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Tissue damage and organ failure are major problems that many people face worldwide. Most of them benefit from treatment related to modern technology’s tissue regeneration process. Tissue engineering is one of the booming fields widely used to replace damaged tissue. Scaffold is a base material in which cells and growth factors are embedded to construct a substitute tissue. Various materials have been used to develop scaffolds. Bio-based natural materials are biocompatible, safe, and do not release toxic compounds during biodegradation. Therefore, it is highly recommendable to fabricate scaffolds using such materials. To date, there have been no singular materials that fulfill all the features of the scaffold. Hence, combining two or more materials is encouraged to obtain the desired characteristics. To design a reliable scaffold by combining different materials, there is a need to choose a good fabrication technique. In this review article, the bio-based natural materials and fine fabrication techniques that are currently used in developing scaffolds for tissue regeneration applications, along with the number of articles published on each material, are briefly discussed. It is envisaged to gain explicit knowledge of developing scaffolds from bio-based natural materials for tissue regeneration applications.

Background: Studies show that digoxin use is declining but is still prevalent. Recent data on digoxin prescription and characteristics of digoxin prescribers are unknown, which can help understand its contemporary use., Methods: Using Medicare Part D data from 2013 to 2019, we studied the change in number and proportion of digoxin prescriptions and digoxin prescribers, overall and by specialty. Using logistic regression, we identified prescriber characteristics associated with digoxin prescription., Results: From 2013 to 2019, total digoxin prescriptions (4.6 to 1.8 million) and proportion of digoxin prescribers decreased (9.1% to 4.3% overall; 26.6% to 11.8% among General Medicine prescribers and 65.4% to 48.9% among Cardiology). Of digoxin prescribers from 2013 practicing in 2019 (91.2% remained active), 59.1% did not prescribe digoxin at all, 31.7% reduced, and 9.2% maintained or increased prescriptions. The proportion of all digoxin prescriptions that were prescribed by General Medicine prescribers declined from 59.7% to 48.2% and increased for Cardiology (29% to 38.5%). Among new prescribers in 2019 ( N = 85,508), only 1.9% prescribed digoxin. Digoxin prescribers when compared to non-digoxin prescribers were more likely male, graduated from medical school earlier, were located in the Midwest or South, and belonged to Cardiology (all P < .001)., Conclusions: Digoxin prescriptions continue to decline with over half of 2013 prescribers no longer prescribing digoxin in 2019. This may be a result of the increasing availability of newer heart failure therapies. The decline in digoxin prescription was greater among general medicine physicians than cardiologists, suggesting a change in digoxin use to a medication prescribed increasingly by specialists., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rohan Khera reports a relationship with NEJM Journal Watch that includes: consulting or advisory. Rohan Khera reports a relationship with Evidence2Health that includes: employment. Rohan Khera has pending Provisional Patent Application No. 63/177,177. Harlan Krumholz reports a relationship with UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, and Martin/Baughman Law Firm that includes: consulting or advisory. Harlan Krumholz reports a relationship with Refactor Health and HugoHealth that includes: employment. Harlan Krumholz reports a relationship with the Centers for Medicare & Medicaid Services and Johnson & Johnson that includes: employment. Yuan Lu reports a relationship with National Heart Lung and Blood Institute that includes: funding grants. Karthik Murugiah reports a relationship with National Heart Lung and Blood Institute that includes: funding grants.

Invasive or selective pulmonary angiography has historically been used as the gold standard diagnostic test for the evaluation of a wide array of pulmonary arterial conditions, most commonly pulmonary thromboembolic diseases. With the emergence of various noninvasive imaging modalities, the role of invasive pulmonary angiography is shifting to the assistance of advanced pharmacomechanical therapies for such conditions. Components of invasive pulmonary angiography methodology include optimal patient positioning, vascular access, catheter selections, angiographic positioning, contrast settings, and recognition of angiographic patterns of common thromboembolic and nonthromboembolic conditions. We review the pulmonary vascular anatomy, step-by-step performance, and interpretation of invasive pulmonary angiography., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Younger women experience worse health status than men after their index episode of acute myocardial infarction (AMI). However, whether women have a higher risk for cardiovascular and noncardiovascular hospitalizations in the year after discharge is unknown., Objectives: The aim of this study was to determine sex differences in causes and timing of 1-year outcomes after AMI in people aged 18 to 55 years., Methods: Data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study, which enrolled young patients with AMI across 103 U.S. hospitals, were used. Sex differences in all-cause and cause-specific hospitalizations were compared by calculating incidence rates ([IRs] per 1,000 person-years) and IR ratios with 95% CIs. We then performed sequential modeling to evaluate the sex difference by calculating subdistribution HRs (SHRs) accounting for deaths., Results: Among 2,979 patients, at least 1 hospitalization occurred among 905 patients (30.4%) in the year after discharge. The leading causes of hospitalization were coronary related (IR: 171.8 [95% CI: 153.6-192.2] among women vs 117.8 [95% CI: 97.3-142.6] among men), followed by noncardiac hospitalization (IR: 145.8 [95% CI: 129.2-164.5] among women vs 69.6 [95% CI: 54.5-88.9] among men). Furthermore, a sex difference was present for coronary-related hospitalizations (SHR: 1.33; 95% CI: 1.04-1.70; P = 0.02) and noncardiac hospitalizations (SHR: 1.51; 95% CI: 1.13-2.07; P = 0.01)., Conclusions: Young women with AMI experience more adverse outcomes than men in the year after discharge. Coronary-related hospitalizations were most common, but noncardiac hospitalizations showed the most significant sex disparity., Competing Interests: Funding Support and Author Disclosures The VIRGO study (NCT00597922) was supported by grant R01 HL081153 from the National Heart, Lung, and Blood Institute. In the past 3 years, Dr Krumholz has received expenses and/or personal fees from UnitedHealth, Element Science, Eyedentifeye, and F-Prime; is a co-founder of Refactor Health and HugoHealth; and is associated with contracts, through Yale New Haven Hospital, from the Centers for Medicare & Medicaid Services and through Yale University from the U.S. Food and Drug Administration, Johnson & Johnson, Google, and Pfizer. Dr. Murugiah has received support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under award K08HL157727). Dr. Khera has received support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under award K23HL153775) and the Doris Duke Charitable Foundation (under award, 2022060); receives research support, through Yale, from Bristol Myers Squibb and Novo Nordisk; is a coinventor of U.S. Provisional Patent Applications 63/177,117, 63/428,569, and 63/346,610, unrelated to current work; and is a founder of Evidence2Health, a precision health platform to improve evidence-based cardiovascular care. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Data on depression and stress among patients with spontaneous coronary artery dissection (SCAD) are limited. Using data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study, which prospectively enrolled 3,572 acute myocardial infarction (AMI) patients between 18 and 55 years of age, we identified 67 SCAD cases. We compared Patient Health Questionnaire-9 (PHQ-9) and 14-item Perceived Stress Scale (PSS-14) scores obtained at baseline, 1 month, and 12 months between SCAD and AMI of all other causes. Using longitudinal linear mixed-effects analysis, we compared depression and stress scores between SCAD and other AMI, adjusting for time and selected covariates. Patients with SCAD had lower baseline PHQ-9 scores (6.1 ± 6.0 vs 7.7 ± 6.4 for other patients with AMI, p = 0.03), similar 1-month scores, and lower 12-month scores (3.2 ± 4.3 vs 4.9 ± 5.5, p = 0.004). At baseline and 1 month, patients with SCAD had similar PSS-14 scores to those of other patients with AMI. At 12 months, patients with SCAD had lower scores (18.4 ± 8.8 vs 21.5 ± 9.3 for other patients with AMI, p = 0.009). After adjustment for cardiovascular risk factors, co-morbidities, and clinical acuity, no differences in PHQ-9 or PSS-14 scores remained between SCAD and other AMI. Similar results were obtained in a subgroup analysis of only women with SCAD and other AMI. In conclusion, patients with SCAD had a relatively lower burden of depression and perceived stress than other patients with AMI, potentially because of fewer co-morbidities and favorable socioeconomic factors. However, given high depression and stress burden in both SCAD and other patients with AMI, routine screening can help identify and treat these patients., Competing Interests: Disclosures Dr. Bueno receives research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021 and PI17/01799), Sociedad Española de Cardiología, Astra-Zeneca, Bayer, PhaseBio, and Novartis; has received consulting fees from Astra-Zeneca, Novartis, and Organon; speaking fees from Novartis, and is a scientific advisor for MEDSCAPE-the heart.org. In the past 3 years, Dr. Krumholz received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, and Martin/Baughman Law Firm. He is a co-founder of Refactor Health and HugoHealth, and is associated with contracts, through Yale New Haven Hospital, with the Centers for Medicare & Medicaid Services and through Yale University with Johnson & Johnson. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: An increasing proportion of people in the US hospitalized for acute myocardial infarction (AMI) are younger than 55 years, with the largest increase in young women. Effective prevention requires an understanding of risk factors associated with risk of AMI in young women compared with men., Objectives: To assess the sex-specific associations of demographic, clinical, and psychosocial risk factors with first AMI among adults younger than 55 years, overall, and by AMI subtype., Design, Setting, and Participants: This study used a case-control design with 2264 patients with AMI, aged 18 to 55 years, from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study and 2264 population-based controls matched for age, sex, and race and ethnicity from the National Health and Nutrition Examination Survey from 2008 to 2012. Data were analyzed from April 2020 to November 2021., Exposures: A wide range of demographic, clinical, and psychosocial risk factors., Main Outcomes and Measures: Odds ratios (ORs) and population attributable fractions (PAF) for first AMI associated with demographic, clinical, and psychosocial risk factors., Results: Of the 4528 case patients and matched controls, 3122 (68.9%) were women, and the median (IQR) age was 48 (44-52) years. Seven risk factors (diabetes [OR, 3.59 (95% CI, 2.72-4.74) in women vs 1.76 (1.19-2.60) in men], depression [OR, 3.09 (95% CI, 2.37-4.04) in women vs 1.77 (1.15-2.73) in men], hypertension [OR, 2.87 (95% CI, 2.31-3.57) in women vs 2.19 (1.65-2.90) in men], current smoking [OR, 3.28 (95% CI, 2.65-4.07) in women vs 3.28 (2.65-4.07) in men], family history of premature myocardial infarction [OR, 1.48 (95% CI, 1.17-1.88) in women vs 2.42 (1.71-3.41) in men], low household income [OR, 1.79 (95% CI, 1.28-2.50) in women vs 1.35 (0.82-2.23) in men], hypercholesterolemia [OR, 1.02 (95% CI, 0.81-1.29) in women vs 2.16 (1.49-3.15) in men]) collectively accounted for the majority of the total risk of AMI in women (83.9%) and men (85.1%). There were significant sex differences in risk factor associations: hypertension, depression, diabetes, current smoking, and family history of diabetes had stronger associations with AMI in young women, whereas hypercholesterolemia had a stronger association in young men. Risk factor profiles varied by AMI subtype, and traditional cardiovascular risk factors had higher prevalence and stronger ORs for type 1 AMI compared with other AMI subtypes., Conclusions and Relevance: In this case-control study, 7 risk factors, many potentially modifiable, accounted for 85% of the risk of first AMI in young women and men. Significant differences in risk factor profiles and risk factor associations existed by sex and by AMI subtype. These findings suggest the need for sex-specific strategies in risk factor modification and prevention of AMI in young adults. Further research is needed to improve risk assessment of AMI subtypes.

Importance: Historically marginalized racial and ethnic groups are generally more likely to experience sleep deficiencies. It is unclear how these sleep duration disparities have changed during recent years., Objective: To evaluate 15-year trends in racial and ethnic differences in self-reported sleep duration among adults in the US., Design, Setting, and Participants: This serial cross-sectional study used US population-based National Health Interview Survey data collected from 2004 to 2018. A total of 429 195 noninstitutionalized adults were included in the analysis, which was performed from July 26, 2021, to February 10, 2022., Exposures: Self-reported race, ethnicity, household income, and sex., Main Outcomes and Measures: Temporal trends and racial and ethnic differences in short (<7 hours in 24 hours) and long (>9 hours in 24 hours) sleep duration and racial and ethnic differences in the association between sleep duration and age., Results: The study sample consisted of 429 195 individuals (median [IQR] age, 46 [31-60] years; 51.7% women), of whom 5.1% identified as Asian, 11.8% identified as Black, 14.7% identified as Hispanic or Latino, and 68.5% identified as White. In 2004, the adjusted estimated prevalence of short and long sleep duration were 31.4% and 2.5%, respectively, among Asian individuals; 35.3% and 6.4%, respectively, among Black individuals; 27.0% and 4.6%, respectively, among Hispanic or Latino individuals; and 27.8% and 3.5%, respectively, among White individuals. During the study period, there was a significant increase in short sleep prevalence among Black (6.39 [95% CI, 3.32-9.46] percentage points), Hispanic or Latino (6.61 [95% CI, 4.03-9.20] percentage points), and White (3.22 [95% CI, 2.06-4.38] percentage points) individuals (P < .001 for each), whereas prevalence of long sleep changed significantly only among Hispanic or Latino individuals (-1.42 [95% CI, -2.52 to -0.32] percentage points; P = .01). In 2018, compared with White individuals, short sleep prevalence among Black and Hispanic or Latino individuals was higher by 10.68 (95% CI, 8.12-13.24; P < .001) and 2.44 (95% CI, 0.23-4.65; P = .03) percentage points, respectively, and long sleep prevalence was higher only among Black individuals (1.44 [95% CI, 0.39-2.48] percentage points; P = .007). The short sleep disparities were greatest among women and among those with middle or high household income. In addition, across age groups, Black individuals had a higher short and long sleep duration prevalence compared with White individuals of the same age., Conclusions and Relevance: The findings of this cross-sectional study suggest that from 2004 to 2018, the prevalence of short and long sleep duration was persistently higher among Black individuals in the US. The disparities in short sleep duration appear to be highest among women, individuals who had middle or high income, and young or middle-aged adults, which may be associated with health disparities.

Background: Data on health status outcomes after spontaneous coronary artery dissection (SCAD) are limited., Methods and Findings: Using the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study we compared patients with SCAD and other acute myocardial infarction (AMI) at presentation (baseline), 1-month, and-12 months using standardized health status instruments. Among 3572 AMI patients ≤ 55 years, 67 had SCAD. SCAD patients were younger (median age (IQR) 45 (40.5-51) years vs. 48 (44-52) in other AMI, p = 0.003), more often female (92.5% vs. 66.6%), have college education (73.1% vs. 51.7%) and household income >$100,000 (43.3% vs. 17.7% (All p<0.001). SCAD patients at baseline had higher mean ± SD Short Form-12 [SF-12] physical component scores [PCS] (48.7±10.2 vs. 43.8±12.1, p<0.001) and mental component scores [MCS] (49.6±12.4 vs. 45.4±12.5, p = 0.008), and at 12-months [PCS (50.1±9.0 vs. 44.3±12.3, p<0.001) and MCS (53±10.1 vs 50.2±11.0, p = 0.045)]. The Euro-Quality of Life Scale [EQ-5D] VAS and EQ-5D index scores were similar at baseline, but higher at 12-months for SCAD (EQ-5D VAS: 82.2±10.2 vs. 72.3±21.0, p<0.001; EQ-5D index scores; 90.2±15.3 vs. 83.7±19.8, p = 0.012). SCAD patients had better baseline Seattle Angina Questionnaire [SAQ] physical limitation (88.8±20.1 vs. 81.2±25.4, p = 0.017). At 12-months SCAD patients had better physical limitation (98.0±8.5 vs. 91.4±18.8, p = 0.007), angina frequency (96.4±8.8 vs. 91.3±16.8, p = 0.018) and quality of life scores (80.7±14.7 vs 72.2±23.2, p = 0.005). Magnitude of change in health status from baseline to 12-months was not statistically different between the groups. After adjustment for time and comorbidities there remained no difference in most health status outcomes., Conclusions: SCAD patients fare marginally better than other AMI patients on most health status instruments and have similar 12-month health status recovery. Better pre-event health status suggests a need to modify exercise prescriptions and cardiac rehabilitation protocols to better assist this physically active population to recover., Competing Interests: The authors have declared that no competing interests exist.

Importance: Contemporary national clinical practice guidelines recommend direct-acting oral anticoagulants (DOACs) as the first-line anticoagulant strategy over warfarin for most indications, especially among older individuals with an elevated bleeding risk., Objective: To evaluate anticoagulant prescribing and DOAC uptake by US clinicians in the Medicare population., Design, Setting, and Participants: This retrospective cohort study included all US clinicians with more than 10 Medicare oral anticoagulant prescription claims, who were included in the national Medicare Provider Utilization and Payment Data (2013-2018). Data analyses were conducted between October 2020 and October 2021., Exposures: DOAC prescription in 2013., Main Outcomes and Measures: Clinicians were categorized based on 2013 prescribing as solely prescribing warfarin, DOAC, or both, and their temporal trajectories of proportionate DOAC use were examined., Results: The analysis included 325 666 unique clinicians with more than 10 oral anticoagulant prescriptions between 2013 and 2018 (26 620 [8.2%] cardiologists, 85 563 [26.3%] internal medicine physicians, 84 369 [25.9%] family medicine physicians, and 81 161 [24.9%] advanced practice clinicians, including nurse practitioners and physician assistants). In 2013, among 91 837 prescribers, 54 501 (59.3%) prescribed only warfarin, 1918 (2.1%) prescribed only a DOAC, and 35 418 (38.6%) prescribed both. During the study period, the number of clinicians prescribing DOACs increased, but 19% continued to prescribe only warfarin in 2018. While 359 cardiologists prescribing anticoagulants (1.6%) were warfarin-only prescribers, 10 414 (20.0%) and 6296 (12.6%) of family and internal medicine physicians also prescribed only warfarin, respectively. Clinicians prescribing only warfarin in 2013 had lower proportionate DOAC use throughout the study compared with 2013 DOAC prescribers, which represents a median (IQR) of 41.9% (20.3%-61.9%) of their anticoagulant prescriptions in 2018 vs 67.0% (49.9%-82.8%) for DOAC prescribers., Conclusions and Relevance: Despite the increase in DOAC use among Medicare beneficiaries, many clinicians in this study continued to use warfarin as their predominant or only anticoagulant instead of DOACs. There is a need to address barriers to the uptake of these medications to realize their potential benefits for patients.

The contemporary scope of practice of interventional cardiologists (ICs) in the United States and recent trends are unknown. Using Medicare claims from 2013 to 2017, we categorized ICs into 4 practice categories (only percutaneous coronary intervention [PCI], PCI with noninvasive imaging, PCI with specialized interventions [peripheral/structural], and all 3 services) and evaluated associations with region, hospital bed size and teaching status, gender, and graduation year. Of 6,083 ICs in 2017, 10.9% performed only PCI, 68.3% PCI with noninvasive imaging, 5.7% PCI with specialized interventions, and 15.1% all 3 services. A higher proportion of Northeast ICs (vs South ICs) were performing only PCI (24.8% vs 7.3%) and PCI with specialized interventions (12% vs 3.4%), but lower PCI and noninvasive imaging (53.8% vs 71.7%) and all 3 services (9.3% and 17.6%). Regarding ICs at larger hospitals (bed size >575 vs <218), a higher proportion was performing only PCI (23.8% vs 5.2%) or PCI with specialized interventions (13.5% vs 1.7%) and lower proportion was performing PCI with noninvasive imaging (48.8% vs 78%), similar to teaching hospitals. Female ICs (vs male ICs) more frequently performed only PCI (18.9% vs 10.6%) and less frequently all 3 services (8.3% vs 15.4%). A lower proportion of recent graduates (2001 to 2016) performed only PCI (9.8% vs 13.8%) and PCI with noninvasive imaging (66.3% vs 72.6%) but a higher proportion performed all 3 services (18% vs 8.4%) than earlier graduates (1959 to 1984). From 2013 to 2017, only PCI and PCI with noninvasive imaging decreased, whereas PCI and specialized interventions and all 3 services increased (all p <0.001). In conclusion, there is marked heterogeneity in practice responsibilities among ICs, which has implications for training and competency assessments., Competing Interests: Disclosures Dr. Krumholz reported that he has contracts through Yale New Haven Hospital with the Centers for Medicare & Medicaid Services to support quality measurement programs and through Yale with UnitedHealth Group to engage in collaborative research. He was a recipient of a research grant, through Yale, from Medtronic for data sharing; from the US Food and Drug Administration to develop methods for postmarket surveillance of medical devices; from Johnson & Johnson to support data sharing; and from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion. He is an advisor to the National Center for Cardiovascular Diseases in Beijing, was an expert witness for the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation, and is an expert witness for the Martin/Baughman Law Firm for work related to the Cook Celect IVC filter litigation and to the C.R. Bard Recovery IVC filter litigation and for the Siegfried and Jensen Law Firm for work related to the Vioxx litigation. He chairs a cardiac scientific advisory board for UnitedHealth; was a member of the IBM Watson Health Life Sciences Board; and is a member of the advisory board for Element Science, the healthcare advisory board for Facebook, and the physician advisory board for Aetna. He is the cofounder of HugoHealth, a personal health information platform, and cofounder of Refactor Health, an enterprise health care artificial intelligence–augmented data management company. He is a venture partner at F-Prime. Dr. Murugiah is supported by contracts through Yale New Haven Hospital with the Centers for Medicare & Medicaid Services to support quality measurement programs. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Access to acute cardiovascular care has improved and health services capacity has increased over the past decades. We assessed national changes in (1) patient characteristics, (2) in-hospital management and (3) patient outcomes among patients presenting with ST segment elevation myocardial infarction (STEMI) in 2011-2015 in China., Methods: In a nationally representative sample of hospitals in China, we created two random cohorts of patients in 2011 and 2015 separately. We weighted our findings to estimate nationally representative numbers and assessed changes from 2011 to 2015. Data were abstracted from medical charts centrally using standardised definitions., Results: While the proportion of patients with STEMI among all patients with acute myocardial infarction decreased over time from 82.5% (95% CI 81.7 to 83.3) in 2011 to 68.5% (95% CI 67.7 to 69.3) in 2015 (p<0.0001), the weighted national estimate of patients with STEMI increased from 210 000 to 380 000. The rate of reperfusion eligibility among patients with STEMI decreased from 49.3% (95% CI 48.1 to 50.5) to 42.2% (95% CI 41.1 to 43.4) in 2015 (p<0.0001); ineligibility was principally driven by larger proportions with prehospital delay exceeding 12 hours (67.4%-76.7%, p<0.0001). Among eligible patients, the proportion receiving reperfusion therapies increased from 54% (95% CI 52.3 to 55.7) to 59.7% (95% CI 57.9 to 61.4) (p<0.0001). Crude and risk-adjusted rates of in-hospital death did not differ significantly between 2011 and 2015., Conclusions: In this most recent nationally representative study of STEMI in China, the use of acute reperfusion increased, but no significant improvement occurred in outcomes. There is a need to continue efforts to prevent cardiovascular diseases, to monitor changes in in-hospital treatments and outcomes, and to reduce prehospital delay., Competing Interests: Competing interests: JL reported receiving research grants, through Fuwai Hospital, from the People’s Republic of China for work to improve the management of hypertension and blood lipids and to improve care quality and patient outcomes of cardiovascular disease; receiving research agreements, through the National Center for Cardiovascular Diseases and Fuwai Hospital, from Amgen for a multicentre clinical trial assessing the efficacy and safety of omecamtiv mecarbil and for dyslipidaemic patient registration; receiving a research agreement, through Fuwai Hospital, from Sanofi for a multicentre clinical trial on the effects of sotagliflozin; receiving a research agreement, through Fuwai Hospital, with the University of Oxford for a multicentre clinical trial of empagliflozin; receiving a research agreement, through the National Center for Cardiovascular Diseases, from AstraZeneca for clinical research methods training, outside the submitted work; and receiving a research agreement, through the National Center for Cardiovascular Diseases, from Lilly for physician training, outside the submitted work. HK works under contract with the Centers for Medicare & Medicaid Services to support quality measurement programmes; was a recipient of a research grant, through Yale, from Medtronic and the US Food and Drug Administration to develop methods for postmarket surveillance of medical devices; was a recipient of a research grant with Medtronic and is the recipient of a research grant from Johnson & Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold & Porter law firm for work related to the Sanofi clopidogrel litigation, from the Martin/Baughman law firm for work related to the Cook IVC filter litigation, and from the Siegfried and Jensen law firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a participant/participant representative of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook and the Physician Advisory Board for Aetna; and is the founder of Hugo Health, a personal health information platform, and cofounder of Refactor Health, an enterprise healthcare AI-augmented data management company. FM has a contract with the American College of Cardiology as the Chief Scientific Advisor for the NCDR and has received travel expenses from the Fuwai Hospital. YL is supported by the National Heart, Lung, and Blood Institute (K12HL138037) and was a recipient of a research agreement, through Yale, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: The elimination of racial and ethnic differences in health status and health care access is a US goal, but it is unclear whether the country has made progress over the last 2 decades., Objective: To determine 20-year trends in the racial and ethnic differences in self-reported measures of health status and health care access and affordability among adults in the US., Design, Setting, and Participants: Serial cross-sectional study of National Health Interview Survey data, 1999-2018, that included 596 355 adults., Exposures: Self-reported race, ethnicity, and income level., Main Outcomes and Measures: Rates and racial and ethnic differences in self-reported health status and health care access and affordability., Results: The study included 596 355 adults (mean [SE] age, 46.2 [0.07] years, 51.8% [SE, 0.10] women), of whom 4.7% were Asian, 11.8% were Black, 13.8% were Latino/Hispanic, and 69.7% were White. The estimated percentages of people with low income were 28.2%, 46.1%, 51.5%, and 23.9% among Asian, Black, Latino/Hispanic, and White individuals, respectively. Black individuals with low income had the highest estimated prevalence of poor or fair health status (29.1% [95% CI, 26.5%-31.7%] in 1999 and 24.9% [95% CI, 21.8%-28.3%] in 2018), while White individuals with middle and high income had the lowest (6.4% [95% CI, 5.9%-6.8%] in 1999 and 6.3% [95% CI, 5.8%-6.7%] in 2018). Black individuals had a significantly higher estimated prevalence of poor or fair health status than White individuals in 1999, regardless of income strata (P < .001 for the overall and low-income groups; P = .03 for middle and high-income group). From 1999 to 2018, racial and ethnic gaps in poor or fair health status did not change significantly, with or without income stratification, except for a significant decrease in the difference between White and Black individuals with low income (-6.7 percentage points [95% CI, -11.3 to -2.0]; P = .005); the difference in 2018 was no longer statistically significant (P = .13). Black and White individuals had the highest levels of self-reported functional limitations, which increased significantly among all groups over time. There were significant reductions in the racial and ethnic differences in some self-reported measures of health care access, but not affordability, with and without income stratification., Conclusions and Relevance: In a serial cross-sectional survey study of US adults from 1999 to 2018, racial and ethnic differences in self-reported health status, access, and affordability improved in some subgroups, but largely persisted.

Background Despite its clinical significance, the risk of severe infection requiring hospitalization among outpatients with severe acute respiratory syndrome coronavirus 2 infection who receive angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) remains uncertain. Methods and Results In a propensity score-matched outpatient cohort (January-May 2020) of 2263 Medicare Advantage and commercially insured individuals with hypertension and a positive outpatient SARS-CoV-2, we determined the association of ACE inhibitors and ARBs with COVID-19 hospitalization. In a concurrent inpatient cohort of 7933 hospitalized with COVID-19, we tested their association with in-hospital mortality. The robustness of the observations was assessed in a contemporary cohort (May-August). In the outpatient study, neither ACE inhibitors (hazard ratio [HR], 0.77; 0.53-1.13, P =0.18) nor ARBs (HR, 0.88; 0.61-1.26, P =0.48) were associated with hospitalization risk. ACE inhibitors were associated with lower hospitalization risk in the older Medicare group (HR, 0.61; 0.41-0.93, P =0.02), but not the younger commercially insured group (HR, 2.14; 0.82-5.60, P =0.12; P -interaction 0.09). Neither ACE inhibitors nor ARBs were associated with lower hospitalization risk in either population in the validation cohort. In the primary inpatient study cohort, neither ACE inhibitors (HR, 0.97; 0.81-1.16; P =0.74) nor ARBs (HR, 1.15; 0.95-1.38, P =0.15) were associated with in-hospital mortality. These observations were consistent in the validation cohort. Conclusions ACE inhibitors and ARBs were not associated with COVID-19 hospitalization or mortality. Despite early evidence for a potential association between ACE inhibitors and severe COVID-19 prevention in older individuals, the inconsistency of this observation in recent data argues against a role for prophylaxis.

Introduction: The cardiac catheterization laboratory (CCL) is a focal point for cardiovascular programs and the CCL director represents the key personnel. We outline profiles of CCL directors at the 2017 U.S. News & World Report top 100 U.S. cardiovascular hospitals., Methods: Using hospital websites, LinkedIn, Healthgrades, Medicare Provider Utilization and Payment Data 2017, and Scopus, we described CCL directors (in 2017) by age, gender, years since medical graduation, international medical school graduate (IMG) status, academic rank, provider clinical focus, and Hirsch (h)-index., Results: Nearly all CCL directors were male (97%). The median age (interquartile range [IQR]) was 53 (49-61) years and median (IQR) years since medical school graduation was 28 (23-35) years. Over a third of CCL directors (39.4%) were IMGs and 38.4% had completed fellowship training at the same facility where they were CCL director. The median (IQR) h-index was 11 (6-22). Of the 69.7% CCL directors who held faculty positions, 60.9% were professors and 30.4% were associate professors. From Medicare data, 45.5% performed only percutaneous coronary interventions, 41.4% performed structural interventions, 3.0% peripheral interventions, and 2.0% performed both structural and peripheral. CCL directors at the top 25 hospitals had higher h-indexes, and more likely to have completed fellowship training at their own institution., Conclusions: There are very few women CCL directors at the top U.S. cardiovascular hospitals. A third of the CCL directors were IMGs. A significant proportion of CCL directors primarily performed structural interventions and trained at the same institution, more so at the top 25 hospitals., (© 2021 Wiley Periodicals LLC.)

Importance: Isolated systolic hypertension (ISH) is increasing in prevalence among young and middle-aged adults. However, most studies of ISH are limited to older individuals, and a substantial knowledge gap exists regarding younger adults with ISH., Objective: To assess the prevalence, awareness, and characteristics of ISH among younger and middle-aged adults in China., Design, Setting, and Participants: This cross-sectional study was performed as part of the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project, which enrolled 3.1 million community residents aged 35 to 75 years from all of the 31 provinces in China between December 15, 2014, and May 15, 2019. The present analysis included only participants younger than 50 years. Data were analyzed from May to November 2019., Main Outcomes and Measures: Prevalence and awareness of ISH (defined as systolic blood pressure of 140 mm Hg or higher and diastolic blood pressure of less than 90 mm Hg) and individual characteristics of participants with ISH., Results: Among 898 929 participants aged 35 to 49 years, the mean (SD) age was 43.8 (3.9) years; 548 657 participants (61.0%) were women, and 235 138 participants (26.2%) had hypertension. Of those with hypertension, 62 819 participants (26.7%; 95% CI, 26.5%-26.9%) had ISH (mean [SD] age, 45.0 [3.5] years; 41 417 women [65.9%]), and 54 463 of those with ISH (86.7%; 95% CI, 86.4%-87.0%) had not received treatment. The prevalence of ISH was higher among individuals who were older, were female, were farmers, resided in the eastern region of China, and had an educational level of primary school or lower. Women and older individuals were more likely to have ISH than to be normotensive or to have other hypertension subtypes. Participants who were obese, currently used alcohol, had diabetes, and experienced previous cardiovascular events were more likely to have other types of hypertension and less likely to have normotension than to have ISH. Among the 54 463 participants with ISH who had not received treatment, only 3682 individuals (6.8%; 95% CI, 6.6%-7.0%) were aware of having hypertension, and awareness rates remained low even among those with systolic blood pressure of 160 mm Hg or higher (7135 individuals [13.1%; 95% CI, 12.4%-13.9%])., Conclusions and Relevance: In this study, ISH was identified in 1 of 4 young and middle-aged adults with hypertension in China, most of whom remained unaware of having hypertension. These results highlight the increasing need for better guidance regarding the management of ISH in this population.

Background: A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries., Methods: We conducted a multicenter, hospital-based, active surveillance study at 27 hospitals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was ascertained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case-control analysis was performed, with matching for age, sex, and location., Results: From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence, 0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case-control analysis., Conclusions: The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Foundation and others.)., (Copyright © 2020 Massachusetts Medical Society.)

Background The likelihood of undergoing reoperative coronary artery bypass graft surgery (CABG) is important for older patients who are considering first-time CABG. Trends in the reoperative CABG for these patients are unknown. Methods and Results We used the Medicare fee-for-service inpatient claims data of adults undergoing isolated first-time CABG between 1998 and 2017. The primary outcome was time to first reoperative CABG within 5 years of discharge from the index surgery, treating death as a competing risk. We fitted a Cox regression to model the likelihood of reoperative CABG as a function of patient baseline characteristics. There were 1 666 875 unique patients undergoing first-time isolated CABG and surviving to hospital discharge. The median (interquartile range) age of patients did not change significantly over time (from 74 [69-78] in 1998 to 73 [69-78] in 2017); the proportion of women decreased from 34.8% to 26.1%. The 5-year rate of reoperative CABG declined from 0.77% (95% CI, 0.72%-0.82%) in 1998 to 0.23% (95% CI, 0.19%-0.28%) in 2013. The annual proportional decline in the 5-year rate of reoperative CABG overall was 6.6% (95% CI, 6.0%-7.1%) nationwide, which did not differ across subgroups, except the non-white non-black race group that had an annual decline of 8.5% (95% CI, 6.2%-10.7%). Conclusions Over a recent 20-year period, the Medicare fee-for-service patients experienced a significant decline in the rate of reoperative CABG. In this cohort of older adults, the rate of declining differed across demographic subgroups.

Background: Incidence, predictors, and prognostic impact of recurrent acute myocardial infarction (AMI) after initial AMI remain poorly understood. Data on recurrent AMI in China is unknown., Methods: Using the China Patient-centred Evaluative Assessment of Cardiac Events (PEACE)-Prospective AMI Study, we studied 3387 patients admitted to 53 hospitals for AMI and discharged alive. The association of recurrent AMI with 1-year mortality was evaluated using time-dependent Cox regression. Recurrent AMI events were classified as early (1-30 days), late (31-180 days), and very late (181-365 days). Their impacts on 1-year mortality were estimated by Kaplan-Meier methodology and compared by the log-rank test. Multivariable modelling was used to identify factors associated with recurrent AMI., Results: The mean (SD) age was 60.7 (11.9) years and 783 (23.1%) were women. The observed 1-year recurrent AMI rate was 2.5% (95% CI 2.00 to 3.07) with 35.7% events occurring within the first 30 days. Recurrent AMI was associated with 1-year mortality with an adjusted HR of 25.42 (95% CI 15.27 to 42.34). Early recurrent AMI was associated with the highest 1-year mortality rate of 53.3% (log-rank p<0.001). Predictors of recurrent AMI included age 75-84, in-hospital percutaneous coronary intervention, heart rate >90 min/beats at initial admission, renal dysfunction, and not being prescribed any of guideline-based medications at discharge., Conclusions: One-third of recurrent AMI events occurred early. Recurrent AMI is strongly associated with 1-year mortality, particularly if early. Heightened surveillance during this early period and improving prescription of recommended discharge medications may reduce recurrent AMI in China., Competing Interests: Competing interests: HMK is the recipient of a research grant from Medtronic and Johnson & Johnson, through Yale University, to develop methods of clinical trial data sharing; chairs a cardiac scientific advisory board for United Health; works under contract with the Centers for Medicare & Medicaid Services to develop and maintain performance measures that are publicly reported; is a participant/participant representative of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science and the Physician Advisory Board for Aetna; and is the founder of Hugo, a personal health information platform. HMK and KM work under contract with the Centers for Medicare & Medicaid Services to develop and maintain performance measures that are publicly reported, (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Over the past 2 decades, guidelines for digoxin use have changed significantly. However, little is known about the national-level trends of digoxin use, hospitalizations for toxicity, and subsequent outcomes over this time period., Methods: To describe digoxin prescription trends, we conducted a population-level, cohort study using data from IQVIA, Inc.'s National Prescription Audit (2007-2014) for patients aged ≥65 years. Further, in a national cohort of Medicare fee-for-service beneficiaries aged ≥65 years in the United States, we assessed temporal trends of hospitalizations associated with digoxin toxicity and the outcomes of these hospitalizations between 1999 and 2013., Results: From 2007 through 2014, the number of digoxin prescriptions dispensed decreased by 46.4%; from 8,099,856 to 4,343,735. From 1999 through 2013, the rate of hospitalizations with a principal or secondary diagnosis of digoxin toxicity decreased from 15 to 2 per 100,000 person-years among Medicare fee-for-service beneficiaries. In-hospital and 30-day mortality rates associated with hospitalization for digoxin toxicity decreased significantly among Medicare fee-for-service beneficiaries; from 6.0% (95% confidence interval [CI], 5.2-6.8) to 3.7% (95% CI, 2.2-5.7) and from 14.0% (95% CI, 13.0-15.2) to 10.1% (95% CI, 7.6-13.0), respectively. Rates of 30-day readmission for digoxin toxicity decreased from 23.5% (95% CI, 22.1-24.9) in 1999 to 21.7% (95% CI, 18.0-25.4) in 2013 (P < .05)., Conclusion: While digoxin prescriptions have decreased, it is still widely prescribed. However, the rate of hospitalizations for digoxin toxicity and adverse outcomes associated with these hospitalizations have decreased. These findings reflect the changing clinical practice of digoxin use, aligned with the changes in clinical guidelines., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Efforts to decrease hospitalization costs could increase post-acute care costs. This effect could undermine initiatives to reduce overall episode costs and have implications for the design of health care under alternative payment models., Methods: Among Medicare fee-for-service beneficiaries aged ≥65 years hospitalized with acute myocardial infarction (AMI) between July 2010 and June 2013 in the Premier Healthcare Database, we studied the association of in-hospital and post-acute care resource utilization and outcomes by in-hospital cost tertiles., Results: Among patients with AMI at 326 hospitals, the median (range) of each hospital's mean per-patient in-hospital risk-standardized cost (RSC) for the low, medium, and high cost tertiles were $16,257 ($13,097-$17,648), $18,544 ($17,663-$19,875), and $21,831 ($19,923-$31,296), respectively. There was no difference in the median (IQR) of risk-standardized post-acute payments across cost-tertiles: $5014 (4295-6051), $4980 (4349-5931) and $4922 (4056-5457) for the low (n = 90), medium (n = 98), and high (n = 86) in-hospital RSC tertiles (p = 0.21), respectively. In-hospital and 30-day mortality rates did not differ significantly across the in-hospital RSC tertiles; however, 30-day readmission rates were higher at hospitals with higher in-hospital RSCs: median = 17.5, 17.8, and 18.0% at low, medium, and high in-hospital RSC tertiles, respectively (p = 0.005 for test of trend across tertiles)., Conclusions: In our study of patients hospitalized with AMI, greater resource utilization during the hospitalization was not associated with meaningful differences in costs or mortality during the post-acute period. These findings suggest that it may be possible for higher cost hospitals to improve efficiency in care without increasing post-acute care utilization or worsening outcomes.

Background: The current acute kidney injury (AKI) risk prediction model for patients undergoing percutaneous coronary intervention (PCI) from the American College of Cardiology (ACC) National Cardiovascular Data Registry (NCDR) employed regression techniques. This study aimed to evaluate whether models using machine learning techniques could significantly improve AKI risk prediction after PCI., Methods and Findings: We used the same cohort and candidate variables used to develop the current NCDR CathPCI Registry AKI model, including 947,091 patients who underwent PCI procedures between June 1, 2009, and June 30, 2011. The mean age of these patients was 64.8 years, and 32.8% were women, with a total of 69,826 (7.4%) AKI events. We replicated the current AKI model as the baseline model and compared it with a series of new models. Temporal validation was performed using data from 970,869 patients undergoing PCIs between July 1, 2016, and March 31, 2017, with a mean age of 65.7 years; 31.9% were women, and 72,954 (7.5%) had AKI events. Each model was derived by implementing one of two strategies for preprocessing candidate variables (preselecting and transforming candidate variables or using all candidate variables in their original forms), one of three variable-selection methods (stepwise backward selection, lasso regularization, or permutation-based selection), and one of two methods to model the relationship between variables and outcome (logistic regression or gradient descent boosting). The cohort was divided into different training (70%) and test (30%) sets using 100 different random splits, and the performance of the models was evaluated internally in the test sets. The best model, according to the internal evaluation, was derived by using all available candidate variables in their original form, permutation-based variable selection, and gradient descent boosting. Compared with the baseline model that uses 11 variables, the best model used 13 variables and achieved a significantly better area under the receiver operating characteristic curve (AUC) of 0.752 (95% confidence interval [CI] 0.749-0.754) versus 0.711 (95% CI 0.708-0.714), a significantly better Brier score of 0.0617 (95% CI 0.0615-0.0618) versus 0.0636 (95% CI 0.0634-0.0638), and a better calibration slope of observed versus predicted rate of 1.008 (95% CI 0.988-1.028) versus 1.036 (95% CI 1.015-1.056). The best model also had a significantly wider predictive range (25.3% versus 21.6%, p < 0.001) and was more accurate in stratifying AKI risk for patients. Evaluated on a more contemporary CathPCI cohort (July 1, 2015-March 31, 2017), the best model consistently achieved significantly better performance than the baseline model in AUC (0.785 versus 0.753), Brier score (0.0610 versus 0.0627), calibration slope (1.003 versus 1.062), and predictive range (29.4% versus 26.2%). The current study does not address implementation for risk calculation at the point of care, and potential challenges include the availability and accessibility of the predictors., Conclusions: Machine learning techniques and data-driven approaches resulted in improved prediction of AKI risk after PCI. The results support the potential of these techniques for improving risk prediction models and identification of patients who may benefit from risk-mitigation strategies., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: SSD is supported by the Department of Veterans Affairs. WLS is a consultant for Hugo, a personal health information platform. CIM is a consultant for Cook, Bard, Medtronic, Abbott and Cardinal Health. FPW is supported by the National Science Foundation grant R01DK113191. JSR is the Chief Innovation Officer for the American College of Cardiology. HMK is a recipient of research agreements from Medtronic and from Johnson & Johnson (Janssen), through Yale University, to develop methods of clinical trial data sharing; was the recipient of a grant from the Food and Drug Administration and Medtronic to develop methods for postmarket surveillance of medical devices; works under contract with the Centers for Medicare and Medicaid Services to develop and maintain performance measures; chairs a cardiac scientific advisory board for UnitedHealth; is a member of the Advisory Board for Element Science and the Physician Advisory Board for Aetna; is a participant/participant representative of the IBM Watson Health Life Sciences Board; and is the founder of Hugo, a personal health information platform. JAS is supported by grants from Gilead, Genentech, Lilly, Amorcyte, and EvaHeart and has a patent for the Seattle Angina Questionnaire with royalties paid. He also owns the copyright to the Seattle Angina Questionnaire. He is the PI of an Analytic Center for the American College of Cardiology Foundation and has an equity interest in Health Outcomes Sciences. FAM has a contract (through his primary institution) for his role as Chief Science Officer of the NCDR. BJM is an associate editor for PLOS ONE, which is involved in this special issue. He has a relationship with the American College of Cardiology in selecting and pursuing innovative research based upon their registry data (unrelated to this paper). He has a pending patent application for an EHR-based prediction tool in Yale New Haven Health, as well as two funded studies, one by the DoD-Advanced Research Projects Agency and one with the NSF to support student travel to conferences in the body sensor networks field. American College of Cardiology may incorporate this work, or future iterations, into its registry. No other organisation named above has a competing interest in relation to this work. The other authors report no potential competing interests.

Objectives: To understand the discrepancy between the published 10-year cardiovascular risk and 10-year cardiovascular risk generated from raw data using the Framingham Risk Score for participants in the Systolic Blood Pressure Intervention Trial (SPRINT)., Design: Secondary analysis of SPRINT data published in The New England Journal of Medicine ( NEJM ) and made available to researchers in late 2016., Setting: SPRINT clinical trial sites., Participants: Study participants enrolled into SPRINT., Results: The number of SPRINT study participants identified as having ≥15% 10-year cardiovascular risk was not consistent with what was reported in the original publication. Using the data from the trial, the Framingham Risk Score indicated ≥15% 10-year cardiovascular risk for 7089 participants compared with 5737 reported in the paper, a change from 61% to 76% of the total study population., Conclusions: The analysis of the clinical trial data by independent investigators identified an error in the reporting of the risk of the study population. The SPRINT trial enrolled a higher risk population than was reported in the initial publication, which was brought to light by data sharing., Competing Interests: Competing interests: Drs HMK and JSR are recipients of research agreements from Medtronic and Johnson & Johnson (Janssen), through Yale, to develop methods of clinical trial data sharing and of a grant from Medtronic and the Food and Drug Administration, through Yale, to develop methods for postmarket surveillance of medical devices and work under contract with the Centers for Medicare and Medicaid Services to develop and maintain performance measures that are publicly reported. Dr HMK chairs a cardiac scientific advisory board for United Health, is a participant/participant representative of the IBM Watson Health Life Sciences Board, is a member of the Advisory Board for Element Science and the Physician Advisory Board for Aetna and is the founder of Hugo, a personal health information platform. Dr JSR has received research support from the Blue Cross Blue Shield Association to better understand medical technology evidence generation. The other co-authors report no potential competing interests., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In response to urban-rural disparities in healthcare resources, China recently launched a healthcare reform with a focus on improving rural care during the past decade. However, nationally representative studies comparing medical care and patient outcomes between urban and rural areas in China during this period are not available., Methods and Results: We created a nationally representative sample of patients in China admitted for ST-segment-elevation myocardial infarction in 2001, 2006, and 2011, using a 2-stage random sampling design in 2 urban and 3 rural strata. In China, evidence-based treatments were provided less often in 2001 in rural hospitals, which had lower volume and less availability of advanced cardiac facilities. However, these differences diminished by 2011 for reperfusion therapy (54% in urban versus 57% in rural; P =0.1) and reversed for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (66% versus 68%; P =0.04) and early β-blockers (56% versus 60%; P =0.01). The risk-adjusted rate of in-hospital death or withdrawal from treatment was not significantly different between urban and rural hospitals in any study year, with an adjusted odds ratio of 1.13 (0.77-1.65) in 2001, 0.99 (0.77-1.27) in 2006, and 0.94 (0.74-1.19) in 2011., Conclusions: Although urban-rural disparities in evidence-based treatment for myocardial infarction in China have largely been eliminated, substantial gaps in quality of care persist in both settings. In addition, urban hospitals providing more resource-intensive care did not achieve better outcomes., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01624883., (© 2017 American Heart Association, Inc.)

Background: Millions of Americans live in the US territories, but health outcomes and payments among Medicare beneficiaries in these territories are not well characterized., Methods: Among Fee-for-Service Medicare beneficiaries aged 65 years and older hospitalized between 1999 and 2012 for acute myocardial infarction (AMI), heart failure (HF), and pneumonia, we compared hospitalization rates, patient outcomes, and inpatient payments in the territories and states., Results: Over 14 years, there were 4,350,813 unique beneficiaries in the territories and 402,902,615 in the states. Hospitalization rates for AMI, HF, and pneumonia declined overall and did not differ significantly. However, 30-day mortality rates were higher in the territories for all 3 conditions: in the most recent time period (2008-2012), the adjusted odds of 30-day mortality were 1.34 [95% confidence interval (CI), 1.21-1.48], 1.24 (95% CI, 1.12-1.37), and 1.85 (95% CI, 1.71-2.00) for AMI, HF, and pneumonia, respectively; adjusted odds of 1-year mortality were also higher. In the most recent study period, inflation-adjusted Medicare in-patient payments, in 2012 dollars, were lower in the territories than the states, at $9234 less (61% lower than states), $4479 less (50% lower), and $4403 less (39% lower) for AMI, HF, and pneumonia hospitalizations, respectively (P<0.001 for all)., Conclusions and Relevance: Among Medicare Fee-for-Service beneficiaries, in 2008-2012 mortality rates were higher, or not significantly different, and hospital reimbursements were lower for patients hospitalized with AMI, HF, and pneumonia in the territories. Improvement of health care and policies in the territories is critical to ensure health equity for all Americans.

Aims: ST-segment elevation myocardial infarctions (STEMI) in China and other low- and middle-income countries outnumber non-ST-segment elevation myocardial infarctions (NSTEMI). We hypothesized that the STEMI predominance was associated with lower biomarker use and would vary with hospital characteristics., Methods and Results: We hypothesized that the STEMI predominance was associated with lower biomarker use and would vary with hospital characteristics. Using data from the nationally representative China PEACE-Retrospective AMI Study during 2001, 2006, and 2011, we compared hospital NSTEMI proportion across categories of use of any cardiac biomarker (CK, CK-MB, or troponin) and troponin, as well as across region, location, level, and teaching status. Among 15 416 acute myocardial infarction (AMI) patients, 14% had NSTEMI. NSTEMI patients were older, more likely female, and to have comorbidities. Median hospital NSTEMI proportion in each study year was similar across categories of any cardiac biomarker use, troponin, region, location, level, and teaching status. For instance, in 2011 the NSTEMI proportion at hospitals without troponin testing was 11.2% [inter quartile range (IQR) 4.4-16.7%], similar to those with ≥ 75% troponin use (13.0% [IQR 8.7-23.7%]) (P-value for difference 0.77). Analysed as continuous variables there was no relationship between hospital NSTEMI proportion and proportion biomarker use. With troponin use there was no relationship in 2001 and 2006, but a modest correlation in 2011 (R = 0.16, P = 0.043). Admissions for NSTEMI increased from 0.3/100 000 people in 2001 to 3.3/100 000 people in 2011 (P-value for trend < 0.001)., Conclusion: STEMI is the dominant presentation of AMI in China, but the proportion of NSTEMI is increasing. Biomarker use and hospital characteristics did not account for the low NSTEMI rate., Clinical Trial Registration: www.clinicaltrials.gov (NCT01624883)., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.)

Background: China has gaps in the quality of care provided to patients with ST-elevation myocardial infarction, but little is known about how quality varies between hospitals., Methods and Results: Using nationally representative data from the China PEACE-Retrospective AMI Study, we characterized the quality of care for ST-elevation myocardial infarction at the hospital level and examined variation between hospitals. Two summary measures were used to describe the overall quality of care at each hospital and to characterize variations in quality between hospitals in 2001, 2006, and 2011. The composite rate measured the proportion of opportunities a hospital had to deliver 6 guideline-recommended treatments for ST-elevation myocardial infarction that were successfully met, while the defect-free rate measured the proportion of patients at each hospital receiving all guideline-recommended treatments for which they were eligible. Risk-standardized mortality rates were calculated. Our analysis included 12 108 patients treated for ST-elevation myocardial infarction at 162 hospitals. The median composite rate increased from 56.8% (interquartile range [IQR], 45.9-72.0) in 2001 to 80.5% (IQR, 74.7-84.8) in 2011; however, substantial variation remained in 2011 with defect-free rates ranging from 0.0% to 76.9%. The median risk-standardized mortality rate increased from 9.9% (IQR, 9.1-11.7) in 2001 to 12.6% (IQR, 10.9-14.6) in 2006 before falling to 10.4% (IQR, 9.1-12.4) in 2011., Conclusions: Higher rates of guideline-recommended care and a decline in variation between hospitals are indicative of an improvement in quality. Although some variation persisted in 2011, very top-performing hospitals missed few opportunities to provide guideline-recommended care. Quality improvement initiatives should focus on eliminating residual variation as well as measuring and improving outcomes., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01624883., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Hyperglycemia on admission has been found to elevate risk for mortality and adverse clinical events after acute myocardial infarction (AMI), but there are evidences that the relationship of blood glucose and mortality may differ between diabetic and nondiabetic patients. Prior studies in China have provided mixed results and are limited by statistical power. Here, we used data from a large, nationally representative sample of patients hospitalized with AMI in China in 2001, 2006, and 2011 to assess if admission glucose is of prognostic value in China and if this relationship differs depending on the presence or absence of diabetes., Methods: Using a nationally representative sample of patients with AMI in China in 2001, 2006, and 2011, we categorized patients according to their glucose levels at admission (Results: Compared to patients with euglycemia (5.8%), patients with moderate hyperglycemia (13.1%, odds ratio [OR] = 2.44, 95% confidence interval [CI, 2.08-2.86]), severe hyperglycemia (21.5%, OR = 4.42, 95% CI [3.78-5.18]), and hypoglycemia (13.8%, OR = 2.59, 95% CI [1.68-4.00]), all had higher crude in-hospital mortality after AMI regardless of the presence of recognized diabetes mellitus. After adjustment for patients' characteristics and clinical status, however, the relationship between admission glucose and in-hospital mortality was different for diabetic and nondiabetic patients (P for interaction = 0.045). Among diabetic patients, hypoglycemia (OR = 3.02, 95% CI [1.20-7.63]), moderate hyperglycemia (OR = 1.75, 95% CI [1.04-2.92]), and severe hyperglycemia (OR = 2.97, 95% CI [1.87-4.71]) remained associated with elevated risk for mortality, but among nondiabetic patients, only patients with moderate hyperglycemia (OR = 2.34, 95% CI [1.93-2.84]) and severe hyperglycemia (OR = 3.92, 95% CI [3.04-5.04]) were at elevated mortality risk and not hypoglycemia (OR = 1.12, 95% CI [0.60-2.08]). This relationship was consistent across different study years (P for interaction = 0.900)., Conclusions: The relationship between admission glucose and in-hospital mortality differs for diabetic and nondiabetic patients. Hypoglycemia was a bad prognostic marker among diabetic patients alone. The study results could be used to guide risk assessment among AMI patients using admission glucose., Trial Registration: www.clinicaltrials.gov, NCT01624883; https://clinicaltrials.gov/ct2/show/NCT01624883.

Background: Compared with men, women are at higher risk of rehospitalization in the first month after discharge for acute myocardial infarction (AMI). However, it is unknown whether this risk extends to the full year and varies by age. Explanatory factors potentially mediating the relationship between sex and rehospitalization remain unexplored and are needed to reduce readmissions. The aim of this study was to assess sex differences and factors associated with 1-year rehospitalization rates after AMI., Methods: We recruited 3536 patients (33% women) ≥18 years of age hospitalized with AMI from 24 US centers into the TRIUMPH study (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status). Data were obtained by medical record abstraction and patient interviews, and a physician panel adjudicated hospitalizations within the first year after AMI. We compared sex differences in rehospitalization using a Cox proportional hazards model, following sequential adjustment for covariates and testing for an age-sex interaction., Results: One-year crude all-cause rehospitalization rates for women were significantly higher than men after AMI (hazard ratio, 1.29 for women; 95% confidence interval, 1.12-1.48). After adjustment for demographics and clinical factors, women had a persistent 26% higher risk of rehospitalization (hazard ratio, 1.26; 95% confidence interval, 1.08-1.47). However, after adjustment for health status and psychosocial factors (hazard ratio, 1.14; 95% confidence interval, 0.96-1.35), the association was attenuated. No significant age-sex interaction was found for 1-year rehospitalization, suggesting that the increased risk applied to both older and younger women., Conclusions: Regardless of age, women have a higher risk of rehospitalization compared with men over the first year after AMI. Although the increased risk persisted after adjustment for clinical factors, the poorer health and psychosocial state of women attenuated the difference., (© 2017 American Heart Association, Inc.)

We evaluated whether community-level home health agencies and nursing home performance is associated with community-level hospital 30-day all-cause risk-standardized readmission rates for Medicare patients used data from the Centers for Medicare & Medicaid Service from 2010 to 2012. Our final sample included 2,855 communities that covered 4,140 hospitals with 6,751,713 patients, 13,060 nursing homes with 1,250,648 residents, and 7,613 home health agencies providing services to 35,660 zipcodes. Based on a mixed effect model, we found that increasing nursing home performance by one star for all of its 4 measures and home health performance by 10 points for all of its 6 measures is associated with decreases of 0.25% (95% CI 0.17-0.34) and 0.60% (95% CI 0.33-0.83), respectively, in community-level risk-standardized readmission rates., Competing Interests: Financial Disclosures: The other authors report no conflicts of interest.