Citations

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

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous entity including patients with different phenotypes of near normal, normal, and supernormal left ventricular (LV) function. Objectives To assess the value of resting LV elastance (also known as force) with transthoracic echocardiography (TTE) to identify HFpEF phenotypes. Methods In a prospective, observational, multicenter study, 2380 HFpEF patients were recruited from July 2016 to May 2024. Systolic blood pressure (SBP) was measured. We assessed LV end-diastolic volume (EDV), end-systolic volume (ESV), EF, force (SBP/ESV), stroke volume (SV), arterial elastance (AE), ventricular-arterial coupling (VAC), and left atrial volume index (LAVI). Global longitudinal strain (GLS) was available in 1164 (48.9%) patients. 680 patients finished follow-up with a composite end-point of major adverse cardiac events (MACEs). Patients were divided into three groups: low force (< 25th percentile, Group 1, < 3.24 mmHg/ml), intermediate force (≥ 25th percentile and ≤ 75 thpercentile, Group 2, 3.24-5.48 mmHg/ml), and high force (> 75 th percentile, Group 3, >5.48 mmHg/ml). Results The 3 groups showed a gradient with descending values (Group 3>2>1) for SBP, EF, GLS, AE, and VAC, with the opposite gradient (Group 1> 2> 3) for EDV, ESV, SV, and LAVI values (all P<0.01). After a median follow-up of 16 months, 205 MACEs occurred in 138 patients. Cumulative MACEs rate was lowest in group 2 (14.7% person-year), higher in group 1 (16.1% person-year) and 3 (22.9% person-year, log rank p = 0.036). Conclusions HFpEF patients present with different LV contractile phenotypes, easily identified with resting LV force and volumetric TTE. The dominant hemodynamic feature of hypocontractile phenotype is a preload recruitment with larger LV EDV and normal SV, while the hypercontractile phenotype is characterized by a small LV with reduced SV. The hypercontractile and hypocontractile phenotypes are associated with a higher risk of subsequent events.

Abstract Key unanswered questions in biology center on the causes, consequences, and maintenance of sexual reproduction (“sex”). Genome-driven processes are central to the evolutionary and genetic mechanisms inherent to sex, making genomic resources a fundamental part of answering these questions. We present the first genome assembly for a species that is uniquely well-suited for the study of (a)sex in nature, Potamopyrgus antipodarum. This New Zealand snail is unusual in featuring multiple separate transitions from obligately sexual to obligately asexual reproduction, leading to the coexistence of phenotypically similar sexual and asexual forms, a feature that is required to directly study the maintenance of sex. These separately derived asexual lineages constitute separate evolutionary experiments, providing a powerful means of characterizing how the absence of sex affects genome evolution. Our genome assembly provides critical steps toward understanding the causes and consequences of sex in this system and important resources for the rapidly growing P. antipodarum and molluscan genomics research community. In characterizing this genome, we uncovered unexpected evidence for a recent whole-genome duplication (WGD) in P. antipodarum. This discovery sets the stage for using P. antipodarum to evaluate processes of rediploidization following WGD and to assess whether WGD might drive transitions to asexuality.

Abstract Background Obesity is strongly associated with the development of heart failure (HF) with preserved ejection fraction (HFpEF). Beyond increased body mass index (BMI), an abundance of epicardial adipose tissue (EAT) may play a role in its pathophysiology. Purpose To study the associations between increased EAT, functional status and invasive exercise hemodynamics in a large cohort of HFpEF patients. Methods This is a sub-analysis from a large randomized clinical trial that investigated an atrial shunt device in patients with HF with left ventricular ejection fraction ≥40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25mmHg. At baseline, all patients underwent echocardiography, 6-minute walk distance (6-MWD) test, Kansas City Cardiomyopathy Questionnaire (KCCQ) and invasive hemodynamic assessment at rest and during supine ergometry. EAT thickness was measured on the free wall of the right ventricle on echocardiography, expressed in mm and patients were divided according to EAT tertiles. Results In total, 566 patients were examined. Their mean age was 72±8 years, 62% were women, mean BMI was 33±6 kg/m2 and mean EAT thickness was 6.0±2.4 mm, ranging from 1.7 to 17.2 mm. With increasing EAT thickness tertiles, 6-MWD and KCCQ overall summary score were significantly lower (320 vs. 315 vs. 287m, p=.01; 51 vs. 45 vs. 41, p=.003; respectively, Figure 1A-B). The association between increased EAT and lower KCCQ score was independent of BMI (p=.004, β: -2.6), whereas the association with lower 6-MWD was not independent of BMI (p=.1, β: -6.9). At rest, invasive hemodynamics were not different across EAT tertiles. At peak exercise, patients in the highest EAT thickness tertile had higher PCWP and PCWP to right atrial pressure gradient, as compared to patients in the first and second EAT thickness tertiles (36±8 vs. 34±8 mmHg, p=.009; 18±7 vs. 16±7 mmHg, p=.002, respectively, Figure 1C). Conclusion Excess EAT is common in patients with HFpEF and is associated with lower functional status and with higher left-sided filling pressures at peak exercise. These data suggest that EAT plays a significant role in functional status and exercise hemodynamics in HFpEF.Figure 1