Citations

Abstract Aims We evaluated clinical outcomes with GLP-1 RA use post-TAVI in patients with T2D. GLP-1 receptor agonists (GLP1-RAs) lower cardiovascular risk in type 2 diabetes (T2D), but their impact in patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), remained unexplored. Methods and results We conducted a retrospective cohort study using the TriNetX network, including 25 184 adults (≥18 years) with T2D who underwent TAVI (2015–2023). Patients were stratified based on GLP1-RA initiation within 14 days post-TAVI. Baseline characteristics, comorbidities, medications, and laboratory data were balanced using 1:1 propensity score matching (PSM). Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for events from one-month post-TAVI until the most recent follow-up. PSM yielded 1101 patients per group, with a mean age of 73 years and 39% female. Mean follow-up duration was 2.2 ± 1.1 and 2.6 ± 1.8 years for GLP1-RA users and non-users, respectively. GLP1-RA use was also associated higher survival probability (HR: 0.708 [95% CI: 0.583–0.859]), and lower rates of all-cause hospitalization (HR: 0.790 [95% CI, 0.706–0.885]), major cardiovascular events (HR: 0.849 [95% CI: 0.749–0.963]), and acute heart failure exacerbation (HR: 0.785 [95% CI: 0.677–0.909]), acute kidney injury (HR: 0.843 [95% CI: 0.719–0.988]), and major kidney events (HR: 0.665 [95% CI: 0.510–0.866]). No differences were observed in acute myocardial infarction, cerebral infarction, or cardiac arrest. Conclusion In patients with T2D undergoing TAVI, GLP1-RA use is associated with significant survival benefits and improved cardiorenal outcomes. However, these findings are limited by the observational design, high comorbidity burden, lack of data on medication compliance, and specific cause of death. Prospective trials are warranted to confirm these benefits.

Abstract This brief report details the initial findings from a Phase 1b/2 trial of TN-201, an adeno-associated virus serotype 9 (AAV9) gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), a condition with significant morbidity, increased risk of mortality, and no approved therapy for the majority of patients. TN-201 was well tolerated, and changes to the management of potential immune responses resulted in a shorter period of immunosuppression. These results show consistent transduction and expression of TN-201 in cardiomyocytes, corresponding with increases in MyBP-C levels, reductions or stabilization of cardiac biomarkers, and reductions in key measures of left ventricular (LV) hypertrophy.

Abstract Background Central nervous system (CNS) tumors are a significant cause of morbidity and mortality in sub-Saharan Africa (SSA). To date, no large-scale efforts have focused on brain tumor genetics within this region. This study aimed to assess and map the current neuro-oncology capacity in SSA, including workforce availability and existing services for brain tumor registries and biobanks. The results represent the final analysis representing respondents from 70 healthcare institutions. Methods This cross-sectional study utilized an online survey to collect data from healthcare professionals involved in CNS tumor care across SSA through the Society for Neuro-Oncology SSA (SNOSSA). The survey gathered information on the availability of neuro-oncology practitioners, neuropathology and molecular diagnostic capacity, brain tumor management, cancer registries, and biobanking of specimens. Purposive sampling was used to identify participants, with the questionnaire provided in English, French, and Swahili. Results A total of 145 respondents from 22 countries and 70 healthcare institutions participated. Among the 70 institutions, neurosurgery was available in 89%, anatomic pathology in 74%, and medical oncology in 71%. For radiologic evaluation, 64% of institutions reported having both CT and MRI, while 17% had CT only. Molecular testing through IHC or NGS was available in 46% of institutions. Multidisciplinary tumor boards for CNS cases were present in 86% of institutions. General cancer registries were available in 66% of institutions, while 29% had brain tumor-specific registries, and 10% maintained brain tumor biorepositories. Conclusion This study provides a comprehensive summary of the neuro-oncology capacity in SSA. Next steps are to reach out to institutions who have registries and determine what data are being collected, with the hopes of defining a set of common elements to expand registry efforts across SSA. Similarly, to reach out to institutions that have ongoing brain tumor biobanks and CT/MRI capacity to determine what infrastructure exists.

Abstract Advocacy has long been at the core of the infectious diseases (ID) field, with clinicians and researchers advocating to ensure patients can access the care they need on an individual and global scale. The Infectious Diseases Society of America Training Program Directors’ (PD) Committee met in 2024 and discussed ways that advocacy is and should be incorporated into fellowship training, as well as highlighted the role PDs play in advocating for their trainees. Policies with a negative impact on ID clinical care, public health, and research underscore the importance of mobilizing the field of ID to advocate for the patients and communities we serve, as well as for ourselves. This paper presents ideas generated at this meeting and is meant to serve as a reference for ID PDs, as well as the wider ID community, as a call to action for teaching and participating in advocacy work.

Abstract Aims Alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are interconnected and highly prevalent. Integrating substance use disorder (SUD) treatment into medical clinics may increase access to specialized care and improve liver-related outcomes. Methods A scoping review and quantitative analysis were completed on published literature before 4 September 2024. Included articles described SUD treatment integrated in medical settings for adults with liver disease and alcohol use. Specific focus in the analysis was placed on integrations that utilized telehealth formats, facilitated access to medications for AUD (MAUD), and intervened in liver transplant populations. Results Twenty-three full-length manuscripts and 10 conference abstracts met the inclusion criteria. Fourteen articles discussed MAUD access in ALD populations. Nine utilized telehealth interventions, and 12 focused on pre- and post-liver transplant populations considered high-risk for returning to alcohol use. Nine full-length manuscripts were included in a quantitative analysis, which showed a 9.7% risk difference (95% CI: 5.9–13.4) in any alcohol use, favoring integrated care over treatment as usual. Conclusions Integrated care for AUD and concurrent ALD populations can effectively reduce returns to alcohol use and be successfully integrated in a medical setting. The core ingredient of such interventions was the inclusion of an addiction medicine specialist into a medical setting, rather than an outside referral. Strategic telehealth utilization can further reduce geographic and specialty-specific barriers to SUD care in medically ill populations. More consensus is needed on key components, processes, and optimal outcomes for such integrated programs for people with concurrent liver disease and AUD.

Abstract Background Angina with non-obstructive coronary artery disease (ANOCA) is increasingly recognized in clinical practice but effective therapy is difficult to apply due to the heterogeneity of pathophysiological substrates: structural coronary microvascular dysfunction (CMD), functional (vasospastic) CMD, epicardial artery vasospasm, non-cardiac chest pain. Current guidelines recommend invasive coronary function testing with inherent limitations in cost, risk, and access. Objective To evaluate the feasibility of a step-wise, multi-marker, multi-stress assessment of ANOCA patients by stress echocardiography (SE). Methods In an observational, prospective, multicenter, international study, we enrolled 1146 ANOCA patients (age =65.6±11.6years, 636 men, 55, %). All patients underwent a vasodilator SE (adenosine or dipyridamole) with coronary flow velocity reserve (CFVR) measurement in the mid-distal left anterior descending artery (LAD). In a subset of patients with a normal CFVR and strong clinical suspicion for vasospasm, a hyperventilation (HYPER) test (30 deep breaths/min for 5 min) was performed, followed by semi-supine exercise (EX) if negative. Positivity criteria were stress-specific: CFVR < 2.0 for vasodilators; coronary flow velocity (CFV) reduction ≤ 10% from baseline with HYPER; inducible RWMA 2.for HYPER and HYPER-EX Results Of the 1146 patients, 244 (21%) showed abnormal CFVR i.e. structural CMD (Figure 1). In the subset of 68 patients with normal vasodilator CFVR , entering a strategy of sequential stepwise approach, 40 pts underwent HYPER showing a paradoxical vasoconstrictor response despite the increase in the double product (59 %), with RWMA in 11 (16%). Of the remaining patients with normal CFVR and normal response to HYPER, 28 underwent HYPER-EX showing inducible RWMA in 7 (10%) patients. The remaining 21 patients (31%) showed all 3 tests normal: see figure 2. Conclusion In patients with ANOCA, a stepwise multi-marker (CFVR and RWMA) and multi-stress (vasodilators, HYPER, and EX) SE identifies 4 distinct phenotypes and actionable therapeutic targets: structural CMD (reduced CFVR with vasodilator); functional vasospastic CMD (paradoxical decrease of CFV with HYPER), epicardial artery vasospasm (inducible RWMA with HYPER or HYPER-EX); non-cardiac chest pain with normal response all tests and all markers. Our research emphasizes the usefulness of versatile, patient-tailored noninvasive testing in patients with ANOCA to unmask the functional heterogeneity of the endotypes underlying the same phenotype. Figures: 1. Overall population of ANOCA (N=1146)-vasodilator CFVR 2. Pilot study in ANOCA with CFVR>2.0 (N=68)Overall population of ANOCA (N=1146) Pilot study in ANOCA with CFVR>2.0

Abstract Background Global longitudinal strain (GLS) by 2D speckle tracking echocardiography (2D-STE) has been widely utilized to detect early underlying systolic myocardial dysfunction in patients with normal ejection fraction (EF). Reduced GLS is observed in patients with hypertrophic and amyloid cardiomyopathies. However, the impact of chronic kidney disease (CKD) on GLS remains underexplored. CKD patients present with multiple cardiovascular comorbidities, increased left ventricular mass index (LVMI), and altered cardiac remodeling which is a dynamic and adaptive physiological response. Left ventricular (LV) remodeling is classified based on relative wall thickness (RWT ≤ or > 0.42) and LVMI (≤ or > 88 g/m² for women and ≤ or > 102 g/m² for men) into four distinct categories: normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). Purpose To assess and describe the LV-GLS values (SD) in male and female patients with CKD across different remodeling patterns and compare them to controls without comorbidities Methods A retrospective echocardiographic analysis was conducted on patients evaluated from 01/01/2008 to 12/31/2018. A total of 546 CKD patients and 1041 controls were identified and matched in a ≈2:1 ratio by age, gender, and cardiac geometry. ANOVA and Tukey-Kramer analysis compared GLS across groups, with data distributions visualized via box plots. P-values <0.05 were considered significant. Results The mean age of CKD patients and controls was 63.3 (SD 12.7) and 63.1 (SD 12.6) years, respectively. Overall, GLS values in CKD patients were comparable to controls, with significant differences in select subgroups. In females with eccentric hypertrophy, GLS was lower in CKD stage V vs. controls (-16.2 ± 2.5 vs. -20.7 ± 2.3, p < 0.05), CKD stage III (-16.2 ± 2.5 vs. -19.5 ± 2.4, p < 0.05), and CKD stage IV (-16.2 ± 2.5 vs. -20.2 ± 2.4, p < 0.05) (Table 1). Across CKD stages, GLS trended toward the lower limit of normality, particularly in advanced CKD. In males with normal geometry, GLS values for controls and CKD stages I, II, III, IV and V were -20.3 ± 1.9, -19.1 ± 2.3, -19.4 ± 2.7, -19.5 ± 2.8, -19.8 ± 3.6, and -17.7 ± 2.7 (Figure 1a). In females, corresponding values were -21.0 ± 2.2, -19.9 ± 2.7, -20.2 ± 2.0, -20.8 ± 2.5, -20.2 ± 3.4, and -18.8 ± 3.4, respectively (Figure 1b). Conclusion GLS values in CKD patients were largely comparable to controls for both genders. However, those with CKD V exhibited GLS values near the lower limit of normality, particularly in eccentric hypertrophy. These findings suggest that in this group of patients there is subclinical myocardial dysfunction, warranting further investigation. The values reported may serve as reference points for GLS assessment in CKD patients.

Abstract Background Stress echocardiography (SE) was recently upgraded to the ABCDE protocol: step A, regional wall motion abnormalities; step B, B-lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in left anterior descending coronary artery; and step E, EKG-based heart rate reserve. Aim to assess the prognostic value of ABCDE-SE in a prospective, large-scale, multicenter, international, effectiveness study. Methods From July 2016 to November 2024, we enrolled 7896 all-comers (age 65±11 years, 4742 [60.0%] males, ejection fraction 59±10%) with known or suspected chronic coronary syndromes (CCS) referred from 27 certified laboratories. All patients underwent clinically indicated ABCDE-SE, with ACE in all patients, step D in 6286, step B in 5951 and all 5 steps in 5918 pts. The employed stress modality was exercise (n=2407) or pharmacological stress (n=5489; with vasodilator, n=4503; or dobutamine, n=986). Each step was scored from 0 (normal) to 3 (severely abnormal) following EACVI recommendations 2024. SE response ranged from a score of 0 (all steps normal) to a score of 15 (all steps severely abnormal). All-cause death was the only end-point. Results During a median follow-up of 685 days (interquartile range: 387-1227), 370 deaths occurred. Step A negativity was associated with a 1.5% annual mortality. Annual mortality rate ranged from 0.4% persons/year for score 0 (n=958, 12.1%) up to 6.19% person/year for score ≥10 (n=346, 4.3%). (Figure). At multivariate logistic regression analysis, age (hazard ratio [HR] 1.008, 95% interquartile range [IQ]: 1.006-1.010, p<0.001), diabetes (HR 1.564, 95% CI: 1.263-1.936, p<0.001), resting ejection fraction (HR 0.983, 95% CI: 0.974-0.993, p=0.001), and ABCDE score 3-5 (HR 3.111, 95% CI 1.597-6.060, p=0.001), score 6-9 (HR 5.442, 95% CI 2.761-10.729, p<0.001), and score ≥10 (HR 8.826, CI 4.197-18.654, p<0.001) were independent predictors of mortality. Conclusion In patients with known or suspected CCS, SE negativity by simple wall motion criterion is unable to identify a low-risk group. ABCDE-SE allows an effective prediction of survival.Figure