Closing the Last Mile Gap in Access to Multimodality Imaging in Rural Settings: Design of the Imaging Core of the Risk Underlying Rural Areas Longitudinal Study.

Achieving optimal cardiovascular health in rural populations can be challenging for several reasons including decreased access to care with limited availability of imaging modalities, specialist physicians, and other important health care team members. Therefore, innovative solutions are needed to optimize health care and address cardiovascular health disparities in rural areas. Mobile examination units can bring imaging technology to underserved or remote communities with limited access to health care services. Mobile examination units can be equipped with a wide array of assessment tools and multiple imaging modalities such as computed tomography scanning and echocardiography. The detailed structural assessment of cardiovascular and lung pathology, as well as the detection of extracardiac pathology afforded by computed tomography imaging combined with the functional and hemodynamic assessments acquired by echocardiography, yield deep phenotyping of heart and lung disease for populations historically underrepresented in epidemiological studies. Moreover, by bringing the mobile examination unit to local communities, innovative approaches are now possible including engagement with local professionals to perform these imaging assessments, thereby augmenting local expertise and experience. However, several challenges exist before mobile examination unit-based examinations can be effectively integrated into the rural health care setting including standardizing acquisition protocols, maintaining consistent image quality, and addressing ethical and privacy considerations. Herein, we discuss the potential importance of cardiac multimodality imaging to improve cardiovascular health in rural regions, outline the emerging experience in this field, highlight important current challenges, and offer solutions based on our experience in the RURAL (Risk Underlying Rural Areas Longitudinal) cohort study.

Patterns, Prognostic Implications, and Rural-Urban Disparities in Optimal GDMT Following HFrEF Diagnosis Among Medicare Beneficiaries.

BACKGROUND: Patterns and disparities in guideline-directed medical therapy (GDMT) uptake for heart failure with reduced ejection fraction (HFrEF) across rural vs urban regions are not well described. OBJECTIVES: This study aims to evaluate patterns, prognostic implications, and rural-urban differences in GDMT use among Medicare beneficiaries following new-onset HFrEF. METHODS: Patients with a diagnosis of new-onset HFrEF in a 5% Medicare sample with available data for Part D medication use were identified from January 2015 through December 2020. The primary exposure was residence in rural vs urban zip codes. Optimal triple GDMT was defined as ≥50% of the target daily dose of beta-blockers, ≥50% of the target daily dose of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker or any dose of sacubitril/valsartan, and any dose of mineralocorticoid receptor antagonist. The association between the achievement of optimal GDMT over time following new-onset HFrEF diagnosis and risk of all-cause mortality and subsequent HF hospitalization was also evaluated using adjusted Cox models. The association between living in rural vs urban location and time to optimal GDMT achievement over a 12-month follow-up was assessed using cumulative incidence curves and adjusted Fine-Gray subdistribution hazard models. RESULTS: A total of 41,296 patients (age: 76.7 years; 15.0% Black; 27.6% rural) were included. Optimal GDMT use over the 12-month follow-up was low, with 22.5% initiated on any dose of triple GDMT and 9.1% on optimal GDMT doses. Optimal GDMT on follow-up was significantly associated with a lower risk of death (HR: 0.89 [95% CI: 0.85-0.94]; P < 0.001) and subsequent HF hospitalization (HR: 0.93 [95% CI: 0.87-0.98]; P = 0.02). Optimal GDMT use at 12 months was significantly lower among patients living in rural (vs urban) areas (8.4% vs 9.3%; P = 0.02). In adjusted analysis, living in rural (vs urban) locations was associated with a significantly lower probability of achieving optimal GDMT (HR: 0.92 [95% CI: 0.86-0.98]; P = 0.01 Differences in optimal GDMT use following HFrEF diagnosis accounted for 16% of excess mortality risk among patients living in rural (vs urban) areas. CONCLUSIONS: Use of optimal GDMT following new-onset HFrEF diagnosis is low, with substantially lower use noted among patients living in rural vs urban locations. Suboptimal GDMT use following new-onset HFrEF was associated with an increased risk of mortality and subsequent HF hospitalization.

Hospital at Home as a Treatment Strategy for Worsening Heart Failure.

Hospital at home (HaH) is an innovative care model that may be particularly suited for heart failure (HF). Outpatient visits and inpatient care have been the 2 traditional settings for HF care, yet may not match the social and medical needs of patients at all times. Alternative models such as HaH may represent an effective and patient-centered option for select patients with worsening HF. To date, limited research in HF and other disease states has supported HaH as being safe and lower cost than traditional inpatient admission. Supporting HaH are new payment structures, such as Medicare's Acute Hospital Care at Home waiver program. In combination with outpatient visits, outpatient intravenous diuretic clinics, inpatient care, and cardiac intensive care, HaH could be a core component of a comprehensive care model with the potential to match resource utilization with the needs of patients across the spectrum of HF severity, and improve patient outcomes.

Demographic and Regional Trends of Cardiovascular Diseases and Diabetes Mellitus-Related Mortality in the United States From 1999 to 2019.

OBJECTIVE: The purpose of this research was to study the contemporary trends in cardiovascular disease (CVD) and diabetes mellitus (DM)-related mortality. METHODS: We used the Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) database to identify adults ≥25 years old where both CVD and DM were listed as an underlying or contributing cause of death between 1999 and 2019. Crude and age-adjusted mortality rates per 100,000 population were determined. RESULTS: The overall age-adjusted mortality rate was 99.18 in 1999 and 91.43 in 2019, with a recent increase from 2014-2019 (annual percent change 1.0; 95% confidence interval [CI], 0.3-1.6). Age-adjusted mortality rate was higher for males compared with females, with increasing mortality in males between 2014 and 2019 (annual percent change 1.5; 95% CI, 0.9-2.0). Age-adjusted mortality rate was highest for non-Hispanic Black adults and was ∼2-fold higher compared with non-Hispanic White adults. Young and middle-aged adults (25-69 years) had increasing age-adjusted mortality rates in recent years. There were significant urban-rural disparities, and age-adjusted mortality rates in rural counties increased from 2014 to 2019 (annual percent change 2.2; 95% CI, 1.5-2.9); states in the 90th percentile of mortality had age-adjusted mortality rates that were ∼2-fold higher than those in the bottom 10th percentile of mortality. CONCLUSION: After an initial decrease in DM + CVD-related mortality for a decade, this trend has reversed, with increasing mortality from 2014 to 2019. Significant geographic and demographic disparities persist, requiring targeted health policy interventions to prevent the loss of years of progress.

Applicability of Vericiguat to Patients Hospitalized for Heart Failure in the United States.

BACKGROUND: In January 2021, vericiguat, a soluble guanylate cyclase stimulator, was approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of cardiovascular death and heart failure (HF) hospitalization among patients with a recent worsening HF event based on the VICTORIA (VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial. OBJECTIVES: This study sought to leverage a contemporary U.S. registry of patients hospitalized for heart failure (HF) to characterize patients who may be candidates for vericiguat based on FDA label and the VICTORIA trial eligibility criteria. METHODS: The authors studied patients hospitalized for HF with ejection fraction (EF) <45% across 525 sites in the GWTG-HF (Get With The Guidelines-Heart Failure) registry between January 2014 and December 2020. Approximate FDA label criteria (excluding estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2, dialysis, or patients with heart transplantation or durable mechanical circulatory support) and eligibility criteria for the VICTORIA trial were applied to the GWTG-HF cohort. RESULTS: Among 241,057 patients with EF <45% in the GWTG-HF registry, 221,730 (92%) could be candidates for vericiguat under the FDA label and 92,249 (38%) would have been eligible for the VICTORIA trial. The most frequent reasons for ineligibility for the FDA label were eGFR <15 mL/min/1.73 m2 (5.7%) and dialysis (1.6%). Although there were greater proportions of women and Black patients in the GWTG-HF registry, most clinical characteristics were qualitatively similar with patients enrolled in the VICTORIA trial. Among Medicare beneficiaries in the GWTG-HF registry eligible for vericiguat by either FDA label or VICTORIA trial criteria, 12-month postdischarge rates of mortality (36%-37%), HF hospitalization (33%-35%), all-cause hospitalization (64%-66%), and mean health care expenditure (U.S. $25,106-$25,428) were high. CONCLUSIONS: Data from a large, contemporary U.S. registry of patients actively hospitalized for HF with EF <45% suggest that approximately 4 in 10 patients meet the criteria of the VICTORIA trial and that more than 9 in 10 patients are potential candidates for vericiguat based on the FDA label. Contemporary Medicare beneficiaries hospitalized for HF with EF <45% and eligible for vericiguat face high rates of postdischarge mortality and readmission and accrue substantial health care costs.

Subjective Financial Hardship due to Medical Bills Among Patients With Heart Failure in the United States: The 2014-2018 Medical Expenditure Panel Survey.

BACKGROUND: Heart failure (HF) poses a substantial economic burden on the United States (US) health care system. In contrast, little is known about the financial challenges faced by patients with HF. In this study, we examined the scope and sociodemographic predictors of subjective financial hardship due to medical bills incurred by patients with HF. METHODS: In the Medical Expenditure Panel Survey (MEPS; years 2014--2018), a US nationally representative database, we identified all patients who reported having HF. Any subjective financial hardship due to medical bills was assessed based on patients' reporting either themselves or their families (1) having difficulties paying medical bills in the past 12 months, (2) paying bills late or (3) being unable to pay bills at all. Logistic regression was used to evaluate independent predictors of financial hardship among patients with HF. All analyses took into consideration the survey's complex design. RESULTS: A total of 116,563 MEPS participants were included in the analysis, of whom 858 (0.7%) had diagnoses of HF, representing 1.8 million (95% CI 1.6-2.0) patients annually. Overall, 33% (95% CI 29%-38%) reported any financial hardship due to medical bills, and 13.2% were not able to pay bills at all. Age ≤ 65 years and lower educational attainment were independently associated with higher odds of subjective financial hardship due to medical bills. CONCLUSION: Subjective financial hardship is a prevalent issue for patients with HF in the US, particularly those who are younger and have lower educational attainment. There is a need for policies that reduce out-of-pocket costs for the care of HF, an enhanced identification of this phenomenon in the clinical setting, and approaches to help minimize financial toxicity in patients with HF while ensuring optimal quality of care.

Cellulose and its derivatives, coffee grounds, and cross-linked, ß-cyclodextrin in the race for the highest sorption capacity of cationic dyes in accordance with the principles of sustainable development.

In this study, seven different materials were analyzed and includes coffee grounds (CG), two types of cellulose (CGC and CC), two types of modified cellulose (CT and CTCD), and cross-linked ß-cyclodextrin (CD-1 and CD-2) were tested as adsorbents for the removal of dyes from the wastewater. The composition, morphology, and presence of functional groups in the obtained sorption materials were characterized by elemental analysis, SEM, TG/DTA, and FTIR spectroscopy. The sorption processes of the model contaminant, crystal violet (CV), were studied by kinetics and equilibrium models. The results showed, that using CTCD, the dye was adsorbed rapidly in 1 min and the slowest adsorption occurred in 20 min by CG. The time evolution was adjusted using a two-model, pseudo second-order model (CG and CGC) and pseudo first-order model in the rest adsorbents. According to the Langmuir and Sips isotherm models, the maximum adsorption capacities were very high in each case ranging from 1092.24 to 1220.40 mg g-1. Moreover, the adsorption capacity of the near-natural materials remained even higher after five regeneration cycles. The regeneration is almost waste-free and the materials used can be decomposed during composting. In addition, almost complete removal of cationic dyes was observed during the treatment of real wastewater samples.

Potential Role and Limitations of Estimated Glomerular Filtration Rate Slope Assessment in Cardiovascular Trials: A Review.

Importance: Cardiovascular trials have traditionally been underpowered to assess advanced chronic kidney disease (CKD) outcomes, and when included as a secondary end point, trials have used progression of CKD as incidence of some variation of a composite of end-stage kidney disease (ESKD) outcomes. Such outcomes are infrequent or occur late in cardiovascular outcome trials, which highlights the need for alternate markers for assessing the impact of interventions on kidney function at an earlier stage of the disease and, from the prevention perspective, more relevant stage of the disease. Observations: Estimated glomerular filtration rate (eGFR) slope has demonstrated strong association with subsequent progression to ESKD. With adequate sample size, treatment effects in the range of 0.5 to 1.00 mL/min/1.73 m2/y had 96% probability of predicting CKD progression, defined as doubling of serum creatinine, eGFR less than 15 mL/min/1.73 m2, or ESKD. eGFR slope can be used in patients with higher baseline values and may provide CKD progression insights when few hard kidney events are observed, especially in trials with limited follow-up. However, among trials that have determined eGFR slope, significant variations exist regarding inclusion of baseline values, calculation of eGFR values, and the follow-up period, which make it difficult to compare and gauge the incremental benefit of the interventions. There are multiple challenges in computing eGFR slope in cardiovascular trials, such as accounting for initial eGFR dip, nonlinearity, and heteroscedasticity. Conclusions and Relevance: eGFR slope may serve as a valuable marker to determine progression of CKD in cardiovascular trials. Further work is required to standardize data collection, follow-up duration, time points for kidney function assessment, and analytic methods to compute eGFR slope in cardiovascular trials.

Clinical Outcomes With Metformin and Sulfonylurea Therapies Among Patients With Heart Failure and Diabetes.

OBJECTIVES: The authors sought to characterize associations between initiation of metformin and sulfonylurea therapy and clinical outcomes among patients with comorbid heart failure (HF) and diabetes (overall and by ejection fraction [EF] phenotype). BACKGROUND: Metformin and sulfonylureas are frequently prescribed to patients with diabetes for glycemic control. The impact of these therapies on clinical outcomes among patients with comorbid HF and diabetes is unclear. METHODS: The authors evaluated Medicare beneficiaries hospitalized for HF in the Get With The Guidelines-Heart Failure Registry between 2006 and 2014 with diabetes and not prescribed metformin or sulfonylurea before admission. In parallel separate analyses for metformin and sulfonylurea, patients with newly prescribed therapy within 90 days of discharge were compared with patients not prescribed therapy. Multivariable models landmarked at 90 days evaluated associations between prescription of therapy, and mortality and hospitalization for HF (HHF) at 12 months. Negative control (falsification) endpoints included hospitalization for urinary tract infection, hospitalization for gastrointestinal bleed, and influenza vaccination. Prespecified subgroup analyses were stratified by EF ≤40% versus >40%. RESULTS: Of 5,852 patients, 454 (7.8%) were newly prescribed metformin and 504 (8.6%) were newly prescribed sulfonylurea. After adjustment, metformin prescription was independently associated with reduced risk of composite mortality/HHF (HR: 0.81; 95% CI: 0.67-0.98; P = 0.03), but individual components were not statistically significant. Findings among patients with EF >40% accounted for associations with mortality/HHF (HR: 0.68; 95% CI: 0.52-0.90) and HHF (HR: 0.58; 95% CI: 0.40-0.85) endpoints (all P for interaction ≤0.04). After adjustment, sulfonylurea initiation was associated with increased risk of mortality (HR: 1.24; 95% CI: 1.00-1.52; P = 0.045) and HHF (HR: 1.22; 95% CI: 1.00-1.48; P = 0.050) with nominal statistical significance. Associations between sulfonylurea initiation and endpoints were consistent regardless of EF (all P for interaction >0.11). Neither metformin initiation nor sulfonylurea initiation were associated with negative control endpoints. CONCLUSIONS: In this population of older U.S. adults hospitalized for HF with comorbid diabetes, metformin initiation was independently associated with substantial improvements in 12-month clinical outcomes, driven by findings among patients with EF >40%. By contrast, sulfonylurea initiation was associated with excess risk of death and HF hospitalization, regardless of EF.

Kidney function assessment and endpoint ascertainment in clinical trials.

Heterogeneity in the reporting of kidney function, kidney outcomes, and definitions for kidney endpoints in clinical trials makes it challenging to compare results and gauge incremental benefit of interventions across trials. We conducted a systematic review of the ascertainment of baseline kidney variables, reporting of kidney endpoints, and definitions used to characterize these endpoints in type 2 diabetes mellitus (T2DM), kidney, and heart failure (HF) trials. Medline, Scopus, and ClinicalTrials.gov were searched from January 2014 through January 2021 for large (>1000 participants) T2DM, HF, and kidney disease trials and their secondary analyses. Trial publication and supplementary appendices were searched to abstract relevant data. Thirty-three trials (16 T2DM; 10 HF; 7 kidney diseases) were included. Thirteen trials did not include patients with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and for trials that did, representation of this cohort ranged from 0.1% to 15%. Reporting of baseline kidney function and albuminuria remained low, especially in HF trials. Variability was observed in the definition of chronic kidney disease, sustained decline in eGFR, end-stage kidney disease, kidney death, and kidney composite endpoint across trials. eGFR slope was reported in less than half trials, with differences observed in statistical models, definition of acute or chronic slope, and follow-up duration across trials. Significant heterogeneity in reporting of kidney function and kidney outcomes in large T2DM, kidney, and HF trials underscores the need for future stakeholders to draft a consensus solution. Detailed profiling of patients at baseline, accrual of more patients with advanced kidney disease, and standardization of definitions in trials may improve the ability to compare the results across trials.

Representation of sex, race, and ethnicity in pivotal clinical trials for dermatological drugs.

BACKGROUND: It is of paramount importance that clinical trials are designed with adequate health equity considerations to prevent disproportionate analyses of specific demographics. OBJECTIVE: In this study, we investigated the representation of sex, race, and ethnicity in pivotal clinical trials for drugs with dermatological disease indications approved by the U.S. Food and Drug Administration between 1995 and 2019. METHODS: Thirty-six novel drugs with indications to treat dermatological diseases, approved by the U.S. Food and Drug Administration between January 1995 and December 2019 were abstracted from Drugs@FDA. The drug approval label, statistical review, official record, and trial publication were reviewed for data on disease indication, approval year, pathway, number of participants, participant demographics (sex, race, and ethnicity), location, and sponsor type. RESULTS: The overall female representation was 45.6% (n = 17,492 of 38,320). Adequate female representation was noted for five of six disease indications. Caucasians were predominantly overrepresented (80.4%; n = 28,065 of 34,890); Blacks (9.8%; n = 3242 of 33,240) and Asians (5.5%; n = 1535 of 27,696) were consistently underrepresented. Across sponsor types, there was a significant difference in the distribution of women (χ2 = 6.332; p = .042), as well as Caucasians (χ2 = 12.813; p = .002), Blacks (χ2 = 13.002; p = .002), and Hispanics/Latinos (χ2 = 7.747; p = .021). CONCLUSION: Persistence of disparities disproportionately affect the quality of data behind therapies for certain demographics; as such, enrollment practices must continue to address the issue of underrepresentation. Efforts to facilitate demographic equity among clinical trial participants must be supported to ensure that safety and efficacy conclusions are drawn from representative population samples.

Diuretic Changes, Health Care Resource Utilization, and Clinical Outcomes for Heart Failure With Reduced Ejection Fraction: From the Change the Management of Patients With Heart Failure Registry.

BACKGROUND: Diuretics are a mainstay therapy for the symptomatic treatment of heart failure. However, in contemporary US outpatient practice, the degree to which diuretic dosing changes over time and the associations with clinical outcomes and health care resource utilization are unknown. METHODS: Among 3426 US outpatients with chronic heart failure with reduced ejection fraction in the Change the Management of Patients with Heart Failure registry with complete medication data and who were prescribed a loop diuretic, diuretic dose increase was defined as: (1) change to a total daily dose higher than their previous total daily dose, (2) addition of metolazone to the regimen, (3) change from furosemide to either bumetanide or torsemide, and the change persists for at least 7 days. Adjusted hazard ratios or rate ratios along with 95% CIs were reported for clinical outcomes among patients with an increase in oral diuretic dose versus no increase in diuretic dose. RESULTS: Overall, 796 (23%) had a diuretic dose increase (18 episodes per 100 patient-years). The proportion of patients with dyspnea at rest (38% versus 26%), dyspnea at exertion (79% versus 67%), orthopnea (32% versus 21%), edema (60% versus 43%), and weight gain (40% versus 23%) were significantly (all P <0.001) higher in the diuretic increase group. Baseline angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (hazard ratio, 0.75 [95% CI, 0.65-0.87]) use were associated with lower likelihood of diuretic increase over time. Patients with a diuretic dose increase had a significantly higher number of heart failure hospitalizations (rate ratio, 2.53 [95% CI, 2.10-3.05]), emergency department visits (rate ratio, 1.84 [95% CI, 1.56-2.17]), and home health visits (rate ratio, 1.88 [95% CI, 1.39-2.54]), but not all-cause mortality (hazard ratio, 1.10 [95% CI, 0.89-1.36]). Similarly, greater furosemide dose equivalent increases were associated with greater resource utilization but not with mortality, compared with smaller increases. CONCLUSIONS: In this contemporary US registry, 1 in 4 patients with heart failure with reduced ejection fraction had outpatient escalation of diuretic therapy over longitudinal follow-up, and these patients were more likely to have sign/symptoms of congestion. Outpatient diuretic dose escalation of any magnitude was associated with heart failure hospitalizations and resource utilization, but not all-cause mortality.

Clinical and Economic Burden of Stroke Among Young, Midlife, and Older Adults in the United States, 2002-2017.

OBJECTIVE: To assess trends of stroke hospitalization rates, inpatient mortality, and health care resource use in young (aged ≤44 years), midlife (aged 45-64 years), and older (aged ≥65 years) adults. PATIENTS AND METHODS: We studied the National Inpatient Sample database (January 1, 2002 to December 31, 2017) to analyze stroke-related hospitalizations. We identified data using the International Classification of Diseases, Ninth/Tenth Revision codes. RESULTS: Of 11,381,390 strokes, 79% (n=9,009,007) were ischemic and 21% (n=2,372,383) were hemorrhagic. Chronic diseases were more frequent in older adults; smoking, alcoholism, and migraine were more prevalent in midlife adults; and coagulopathy and intravenous drug abuse were more common in young patients with stroke. The hospitalization rates of stroke per 10,000 increased overall (31.6 to 33.3) in young and midlife adults while decreasing in older adults. Although mortality decreased overall and in all age groups, the decline was slower in young and midlife adults than older adults. The mean length of stay significantly decreased in midlife and older adults and increased in young adults. The inflation-adjusted mean cost of stay increased consistently, with an average annual growth rate of 2.44% in young, 1.72% in midlife, and 1.45% in older adults owing to the higher use of health care resources. These trends were consistent in both ischemic and hemorrhagic stroke. CONCLUSION: Stroke-related hospitalization and health care expenditure are increasing in the United States, particularly among young and midlife adults. A higher cost of stay counterbalances the benefits of reducing stroke and mortality in older patients.

Trends in 30- and 90-Day Readmission Rates for Heart Failure.

BACKGROUND: The impact of hospital readmission reduction program (HRRP) on heart failure (HF) outcomes has been debated. Limited data exist regarding trends of HF readmission rates beyond 30 days from all-payer sources. The aim of this study was to investigate temporal trends of 30- and 90-day HF readmissions rates from 2010 to 2017 in patients from all-payer sources. METHODS: The National Readmission Database was utilized to identify HF hospitalizations between 2010 and 2017. In the primary analysis, a linear trend in 30-day and 90-day readmissions from 2010 to 2017 was assessed. While in the secondary analysis, a change in aggregated 30- and 90-day all-cause and HF-specific readmissions pre-HRRP penalty phase (2010-2012) and post-HRRP penalties (2013-2017) was compared. Subgroup analyses were performed based on (1) Medicare versus non-Medicare insurance, (2) low versus high HF volume, and (3) HF with reduced versus preserved ejection fraction (heart failure with reduced ejection fraction and heart failure with preserved ejection fraction). Multiple logistic and adjusted linear regression analyses were performed for annual trends. RESULTS: A total of 6 669 313 index HF hospitalizations for 30-day, and 5 077 949 index HF hospitalizations for 90-day readmission, were included. Of these, 1 213 402 (18.2%) encounters had a readmission within 30 days, and 1 585 445 (31.2%) encounters had a readmission within 90 days. Between 2010 and 2017, both 30 and 90 days adjusted HF-specific and all-cause readmissions increased (8.1% to 8.7%, P trend 0.04, and 18.3% to 19.9%, P trend <0.001 for 30-day and 14.8% to 16.0% and 30.9% to 34.6% for 90-day, P trend <0.001 for both, respectively). Readmission rates were higher during the post-HRRP penalty period compared with pre-HRRP penalty phase (all-cause readmission 30 days: 18.6% versus 17.5%, P<0.001, all-cause readmission 90 days: 32.0% versus 29.9%, P<0.001) across all subgroups except among the low-volume hospitals. CONCLUSIONS: The rates of adjusted HF-specific and all-cause 30- and 90-day readmissions have increased from 2010 to 2017. Readmissions rates were higher during the HRRP phase across all subgroups except the low-volume hospitals.

Assessment of Heterogeneity in Heart Failure-Related Meta-Analyses.

BACKGROUND: Assessment of heterogeneity in meta-analyses is critical to ensure the consistency of pooled results. Therefore, we sought to assess the evaluation and reporting of heterogeneity in heart failure (HF) meta-analyses. METHODS: Study level meta-analyses pertaining to HF were selected from January 2009 to July 2019, published in 11 high impact factor journals. We tabulated the overall proportion of the meta-analyses reporting statistical heterogeneity and specific metrics and methods employed to quantify and explore heterogeneity. RESULTS: Of 126 HF meta-analyses (612 outcomes), heterogeneity was reported for 422 outcomes (68.9 %) in 108 meta-analyses. Out of the 422 outcomes reporting statistical heterogeneity, 137 outcomes (32.5%) had no observable heterogeneity: (I2=0%), 40 outcomes (9.5%) had low heterogeneity (I2<25%), 76 outcomes (18%) had moderate heterogeneity (I2=25%-50%), and 169 outcomes (40%) had high heterogeneity (I2>50%). Reporting of statistical heterogeneity was not significantly associated with year of publication, funding source, disclosure information, or the type of studies pooled. Sensitivity analysis (n=68) was the most common statistical technique employed to evaluate the source of heterogeneity followed by subgroup analyses (n=59) and meta-regression (n=40). CONCLUSIONS: Despite being an essential component of meta-analyses, heterogeneity was not reported for nearly 30% of outcomes and variably handled in contemporary HF meta-analyses. As meta-analyses increase across HF science, interpreting and handling of heterogeneity should be standardized.

Ten-Year Trends in Enrollment of Women and Minorities in Pivotal Trials Supporting Recent US Food and Drug Administration Approval of Novel Cardiometabolic Drugs.

Background In 1993, the US Food and Drug Administration established guidelines to increase diversity by sex and race/ethnicity of participants in clinical trials supporting novel drug approvals. In this study we investigated the 10-year trends of participation of women and minorities in pivotal trials supporting approval of new molecular entities in cardiometabolic drugs from January 2008 to December 2017. Methods and Results A list of new molecular entities was abstracted from publicly available data at Drugs@Fda. Sex and race/ethnicity data were collected from trial publications. Linear regression analysis was performed to assess the relation between drug approval year and proportion of women and minorities enrolled. Thirty-five novel cardiovascular (n=24) and diabetes mellitus (n=11) drugs were approved by the US Food and Drug Administration during the study period. The median number of participants supporting each drug was 5930 (interquartile range, 3175-10 942). Women represented 36% (n=108 052) of trial participants (n=296 163). Women were underrepresented compared with their proportion of the disease population in trials of coronary heart disease (participation-to-prevalence ratio, 0.52), heart failure (participation-to-prevalence ratio, 0.58), and acute coronary syndrome (participation-to-prevalence ratio, 0.68). Among trial participants, 81% were white, 4% black, 12% Asian, and 11% Hispanic/Latino. There was no significant association between enrollment of women (P=0.29) or underrepresented minorities (P=0.45) with the drug approval year. Conclusions Over the past decade (2008-2017), women and minorities, particularly blacks, have continued to be inadequately represented in pivotal cardiometabolic clinical trials that support US Food and Drug Administration approval of new molecular entities. This may have major implications in determining efficacy of such therapies in these groups, and may impair generalizability of trial results to routine clinical practice.

How well do we represent ourselves: an analysis of cardiology fellowships website content.

Background: The Internet is the primary source of information for prospective cardiology fellowship aspirants. The objective of this study was to evaluate cardiology fellowship programs' online profile. Materials & methods: Two independent reviewers accessed 221 US based cardiology fellowship program websites obtained through Fellowship and Residency Electronic Interactive Database for pre-selected 20 criteria. The update status of websites was assessed using 6-point criteria. Results: Only 25 (11.3%) websites were fully up-to-date; 23 (10.4%) fulfilled 80% of the 20-point criteria and 85 (38.5%) program websites had fewer than 50% of the criteria listed. Conclusion: Most cardiology fellowship program websites lack crucial details. In this technology driven age, efforts should be made to ensure updated websites.