Elevated IL-6 and Tumor Necrosis Factor-α in Immune Checkpoint Inhibitor Myocarditis.

INTRODUCTION: The impact of peripheral cytokine levels on the prognosis and treatment of immune checkpoint inhibitor (ICI) myocarditis has not been well studied. OBJECTIVES: This study aimed to identify cytokines that can prognosticate and direct the treatment of ICI myocarditis. METHODS: This was a single-center, retrospective cohort study of patients with ICI myocarditis who had available peripheral cytokine levels between January 2011 and May 2022. Major adverse cardiovascular events (MACEs) were defined as a composite of heart failure with/without cardiogenic shock, arterial thrombosis, life-threatening arrhythmias, pulmonary embolism, and sudden cardiac death. RESULTS: In total, 65 patients with ICI myocarditis had cytokine data available. Patients were mostly males (70%), with a mean age of 67.8 ± 12.7 years. Interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were the most common cytokines to be elevated with 48/65 (74%) of patients having a peak IL-6 above normal limits (>5 pg/mL) and 44/65 (68%) of patients with peak TNF-α above normal limits (>22 pg/mL). Patients with elevated peak IL-6 had similar 90-day mortality and MACE outcomes compared to those without (10.4% vs. 11.8%, p = 0.878 and 8.8% vs. 17.7%, p = 0.366, respectively). Similarly, those with elevated peak TNF-α had similar 90-day mortality and MACEs compared to those without (29.6% vs. 14.3%, p = 0.182 and 13.6% vs. 4.8%, p = 0.413, respectively). Kaplan-Meier survival analysis also showed that there was not a significant difference between MACE-free survival when comparing elevated and normal IL-6 and TNF-α levels (p = 0.182 and p = 0.118, respectively). MACEs and overall survival outcomes were similar between those who received infliximab and those who did not among all patients and those with elevated TNF-α (p-value 0.70 and 0.83, respectively). CONCLUSION: Peripheral blood levels of IL-6 and TNF-α are the most commonly elevated cytokines in patients with ICI myocarditis. However, their role in the prognostication and guidance of immunomodulatory treatment is currently limited.

Navigating P2Y12 inhibition in the labyrinth of cardio-oncology care: cangrelor bridging in patients with cancer.

Cangrelor, a potent intravenous P2Y12 platelet inhibitor, has demonstrated effectiveness in reducing ischemic events without a corresponding increase in severe bleeding during percutaneous coronary intervention, as evidenced by the CHAMPION-PHOENIX trial. Its off-label role as a bridging antiplatelet agent for patients facing high thrombotic risks who must temporarily stop oral P2Y12 inhibitor therapy further underscores its clinical utility. This is the first case series to shed light on the application of cangrelor in cancer patients needing to pause dual antiplatelet therapy for a range of medical interventions, marking it as a pioneering effort in this domain. The inclusion of patients with a variety of cancer types and cardiovascular conditions in this series underlines the adaptability and critical role of cangrelor in managing the dual challenges of bleeding risk and the need for uninterrupted antiplatelet protection. By offering a bridge for high-risk cancer patients who have recently undergone percutaneous coronary intervention and need to halt oral P2Y12 inhibitors temporarily, cangrelor presents a practical solution. Early findings indicate it can be discontinued safely 2-4 h before medical procedures, allowing for the effective reintroduction of oral P2Y12 inhibitors without adverse effects. This evidence calls for expanded research to validate and extend these preliminary observations, emphasizing the importance of further investigation into cangrelor's applications in complex patient care scenarios.

Outcomes by Class of Anticoagulant Use for Nonvalvular Atrial Fibrillation in Patients With Active Cancer.

Background: The choice of anticoagulant agent for patients with nonvalvular atrial fibrillation (NVAF) in the setting of active cancer has not been well studied. Objectives: The aim of this study was to compare the rates of cerebrovascular accident (CVA), gastrointestinal bleeding (GIB), and intracranial hemorrhage (ICH) in patients treated with direct oral anticoagulant agents (DOACs) compared with warfarin for NVAF in patients with active cancer. Methods: This was a retrospective electronic medical record review of eligible patients treated at a cancer hospital. The outcome events were CVA; GIB; ICH; the composite of GIB, CVA, or ICH; and overall mortality. Propensity score matching (1:1) was conducted to select comparable patients receiving warfarin vs DOACs. Fine-Gray models were fitted for each outcome event. Results: The study cohort included 1,133 patients (mean age 72 ± 8.8 years, 42% women), of whom 74% received DOACs (57% received apixaban). After propensity score matching, 195 patients were included in each anticoagulant agent group. When comparing warfarin with DOACs, there were similar risks for CVA (subdistribution HR: 0.738; 95% CI: 0.334-1.629); ICH (subdistribution HR: 0.295; 95% CI: 0.032-2.709); GIB (subdistribution HR: 1.819; 95% CI: 0.774-4.277); and the composite of GIB, CVA, or ICH (subdistribution HR: 1.151; 95% CI: 0.645-2.054). Conclusions: Patients with active cancer had similar risks for CVA, ICH, and GIB when treated with DOACs compared with warfarin for NVAF.

Natural History of Functional Tricuspid Regurgitation Quantified by Cardiovascular Magnetic Resonance.

BACKGROUND: Quantitation of tricuspid regurgitant (TR) severity can be challenging with conventional echocardiographic imaging and may be better evaluated using cardiovascular magnetic resonance (CMR). OBJECTIVES: In patients with functional TR, this study sought to examine the relationship between TR volume (TRVol) and TR fraction (TRF) with all-cause mortality. METHODS: We examined 547 patients with functional TR using CMR to quantify TRVol and TRF. The primary outcome was all-cause mortality. Thresholds for mild, moderate, and severe TR were derived based on natural history outcome data. RESULTS: During a median follow-up of 2.6 years (interquartile range: 1.7 to 3.3 years), there were 93 deaths, with an estimated 5-year survival of 79% (95% confidence interval [CI]: 73% to 83%). After adjustment of clinical and imaging variables, including RV function, both TRF (adjusted hazard ratio [AHR] per 10% increment: 1.26; 95% CI: 1.10 to 1.45; p = 0.001) and TRVol (AHR per 10-ml increment: 1.15; 95% CI: 1.04 to 1.26; p = 0.004) were associated with mortality. Patients in the highest-risk strata of TRVol ≥45 ml or TRF ≥50% had the worst prognosis (AHR: 2.26; 95% CI: 1.36 to 3.76; p = 0.002 for TRVol and AHR: 2.60; 95% CI: 1.45 to 4.66; p = 0.001 for TRF). CONCLUSIONS: This is the first study to use CMR to assess independent prognostic implications of functional TR. Both TRF and TRVol were associated with increased mortality after adjustment for clinical and imaging covariates, including right ventricular ejection fraction. A TRVol of ≥45 ml or TRF of ≥50% identified patients in the highest-risk strata for mortality. These CMR thresholds should be used for patient selection in future trials to determine if tricuspid valve intervention improves outcomes in this high-risk group.

Fluorodeoxyglucose Applications in Cardiac PET: Viability, Inflammation, Infection, and Beyond.

With its high temporal and spatial resolution and relatively low radiation exposure, positron emission tomography (PET) is increasingly being used in the management of cardiac patients, particularly those with inflammatory cardiomyopathies such as sarcoidosis. This review discusses the role of PET imaging in assessing myocardial viability, inflammatory cardiomyopathies, and endocarditis; describes the different protocols needed to acquire images for specific imaging tests; and examines imaging interpretation for each image dataset-including identification of the mismatch defect in viability imaging, which is associated with significant improvement in LV function after revascularization. We also review the role of fluorodeoxyglucose PET in cardiac sarcoidosis diagnosis, the complementary role of magnetic resonance imaging in inflammatory cardiomyopathy, and the emerging use of cardiac PET in prosthetic valve endocarditis.

Assessment of myocardial viability by PET.

PURPOSE OF REVIEW: Viability assessment has a key role in the management of patients with ischemic heart disease. Positron emission tomography (PET) is a unique modality that evaluates myocardial viability via assessing the tissues metabolic and perfusion properties. The mainstay of metabolic imaging relies on glucose metabolism using fluorodeoxyglucose, a radiolabeled glucose analog. Mismatch in perfusion metabolism data denotes hibernating myocardium with a high likelihood of functional recovery following revascularization. Matched absence or reduction in perfusion metabolism data represents scar with a low likelihood of functional recovery following revascularization. This review will focus on PET radiotracers and techniques used to assess myocardial viability. RECENT FINDINGS: Single-center studies have shown that patients with PET mismatch undergoing bypass grafting had improved survival compared with those on medical therapy. In addition to survival benefit, the patients who underwent PET-guided revascularization had significant improvement in angina and heart failure symptomology. Recent technological advancements in the field of PET-magnetic resonance (MR) opens a new frontier in the field of advanced imaging as it combines anatomical, functional, tissue characterization, and metabolic perfusion data obtained in one setting. The incremental value of PET/MRI is best established in diagnosing and monitoring disease activity in patients with cardiac sarcoidosis and occult malignancies, but more studies are needed to assess it value in viability assessment. SUMMARY: In conclusion, imaging myocardial viability by PET provides assessment of both physiological perfusion and myocardial tissue's metabolic activity to differentiate hibernating from scarred myocardium.

Unconventional Path to Healing: Diagnostic Value of CMR in a Patient With Incessant VT.

A 58-year-old male patient with incessant ventricular tachycardia was referred to cardiac magnetic resonance for scar assessment. He was found to have metastatic amelanotic melanoma of the heart. The cardiac magnetic resonance-based diagnosis of cardiac malignancy critically altered the subsequent clinical management. There was a marked response to immunotherapy as evidenced by follow-up imaging studies. (Level of Difficulty: Intermediate.).

Heart Failure in Women.

Heart failure is an important cause of morbidity and mortality in women, and they tend to develop it at an older age compared to men. Heart failure with preserved ejection fraction is more common in women than in men and accounts for at least half the cases of heart failure in women. When comparing men and women who have heart failure and a low left ventricular ejection fraction, the women are more symptomatic and have a similarly poor outcome. Overall recommendations for guideline-directed medical therapies show no differences in treatment approaches between men and women. Overall, women are generally underrepresented in clinical trials for heart failure. Further studies are needed to shed light into different mechanisms, causes, and targeted therapies of heart failure in women.

Artificial neural network modeling enhances risk stratification and can reduce downstream testing for patients with suspected acute coronary syndromes, negative cardiac biomarkers, and normal ECGs.

Despite uncertain yield, guidelines endorse routine stress myocardial perfusion imaging (MPI) for patients with suspected acute coronary syndromes, unremarkable serial electrocardiograms, and negative troponin measurements. In these patients, outcome prediction and risk stratification models could spare unnecessary testing. This study therefore investigated the use of artificial neural networks (ANN) to improve risk stratification and prediction of MPI and angiographic results. We retrospectively identified 5354 consecutive patients referred from the emergency department for rest-stress MPI after serial negative troponins and normal ECGs. Patients were risk stratified according to thrombolysis in myocardial infarction (TIMI) scores, ischemia was defined as >5 % reversible perfusion defect, and obstructive coronary artery disease was defined as >50 % angiographic obstruction. For ANN, the network architecture employed a systematic method where the number of neurons is changed incrementally, and bootstrapping was performed to evaluate the accuracy of the models. Compared to TIMI scores, ANN models provided improved discriminatory power. With regards to MPI, an ANN model could reduce testing by 59 % and maintain a 96 % negative predictive value (NPV) for ruling out ischemia. Application of an ANN model could also avoid 73 % of invasive coronary angiograms while maintaining a 98 % NPV for detecting obstructive CAD. An online calculator for clinical use was created using these models. The ANN models improved risk stratification when compared to the TIMI score. Our calculator could also reduce downstream testing while maintaining an excellent NPV, though further study is needed before the calculator can be used clinically.

Novel Oral Anticoagulants for DC Cardioversion Procedures: Utilization and Clinical Outcomes Compared with Warfarin.

BACKGROUND: Novel oral anticoagulant (NOAC) agents dabigatran, rivaroxaban, and apixaban are increasingly utilized as thromboembolic prevention for patients with atrial fibrillation undergoing direct current cardioversion (DCCV) with post hoc analyses of clinical trials suggesting satisfactory safety and efficacy. This study characterizes utilization, effectiveness, and complications of NOAC agents for stroke prophylaxis in the setting of DCCV. METHODS: Comparison of warfarin and NOAC agents as periprocedural anticoagulation for DCCV procedures performed at Cleveland Clinic from January 2009 through December 2013. Variables of interest include utilization rates for each NOAC agent stratified by clinical parameters including CHADS2 score, and associated clinical outcomes including cerebrovascular accident (CVA), transient ischemic attack (TIA), peripheral arterial embolism (PAE), and bleeding events during 8 weeks of postprocedure follow-up. RESULTS: Among 5,320 DCCV procedures, 673 (12.6%) cases were excluded due to inadequate follow-up. Warfarin was utilized in 3,721 (80.1%), dabigatran in 719 (15.5%), rivaroxaban in 159 (3.4%), and apixaban in 48 (1.0%) with a steady increase in NOAC utilization from 2011 to 2013. There were low rates of CVA/TIA (warfarin: 0.97% vs NOAC 1.62%, P = 0.162) and bleeding (warfarin: 1.02% vs NOAC: 0.5%, P = 0.247) and no significant differences detected between agents. Higher CHADS2 /CHA2 DS2 -VASC scores were associated with thromboembolic and bleeding risk. Increasing age, chronic kidney disease, diabetes, coronary disease, and deep vein thrombosis/pulmonary embolism were associated with increased bleeding risk. CONCLUSION: In a high-volume, single-center experience, NOAC utilization has grown to account for over a third of cardioversion procedures, and these agents appear safe and effective compared to warfarin with low rates of thromboembolic and bleeding complications.

Myocardial perfusion imaging in emergency department patients with negative cardiac biomarkers: yield for detecting ischemia, short-term events, and impact of downstream revascularization on mortality.

BACKGROUND: In patients with possible acute coronary syndromes, guidelines recommend routine provocative testing after negative cardiac biomarkers. We hypothesized that myocardial perfusion imaging would be low yield with limited short-term value and that early revascularization would not affect mortality. METHODS AND RESULTS: We identified consecutive patients referred from our emergency department between October 2004 and September 2011 who had myocardial perfusion imaging after negative troponin T tests and nondiagnostic ECGs. We assessed the incidence of abnormal myocardial perfusion imaging, coronary angiography, revascularization, and mortality. In a cohort of 5354 patients (58.7% female, age 59 ± 13, 78.6% thrombolysis in myocardial infarction [TIMI] ≤2), 9% had >5% and 3.6% had >10% ischemic myocardium. Among patients with TIMI scores ≤2, 6.1% had >5% ischemic myocardium compared with 19.6% of patients with TIMI scores ≥3 (P<0.001). At 30 days, 7 patients were deceased, 187 had revascularization, and 6 had revascularization for an acute myocardial infarction. Over 3.4 ± 1.9 years of follow-up, 347 patients died. In propensity-matched groups of patients with ischemia, there was no association between early revascularization and mortality (hazard ratio, 1.00; 95% confidence interval, 0.49-2.07). CONCLUSIONS: Routine provocative testing to detect ischemia before emergency department discharge is low yield in patients with negative troponins and TIMI scores ≤2 and modest yield in patients with TIMI scores ≥3. In all patients, 30 days events are rare. Finally, in patients with ischemia, we are unable to demonstrate a mortality benefit with early revascularization.

Stress positron emission tomography is safe and can guide coronary revascularization in high-risk patients being considered for transcatheter aortic valve replacement.

BACKGROUND: The safety and accuracy of regadenoson stress positron emission tomography (PET) in patients with significant aortic stenosis (AS) is unknown. In patients undergoing surgical aortic valve replacement, coronary artery bypass grafting for coronary artery disease is standard, but the appropriate revascularization strategy in patients undergoing TAVR is uncertain. Stress PET may identify patients that benefit from revascularization. METHODS: Fifty consecutive patients who were referred for consideration of TAVR and underwent a stress PET study were retrospectively identified. We assessed major adverse cardiac events and significant decreases in systolic blood pressure. The percentage of jeopardized myocardium was determined by combining ischemic and hibernating myocardium. RESULTS: Our patients were high risk with a mean Society of Thoracic Surgeons mortality score of 11.4% and had severe AS with a moderately reduced left ventricular ejection fraction (EF) (mean aortic valve area of 0.78 ± 0.25 cm(2) and mean EF of 39 ± 16%). There were no major adverse events during testing. Transient hypotension occurred in 16% of the patients. Revascularization was performed in 44% of patients, and 91% of these patients had revascularization to territories jeopardized on PET. These patients had substantial jeopardized myocardium (median 19%), and only 3 patients underwent revascularization despite less than 10% jeopardized myocardium. CONCLUSIONS: Stress cardiac PET with regadenoson can be performed safely in patients with severe AS. Results of the PET study can accurately direct subsequent revascularization.

Complications arising from splenic artery embolization: a review of an 11-year experience.

BACKGROUND: Splenic artery embolization (SAE) is a staple adjunct in the management of blunt splenic trauma. We examined complications of SAE over an 11-year period. METHODS: Patients who underwent SAE were identified. Demographic data and the location of the SAE-proximal, distal, or combined-were noted. Major and minor complications were identified. RESULTS: Of 1,383 patients with blunt splenic trauma, 298 (21.5%) underwent operative management, and 1,085 (78.5%) underwent nonoperative management (NOM). SAE was performed in 8.1% of the NOM group. Major complications which occurred in 14% of patients, included splenic abscesses, infarction, cysts, and contrast-induced renal insufficiency. Three-fourths of patients with major complications underwent distal embolization. There were more complications in patients who underwent distal embolization (24% distal vs 6% proximal alone; P = .02). Minor complications, which occurred in 34% of patients, included left-sided pleural effusions, coil migration, and fever. CONCLUSIONS: SAE is a useful tool for managing splenic injuries. Major and minor complications can occur. Distal embolization is associated with more major complications.

Pan-antimicrobial failure of alexidine as a contact lens disinfectant when heated in Bausch & Lomb plastic containers: implications for the worldwide Fusarium keratitis epidemic of 2004 to 2006.

OBJECTIVE: ReNu with MoistureLoc (ReNuML), containing the antimicrobial agent alexidine 0.00045%, was associated with the Fusarium keratitis epidemic of 2004 to 2006. Although a single-point source contamination was ruled out, only Fusarium organisms were reported during the outbreak. This study investigated whether the reported loss of antimicrobial effectiveness toward Fusarium of ReNuML after exposure to heat in high-density polyethylene (HDPE) plastic containers could also be demonstrated with other common fungal and bacterial agents of keratitis. METHODS: A buffered solution of alexidine 0.00045% was incubated in glass and ReNu HDPE plastic containers at room temperature (RT) and 56°C for 4 weeks, serially diluted, and tested for its ability to inhibit the growth of 20 bacterial isolates, 12 non-Fusarium fungal isolates, and 7 Fusarium isolates originally involved in the keratitis epidemic. RESULTS: A statistically significant loss of antimicrobial capability was seen with all fungi, all gram-positive bacteria, and all isolates of Klebsiella when alexidine 0.00045% was incubated at 56°C in ReNu HDPE containers compared with RT or glass incubation (P≤0.0001). CONCLUSIONS: Heating of an alexidine solution in ReNu HDPE plastic (but not glass) containers results in the same loss of anti-Fusarium activity as reported when testing the original ReNuML solution. This loss of inhibitory activity is not specific to Fusarium and occurs with other fungi and bacteria that cause keratitis. The reasons for the lack of reports of bacterial and/or non-Fusarium fungal keratitis during the original Fusarium keratitis epidemic remain unclear at this time.