Oncologic emergencies and urgencies: A comprehensive review.

Patients with advanced cancer generate 4 million visits annually to emergency departments (EDs) and other dedicated, high-acuity oncology urgent care centers. Because of both the increasing complexity of systemic treatments overall and the higher rates of active therapy in the geriatric population, many patients experiencing acute decompensations are frail and acutely ill. This article comprehensively reviews the spectrum of oncologic emergencies and urgencies typically encountered in acute care settings. Presentation, underlying etiology, and up-to-date clinical pathways are discussed. Criteria for either a safe discharge to home or a transition of care to the inpatient oncology hospitalist team are emphasized. This review extends beyond familiar conditions such as febrile neutropenia, hypercalcemia, tumor lysis syndrome, malignant spinal cord compression, mechanical bowel obstruction, and breakthrough pain crises to include a broader spectrum of topics encompassing the syndrome of inappropriate antidiuretic hormone secretion, venous thromboembolism and malignant effusions, as well as chemotherapy-induced mucositis, cardiomyopathy, nausea, vomiting, and diarrhea. Emergent and urgent complications associated with targeted therapeutics, including small molecules, naked and drug-conjugated monoclonal antibodies, as well as immune checkpoint inhibitors and chimeric antigen receptor T-cells, are summarized. Finally, strategies for facilitating same-day direct admission to hospice from the ED are discussed. This article not only can serve as a point-of-care reference for the ED physician but also can assist outpatient oncologists as well as inpatient hospitalists in coordinating care around the ED visit.

Myocardial strain is associated with adverse cardiac events in patients treated with chimeric antigen receptor (CAR) T-cell therapy.

BACKGROUND: Cardiovascular events, including heart failure and arrhythmias, following chimeric antigen receptor (CAR) T-cell therapy are increasingly recognized. Although global longitudinal strain (GLS) has demonstrated prognostic utility for other cancer therapy-related cardiac dysfunction, less is known regarding the association of GLS with adverse cardiac events following CAR T-cell therapy. OBJECTIVES: To determine the association of baseline GLS with adverse cardiovascular events in adults receiving CAR-T cell therapy. METHODS: Patients who had an echocardiogram within 6 months prior to receiving CAR T-cell therapy were retrospectively identified. Clinical data and cardiac events were collected via chart review. Echocardiograms were analyzed offline for GLS, left ventricular ejection fraction, and Doppler parameters. Multivariable logistic regression was used to determine the association between adverse cardiovascular events and echocardiographic parameters. RESULTS: Among 75 CAR T-cell therapy patients (mean age 63.9, 34.7% female), nine patients (12%) experienced cardiac events (CEs) including cardiovascular death, new/worsening heart failure, and new/worsening arrhythmia within 1 year of treatment. In univariable models, higher baseline GLS (OR 0.78 [0.63, 0.96], p = .021) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.40 [1.08, 1.81], p = .012) was associated with a higher risk of CE. After adjusting for age and LDH, higher baseline GLS (OR 0.65 [0.48-0.88], p = <.01) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.56 [1.06, 2.29], p = .024) was associated with a higher risk of CE. CONCLUSION: Lower GLS and higher mitral E/e' on a baseline echocardiogram were associated with higher risk for CEs in patients receiving CAR T-cell therapy.

Echocardiographic correlates of major adverse cardiac events at 1 year in patients with apical ballooning takotsubo syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is characterized by transient left ventricular dysfunction and associated with considerable morbidity and mortality. We sought to evaluate the association between change in cardiac mechanics after diagnosis of TTS with 1-year incidence of major adverse cardiovascular events (MACE). METHODS: We retrospectively identified 85 patients with apical TTS based on ICD 9/10 codes and chart adjudication, who had a follow-up echocardiogram within 6 months of diagnosis. Echocardiograms were analyzed for left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), GLS ratio, global circumferential strain (GCS), and global radial strain (GRS). Multivariable logistic regression was performed to identify parameters associated with MACE (all-cause mortality, heart failure, stroke, and coronary artery disease [CAD] requiring percutaneous coronary intervention [PCI]) at 1 year. Event-free survival was assessed in patients with GLS (≤-18% vs. >18%) and LVEF (≥53% vs. <53%). RESULTS: Within 1 year of diagnosis, MACE occurred in 15 (18%) patients. Between baseline and follow-up echocardiogram (median 15 [range 1-151] days), there were significant differences in change in LVEF and GLS in patients with versus without incident MACE. In multivariate analysis, change in LVEF (odds ratio [OR] = .93 [.87, .98], p = .013) and change in GLS (OR = 1.32 [1.04, 1.67], p = .022) were independently associated with MACE; however, the association with change in GLS was attenuated (odds ratio [OR] = 1.13 [.94, 1.36], p = .21) after adjustment for baseline and change in LVEF. Among patients with normalized LVEF at follow-up, there were five (14.7%) MACE; whereas, there were no events among patients with normalized GLS. CONCLUSIONS: In patients with apical TTS, recovery in GLS and LVEF at follow-up was associated with significantly lower MACE at 1 year. Normalization of GLS at follow-up was better able to discriminate event-free survival than normalization of LVEF.

Challenges in Cardiovascular Imaging in Women with Breast Cancer.

Cardiovascular imaging in breast cancer patients is paramount for the surveillance of cancer therapy-related cardiac dysfunction (CTRCD); however, it comes with specific limitations. PURPOSE OF REVIEW: This review aims to describe the unique challenges faced in cardiovascular imaging of breast cancer patients, discuss evidence to support the utility of various imaging modalities, and provide solutions for improvement in imaging this unique population. RECENT FINDINGS: Updated clinical society guidelines have introduced more unifying surveillance of CTRCD, although there remains a lack of a universally accepted definition. Traditional and novel multi-modality imaging can be used to detect CTRCD and myocarditis in breast cancer patients. Cardiovascular imaging in breast cancer patients is difficult due to reconstructive surgery. Although echocardiography with myocardial strain is the cornerstone, multi-modality imaging can be used to evaluate for CTRCD and myocarditis. Novel imaging techniques to improve the diagnosis of cardiotoxicities in breast cancer patients are needed.

Social Risk Factors That Increase Cardiovascular and Breast Cancer Risk.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) and breast cancer (BC) are significant causes of mortality globally, imposing a substantial health burden. This review article aims to examine the shared risk factors and social determinants that contribute to the high prevalence of both diseases, with a focus on social risk factors. RECENT FINDINGS: The common risk factors for CVD and BC, such as hypertension, diabetes, obesity, aging, and physical inactivity, are discussed, emphasizing their modifiability. Adhering to ideal cardiovascular health behaviors has shown a trend toward lower BC incidence. Increased risk of CVD-related mortality is significantly impacted by age and race in BC patients, especially those over 45 years old. Additionally, racial disparities in both diseases highlight the need for targeted interventions. Social determinants of health, including socioeconomic status, education, employment, and neighborhood context, significantly impact outcomes for both CVD and BC. Addressing social factors is vital in reducing the burden of both CVD and BC and improving overall health equity.

Heart failure prevention and monitoring strategies in HER2-positive breast cancer: a narrative review.

PURPOSE: Cardiotoxicity from anti-human epidermal growth factor receptor 2 (HER2) therapy carries a short- and long-term risk of incident heart failure and increased cardiovascular mortality in patients with breast cancer. Interruptions in anti-HER2 therapy due to cardiotoxicity can lead to suboptimal cancer treatment. The purpose of this narrative review is to outline opportunities to optimize cardiovascular care in patients with HER2-positive breast cancer to prevent interruptions in therapy. METHODS: This case-based review presents the current literature on evidence-based strategies for personalized cardiotoxicity risk assessment, risk mitigation interventions, cardiac function surveillance tools, and management of asymptomatic left ventricular dysfunction in breast cancer patients receiving anti-HER2 therapy. RESULTS: Pretreatment cardiac risk assessment incorporates both treatment-related risk factors and patient-related risk factors for the development of cardiac dysfunction. Prevention and monitoring strategies while on treatment utilize risk factor modification, imaging and biomarker surveillance. Management of asymptomatic left ventricular dysfunction due to anti-HER2 therapy is evolving. Permissive cardiotoxicity in asymptomatic patients while starting cardioprotective therapies requires close collaboration between oncology and cardiology, and referral to cardio-oncology if available. CONCLUSIONS: Patient-centered, multimodal strategies to prevent, detect, and manage cardiotoxicity from anti-HER2 therapy are necessary to improve outcomes in patients with HER2-positive breast cancer.

Cardiac risk stratification of breast cancer patients in a cardio-oncology clinic.

PURPOSE: The field of cardio-oncology aims to optimize the cardiac health of cancer patients. The goals of this study are to (1) describe the demographics of a cardio-oncology clinic and (2) apply the American Society of Clinical Oncology (ASCO) cardiac risk stratification guidelines among breast cancer patients to assess the development of cardiovascular events, primarily heart failure (HF). METHODS: We performed a retrospective chart review on 203 consecutive cardio-oncology patients who were seen between January 2019 and March 2020. Mean follow-up for the cohort was 29.2 ± 3.1 months (range 0-113). We applied the ASCO guidelines to the breast cancer subgroup. RESULTS: The plurality of patients 82/203 (40%) referred to clinic had breast cancer. The most common reason for referral was asymptomatic left ventricular (LV) dysfunction or HF (40%). Only 36/203 (18%) of patients were referred for a pre-chemotherapy evaluation. In breast cancer patients, there was a trend toward significance in up-titrating or initiating beta-blockers in the high vs. low risk ASCO groups [46/69 (67%) vs. 5/13 (38%), p = 0.054]. Approximately 13/82 (16%) of breast cancer patients required alterations to their anti-cancer therapy. HF events occurred in 1/36 (3%) of cancer treatment naïve patients and 14/167 (8%) of those with prior therapy, specifically 9% of the breast cancer subset. CONCLUSION: Our study provides insight into referral practices, interventions, and outcomes at a cardio-oncology clinic. Furthermore, breast cancer patients continue to have high rates of HF. These findings suggest a need to shift referral practices upstream for a pre-chemotherapy evaluation to optimize cardiovascular health.

Cardiovascular Toxicities of CAR T-cell Therapy.

PURPOSE OF REVIEW: This review provides a contemporary overview of current studies outlining the incidence and characteristics of CAR T-cell cardiotoxicity in an effort to identify future directions for research and potential opportunities for prevention and intervention. RECENT FINDINGS: Cardiovascular events occurred in anywhere between 10 and 36% of patients in CAR T-cell clinical trials, ranging from tachycardia, hypotension, arrhythmia, decreased left ventricular systolic function to cardiogenic shock and death. Cardiac events are more often associated higher grades (> 2) of cytokine release syndrome and frequently proceeded by an elevated troponin. There is a growing recognition of cardiotoxicities of CAR T-cell therapy but has a limited study in this area. The mechanism of left ventricular dysfunction due to CAR T-cell therapy is also unknown. As CAR T-cell use expands, it becomes imperative to truly understand the mechanism behind cardiac injury and to assess long-term follow-up data as this will allow for surveillance, early intervention, and potentially prevention of cardiotoxicity.

Circulating Biomarkers for Cardiotoxicity Risk Prediction.

OPINION STATEMENT: Improvements in cancer survival have led to the emergence of cardiovascular disease as an important determinant of adverse outcome in survivors. Cancer therapeutics-related cardiac dysfunction is the most well-known form of cardiotoxicity. However, newer cancer therapies bring a broader range of cardiotoxicities. The optimal method to identify patients at risk of these complications is unclear, but circulating biomarkers comprise one possible approach. Troponins and natriuretic peptides have garnered the broadest evidence base for cardiotoxicity risk prediction, but other markers are being investigated. In this review, we explore evidence for circulating biomarkers in cardiotoxicity prediction associated with cancer therapies.

A possible mechanism of hyperlipidemia in a patient with metastatic non-small cell lung cancer on lorlatinib therapy.

INTRODUCTION: We report the case of a woman who developed hyperlipidemia on lorlatinib therapy found to have minimal change disease. We review therapies for cancer known to alter the lipid profile, in addition to reviewing secondary hyperlipidemia workup. We also propose a mechanism for lorlatinib-induced hyperlipidemia. CASE REPORT: A 63 year old woman with non-small cell lung adenocarcinoma on lorlatinib therapy develops marked hyperlipidemia.Management & outcome: A secondary hyperlipidemia workup is performed which reveals nephrotic range proteinuria. Minimal change disease is found on renal biopsy. The hyperlipidemia was initially responsive to statin therapy, then required addition of ezetimibe. DISCUSSION: This is a case of hyperlipidemia in a patient on lorlatinib. The case highlights that therapies for lung cancer and other malignancies have the potential to alter the lipid profile. We propose minimal change disease as a possible mechanism for lorlatinib-induced dyslipidemia. Additionally, we discuss the crucial aspects of secondary hyperlipidemia workup.

Utilizing left atrial strain to identify patients at risk for atrial fibrillation on ibrutinib.

BACKGROUND: Ibrutinib is associated with atrial fibrillation (AF), though echocardiographic predictors of AF have not been studied in this population. We sought to determine whether left atrial (LA) strain on transthoracic echocardiography could identify patients at risk for developing ibrutinib-related atrial fibrillation (IRAF). METHODS: We performed a retrospective review of 66 patients who had an echocardiogram prior to ibrutinib treatment. LA strain was measured with TOMTEC Imaging Systems, obtaining peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) on 4-chamber and 2-chamber views. Statistical analysis was performed with chi-square analysis, t test, or binomial regression analysis, with a P-value < .05 considered statistically significant. RESULTS: Twenty-two patients developed IRAF (33%). Age at initiation of ibrutinib was significantly associated with IRAF (65.1 years vs 74.1 years, P = .002). Mean ibrutinib dose was lower among patients who developed IRAF (388.2 ± 121.7 vs 448.6 ± 88.4, P = .025). E/e' was significantly higher among patients who developed IRAF (11.5 vs 9.3, P = .04). PALS was significantly lower in patients who developed AF (30.3% vs 36.3%, P = .01). On multivariate regression analysis, age, PALS, and PACS were significantly associated with IRAF. On multivariate regression analysis, only PACS remained significantly associated with IRAF while accounting for age. CONCLUSIONS: Age, ibrutinib dose, E/e', and PALS on pre-treatment echocardiogram were significantly associated with development of IRAF. On multivariate regression analyses, age, PALS, and PACS remained significantly associated with IRAF. Impaired LA mechanics add to the assessment of patients at risk for IRAF.

Echocardiographic parameters associated with in-hospital adverse outcomes in patients with Takotsubo syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is an acute heart failure syndrome that leads to significant morbidity and mortality. We sought to evaluate the association of cardiac mechanics on presentation with in-hospital adverse outcomes in patients with apical TTS. METHODS: We retrospectively identified 468 patients with TTS based on ICD-9/10 codes between 2006 and 2017. The association of echocardiographic parameters with a composite outcome of heart failure and all-cause mortality during the index hospitalization was analyzed. RESULTS: One hundred and forty one patients with the apical subtype and adequate imaging were included. 113 (80.1%) were female, left ventricular ejection fraction (LVEF) was 41.7% ± 12.4%, and global longitudinal strain was -10.1% ± 3.2%. The composite outcome occurred in 58 patients (41%), with heart failure occurring in 55 patients and death occurring in nine patients. Global longitudinal strain, global circumferential strain, global radial strain, right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular free wall strain were significantly worse in patients who experienced the composite outcome in univariate analyses. However, only LVEF was independently associated with the composite outcome in multivariable-adjusted analysis. CONCLUSIONS: In patients with apical TTS, the strain has limited prognostic utility in the acute setting compared to LVEF, which was the only echocardiographic parameter associated with in-hospital heart failure and all-cause mortality.

Two-dimensional speckle-tracking strain detects subclinical cardiotoxicity in older patients treated for acute myeloid leukemia.

BACKGROUND: Patients with acute myeloid leukemia (AML) are surviving longer. There are no data on changes in myocardial mechanics from standard of care low-dose anthracycline-based induction chemotherapy in older patients with AML. The aim of this study was to demonstrate the potential utility of strain imaging in detecting early changes in left ventricular function in this patient population after induction chemotherapy. METHODS: Thirty two patients enrolled in the ECOG-ACRIN E2906 study (cytarabine and daunorubicin vs clofarabine [Genzyme/Sanofi]) from 2011 to 2014 were evaluated retrospectively. Two-dimensional transthoracic echocardiography (TTE) imaging with Doppler and two-dimensional speckle-tracking echocardiography (2DSTE) using EchoInsight software (Epsilon imaging) were performed before and after induction chemotherapy. RESULTS: Eighteen patients received cytarabine and daunorubicin (7 + 3) and 14 received clofarabine. The clofarabine group was older than the 7 + 3 cohort (67.8 ± 4.0 vs 63.7 ± 3.8, P = .007). There were no other significant differences in cardiac risk factors between groups. The 7 + 3 group had a decrease in average peak systolic global longitudinal (-19.1 ± 2.8 to -17.2 ± 3.0, P = .01) and circumferential strain (-29.4 ± 6.3 to -23.9 ± 4.3, P = .011). These changes were not demonstrated in the clofarabine group and were not associated with a decline in left ventricular ejection fraction (LVEF). CONCLUSIONS: In older AML patients, standard cytarabine and daunorubicin chemotherapy causes early changes in global longitudinal and circumferential strain not seen with clofarabine therapy. These findings demonstrate subclinical left ventricular dysfunction after exposure to low cumulative doses of anthracycline-based induction chemotherapy and may help us better identify those patients at risk for adverse long-term cardiovascular outcomes.

Strategies for early detection of cardiotoxicities from anticancer therapy in adults: evolving imaging techniques and emerging serum biomarkers.

Significant advances have been made in detecting cancer therapeutics-related cardiac dysfunction with serum biomarkers, cardiovascular MRI, echocardiography and multi-modality approaches. Serum biomarkers, notably cardiac troponins and natriuretic peptides, have been evaluated for their prognostic ability in predicting left ventricular dysfunction. Imaging modalities, such as cardiovascular MRI and echocardiography, have been used for cardiac surveillance of patients with cancer undergoing chemotherapy. Developments in imaging, specifically myocardial deformation imaging, also known as strain, have been shown to be sensitive tools in detecting early changes in cardiac function. This review aims to synthesize the evidence that supports emerging serum biomarkers and complementary imaging modalities that continue to enhance the detection of cancer therapeutics-related cardiac dysfunction.

Identification of prolapsing mitral valve scallops by a three-dimensional multiplanar reconstruction method.

BACKGROUND: The objectives of this study were twofold: to assess the diagnostic utility of three-dimensional (3D) multiplanar reconstruction (MPR) in identifying prolapsing mitral valve (MV) scallops, and (2) to compare two-dimensional (2D) transthoracic echocardiography (TTE) and 3DMPR to (2D) transesophageal echocardiography (TEE) approaches among patients with mitral valve prolapse (MVP). METHODS: Fifty-five patients with MVP who underwent MV repair or replacement were retrospectively analyzed using 3 types of echocardiographic studies (2DTEE, 2DTTE, 3DMPR). The operative (OR) findings were considered the gold standard. RESULTS: When 3DMPR was combined with 2DTTE, the agreement with the OR findings was moderately strong for the A2 scallop (P < 0.001) and strong for the A3 scallop (P = 0.001), entire anterior leaflet (P < 0.001), P2 scallop (P < 0.001) and the entire posterior leaflet (P < 0.001). In comparison to the OR findings, 2DTEE demonstrated moderately strong agreement for the A2 scallop (P = 0.010) and the entire anterior leaflet (P < 0.001), and strong agreement for the P2 scallop (P < 0.001) and entire posterior leaflet (P < 0.001). CONCLUSIONS: Three-dimensional MPR should be added to the armamentarium of complementary echo techniques in the evaluation of MVP. There is increased benefit in combining 3DMPR with 2DTTE findings as part of the preoperative evaluation of patients with MVP.

An update on the risk prediction and prevention of anticancer therapy-induced cardiotoxicity.

PURPOSE OF REVIEW: Cardiotoxicity is a well established complication of anticancer therapy. As cancer survivorship and life expectancy for cancer patients improves, the morbidity and mortality of anticancer therapy-related cardiotoxicity has become more problematic. It is of utmost importance to identify patients at the highest risk for the development of cardiotoxicity and to determine strategies for prevention, early detection and treatment. RECENT FINDINGS: Clinical risk factors, biomarkers, advanced cardiac imaging and pharmacogenomics may be used to classify patients at risk for therapy-induced cardiotoxicity. A much broader armamentarium of imaging modalities for risk prediction, in addition to simple two-dimensional echocardiogram and radionucleotide angiography, has also shown clinical utility in identifying early-onset cardiotoxicity and areas of reversible myocardial injury. Exciting new research aimed at predicting cardiotoxicity and developing cardioprotective strategies may lead to changes in the administration of cardiotoxic chemotherapies. SUMMARY: Personalized assessments of the risks and benefits of therapy should be used as opposed to standardized dosing and schedules. Patients at higher risk for cardiotoxicity should receive closer monitoring, cardioprotective agents, dose adjustment or alternative regimens in an effort to reduce cardiovascular morbidity and mortality. Future research will hopefully define specific risk prediction tools and clinical protocols to prevent irreversible cardiotoxicity.

Cardiovascular toxicity of biologic agents for cancer therapy.

There has been significant progress in the development of new anticancer therapies over the last decade.Targeted therapies, including anti-human epidermal growth factor receptor 2 agents, vascular endothelial growth factor inhibitors, and tyrosine kinase inhibitors, have been important components of current treatment strategies. However, many of these therapies have been associated with chemotherapy-related cardiac dysfunction. While newer targeted agents provide "on-target" anticancer activity, their "off-target" drug effects encompass a wide range of cardiovascular toxicities. Many of these toxicities are reversible, but they may limit the use and length of treatment and compromise its efficacy. Oncologists are often the first to diagnose chemotherapy-related cardiac dysfunction, although patients with advanced cardiotoxicity are referred to cardiologists for further care. The field of cardio-oncology has emerged as a necessary discipline to address these disabling complications. In order to prevent late-stage cardiotoxicity, an early collaborative effort between oncologists and cardiologists is warranted to risk-stratify patients prior to therapy and to treat at the earliest signs of cardiotoxicity. It is therefore of utmost importance for oncologists to be aware of the cardiotoxicities of anticancer therapies, and to be familiar with modifiable risk factors and early interventions that can prevent long-term cardiac damage.

Checkpoint inhibitor myocarditis with preceding immunosuppression and tolerance of sequential anthracycline therapy.

A man in his 50s with no known cardiac history and diffuse large B-cell lymphoma on nivolumab presented with acute dyspnoea and swelling. Physical examination revealed volume overload. Work-up noted new elevation of B-type natriuretic peptide and troponin, with new lateral T-wave inversions on ECG. He was admitted to cardiac intensive care for decompensated heart failure. Echocardiography showed ejection fraction 51% with diffuse hypokinesis and reduction of global longitudinal strain. Cardiac MRI demonstrated diffuse myocardial fibrosis with oedema suggesting acute injury. Endomyocardial biopsy revealed lymphocytic and macrophagic infiltrate with cardiomyocyte damage, compatible with immune checkpoint inhibitor (ICI) myocarditis. Immunotherapy was discontinued and he was treated with diuresis, steroids and initiation of goal-directed medical therapy for heart failure. He required additional treatment with anthracyclines. He was monitored with cardio-oncology follow-up after every cycle of anthracycline and tolerated a cumulative 312 mg/m2 therapy. The safety of anthracycline administration after ICI-myocarditis has not been described.

The risk vs. benefit calculus of anticoagulation in patients with ibrutinib-related atrial fibrillation.

For ibrutinib-related atrial fibrillation (IRAF), guidelines for anticoagulation do not exist. We sought to describe stroke, bleeding, and anticoagulation rates among patients with IRAF. We performed a single-center retrospective review of 168 patients treated with ibrutinib followed from 2013 to 2022. Over a median follow-up of 6.4 years, 44 (26.0%) patients developed IRAF of which 38 (86.4%) had a CHA2DS2-VASc ≥2 and 7 (15.9%) had a HAS-BLED ≥3. Anticoagulation was initiated in 20 (45.5%) without a clear pattern in scores, risk factors, or cumulative dose, besides having another reason for anticoagulation. Few patients with IRAF developed non-hemorrhagic CVA (n = 3, 6.8%) or significant bleeding (n = 3, 6.8%). Among those with each adverse outcome, 2 in each group were anticoagulated and all were older than 65 years old. In conclusion, decisions for anticoagulation vary widely and patients who are elderly or with HTN may be most at risk for CVA or significant bleed.

Predictors and Risk Score for Immune Checkpoint-Inhibitor-Associated Myocarditis Severity.

Background: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this "cardiomyotoxicity" are lacking. Methods: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated. Results: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events. Conclusions: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well. Trial registration number: NCT04294771 and NCT05454527.