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Purpose of Review Radiation is foundational to the treatment of cancer and improves overall survival. Yet, it is important to recognize the potential cardiovascular effects of radiation therapy and how to best minimize or manage them. Screening—both through imaging and with biomarkers—can potentially identify cardiovascular effects early, allowing for prompt initiation of treatment to mitigate late effects. Recent Findings Cardiac echocardiography, magnetic resonance imaging (MRI), computed tomography, and measurements of troponin and natriuretic peptides serve as the initial screening tests of choice for RICD. Novel imaging applications, including positron emission tomography and specific MRI parameters, and biomarker testing, including myeloperoxidase, growth differentiation factor 15, galectin 3, micro-RNA, and metabolomics, hold promise for earlier detection and more specific characterization of RICD. Summary Advances in imaging and novel applications of biomarkers have potential to identify subclinical RICD and may reveal opportunities for early intervention. Further research is needed to elucidate optimal imaging screening modalities, biomarkers, and surveillance strategies.

Aims The accuracy of an apical‐sparing strain pattern on transthoracic echocardiography (TTE) for predicting cardiac amyloidosis (CA) has varied in prior studies depending on the underlying cohort. We sought to evaluate the performance of apical sparing and other TTE strain findings to screen for CA in an unselected population and determine the frequency that patients with echocardiographic concern for CA undergo evaluation for amyloidosis in clinical practice. Methods and results As strain is routinely performed at our institution on all clinical TTEs, we identified all TTEs performed from 2016 through 2019 with reported concern for CA or apical sparing. We determined the performance characteristics for echocardiographic strain findings in discriminating CA including apical sparing, the ejection fraction to global longitudinal strain ratio (EF/GLS), and the septal apical–septal basal ratio (SA/SB); other clinical predictors of confirmed CA; and predictors of patients who underwent complete evaluation for CA. CA was confirmed by endomyocardial biopsy or diagnostic cardiac imaging. A total of 547 TTEs, representing 451 patients, reported concern for CA and had adequate strain for analysis. A total of 111 patients underwent complete evaluation for amyloidosis with 100 patients undergoing complete cardiac evaluation for CA. In those 100 patients, multivariable predictors of confirmed CA were age [odds ratio (OR) 3.37 per 5 years], a visual apical‐sparing pattern (OR 10.85), and left ventricular ejection fraction (LVEF)/GLS > 4.1 (OR 35.37). CA was less likely in those with coronary artery disease (OR 0.04), hypertension (OR 0.18), and increased systolic blood pressure (OR 0.60 per 5 mm Hg increase). SA/SB [area under the curve (AUC) 0.72, 95% confidence interval (CI) 0.60–0.84] and LVEF/GLS (AUC 0.72, 95% CI 0.60–0.84) both had improved discrimination for CA compared with the apical‐sparing ratio (AUC 0.66, 95% CI 0.54–0.79). Many patients with suggestive TTE findings did not receive an evaluation for amyloidosis. Complete evaluation was more likely with Caucasian race (OR 2.1), increased septal thickness (OR 1.4), increased body mass index (OR 1.2), and if the report specifically stated ‘amyloid’ (OR 1.9). Evaluations were less likely in patients with comorbidities. While hypertension reduced the likelihood of evaluating for CA, 34% of patients with CA had hypertension (>130/80 mm Hg) at time of diagnosis. Conclusions In a broad population of patients undergoing TTE, apical sparing on strain imaging increased the likelihood of CA diagnosis but with modest sensitivity and specificity. GLS/EF ratio may be a more reliable tool to screen for CA. The low rate of complete evaluation in patients with concerning TTE findings indicates a strong need for practice improvement and enhanced disease awareness.

Background Stem Cell Transplantation (SCT) is a cornerstone therapy in managing several malignant and benign hematological conditions. Atrial fibrillation/atrial flutter (AF) are commonly encountered in patients receiving SCT. There is a paucity of large-scale data on the prevalence of AF and their effect on outcomes following SCT. Methods The United States National Readmission Database (NRD) was used to identify hospitalized patients who underwent SCT. Baseline demographics, comorbidities, the presence or absence of AF, the indication, and type of SCT were identified using diagnostic and procedural International Classification of Diseases 10th Edition (ICD-10) codes. Patients with AF were compared to those without AF for differences in baseline characteristics, in-hospital mortality, cardiovascular (CV) complications, length and cost of hospitalization, and post-discharge 90-day readmissions and mortality. Results Between January 2016 and September 2020 there were 59,284 weighted admissions for SCT, of which 5797 (9.8%) patients had AF. Patients in the AF group were more likely to be older males with an increased burden of baseline comorbidities compared to the no-AF group ((64 [9] vs. 56 [14] years, p  < 0.001) and (3893 [67%] vs. 30,886 [58%] males, p  < 0.001) respectively). Adjusted for differences in baseline demographics, comorbidities, indication and type of SCT, patients with AF had higher in-hospital mortality (adjusted odds ratio (AOR) 3.65 [3.02–4.41]) and adverse events including cardiac complications [composite of acute heart failure, acute myocardial infarction, cardiogenic shock, and cardiac arrest] (AOR 4.92 [4.22–5.75]), bleeding (AOR 1.32 [1.15–1.53]), and respiratory failure (AOR 3.40 [2.97–3.90]) compared to patients without AF. Additionally, the AF group had longer hospitalizations (21 [16–27] vs. 19 [15–25] days, p  < 0.001) with higher cost ($268,031 [$170,957-$455739] vs. $250,178 [$153,680-$415239], p < 0.001) compared to the no-AF group. Among survivors to hospital discharge, patients with AF also had higher adjusted 90-day all-cause inpatient mortality (adjusted hazard ratio (AHR) 1.54 [1.19–1.99], p  = 0.001), all-cause readmissions (AHR 1.15 [1.07–1.24], p  < 0.001), and CV readmissions (AHR 2.29 [1.85–2.82], p  < 0.001). Conclusions In a large national cohort of SCT recipients, AF were common and independently associated with increased in-hospital mortality and CV adverse events, along with increased 90-day mortality and readmissions among survivors to hospital discharge.

Background Immune checkpoint inhibitor (ICI) myocarditis is associated with high morbidity and mortality. While endomyocardial biopsy (EMB) is considered a gold standard for diagnosis, the sensitivity of EMB is not well defined. Additionally, the pathological features that correlate with the clinical diagnosis of ICI-associated myocarditis remain incompletely understood. Methods We retrospectively identified and reviewed the clinicopathological features of 26 patients with suspected ICI-associated myocarditis based on institutional major and minor criteria. Seventeen of these patients underwent EMB, and the histopathological features were assessed by routine hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for CD68, a macrophage marker. Results Only 2/17 EMBs obtained from patients with suspected ICI myocarditis satisfied the Dallas criteria. Supplemental IHC staining and quantification of CD68 + macrophages identified an additional 7 patients with pathological features of myocardial inflammation (> 50 CD68 + cells/HPF). Macrophage abundance positively correlated with serum Troponin I ( P  = 0.010) and NT-proBNP (N-terminal pro-brain natriuretic peptide, P  = 0.047) concentration. Inclusion of CD68 IHC could have potentially changed the certainty of the diagnosis of ICI-associated myocarditis to definite in 6/17 cases. Conclusions While the Dallas criteria can identify a subset of ICI-associated myocarditis patients, quantification of macrophage abundance may expand the diagnostic role of EMB. Failure to meet the traditional Dallas Criteria should not exclude the diagnosis of myocarditis.

Background Cancer survival rates have been steadily improving in the adolescent and young adult (AYA) population, but survivors are at increased risk for cardiovascular disease (CVD). The cardiotoxic effects of anthracycline therapy have been well studied. However, the cardiovascular toxicity associated with newer therapies, such as the vascular endothelial growth factor (VEGF) inhibitors, is less well understood. Objective This retrospective study of AYA cancer survivors sought to gain insight into their burden of cardiovascular toxicities (CT) following initiation of anthracycline and/or VEGF inhibitor therapy. Methods Data were extracted from electronic medical records over a fourteen-year period at a single institution. Cox proportional hazards regression modeling was used to examine risk factors for CT within each treatment group. Cumulative incidence was calculated with death as a competing risk. Results Of the 1,165 AYA cancer survivors examined, 32%, 22%, and 34% of patients treated with anthracycline, VEGF inhibitor, or both, developed CT. Hypertension was the most common outcome reported. Males were at increased risk for CT following anthracycline therapy (HR: 1.34, 95% CI 1.04–1.73). The cumulative incidence of CT was highest in patients who received both anthracycline and VEGF inhibitor (50% at ten years of follow up). Conclusions CT was common among AYA cancer survivors who received anthracycline and/or VEGF inhibitor therapy. Male sex was an independent risk factor for CT following anthracycline treatment. Further screening and surveillance are warranted to continue understanding the burden of CVD following VEGF inhibitor therapy.

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. At high cumulative dosage, the negative effect of oxaliplatin on the heart becomes evident and is linked to a growing number of clinical reports. The aim of this study was to determine how chronic oxaliplatin treatment causes the changes in energy-related metabolic activity in the heart that leads to cardiotoxicity and heart damage in mice. C57BL/6 male mice were treated with a human equivalent dosage of intraperitoneal oxaliplatin (0 and 10 mg/kg) once a week for eight weeks. During the treatment, mice were followed with ECG, histology and RNA sequencing of the heart. We identified that oxaliplatin induces strong changes in the heart and affects the heart’s energy-related metabolic profile. Histological post-mortem evaluation identified focal myocardial necrosis infiltrated with a small number of associated neutrophils. Accumulated doses of oxaliplatin led to significant changes in gene expression related to energy related metabolic pathways including fatty acid (FA) oxidation and glycolysis leading to the glycolysis switch. Our study can be used for the development of diagnostic methods to detect oxaliplatin-induced cardiotoxicity at an early stage and identifying therapeutic methods to minimize heart failure.

Background Chimeric Antigen Receptor (CAR) T-cell therapy (CAR-T) has emerged as a promising treatment for specific hematological malignancies. While some studies suggest an association between CAR-T and atrial fibrillation (AF), more data are needed on the association of AF with CAR-T outcomes. Methods This retrospective cohort study utilized the National Inpatient Sample (NIS) 2017–2020 to explore in-hospital outcomes in cancer patients with AF while undergoing CAR-T. Comparisons were drawn between patients with and without AF during the hospitalization, assessing various parameters including mortality rates, length of hospital stay, and occurrences of acute heart failure, pulmonary edema, and gastrointestinal (GI) bleeding. Results Of the 236,270 cancer-related hospitalizations, 1,030 cases (0.44%) received CAR-T. The average age of CAR-T recipients was 55.6 years ± 18.1 years, and females constituted 40.5% of the total CAR-T recipients. Of the 1030 patients receiving CAR-T, 97 (9.4%) had an associated diagnosis of AF during their hospitalization. A multivariable logistic regression analysis, adjusted for age, sex, race, comorbidity, and income, revealed that hospitalized cancer patients who underwent CAR-T therapy with AF had increased odds of in-hospital mortality (adjusted odds ratio, aOR: 3.87), acute pulmonary edema (aOR: 3.29), GI bleeding (aOR: 5.46), acute heart failure (aOR: 10.2), and extended hospital stays (Beta coefficient: 0.18) compared to hospitalizations with CAR-T but without AF. Similar results were observed in two sensitivity analyses: one limited to patients with diffuse B-cell lymphoma, and another excluding patients who had sepsis or respiratory failure while receiving CAR-T therapy. Conclusions In cancer patients receiving CAR-T, inpatient AF is independently associated with a higher risk of in-hospital mortality, acute pulmonary edema, gastrointestinal bleeding, acute heart failure, and prolonged hospitalization. Highlights Hypotension and arrhythmias are common adverse cardiovascular events in hospitalized patients receiving Chimeric Antigen Receptor T-cell therapy (CAR-T). Atrial fibrillation was present in close to 10% of patients receiving CAR-T while hospitalized. Atrial fibrillation (at any time) was associated with increased in-hospital mortality, gastrointestinal bleeding, acute heart failure, pulmonary edema, and extended hospitalizations in cancer patients receiving CAR-T.

Background CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, has demonstrated significantly improved overall survival in acute myeloid leukemia (AML) compared with 7 + 3, but its impact on cardiac function remains unclear. In a post hoc analysis of the pivotal clinical trial, we sought to determine the relative cardiotoxicity of CPX-351 vs. 7 + 3 in high-risk AML. Methods We evaluated cardiotoxicity in 102 patients with AML (CPX-351, n = 57; 7 + 3, n = 45) who had normal baseline left ventricular ejection fraction (LVEF) ≥ 53% and at least one post-baseline echocardiographic assessment. Cardiotoxicity was assessed through reported cardiac adverse events (AEs) and core lab assessment of echocardiograph changes in LVEF and/or left ventricular global longitudinal strain (GLS). Results A clinically significant change in LVEF (absolute change from baseline > 10% and LVEF <53%) and GLS (relative change from baseline > 12% and GLS < 18%) was less common with CPX-351 vs. 7 + 3 at follow-up 1 and/or 2 (8.8% vs. 20.0% and 21.1% vs. 44.4%, respectively). No CPX‑351-treated patients evaluated at final follow-up (follow-up 2) had decreased LVEF < 53% at follow-up 2, compared to 17.8% of 7 + 3-treated patients. The frequency of reported cardiac AEs was similar with CPX-351 (40.4%) and 7 + 3 (42.2%); most frequent were tachycardia in CPX-351-treated patients (CPX-351, 21.1%; 7 + 3, 8.9%) and atrial fibrillation/flutter in 7 + 3-treated patients (CPX-351, 7.0%; 7 + 3, 11.1%).  Conclusion In addition to improving overall survival as demonstrated in the pivotal trial, CPX-351 may also be associated with less cardiotoxicity than 7 + 3 in high-risk AML patients.

Background Patients with non-small cell lung cancer (NSCLC) undergoing thoracic radiation are at high cardiovascular risk. Semiquantitative assessment of coronary artery calcification (CAC) on baseline planning non-gated chest computed tomography (CT) scans may help further risk stratify patients. Objectives This study aimed to characterize the association between CAC and major adverse cardiovascular events (MACE; myocardial infarction or stroke) and assess the utility of semiquantitative assessment of CAC. Methods Patients with NSCLC with non-contrast planning chest CT scans were evaluated for CAC. Planning scans were visually graded using the CAC-DRS method, stratifying patients into no, mild, moderate, and severe CAC groups. Demographics, comorbidities, and radiation treatment characteristics were gathered, and CAC groups were assessed for the incidence of MACE after initiation of radiation therapy. Results Out of 137 patients, 39 patients had no CAC, and 98 patients had any CAC (38 with mild CAC, 34 with moderate CAC, and 26 with severe CAC). There was 1 MACE event in the no CAC group and 11 in patients with any CAC. The presence of CAC was associated with increased MACE compared to no CAC ( p  = 0.034). Semiquantitative CAC analysis correlated with formal CAC scoring. Conclusion There is a significantly lower incidence of MACE in patients with no CAC on planning CT compared to patients with higher burdens of CAC. CAC burden is an important risk factor for adverse cardiovascular events in patients with NSCLC undergoing thoracic radiation. Semiquantitative CAC scoring may be a useful proxy when formal CAC scoring is unavailable.