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Abstract Funding Acknowledgements Type of funding sources: None. Background. Recent evidence shows that increased epicardial adipose tissue (EAT) thickness is associated with metabolic syndrome, microvascular dysfunction and enhanced pericardial restraint. Purpose. We measured echocardiography-derived EAT thickness in a population of heart failure (HF) patients with reduced (HFrEF) and preserved (HFpEF) ejection fraction to examine the relationship between EAT and prognosis at clinical follow-up. Methods. We prospectively enrolled 393 consecutive HF outpatients (205 HFrEF, 188 HFpEF) who had been referred to our hospital due to dyspnoea and/or effort intolerance. We performed a resting clinical and biohumoral evaluation, followed by combined cardiopulmonary-echocardiography exercise stress. We considered a composite endpoint of cardiovascular death and HF-related hospitalization during follow-up. Results. Patients with HFpEF displayed greater EAT thickness (median 8 mm, interquartile range [IQR] 4–12 mm) than HFrEF (median 3 mm, IQR 2–6 mm; p < 0.0001). During a median follow-up of 20.9 months (IQR 15-25 months), 34 cardiovascular deaths and 146 HF hospitalizations were reported, with no significant differences between the two HF phenotypes. EAT was shown to predict adverse events independently from body mass index, waist circumference and other well-established prognostic markers in HF (such as NT-proBNP and peak oxygen consumption). The risk of adverse events increased with increasing EAT thickness in HFpEF and with EAT thinning in HFrEF. Kaplan-Meier analyses for the composite endpoint showed that in HFpEF, the survival probability was significantly lower in patients with thicker EAT than those with thinner EAT. In HFrEF, conversely, patients with increased EAT thickness had a higher survival probability than those with reduced EAT thickness (Figure 1). Conclusion. EAT accumulation is increased in HFpEF compared to HFrEF and carries different prognostic meanings in the two subsets. In HFpEF, EAT thickening portends adverse outcomes, which may be due to the secretion of pro-inflammatory and pro-atherogenic adipokines and increased mechanical restraint. In HFrEF, EAT thinning is associated with a worse prognosis, probably reflecting a more advanced catabolic state (e.g., cardiac cachexia). Larger studies are needed to determine whether or not EAT has a causal role in influencing progression and survival in the different HF phenotypes. Abstract Figure 1

ABSTRACT Background The COVID-19 pandemic displaced newly matched emergency medicine “pre-interns” from in-person educational experiences at the end of medical school. This called for novel remote teaching modalities. Objective This study assesses effectiveness of a multisite Accreditation Council for Graduate Medical Education (ACGME) sub-competency-based curricular implementation on Slack during the first wave of the COVID-19 pandemic in the United States. Methods Emergency medicine residency programs were recruited via national organization listservs. Programs designated instructors to manage communications and teaching for the senior medical students who had matched to their programs (pre-interns) in spring/summer 2020. Pre- and post-surveys of trainees and instructors assessed perceived preparedness for residency, perceived effectiveness of common virtual educational modalities, and concern for the pandemic's effects on medical education utilizing a Likert scale of 1 (very unconcerned) to 5 (very concerned). Data were analyzed using descriptive statistics and the t test. Results Of 276 possible residency programs, 28 enrolled. Of 324 possible pre-interns, 297 (91.7%) completed pre-surveys in April/May and 249 (76.9%) completed post-surveys in June/July. The median weeks since performing a physical examination was 8 (IQR 7–12), since attending in-person didactics was 10 (IQR 8–15) and of rotation displacement was 4 (IQR 2–6). Perceived preparedness increased both overall and for 14 of 21 ACGME Milestone topics taught. Instructors reported higher mean concern (4.32, 95% CI 4.23–4.41) than pre-interns (2.88, 95% CI 2.74–3.02) regarding the pandemic's negative effects on medical education. Conclusions Pre-interns reported improvements in residency preparedness after participating in this ACGME sub-competency-based curriculum on Slack.

Abstract Background Increased epicardial adipose tissue (EAT) thickness correlates with metabolic syndrome, insulin resistance, microvascular dysfunction and enhanced pericardial restraint. Purpose We measured echocardiographic EAT thickness in heart failure (HF) patients with reduced (HFrEF) or preserved (HFpEF) ejection fraction to determine whether EAT could bear prognostic significance at clinical follow-up. Methods We prospectively enrolled 393 consecutive HF outpatients (205 HFrEF, 188 HFpEF) referred to our hospital due to dyspnoea and/or effort intolerance. We performed a resting clinical and biohumoral evaluation, followed by combined cardiopulmonary-echocardiography exercise stress. A composite of cardiovascular death and HF-related hospitalization was chosen as endpoint during follow-up. Results Patients with HFpEF displayed higher EAT thickness (median 8 mm, interquartile range [IQR] 4–12 mm) than HFrEF (median 3 mm, IQR 2–6 mm; p<0.0001). During a median follow-up of 20.9 months (IQR 15–25 months), we reported 34 cardiovascular deaths and 146 HF hospitalizations, with no significant differences between the two HF subsets. EAT predicted adverse events independently from body mass index and well-established markers of poor prognosis (e.g., NT-proBNP, peak oxygen consumption). The risk of adverse events increased with increasing EAT thickness in HFpEF and with EAT thinning in HFrEF. Kaplan-Meier analyses for the composite endpoint showed that in HFpEF, the survival probability was significantly lower in patients with thicker EAT than those with thinner EAT. In HFrEF, conversely, patients with thicker EAT had a higher survival probability than those with reduced EAT thickness (Figure 1). Conclusion EAT accumulation is more marked in HFpEF than HFrEF and carries different prognostic meanings in the two subsets. In HFpEF, EAT thickening portends adverse outcome, which may be due to increased mechanical restraint and secretion of pro-inflammatory and pro-atherogenic adipokines. In HFrEF, greater EAT thickness seems to have a protective role, while EAT thinning is associated with a worse prognosis, likely reflecting a catabolic state (i.e. cardiac cachexia). Larger studies will clarify whether EAT is a bystander or an active player in the different HF phenotypes. Funding Acknowledgement Type of funding sources: None. Figure 1

Abstract Background Epicardial adipose tissue (EAT) acts as a paracrine organ and could exert direct mechanical compression on the myocardium. Purpose We investigated the impact of echocardiographic EAT thickness on metabolic profile and cardiovascular hemodynamics at rest and during exercise in heart failure (HF) patients with reduced (HFrEF) and preserved (HFpEF) ejection fraction Methods We prospectively enrolled 393 consecutive HF outpatients (205 HFrEF, 188 HFpEF) referred to the our hospital due to dyspnoea and/or effort intolerance. We performed a resting clinical and biohumoral evaluation, followed by combined cardiopulmonary-echocardiography exercise stress. The protocol also included 44 healthy controls. Results Patients with HFpEF displayed the greatest EAT thickness (median 8 mm, interquartile range [IQR] 4–12 mm), while those with HFrEF had thinner EAT (median 3 mm, IQR 2–6 mm) than controls (median 5 mm, IQR 3–7 mm; p<0.0001). In HFrEF, EAT thickness was inversely associated with natriuretic peptides, Troponin T, and C-reactive protein levels. In HFpEF, it was directly correlated with Troponin-T and C-reactive protein levels. EAT thickness was inversely correlated with peak oxygen consumption (VO2) and peripheral oxygen extraction (AVO2diff) in HFpEF, while a direct association was observed in HFrEF (Fig 1). EAT resulted in an independent predictor of peak VO2 and AVO2diff in HFrEF and HFpEF regardless of body mass index, but the relationships were direct in HFrEF (standard regression coefficient [SRC] for peak VO2: 0.18, p=0.02; SRC for peak AVO2diff: 0.17, p=0.03) and indirect in HFpEF (SRC for peak VO2: −0.33, p<0.0001; SRC for peak AVO2diff: −0.25, p<0.0001). The analysis of cardiac mechanics revealed that thinner EAT was associated with worse left ventricle systolic dysfunction (average S') and remodeling (3D left ventricle mass) in HFrEF. In HFpEF, increased EAT was related to more severe left atrio-ventricular (left atrium reservoir strain/left ventricle global longitudinal strain) and right ventriculo-arterial (tricuspid annular plane systolic excursion/systolic pulmonary artery pressure) coupling (Figure 2). Conclusion In HFpEF, EAT accumulation is associated with worse hemodynamic and metabolic profile. In HFrEF, conversely, EAT thinning portends more severe LV dysfunction and impaired global functional capacity. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, morbid, potentially curable subtype of pulmonary hypertension that negatively impacts health‐related quality of life (HRQoL). Little is known about differences in HRQoL and hospitalization between CTEPH patients and idiopathic pulmonary arterial hypertension (IPAH) patients. Using multivariable linear regression and mixed effects models, we examined differences in HRQoL assessed by emPHasis‐10 (E10) and SF‐12 between CTEPH and IPAH patients in the Pulmonary Hypertension Association Registry, a prospective multicenter cohort of patients newly evaluated at a Pulmonary Hypertension Care Center. Multivariable negative binomial regression models were used to estimate incidence rate ratios (IRR) for hospitalization amongst the two groups. We included 461 IPAH patients and 169 CTEPH patients. Twenty‐one percent of CTEPH patients underwent pulmonary thromboendarterectomy (PTE) before the end of follow‐up. At baseline, patients with CTEPH had significantly worse HRQoL (higher E10 scores) (ß 2.83, SE 1.11, p = 0.01); however, differences did not persist over time. CTEPH patients had higher rates of hospitalization (excluding the hospitalization for PTE) compared to IPAH patients after adjusting for age, sex, body mass index, WHO functional class and six‐minute walk distance (IRR 1.66, 95%CI 1.04–2.65, p = 0.03). CTEPH patients who underwent PTE had improved HRQoL as compared to those who were medically managed, but patients who underwent PTE were younger, had higher cardiac outputs and greater six‐minute walk distances. In this large, prospective, multicenter cohort, CTEPH patients had significantly worse baseline HRQoL and higher rates of hospitalizations than those with IPAH. CTEPH patients who underwent PTE had significant improvements in HRQoL.

Abstract Aims We evaluated the impact of echocardiographic epicardial adipose tissue (EAT) on cardiovascular haemodynamics, metabolic profile and prognosis in heart failure (HF) using combined cardiopulmonary‐echocardiography exercise stress. Methods and results We analysed EAT thickness of HF patients with reduced (HFrEF, n = 205) and preserved (HFpEF, n = 188) ejection fraction, including 44 controls. HFpEF patients displayed the highest EAT, while HFrEF patients had lower values than controls. EAT showed an inverse correlation with natriuretic peptides, troponin T and C‐reactive protein in HFrEF, while having a direct association with troponin T and C‐reactive protein in HFpEF. EAT was independently associated with peak oxygen consumption (VO 2 ) and peripheral extraction (AVO 2 diff), regardless of body mass index. EAT was inversely correlated with peak VO 2 and AVO 2 diff in HFpEF, while a direct association was observed in HFrEF, where lower EAT values were associated with worse left ventricular systolic dysfunction. In HFpEF, increased EAT was related to right ventriculo–arterial (tricuspid annular plane systolic excursion/systolic pulmonary artery pressure) uncoupling. After 21 months of follow‐up, 146 HF hospitalizations and 34 cardiovascular deaths were recorded in the HF population. Cox multivariable analysis supported an independent differential role of EAT in HF cohorts (interaction P = 0.01): higher risk of adverse events for increasing EAT in HFpEF [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.04–1.37] and for decreasing EAT in HFrEF (HR 0.75, 95% CI 0.54–0.91). Conclusion In HFpEF, EAT accumulation is associated with worse haemodynamic and metabolic profile, also affecting survival. Conversely, lower EAT values imply higher left ventricular dysfunction, global functional impairment and adverse prognosis in HFrEF.

OBJECTIVE We aimed to test whether type 2 diabetes (T2D)–associated TCF7L2 genetic variants affect insulin sensitivity or secretion in autoantibody-positive relatives at risk for type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS We studied autoantibody-positive TrialNet Pathway to Prevention study participants (N = 1,061) (mean age 16.3 years) with TCF7L2 single nucleotide polymorphism (SNP) information and baseline oral glucose tolerance test (OGTT) to calculate indices of insulin sensitivity and secretion. With Bonferroni correction for multiple comparisons, P values < 0.0086 were considered statistically significant. RESULTS None, one, and two T2D-linked TCF7L2 alleles were present in 48.1%, 43.9%, and 8.0% of the participants, respectively. Insulin sensitivity (as reflected by 1/fasting insulin [1/IF]) decreased with increasing BMI z score and was lower in Hispanics. Insulin secretion (as measured by 30-min C-peptide index) positively correlated with age and BMI z score. Oral disposition index was negatively correlated with age, BMI z score, and Hispanic ethnicity. None of the indices were associated with TCF7L2 SNPs. In multivariable analysis models with age, BMI z score, ethnicity, sex, and TCF7L2 alleles as independent variables, C-peptide index increased with age, while BMI z score was associated with higher insulin secretion (C-peptide index), lower insulin sensitivity (1/IF), and lower disposition index; there was no significant effect of TCF7L2 SNPs on any of these indices. When restricting the analyses to participants with a normal OGTT (n = 743; 70%), the results were similar. CONCLUSIONS In nondiabetic autoantibody-positive individuals, TCF7L2 SNPs were not related to insulin sensitivity or secretion indices after accounting for BMI z score, age, sex, and ethnicity.

Abstract Funding Acknowledgements Type of funding sources: None. Aims. Combined cardiopulmonary exercise test (CPET) and exercise stress echocardiography (ESE) provides a non-invasive tool to study cardiopulmonary pathophysiology. We analyzed how cardiac functional reserve during exercise relates to peak oxygen consumption (VO2). Methods and Results. We performed a symptom-limited graded ramp bicycle CPET-ESE in 30 healthy controls and 357 patients: 113 at risk of developing heart failure (American College of Cardiology/American Heart Association HF Stages A-B) and 244 in HF Stage C with preserved (HFpEF, n = 101) or reduced ejection fraction (HFrEF, n = 143). Peak VO2 significantly decreased from controls to Stage A-B and Stage C (Table 1). A multivariable regression model to predict peak VO2 revealed peak left ventricular systolic annulus tissue velocity (S"), peak TAPSE/PAPs (tricuspid annular plane systolic excursion/systolic pulmonary artery pressure) and low-load left atrial reservoir strain/E/e’ were independent predictors, in addition to peak heart rate, stroke volume and workload (adjusted R²=0.76, p < 0.0001). The model was successfully tested in subjects with atrial fibrillation (n = 49), and with (n = 224) and without (n = 163) beta-blockers (all p < 0.01). Peak S’ showed the highest accuracy in predicting peak VO2 < 10 mL/kg/min (cut-point ≤ 7.5 cm/s; AUC = 0.92, p < 0.0001) and peak VO2 > 20 mL/kg/min (cut-point > 12.5 cm/s; AUC = 0.84, p < 0.0001) in comparison to the other cardiac variables of the model (p < 0.05). Conclusions. A model incorporating different measures of cardiac mechanics is strongly related to peak aerobic capacity and may help in identifying different causes of effort intolerance from HF Stage A to C. Table 1 Variable Overall population (n = 387) Controls (n = 30) Stage A-B (n = 113) Stage C-HFpEF (n = 101) Stage c-HFrEF (n = 143) p-value Age, years 68.9 ± 11.1 67.1 ± 10.6 67.7 ± 10.4 70.5 ± 10.1 68.5 ± 11 0.1 Male, n (%) 247 (64) 18 (60) 70 (62) 57 (56) 102 (71) 0.1 VO2 @peak, mL/min/kg 15.7 (12.1-19.6) 23 (21.7- 29.7) 18 (15.4- 20.7)* 13.6 (11.8- 16.8)*† 14.2 (10.7- 17.5)*† <0.0001 Workload @peak, W 90 (65-120) 130 (115-195) 110 (84-130)* 70 (55-100)*† 80 (60-110)*† <0.0001 Heart rate @peak, bpm 123 ± 22 142 ± 12 130 ± 20* 115 ± 17*† 119 ± 23*† <0.0001 Stroke volume @peak, mL 83 (71-99) 98 (85-114) 86 (76-107) 83 (74-97)* 75 (63-95)*† <0.0001 Average S" @peak, cm/s 11.2 ± 3.8 17.1 ± 3.9 13.3 ± 2.9* 10.6 ± 2.5*† 8.7 ± 2.7*†‡ <0.0001 TAPSE/PAPs @peak, mm/mmHg 0.75 (0.46-0.97) 1.05 (0.93- 1.16) 0.81 (0.52- 0.91)* 0.52 (0.38- 0.83)*† 0.58 (0.41- 0.89)*† <0.0001 Left atrial reservoir strain/E/e" @low-load, % 2.25 (1.17-5.04) 6.23 (4.45-6.77) 4.34 (3.89- 5.58)* 2.23 (1.31- 2.86)*† 1.91 (1.07-2.44)*†‡ <0.0001 * p < 0.01 vs Controls; † p < 0.01 vs Stage A-B; ‡ p < 0.01 vs Stage C-HFpEF. PAPs systolic pulmonary artery pressure; TAPSE: tricuspid annular plane systolic excursion; VO2: oxygen consumption. Abstract Figure 1