Koepke, Laura

Abstract Background Treatment with immune-checkpoint inhibitors (ICI) may be associated with adverse cardiac events. Troponin elevation is part of the diagnostic criteria for ICI related myocarditis (ICIrM) and myocardial infarction (MI), however there is limited data for causes of troponin elevation independent of MI and ICIrM and their clinical outcomes with ICI therapy. Purpose To assess the diagnostic and prognostic value of high-sensitivity troponin T (hs-TnT) in patients treated with ICI based on different etiologies and association with cardiac events. Methods All patients treated with ICI who had hs-TnT measured at a multi-center institution from 2011 to 2022 were included. Medical records were reviewed for baseline characteristics and long-term outcomes, including cardiac death and MACE (MI, stroke, heart failure [HF]), and cause of hs-TnT elevation. Risk of cardiac events and mortality were compared for the different etiologies of hs-TnT elevation. Results Of 5,423 patients treated with ICI, 1669 had post-ICI hs-TnT measurement. Mean age was 68.7±11.3 years, 58.3% were male, with follow-up through one year from ICI first administration. Elevated hs-TnT was seen in 1136 patients, with the different causes for elevation depicted in Figure 1, panel A. ICIrM patients exhibited the highest median hs-TnT value of 364 ng/L (IQR 1096), followed by a median of 98 ng/L for MI/Type 2 ischemia, 61 ng/L for infection/sepsis, 51 ng/L for pulmonary embolus, 50 ng/L for HF and 27 ng/L for indeterminate causes, Figure 1, panel B. Additionally, median time from first ICI dose to hs-TnT elevation according to each of the diagnoses are depicted in Figure 1, panel C, with ICIrM showing the shortest median time of 44 days (IQR 74). Hs-TnT elevation in patients with ICIrM had the highest risk for cardiac death (HR 52.7, 95% CI 11.7-238.0, p<0.001), followed by hs-TnT elevation due to HF (HR 15.9, 95% CI 2.9-87.0, p=0.001), MI/type 2 ischemia (HR 11.6, 95% CI 2.4-56.1, p=0.002), and infection/sepsis (HR 5.7, 95% CI 1.0-31.0, p=0.045) compared to those with no hs-TnT elevation, Figure 2, panel A. Similarly, patients with ICIrM had highest risk for MACE (HR 8.2, 95% CI 4.4-15.3, p<0.001), followed by increased hs-TnT due to MI/type 2 ischemia (HR 8.1, 95% CI 5.0-13.1, p<0.001), HF (HR 7.6, 95% CI 4.2-13.7, p<0.001), pulmonary embolism (HR 5.1, 95% CI 2.5-10.8, p<0.001), infection/sepsis (HR 4.1, 95% CI 2.4-7.0, p<0.001), and indeterminate cause (HR 2.4, 95% CI 1.5-3.8, p<0.001), Figure 2, panel B. Conclusions Hs-TnT measurements have prognostic value for cardiac events in cancer patients receiving ICI therapy, including in those without ICIrM. Patients with ICIrM demonstrated the highest median hs-TnT levels and the poorest outcomes, with a graded response observed; the worst prognosis was seen in patients with hs-TnT elevation due to ICIrM, followed by other causes, and those without hs-TnT elevation had the best prognosis.Figure 1 Figure 2

Background Immune‐checkpoint inhibitors (ICI) are associated with adverse cardiac events. Although troponin elevation is a diagnostic criterion for ICI‐related myocarditis (ICIrM) and myocardial infarction, data on other causes of troponin elevation and their outcomes in ICI‐treated patients are limited. Methods All patients treated with ICI who had hs‐TnT (high‐sensitivity troponin T) measured at a multicenter institution from 2011 to 2022 were included. Clinical data, outcomes (cardiac death, heart failure (HF), major adverse cardiovascular events [myocardial infarction, stroke, heart failure]), and cause of hs‐TnT elevation were assessed. Risks of cardiac events were compared across hs‐TnT elevation causes. Results Of 5423 patients treated with ICI, 1669 had post‐ICI hs‐TnT measurement (mean age 68.7±11.3 years, 58.3% male), with 1‐year follow‐up. Hs‐TnT elevation in patients with ICIrM (n=59) was associated with the highest risk for cardiac death (hazard ratio [HR], 52.7 [95% CI, 11.7–238.0], P <0.001), followed by hs‐TnT elevation due to heart failure (HR, 15.9), myocardial infarction/type 2 ischemia (HR, 11.6), and infection/sepsis (HR, 5.7), compared with those with no hs‐TnT elevation. ICIrM also carried highest risk for major adverse cardiovascular events (HR, 8.2, [95% CI, 4.4–15.3], P <0.001), followed by myocardial infarction/type 2 ischemia (HR, 8.1), heart failure (HR, 7.6), pulmonary embolus (HR, 5.1), infection/sepsis (HR, 4.1), and indeterminate cause (HR, 2.4). Among ICIrM, HsTnT value >576 ng/L best predicted risk for cardiac death and >319 ng/L for major adverse cardiovascular events. Conclusions Hs‐TnT elevation after ICI therapy is associated with increased risk of cardiac events, particularly in ICIrM, and a graded prognostic association depending on the cause of hs‐TnT elevation. Identifying the underlying cause and troponin thresholds may guide risk stratification and management.

Background: ICI-related myocarditis is challenging to diagnose and associated with adverse cardiovascular events and mortality. ICI therapy has also been associated with acute coronary events. There is limited data regarding cardiac troponin T (cTnT) and its association with these cardiovascular outcomes. Methods: All patients treated with ICI at a tertiary institution from 2011 to 2022 were identified, and the charts of those with cTnT measurements were reviewed. In patients with cTnT elevation (cutoff of >14 ng/L), if the Bonaca criteria for myocarditis were met, these patients were labeled as cTnT+/myocarditis+, otherwise as cTnT+/myocarditis-. Patients with non-elevated cTnT values were labeled cTnT-. Medical records were reviewed for baseline characteristics and long-term outcomes, including cardiac death, new heart failure (HF) diagnosis, and MACE (myocardial infarction, TIA/stroke, new HF diagnosis). Kaplan-Meier curves were created to plot the comparison between the three groups. Results: A total of 1669 cancer patients who received ICI therapy had post-ICI cTnT measurements. Mean age was 68.7±11.3, 58.3% were male, with follow-up at 1 year post ICI administration. Of these, 59 patients were cTnT+/myocarditis+, 1077 patients were cTnT+/myocarditis-, and 533 were cTnT-. Survival free of cardiac death, MACE and new HF diagnosis showed a graded response from worst in cTnT+/myocarditis+ patients and best in cTnT- patients; cTnT+/myocarditis- patients had a more favorable but still worse prognosis than cTnT- patients (Figure 1). A cTnT value of 95 ng/L was identified as the best cutoff for the diagnosis of ICI-related myocarditis (AUC 0.82, sensitivity 81.36%, specificity 81.62%). The optimal cTnT cutoff for cardiac death was 576 ng/L (0.70, sensitivity 72%, specificity of 61%) and for MACE 319 ng/L (AUC 0.61, sensitivity 70%, specificity of 52%). Conclusion: In cancer patients receiving ICI therapy cTnT elevations indicate a higher risk of MACE, HF, and cardiac mortality even in patients without myocarditis. Although worst outcomes are seen in those meeting diagnostic criteria for myocarditis.

Abstract Aims Cardiac amyloidosis (CA) is common in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Cardiac amyloidosis has poor outcomes, and its assessment in all TAVR patients is costly and challenging. Electrocardiogram (ECG) artificial intelligence (AI) algorithms that screen for CA may be useful to identify at-risk patients. Methods and results In this retrospective analysis of our institutional National Cardiovascular Disease Registry (NCDR)-TAVR database, patients undergoing TAVR between January 2012 and December 2018 were included. Pre-TAVR CA probability was analysed by an ECG AI predictive model, with &gt;50% risk defined as high probability for CA. Univariable and propensity score covariate adjustment analyses using Cox regression were performed to compare clinical outcomes between patients with high CA probability vs. those with low probability at 1-year follow-up after TAVR. Of 1426 patients who underwent TAVR (mean age 81.0 ± 8.5 years, 57.6% male), 349 (24.4%) had high CA probability on pre-procedure ECG. Only 17 (1.2%) had a clinical diagnosis of CA. After multivariable adjustment, high probability of CA by ECG AI algorithm was significantly associated with increased all-cause mortality [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.01–1.96, P = 0.046] and higher rates of major adverse cardiovascular events (transient ischaemic attack (TIA)/stroke, myocardial infarction, and heart failure hospitalizations] (HR 1.36, 95% CI 1.01–1.82, P = 0.041), driven primarily by heart failure hospitalizations (HR 1.58, 95% CI 1.13–2.20, P = 0.008) at 1-year follow-up. There were no significant differences in TIA/stroke or myocardial infarction. Conclusion Artificial intelligence applied to pre-TAVR ECGs identifies a subgroup at higher risk of clinical events. These targeted patients may benefit from further diagnostic evaluation for CA.

Introduction: Syncope was reported to be associated with sudden cardiac death in heart failure patients regardless of the etiology of syncope. We attempted to use unsupervised machine learning to identify the prognostically distinct phenotypes in a large population of heart failure patients presenting with syncope. Hypothesis: Unsupervised machine learning can identify prognostically distinct phenotypes in a large population of heart failure patients presenting with syncope. Methods: Patients with a diagnosis of systolic or diastolic heart failure and syncope at Mayo Clinic sites were identified for baseline and follow-up data. Variables with ≥ 20% missing data were excluded; a total of 57 variables were used for k-means clustering analysis. Patients were grouped according to 4 distinct k-means determined clusters for statistical analysis. Results: A total of 3,557 patients with proper follow-up and echocardiography data were included in the final analysis. The median follow-up duration was 36.3 months, and 2908 (81.7%) patients died. Cluster 2 (n= 680) was identified as the cluster with the highest mortality (92%), which contained patients with high proportions of cardiovascular comorbidities, especially chronic kidney disease. The Kaplan-Meier survival curves are shown in Figure 1. In multivariate Cox regression analysis, the presence of CKD independently predicts mortality (HR 1.62, 95%CI 1.50-1.76, p <0.0001) after adjusting for age and sex. Conclusions: Unsupervised machine learning identified patients with CKD, CAD and DM are high-risk phenotypes in heart failure patients with syncope, and can be used to guide future studies in this highly heterogeneous, unexplored population.

Abstract Background: Inpatient status has been shown to be a predictor of poor bowel preparation for colonoscopy; however, the optimal bowel preparation regimen for hospitalized patients is unknown. Our aim was to compare the efficacy of bowel preparation volume size in hospitalized patients undergoing inpatient colonoscopy.Methods: This prospective, single blinded (endoscopist), randomized controlled trial was conducted as a pilot study at a tertiary referral medical center. Hospitalized patients undergoing inpatient colonoscopy were assigned randomly to receive a high, medium, or low-volume preparation. Data collection included colon preparation quality, based on the Boston Bowel Preparation Scale, and a questionnaire given to all subjects evaluating the ability to completely finish bowel preparation and adverse effects (unpleasant taste, nausea, and vomiting). Results: Twenty-five colonoscopies were performed in 25 subjects. Patients who received low-volume preparation averaged a higher mean total BBPS (7.4, SD 1.62), in comparison to patients who received high-volume (7.0, SD 1.41) and medium-volume prep (6.9, SD 1.55), P = 0.77. When evaluating taste a higher score meant worse taste. The low-volume group scored unpleasant taste as 0.6 (0.74), while the high-volume group gave unpleasant taste a score of 2.2 (0.97) and the medium-volume group gave a score of 2.1 (1.36), P < 0.01.Conclusion: In this pilot study we found that low-volume colon preparation may be preferred in the inpatient setting due its better rate of tolerability and comparable bowel cleanliness when compared to larger volume preparation, although we cannot overreach any definitive conclusion. Further more robust studies are required to confirm these findings.Trial registration: The Affect of Low-Volume Bowel Preparation for Hospitalized Patients Colonoscopies. Trial registration: NCT01978509 (terminated). Retrospectively registered on November 07, 2013.

Abstract Background: Inpatient status has been shown to be a predictor of poor bowel preparation for colonoscopy; however, the optimal bowel preparation regimen for hospitalized patients is unknown. Our aim was to compare the efficacy of bowel preparation volume size in hospitalized patients undergoing inpatient colonoscopy.Methods: This prospective, single blinded (endoscopist), randomized controlled trial was conducted as a pilot study at a tertiary referral medical center. Hospitalized patients undergoing inpatient colonoscopy were assigned randomly to receive a high, medium, or low-volume preparation. Data collection included colon preparation quality, based on the Boston Bowel Preparation Scale, and a questionnaire given to all subjects evaluating the ability to completely finish bowel preparation and adverse effects (unpleasant taste, nausea, and vomiting). Results: Twenty-five colonoscopies were performed in 25 subjects. Patients who received low-volume preparation averaged a higher mean total BBPS (7.4, SD 1.62), in comparison to patients who received high-volume (7.0, SD 1.41) and medium-volume prep (6.9, SD 1.55), P = 0.77. When evaluating taste a higher score meant worse taste. The low-volume group scored unpleasant taste as 0.6 (0.74), while the high-volume group gave unpleasant taste a score of 2.2 (0.97) and the medium-volume group gave a score of 2.1 (1.36), P < 0.01.Conclusion: In this pilot study we found that low-volume colon preparation may be preferred in the inpatient setting due its better rate of tolerability and comparable bowel cleanliness when compared to larger volume preparation, although we cannot overreach any definitive conclusion. Further more robust studies are required to confirm these findings.Trial registration: The Affect of Low-Volume Bowel Preparation for Hospitalized Patients Colonoscopies. Trial registration: NCT01978509 (terminated). Retrospectively registered on November 07, 2013.

Abstract Background: Inpatient status has been shown to be a predictor of poor bowel preparation for colonoscopy; however, the optimal bowel preparation regimen for hospitalized patients is unknown. Our aim was to compare the efficacy of bowel preparation volume size in hospitalized patients undergoing inpatient colonoscopy.Methods: This prospective, single blinded (endoscopist), randomized controlled trial was conducted as a pilot study at a tertiary referral medical center. Hospitalized patients undergoing inpatient colonoscopy were assigned randomly to receive a high, medium, or low-volume preparation. Data collection included colon preparation quality, based on the Boston Bowel Preparation Scale, and a questionnaire given to all subjects evaluating the ability to completely finish bowel preparation and adverse effects (unpleasant taste, nausea, and vomiting). Results: Twenty-five colonoscopies were performed in 25 subjects. Patients who received low-volume preparation averaged a higher mean total BBPS (7.4, SD 1.62), in comparison to patients who received high-volume (7.0, SD 1.41) and medium-volume prep (6.9, SD 1.55), P = 0.77. When evaluating taste a higher score meant worse taste. The low-volume group scored unpleasant taste as 0.6 (0.74), while the high-volume group gave unpleasant taste a score of 2.2 (0.97) and the medium-volume group gave a score of 2.1 (1.36), P < 0.01.Conclusion: In this pilot study we found that low-volume colon preparation may be preferred in the inpatient setting due its better rate of tolerability and comparable bowel cleanliness when compared to larger volume preparation, although we cannot overreach any definitive conclusion. Further more robust studies are required to confirm these findings.Trial registration: clinicaltrials.gov NCT01978509

Abstract Background: Inpatient status has been shown to be a predictor of poor bowel preparation for colonoscopy; however, the optimal bowel preparation regimen for hospitalized patients is unknown. Our aim was to compare the efficacy of bowel preparation volume size in hospitalized patients undergoing inpatient colonoscopy. Methods: This prospective, single blinded (endoscopist), randomized controlled trial was conducted as a pilot study at a tertiary referral medical center. Hospitalized patients undergoing inpatient colonoscopy were assigned randomly to receive a high, medium, or low-volume preparation. Data collection included colon preparation quality, based on the Boston Bowel Preparation Scale, and a questionnaire given to all subjects evaluating the ability to completely finish bowel preparation and adverse effects (unpleasant taste, nausea, and vomiting). Results: Twenty-five colonoscopies were performed in 25 subjects. Patients who received low-volume preparation averaged a higher mean total BBPS (7.4, SD 1.62), in comparison to patients who received high-volume (7.0, SD 1.41) and medium-volume prep (6.9, SD 1.55), P = 0.77. When evaluating taste a higher score meant worse taste. The low-volume group scored unpleasant taste as 0.6 (0.74), while the high-volume group gave unpleasant taste a score of 2.2 (0.97) and the medium-volume group gave a score of 2.1 (1.36), P < 0.01. Conclusion: In this pilot study, the low-volume colon preparation Prepopik® may be preferred in the inpatient setting due its better rate of tolerability and comparable bowel cleanliness when compared to larger volume preparation, although we cannot overreach any definitive conclusion. Further more robust studies are required to confirm these findings.

Abstract Background: Inpatient status has been shown to be a predictor of poor bowel preparation for colonoscopy; however, the optimal colon cleansing regimen protocol for hospitalized patients is unknown. Our aim was to compare the efficacy of bowel preparation volume size in hospitalized patients undergoing inpatient colonoscopy.Methods: This prospective, single blinded (endoscopist), randomized controlled trial was conducted as a pilot study at a tertiary referral medical center. Hospitalized patients undergoing inpatient colonoscopy were assigned randomly to receive a high, medium, or low-volume solution. Data collection included colon preparation quality based on the Boston Bowel Preparation Scale and a questionnaire given to all subjects, in which we evaluated the ability to completely finish bowel preparation and adverse effects (unpleasant taste, nausea, and vomiting). Results: Twenty-five colonoscopies were performed in 25 subjects. Patients who received low-volume prep averaged a higher mean total BBPS (7.4, SD 1.62), in comparison to patients who received high-volume (6.6, SD 2.19) and medium-volume prep (6.9, SD 1.55), P = 0.64. The low-volume group scored unpleasant taste as 0.6 (0.74), while the high-volume group gave unpleasant taste a score of 2.2 (0.97) and the medium-volume group gave a score of 2.1 (1.36), P < 0.01.Conclusion: Although not statistically significant, a low-volume colon preparation showed a trend of equivalent quality of bowel preparation measured by BBPS in comparison to traditional volume regimens, with less unpleasant taste, which may contribute to better patient compliance and therefore better bowel preparation in the inpatient setting. Further more robust studies are required to confirm these findings.Trial registration: clinicaltrials.gov NCT01978509