiac neoplasm-related admissions had a median cost 5 times higher than an average admission. Among these patients, 2.78% died during the admission. Atrial arrhythmias (28.93%), stroke (14.76%), and endocarditis (1.91%) were common complications.

Cardiac Metastasis of Lingual Squamous Cell Carcinoma, A Systematic Review of Presentation, Management, and Outcomes
By Connor C Kerndt

• In this systematic review, the authors characterized cardiac metastases of lingual squamous cell carcinoma. Among the 31 cases found, shortness of breath and chest pain were the most common presenting symptoms. The majority (56.7%) of metastases were right sided with pericardial effusion (21.2%) and right ventricular outflow tract obstruction (18.2%) being the most common echocardiographic findings. Surgical resection was done in 80.6% of patients and radiotherapy in 74.2%. All patients died within 1 year of diagnosis of cardiac metastases.

An Unusual Case of Malignant Hypertension and Stress Cardiomyopathy Originating From the Urinary Bladder
By Anjali Rao

• The authors described a case of an otherwise healthy 39-year-old man who developed malignant hypertension and stress cardiomyopathy during an elective knee surgery. Evaluation found normal coronary arteries, no adrenal mass, normal serum aldosterone levels, and normal renal arteries. Further evaluation found elevated plasma and urine normetanephrines as well as a bladder mass on contrast computed tomography (CT) imaging that was found to be a paraganglioma. The patient also had a succinate dehydrogenase subunit B gene heterozygous pathogenic variant, which is associated with extra-adrenal catecholamine production. Symptoms resolved following mass and lymph node resection.

Long-term Outcomes of Aortic Body Tumors: A Nationwide Study
By Edgar Aranda-Michel

• In this study using the National Cancer Database (2004-2015), the authors retrospectively reviewed all aortic body tumors (n = 87) to compare long-term outcomes between those being treated with surgery versus chemotherapy or radiation. Nearly 20% of patients had metastatic disease at time of diagnosis. Most patients received surgery (54%), with fewer receiving radiation (44.8%) or chemotherapy (20.7%). Median survival was 8.25 years after diagnosis. In multivariable analysis, surgery was independently associated with survival (HR 0.32; p = 0.01). Metastatic disease was associated with higher mortality (HR 8.49; p = 0.001).

IV. Echocardiography

The Utility of Tei Index in Subclinical Cardiotoxicity After Chemotherapy
By Yuki Hamamoto

• The authors describe a retrospective cohort study of 30 individuals with malignant lymphoma or acute myeloid leukemia receiving anthracycline-based chemotherapy from 2010 to 2019, with echocardiograms performed before and after chemotherapy. Patients with a decrement in left ventricular (LV) GLS of 15% or more had greater changes in LV Tei index (0.22 ± 0.10 vs. 0.15 ± 0.03; p = 0.032) and right ventricular Tei index (0.18 ± 0.08 vs. 0.14 ± 0.02; p = 0.014).

Chamber Volumes and Deformation Measures are Abnormal in Chemotherapy-Naïve Cancer Patients: Potential Implications for Surveillance and Definitions of Cardiotoxicity
By Dina Labib

• This study compared cardiac magnetic resonance parameters between patients with cancer with planned anthracycline-based chemotherapy (n = 394) and healthy controls (n = 102) with mean age 54 ± 13 years, 78% female. Prior to initiation of chemotherapy, patients with cancer had smaller LV chamber sizes (67 ± 12 vs. 78 ± 12 ml/m2; p < 0.001), higher LV mass (45 ± 8 vs. 41 ± 7 g/m2; p = 0.008), and higher radial, circumferential, and maximal principal strain amplitude. Baseline LVEF and GLS were similar between patients with cancer and non-cancer controls.

Determination of Etiology of Left Ventricular Ejection Fracture Decline in Chemotherapy Related Cardiac Dysfunction
By Jay B. Patel

• In this retrospective, single-center study of patients referred to a cardio-oncology clinic for chemotherapy-related cardiac dysfunction meeting American Society of Echocardiography and European Association of Cardiovascular Imaging criteria of a 10% or greater drop in LVEF from the lower limit of normal (n = 616), the authors sought to identify the etiology of LV dysfunction. After adjudication, they found 31% of events due to isolated chemotherapy, 24% related to hospitalizations, 13% multifactorial, and 11% misdiagnosed. The authors suggest that isolated chemotherapy related LV dysfunction is uncommon.

Echocardiographic Predictors of Symptomatic Cardiotoxicity Among Patients Undergoing Chemotherapy: Systematic Review and Meta-analysis
By Muhammad Umer Siddiqui

• In this systematic review and meta-analysis through March 2019, 8 studies that reported imaging predictors symptomatic cardiotoxicity (symptomatic HF, decline in LVEF to <50%, and cardiac death) in patients undergoing chemotherapy were included. Six studies analyzed the association between LVEF and symptomatic cardiotoxicity with a significant association (HR 1.27; 95% CI, 1.02-1.57). Two studies that analyzed GLS reported an association between GLS and systematic cardiotoxicity in patients undergoing chemotherapy (HR 1.46; 95% CI, 1.34-1.58).

Pericardial Effusion in Children After Bone Marrow Transplant
By Niti Dham

• In this retrospective, single-center study of pediatric patients who underwent bone marrow transplantation, the authors examined the incidence and predictors of moderate to large pericardial effusion post-transplant. Of 180 patients, 15 developed symptomatic pericardial effusions requiring intervention. The authors found that the time to pericardial effusion correlated with LV diameter, septal E', and E/E' measured pre-transplant.

V. Immune Checkpoint Inhibitors

Natural History of Immune Checkpoint Inhibitor Associated Myocarditis With Preserved Ejection Fraction
By Joseph Nowatzke

• The authors described the natural history of immune checkpoint inhibitor-associated myocarditis with initial LVEF above 50% at the time of presentation utilizing a multicenter case registry. Among 83 cases of definite or probable myocarditis presenting with an LVEF above 50%, 90-day mortality was high (37%), and 15 developed worsening LVEF to <50% during the hospitalization. Compared to those with normal LVEF throughout the hospitalization, those who developed worsening LVEF had a lower systolic blood pressure at baseline (111 vs. 129 mmHg; p = 0.01), higher peak troponin elevations during the hospitalization (432 vs. 41; p = 0.021), higher rates of fulminant myocarditis (73% vs. 26%; p < 0.01), higher in-hospital mortality (46% vs. 17%; p = 0.015); and higher 90-day mortality (72% vs. 29%; p = 0.007).

Retrospective Analysis of Cardiovascular Events With the Use of Immune Checkpoint Inhibitors
By Tushar Tarun

• The authors described a retrospective analysis of 150 patients treated with immune checkpoint inhibitors at a single center. Six percent of patients developed new onset HF, 1.3% experienced an MI, 2% had newly diagnosed AF, and 0.6% were diagnosed with fulminant myocarditis. Patients who developed cardiac events were more likely to have a history of cardiac disease compared to those who did not develop cardiac events (p < 0.05).

Risk Stratification and Real World Incidence of Cardiac Toxicity With Immune Checkpoint Inhibitors
By Jian Hu

• The authors reported a retrospective analysis of patients treated with immune checkpoint inhibitors for lung cancer (50%), melanoma (15%), or other malignancies (34%) at a single center (n = 344). Cardiac risk factors were common. Pre-immune checkpoint inhibitor cardiac testing included electrocardiogram (ECG) in 60% and echocardiogram in 37%. Fewer than 20% were seen by cardiology prior to treatment despite 81% of individuals having 2 or more atherosclerotic cardiovascular disease risk factors. Cardiac events after immune checkpoint inhibitor initiation occurred in 12% of patients and were more common in those with atherosclerotic cardiovascular disease risk factors or a history of AF.

Gender Differences in the Incidence of Adverse Cardiovascular Events in Cancer Patients Treated With Immune Checkpoint Inhibitors
By Sheharyar Minhas

• The authors used the MarketScan Databases to compare cardiovascular adverse events by gender in patients who were treated with immune checkpoint inhibitors (nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and ipilimumab) from 2011 to 2018. Cardiovascular events occurred in 3,804 (23%) of the 16,574 individuals in the cohort. There was no difference in cardiovascular events by gender in those less than 60 years of age. In the subset of the cohort older than 60 years, male gender was associated with higher rates of cardiovascular events (HR 1.18).

Electrocardiographic Manifestations of Immune Checkpoint Inhibitor Associated Myocarditis
By Sheharyar Minhas

• The authors reviewed ECGs of 130 cases of immune checkpoint inhibitor myocarditis and compared the baseline ECGs when available and with ECGs from 50 patients with heart transplant acute cellular rejection. Compared with baseline ECGs, immune checkpoint inhibitor myocarditis patient presenting ECGs were more likely to have a prolonged QRS (26% vs. 13%; p = 0.008), ST and T wave changes (50% vs. 24%; p = 0.004), and premature ventricular contractions (16% vs. 6%). Compared with ECGs from transplant patients with acute cellular rejection, presenting ECGs from immune checkpoint inhibitor myocarditis patients showed more premature ventricular contractions (16% versus 2%). Pathologic Q waves, QRS prolongation, left bundle branch block, and supraventricular arrhythmias on presenting ECGs of immune checkpoint inhibitor myocarditis were significantly associated with the composite endpoint of life-threatening arrhythmia or myocarditis-related death.

Pre-existing Autoimmune Disease and the Risk for Cardiovascular and Non-cardiovascular Immune Mediated Adverse Events With Immune Checkpoint Inhibitors
By Charlotte Lee

• In this retrospective study of 2,845 individuals treated with immune checkpoint inhibitors, patients with a history of autoimmune diagnoses prior to cancer diagnoses were matched 1:2 to controls without a history of autoimmune disease. The primary endpoint was a composite of cardiovascular events that included MI, PCI, coronary artery bypass grafting, stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, and myocarditis. Out of 2,845, 93 (3.3%) had a history of autoimmune disease. Patients with a history of autoimmune disease were more likely to be older and have a history of coronary artery disease, HF, chronic kidney disease, hypertension, and diabetes. There were 12 cardiovascular events in the subgroup with prior autoimmune disease over a median follow-up of 300 days. Compared to those without a history of autoimmune disease, cardiovascular events occurred in 13% versus 9.1% (p = 0.41). There was a significantly increased rate of pneumonitis (14% vs. 4%; p < 0.001) and skin toxicity (16% vs. 0%; p < 0.001) in those with a history of autoimmune disease compared to those without.

In Patients Treated With Immune Checkpoint Inhibitors, Myocarditis is Infrequent Compared With Other Cardiovascular Events
By Judith A Hsia

• The authors reported a retrospective analysis of adults treated with immune checkpoint inhibitors from 2011 to 2019 for melanoma (40%), lung cancer (31%), and other cancers (29%) at a single center (n = 1813). Cardiac risk factors were common (48% with hypertension, 16% with diabetes, and 57% were current or former smokers), and 16% had a prior coronary artery revascularization. After immune checkpoint inhibitor initiation, MI occurred in 3%, stroke in 4%, and myocarditis in 0.5%.

VI. Multimodality Imaging

Myocardial Damage Assessed by Late Gadolinium Enhancement on Cardiovascular Magnetic Resonance Imaging in Cancer Patients Treated With Anthracyclines and/or Trastuzumab
By Kalpit Modi

• In a cohort of 298 consecutive cancer patients with suspected cardiotoxicity from anthracyclines and/or trastuzumab, 31 (10.4%) had late gadolinium enhancement (LGE) varying in extent and locations. LGE was present in an ischemic pattern in 20 of 31 (65%), and there was an alternative explanation for the non-ischemic LGE in 7 of 11 (64%). In an age-matched cohort of 100 patients with cancer who received neither anthracyclines nor trastuzumab, LGE was present in 27% while the extent and proportion of LGE were not different.

Coronary and Aortic Calcification Are Common in Men With Recurrent Prostate Cancer Undergoing PET/CT Imaging
By Avira Som

• Coronary and aortic calcifications were qualitatively assessed in a retrospective cohort of 211 patients (median age 69 years) who underwent positron emission tomography (PET)/CT scans for recurrent prostate cancer. Of the cohort, 21% had a clinical diagnosis of coronary artery disease, and cardiac risk factors were common: 70% hypertension, 65% hyperlipidemia, 20% diabetes, and 47% current or former smoking. A total of 147 patients (70%) had coronary artery calcification, and 90% had aortic calcifications on CT imaging.

Vascular Calcification is Associated With Major Adverse Cardiovascular Events and Mortality in Men With Recurrent Prostate Cancer Undergoing PET/CT Imaging
By Preet Ayoub Shaikh

• Coronary and aortic calcifications were qualitatively assessed in a retrospective cohort of 211 patients (median age 69 years) who underwent PET/CT scans for recurrent prostate cancer. Major adverse cardiovascular events (MI, stroke, coronary or peripheral revascularization, HF hospitalization, or all cause-mortality) occurred in 8 (4%) over a median follow-up of 16.5 months. Age, hypertension (RR 1.3), hyperlipidemia (RR 1.4), diabetes mellitus (RR 1.3), severe coronary calcification (RR 6.1; 95% CI, 1.6-23.2), and severe thoracic aortic calcification (RR 9.9, 95% CI, 2.0-47.6) were associated with increased risk of major adverse cardiovascular events.

Coronary Calcification is Associated With Prior GnRH Agonist Therapy in Men With Recurrent Prostate Cancer Undergoing PET/CT Imaging
By Avira Som

• In this respective cohort study of 186 men with prostate cancer who underwent PET/CT scans, coronary artery calcium was qualitatively assessed on non-gated CT scans. The association between prior gonadotropin-releasing hormone agonists and presence or absence of coronary calcium on CT scan was reported as a stratified OR. Men who had been treated with prior gonadotropin-releasing hormone agonist therapy were older (median age 71.4 vs. 68.4). In unadjusted analyses, men with coronary calcifications were more likely to have received prior gonadotropin-releasing hormone agonist therapy (OR 3.0; 95% CI, 1.2-7.1).

CT Pulmonary Angiography Yield in Patients With an Active Malignancy: Lack of Non-invasive Screening
By Olivia Lamping

• In this retrospective study of 2,226 patients undergoing CT pulmonary artery angiography studies in an emergency department setting, the authors found no significant difference in pulmonary embolism diagnosis between patients with and without a history of cancer (8.5% vs. 7.4%; p = 0.47). Patients with cancer history had higher clinical prediction scores for pulmonary embolism (Wells score, PERC rule, Geneva score) and were less likely to receive pre-CT scan D-dimer, troponin, or chest X-ray testing.

VII. Epidemiology

Cardiovascular Disease in Head Neck Squamous Cell Carcinoma Patients - A Case-Control Study Using Electronic Medical Records Data
By Amrita Mukherjee

• In this single-center, case-control retrospective study, the authors assessed the association of cardiac risk factors and outcomes among patients with head and neck squamous cell carcinoma (n = 2,391). Ischemic disease and/or HF occurred in 16.1% of patients. In multivariable analysis, hypertension, diabetes, and hyperlipidemia were associated with cardiovascular outcomes. Advanced stage oropharyngeal cancer was associated with lower odds of the outcomes (OR 0.38; 95% CI, 0.30-0.92), whereas stage was not associated with cardiovascular outcomes among patients with oral cavity cancers.

Epidemiological Profile of Cardiovascular Risk Factors and Outcomes in Patients With Solid Organ and Haematological Malignancies
By David Chandrakumar

• In this single-center retrospective study, the authors compared the baseline cardiovascular risk profiles and development of a composite endpoint of new HF and/or arrhythmias in patients undergoing chemotherapy for solid organ malignancies (n = 435) versus hematologic malignancies (n = 545). Patients with solid organ malignancies had more cardiac risk factors at baseline, but the incidence of the composite endpoint was not significantly different between the 2 groups (9.4% vs. 9.0%; p = 0.45).

Incidence, Risk Factors, and Outcomes of Atrial Fibrillation After Blood and/or Marrow Transplant
By Daniel Pinkhas

• In this retrospective, single-center cohort study of patients undergoing bone marrow transplantation (n = 1,159), the authors examined the incidence and predictors of AF. They found that 5.3% of patients developed AF within the first 90 days post-transplant. Risk factors included prior history of AF and radiation therapy. The development of AF was independently associated with an increased risk of mortality at 90 days (HR 7.6; 95% CI, 3.5-16.5).

Differences of Cancer Types in Hospital Mortality in Patients With Venous Thromboembolism
By Okushi Yuichiro

• The authors used propensity-score matching to compare the clinical characteristics of patients with (n = 12,418) and without (n = 15,829) cancer who suffered from venous thromboembolism using the Japanese Registry of All Cardiac and Vascular Datasets. They found that patients with cancer had higher in-hospital mortality compared to those without cancer (9.5% vs. 3.8%). Pancreatic, biliary, and liver cancer were associated with the highest mortality.

Cancer Diagnosis Following Bleeding in Patients With Atrial Fibrillation Undergoing Anticoagulation Therapy
By Maria Cespon-Fernandez

• The authors used the CardioCHUVI-AF_75 registry to determine whether bleeding in patients with AF on oral anticoagulation was associated with a higher risk of incident cancer diagnosis. The registry included all patients ≥75 years with AF in the region of Galicia, Spain (n = 8,753). They identified 2,171 (24.8%) patients who experienced bleeding and 479 (5.5%) with a new diagnosis of cancer at a mean follow-up of 3 years. New bleeding was associated with a threefold higher risk of incident cancer diagnosis. Notably, gastrointestinal bleeding, genitourinary bleeding, and bronchopulmonary bleeding were associated with a 13-fold, 18-fold, and 15-fold increase in the risk of incident cancer, respectively.

Obesity is Associated With Incident Cancer in the Community
By Elizabeth E Liu

• The authors used the Framingham Heart Study and Prevention of Renal and Vascular End-Stage Disease Study to evaluate the effect of obesity on future cancer. Body mass index ≥30 kg/m2 was associated with increased hazard of future gastrointestinal cancer (HR 1.3; 95% CI, 1.05-1.6) and gynecologic cancers (HR 1.6; 95% CI, 1.08-2.45) after adjusting for age, sex, diabetes, systolic blood pressure, hypertension treatment, smoking status, and cholesterol ratio. Visceral adiposity was defined using CT scans and was associated with incident cancer (HR 1.2; 95% CI, 1.03-1.31).

Association Between Life's Simple 7 and Cardiovascular Disease in Cancer Patients Compared to Noncancer Controls in the Aric Cohort
By Evelyn J Song

• The authors used the Atherosclerosis Risk in Communities Study cohort to compare Life's Simple 7 metrics among individuals with cancer (n = 2,950) and non-cancer controls matched on age, sex, race, study center, and time of cancer diagnosis (n = 5,900). Compared with matched non-cancer controls, those who developed cancer were less likely to have an ideal Life's Simple 7 score (18% vs. 23%; p < 0.0001) and less likely to have an ideal level of smoking, body mass index, glucose control, physical activity level, and diet. Compared to inadequate, an ideal Life's Simple 7 score was associated with lower cardiovascular disease events (coronary heart disease, HF, or stroke) in persons with (HR 0.37; 95% CI, 0.26-0.52) and without cancer (HR 0.40; 95% CI, 0.32-0.50), with no interaction between Life's Simple 7 score and cancer status (p = 0.59).

Racial/Ethnic Differences in Cardiac Surveillance Evaluation for Cancer Patients Treated With Anthracycline-based Chemotherapy: The Oneflorida Clinical Research Consortium
By Nam K. Nguyen

• The authors evaluated echocardiography and cardiac biomarker assessment in a cohort of anthracycline-treated adults in the OneFlorida Consortium (n = 2,758). Among the entire cohort of anthracycline-treated patients, 43% had a baseline echocardiogram, 18% had an echocardiogram at 6 months, and 21% had one at 12 months. B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide monitoring rates were low: 5.3% at baseline, 6.5% at 6 months, and 8.7% at 12 months. Compared to White patients, Black patients (OR 0.56; 95% CI, 0.45-0.70) and Hispanic patients (OR 0.52, 95% CI, 0.43-0.64) were less likely to receive an echocardiogram at baseline. Hispanic patients had lower echocardiographic assessment at 6 months and 12 months, suggesting racial and ethnic disparities in surveillance.

Association Between Breast Cancer and Cardiac Autonomic Function as Measured by Heart Rate Variability in the Women's Health Initiative
By Mary Branch

• In this retrospective study utilizing the Women's Health Initiative cohort, the authors compared heart rate variability between patients with incident breast cancer and controls as a marker of autonomic dysfunction. They found that heart rate variability as measured by serial ECGs was significantly lower at 3 years (p = 0.0002) and 6 years (p = 0.03) among those diagnosed with breast cancer compared to controls, suggestive of autonomic dysfunction.

Quantitative Assessment of Cardiovascular Autonomic Impairment in Cancer Survivors: A Single Center Experience
By Benjamin Noor

• In this retrospective, single-center study of cancer survivors referred for suspected autonomic dysfunction (n = 24), the authors sought to characterize patient diagnoses after positive autonomic reflex testing (n = 22). Of these, half were diagnosed with orthostatic hypotension (50%), inappropriate sinus tachycardia (20.8%), and postural orthostatic tachycardia syndrome (12.5%). Of these patients, more than half had received vinca alkaloids, alkylating agents, and/or anthracyclines. The majority had symptomatic improvement following therapy.

VIII. Pharmacotherapies

Dexrazoxane Role in the Prevention of Anthracycline Cardiotoxicity in Sarcoma Patients - A Meta-analysis
By Jose Pedro Sousa

• In this systematic review and meta-analysis that included 11 studies (1,574 patients, 679 treated with dexrazoxane), 5 were prospective studies, and 9 studies were conducted in children. The primary endpoint was a composite of HF, ventricular arrhythmias, and LV systolic deterioration (73 events). The cumulative doxorubicin dose was higher in the dexrazoxane arm. Nevertheless, dexrazoxane was associated with reduced odds of the primary endpoint (OR 0.37; 95% CI, 0.2-0.71), with numerically decreased acute HF events (OR 0.15; 95% CI, 0.02-1.09) and significantly halted LV systolic deterioration (mean difference 5.25%; 95% CI, 1.98-8.53). Primary cancer outcome and the risk of secondary malignancy did not differ between the 2 arms (OR 1; 95% CI, 0.47-2.15 vs. OR 0.98; 95% CI, 0.4-2.5).

Cardiovascular Adverse Events Associated With Androgen Receptor-targeted Therapy Used in the Treatment of Prostate Cancer
By Bishesh Shrestha

• This was a meta-analysis of 13 randomized phase III clinical trials that included one of the anti-androgens (abiraterone, enzalutamide, apalutamide, and darolutamide) for the treatment of prostate cancer. In those treated with abiraterone (n = 3,492), clinical trial reporting identified hypertension in 16%, AF in 1%, and other cardiovascular events (including MI, supraventricular tachycardia, ventricular tachycardia, and HF) in 9.5%. In enzalutamide individuals (n = 4,094), hypertension was reported in 10.6%, ischemic heart disease in 1.9%, and AF in 0.4%. With apalutamide (n = 1,327), hypertension was reported in 22%. With darolutamide (n = 954), hypertension was reported in 6.6%, coronary artery disease in 3.2%, and HF in 1.9%.

Cardiovascular Safety Profile of Gonadotropin Releasing Hormone (GnRH) Antagonist Compared to GnRH Agonist Among Patients With Prostate Cancer: A Meta-Analysis
By Courtney Campbell

• The authors performed a systematic review to identify randomized studies from 2000 to 2020 that compared gonadotrophin-releasing hormone antagonists to gonadotrophin-releasing hormone agonists in patients with prostate cancer. Seven studies that included 3,298 individuals were identified. When compared with gonadotrophin-releasing hormone agonists, the incidence of major adverse cardiovascular events (RR 0.52; 95% CI, 0.35-0.76) and coronary artery disease (RR 0.46; 95% CI, 0.27-0.77) were lower in men receiving gonadotrophin-releasing hormone antagonists.

Identification of Cardiovascular Adverse Effects Associated With Midostaurin - A WHO Pharmacovigilance Database Analysis
By Arrush Choudhary

• The authors used VigiBase, the World Health Organization's global database of individual case safety reports to identify cardiovascular events associated with midostaurin, an oral kinase inhibitor approved for the treatment of acute myeloid leukemia and systemic mastocytosis. Midostaurin was associated with higher reporting of QT prolongation, HF, AF, and pericardial diseases, with information component analysis suggesting significance at the 95% credibility interval and most of the adverse events occurring within 50 days of midostaurin initiation. Fatalities occurred in 8.7%, 43%, and 42% of cases of QT prolongation, HF, and AF, respectively.

Beta Blocker Use and Peri-operative Outcomes in Cancer Patients Receiving Immunotherapy
By Ohad Oren

• In this retrospective, single-center study, the authors reviewed the association between peri-operative beta-blocker use and mortality of 233 patients with malignancy undergoing surgery within 90 days of receiving immune checkpoint inhibitors. The most common procedure was skin resection (32%) followed by wound repair (20.2%). The 30-day mortality was 10.3%. Pre-operative use of beta-blockers was associated with a lower risk of death within 30 days from surgery (OR 0.34; 95% CI, 0.13-0.87; p = 0.024).

Direct Oral Anticoagulants versus Low Molecular Weight Heparin for Treatment of Venous Thromboembolism in Patients With Cancer: Updated Meta-analysis of Randomized Controlled Trials
By Kirtipal Singh Bhatia

• In this meta-analysis of 4 trials comparing direct oral anticoagulants to low-molecular weight heparin for the treatment of cancer-associated venous thromboembolism (n = 2,894), the authors found that recurrent venous thromboembolism at 6 months was lower in the direct oral anticoagulant group compared to those treated with low-molecular weight heparin (5.2% vs. 8.2%), with no significant difference in major bleeding or all-cause morality and low heterogeneity (I2 = 30%) between studies.

Cardiovascular Toxicities of Cyclin Dependent Kinase (cdk) 4/6 Inhibitors in Metastatic Breast Cancer Patients
By Michael George Fradley

• In this retrospective study using the OneFlorida Data Trust, the authors identified patients without cardiovascular disease who had received CDK4/6 inhibitors between 2012 and 2018 (n = 1,035) and assessed the incidence of cardiotoxicity. Cardiotoxicity occurred in 174 (16.8%), arrhythmias in 61 (5.89%), and incident hypertension in 97 (9.37%). Mortality was reportedly higher in those who experienced cardiotoxicity compared to those who did not.

IX. Basic Science

Disease Modeling Doxorubicin-induced Cardiotoxicity Using Human Induced Pluripotent Stem Cells-derived Cardiomyocytes From Healthy and Type 2 Diabetic Patients
By Tarun Pant

• Human-induced pluripotent stem cell-derived cardiomyocytes from individuals with type 2 diabetes and individuals without diabetes were exposed to different concentrations of doxorubicin. Human-induced pluripotent stem cell-derived cardiomyocytes from individuals with diabetes had increased lactate dehydrogenase release, decreased cellular viability (assessed using alamarBlue [Thermo Fisher Scientific Inc.; Waltham, MA] assay), and decreased troponin T and troponin I mRNA expression.

Lactate Dehydrogenase B and Pyruvate Oxidation Associated With Carfilzomib-Related Cardiotoxicity in Multiple Myeloma Patients: A Multi-omics Study
By Marwa Tantawy

• This pilot study applied global metabolomic profiling to plasma samples of 13 patients with multiple myeloma treated with carfilzomib (7 with symptomatic HF and 6 with no HF). Proteomic data identified higher levels lactate dehydrogenase B (fold change = 8.2; p = 0.01) in patients with HF compared with those without HF. Metabolomics analysis showed lower plasma pyruvate (fold change = 0.16; p = 0.004) and higher abundance of lactate (fold change = 2.4; p = 0.0001) in patients with HF. miRNA analysis suggested lactate dehydrogenase B regulated by miR-139 was downregulated in patients with HF (fold change = 0.03). These analyses suggest that pyruvate fermentation to lactate (pyruvate oxidation) is associated with carfilzomib-related HF and that miR-139 may regulate this pathway.

Novel Dual mTOR Inhibitor/AMPK Activator Mitigates Doxorubicin Cardiotoxicity and Potentiates Its Chemotherapeutic Efficacy Against Triple Negative Breast Cancer
By Anindita Das

• Using an experimental mouse model, the authors evaluated the efficacy of NM922 (NovoMedix; San Diego, CA), a novel mTOR inhibitor/AMPK activator in isolation and in combination with doxorubicin against breast cancer and to evaluate its cardiotoxicity. NM922 alone and in conjunction with doxorubicin reduced tumor growth compared to control, with higher doses of NM922 alone and in conjunction with doxorubicin being more efficacious than doxorubicin alone. Doxorubicin-induced LV dysfunction was attenuated with high-dose NM922 treatment. The authors suggest NM922 may have a role as being both efficacious against breast cancer and in reducing doxorubicin cardiotoxicity.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Arrhythmias and Clinical EP, Cardiac Surgery, Cardio-Oncology, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Pericardial Disease, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Stable Ischemic Heart Disease, Anticoagulation Management and ACS, Anticoagulation Management and Atrial Fibrillation, Anticoagulation Management and Venothromboembolism, Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Cardiac Surgery and SIHD, Acute Heart Failure, Mechanical Circulatory Support, Interventions and ACS, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Echocardiography/Ultrasound, Magnetic Resonance Imaging, Nuclear Imaging, Hypertension, Chronic Angina

Keywords: AHA Annual Scientific Sessions, AHA20, Cardio-oncology, Cardiotoxicity, Cardiovascular Diseases, Gadolinium, Cross-Sectional Studies, Transcatheter Aortic Valve Replacement, AMP-Activated Protein Kinases, Contrast Media, Dexrazoxane, Anthracyclines, Receptors, Androgen, Heparin, Low-Molecular-Weight, Carotid Body Tumor, Venous Thromboembolism, Atrial Fibrillation, Heart-Assist Devices, ST Elevation Myocardial Infarction, Triple Negative Breast Neoplasms, American Heart Association, Ventricular Function, Right, Myocarditis, Takotsubo Cardiomyopathy, Pericardial Effusion, Acute Coronary Syndrome, Myocytes, Cardiac, Hospital Mortality, Case-Control Studies, Case-Control Studies, Multiple Myeloma, Patient Readmission, Heart Rate, Pharmacovigilance, Retrospective Studies, Hypertension, Malignant, Induced Pluripotent Stem Cells, Electronic Health Records, Urinary Bladder, Aortic Bodies, Bone Marrow, Stroke Volume, Risk Factors, Heart Failure, Magnetic Resonance Imaging, Cine, Magnetic Resonance Imaging, Immunotherapy, Echocardiography, Anticoagulants, Carcinoma, Squamous Cell, Sarcoma, Percutaneous Coronary Intervention, Doxorubicin, Leukemia, Myeloid, Acute, Amyloidosis, Gonadotropin-Releasing Hormone, Vascular Calcification, Obesity, Hospitals, Angiography, Stents, Diabetes Mellitus, Type 2, Risk Assessment, Cyclin-Dependent Kinases, Autoimmune Diseases, Pyruvates, World Health Organization, TOR Serine-Threonine Kinases

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