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Background: Rivaroxaban is a novel oral anticoagulant suggested as an alternative to low molecular weight heparin (LMWH). However, its efficacy and safety compared to LMWH for treating venous thromboembolism (VTE) in cancer patients remain unclear. Hypothesis: This study aims to compare the efficacy and safety of rivaroxaban against LMWH for treating VTE in cancer patients. Methods: We conducted a literature search for relevant articles on PubMed, Google Scholar, and Embase. Outcomes were pooled using the DerSimonian and Laird random-effects model as risk ratios (RR) with 95% confidence intervals (CI). A p-value of <0.05 was considered statistically significant. Results: A total of 14368 cancer patients (Rivaroxaban: 4378 and LMWH: 9990) from 13 studies were included with an average age of 62.5 and 61.9 respectively. At 3 months, rivaroxaban was associated with a decreased risk of recurrent VTE (RR 0.73, 95% CI: 0.59, 0.86, p<0.05) and bleeding-related hospitalization (RR 0.79, 95% CI: 0.61, 0.97, p<0.05) with statistical signifcant whereas, major bleeding (RR 0.87, 95% CI: 0.09, 1.65), non-major bleeding (RR 0.84, 95% CI: 0.60, 1.08) and all-cause mortality (RR 0.91, 95% CI: 0.72, 1.09) were comparable. At 6 months, rivaroxaban was associated with a decreased risk of all-cause mortality (RR 0.80, 95% CI: 0.62, 0.97, p<0.05), and bleeding-related hospitalization (RR 0.81, 95% CI: 0.65, 0.98, p<0.05) whereas major bleeding (RR 0.88, 95% CI: 0.52, 1.24), non-major bleeding (RR 0.85, 95% CI: 0.42, 1.29) and recurrent VTE (RR 0.83, 95% CI: 0.64, 1.01) were comparable. At 12 months, rivaroxaban was associated with a decreased risk of mortality (RR 0.71, 95% CI: 0.50, 0.92, p<0.05), however non-major bleeding (RR 1.38, 95% CI: 0.83, 1.94), cancer-associated thrombosis recurrence (RR 0.94, 95% CI: 0.73, 1.16), and bleeding (RR 0.70, 95% CI: 0.26, 1.15) were comparable. Conclusion: While rivaroxaban is associated with low adverse outcomes suggesting its use in treating VTE in cancer patients, further research is recommended.

Introduction: Patients with heart failure with preserved ejection fraction (HFpEF) have a high burden of comorbidities. To recognize the complex interplay of obesity, diabetes, and chronic kidney disease (CKD) in patients with cardiovascular disease, the cardiovascular-kidney-metabolic (CKM) syndrome was recently defined, but data on the burden of CKM in HFpEF is limited. Aim: We sought to describe the prevalence of CKM components in HFpEF leveraging data from control participants in clinical trials and NHANES. Methods: We analyzed data presented in publications from four randomized clinical trials that enrolled participants with HFpEF (all of which are available via NHLBI BioLINCC and will be included in the extant HeartShare dataset): TOPCAT, RELAX, NEAT-HFpEF, and INDIE. We abstracted baseline demographic and clinical variables from study publications to define CKM components (e.g., body mass index [BMI], diabetes status, hypertension, CKD status). We compared prevalence of CKM in these trials with a representative sample of US adults with self-reported history of heart failure (HF) from NHANES 2011-2018. Results: We included 1937 patients with HFpEF from four trials with enrollment between 2006-2016 and 715 adults representing 5.6 million adults aged ≥40 years with a self-report of HF between 2011-2018 from NHANES ( Table ). Mean age was similar among enrolled trial participants with HFpEF and those with HF in NHANES (~68-69 years). Mean BMI was in the obesity range and was similar among trial participants with HFpEF and HF in NHANES (31-35 kg/m 2 ). A significant proportion of individuals had hypertension in HFpEF trials (>80%) and in the NHANES sample with HF (89%). The proportion of stage ≥ 3 CKD in HFpEF trials (≥ 37%) was similar to the NHANES sample with HF (37%). Results are shown in Table . Conclusions: Patients with HFpEF enrolled in clinical trials and those with HF in general population are significantly enriched with CKM components that may contribute to morbidity and mortality. Similar prevalence estimates were observed despite variability in trial inclusion criteria and heterogeneity in defining HFpEF and highlight CKM as a central target for HFpEF management.

Background: Pulmonary hypertension (PH) and secondary right ventricle dysfunction is present in 20% of adults with coarctation of aorta (COA) based on echocardiographic studies. There are limited data about invasive hemodynamic characterization of PH in COA. The purpose of this study was to delineate the clinical features, hemodynamics, and outcomes of PH in COA. Method: Retrospective cohort study of adults with repaired COA that underwent right heart catheterization (RHC). PH was defined as pulmonary artery (PA) mean pressure >20 mmHg, and PH was classified as isolated precapillary PH and combined pre/postcapillary PH. Results: Of 99 COA patients that underwent RHC, 57 (58%) had PH. Of the patients with PH, 14 (25%) had isolated precapillary PH while 43 (75%) had postcapillary PH with or without precapillary disease. The correlates of PH were PA compliance (adjusted OR 0.79, 95% CI 0.71-0.86 per 1 ml/mmHg), left atrial reservoir strain (adjusted OR 0.95, 95% CI 0921-0.98 per 1%), and atrial fibrillation (adjusted OR 2.18, 95% CI 1.20-13.5). Higher PA mean pressure was associated with risk of cardiovascular events (adjusted HR 1.04, 95% CI 1.02-1.06 per 1 mmHg) and all-cause mortality (adjusted HR 1.05, 95% CI 1.02-1.08 per 1 mmHg). Conclusions: PH was present in over half of adults with COA referred for RHC, and one-quarter of the patients with PH presented with isolated precapillary PH suggesting an underlying PA vascular dysfunction as a contributing mechanism. Further studies are required to determine optimal therapies and strategies for prevention and treatment of PH in this population.

Introduction: Obesity is rising in prevalence worldwide and co-exists in patients with group 1 pulmonary hypertension (PH). Clinical and hemodynamic implications of having obesity in group 1 PH remain unknown. Hypothesis . We hypothesized that obese patients with group 1 PH would exhibit worse hemodynamic parameters including higher right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) compared to non-obese patients. Aims: To compare hemodynamic parameters obtained from right heart catheterization (RHC) and echo among group 1 PH with and without obesity. Methods: We evaluated a cohort of patients with group 1 PH who underwent RHC at Mayo Clinic Rochester between 2002 to 2021 with diagnosis adjudicated by detailed chart review and initiation of pulmonary vasodilator therapy. Patients with a mean pulmonary artery pressure (mPAP) ≥ 25 mm who were clinically diagnosed with WHO Group 1 PH and recommended pulmonary vasodilator therapy initiation were included. Results: Of 822 participants with group 1 PH, obesity was common, present in 325 patients (40%). There was no difference in survival among patients with and without obesity (HR 1.15; 95% CI 0.95-1.38; p=.15). Obese patients had higher RAP (12.8 ± 6.8 vs 10.4 ± 6.5 mm of Hg, p<.0001) and cardiac output (5.2 ± 2.2 vs 4.5 ± 1.8 L/min, p<.0001) compared to non-obese group (Table 1). Despite having group 1 PH, pulmonary capillary wedge pressure (PCWP) was higher with obesity (13.8 ± 6.3 vs 12.2 ± 6.5 mm of Hg, p=.001) compared to those without obesity. Along with higher PCWP, there was less pulmonary vascular disease severity with obese group 1 PH, with higher pulmonary artery compliance (PAC, 1.65 ± 1.06 vs 1.38 ± 0.84 mL/mm of Hg, p=.0002) and lower pulmonary vascular resistance (PVR, 7.9 ± 5.2 vs 9.4 ± 7.7 Wood Units, p=.0007). After accounting for age, gender, diabetes mellitus and systemic hypertension, the RAP, cardiac output, PAC and PCWP remained significantly higher, and PVR remained lower in obese patients (p<0.05 for all). Conclusions: Comorbid obesity is associated with higher biventricular filling pressures, higher cardiac output and lower pulmonary vascular disease severity in otherwise clinically diagnosed group 1 PH. These findings call for further study of whether targeting obesity with novel weight loss drugs such as glucagon like peptide 1 receptor agonists or other drugs can lower biventricular filling pressures and associated pulmonary hypertension in group 1 PH with obesity.

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.

Background: Atrial fibrillation (AF), the most common clinically managed cardiac arrhythmia, is known to increase the risk of heart failure, stroke, and mortality. Lipoprotein(a) [Lp(a)], a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD), also plays a role in cardiovascular health. However, the influence of Lp(a) on the development of AF, independent of its association with ASCVD, remains unclear. Hypothesis: Elevated Lp(a) may be associated with increased risk of new-onset AF. Methods: A retrospective study was conducted on patients from the three Mayo Clinic sites who had their Lp(a) levels measured and had no prior history of AF. Patients were categorized into two groups based on their serum Lp(a) concentrations: high Lp(a) (≥50 mg/dL) and low Lp(a) (<50 mg/dL). New AF diagnoses were identified during the follow-up period. Survival probabilities between the two Lp(a) groups were compared using the Kaplan–Meier curve and the Log-Rank test. Cox regression analyses, both univariable and multivariable, were performed to evaluate established risk factors and compare the risk of new-onset AF between the high and low Lp(a) groups. Results: A total of 108,930 patients were included (median age: 55 years, 58% males), with a follow-up duration for up to 10 years. Incident AF was detected in 8432 (7.7%) patients. Median serum levels of Lp(a) were significantly higher in patients with AF versus non-AF patients: 15 (IQR 43) vs. 12 (IQR 34) mg/dL, p<0.001. The percentage of patients having elevated Lp(a) was significantly higher in the AF group versus non-AF group: 2119 (25%) vs 21151 (21%), p<0.001. Survival probability for new-onset AF was significantly lower in patients with elevated Lp(a) compared with those with low Lp(a) (log rank p<0.001, Figure 1). In the univariate analysis, high Lp(a) levels were associated with a 17% increase in the risk of AF (HR = 1.17, 95% CIs: 1.12 to 1.23). The multivariate analysis adjusted for well-established risk factors for AF showed a less strong but still significant association, with a 10% increase in AF risk (HR = 1.10, 95% CI: 1.05 to 1.15). Conclusion: Our study suggests that elevated Lp(a) (≥50 mg/dL) seems to be an independent risk factor for new-onset AF. Future prospective studies are still warranted to validate our results.

Background: Mavacamten was approved by the US Food and Drug Administration (FDA) in April 2022 for the treatment of adults with New York Heart Association (NYHA) class II-III symptomatic obstructive hypertrophic cardiomyopathy (HCM). Few studies have reported on the long-term real-world effectiveness and safety of mavacamten. We evaluated clinical outcomes in patients on mavacamten in multiple health centers across the United States. Research Questions: This study assessed the real-world effectiveness and safety of mavacamten in patients with symptomatic obstructive HCM. Methods: In this multi-center observational study, we evaluated patient characteristics at baseline, NYHA class, left ventricular outflow tract gradients (LVOTg) at rest and Valsalva, and left ventricular ejection fraction (LVEF) in patients with symptomatic obstructive HCM treated with mavacamten for up to 72 weeks. Results: Mavacamten was initiated in 172 patients across 4 US centers (UCSF, Mayo Arizona, Stanford, and Atlantic Health System/Morristown Medical Center). Baseline characteristics included: 56% female, mean age 64 (standard deviation ±13) years, 47% NYHA class III, mean resting LVOTg of 47 mmHg and mean Valsalva LVOTg of 89 mmHg, and 23% non-White. Comorbidities included hypertension (56%) and atrial fibrillation (25%) at baseline (Table). Patients experienced a notable early response to mavacamten in resting and Valsalva gradients by week 4, which was sustained through week 72 (Figure A). No patients were NYHA class III at week 72, compared to 47% at baseline (Figure B). Mean LVEF did not change substantially between baseline and week 72. No patients experienced an LVEF of <40% and 2% experienced an LVEF of <50%. Conclusions: This is the largest observational study to date demonstrating the effectiveness and safety of mavacamten with substantial sustained reductions in resting and Valsalva LVOTg, and progressive improvements in NYHA class without considerable changes in mean LVEF up to 72 weeks.

Background and Objective: Decline of cardiovascular (CV) function is commonly observed in patients with severe acute pancreatitis (AP), which is associated with high mortality and morbidity. While the pathological changes in the pancreas during severe AP have been extensively studied, the impact on the CV system has not been well characterized. Furthermore, obesity is a major risk factor for severe AP. Hereby we utilized an obesity-associated mouse AP model to assess potential alterations in vascular integrity and cardiac function, two major components of circulatory failure. Methods: Wild-type male C57BL6J mice were fed a normal or a high fat (to induce obesity) diet. Both groups received intraperitoneal injection of cerulein (100 mg/kg/h x12) to induce AP. H&E and TUNEL staining of pancreas were performed to assess histology and cell death. To measure vascular integrity, we measured the leakiness of a fluorescein-conjugated dextran (70 kDa) in tissue parenchyma and serum levels of soluble vascular endothelial (VE)-cadherin, which has recently shown to be shed from endothelial cells with disrupted adherens junctions. Cardiac systolic and diastolic function were assessed by echocardiography at baseline and post-AP induction. Results: Compared to lean mice, obese mice developed more severe pancreatic edema, cell death and inflammatory cell infiltration, along with significantly increased accumulation of fluorescent dextran in multiple organs including pancreas, heart, lung, and kidney, suggesting systemic disruption of vascular integrity. Increased serum levels of soluble VE-cadherin in obese mice (vs. lean) after AP induction further supported compromised endothelial cell barrier function. At baseline, obese mice exhibited similar cardiac function to lean mice. However, obese mice, but not lean mice, developed impaired systolic and diastolic function post-AP induction, as supported by decreased ejection fraction and e’ velocity respectively. Conclusion: In this obesity-associated severe AP mouse model, systemic vascular permeability is increased, and cardiac function is substantially compromised. Systemic vascular hyperpermeability and cardiac dysfunction may represent therapeutic targets to enhance the outcomes in severe AP.

Background: Secondary prevention after percutaneous coronary interventions (PCIs) is still challenging and lipoprotein(a) [Lp(a)] is believed to be a residual risk factor in this setting. However, the effect of Lp(a) in case of well-controlled low-density lipoprotein cholesterol (LDL-C) is still unclear. The interaction between Lp(a) and LDL-C has been studied in primary prevention but still needs to be investigated in secondary prevention. Hypothesis: Achieving adequate LDL-C control after PCI may reduce the cardiovascular (CV) risk associated with Lp(a). Methods: A retrospective study of consecutive patients who underwent PCI and reached their LDL-C target levels (<70mg/dL) at three academic centers sites between 2006 and 2017. All included patients must have an Lp(a) measurement before the PCI intervention. Clinical outcomes on 10-year follow-up were collected by reviewing the electronic patients' records. The primary outcomes included all-cause mortality (ACM) and major adverse CV events (MACE) including non-fatal MI, ischemic stroke, coronary revascularization, and CV death. Kaplan-Meier curves were created to compare the survival probabilities among patients with high Lp(a) (≥50mg/dL) versus those with low Lp(a) (<50mg/dL). Univariate and multivariate Cox regression analyses were performed to quantify the association of elevated Lp(a) with outcomes and control for potential confounders. Results: In total, 878 patients (median age = 68 years, 74% males) were included in the analysis. Of them, 242 (27.6%) had high Lp(a) ≥50mg/dL. Kaplan Meier analyses did not reveal any significant difference in survival probabilities across the Lp(a) groups for any of the outcomes (Figure 1). The results were consistent in univariate (MACE, HR: 1.08 [95%CIs 0.85-1.35]; ACM, HR: 0.97 [95% CI 0.76-1.23]) and multivariate analyses (MACE, HR: 1.14, [95% CIs 0.90-1.45]; ACM, HR: 1.08 [95% CI 0.84-1.39]). Conclusion: These findings suggest that, in patients who underwent PCI and achieved an LDL-C target of <70 mg/dL, elevated Lp(a) levels were not associated with and increased risk of MACE or mortality. Controlling the LDL-C should still be the cornerstone in secondary prevention after PCI, however, larger prospective studies are still warranted to validate our results.

Introduction: Psychological resilience is the ability to adapt to significant adversity. Higher resilience has been associated with better quality of life in HF, but its association with outcomes is not known. Herein, we characterize resilience and its association with outcomes in HF. Research Questions/Hypothesis: Greater resilience is associated with better health status and outcomes in high-risk HF. Methods: In a prospective study, adult residents of 11 counties in Southeastern Minnesota with HF who had been hospitalized with decompensated HF or ventricular arrhythmia (“high-risk HF”) in the preceding 1 year were mailed a survey that included questionnaires to assess resilience (Connor Davidson resilience scale, CD-RISC2), health status (KCCQ-12), and other psychosocial constructs in March 2022. Patients were divided into tertiles by resilience scores, and association with outcomes (survival and hospitalization) were examined using Cox proportional hazard regression and Andersen-Gill models, respectively. Results: Among 649 respondents (mean age 76 ± 11.5 years, 40% women, 64.3% HFpEF), patients with greater resilience were older ( p=0.015 ), had lower BMI ( p=0.003 ) and were more often retired or employed (vs disabled or unemployed, p<0.001 ). Greater resilience was moderately correlated with better health status (r=0.33), social support (r=0.27), and health literacy (r=-0.30); and lower treatment burden (r=-0.42), symptom burden (r=-0.41), and fewer depressive symptoms (r=-0.41) ( p<0.001 for all ). At 1-year follow up, patients with the lowest resilience (lowest tertile) were at a significantly increased risk for HF hospitalizations (adjusted HR 2.09, 95% CI 1.06-4.11) and CV mortality (adjusted HR 1.90, 95% CI 1.01-2.57) compared to those with highest resilience. There was no statistically significant association of resilience with risks of all-cause mortality or all-cause hospitalizations after adjustment ( Figures 1A-D ). Conclusion: Higher resilience is associated with better health status and psychosocial profile. Patients with low resilience are at increased risk for HF hospitalizations and CV mortality. Impact of resilience on long term outcomes and response to interventions must be tested in future studies.