Biomarkers and cardiovascular outcomes in chimeric antigen receptor T-cell therapy recipients.

AIMS: Chimeric antigen receptor T-cell therapy (CAR-T) harnesses a patient's immune system to target cancer. There are sparse existing data characterizing death outcomes after CAR-T-related cardiotoxicity. This study examines the association between CAR-T-related severe cardiovascular events (SCE) and mortality. METHODS AND RESULTS: From a multi-centre registry of 202 patients receiving anti-CD19 CAR-T, covariates including standard baseline cardiovascular and cancer parameters and biomarkers were collected. Severe cardiovascular events were defined as a composite of heart failure, cardiogenic shock, or myocardial infarction. Thirty-three patients experienced SCE, and 108 patients died during a median follow-up of 297 (interquartile range 104-647) days. Those that did and did not die after CAR-T were similar in age, sex, and prior anthracycline use. Those who died had higher peak interleukin (IL)-6 and ferritin levels after CAR-T infusion, and those who experienced SCE had higher peak IL-6, C-reactive protein (CRP), ferritin, and troponin levels. The day-100 and 1-year Kaplan-Meier overall mortality estimates were 18% and 43%, respectively, while the non-relapse mortality (NRM) cumulative incidence rates were 3.5% and 6.7%, respectively. In a Cox model, SCE occurrence following CAR-T was independently associated with increased overall mortality risk [hazard ratio (HR) 2.8, 95% confidence interval (CI) 1.6-4.7] after adjusting for age, cancer type and burden, anthracycline use, cytokine release syndrome grade ≥ 2, pre-existing heart failure, hypertension, and African American ancestry; SCEs were independently associated with increased NRM (HR 3.5, 95% CI 1.4-8.8) after adjusting for cancer burden. CONCLUSION: Chimeric antigen receptor T-cell therapy recipients who experience SCE have higher overall mortality and NRM and higher peak levels of IL-6, CRP, ferritin, and troponin.

Recurrent Coronary Vasospasm: A Case of Kounis Syndrome from Anaphylaxis to Contrast Dye.

Kounis syndrome is characterized by acute coronary syndrome due to coronary vasospasm or thrombosis following exposure to an allergic stimulus. The presentation can be compounded by cardiovascular collapse due to cardiogenic shock from coronary vasospasm and associated vasodilatory shock from anaphylaxis. A high index of suspicion is crucial for prompt initiation of treatment, which focuses on managing the allergic or anaphylactic process. Here we present a case of coronary vasospasm and anaphylactic shock due to contrast dye exposure during percutaneous coronary intervention of an unstable coronary lesion and its associated diagnostic and therapeutic challenges.

Coexistent transthyretin amyloid cardiomyopathy and monoclonal gammopathy: Diagnostic challenges and prognostic implications.

Establishing an accurate diagnosis of amyloid subtype in patients with coexistent cardiac amyloidosis and monoclonal gammopathy is crucial due to treatment and prognostic implications. Here, we discuss a case of coexistent diagnoses of transthyretin amyloid cardiomyopathy and smoldering multiple myeloma, highlighting the challenges associated with the possibility of several disease combinations and the limitations of diagnostic testing. In addition, the importance of clinical clues such as disease course and progression, patient preference, and multidisciplinary collaboration should not be discounted in the diagnostic and management approach of these patients.

Asystole following Regadenoson administration: Review of literature, risk factors and management.

Regadenoson, a selective A2A receptor agonist, is widely used for vasodilator stress myocardial perfusion imaging and has a superior adverse effect profile when compared with other agents. However, with widespread use, there have been several reported cases of Regadenoson induced bradyarrhythmias and even asystole in patients with no known conduction system disease. In this article, we report a case of asystole following Regadenoson administration, evaluate mechanisms and risk factors for Regadenoson induced bradyarrhythmias to better identify patients at risk. We also review the available treatment options and propose recommendations for limiting its risk.

Incremental Value of Global Longitudinal Strain for Predicting Survival in Patients With Advanced AL Amyloidosis.

BACKGROUND: Advanced light-chain (AL) amyloidosis is associated with poor prognosis, with a 5-year survival rate of <25%. Prognostication is based on the revised Mayo (rMayo) staging according to serum cardiac biomarkers. OBJECTIVES: This study sought to determine whether global longitudinal strain (GLS) can provide incremental prognostic value in patients with advanced disease. METHODS: Baseline (pre-treatment) clinical, 2-dimensional echocardiogram with GLS and laboratory data were collected prospectively in 94 patients with newly diagnosed AL amyloidosis with rMayo stage III or IV disease. Overall survival (OS) was defined as time from baseline echocardiography to death. RESULTS: Of 94 patients, 60% (n = 56) had rMayo stage III and 40% (n = 38) had stage IV disease. Ninety of the 94 patients underwent plasma cell-directed therapy. The median left ventricular ejection fraction (LVEF) was 60%, and the median GLS was 13.2%. Of 94 patients, 64 died during follow-up. The median OS was 11.2 months, with an estimated 5-year OS of 21%. In univariable analysis, brain natriuretic peptides, GLS, LVEF, E/e' ratio, and rMayo stage were significantly associated with OS. In Cox regression, GLS provided incremental value over brain natriuretic peptide, troponin, and LVEF for predicting OS. Patients with GLS < -14.2% had a corresponding median OS and 5-year OS rate of 33.2 months and 39%, respectively, versus 7.7 months and 6% for those with GLS ≥ -14.2%. This difference was maintained despite further stratification by rMayo stage. CONCLUSIONS: Baseline GLS is an independent predictor of OS beyond the circulating biomarkers and can identify groups with different survival outcomes beyond the Mayo Staging.

Cardiovascular Complications Associated with Mediastinal Radiation.

PURPOSE OF REVIEW: Radiation-induced heart disease (RIHD) encompasses a broad range of pathologies and is a significant source of morbidity and mortality among cancer survivors. Increased awareness of the early and late consequences of mediastinal radiation has led to the development of strategies for cardiac risk reduction to improve outcomes through active surveillance and early detection of RIHD. This review aims to discuss the current knowledge on the presentation, diagnosis, and management of RIHD. RECENT FINDINGS: Decades' worth of cohort data demonstrates an increased risk of RIHD as cancer survivors age. Additionally, interventional/surgical management of irradiated patients poses unique considerations and can be technically challenging. Used in conjunction with echocardiography, multimodality imaging for morphologic and functional assessment adds complementary value in screening, surveillance, and targeted symptom investigation in patients at risk for RIHD. Furthermore, sensitive imaging parameters and biomarkers have shown potential in detecting subclinical RIHD. Despite the development of techniques which minimize cardiac exposure to ionizing radiation, their effects on the long-term development of RIHD remain to be seen. Due to the morbidity and mortality associated with RIHD, both patients and clinicians should be aware of the lifelong cardiovascular risks of mediastinal radiation exposure. RIHD surveillance should be a consideration throughout the survivorship period. Studies to evaluate the clinical consequences of contemporary radiation therapy strategies aimed at minimizing cardiac doses and the value of novel, more sensitive metrics for the early detection or prognostication of RIHD are ongoing.

Cardiotoxicity of Contemporary Breast Cancer Treatments.

OPINION STATEMENT: Treatment-related cardiotoxicity remains a significant concern for breast cancer patients undergoing cancer treatment and extends into the survivorship period, with adverse cardiovascular (CV) outcomes further compounded by the presence of pre-existing CV disease or traditional CV risk factors. Awareness of the cardiotoxicity profiles of contemporary breast cancer treatments and optimization of CV risk factors are crucial in mitigating cardiotoxicity risk. Assessment of patient- and treatment-specific risk with appropriate CV surveillance is another key component of care. Mismatch between baseline cardiotoxicity risk and intensity of cardiotoxicity surveillance can lead to unnecessary downstream testing, increased healthcare expenditure, and interruption or discontinuation of potentially life-saving treatment. Efforts to identify early imaging and/or circulating biomarkers of cardiotoxicity and develop effective management strategies are needed to optimize the CV and cancer outcomes of breast cancer survivors.

Myocarditis Surveillance in Patients with Advanced Melanoma on Combination Immune Checkpoint Inhibitor Therapy: The Memorial Sloan Kettering Cancer Center Experience.

This letter to the editor describes myocarditis screening among patients undergoing combination immune checkpoint inhibitor therapy, in light of the consensus document from the Checkpoint Inhibitor Safety Working Group.

Assessment of Early Radiation-Induced Changes in Left Ventricular Function by Myocardial Strain Imaging After Breast Radiation Therapy.

BACKGROUND: Radiation therapy (RT)-induced cardiotoxicity is among the concerning sequelae of breast cancer (BCA) treatment, particularly in HER2-positive BCA patients who receive anthracyclines and trastuzumab-based therapy. The aim of this study was to assess for early RT-induced changes in echocardiographic and circulating biomarkers of left ventricular (LV) function and evaluate their association with radiation dose to the heart among patients with HER2-positive BCA treated with contemporary RT. METHODS: A total of 47 women with HER2-positive BCA who were treated with an anthracycline, trastuzumab, and RT to the breast and/or chest wall ± regional lymph nodes were included in this study. Two-dimensional echocardiography with speckle-tracking imaging was performed at baseline (prechemotherapy), prior to and after RT (pre-RT and post-RT), and 6 months post-RT. High-sensitivity troponin I (hsTnI) was measured pre-RT and post-RT. Associations between mean heart dose (MHD) and changes in LV function after RT were examined in multivariable linear regression models. RESULTS: The MHD was 1.8 ± 1.5 Gy for patients receiving left-sided RT (n = 26) and 1.1 ± 1.3 Gy for patients receiving right-sided RT (n = 21). Pre-RT, post-RT, and 6-month post-RT echocardiograms were performed at median (interquartile range) of 49 days (27, 77) before and 54 days (25, 78) and 195 days (175, 226) after RT, respectively. Compared with pre-RT, a minimal decrease in LV ejection fraction was observed post-RT (61% ± 7% vs 59% ± 8%; P = .003) without any significant change in global longitudinal, circumferential, or radial strain or diastolic indices at the post-RT timepoint. Median (interquartile range) concentrations of hsTnI decreased from 5.7 pg/mL (3.0, 8.7) pre-RT to 3.7 pg/mL (2.0, 5.9) post-RT. There was no significant change in systolic or diastolic indices of LV function at 6 months post-RT compared with pre-RT. MHD was not associated with changes in echocardiographic parameters of LV function after RT. CONCLUSIONS: Breast RT using contemporary techniques can be delivered without evidence of early subclinical LV dysfunction or injury as measured by echocardiography and hsTnI in patients treated with anthracyclines and trastuzumab. Future studies should focus on identifying alternative biomarkers to elucidate early RT-induced cardiovascular effects and further characterizing long-term cardiovascular outcomes associated with contemporary breast RT.

Cardiovascular and Metabolic Effects of Androgen-Deprivation Therapy for Prostate Cancer.

Androgen-deprivation therapy (ADT) entails lowering serum testosterone levels to castrate levels and forms a cornerstone of the management of hormone-sensitive advanced prostate cancer; however, the benefit of ADT is partially offset by its detrimental metabolic and cardiovascular adverse effects. ADT decreases insulin sensitivity while promoting dyslipidemia and sarcopenic obesity, which leads to an increased risk of cardiovascular morbidity and potentially mortality. The risk seems to be highest in elderly patients who have had recent cardiovascular events before starting ADT. It is prudent to engage in an individualized risk-benefit discussion and develop a cohesive multidisciplinary management plan to medically optimize and closely observe these patients before and during treatment with ADT.

The long-term prognostic value of highly sensitive cardiac troponin I in patients with acute pulmonary embolism.

BACKGROUND: In patients with acute pulmonary embolism (PE), detectable levels of cardiac troponin I (cTnI) using a highly sensitive assay have been associated with increased in-hospital mortality. We sought to investigate the impact of detectable cTnI on long-term survival following acute PE. HYPOTHESIS: Detectable cTnI levels in patients presenting with acute PE predict increased long-term mortality following hospital discharge. METHODS: In a retrospective cohort study, we analyzed consecutive patients with confirmed acute PE and cTnI assay available from the index hospitalization. The detectable cTnI level was ≥0.012 ng/mL. Patients were classified into low and high clinical risk groups according to the Pulmonary Embolism Severity Index (PESI) at presentation. Subjects were followed for all-cause mortality subsequent to hospital discharge using chart review and Social Security Death Index. RESULTS: A cohort of 289 acute PE patients (mean age 56 years, 51% men), of whom 152 (53%) had a detectable cTnI, was followed for a mean of 3.1 ± 1.8 years after hospital discharge. A total of 71 deaths were observed; 44 (29%) and 27 (20%) in the detectable and undetectable cTnI groups, respectively (P = 0.05). Detectable cTnI was predictive of long-term survival among low-risk (P = 0.009) but not high-risk patients (P = 0.78) who had high mortality rates irrespective of cTnI status. CONCLUSIONS: In patients with acute PE, detectable cTnI is predictive of long-term mortality, particularly among patients who were identified as low risk according to PESI score.