THE IMPACT OF ROUTINE CARDIAC TROPONIN I-BASED CARDIOTOXICITY SCREENING ON CLINICAL OUTCOMES IN PATIENTS ON CANCER IMMUNOTHERAPY.

Purpose: Immune checkpoint inhibitors (ICI) used as cancer therapy have been associated with a range of cardiac immune-related adverse events (irAEs), including fulminant myocarditis with a high case fatality rate. Early detection through cardiotoxicity screening by biomarker monitoring can lead to prompt intervention and improved patient outcomes. In this study, we investigate the association between cardiotoxicity screening with routine serial troponin I monitoring in asymptomatic patients receiving ICI, cardiovascular adverse event (CV AE) detection, and overall survival (OS). Methods: We instituted a standardized troponin I screening protocol at baseline and with each ICI dose (every 2-4 weeks) in all patients receiving ICI at our center starting Jan 2019. We subsequently collected data in 825 patients receiving ICI at our institution from January 2018 to October 2021. Of these patients, 428 underwent cardiotoxicity screening with serial troponin I monitoring during ICI administration (Jan 2019-Oct 2021) and 397 patients were unmonitored (Jan 2018-Dec 2018). We followed patients for nine months following their first dose of ICI and compared outcomes of CV AEs and OS between monitored and unmonitored patients. Additionally, we investigated rates of CV AEs, all-cause mortality, and oncologic time-to-treatment failure (TTF) between patients with an elevated troponin I value during the monitoring period versus patients without elevated troponin I. Results: We found a lower rate of severe (grades 4-5) CV AEs, resulting in critical illness or death, in patients who underwent troponin monitoring (0.5%) compared to patients who did not undergo monitoring (1.8%), (HR 0.17, 95% CI 0.02-0.79, p = 0.04). There was no difference in overall CV AEs (grades 3-5) or OS between monitored and unmonitored patients. In the entire cohort, patients with at least one elevated troponin I during the follow up period, during routine monitoring or unmonitored, had a higher risk of overall CV AEs (HR 10.96, 95% CI 4.65-25.85, p<0.001) as well as overall mortality (HR 2.67, 95% CI 1.69 - 4.10, p<0.001) compared to those without elevated troponin. Oncologic time-to-treatment failure (TTF) was not significantly different in a sub-cohort of monitored vs. unmonitored patients. Conclusions: Patients undergoing cardiotoxicity screening with troponin I monitoring during ICI therapy had a lower rate of severe (grade 4-5) CV AEs compared patients who were not screened. Troponin I elevation in screened and unscreened patients was significantly associated with increased CV AEs as well as increased mortality. Troponin I monitoring did not impact oncologic time-to-treatment-failure in a sub-cohort analysis of patients treated with ICI. These results provide preliminary evidence for clinical utility of cardiotoxicity screening with troponin I monitoring in patients receiving ICI therapy.

Immunotherapy-Associated Atherosclerosis: A Comprehensive Review of Recent Findings and Implications for Future Research.

Purpose of the Review: Even as immune checkpoint inhibitors (ICIs) have transformed the lifespan of many patients, they may also trigger acceleration of long-term cardiovascular disease. Our review aims to examine the current landscape of research on ICI-mediated atherosclerosis and address key questions regarding its pathogenesis and impact on patient management. Recent Findings: Preclinical mouse models suggest that T cell dysregulation and proatherogenic cytokine production are key contributors to plaque development after checkpoint inhibition. Clinical data also highlight the significant burden of atherosclerotic cardiovascular disease (ASCVD) in patients on immunotherapy, although the value of proactively preventing and treating ASCVD in this population remains an open area of inquiry. Current treatment options include dietary/lifestyle modification and traditional medications to manage hypertension, hyperlipidemia, and diabetes risk factors; no current targeted therapies exist. Summary: Early identification of high-risk patients is crucial for effective preventive strategies and timely intervention. Future research should focus on refining screening tools, elucidating targetable mechanisms driving ICI atherosclerosis, and evaluating long-term cardiovascular outcomes in cancer survivors who received immunotherapy. Moreover, close collaboration between oncologists and cardiologists is essential to optimize patient outcomes.

Taken to heart-arrhythmic potential of heart-leaf sida, a banned ephedrine alkaloid: a case report.

BACKGROUND: Ephedra and ephedrine alkaloids were commonly used in herbal supplements before being prohibited by the European Commission and US Food and Drug Administration. However, ongoing, unknowing use by consumers can lead to potential adverse cardiovascular effects, such as arrhythmias. CASE SUMMARY: A 65-year-old-man with a history of idiopathic pulmonary fibrosis status post-right single lung transplant was admitted for dizziness and resting tachycardia. Electrocardiogram showed a narrow complex, long R-P tachycardia with upright P-waves in lead V 1. An initial workup suggested an arrhythmia associated with the consumption of an herbal supplement containing heart-leaf sida, a banned botanical ephedrine alkaloid. After the supplement was discontinued, the patient's heart rate abruptly decreased without other intervention. Electrocardiogram showed a change in P-wave morphology in lead V 1 from upright to biphasic (+/-) after conversion to normal sinus rhythm. Thus, a diagnosis of atrial tachycardia originating at or near the donor right superior pulmonary vein was favoured. DISCUSSION: Atrial tachycardia can be precipitated by the proarrhythmic effects of ephedrine alkaloids, especially in patients with underlying risk factors and susceptible atrial anatomical substrate post-lung transplantation. Despite being banned by the European Union and the USA, ephedrine alkaloids continue to be used in over-the-counter herbal supplements and may go undetected by consumers. Ongoing vigilance for ephedrine alkaloids, more rigorous regulation, and active patient education can help reduce potential cardiovascular adverse events.

Bradyarrhythmias in Cardio-Oncology.

The relationship between bradyarrhythmias and cancer therapies has not been well described but is increasingly recognized. There have been extensive advances in oncological pharmacotherapy, with several new classes of drugs available including targeted agents, immune checkpoint inhibitors and CAR T cell therapy. This increasing repertoire of available drugs has revolutionized overall prognosis and survival of cancer patients but the true extent of their cardiovascular toxicity is only beginning to be understood. Previous studies and published reviews have traditionally focused on conventional chemotherapies and in arrhythmias in general, particularly tachyarrhythmias. The number of patients with both cancer and cardiovascular problems is increasing globally and oncologists and cardiologists need to be adept at managing arrythmia based scenarios. Greater collaboration between the two specialties including studies with prospective data collection in Cardio-Oncology are much needed to fill in knowledge gaps in this arena. This case-based review summarizes current available evidence of cancer treatment-related bradyarrhythmia incidence (including its different subtypes), possible mechanisms and outcomes. Furthermore, we propose a stepwise surveillance and management protocol for patients with suspected bradyarrhythmia related to cancer treatment.

Long-term vs. recent-onset obesity: their contribution to cardiometabolic risk in adolescence.

BACKGROUND: The contribution of long-term vs. recent-onset obesity to cardiometabolic risk in adolescence remains controversial. Here, we aimed to investigate the association of time of onset and length of obesity with the cardiometabolic profile of adolescence. METHODS: Prospective study in 678 16-year-olds. BMI was measured at birth-1-5-10-16 years and BMI trajectories were interpolated using cubic splines. BMI > 2 SD at <6 years was defined as early obesity. Waist circumference (WC), blood pressure, lipid and glucose profiles were measured at 16 years. A cardiometabolic risk score was computed (MetS_score). According to the BMI trajectory, four groups were defined: participants who were never obese (NOB), participants with obesity during adolescence (recent-onset obese (ROB)), participants who were obese in early childhood but transitioned to normal/overweight as preadolescents (formerly obese (FOB)), and participants who were obese in early childhood and remained obese (persistently obese (POB)). RESULTS: ROBs and POBs had significantly unhealthier cardiometabolic profile than NOBs. No differences were observed in the cardiometabolic profile of ROBs compared to POBs. Although FOBs had higher WC and MetS_score than NOBs, no differences were found in other biomarkers. FOBs were in healthier cardiometabolic condition than ROBs and POBs. CONCLUSIONS: Both long-term and recent-onset obesity increase the cardiometabolic risk in adolescents.

Light smoking is associated with metabolic syndrome risk factors in Chilean young adults.

AIMS: Metabolic syndrome (MetS) is a cluster of risk factors for cardiometabolic diseases. While cigarette smoking is associated with MetS in adults, young adulthood is an under-studied, susceptible period for developing long-term morbidity from MetS. We examined associations between cigarette smoking and MetS risk factors. METHODS: We studied 430 participants in Santiago, Chile who have been followed in a longitudinal cohort since infancy and assessed in adolescence for MetS. Participants were evaluated at 22 years from May 2015 to July 2017. Adiposity, blood pressure, and blood samples were measured. MetS was defined using International Diabetes Federation criteria. A continuous MetS score was calculated using z-scores. Participants self-reported cigarette and alcohol consumption using standardized questionnaires. We used multivariate regressions to examine associations between smoking and MetS risk factors, adjusting for sex, MetS in adolescence, alcohol consumption, and socioeconomic status. RESULTS: Thirteen percent of participants had MetS and 50% were current smokers. Among smokers, mean age of initiation was 14.9 years and consumption was 29 cigarettes weekly. Smokers had larger waist circumferences, higher BMIs, and lower high-density lipoprotein (HDL) cholesterol compared to non-smokers. Being a current smoker was significantly associated with higher waist circumference (ß = 2.82; 95% CI 0.63, 5.02), lower HDL (ß = - 3.62; 95% CI - 6.19, - 1.04), higher BMI (ß = 1.22; 95% CI 0.16, 2.28), and higher MetS score (ß = 0.13, 95% CI 0.02, 0.24). CONCLUSIONS: Cigarette smoking at light levels (mean < 30 cigarettes weekly) was associated with MetS risk factors in a sample of Chilean young adults.