Equity in Cardio-Oncology Care and Research: A Scientific Statement From the American Heart Association.

Advances in cancer therapeutics have revolutionized survival outcomes in patients with cancer. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Recent studies have uncovered excess risks of these cardiotoxic events, especially in traditionally underrepresented populations. Despite advances in strategies to limit the risks of cardiovascular events among cancer survivors, relatively limited guidance is available to address the rapidly growing problem of disparate cardiotoxic risks among women and underrepresented patient populations. Previously decentralized and sporadic evaluations have led to a lack of consensus on the definitions, investigation, and potential optimal strategies to address disparate cardiotoxicity in contemporary cancer care (eg, with immunotherapy, biologic, or cytotoxic therapies) settings. This scientific statement aims to define the current state of evidence for disparate cardiotoxicity while proposing uniform and novel methodological approaches to inform the identification and mitigation of disparate cardio-oncology outcomes in future clinical trials, registries, and daily clinical care settings. We also propose an evidence-based integrated approach to identify and mitigate disparities in the routine clinical setting. This consensus scientific statement summarizes and clarifies available evidence while providing guidance on addressing inequities in the era of emerging anticancer therapies.

Cardiovascular Imaging in Contemporary Cardio-Oncology: A Scientific Statement From the American Heart Association.

Advances in cancer therapeutics have led to dramatic improvements in survival, now inclusive of nearly 20 million patients and rising. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Advances in cardiovascular imaging have solidified the critical role for robust methods for detecting, monitoring, and prognosticating cardiac risk among patients with cancer. However, decentralized evaluations have led to a lack of consensus on the optimal uses of imaging in contemporary cancer treatment (eg, immunotherapy, targeted, or biological therapy) settings. Similarly, available isolated preclinical and clinical studies have provided incomplete insights into the effectiveness of multiple modalities for cardiovascular imaging in cancer care. The aims of this scientific statement are to define the current state of evidence for cardiovascular imaging in the cancer treatment and survivorship settings and to propose novel methodological approaches to inform the optimal application of cardiovascular imaging in future clinical trials and registries. We also propose an evidence-based integrated approach to the use of cardiovascular imaging in routine clinical settings. This scientific statement summarizes and clarifies available evidence while providing guidance on the optimal uses of multimodality cardiovascular imaging in the era of emerging anticancer therapies.

Ventricular arrhythmias and sudden death events following acalabrutinib initiation.

Acalabrutinib, a next-generation Bruton's tyrosine kinase inhibitor (BTKi), associates with dramatic efficacy against B-cell malignancies. Recently, unexplained ventricular arrhythmias (VAs) with next-generation BTKi-therapy have been reported. Yet, whether acalabrutinib associates with VAs in long-term follow-up is unknown. Leveraging a large-cohort of 290 consecutive B-cell malignancy patients treated with acalabrutinib from 2014 to 2020, we assessed the incidence of VAs. The primary-endpoint was incident VA development (ventricular fibrillation, ventricular tachycardia, and symptomatic premature ventricular contractions). Probability-scores were assessed to determine likelihood of acalabrutinib-association. Incident rates as function of time-on-therapy were calculated. Weighted average observed incidence rates were compared with expected population rates using relative-risks. Absolute excess risk (AER) for acalabrutinib-associated VAs was estimated. Over 1063 person-years of follow-up, there were 8 cases of incident-VAs, including 6 in those without coronary disease (CAD) or heart failure (HF) and 1 sudden-death; median time-to-event 14.9 months. Among those without prior ibrutinib-use, CAD, or HF, the weighted average incidence was 394 per 100 000 person years compared with a reported incidence of 48.1 among similar-aged non-BTKi-treated subjects (relative risk, 8.2; P < .001; AER, 346). Outside of age, no cardiac or electrocardiographic variables associated with VA development. Collectively, these data suggest VAs may be a class-effect of BTKi therapies.

Targeting OCT3 attenuates doxorubicin-induced cardiac injury.

Doxorubicin is a commonly used anticancer agent that can cause debilitating and irreversible cardiac injury. The initiating mechanisms contributing to this side effect remain unknown, and current preventative strategies offer only modest protection. Using stem-cell-derived cardiomyocytes from patients receiving doxorubicin, we probed the transcriptomic landscape of solute carriers and identified organic cation transporter 3 (OCT3) (SLC22A3) as a critical transporter regulating the cardiac accumulation of doxorubicin. Functional validation studies in heterologous overexpression models confirmed that doxorubicin is transported into cardiomyocytes by OCT3 and that deficiency of OCT3 protected mice from acute and chronic doxorubicin-related changes in cardiovascular function and genetic pathways associated with cardiac damage. To provide proof-of-principle and demonstrate translational relevance of this transport mechanism, we identified several pharmacological inhibitors of OCT3, including nilotinib, and found that pharmacological targeting of OCT3 can also preserve cardiovascular function following treatment with doxorubicin without affecting its plasma levels or antitumor effects in multiple models of leukemia and breast cancer. Finally, we identified a previously unrecognized, OCT3-dependent pathway of doxorubicin-induced cardiotoxicity that results in a downstream signaling cascade involving the calcium-binding proteins S100A8 and S100A9. These collective findings not only shed light on the etiology of doxorubicin-induced cardiotoxicity, but also are of potential translational relevance and provide a rationale for the implementation of a targeted intervention strategy to prevent this debilitating side effect.

Vascular Inflammation, Cancer, and Cardiovascular Diseases.

PURPOSE OF REVIEW: Cancer and cardiovascular disease are among the leading causes of morbidity and mortality in the USA. Cancer and cardiovascular disease have inflammatory underpinnings that have been associated with both the development and progression of these disease states. RECENT FINDINGS: Inflammatory signaling has been found to be a critical event in both cardiovascular disease and cancer formation and progression. Further, many chemotherapeutic agents potentiate inflammation exacerbating existing cardiovascular disease or leading to its presence. The exact mechanisms of these interactions remain poorly understood. The proinflammatory milieu observed in both cancer and cardiovascular disease likely plays an important role in the development and potentiation of both conditions. Further evaluation of this relationship will be critical in the development of new diagnostic and therapeutic modalities.

Cardiovascular Toxicities Associated with Tyrosine Kinase Inhibitors.

PURPOSE OF REVIEW: To provide a detailed overview of cardiovascular adverse events associated with the use of tyrosine kinase inhibitors across different tumor types. RECENT FINDINGS: Despite an undeniable survival advantage of tyrosine kinase inhibitors (TKIs) in patients with hematologic or solid malignancies, the accompanying off-target cardiovascular adverse events can be life-threatening. In patients with B cell malignancies, the use of Bruton tyrosine kinase inhibitors has been associated with atrial and ventricular arrhythmias, as well as hypertension. Cardiovascular toxic profiles are heterogeneous among the several approved breakpoint cluster region (BCR)-ABL TKIS. Notably, imatinib might be cardioprotective. Vascular endothelial growth factor TKIs, constituting the central axis in the treatment of several solid tumors, including renal cell carcinoma and hepatocellular carcinoma, have strongly been associated with hypertension and arterial ischemic events. Epidermal growth factor TKIs as therapy for advanced non-small cell lung cancer (NSCLC) have been reported to be infrequently associated with heart failure and QT prolongation. While tyrosine kinase inhibitors have been demonstrated to increase overall survival across different types of cancers, special consideration should be given to cardiovascular toxicities. High-risk patients can be identified by undergoing a comprehensive workup at baseline.

Cardiotoxicity of Anti-Cancer Radiation Therapy: a Focus on Heart Failure.

PURPOSE OF REVIEW: As the percentage of patients achieving long-term survival following treatment of their cancer grows, it is increasingly important to understand the long-term toxicities of cancer-directed treatment. In this review, we highlight the recent findings regarding radiation-induced cardiotoxicity across multiple disease sites, with a particular focus on heart failure. RECENT FINDINGS: Despite its relative lack of study historically, radiation-induced heart failure has now recently been implicated in several studies of breast cancer, lung cancer, esophageal cancer, and lymphoma as a non-trivial potential consequence of thoracic radiotherapy. Data regarding specific cardiac dosimetric endpoints relevant to cardiotoxicity continue to accumulate. Radiation-induced heart failure is a rare but significant toxicity of thoracic radiotherapy, that is likely underreported. Important areas for future focus include understanding the interplay between thoracic radiotherapy and concurrent cardiotoxic systemic therapy as well as development of potential mitigation strategies and novel therapeutics.

Incidence, risk factors, and mortality of atrial fibrillation in breast cancer: a SEER-Medicare analysis.

AIMS: The national incidence, risk factors, and associated mortality of atrial fibrillation (AF) in breast cancer patients are unknown. METHODS AND RESULTS: Using the Surveillance, Epidemiology, and End Results-Medicare-linked database, we identified females, ≥66 years old, with a new primary diagnosis of breast cancer from 2007 through 2014. These patients were individually matched 1:1 to Medicare enrolees without cancer, and each pair was followed for 1 year to identify a primary outcome of AF. Cumulative incidence was calculated using competing risk survival statistics. Following this, identifying risk factors of AF among breast cancer patients was conducted using the adjusted Cox proportional hazards model. Finally, Kaplan-Meier methods and adjusted Cox proportional hazards modelling were performed to estimate mortality in breast cancer patients with incident and prevalent AF. This study included 85 423 breast cancer patients. Among these 9425 (11.0%) had AF diagnosis prior to the breast cancer diagnosis. New-onset AF was diagnosed in 2993 (3.9%) patients in a 1-year period after the breast cancer diagnosis [incidence 3.3%, 95% confidence interval (CI) 3.0-3.5%, at 1 year; higher rate in the first 60 days (0.6%/month)]. Comparatively, the incidence of new-onset AF in matched non-cancer controls was 1.8% (95% CI 1.6-2.0%). Apart from traditional demographic and cardiovascular risk factors, breast cancer stage was strongly associated with the development of AF [American Joint Committee on Cancer (AJCC) Stage II/III/IV vs. I: adjusted hazard ratio (aHR) 1.51/2.63/4.21, respectively]. New-onset AF after breast cancer diagnosis (aHR 3.00) is associated with increased 1-year cardiovascular mortality. CONCLUSION: AF incidence is significantly higher in women after a breast cancer diagnosis. Higher breast cancer stages at diagnos are significantly associated with a higher risk of AF. New-onset AF in the new breast cancer diagnosis setting increases 1-year cardiovascular mortality but not breast cancer-related mortality. KEY QUESTION: What are the incidence, prevalence, risk factors and mortality outcomes of atrial fibrillation (AF) in a multi-ethnic representative United States cohort of breast cancer patients? KEY FINDING: Annual incidence for AF is 3.9% with highest rate in the first 60 days after cancer diagnosis. Cancer stage and grade are the strongest risk factors for AF. New onset AF after breast cancer increases all-cause and cardiovascular mortality. TAKE HOME MESSAGE: AF incidence is higher in breast cancer patients and is associated with later stage and grade at diagnosis of breast cancer. Involving cardio-oncology in those who develop AF after cancer diagnosis should be encouraged to improve their cardiovascular and overall prognosis.

Cardiovascular Disease, Cancer, and Multimorbidity Interactions: Clinical Implications.

BACKGROUND: With the aging population, the frequency of cardiovascular disease (CVD), cancer, and other morbid conditions is increasing dramatically. In addition, one disease may affect the other leading to a vicious cycle. SUMMARY: With aging, the function of organs and systems of the human body declines including the immune system resulting in a diminished response to various pathogens and a chronic inflammatory process; these changes, in addition to other risk factors, contribute to the development of multiple morbid conditions including CVD and cancer. Multimorbidity in the elderly has become the rule rather than the exception today. Further, this association between CVD and cancer, at least partially, is explained by both diseases sharing common risk factors and from accelerated vascular aging due to cancer and its associated therapies. Multiple studies have shown that the incidence of cancer is much higher in patients with CVD compared to the general population. These associations among CVD, cancer, and their connection to systems of the human body provide an opportunity for novel therapies. Development of new drugs should be addressed to focus on multiple systems and not just only to one disease. Further, collecting information from registries and processing large amounts of data using artificial intelligence may assist the clinician when treating an individual patient in the future. KEY MESSAGES: As the aging population increases, CVD, cancer, and multimorbidity will continue to constitute a major health problem in the years to come. The physician who is taking care of such a patient, in addition to knowledge, requires clinical wisdom, clinical experience, and common sense in order to apply the continuous evolving knowledge to the individual patient.

Length of stay and cost of care associated with admissions for atrial fibrillation among patients with cancer.

BACKGROUND: The aim of this study is to assess the burden of AF-related hospitalizations inclusive of inflation-adjusted cost-of-care and length-of-stay (LOS) among cancer patients and the impact of direct current cardioversion (DCCV) on these outcomes. METHODS: Using the National Inpatient Sample (NIS), patients hospitalized with either a primary or secondary diagnosis of AF and comorbid cancer were identified and both cost of hospitalization and LOS were evaluated for each group. Subgroup analyses were performed for specific cancer types (breast, lung, colon, prostate and lymphoma), and those receiving DCCV. RESULTS: The prevalence of co-morbid AF was 8.2 million (16%) and 35.5 million (10%) among those with vs. those without cancer, respectively (odds ratio = 1.6, 95% confidence interval = 1.5-1.7; P < 0.001). Over time, both primary and prevalent AF admissions among those with comorbid cancer increased from 1.1% and 12.3% in 2003 to 1.5% and 21% in 2015, respectively. The total cost of hospitalization increased 94.4% among those with AF and comorbid cancer compared to 23.9% among those without cancer. Among the subgroup of patients with comorbid cancer and primary admission for AF undergoing DCCV, length of stay (2.7 vs. 2.2 days; P < 0.001, model 1) and cost of care ($7,093 vs. 6,152; P < 0.001) were both significantly higher. CONCLUSIONS: AF related admissions are increasing for all populations especially amongst those patients with a comorbid diagnosis of cancer, including all cancer subtypes evaluated. Among those patients who underwent DCCV, cancer patients had longer length of stay and increased health care costs.

Cardiovascular Imaging in Cardio-Oncology: The Role of Echocardiography and Cardiac MRI in Modern Cardio-Oncology.

Cardiovascular (CV) events are an increasingly common limitation of effective anticancer therapy. Over the last decade imaging has become essential to patients receiving contemporary cancer therapy. Herein we discuss the current state of CV imaging in cardio-oncology. We also provide a practical apparatus for the use of imaging in everyday cardiovascular care of oncology patients to improve outcomes for those at risk for cardiotoxicity, or with established cardiovascular disease. Finally, we consider future directions in the field given the wave of new anticancer therapies.

Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS).

PURPOSE: The comparative cardiovascular risk profiles of available hormone therapies for the treatment of prostate cancer is not known. MATERIALS AND METHODS: We queried the U.S. Food and Drug Administration Adverse Event Reporting System, a retrospective, pharmacovigilance database, for cardiovascular adverse event reports in men with prostate cancer receiving gonadotropin releasing hormone (GnRH) agonists, GnRH antagonists, androgen receptor antagonists, and/or androgen synthesis inhibitors from January 2000 to April 2020. RESULTS: Cardiovascular adverse events accounted for 6,231 reports (12.6%) on hormone monotherapy and 1,793 reports (26.1%) on combination therapy. Arterial vascular events were reported most commonly, followed by arrhythmias, heart failure, and venous thromboembolism. Compared to GnRH agonists, GnRH antagonists were associated with fewer cardiovascular adverse event reports as monotherapy (adjusted reporting odds ratio [ROR]=0.70 [95% CI 0.59-0.84], p <0.001) and as combination therapy (ROR=0.47 [0.34-0.67], p <0.0001), driven by reductions in arterial vascular events. Second generation androgen receptor antagonists and abiraterone were associated with more reports of hypertension requiring hospitalization (ROR=1.21 [1.03-1.41], p=0.02 and ROR=1.19 [1.01-1.40], p=0.03, respectively), and more heart failure events when used in combination with GnRH antagonists (ROR=2.79 [1.30-6.01], p=0.009 and ROR=2.57 [1.12-5.86], p=0.03). CONCLUSIONS: In this retrospective analysis of a pharmacovigilance database, arterial vascular events were the most commonly reported cardiovascular adverse events in men on hormone therapy for prostate cancer. GnRH antagonists were associated with fewer reports of overall cardiovascular events and arterial vascular events than GnRH agonists. Additional study is needed to identify optimal strategies to reduce cardiovascular morbidity among men with prostate cancer receiving hormone therapy.

Hypertension and incident cardiovascular events following ibrutinib initiation.

Ibrutinib is associated with dramatic efficacy against B-cell malignancies. Yet, it has been linked with potentially limiting cardiotoxicity, including emerging reports of profound hypertension (HTN). The long-term incidence, severity, and impact of HTN development with ibrutinib are unknown. Therefore, in 562 consecutive patients treated with ibrutinib for B-cell malignancies from 2009 through 2016, we assessed the new/incident or worsened HTN (systolic blood pressure [BP] cutoff, 130 mm Hg). Observed incident HTN rates were compared with Framingham-heart-predicted incident HTN rates. We also evaluated the relationship of HTN to the development of other major adverse cardiovascular events (MACEs), including arrhythmia, myocardial infarction, stroke, heart failure, and cardiovascular death. Further, we assessed the effects of different antihypertensive classes on ibrutinib-related HTN. Overall, 78.3% of ibrutinib users developed new or worsened HTN over a median of 30 months. New HTN developed in 71.6% of ibrutinib users, with a time to 50% cumulative incidence of 4.2 months. Among those without preceding HTN, 17.7% developed high-grade HTN (BP >160/100 mm Hg). In multivariate regression, new or worsened HTN was associated with increased MACEs (hazard ratio [HR], 2.17; 95% confidence interval [CI], 1.08-4.38). No single antihypertensive class was associated with prevention or control of ibrutinib-related HTN. However, antihypertensive initiation was associated with a lower risk of a MACE (HR, 0.40; 95% CI, 0.24-0.66). Collectively, these data suggest that ibrutinib is associated with a substantial increase in the incidence and severity of HTN, and that HTN development carries a higher risk of subsequent cardiotoxic events.

Cardiovascular Toxicities of Androgen Deprivation Therapy.

OPINION STATEMENT: Prostate cancer is the second leading cause of cancer death in men, and cardiovascular disease is the number one cause of death in patients with prostate cancer. Androgen deprivation therapy, the cornerstone of prostate cancer treatment, has been associated with adverse cardiovascular events. Emerging data supports decreased cardiovascular risk of gonadotropin releasing hormone (GnRH) antagonists compared to agonists. Ongoing clinical trials are assessing the relative safety of different modalities of androgen deprivation therapy. Racial disparities in cardiovascular outcomes in prostate cancer patients are starting to be explored. An intriguing inquiry connects androgen deprivation therapy with reduced risk of COVID-19 infection susceptibility and severity. Recognition of the cardiotoxicity of androgen deprivation therapy and aggressive risk factor modification are crucial for optimal patient care.

Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis.

Chimeric antigen receptor (CAR) T cell therapy is approved in the United States for the treatment of acute lymphocytic leukemia and aggressive B cell lymphomas. Multiple cardiovascular adverse events (CVEs) associated with CAR-Ts have been observed in small studies, but no large-scale studies exist. Leveraging the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), we identified all reported adverse events (AEs) associated with CAR-T therapy (tisagenlecleucel and axicabtagene ciloleucel) from 2017 to 2019. Reports with missing age and sex were excluded. CVEs were classified into arrhythmias, heart failure (HF), myocardial infarction (MI), and other CVEs. Logistic regression and hierarchical clustering were used to identify factors associated with CVEs. A total of 996 reported AEs were observed (39.1% associated with tisagenlecleucel and 60% with axicabtagene ciloleucel). Of all patients experiencing AEs, the median age was 54 (interquartile range, 21 to 65) years; 38.9% were females. In total, 19.7% (196) of all AEs reported to the FDA were CVEs. The most common CVEs were arrhythmia (77.6%), followed by HF (14.3%) and MI (0.5%). In adjusted analysis a positive association was observed between those presenting with CVE with neurotoxicity (odds ratio, 1.76; 95% confidence interval, 1.20 to 2.60; P = .004). Additionally, when both CVE and cytokine release syndrome (CRS) are present, neurotoxicity is the most common noncardiac AE, which clusters with them (Jaccard similarity: 73.1). The mortality rate was 21.1% overall but 30.1% for those reporting CVEs. In FAERS, reported CVEs with CAR-T are associated with high reported mortality. The development of either CRS or neurotoxicity should prompt vigilance for cardiovascular events.

Contemporary Understandings of Cardiovascular Disease After Cancer Radiotherapy: a Focus on Ischemic Heart Disease.

PURPOSE OF REVIEW: Radiation-induced cardiovascular disease, including coronary artery disease, is a well-known sequela of radiation therapy and represents a significant source of morbidity and mortality for cancer survivors. This review examines current literature and guidelines to care for this growing population of cancer survivors. RECENT FINDINGS: The development of radiation-induced ischemic heart disease following radiation can lead even to early cardiotoxicities, inclusive of coronary artery disease, which limit cancer treatment outcomes. These coronary lesions tend to be diffuse, complex, and proximal. Early detection with multimodality imaging and targeted intervention is required to minimize these risks. Early awareness, detection, and management of radiation-induced cardiovascular disease are paramount as cancer survivorship continues to grow.

Readmission after inferior vena cava filter placement for acute venous thromboembolism in the United States: Impact of a cancer diagnosis.

BACKGROUND: Inferior vena cava filter (IVCF) use is common after a venous thromboembolic event (VTE). Cancer is associated with higher rates of VTEs and is also seen in a significant proportion of patients requiring IVCF. As hospital readmissions remain a frequently scrutinized metric, we sought to evaluate the impact of cancer on hospital-readmission rates and in-hospital outcomes among patients with VTEs who received an IVCF. METHODS: Leveraging the 2013 to 2014 Nationwide Readmission Database, we identified adult patients presenting with a VTE in the United States and evaluated 30-day readmission rates and readmission in-hospital outcomes postindex-admission. Multivariable logistic regression was used to identify factors associated with readmission after an index-procedure, including traditional and nontraditional cardiovascular risk factors, as well as hospital-level characteristics. RESULTS: Among the 619 241 patients presenting with a VTE at index-admission, 11.2% of patients received IVCF on index-admission, of which 30.9% had cancer. The 30-day readmission rate amongst IVCF recipients was 15.8% (N = 10 927), and 19.9% amongst those with cancer compared to 13.9% in patients without cancer (P < .001). Moreover, cancer patients had longer lengths of stay in the hospital (4.5 ± 0.2 vs 4.0 ± 0.1 days; P = .02), higher cost of care ($10 900 ± 308 vs $9242 ± 206; P = .007), but no difference in mortality (8.3% vs 6.3%; P = .70) during readmission compared to noncancer patients. CONCLUSION: Readmission after IVCF placement is common. In patients readmitted after an IVCF implantation, those with cancer have longer hospital stays and higher costs of care. However, in-hospital mortality is similar to those without cancer.

The effect of catheter-directed thrombolytic use on readmission rates and in-hospital outcomes among cancer patients with venous thromboembolism in the United States.

BACKGROUND: Cancer inducing a hypercoagulable state, venous thromboembolism (VTE) remains a leading cause of morbidity and mortality globally. We assessed the impacts of cancer on the likelihood for readmission after a VTE-targeted procedure. METHODS: We created a new cohort using discharge-level data from all hospitalizations from State Inpatient Databases of geographically dispersed participating states (18-27 states). RESULTS: In those presenting with VTE during index-admission (619 241), 2.4% patients underwent catheter directed thrombolytic therapy (CDL) on index admission and among those 20.3% had cancer. Moreover, the 30-day readmission rate amongst CDL recipients (10 776 overall) was 14.3% in those with cancer compared to 8.8% in those with no cancer history (P < .0001). Additionally, in-hospital mortality (5.7% vs 1.1%; P = 0.009) and cost-of-care ($11 014 ± 914 vs $10 520 ± 534; P = .04) was significantly higher in cancer compared to noncancer. CONCLUSION: The use of CDL does not appear to reduce the risk of returning for a VTE-related admission in cancer.

Personalized Approach to Cancer Treatment-Related Cardiomyopathy.

PURPOSE OF REVIEW: Cancer treatment-related cardiotoxicity (CTRC) represents a significant cause of morbidity and mortality worldwide. The purpose of our review is to summarize the epidemiology, natural history, and pathophysiology of cardiotoxicity-related to cancer treatment. We also summarize appropriate screening, surveillance, and management of CTRC. While cardiotoxicity is characteristically associated with anthracyclines, HER2-B antagonists, and radiation therapy (XRT), there is growing recognition of toxicity with immune checkpoint inhibitors (ICI), tyrosine kinase inhibitors, and proteasome inhibitors. RECENT FINDINGS: Patients at risk for cardiotoxicity should be screened based on available guidelines, generally with serial echocardiograms. The role of medical heart failure (HF) therapies is controversial in patients with asymptomatic left ventricular dysfunction but may be considered in some instances. Once symptomatic HF has developed, treatment should be in accordance with ACC/AHA guidelines. The goal in caring for patients receiving cancer treatment is to optimize cardiac function and prevent interruptions in potentially lifesaving cancer treatment.

Acoustic Mist Ionization Platform for Direct and Contactless Ultrahigh-Throughput Mass Spectrometry Analysis of Liquid Samples.

Mass spectrometry (MS) has many advantages as a quantitative detection technology for applications within drug discovery. However, current methods of liquid sample introduction to a detector are slow and limit the use of mass spectrometry for kinetic and high-throughput applications. We present the development of an acoustic mist ionization (AMI) interface capable of contactless nanoliter-scale "infusion" of up to three individual samples per second into the mass detector. Installing simple plate handling automation allowed us to reach a throughput of 100 000 samples per day on a single mass spectrometer. We applied AMI-MS to identify inhibitors of a human histone deacetylase from AstraZeneca's collection of 2 million small molecules and measured their half-maximal inhibitory concentration. The speed, sensitivity, simplicity, robustness, and consumption of nanoliter volumes of sample suggest that this technology will have a major impact across many areas of basic and applied research.