High Baseline High-Sensitivity Cardiac Troponin T Concentrations and Risk of Index Acute Myocardial Infarction.

OBJECTIVE: To evaluate the diagnostic performance of the previously recommended baseline high-sensitivity cardiac troponin T (hs-cTnT) thresholds of 52 and 100 ng/L in identifying patients at high risk of acute myocardial infarction (AMI). PATIENTS AND METHODS: This study compared the positive predictive value (PPV) for index AMI of these high-risk hs-cTnT thresholds in adult patients in the emergency department undergoing hs-cTnT measurement. RESULTS: The adjudicated MAyo Southwest Wisconsin 5th Gen Troponin T ImplementatiON cohort included 2053 patients, with 157 (7.6%) who received a diagnosis of AMI. The hs-cTnT concentrations of greater than 52 and greater than 100 ng/L resulted in PPVs of 41% (95% CI, 35%-48%) and 57% (95% CI, 48%-66%). In patients with chest discomfort, hs-cTnT concentrations greater than 52 ng/L resulted in a PPV of 66% (95% CI, 56%-76%) and hs-cTnT concentrations greater than 100 ng/L resulted in a PPV of 77% (95% CI, 65%-87%). The CV Data Mart Biomarker cohort included 143,709 patients, and 3003 (2.1%) received a diagnosis of AMI. Baseline hs-cTnT concentrations greater than 52 and greater than 100 ng/L resulted in PPVs of 12% (95% CI, 11%-12%) and 17% (95% CI, 17%-19%), respectively. In patients with chest pain and hs-cTnT concentrations greater than 52 ng/L, the PPV for MI was 17% (95% CI, 15%-18%) and in those with concentrations greater than 100 ng/L, only 22% (95% CI, 19%-25%). CONCLUSION: In unselected patients undergoing hs-cTnT measurement, the hs-cTnT thresholds of greater than 52 and greater than 100 ng/L provide suboptimal performance for identifying high-risk patients. In patients with chest discomfort, an hs-cTnT concentration of greater than 100 ng/L, but not the European Society of Cardiology-recommended threshold of greater than 52 ng/L, provides an acceptable performance but should be used only with other clinical features.

A Pilot Study on Novel Use of Color Doppler Imaging for Navigation of Wiring in Coronary Interventions.

OBJECTIVE: To test the Doppler guide wire (DGW) for navigation of the wire positioning by color Doppler ultrasound in the setting of percutaneous coronary intervention (PCI). METHODS: An acoustically active DGW was tested in a water tank before its in vivo use. A waveform generator was connected to the DGW, and a transducer scanned the DGW to visualize a Doppler shift signal between the vibrating piezoelectric crystal located at the DGW tip and Doppler signal from the transducer as a distinct, instantaneous color marker. An intracoronary injection was tested in four male domestic pigs using an open-chest setting. A Judkins left coronary guiding catheter was inserted into the ascending aorta via the right carotid artery under B-mode ultrasound guidance. The DGW with an infusion catheter or over-the-wire (OTW) balloon catheter was inserted into the guiding catheter. The color marker instantaneously defined the DGW tip and navigated the catheter into the left anterior descending artery (LAD). RESULTS: The tip of the DGW was visualized within the guiding catheter by a distinct color marker and helped to engage the guiding catheter to the left main orifice. The DGW with an infusion or OTW balloon catheter was inserted into the LAD. We confirmed that the catheter was positioned in the proximal LAD by the colored territory perfused by an injected indigo carmine solution. CONCLUSION: Ultrasound navigation using acoustically active DGW was feasible. Our pilot study introduces a new concept of color Doppler-navigated wire positioning in the coronary artery in the setting of PCI.

Cardiovascular toxicities associated with bispecific T-cell engager therapy.

BACKGROUND: Bispecific T-cell engagers (BTEs) are novel agents used to treat hematological malignancies. Early trials were underpowered to define cardiovascular adverse events (CVAE) and no large-scale studies systematically examined the CVAEs associated with BTEs. METHODS: Leveraging the US Food and Drug Administration's Adverse Event Reporting System-(FAERS), we identified the relative frequency of CVAEs after initiation of five BTE products approved by the Food and Drug Administration between 2014 and 2023 for the treatment of hematological malignancies. Adjusted reporting ORs (aROR) were used to identify disproportionate reporting of CVAEs with BTEs compared with background rates in the database. Fatality rates and risk ratios (RRs) for each adverse event (AE) were calculated. RESULTS: From 3668 BTE-related cases reported to FAERS, 747 (20.4%) involved CVAEs. BTEs as a class were associated with fatal CVAEs (aROR 1.29 (95% CI 1.12 to 1.50)), an association mainly driven by teclistamab (aROR 2.44 (95% CI 1.65 to 3.60)). Teclistamab was also associated with a disproportionate risk of myocarditis (aROR 25.70 (95% CI 9.54 to 69.23)) and shock (aROR 3.63 (95% CI 2.30 to 5.74)), whereas blinatumomab was associated with a disproportionate risk of disseminated intravascular coagulation (aROR 3.02 (95% CI 1.98 to 4.60)) and hypotension (aROR 1.59 (95% CI 1.25 to 2.03)). CVAEs were more fatal compared with non-CVAEs (31.1% vs 17.4%; RR 1.76 (95% CI 1.54 to 2.03)). Most CVAEs (83.3%) did not overlap with cytokine release syndrome. CONCLUSION: In the first postmarketing surveillance study of BTEs, CVAEs were involved in approximately one in five AE reports and carried a significant mortality risk.

Mediators of Black-White inequities in cardiovascular mortality among survivors of 18 cancers in the USA.

BACKGROUND: This study aims to quantify Black-White inequities in cardiovascular disease (CVD) mortality among US survivors of 18 adult-onset cancers and the extent to which these inequities are explained by differences in socio-economic and clinical factors. METHODS: Survivors of cancers diagnosed at ages 20-64 years during 2007-16 were identified from 17 Surveillance, Epidemiology and End Results registries. Associations between race and CVD mortality were examined using proportional hazards models. Mediation analyses were performed to quantify the contributions of potential mediators, including socio-economic [health insurance, neighbourhood socio-economic status (nSES), rurality] and clinical (stage, surgery, chemotherapy, radiotherapy) factors. RESULTS: Among 904 995 survivors, 10 701 CVD deaths occurred (median follow-up, 43 months). Black survivors were more likely than White survivors to die from CVD for all 18 cancers with hazard ratios ranging from 1.30 (95% CI = 1.15-1.47) for lung cancer to 4.04 for brain cancer (95% CI = 2.79-5.83). The total percentage mediations (indirect effects) ranged from 24.8% for brain (95% CI=-5.2-59.6%) to 99.8% for lung (95% CI = 61.0-167%) cancers. Neighbourhood SES was identified as the strongest mediator for 14 cancers with percentage mediations varying from 25.0% for kidney cancer (95% CI = 14.1-36.3%) to 63.5% for lung cancer (95% CI = 36.5-108.7%). Insurance ranked second for 12 cancers with percentage mediations ranging from 12.3% for leukaemia (95% CI = 0.7-46.7%) to 31.3% for thyroid cancer (95% CI = 10.4-82.7%). CONCLUSIONS: Insurance and nSES explained substantial proportions of the excess CVD mortality among Black survivors. Mitigating the effects of unequal access to care and differing opportunities for healthy living among neighbourhoods could substantially reduce racial inequities in CVD mortality among cancer survivors.

SGLT2 Inhibitor Use and Risk of Clinical Events in Patients With Cancer Therapy-Related Cardiac Dysfunction.

BACKGROUND: Certain antineoplastic therapies are associated with an increased risk of cardiomyopathy and heart failure (HF). Sodium glucose co-transporter 2 (SGLT2) inhibitors improve outcomes in patients with HF. OBJECTIVES: This study aims to examine the efficacy of SGLT2 inhibitors in patients with cancer therapy-related cardiac dysfunction (CTRCD) or HF. METHODS: The authors conducted a retrospective cohort analysis of deidentified, aggregate patient data from the TriNetX research network. Patients aged ≥18 years with a history of type 2 diabetes mellitus, cancer, and exposure to potentially cardiotoxic antineoplastic therapies, with a subsequent diagnosis of cardiomyopathy or HF between January 1, 2013, and April 30, 2020, were identified. Patients with ischemic heart disease were excluded. Patients receiving guideline-directed medical therapy were divided into 2 groups based on SGLT2 inhibitor use. After propensity score matching, odds ratios (ORs) and Cox proportional HRs were used to compare outcomes over a 2-year follow-up period. RESULTS: The study cohort included 1,280 patients with CTRCD/HF (n = 640 per group; mean age: 67.6 years; 41.6% female; 68% White). Patients on SGLT2 inhibitors in addition to conventional guideline-directed medical therapy had a lower risk of acute HF exacerbation (OR: 0.483 [95% CI: 0.36-0.65]; P < 0.001) and all-cause mortality (OR: 0.296 [95% CI: 0.22-0.40]; P = 0.001). All-cause hospitalizations or emergency department visits (OR: 0.479; 95% CI: 0.383-0.599; P < 0.001), atrial fibrillation/flutter (OR: 0.397 [95% CI: 0.213-0.737]; P = 0.003), acute kidney injury (OR: 0.486 [95% CI: 0.382-0.619]; P < 0.001), and need for renal replacement therapy (OR: 0.398 [95% CI: 0.189-0.839]; P = 0.012) were also less frequent in patients on SGLT2 inhibitors. CONCLUSIONS: SGLT2 inhibitor use is associated with improved outcomes in patients with CTRCD/HF.

Catheter-based therapy for intermediate or high-risk pulmonary embolism is associated with lower in-hospital mortality in patients with cancer: Insights from the National Inpatient Sample.

BACKGROUND: Pulmonary embolism (PE) is a common complication among patients with cancer and is a significant contributor to morbidity and mortality. Catheter-based therapies (CBT), including catheter-directed thrombolysis (CDT) and mechanical thrombectomy, have been developed and are used in patients with intermediate or high-risk PE. However, there is a paucity of data on outcomes in patients with cancer as most clinical studies exclude this group of patients. AIMS: To characterize outcomes of patients with cancer admitted with intermediate or high-risk PE treated with CBT compared with no CBT. METHODS: Patients with an admission diagnosis of intermediate or high-risk PE and a history of cancer from October 2015 to December 2018 were identified using the National Inpatient Sample. Outcomes of interest were in-hospital death or cardiac arrest (CA) and major bleeding. Inverse probability treatment weighting (IPTW) was utilized to compare outcomes between patients treated with and without CBT. Variables that remained unbalanced after IPTW were adjusted using multivariable logistic regression. RESULTS: A total of 2084 unweighted admissions (10,420 weighted) for intermediate or high-risk PE and cancer were included, of which 136 (6.5%) were treated with CBT. After IPTW, CBT was associated with lower death or CA (aOR 0.54, 95% CI 0.46-0.64) but higher major bleeding (aOR 1.41, 95% CI 1.21-1.65). After stratifying by PE risk type, patients treated with CBT had lower risk of death or CA in both intermediate (aOR 0.52, 95% CI 0.36-0.75) and high-risk PE (aOR 0.48, 95% CI 0.33-0.53). However, patients with CBT were associated with increased risk of major bleeding in intermediate-risk PE (aOR 2.12, 95% CI 1.67-2.69) but not in those with high-risk PE (aOR 0.84, 95% CI 0.66-1.07). CONCLUSIONS: Among patients with cancer hospitalized with intermediate or high-risk PE, treatment with CBT was associated with lower risk of in-hospital death or CA but higher risk of bleeding. Prospective studies and inclusion of patients with cancer in randomized trials are warranted to confirm our findings.

Incorporating Exercise Training into Cardio-Oncology Care: Current Evidence and Opportunities: JACC: CardioOncology State-of-the-Art Review.

Cancer treatment-induced cardiotoxicities are an ongoing concern throughout the cancer care continuum from treatment initiation to survivorship. Several "standard-of-care" primary, secondary, and tertiary prevention strategies are available to prevent the development or further progression of cancer treatment-induced cardiotoxicities and their risk factors. Despite exercise's established benefits on the cardiovascular system, it has not been widely adopted as a nonpharmacologic cardioprotective strategy within cardio-oncology care. In this state-of-the-art review, the authors discuss cancer treatment-induced cardiotoxicities, review the existing evidence supporting the role of exercise in preventing and managing these sequelae in at-risk and affected individuals living after cancer diagnoses, and propose considerations for implementing exercise-based services in cardio-oncology practice.

Impact of Age and Variant Time Period on Clinical Presentation and Outcomes of Hospitalized Coronavirus Disease 2019 Patients.

Objective: To evaluate the impact of age and COVID-19 variant time period on morbidity and mortality among those hospitalized with COVID-19. Patients and Methods: Patients from the American Heart Association's Get With The Guidelines COVID-19 cardiovascular disease registry (January 20, 2020-February 14, 2022) were divided into groups based on whether they presented during periods of wild type/alpha, delta, or omicron predominance. They were further subdivided by age (young: 18-40 years; older: more than 40 years), and characteristics and outcomes were compared. Results: The cohort consisted of 45,421 hospitalized COVID-19 patients (wild type/alpha period: 41,426, delta period: 3349, and omicron period: 646). Among young patients (18-40 years), presentation during delta was associated with increased odds of severe COVID-19 (OR, 1.6; 95% CI, 1.3-2.1), major adverse cardiovascular events (MACE) (OR, 1.8; 95% CI, 1.3-2.5), and in-hospital mortality (OR, 2.2; 95% CI, 1.5-3.3) when compared with presentation during wild type/alpha. Among older patients (more than 40 years), presentation during delta was associated with increased odds of severe COVID-19 (OR, 1.2; 95% CI, 1.1-1.3), MACE (OR, 1.5; 95% CI, 1.4-1.7), and in-hospital mortality (OR, 1.4; 95% CI, 1.3-1.6) when compared with wild type/alpha. Among older patients (more than 40 years), presentation during omicron associated with decreased odds of severe COVID-19 (OR, 0.7; 95% CI, 0.5-0.9) and in-hospital mortality (OR, 0.6; 95% CI, 0.5-0.9) when compared with wild type/alpha. Conclusion: Among hospitalized adults with COVID-19, presentation during a time of delta predominance was associated with increased odds of severe COVID-19, MACE, and in-hospital mortality compared with presentation during wild type/alpha. Among older patients (aged more than 40 years), presentation during omicron was associated with decreased odds of severe COVID-19 and in-hospital mortality compared with wild type/alpha.

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.

Global Cardio Oncology Registry (G-COR): Registry Design, Primary Objectives, and Future Perspectives of a Multicenter Global Initiative.

BACKGROUND: Global collaboration in cardio-oncology is needed to understand the prevalence of cancer therapy-related cardiovascular toxicity in different risk groups, practice settings, and geographic locations. There are limited data on the socioeconomic and racial/ethnic disparities that may impact access to care and outcomes. To address these gaps, we established the Global Cardio-Oncology Registry, a multinational, multicenter prospective registry. METHODS: We assembled cardiologists and oncologists from academic and community settings to collaborate in the first Global Cardio-Oncology Registry. Subsequently, a survey for site resources, demographics, and intention to participate was conducted. We designed an online data platform to facilitate this global initiative. RESULTS: A total of 119 sites responded to an online questionnaire on their practices and main goals of the registry: 49 US sites from 23 states and 70 international sites from 5 continents indicated a willingness to participate in the Global Cardio-Oncology Registry. Sites were more commonly led by cardiologists (85/119; 72%) and were more often university/teaching (81/119; 68%) than community based (38/119; 32%). The average number of cardio-oncology patients treated per month was 80 per site. The top 3 Global Cardio-Oncology Registry priorities in cardio-oncology care were breast cancer, hematologic malignancies, and patients treated with immune checkpoint inhibitors. Executive and scientific committees and specific committees were established. A pilot phase for breast cancer using Research Electronic Data Capture Cloud platform recently started patient enrollment. CONCLUSIONS: We present the structure for a global collaboration. Information derived from the Global Cardio-Oncology Registry will help understand the risk factors impacting cancer therapy-related cardiovascular toxicity in different geographic locations and therefore contribute to reduce access gaps in cardio-oncology care. Risk calculators will be prospectively derived and validated.

Using Artificial Intelligence in Predicting Ischemic Stroke Events After Percutaneous Coronary Intervention.

BACKGROUND: Ischemic stroke (IS) is an uncommon but severe complication in patients undergoing percutaneous coronary intervention (PCI). Despite significant morbidity and economic cost associated with post PCI IS, a validated risk prediction model is not currently available. AIMS: We aim to develop a machine learning model that predicts IS after PCI. METHODS: We analyzed data from Mayo Clinic CathPCI registry from 2003 to 2018. Baseline clinical and demographic data, electrocardiography (ECG), intra/post-procedural data, and echocardiographic variables were abstracted. A random forest (RF) machine learning model and a logistic regression (LR) model were developed. The receiver operator characteristic (ROC) analysis was used to assess model performance in predicting IS at 6-month, 1-, 2-, and 5-years post-PCI. RESULTS: A total of 17,356 patients were included in the final analysis. The mean age of this cohort was 66.9 ± 12.5 years, and 70.7% were male. Post-PCI IS was noted in 109 patients (.6%) at 6 months, 132 patients (.8%) at 1 year, 175 patients (1%) at 2 years, and 264 patients (1.5%) at 5 years. The area under the curve of the RF model was superior to the LR model in predicting ischemic stroke at 6 months, 1-, 2-, and 5-years. Periprocedural stroke was the strongest predictor of IS post discharge. CONCLUSIONS: The RF model accurately predicts short- and long-term risk of IS and outperforms logistic regression analysis in patients undergoing PCI. Patients with periprocedural stroke may benefit from aggressive management to reduce the future risk of IS.

Ventricular Arrhythmia in Cancer Patients: Mechanisms, Treatment Strategies and Future Avenues.

Cardiovascular disease and cancer are the leading causes of morbidity and mortality in the US. Despite the significant progress made in cancer treatment leading to improved prognosis and survival, ventricular arrhythmias (VA) remain a known cardiovascular complication either exacerbated or induced by the direct and indirect effects of both traditional and novel cancer treatments. Although interruption of cancer treatment because of VA is rarely required, knowledge surrounding this issue is essential for optimising the overall care of patients with cancer. The mechanisms of cancer-therapeutic-induced VA are poorly understood. This review will discuss the ventricular conduction (QRS) and repolarisation abnormalities (QTc prolongation), and VAs associated with cancer therapies, as well as existing strategies for the identification, prevention and management of cancer-treatment-induced VAs.

Interventional Cardio-Oncology: Unique Challenges and Considerations in a High-Risk Population.

OPINION STATEMENT: Patients with cancer are at risk of developing cardiovascular disease (CVD) including atherosclerotic heart disease (AHD), valvular heart disease (VHD), and atrial fibrillation (AF). Advances in percutaneous catheter-based treatments, including percutaneous coronary intervention (PCI) for AHD, percutaneous valve replacement or repair for VHD, and ablation and left atrial appendage occlusion devices (LAAODs) for AF, have provided patients with CVD significant benefit in the recent decades. However, trials and registries investigating outcomes of these procedures often exclude patients with cancer. As a result, patients with cancer are less likely to undergo these therapies despite their benefits. Despite the inclusion of cancer patients in randomized clinical trial data, studies suggest that cancer patients derive similar benefits of percutaneous therapies for CVD compared with patients without cancer. Therefore, percutaneous interventions for CVD should not be withheld in patients with cancer, as they may still benefit from these procedures.

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.

Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Cancer.

Background: The prevention of stroke in patients with atrial fibrillation (AF) and cancer is challenging because patients are at increased bleeding and thrombotic risk. Objectives: The authors sought to assess left atrial appendage occlusion (LAAO) as a safe and effective strategy for reducing stroke at no increased bleeding risk in cancer patients with AF. Methods: We reviewed patients with nonvalvular AF who underwent LAAO at Mayo Clinic sites from 2017 to 2020 and identified those who had undergone prior or current treatment for cancer. We compared the incidence of stroke, bleeding, device complications, and death with a control group who underwent LAAO without malignancy. Results: Fifty-five patients were included; 44 (80.0%) were male, and the mean age was 79.0 ± 6.1 years. The median CHA2Ds2-VASc score was 5 (Q1-Q3: 4-6), with 47 (85.5%) having a prior bleeding event. Over the first year, ischemic stroke occurred in 1 (1.4%) patient, bleeding complications in 5 (10.7%) patients, and death in 3 (6.5%) patients. Compared with controls who underwent LAAO without cancer, there was no significant difference in ischemic stroke (HR: 0.44; 95% CI: 0.10-1.97; P = 0.28), bleeding complication (HR: 0.71; 95% CI: 0.28-1.86; P = 0.19), or death (HR: 1.39; 95% CI: 0.73-2.64; P = 0.32). Conclusions: Within our cohort, LAAO in cancer patients was achieved with good procedural success and offered a reduction in stroke at no increased bleeding risk similar to noncancer patients.