Background:Artificial intelligence (AI) enabled algorithms can detect or predict cardiovascular conditions using electrocardiogram (ECG) data. Clinical studies have evaluated ECG-AI algorithms, including a recent single-center study which evaluated outcomes when clinicians were provided with ECG-AI results. A Multicenter Pragmatic IMplementation Study of ECG-AI-Based Clinical Decision Support Software to Identify Low LVEF (AIM ECG-AI) will evaluate clinical impacts of clinical decision support software (CDSS) integrated within the electronic health record (EHR) to provide point-of-care ECG-AI results to clinicians during routine outpatient care. Methods:AIM ECG-AI is a multicenter, cluster-randomized trial recruiting and randomizing clinicians to receive access to the CDSS (intervention) or provide usual care. Clinicians are recruited from 5 geographically distinct health systems and clustered at the care team level. AIM ECG-AI will evaluate clinical care provided during >32,000 eligible clinical encounters with adult patients with no history of low LVEF and who have a digital ECG documented within the health system's EHR, with 90 day follow up. Results:Study data includes clinician surveys, study software metrics, and EHR data as a read-out for clinician decision-making. AIM ECG-AI will evaluate detection of left ventricular ejection fraction ≤40 % by echocardiography, with exploratory endpoints. Subgroup analyses will evaluate the health system, clinician, and patient-level characteristics associated with outcomes (NCT05867407). Conclusion:AIM ECG-AI is the first multisite clinical evaluation of an EHR-integrated, point-of-care CDSS to provide ECG-AI results in the clinical workflow. The findings will provide valuable insights for clinically focused software design to bring AI into routine clinical practice.

Abstract Introduction Hospitalizations for worsening heart failure (HF) represent an enormous public health and financial burden. Accordingly, select centers have developed outpatient worsening HF (WHF) management strategies focused on care in emergency departments (ED), observation units, or intravenous (IV) diuretic clinics. However, broad use of these outpatient strategies and the associated outcomes and healthcare costs remain unclear. Methods Among US Medicare beneficiaries age ≥65 years hospitalized for HF in the Get With The Guidelines Heart Failure registry 2010-2018, we identified patients with a post-discharge non-fatal WHF event. Patients were divided into 4 mutually exclusive groups defined by type of first post-discharge WHF event (HF hospitalization, ED visit with ED discharge, observation unit stay, and outpatient clinic visit with IV diuretics). Following each type of WHF event, mortality, home-time (days alive and out of any healthcare institution), and healthcare costs were compared over the subsequent 12-months. Costs of the initial WHF management strategy were also assessed. Results Among 181,827 patients hospitalized for HF, during the 12-months post-discharge, 83,971 (46.2%) survived with no WHF event, 36,697 (20.2%) died prior to a WHF event, and 61,159 (33.6%) had a WHF event. Of patients with a WHF event, 48,612 were managed with HF hospitalization (79.5%), 8,139 (13.3%) with an ED visit, 1,767 (2.9%) with an observation unit stay, and 2,641 (4.3%) with an outpatient IV diuretic visit. Compared with HF hospitalization, patients with WHF managed in the ED, observation unit, or IV diuretic clinic experienced lower subsequent mortality (Figure 1). Mean 12-month home-time was lowest following HF hospitalization (207 ± 144 days), intermediate following ED (238 ±136 days) and outpatient IV diuretic visits (252 ±128 days), and highest following observation unit stays (277 ± 125 days). For the initial WHF event, median (25th, 75th) total per-patient costs were highest for HF hospitalization and lowest for outpatient IV diuretic visits (Figure 2). Over the 12-months following the WHF event, median total per-patient costs were highest following outpatient IV diuretic visits, intermediate following HF hospitalization and ED stays, and lowest following observation unit stays. Conclusions In a nationwide analysis of older US adults, 1 in 5 episodes of recurrent WHF were exclusively managed as an outpatient within the ED, observation unit, or IV diuretic clinic. High rates of death and substantial reductions in home-time occurred following WHF regardless of inpatient or outpatient management, but were worse following HF hospitalization. Outpatient IV diuretic administration was the least expensive initial management strategy, but was associated with the highest per-patient costs over the subsequent 12 months.

Abstract Background Despite evidence that guideline-directed medical therapy (GDMT) improves outcomes in heart failure with reduced ejection fraction (HFrEF), many eligible patients remain untreated in the United States (US). Purpose To explore reasons why patients are not receiving GDMT and physician perceptions in management of their patients. Methods We conducted a cross-sectional survey of HF treatment practices (Adelphi Real World Heart Failure Disease Specific Programme) between August 2022 and February 2023, following publication of the 2022 US HF guidelines recommended that patients with HFrEF receive: angiotensin receptor/neprilysin inhibitors (ARNI), beta-blocker, mineralocorticoid receptor antagonists (MRA), and SGLT-2 inhibitors (SGLT2i). A total of 63 cardiologists and 39 primary care physicians in the US provided clinical and treatment patterns data on adult patients with HFrEF (ejection fraction ≤ 40%) and completed an attitudinal survey detailing reasons for treatment initiation. Results The study group included 323 patients with HFrEF (median age of 67 years [IQR 56-74]; 39% females) of which 59.4% were White, 19.8% African American and 9.6% Hispanic; half of the sample was insured by Medicare (50.2%), followed by commercial insurance (36.5%). GDMT prescription rates are presented in Table 1. Overall, 57.3% were not prescribed ARNI (185/323), 16.4% (53/323) were not prescribed a beta-blocker; 71.5% (231/323) were not prescribed MRA, and 65.3% (211/323) were not prescribed SGLT2i. Among patients not receiving GDMT, the most frequently reported physician reason for not prescribing ARNIs (54.1%), beta-blockers (43.4%), MRAs (54.5%) or SGLT-2is (53.6%) was physician deemed the patient to be clinically stable (Table 2). Most physicians (93.5%) reported being satisfied with treatment for patients with HFrEF and most (80.3%) believed that their patients with HFrEF were fully compliant with their treatments. Most physicians (91.2%) stated that they based their treatment decisions on both clinical experience and laboratory tests, as opposed to laboratory tests/imaging only (9.8%) or personal judgement only (16.7%). Conclusions In this cohort of patients with HFrEF from the US, the most common primary reason physicians reported for their patients not receiving GDMT was that the patient was clinically stable. Patient medication costs, contraindications, and proven intolerance were each reported as primary reasons for non-treatment in only a small minority of cases. These data suggest a strong culture of clinical inertia and lack of therapeutic urgency as the dominant driver of large gaps in use of GDMT in the US.GDMT prescriptions in HFrEF (n = 323)Physician-reasons for no GDMT

Abstract Background Sex differences in 5-year outcomes across heart failure (HF) ejection fraction (EF) subtypes are not well known. Purpose To assess the interaction between sex and EF for risk of long-term adverse outcomes after hospitalization with HF. Methods Patients from American Heart Association’s Get With The Guidelines – Heart Failure registry enrolled between 1/1/2006 – 12/31/2014 with age ≥ 65 years with available 5-year follow-up data, ascertained through linkage with Medicare fee-for-service Part A administrative claims, were included. HF subtypes included HF with reduced EF (HFrEF) with EF ≤ 40%, HF with mildly reduced EF (HFmrEF) with EF 41-49%, and HF with preserved EF (HFpEF) with EF ≥ 50%. Sex differences in 5-year all-cause mortality and readmission for each HF subtype were assessed using unadjusted cumulative incidence methods and adjusted Cox models. Median survival across HF subtypes was compared to median survival of U.S. adults. Results 155,670 patients (mean age 81 years, 53.4% females) were included. Male patients were younger and had a higher prevalence of prior myocardial infarction or coronary artery bypass graft surgery and were more likely to have HFrEF, while women were more likely to have history of hypertension and HFpEF. The median post-hospitalization survival of patients with HF was substantially lower than the age- and sex-specific U.S. life expectancy across each HF subtype (Figure 1).Patients with HF had high 5-year mortality rates (HFrEF male: 81.3%, female: 78.4%; HFpEF male: 80.5% vs female 79.5%). In adjusted analysis, female (vs. male) patients had a significantly lower 5-year mortality risk (HR [95%CI]: 0.89 [0.87 – 0.90], p<0.01) and a higher 5-year readmission risk (all-cause: 1.03 [1.02 – 1.04]), CV: 1.05 [1.04 – 1.07]), HF: 1.06 [1.04 – 1.08], p<0.01 for each). HF subtype modified the association between sex and 5-year outcomes (pinteraction <0.05 for mortality and CV and HF readmission), with the greatest risk reduction of mortality for female vs. male patients with HFrEF and the greatest risk increase of readmission (CV and HF) among female vs. male patients with HFmrEF and HFpEF (Figure 2). Conclusion Among patients with HF, the overall survival post-HF hospitalization is very low for each HF subtype. Female patients have a lower 5-year mortality risk but a higher risk of HF or CV readmission regardless of EF.Figure 1Figure 2

Abstract Introduction Recent clinical trials of heart failure with preserved ejection fraction (HFpEF) have observed varying patient profiles by ejection fraction (EF), with attenuation of treatment benefits as EF increases. In routine clinical practice, the degree to which patients hospitalized for HF with EF≥60% may differ from those with lower EF is unknown. Purpose To compare patient characteristics, treatment patterns, and clinical outcomes across the range of EF among patients hospitalized for HFpEF. Methods Using the Humedica electronic medical records database between Jan 2010 and Dec 2020, patients hospitalized for a primary diagnosis of HF with EF>40% and who were haemodynamically stable at admission, without concurrent acute coronary syndrome or end-stage renal disease, and treated with intravenous (IV) diuretic agents within 48 h of admission were identified. Patient characteristics, treatment patterns, and clinical outcomes were compared by EF ranges of 41–49%, 50–59%, and ≥60%. Results Of 47,026 patients hospitalized with HFpEF, 6,335 (13%) had EF 41–49%, 18,603 (40%) had EF 50–59%, and 22,088 (47%) had EF≥60%. Across all 3 groups, patients were similar with respect to age (median 77 years for each group), race (83–84% White, 12–13% Black), systolic blood pressure (137–138 mmHg at admission), and eGFR (63–64 mL/min/1.73 m2 at admission). With progressively higher EF group, the proportion of women increased (45% vs 54% vs 65%) and median NT-proBNP decreased (4,221 vs 2,945 vs 2,234 pg/mL). Patients with EF ≥60% had the lowest rates of coronary artery disease and atrial fibrillation, and the highest rates of chronic pulmonary disease (Figure 1, Panel A). Discharge medications were generally similar, with exception of less beta-blocker use and more calcium channel blocker use among those with EF ≥60% (Figure 1, Panel B). Discharge use of angiotensin receptor-neprilysin inhibitor and sodium glucose cotransporter-2 inhibitor therapies were each <1% in all groups. Hospital length of stay (median 4 days for each group) and in-hospital mortality (1.1–1.3%) were similar across groups, but rates of in-hospital acute respiratory failure were higher among patients with EF ≥60% (27% vs 230-25% for lower EF groups). Rates of 30-day and 12-month post-discharge clinical events were high irrespective of EF, without meaningful differences between groups (Figure 2). Conclusion In a contemporary real-world population of US patients hospitalized for HF with EF >40%, nearly half had an EF≥60%. While clinical profiles and discharge medications varied, post-discharge outcomes were similarly poor irrespective of EF. There remain important opportunities to improve the care and outcomes for patients with HF across the range of preserved ejection fraction. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): MyoKardia, Inc., a wholly owned subsidiary of Bristol Myers Squibb

Introduction: The Centers for Medicare and Medicaid Services(CMS) expanded coverage for cardiac rehabilitation(CR) in 2014 for patients with clinically stable heart failure(HF) with reduced ejection fraction. Contemporary CR referral and participation rates among eligible patients with HFrEF are not known. Methods: Patients hospitalized for HF with ejection fraction ≤35% in the American Heart Association Get With The Guidelines®-HF(GWTG-HF) registry from 2010-2020 were included. Trends in rate of referrals and predictors of referral were determined. Among subset of participants with available Medicare-linked data, rate of CR participation was assessed, and 1-year outcomes were compared among patients referred vs. not referred to CR. Results: Of 69,441 HF patients eligible for CR, 17,076(24.6%) were referred to CR. There was substantial variability in referral across GWTG-HF participating centers (range 0-100%, IQR 4%-50%). Of patients with fee-for-service Medicare referred to CR, only 4.2% participated in CR in the year following HF hospitalization (median sessions: 3, range 1-76). Referral rate increased from 2010-2020, with significant increase since 2014 CMS coverage expansion (p trend <0.001). Patients not referred were more likely to be older, of minority race, and with greater burden of comorbidities. Patients admitted to rural hospitals and those in the Northeast were less likely to be referred to CR. Among patients free of HF events within 30 days post-discharge, CR referral was independently associated with lower risk of 1-year all-cause mortality vs. those not referred (HR 0.84, 95% CI (0.73 - 0.98, p = 0.0267), without significant difference in 1-year HF-related or all-cause readmission. Conclusions: Although CR referrals have increased among eligible HF patients since CMS expanded coverage in 2014, absolute referral and participation rates remain low. Age, race, and burden of comorbidities were independently associated with CR referral.

Abstract Background For the results of randomized controlled trials (RCTs) to be generalizable, they should report on and include the broad range of patients who have the disease. Purpose We assessed temporal trends and trial factors associated with 1) the reporting of race or ethnicity data and 2) the enrolment of Black, Indigenous, and people of colour (BIPOC) in Heart Failure (HF) RCTs. Methods We searched MEDLINE, EMBASE, and CINAHL for RCTs that recruited adults with HF and were published in journals with an impact factor ≥10 between January 1, 2000 and June 17, 2020. We extracted data in duplicate and used the Cochran-Armitage and Jonchkeere-Terpstra tests to examine temporal trends. We used multivariable regression to assess the independent association between trial factors and the outcomes of interest. Results A total of 414 RCTs met inclusion criteria, of which a vast majority (90.6%; 95% CI 87.4–93.2%) were coordinated in either Europe or North America. Only 157 of the 414 RCTs (37.9%; 95% CI 33.2–42.8%) reported race/ethnicity data; among the 158,200 participants in these trials, only 29,512 (18.7%; 95% CI 18.5–18.9%) were BIPOC. There was a significant increase in the reporting of race or ethnicity data (from 26.9% in 2000–2001 to 54.2% in 2019–2020, p<0.001) and in enrollment of BIPOC (from 16.5% in 2000–2001 to 23.9% in 2019–2020, p=0.038) between 2000–2020. Trial leadership by a woman was associated with twice the adjusted odds of reporting of race or ethnicity data (OR 2.0; 95% CI 1.1–3.8; p=0.028) and an 8.4% (95% CI 1.9–15.0%; p=0.012) adjusted increase in enrollment of BIPOC. The race/ethnicity of trial leaders was not available for analysis. Conclusions Among HF RCTs published between 2000–2020, <38% reported data on race or ethnicity, although this increased over time. Among trials reporting such data, <19% of participants were BIPOC, with modest increases in enrollment over time. Trials led by women had greater adjusted odds of reporting race/ethnicity data and enrollment of BIPOC. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): CIHR

Dyspnea is the most common presenting symptom for acute heart failure (AHF) patients. As such, dyspnea relief has been a common endpoint in AHF clinical trials. However, there is no consensus on how to best measure dyspnea and multiple grading instruments are widely used. The objective of the DYSPNEA-AHF pilot study was to compare multiple grading instruments of dyspnea severity and improvement among AHF patients presenting to the emergency department (ED). We sought to compare their level of agreement, ability to reflect dyspnea improvement, correlation with urine output and overall quality of life, and association with in-hospital and 30-day outcomes. The DYSPNEA-AHF study is a prospective observational study of patients presenting to the ED with dyspnea due to AHF. The study is enrolling ED patients presenting with dyspnea likely secondary to AHF from 2 study sites with a target sample size of 40. Exclusion criteria include inability to self-assess dyspnea using written questionnaires (in English), a history of a durable ventricular assist device or heart transplantation, or fever at time of screening. Patients are required to be enrolled within 2 hours of first ED clinician evaluation. At time of enrollment, dyspnea is assessed by patients using 3 grading instruments (5-point Likert scale, 10-cm visual analogue scale, provocative dyspnea score) and study personnel using 1 grading instrument (4-point scale). Approximately 6 hours following enrollment, dyspnea is reassessed by patients using 4 grading instruments (as above plus 7-point Likert scale) and study personnel using the 4-point scale. Vitals signs, clinical exam, medical therapy administered, and urine output will be recorded at baseline and 6-hour dyspnea assessments. Medical record review and post-discharge phone calls will be used to ascertain clinical endpoints, including ED disposition, in-hospital mortality, 30-day mortality, and 30-day ED recidivism or hospitalization, and 30-day health-related quality of life. Patient-reported and study personnel reported dyspnea instruments will undergo pairwise comparison to assess correlation for baseline dyspnea severity and dyspnea improvement. Associations between baseline dyspnea and dyspnea improvement with clinical endpoints will be evaluated and compared for all dyspnea instruments. Interim results will be available in October 2018. The DYSPNEA-AHF study will provide pilot data evaluating the degree of agreement between multiple commonly used dyspnea measurement instruments in AHF and the comparative ability of these instruments to correlate with common measures of decongestion, clinical outcomes, and patient quality of life.

Introduction: Hemoconcentration during hospitalization for acute heart failure (HF) correlates with superior decongestion and improved post-discharge outcomes. However, the relationship between early post-discharge hemodilution, markers of congestion, and clinical outcomes is unknown.Methods: The EV

Integrative veterinary medicine (IVM) describes the combination of complementary and alternative therapies with conventional care and is guided by the best available evidence. Veterinarians frequently encounter questions about complementary and alternative veterinary medicine (CAVM) in practice, and the general public has demonstrated increased interest in these areas for both human and animal health. Consequently, veterinary students should receive adequate exposure to the principles, theories, and current knowledge supporting or refuting such techniques. A proposed curriculum guideline would broadly introduce students to the objective evaluation of new veterinary treatments while increasing their preparation for responding to questions about IVM in clinical practice. Such a course should be evidence-based, unbiased, and unaffiliated with any particular CAVM advocacy or training group. All IVM courses require routine updating as new information becomes available. Controversies regarding IVM and CAVM must be addressed within the course and throughout the entire curriculum. Instructional honesty regarding the uncertainties in this emerging field is critical. Increased training of future veterinary professionals in IVM may produce an openness to new ideas that characterizes the scientific method and a willingness to pursue and incorporate evidence-based medicine in clinical practice with all therapies, including those presently regarded as integrative, complementary, or alternative.

It is commonly agreed that there is an association of chronic inflammation with tumorigenesis. COX-2, a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth; thus, overexpression of COX-2 is often found in tumor tissues. Therefore, a better understanding of the regulatory mechanism(s) of COX-2 could lead to novel targeted cancer therapies. In this study, we investigated the mechanism of microRNA-101 (miR-101)-regulated COX-2 expression and the therapeutic potential of exogenous miR-101 for COX-2–associated cancer. A stably expressing exogenous miR-101 prostate cancer cell line (BPH1CmiR101) was generated by using lentiviral transduction as a tool for in vitro and in vivo studies. We found that miR-101 inhibited COX-2 posttranscriptional expression by directly binding to the 3′-untranslated region (3′-UTR) of COX-2 mRNA. The regulatory function of miR-101 was also confirmed by using antisense DNA. As a result, exogenous miR-101 is able to effectively suppress the growth of cultured prostate cancer cells and prostate tumor xenografts. The average tumor weight was significantly lower in the BPH1CmiR101 group (0.22 g) than the BPH1Cvec group (0.46 g). Expression levels of the cell growth regulators, such as cyclin proteins, PCNA (proliferating cell nuclear antigen), EGFR (epidermal growth factor receptor), were also studied. In conclusion, COX-2 is a direct target in miR-101 regulation of posttranscription. Exogenous miR-101 suppresses the proliferation and growth of prostate cancer cells in vitro and in vivo. These data suggest that exogenous miR-101 may provide a new cancer therapy by directly inhibiting COX-2 expression. Cancer Prev Res; 4(7); 1073–83. ©2011 AACR.

We report on the results of a 6-month photometric study of the main-belt binary C-type Asteroid 121 Hermione, performed during its 2007 opposition. We took advantage of the rare observational opportunity afforded by one of the annual equinoxes of Hermione occurring close to its opposition in June 2007. The equinox provides an edge-on aspect for an Earth-based observer, which is well suited to a thorough study of Hermione’s physical characteristics. The catalog of observations carried out with small telescopes is presented in this work, together with new adaptive optics (AO) imaging obtained between 2005 and 2008 with the Yepun 8-m VLT telescope and the 10-m Keck telescope. The most striking result is confirmation that Hermione is a bifurcated and elongated body, as suggested by Marchis, et al. [Marchis, F., Hestroffer, D., Descamps, P., Berthier, J., Laver, C., de Pater, I., 2005. Icarus 178, 450–464]. A new effective diameter of 187±6km was calculated from the combination of AO, photometric and thermal observations. The new diameter is some 10% smaller than the hitherto accepted radiometric diameter based on IRAS data. The reason for the discrepancy is that IRAS viewed the system almost pole-on. New thermal observations with the Spitzer Space Telescope agree with the diameter derived from AO and lightcurve observations. On the basis of the new AO astrometric observations of the small 32-km diameter satellite we have refined the orbit solution and derived a new value of the bulk density of Hermione of 1.4+0.5/−0.2gcm−3. We infer a macroscopic porosity of ∼33+5/−20%.