Worldwide trends in mortality for hypertensive heart disease from 1990 to 2019 with projection to 2034: data from the Global Burden of Disease 2019 study.

AIMS: This study aims to analyse the worldwide trends in hypertensive heart disease (HHD) mortality and associations with age, period, and birth cohort and predict the future burden of HHD deaths. METHODS AND RESULTS: Mortality estimates were obtained from Global Burden of Disease 2019 study. We used age-period-cohort (APC) model to examine the age, period, and cohort effects on HHD mortality between 1990 and 2019. Bayesian APC model was utilized to predict HHD deaths to 2034. The global HHD deaths were 1.16 million in 2019 and were projected to increase to 1.57 million in 2034, with the largest increment in low- and middle-income countries (LMICs). Between 1990 and 2019, middle/high-middle socio-demographic index (SDI) countries had the largest mortality reductions (annual percentage change = -2.06%), whereas low SDI countries saw a lagging performance (annual percentage change = -1.09%). There was a prominent transition in the age distribution of deaths towards old-age population in middle/high-middle SDI countries, while the proportion of premature deaths (aged under 60 years) remained at 24% in low SDI countries in 2019. Amongst LMICs, Brazil, China, and Ethiopia showed typically improving trends both over time and in recent birth cohorts, whereas 63 countries including Indonesia, the Philippines, and Pakistan had unfavourable or worsening risks for recent periods and birth cohorts. CONCLUSION: The HHD death burden in 2019 is vast and is expected to increase rapidly in the next decade, particularly for LMICs. Limited progress in HHD management together with high premature mortality would exact huge human and medical costs in low SDI countries. The examples from Brazil, China, and Ethiopia suggest that efficient health systems with action on improving hypertension care can reduce HHD mortality effectively in LMICs.

This study provides the first comprehensive analysis of the age, period, and cohort trends in mortality for hypertensive heart disease (HHD) across 204 countries and territories from 1990 to 2019, with projection to 2034. The death burden of HHD is substantial and growing rapidly in most of the world, particularly in low- and middle-income countries (LMICs). Wide disparities exist within LMICs in HHD management, with most low socio-demographic index countries showing little progress in reducing HHD mortality. The examples from Brazil, China, and Ethiopia suggest that prevention policies for HHD can reduce risks for younger birth cohorts and shift the risks for all age groups over time.

Corrigendum to "Inpatient costs of congenital heart surgery in China: results from the National Centre for Cardiovascular Diseases" [The Lancet Regional Health - Western Pacific 2023; 31:100623].

[This corrects the article DOI: 10.1016/j.lanwpc.2022.100623.].

The SUPER reporting guideline suggested for reporting of surgical technique.

Background: Existing reporting guidelines pay insufficient attention to the detail and comprehensiveness reporting of surgical technique. The Surgical techniqUe rePorting chEcklist and standaRds (SUPER) aims to address this gap by defining reporting standards for surgical technique. The SUPER guideline intends to apply to articles that encompass surgical technique in any study design, surgical discipline, and stage of surgical innovation. Methods: Following the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach, 16 surgeons, journal editors, and methodologists reviewed existing reporting guidelines relating to surgical technique, reviewed papers from 15 top journals, and brainstormed to draft initial items for the SUPER. The initial items were revised through a three-round Delphi survey from 21 multidisciplinary Delphi panel experts from 13 countries and regions. The final SUPER items were formed after an online consensus meeting to resolve disagreements and a three-round wording refinement by all 16 SUPER working group members and five SUPER consultants. Results: The SUPER reporting guideline includes 22 items that are considered essential for good and informative surgical technique reporting. The items are divided into six sections: background, rationale, and objectives (items 1 to 5); preoperative preparations and requirements (items 6 to 9); surgical technique details (items 10 to 15); postoperative considerations and tasks (items 16 to 19); summary and prospect (items 20 and 21); and other information (item 22). Conclusions: The SUPER reporting guideline has the potential to guide detailed, comprehensive, and transparent surgical technique reporting for surgeons. It may also assist journal editors, peer reviewers, systematic reviewers, and guideline developers in the evaluation of surgical technique papers and help practitioners to better understand and reproduce surgical technique. Trial Registration: https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/#SUPER.

Global, regional, and national time trends in cancer mortality attributable to high fasting plasma glucose: an age-period cohort analysis.

BACKGROUND: High fasting plasma glucose (HFPG) is the fastest-growing risk factor for cancer deaths worldwide. We reported the cancer mortality attributable to HFPG at global, regional, and national levels over the past three decades and associations with age, period, and birth cohort. METHODS: Data for this study were retrieved from the Global Burden of Disease Study 2019, and we used age-period-cohort modelling to estimate age, cohort and period effects, as well as net drift (overall annual percentage change) and local drift (annual percentage change in each age group). RESULTS: Over the past 30 years, the global age-standardized mortality rate (ASMR) attributable to HFPG has increased by 27.8%. The ASMR in 2019 was highest in the male population in high sociodemographic index (SDI) areas (8.70; 95% CI, 2.23-18.04). The net drift for mortality was highest in the female population in low SDI areas (2.33; 95% CI, 2.12-2.55). Unfavourable period and cohort effects were found across all SDI quintiles. Cancer subtypes such as "trachea, bronchus, and lung cancers", "colon and rectal cancers", "breast cancer" and "pancreatic cancer" exhibited similar trends. CONCLUSIONS: The cancer mortality attributable to HFPG has surged during the past three decades. Unfavourable age-period-cohort effects on mortality were observed across all SDI quintiles, and the cancer mortality attributable to HFPG is expected to continue to increase rapidly in the future, particularly in lower SDI locations. This is a grim global public health issue that requires immediate attention.

The SUPER reporting guideline suggested for reporting of surgical technique: explanation and elaboration.

Background: Surgical technique plays an essential role in achieving good health outcomes. However, the quality of surgical technique reporting remains heterogeneous. Reporting checklists could help authors to describe the surgical technique more transparently and effectively, as well as to assist reviewers and editors evaluate it more informatively, and promote readers to better understand the technique. We previously developed SUPER (surgical technique reporting checklist and standards) to assist authors in reporting their research that contains surgical technique more transparently. However, further explanation and elaboration of each item are needed for better understanding and reporting practice. Methods: We searched surgical literature in PubMed, Google Scholar and journal websites published up to January 2023 to find multidiscipline examples in various article types for each SUPER item. Results: We explain the 22 items of the SUPER and provide rationales item by item alongside. We provide 69 examples from 53 literature that present optimal reporting of the 22 items. Article types of examples include pure surgical technique, and case reports, observational studies and clinical trials that contain surgical technique. Examples are multidisciplinary, including general surgery, orthopaedical surgery, cardiac surgery, thoracic surgery, gastrointestinal surgery, neurological surgery, oncogenic surgery, and emergency surgery etc. Conclusions: Along with SUPER article, this explanation and elaboration file can promote deeper understanding on the SUPER items. We hope that the article could further guide surgeons and researchers in reporting, and assist editors and peer reviewers in reviewing manuscripts related to surgical technique.

Improving long-term care and outcomes of congenital heart disease: fulfilling the promise of a healthy life.

Advances in the prevention, diagnosis, and treatment for congenital heart disease (CHD), the most common birth defect in China, have drastically improved survival for individuals with the disease. However, China's current health system is not well prepared to manage the growing population of people with CHD and their complex medical needs, which range from early detection of the condition and intervention for physical, neurodevelopmental, and psychosocial impairment, to long-term management of major complications and chronic health problems. Health disparities caused by long-standing regional differences in access to care pose challenges when major complications such as pulmonary hypertension arise, and when individuals with complex CHD become pregnant and give birth. Currently, no data sources track neonates, children, adolescents, and adults with CHD in China and delineate their clinical characteristics and use of health resources. This scarcity of data should warrant attention from the Chinese Government and relevant specialists in the field. In the third paper of the Series on CHD in China, we summarise key literature and current data to identify knowledge gaps and call for concerted efforts by the government, hospitals, clinicians, industries, and charitable organisations to develop an actionable, lifelong framework of congenital cardiac care that is accessible and affordable for all individuals with CHD. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Global, regional, and national time trends in disability-adjusted life years, mortality, and variable risk factors of non-rheumatic calcified aortic valve disease, 1990-2019: an age-period-cohort analysis of the Global Burden of Disease 2019 study.

Background: Non-rheumatic heart valve disease (NRVD) is a common cardiovascular disease, whereas calcific aortic valve disease (CAVD) is a type of disease with the fastest-growing mortality and disability-adjusted life years (DALYs). This study presents an overview of the trends noted in the DALY, CAVD mortality, and the modifiable risk factors in the last 30 years, across 204 countries and territories, and their relationship with the period, age, and birth cohort. Methods: Data were obtained from the Global Burden of Disease (GBD) 2019 database. An age-period-cohort (APC) model was used to assess general annual percentage changes in DALYs and mortality over the past 30 years in 204 countries and territories. Results: In 2019, the age-standardized mortality rate for the entire population in areas with a high socio-demographic index (SDI) was more than 4 times higher than that in low-SDI areas. From 1990 to 2019, the net drift in mortality for the whole population was from -2.1% [95% confidence interval (CI): -2.39% to -1.82%] per year in high-SDI regions to 0.05% (95% CI: -0.13% to 0.23%) per year in low- to medium-SDI regions. The trend of DALYs was similar to that of mortality. The age-wise distribution of deaths exhibited a shift toward older populations in high-SDI regions globally, except for Qatar, Saudi Arabia, and the United Arab Emirates. Over time, in most medium, medium-low, and low SDI regions, there was no significant improvement in the period and birth cohort or even an unfavorable or worsening risk. The main variable risk factors of CAVD death and DALYs lost were high sodium diet, high systolic blood pressure, and lead exposure. Those risk factors only showed a significant downward trend in middle- and high-SDI regions. Conclusions: Health disparities between regions for CAVD are widening and could lead to a heavy disease burden in the future. Health authorities and policymakers in low SDI areas, in particular, need to consider improving resource allocation, increasing access to medical resources, and controlling variable risk factors to stem the growth of the disease burden.

Inpatient costs of congenital heart surgery in China: results from the National Centre for Cardiovascular Diseases.

Background: Economic data on congenital heart disease (CHD) in China are scarce. Therefore, this study aimed to explore the inpatient costs of congenital heart surgery and related healthcare policies from a hospital perspective. Method: We used data from the Chinese Database for Congenital Heart Surgery (CDCHS) to prospectively analyse the inpatient costs of congenital heart surgery from May 2018 to December 2020. The total expenditure was divided into 11 columns (medications, imaging, consumable items, surgery, medical cares, laboratory tests, therapy, examinations, medical services, accommodations, and others), and explored according to the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) category, year, different age group, and CHD complexity. Authority economic data (index for gross domestic product [GDP], GDP per capita, per capita disposable income and average annual exchange rate of 2020 Chinese Yuan against US dollar) were accessed via the National Bureau of Statistics of China to better describe the burden. In addition, potential factors contributing to the costs were also investigated by using generalised linear model. Findings: All values are presented in 2020 Chinese Yuan (¥). A total of 6568 hospitalisations were enrolled. The median of overall total expenditure was ¥64,900 (≈9409 US Dollar [USD], interquartile range [IQR]: ¥35,819), with the lowest in STAT 1 (¥57,014 ≈ 8266 USD, [IQR]: ¥16,774) and the highest in STAT 5 (¥194,862 ≈ 28,251 USD, [IQR]: ¥130,010). The median costs during the 2018 to 2020 period were ¥62,014 (≈8991 USD, [IQR]: ¥32,628), ¥64,846 (≈9401 USD, [IQR]: ¥34,469) and ¥67,867 (≈9839 USD, [IQR]: ¥41,496). Regarding to age, the median costs were highest in the ≤1 month group (¥144,380 ≈ 20,932 USD, [IQR]: ¥92,584). Age, STAT category, emergency, genetic syndrome, delay sternal closure, mechanical ventilation time, and complications were significantly contributed to the inpatient costs. Interpretation: For the first time, the inpatient costs of congenital heart surgery in China are delineated in detail. According to the results, CHD treatment has achieved significant progress in China, but it still causes substantial economic burden to both families and society. In addition, ascending trend of the inpatient costs was observed during the period of 2018-2020, and the neonatal was revealed to be the most challenging group. Funding: This study was supported by the CAMS Innovation Fund for Medical Sciences (CIFMS,2020-I2M-C&T-A-009), Capital Health Research and Development of Special Fund (2022-1-4032), and The City University of Hong Kong New Research Initiatives/Infrastructure Support from Central (APRC, 9610589).

Biopsy-detected myocardial fibrosis predicts adverse cardiac events after pulmonary valve replacement in patients with repaired tetralogy of Fallot.

OBJECTIVES: Risk factors associated with adverse cardiac events (cardiac AEs) after pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot are incompletely understood. In this study, we aimed to determine the relationship between histological myocardial fibrosis and cardiac AEs after PVR in patients with rTOF. METHODS: We consecutively collected clinical, cardiac magnetic resonance, echocardiography and electrocardiogram data of 51 patients with rTOF who underwent surgical PVR. The right ventricular outflow tract tissue was collected during the PVR and the degree of histological myocardial fibrosis was determined by a tailor-made automated image analysis method of picrosirius red staining. RESULTS: The median follow-up time was 4.9 years, and 14 patients had cardiac AEs (a composite of heart failure admission and arrhythmia) during follow-up. The total analysis area of myocardial samples was 5782.18 mm2, and the median percentage of myocardial fibrosis was 20.6% (interquartile range 16.7-27.0%), which were significantly elevated in patients with cardiac AEs compared with patients without cardiac AEs (24.1% vs 19.7%, P = 0.007). Right ventricular ejection fraction and left ventricular end-systolic volume index were significantly associated with myocardial fibrosis in multivariable stepwise linear regression analysis (R2 = 0.238). Cox proportional hazards regression identified degree of myocardial fibrosis [hazard ratio 1.127; 95% confidence interval (CI) 1.047-1.213; P = 0.001] and age at PVR (hazard ratio 1.062; 95% CI 1.010-1.116; P = 0.019) were associated with increased risk of cardiac AEs. The incidence of adverse cardiac events was significantly increased when myocardial fibrosis >20.1% and age at PVR >18.2 years. CONCLUSIONS: Histological myocardial fibrosis was associated with biventricular systolic functions in rTOF. Higher myocardial fibrosis and older age at PVR are independent risk factors for the adverse cardiac events after PVR in patients with rTOF.

Alerting trends in epidemiology for calcific aortic valve disease, 1990-2019: An age-period-cohort analysis for the Global Burden of Disease Study 2019.

AIMS: To assess the trends in calcific aortic valve disease (CAVD) epidemiology, with an emphasis on CAVD mortality, leading risk factors, and their associations with age, period, and birth cohort. METHODS AND RESULTS: Prevalence, disability-adjusted life years, and mortality were derived from the Global Burden of Disease Study 2019. The age-period-cohort model was employed to study the detailed trends of CAVD mortality and its leading risk factors. Globally, CAVD showed unsatisfactory results from 1990 to 2019, with the CAVD deaths of 127 000 in 2019. CAVD mortality was substantially reduced in high socio-demographic index (SDI) countries [-1.45%, 95% confidence interval (CI) (-1.61 to -1.30)], mildly increased in high-middle SDI countries [0.22%, 95% CI (0.06-0.37)], and unchanged in other SDI quintiles. There was a noticeable transition in CAVD deaths from younger to older populations globally. The CAVD mortality increased exponentially with age, and the male had higher mortality than the female before 80 years old. Favourable period [0.69, 95% CI (0.66-0.72)] and birth effects [0.30, 95% CI (0.22-0.43)] were mainly observed in high SDI countries, while unfavourable effects were mostly noticed in high-middle SDI countries. High systolic blood pressure was the leading risk factor of CAVD deaths globally, and it showed favourable trends in high SDI regions. CONCLUSION: Although CAVD mortality reduction was observed globally, unfavourable period, and cohort effects were found in many countries. Increase of mortality rate among the population ≥85 years was the common challenge across all SDI quintiles, stressing the necessity to further improve health care for CAVD patients worldwide.

An electrochemical nitric oxide generator for in-home inhalation therapy in pulmonary artery hypertension.

BACKGROUND: Inhaled NO is a selective pulmonary vasodilator proven to be therapeutic for patients with pulmonary artery hypertension (PAH). The most common NO delivery system in clinical practice is cylinder-based, but unfortunately limited by its high costs, complicated delivery, and the requirement of an extensive supply chain, leaving vast unmet medical needs globally. METHODS: To address the need for rapid, affordable, and safe production of nitric oxide (NO) for in-home inhalation therapy in patients with PAH. We developed a novel portable device to derive NO from a nitrite complex solution with a copper(II)-ligand catalyst, and further examined its effectiveness in a porcine model of PAH. This model was established by using female Bama miniature pig and induced by monocrotaline (MCT) administration. RESULTS: This generator could rapidly and safely produce therapeutic NO at concentrations ranging from 0 to 100 parts per million (ppm) with the least disproportionated nitrogen dioxide (NO2) and byproducts. It could effectively alleviate pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in piglets with PAH, without causing major physiologic disruptions. CONCLUSIONS: Our electrochemical NO generator is able to produce the desired NO doses for pulmonary vasodilation in a safe and sustainable way, with low costs, which paves the way for its subsequent clinical trials in the patient with PAH and other common cardiopulmonary conditions with a high disease burden around the world.

Mapping the early life gut microbiome in neonates with critical congenital heart disease: multiomics insights and implications for host metabolic and immunological health.

BACKGROUND: The early life gut microbiome is crucial in maintaining host metabolic and immune homeostasis. Though neonates with critical congenital heart disease (CCHD) are at substantial risks of malnutrition and immune imbalance, the microbial links to CCHD pathophysiology remain poorly understood. In this study, we aimed to investigate the gut microbiome in neonates with CCHD in association with metabolomic traits. Moreover, we explored the clinical implications of the host-microbe interactions in CCHD. METHODS: Deep metagenomic sequencing and metabolomic profiling of paired fecal samples from 45 neonates with CCHD and 50 healthy controls were performed. The characteristics of gut microbiome were investigated in three dimensions (microbial abundance, functionality, and genetic variation). An in-depth analysis of gut virome was conducted to elucidate the ecological interaction between gut viral and bacterial communities. Correlations between multilevel microbial features and fecal metabolites were determined using integrated association analysis. Finally, we conducted a subgroup analysis to examine whether the interactions between gut microbiota and metabolites could mediate inflammatory responses and poor surgical prognosis. RESULTS: Gut microbiota dysbiosis was observed in neonates with CCHD, characterized by the depletion of Bifidobacterium and overgrowth of Enterococcus, which was highly correlated with metabolomic perturbations. Genetic variations of Bifidobacterium and Enterococcus orchestrate the metabolomic perturbations in CCHD. A temperate core virome represented by Siphoviridae was identified to be implicated in shaping the gut bacterial composition by modifying microbial adaptation. The overgrowth of Enterococcus was correlated with systemic inflammation and poor surgical prognosis in subgroup analysis. Mediation analysis indicated that the overgrowth of Enterococcus could mediate gut barrier impairment and inflammatory responses in CCHD. CONCLUSIONS: We demonstrate for the first time that an aberrant gut microbiome associated with metabolomic perturbations is implicated in immune imbalance and adverse clinical outcomes in neonates with CCHD. Our data support the importance of reconstituting optimal gut microbiome in maintaining host metabolic and immunological homeostasis in CCHD. Video Abstract.

Persistent Liver Dysfunction in Pediatric Patients After Total Cavopulmonary Connection Surgery.

Background: Studies have reported early liver dysfunction (LD) after cardiac surgery is associated with short and long-term mortality. In this study, we aimed to investigate risk factors for persistent LD after total cavopulmonary connection (TCPC) surgery. Methods: This is a retrospective case-control study. We defined persistent LD as LDs occurring between postoperative day 1 (POD1) and POD7 and sustaining at least on POD7, while transient LD as LDs occurring between POD1 and POD7 and recovering at least on POD7. Multivariable logistic regression analysis was applied and central venous pressure (CVP) was considered continuously or in quantiles. Results: Postoperative LD occurred in 111 (27.1%) patients. Transient and persistent LD occurred in 65 (15.9%) and 46 (11.2%) patients, respectively. Aortic cross-clamping (ACC) (odds ratio [OR] 2.55, 95% CI 1.26-5.14) and postoperative CVP (OR 1.34, 95% CI 1.18-1.51) were risk factors for persistent LD, also identified for postoperative any LD and transient LD. Adding postoperative CVP to the model only including ACC significantly improved persistent LD prediction (△AUC 0.15, p = 0.002). Compared with CVP ≤ 14 mmHg, adjusted ORs and 95% CI of persistent LD for CVP of 14-16 and >16 mmHg were 3.11 (1.24, 7.81) and 10.55 (3.72, 29.93), respectively. Patients with persistent LD might have a longer length of mechanical ventilation (mean difference, 13.5 h) and postoperative hospital stay (mean difference, 7 days), and higher postoperative costs (mean difference, 6.7 thousand dollars) compared to those with transient LD. Conclusions: Intra-operative application of ACC and postoperative elevated CVP were independent risk factors for persistent LD in pediatric patients following TCPC surgery. Compared to patients with transient LD, patients with persistent LD might have a longer length of mechanical ventilation and postoperative hospital stay, and higher postoperative costs. We should pay more attention to patients with high postoperative CVP to prevent their persistent LD occurrence.

Global, regional, and national time trends in mortality for congenital heart disease, 1990-2019: An age-period-cohort analysis for the Global Burden of Disease 2019 study.

BACKGROUND: Congenital heart disease (CHD) is the leading cause of morbidity and mortality from birth defects worldwide. We report an overview of trends in CHD mortality in 204 countries and territories over the past 30 years and associations with age, period, and birth cohort. METHODS: Cause-specific CHD mortality estimates were derived from the Global Burden of Disease 2019 study. We utilised an age-period-cohort model to estimate overall annual percentage changes in mortality (net drifts), annual percentage changes from 0 to 4 to 65-69 years (local drifts), period and cohort relative risks (period/cohort effects) between 1990 and 2019. This approach allows for the examination and differentiation of age, period, and cohort effects in the mortality trends, with the potential to identify disparities and treatment gaps in cardiac care. FINDINGS: CHD is the leading cause of deaths from non-communicable diseases (NCDs) in those under 20 years. Global CHD deaths in 2019 were 217,000 (95% uncertainty interval 177,000-262,000). There were 129 countries with at least 50 deaths. India, China, Pakistan, and Nigeria had the highest mortality, accounting for 39.7% of deaths globally. Between 1990 and 2019, the net drift of CHD mortality ranged from -2.41% per year (95% confidence interval [CI] -2.55, -2.67) in high Socio-demographic Index (SDI) countries to -0.62% per year (95% CI: -0.82, -0.42) in low-SDI countries. Globally, there was an emerging transition in the age distribution of deaths from paediatric to adult populations, except for an increasing trend of mortality in those aged 10-34 years in Mexico and Pakistan. During the past 30 years, favourable mortality reductions were generally found in most high-SDI countries like South Korea (net drift = -4.0% [95% CI -4.8 to -3.1] per year) and the United States (-2.3% [-2.5 to -2.0]), and also in many middle-SDI countries like Brazil (-2.7% [-3.1 to 2.4]) and South Africa (-2.5% [-3.2 to -1.8]). However, 52 of 129 countries had either increasing trends (net drifts ≥0.0%) or stagnated reductions (≥-0.5%) in mortality. The relative risk of mortality generally showed improving trends over time and in successively younger birth cohorts amongst high- and high-middle-SDI countries, with the exceptions of Saudi Arabia and Kazakhstan. 14 middle-SDI countries such as Ecuador and Mexico, and 16 low-middle-SDI countries including India and 20 low-SDI countries including Pakistan, had unfavourable or worsening risks for recent periods and birth cohorts. INTERPRETATION: CHD mortality is a useful and accessible indicator of trends in the provision of congenital cardiac care both in early childhood and across later life. Improvements in the treatment of CHD should reduce the risk for successively younger cohorts and shift the risk for all age groups over time. Although there were gains in CHD mortality globally over the past three decades, unfavourable period and cohort effects were found in many countries, raising questions about adequacy of their health care for CHD patients across all age groups. These failings carry significant implications for the likelihood of achieving the Sustainable Development Goal targets for under-5 years and NCD mortality. FUNDING: Supported by the National Natural Science Foundation of China (81525002, 31971048, 82073573 to ZZ and HZ), Shanghai Outstanding Medical Academic Leader program (2019LJ22 to HZ), and Collaborative Innovation Program of Shanghai Municipal Health Commission (2020CXJQ01 to HZ), the Bill & Melinda Gates Foundation for the Global Burden of Disease Project (to NJK) and NHMRC fellowship administered through the University of Melbourne (to GCP).

Neutrophil-to-lymphocyte ratio as a predictor of mortality in intensive care unit patients: a retrospective analysis of the Medical Information Mart for Intensive Care III Database.

OBJECTIVES: Identifying high-risk patients in the intensive care unit (ICU) is important given the high mortality rate. However, existing scoring systems lack easily accessible, low-cost and effective inflammatory markers. We aimed to identify inflammatory markers in routine blood tests to predict mortality in ICU patients and evaluate their predictive power. DESIGN: Retrospective case-control study. SETTING: Single secondary care centre. PARTICIPANTS: We analysed data from the Medical Information Mart for Intensive Care III database. A total of 21 822 ICU patients were enrolled and divided into survival and death groups based on in-hospital mortality. PRIMARY AND SECONDARY OUTCOME MEASURES: The predictive values of potential inflammatory markers were evaluated and compared using receiver operating characteristic curve analysis. After identifying the neutrophil-to-lymphocyte ratio (NLR) as having the best predictive ability, patients were redivided into low (≤1), medium (1-6) and high (>6) NLR groups. Univariate and multivariate logistic regression analyses were performed to evaluate the association between the NLR and mortality. The area under the curve (AUC), net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to assess whether incorporating the NLR could improve the predictive power of existing scoring systems. RESULTS: The NLR had the best predictive ability (AUC: 0.609; p<0.001). In-hospital mortality rates were significantly higher in the low (OR (OR): 2.09; 95% CI 1.64 to 2.66) and high (OR 1.64; 95% CI 1.50 to 1.80) NLR groups than in the medium NLR group. Adding the NLR to the Simplified Acute Physiology Score II improved the AUC from 0.789 to 0.798, with an NRI and IDI of 16.64% and 0.27%, respectively. CONCLUSIONS: The NLR predicted mortality in ICU patients well. Both low and high NLRs were associated with elevated mortality rates, including the NLR may improve the predictive power of the Simplified Acute Physiology Score II.

The Incidence and Risk Factors for Persistent Acute Kidney Injury Following Total Cavopulmonary Connection Surgery: A Single-Center Retrospective Analysis of 465 Children.

Background: Acute kidney injury (AKI) after cardiac surgery contributes to adverse outcomes. We aimed to assess the incidence and identify the predictors for persistent AKI after total cavopulmonary connection (TCPC) surgery. Methods: A retrospective study, including 465 children undergoing TCPC surgery from 2010 to 2019, was conducted. We used pRIFLE criteria to define AKI and defined persistent AKI as AKIs occurring between post-operative day1 (POD1) and POD3 and sustaining at least on POD7. Univariate and multivariate logistic regressions were applied to analyze the predictors for persistent AKI. Results: A total of 35.3% patients developed AKI between POD1 to POD3 and 15.5% patents had persistent AKI after TCPC. Patients with persistent AKI had prolonged mechanical ventilation and ICU stay, and had higher rates of renal replacement treatment and reintubation, which was associated with higher hospitalization costs and in-hospital mortality. The independent predictors for persistent AKI were peripheral oxygen saturation (SpO2) upon admission, intraoperative fluid balance, POD0 maximal lactic acid, renal perfusion pressure (RPP), POD0 estimated glomerular filtration rate and POD0 total bilirubin. The areas under receiver operating characteristic curve (AUC) in the total cohort and the subgroup undergoing TCPC surgery after 2017 were 0.75 (95% CI, 0.66-0.82) and 0.87 (95% CI, 0.77-0.97), respectively. The acceptable AUCs (nearly 0.7) were achieved in other 5 subgroups and good calibration ability (p ≥ 0.05) were achieved in the total cohort and all six subgroups. Conclusions: Persistent AKI after TCPC was common and strongly associated with poorer in-hospital outcomes in Chinese pediatric patients. Six perioperative variables, including SpO2, intraoperative fluid balance, POD0 maximal lactic acid, RPP, POD0 moderate-to-severe kidney injury and POD0 total bilirubin, were identified as independent predictors for persistent AKI. Our findings may help to perform an early risk stratification for these vulnerable patients and improve their outcomes.

The Current Landscape of Congenital Heart Surgery in Northern China: A Geographic and Population-Based Analysis.

Background: Congenital heart disease (CHD) is the leading birth defect in China, and many patients require congenital heart surgery (CHS) to achieve optimal outcomes. However, the current landscape and population accessibility to specialist resources for CHS in China are unclear. Methods: Care facilities performing CHS were identified from the 2018 white book of Chinese cardiovascular surgery and were categorized as full or limited facilities based on specialist capacity. Census-based population data and road data were obtained from administrative sources. Service area analysis of all facilities was performed to estimate geographic accessibility. Results: Of 93 facilities in 14 provinces and municipalities in northern China, only 30.1% had full specialist capacity. The shortage of pediatric cardiologists and mechanical circulatory support was the primary limiting factor. In 2018, 61.3% of facilities performed <200 CHS cases, and 31.6% of all CHS cases (N = 30,921) were performed in limited facilities with substantially lower volume than full-capacity facilities (median value: 85.0 vs. 368.0). Beijing had a disproportionately higher CHS volume (367 cases per million population) than other provinces. Of all children under 5 in northern China, only 12.9% live within 30 km (a typical half-day visit) of the service areas of all facilities. Compared to children from the eastern region (31.4%), 71.8% of children from the central region and 70.2% of children from the western region needed to travel >180 km (a typical overnight visit) to receive care in full-capacity facilities. Conclusions: Many facilities for CHS in northern China had limited specialist capacity, and many CHD patients received suboptimal surgical care. Policy measures should address the significant geographic disparities to receive high-quality surgical care among disadvantaged patients.

Prognostic Value of Preoperative Absolute Lymphocyte Count in Children With Tetralogy of Fallot.

Background Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Absolute lymphocyte count (ALC) is a low-cost and easy-to-obtain inflammatory indicator; however, its association with the prognosis of patients with TOF remains unknown. This study aimed to determine the prognostic value of preoperative ALC in children with TOF. Methods and Results This retrospective study included 707 patients aged <6 years who underwent corrective operations for TOF between January 2016 and December 2018 in Fuwai Hospital, China. The end points were mortality, extracorporeal membrane oxygenation placement, postoperative hospital stay >30 days, and severe postoperative complications; patients were grouped on the basis of prognosis: poor prognosis (n=76) and good prognosis (n=631). Univariable and multivariable logistic regression analyses were performed to identify the independent risk factors for poor prognosis, on which a risk scoring system was based. The receiver operating characteristic curve was used to assess model performance. Using another model without ALC, the effect of the addition of ALC was assessed. Results suggested that ALC was an independent factor with a cutoff point of 4.36×109/L. The addition of ALC improved the area under the curve from 0.771 to 0.781 (P<0.001). To avoid reverse causality and further control for confounding factors, the patients were further divided on the basis of ALC level, and a propensity score matching was performed; 117 paired patients were identified for further analysis. Low ALC levels had an odds ratio of 3.500 (95% CI, 1.413-8.672). Conclusions Low preoperative ALC represents an independent predictor of poor prognosis in children with TOF.

Suppression of Myocardial Hypoxia-Inducible Factor-1α Compromises Metabolic Adaptation and Impairs Cardiac Function in Patients With Cyanotic Congenital Heart Disease During Puberty.

BACKGROUND: Cyanotic congenital heart disease (CCHD) is a complex pathophysiological condition involving systemic chronic hypoxia (CH). Some patients with CCHD are unoperated for various reasons and remain chronically hypoxic throughout their lives, which heightens the risk of heart failure as they age. Hypoxia activates cellular metabolic adaptation to balance energy demands by accumulating hypoxia-inducible factor 1-α (HIF-1α). This study aims to determine the effect of CH on cardiac metabolism and function in patients with CCHD and its association with age. The role of HIF-1α in this process was investigated, and potential therapeutic targets were explored. METHODS: Patients with CCHD (n=25) were evaluated for cardiac metabolism and function with positron emission tomography/computed tomography and magnetic resonance imaging. Heart tissue samples were subjected to metabolomic and protein analyses. CH rodent models were generated to enable continuous observation of changes in cardiac metabolism and function. The role of HIF-1α in cardiac metabolic adaptation to CH was investigated with genetically modified animals and isotope-labeled metabolomic pathway tracing studies. RESULTS: Prepubertal patients with CCHD had glucose-dominant cardiac metabolism and normal cardiac function. In comparison, among patients who had entered puberty, the levels of myocardial glucose uptake and glycolytic intermediates were significantly decreased, but fatty acids were significantly increased, along with decreased left ventricular ejection fraction. These clinical phenotypes were replicated in CH rodent models. In patients with CCHD and animals exposed to CH, myocardial HIF-1α was upregulated before puberty but was significantly downregulated during puberty. In cardiomyocyte-specific Hif-1α-knockout mice, CH failed to initiate the switch of myocardial substrates from fatty acids to glucose, thereby inhibiting ATP production and impairing cardiac function. Increased insulin resistance during puberty suppressed myocardial HIF-1α and was responsible for cardiac metabolic maladaptation in animals exposed to CH. Pioglitazone significantly reduced myocardial insulin resistance, restored glucose metabolism, and improved cardiac function in pubertal CH animals. CONCLUSIONS: In patients with CCHD, maladaptation of cardiac metabolism occurred during puberty, along with impaired cardiac function. HIF-1α was identified as the key regulator of cardiac metabolic adaptation in animals exposed to CH, and pubertal insulin resistance could suppress its expression. Pioglitazone administration during puberty might help improve cardiac function in patients with CCHD.