Serum bile acid measurements in women of European and South Asian ethnicity with or without gestational diabetes mellitus: A cohort study.

OBJECTIVE: Investigation of serum bile acid profiles in pregnancies complicated by gestational diabetes mellitus (GDM) in a multi-ethnic cohort of women who are lean or obese. DESIGN: Prospective cohort study. SETTING: UK multicentre study. POPULATION: Fasting serum from participants of European or South Asian self-reported ethnicity from the PRiDE study, between 23 and 31 weeks of gestation. METHODS: Bile acids were measured using ultra-performance liquid chromatography-tandem mass spectrometry. Log-transformed data were analysed using linear regression in STATA/IC 15.0. MAIN OUTCOME MEASURES: Total bile acids (TBAs), C4, fasting glucose and insulin. RESULTS: The TBAs were 1.327-fold (1.105-1.594) increased with GDM in European women (P = 0.003). Women with GDM had 1.162-fold (1.002-1.347) increased levels of the BA synthesis marker C4 (P = 0.047). In South Asian women, obesity (but not GDM) increased TBAs 1.522-fold (1.193-1.942, P = 0.001). Obesity was associated with 1.420-fold (1.185-1.702) increased primary/secondary BA ratio (P < 0.001) related to 1.355-fold (1.140-1.611) increased primary BA concentrations (P = 0.001). TBAs were positively correlated with fasting glucose (P = 0.039) in all women, and with insulin (P = 0.001) and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (P = 0.001) in women with GDM. CONCLUSIONS: Serum BA homeostasis in late gestation depends on body mass index and GDM in ethnicity-specific ways. This suggests ethnicity-specific aetiologies may contribute to metabolic risk in European and South Asian women, with the relationship between BAs and insulin resistance of greater importance in European women. Further studies into ethnicity-specific precision medicine for GDM are required.

Genetically proxied low-density lipoprotein cholesterol lowering via PCSK9-inhibitor drug targets and risk of congenital malformations.

AIMS: Current guidelines advise against the use of lipid-lowering drugs during pregnancy. This is based only on previous observational evidence demonstrating an association between statin use and congenital malformations, which is increasingly controversial. In the absence of clinical trial data, we aimed to use drug-target Mendelian randomization to model the potential impact of fetal LDL-lowering, overall and through PCSK9 drug targets, on congenital malformations. METHODS AND RESULTS: Instrumental variants influencing LDL levels overall and through PCSK9-inhibitor drug targets were extracted from genome-wide association study (GWAS) summary data for LDL on 1 320 016 individuals. Instrumental variants influencing circulating PCSK9 levels (pQTLs) and liver PCSK9 gene expression levels (eQTLs) were extracted, respectively, from a GWAS on 10 186 individuals and from the genotype-tissue expression project. Gene-outcome association data was extracted from the 7th release of GWAS summary data on the FinnGen cohort (n = 342 499) for eight categories of congenital malformations affecting multiple systems. Genetically proxied LDL-lowering through PCSK9 was associated with higher odds of malformations affecting multiple systems [OR 2.70, 95% confidence interval (CI) 1.30-5.63, P = 0.018], the skin (OR 2.23, 95% CI 1.33-3.75, P = 0.007), and the vertebral, anorectal, cardiovascular, tracheo-esophageal, renal, and limb association (VACTERL) (OR 1.51, 95% CI 1.16-1.96, P = 0.007). An association was also found with obstructive defects of the renal pelvis and ureter, but this association was suggestive of horizontal pleiotropy. Lower PCSK9 pQTLs were associated with the same congenital malformations. CONCLUSION: These data provide genetic evidence supporting current manufacturer advice to avoid the use of PCSK9 inhibitors during pregnancy.

Using genetic techniques to mimic the effects of PCSK9-inhibitors, a group of lipid-lowering medications, this study provides evidence to support recommendations to avoid the use of these medications in pregnancy due to potential risk of multiple malformations in the newborn. This study provides genetic evidence to support potential associations of PCSK9-inhibitor medications with newborn malformations affecting multiple organ systems, the skin, and a cluster of structural defects simultaneously affecting the spine, anus/rectum, heart, throat, kidneys, arms and legs.There was also weaker evidence of an association of PCSK9-inhibitor medications with newborn malformations resulting in blockages of the kidneys and urine system, though the evidence was less certain for these than for the other malformations.

Outcomes following major thoracoabdominal cancer resection in adults with congenital heart disease.

BACKGROUND: While advances in medical and surgical management have allowed >97% of congenital heart disease (CHD) patients to reach adulthood, a growing number are presenting with non-cardiovascular malignancies. Indeed, adults with CHD are reported to face a 20% increase in cancer risk, relative to others, and cancer has become the fourth leading cause of death among this population. Surgical resection remains a mainstay in management of thoracoabdominal cancers. However, outcomes following cancer resection among these patients have not been well established. Thus, we sought to characterize clinical and financial outcomes following major cancer resections among adult CHD patients. METHODS: The 2012-2020 National Inpatient Sample was queried for all adults (CHD or non-CHD) undergoing lobectomy, esophagectomy, gastrectomy, pancreatectomy, hepatectomy, or colectomy for cancer. To adjust for intergroup differences in baseline characteristics, entropy balancing was applied to generate balanced patient groups. Multivariable models were constructed to assess outcomes of interest. RESULTS: Of 905,830 patients undergoing cancer resection, 1,480 (0.2%) had concomitant CHD. The overall prevalence of such patients increased from <0.1% in 2012 to 0.3% in 2012 (P for trend<0.001). Following risk adjustment, CHD was linked with greater in-hospital mortality (AOR 2.00, 95%CI 1.06-3.76), as well as a notable increase in odds of stroke (AOR 8.94, 95%CI 4.54-17.60), but no statistically significant difference in cardiac (AOR 1.33, 95%CI 0.69-2.59) or renal complications (AOR 1.35, 95%CI 0.92-1.97). Further, CHD was associated with a +2.39 day incremental increase in duration of hospitalization (95%CI +1.04-3.74) and a +$11,760 per-patient increase in hospitalization expenditures (95%CI +$4,160-19,360). CONCLUSIONS: While a growing number of patients with CHD are undergoing cancer resection, they demonstrate inferior clinical and financial outcomes, relative to others. Novel screening, risk stratification, and perioperative management guidelines are needed for these patients to provide evidence-based recommendations for this complex and unique cohort.

Center-Level Variation in Failure to Rescue After Pediatric Cardiac Surgery.

BACKGROUND: Although failure to rescue (FTR) is increasingly recognized as a quality metric, studies in congenital cardiac surgery remain sparse. Within a national cohort of children undergoing cardiac operations, we characterized the presence of center-level variation in FTR and hypothesized a strong association with mortality but not complications. METHODS: All children undergoing congenital cardiac operations were identified in the 2013 to 2019 Nationwide Readmissions Database. FTR was defined as in-hospital death after cardiac arrest, ventricular tachycardia/fibrillation, prolonged mechanical ventilation, pneumonia, stroke, venous thromboembolism, or sepsis, among other complications. Hierarchical models were used to generate hospital-specific, risk-adjusted rates of mortality, complications, and FTR. Centers in the highest decile of FTR were identified and compared with others. RESULTS: Of an estimated 74,070 patients, 1.9% died before discharge, at least 1 perioperative complication developed in 43.0%, and 4.1% experienced FTR. After multilevel modeling, decreasing age, nonelective admission, and increasing operative complexity were associated with greater odds of FTR. Variations in overall mortality and FTR exhibited a strong, positive relationship (r = 0.97), whereas mortality and complications had a negligible association (r = -0.02). Compared with others, patients at centers with high rates of FTR had similar distributions of age, sex, chronic conditions, and operative complexity. CONCLUSIONS: In the present study, center-level variations in mortality were more strongly explained by differences in FTR than complications. Our findings suggest the utility of FTR as a quality metric for congenital heart surgery, although further study is needed to develop a widely accepted definition and appropriate risk-adjustment models.

Association of opioid use disorder with outcomes of hospitalizations for acute myocardial infarction in the United States.

OBJECTIVE: While Opioid Use Disorder (OUD) has been linked to inferior clinical outcomes, studies examining the clinical outcomes and readmission of OUD patients experiencing Acute Myocardial Infarction (AMI) remain lacking. The authors analyze the clinical and financial outcomes of OUD in a contemporary cohort of AMI hospitalizations. METHODS: All non-elective adult (≥ 18 years) hospitalizations for AMI were tabulated from the 2016‒2019 Nationwide Readmissions Database using relevant International Classification of Disease codes. Patients were grouped into OUD and non-OUD cohorts. Bivariate and regression analyses were performed to identify the independent association of OUD with outcomes after non-elective admission for AMI, as well as subsequent readmission. RESULTS: Of an estimated 3,318,257 hospitalizations for AMI meeting study criteria, 36,057 (1.1%) had a concomitant diagnosis of OUD. While OUD was not significantly associated with mortality, OUD patients experienced superior cardiovascular outcomes compared to non-OUD. However, OUD was linked to increased odds of non-cardiovascular complications, length of stay, costs, non-home discharge, and 30-day non-elective readmission. CONCLUSIONS: Patients with OUD presented with AMI at a significantly younger age than non-OUD. While OUD appears to have a cardioprotective effect, it is associated with several markers of increased resource use, including readmission. The present findings underscore the need for a multifaceted approach to increasing social services and treatment for OUD at index hospitalization.

Maternal and Fetal Outcomes in Pregnant Patients With Mechanical and Bioprosthetic Heart Valves.

Background Guidelines for choice of prosthetic heart valve in people of reproductive age are not well established. Although biologic heart valves (BHVs) have risk of deterioration, mechanical heart valves (MHVs) require lifelong anticoagulation. This study aimed to characterize the association of prosthetic valve type with maternal and fetal outcomes in pregnant patients. Methods and Results Using the 2008 to 2019 National Inpatient Sample, we identified all adult patients hospitalized for delivery with prior heart valve implantation. Multivariable regressions were used to analyze the primary outcome, major adverse cardiovascular events, and secondary outcomes, including maternal and fetal complications, length of stay, and costs. Among 39 871 862 birth hospitalizations, 4152 had MHVs and 874 had BHVs. Age, comorbidities, and cesarean birth rates were similar between patients with MHVs and BHVs. The presence of a prosthetic valve was associated with over 22-fold increase in likelihood of major adverse cardiovascular events (MHV: adjusted odds ratio, 22.1 [95% CI, 17.3-28.2]; BHV: adjusted odds ratio, 22.5 [95% CI, 13.9-36.5]) as well as increased duration of stay and hospitalization costs. However, patients with MHVs and BHVs had no significant difference in the odds of any maternal outcome, including major adverse cardiovascular events, hypertensive disease of pregnancy, and ante/postpartum hemorrhage. Similarly, fetal complications were more likely in patients with valve prostheses, including a 4-fold increase in odds of stillbirth, but remained comparable between MHVs and BHVs. Conclusions Patients hospitalized for delivery with prior valve replacement carry substantial risk of adverse maternal and fetal events, regardless of valve type. Our findings reveal comparable outcomes between MHVs and BHVs.

Evaluation of hospital readmission rates as a quality metric in adult cardiac surgery.

OBJECTIVE: To assess the reliability of 30-day non-elective readmissions as a quality metric for adult cardiac surgery. BACKGROUND: Unplanned readmissions is a quality metric for adult cardiac surgery. However, its reliability in benchmarking hospitals remains under-explored. METHODS: Adults undergoing elective isolated coronary artery bypass grafting (CABG), surgical aortic valve replacement/repair (SAVR) or mitral valve replacement/repair (MVR) were tabulated from 2019 Nationwide Readmissions Database. Multi-level regressions were developed to model the likelihood of 30-day unplanned readmissions and major adverse events (MAE). Random intercepts were estimated, and associations between hospital-specific risk-adjusted rates of readmissions and were assessed using the Pearson correlation coefficient (r). RESULTS: Of an estimated 86 024 patients meeting study criteria across 298 hospitals, 62.6% underwent CABG, 22.5% SAVR and 14.9% MVR. Unadjusted readmission rates following CABG, SAVR and MVR were 8.4%, 9.3% and 11.8%, respectively. Unadjusted MAE rates following CABG, SAVR and MVR were 35.1%, 32.3% and 37.0%, respectively. Following adjustment, interhospital differences accounted for 4.1% of explained variance in readmissions for CABG, 7.6% for SAVR and 10.0% for MVR. There was no association between readmission rates for CABG and SAVR (r=0.10, p=0.09) or SAVR and MVR (r=0.09, p=0.1). A weak association was noted between readmission rates for CABG and MVR (r=0.20, p<0.001). There was no significant association between readmission and MAE for CABG (r=0.06, p=0.2), SAVR (r=0.04, p=0.4) and MVR (r=-0.03, p=0.6). CONCLUSION: Our findings suggest that readmissions following adult cardiac surgery may not be an ideal quality measure as hospital factors do not appear to influence this outcome.

Identifying the origin of socioeconomic disparities in outcomes of major elective operations.

Background: While the impact of socioeconomic status (SES) on surgical outcomes has been examined in limited series, it remains a significant determinant of healthcare outcomes at the national level. Therefore, the current study aims to determine SES disparities at three time-points: hospital accessibility, in-hospital outcomes, and post-discharge consequences. Methods: The Nationwide Readmissions Database 2010-2018 was used to isolate major elective operations. SES was assigned using previously coded median income quartiles as defined by patient zip-code, with low SES defined as the lowest quartile and high SES as the highest. Results: Of an estimated 4,816,837 patients undergoing major elective operations, 1,037,689 (21.3 %) were categorized as low SES and 1,288,618 (26.5 %) as high. On univariate analysis and compared to those of low SES, high SES patients were more frequently treated at high-volume centers (70.9 vs 55.6 %, p < 0.001), had lower rates of in-hospital complications (24.0 vs 29.0 %, p < 0.001) and mortality (0.4 vs 0.9 %, p < 0.001) as well as less frequent urgent readmissions at 30- (5.7 vs 7.1 %, p < 0.001) and 90-day timepoints (9.4 vs 10.7 %, p < 0.001). On multivariable analysis, high SES patients had higher odds of treatment at high-volume centers (Odds: 1.87, 95 % CI: 1.71-2.06), and lower odds of perioperative complications (Odds: 0.98, 95 % CI: 0.96-0.99), mortality (Odds: 0.70, 95 % CI: 0.65-0.75), and urgent readmissions at 90-days (Odds: 0.95, 95 % CI: 0.92-0.98). Conclusion: This study fills a much-needed gap in the current literature by establishing that all of the aforementioned timepoints include significant disadvantages for those of low socioeconomic status. Therefore, a multidisciplinary approach may be required for intervention to improve equity for surgical patients.

Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom.

This study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people. Five genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency < 5%. Variants were filtered, and annotated to perform rare variant burden analysis, protein structure, and modelling analysis in-silico. Out of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and were mostly heterozygous unless specified. 90 were novel and of those variants, 22 were considered likely pathogenic and 9 pathogenic. We identified variants in volunteers with gallstone disease (n = 31), intrahepatic cholestasis of pregnancy (ICP, n = 16), cholangiocarcinoma and cirrhosis (n = 2). Fourteen novel LoF variants were identified: 7 frameshift, 5 introduction of premature stop codon and 2 splice acceptor variants. The rare variant burden was significantly increased in ABCB11. Protein modelling demonstrated variants that appeared to likely cause significant structural alterations. This study highlights the significant genetic burden contributing to cholestatic liver disease. Novel likely pathogenic and pathogenic variants were identified addressing the underrepresentation of diverse ancestry groups in genomic research.

A contemporary analysis of the volume-outcome relationship for extracorporeal membrane oxygenation in the United States.

BACKGROUND: A paradoxical increase in mortality following extracorporeal membrane oxygenation at high-volume centers has previously been demonstrated. We examined the association between annual hospital volume and outcomes within a contemporary, national cohort of extracorporeal membrane oxygenation patients. METHODS: All adults requiring extracorporeal membrane oxygenation for postcardiotomy syndrome, cardiogenic shock, respiratory failure, or mixed cardiopulmonary failure were identified in the 2016 to 2019 Nationwide Readmissions Database. Patients undergoing heart and/or lung transplantation were excluded. A multivariable logistic regression with hospital extracorporeal membrane oxygenation volume parametrized as restricted cubic splines was developed to characterize the risk-adjusted association between volume and mortality. The volume corresponding to the maximum of the spline (43 cases/year) was used to categorize centers as low- or high-volume. RESULTS: An estimated 26,377 patients met the study criteria, and 48.7% were managed at high-volume hospitals. Patients at low- and high-volume hospitals had similar age, sex, and rates of elective admission. Notably, patients at high-volume hospitals less frequently required extracorporeal membrane oxygenation for postcardiotomy syndrome but more commonly for respiratory failure. After risk adjustment, high-volume hospital status was associated with reduced odds of in-hospital mortality, relative to low-volume hospitals (adjusted odds ratio 0.81, 95% confidence interval 0.78-0.97). Interestingly, patients at high-volume hospitals faced a 5.2-day increment in length of stay (95% confidence interval 3.8-6.5) and $23,500 in attributable costs (95% confidence interval 8,300-38,700). CONCLUSION: The present study found that greater extracorporeal membrane oxygenation volume was associated with decreased mortality but higher resource use. Our findings may help inform policies regarding access to and centralization of extracorporeal membrane oxygenation care in the United States.

Insurance-Based Disparities in Congenital Cardiac Operations in the Era of the Affordable Care Act.

A body of literature has previously highlighted the impact of health insurance on observed disparities in congenital cardiac operations. With aims of improving access to healthcare for all patients, the Affordable Care Act (ACA) expanded Medicaid coverage to nearly all eligible children in 2010. Therefore, the present population-based study aimed to examine the association of Medicaid coverage with clinical and financial outcomes in the era the ACA. Records for pediatric patients (≤ 18 years) who underwent congenital cardiac operations were abstracted from the 2010-2018 Nationwide Readmissions Database. Operations were stratified using the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) Category. Multivariable regression models were developed to evaluate the association of insurance status on index mortality, 30-day readmissions, care fragmentation, and cumulative costs. Of an estimated 132,745 hospitalizations for congenital cardiac surgery from 2010 to 2018, 74,925 (56.4%) were insured by Medicaid. The proportion of Medicaid patients increased from 57.6 to 60.8% during the study period. On adjusted analysis, patients with Medicaid insurance were at an increased odds of mortality (1.35, 95%CI: 1.13-1.60) and 30-day unplanned readmission (1.12, 95%CI: 1.01-1.25), experienced longer lengths of stay (+ 6.5 days, 95%CI 3.7-9.3), and exhibited higher cumulative hospitalization costs (+ $21,600, 95%CI: $11,500-31,700). The total hospitalization cost-burden for patients with Medicaid and private insurance were $12.6 billion and $8.06 billion, respectively. Medicaid patients exhibited increased mortality, readmissions, care fragmentation, and costs compared to those with private insurance. Our results of outcome variation by insurance status indicate the necessity of policy changes to attempt to approach equality in surgical out comes for this high-risk cohort. Baseline characteristics, trends, and outcomes by insurance status over the ACA rollout period 2010-2018.

Development of obstetric-hepatology services: defining optimal care and impact of pregnancy counselling on patient experience.

Objective: Prepregnancy counselling (PPC) is an important aspect of care for women with chronic liver disease (CLD) and liver transplantation (LT), yet its impact has not been well described. This study aims to assess the experience of women attending a joint obstetric-hepatology PPC clinic in a single-centre unit. Design/methods: A retrospective questionnaire-based study in a tertiary unit within the UK where patients who attended the PPC clinic between March 2016 and July 2021 were invited to participate by filling in a questionnaire. Descriptive data and free-text content were subsequently analysed. Results: 108 women attended the PPC clinic over a 5-year period. Overall, 58/108 (54%) completed the questionnaire. Principal concerns regarding pregnancy included fears around deterioration in health (66%), maternal death (24%), pregnancy loss (66%), medication effects (60%) and disease transmission (36%). 17/58 (14%) patients felt the presence of multiple doctors was intimidating, however, perceptions improved by the end of the consultation.Overall, 44/58 (76%) respondents felt the clinic helped them reach a decision about pursuing pregnancy. Almost all respondents would recommend the clinic to others. There were no major differences in pregnancy outcomes between those that received PPC and those that did not. Conclusion: The PPC clinic facilitates a personalised approach to care and is well received by patients with CLD/LT. It is difficult to elucidate whether attendance alone impacts on pregnancy outcomes; registry data may be better placed at addressing this important question.

Race, Insurance, and Sex-Based Disparities in Access to High-Volume Centers for Pancreatectomy.

BACKGROUND: With a large body of literature demonstrating positive volume-outcome relationships for most major operations, minimum volume requirements have been suggested for concentration of cases to high-volume centers (HVCs). However, data are limited regarding disparities in access to these hospitals for pancreatectomy patients. METHODS: The 2005-2018 National Inpatient Sample (NIS) was queried for all elective adult hospitalizations for pancreatectomy. Hospitals performing more than 20 annual cases were classified as HVCs. Mixed-multivariable regression models were developed to characterize the impact of demographic factors and case volume on outcomes of interest. RESULTS: Of an estimated 127,527 hospitalizations, 79.8% occurred at HVCs. Patients at these centers were more frequently white (79.0 vs 70.8%; p < 0.001), privately insured (39.4 vs 34.2%; p < 0.001), and within the highest income quartile (30.5 vs 25.0%; p < 0.001). Adjusted analysis showed that operations performed at HVCs were associated with reduced odds of in-hospital mortality (adjusted odds ratio [AOR], 0.43; 95% confidence interval [CI], 0.34-0.55), increased odds of discharge to home (AOR, 1.17; 95% CI, 1.04-1.30), shorter hospital stay (ß, -0.81 days; 95% CI, -1.2 to -0.40 days), but similar costs. Patients who were female (AOR, 0.88; 95% CI, 0.79-0.98), non-white (black: AOR, 0.66; 95% CI, 0.59-0.75; Hispanic: AOR, 0.56; 95% CI, 0.47-0.66; reference, white), insured by Medicaid (AOR, 0.63; 95% CI, 0.56-0.72; reference, private), and within the lowest income quartile (AOR, 0.73; 95% CI, 0.59-0.90; reference, highest) had decreased odds of treatment at an HVC. CONCLUSIONS: For those undergoing pancreatectomies, HVCs realize superior clinical outcomes but treat lower proportions of female, non-white, and Medicaid populations. These findings may have implications for improving access to high-quality centers.

Assessment of Racial and Ethnic Disparities in Outcomes of Pediatric Hospitalizations for Sepsis Across the United States.

This cross-sectional study examines mortality, prevalence of complex chronic conditions, and admission rates by race and ethnicity of hospitalized children.

The impact of preconception counselling on maternal and fetal outcomes in women with chronic medical conditions: A systematic review.

BACKGROUND: Beyond diabetes mellitus little data reports outcomes of women with chronic medical conditions who have received pre-conception counselling (PCC). This study aimed to perform a systematic review of the literature to evaluate evidence regarding the impact of PCC on maternal and fetal outcomes in women with chronic medical conditions aside from diabetes mellitus. METHODS: A systematic review was conducted in accordance with PRISMA. PubMed, Cochrane, Ovid Medline and Web of Science were searched. Two reviewers screened abstracts and full texts. Inclusion criteria included studies relating to chronic medical disorders of interest published between database inception and 21st May 2022, reporting outcomes relating to disease activity and perinatal outcomes. RESULTS: The search yielded 11,814 results of which six met criteria for inclusion. Two papers describe the demographics of women more likely to receive PCC which included younger age, shorter disease duration, nulliparity, IVF pregnancy and higher education/job security. Two reported the effects of PCC on women's behaviour with improvements demonstrated in correct medication adherence, folic acid intake and smoking cessation. Five studies reported outcomes related to disease activity; those receiving PCC were more likely to have quiescent disease during pregnancy. Improvements in pregnancy outcomes were described including reduced rates of small for gestational age, low birth weight, preterm birth, congenital abnormality and obstetric complications. DISCUSSION: A paucity of data exists relating to pregnancy outcomes in women with chronic medical conditions receiving PCC. Reported outcomes are favorable, supporting the routine inclusion of PCC in preparation for pregnancy in such patients.

Systematic review of long QT syndrome identified during fetal life.

Fetal long QT syndrome (LQTS) may present with sinus bradycardia, functional 2:1 atrioventricular block (AVB), and ventricular arrhythmias (ventricular tachycardia [VT]/torsades de pointes [TdP]) and lead to fetal or postnatal death. We performed a systematic review and individual participant data meta-analysis of 83 studies reporting outcomes of 265 fetuses for which suspected LQTS was confirmed postnatally and determined risk of adverse perinatal and postnatal outcomes using logistic and stepwise logistic regression. A longer fetal QTc was more predictive of death than any other antenatal factor (receiver operating characteristic [ROC] area under the curve [AUC] 0.85; 95% confidence interval [CI] 0.66-1.00). Risk of death was significantly increased with fetal QTc >600 ms. Neither fetal heart rate nor heart rate z-score predicted death (ROC AUC 0.51; 95% CI 0.31-0.71; and ROC AUC 0.59; 95% CI 0.37-0.80, respectively). The combination of antenatal VT/TdP or functional 2:1 AVB and lack of family history of LQTS was also highly predictive of death (ROC AUC 0.82; 95% CI 0.76-0.88). Our data provide clinical screening tools to enable prediction and intervention for fetuses with LQTS at risk of death.

Care Fragmentation After Hospitalization for Acute Myocardial Infarction.

Care fragmentation (CF), or readmission at a nonindex hospital, has been linked to inferior clinical and financial outcomes for patients. However, its impact on patients with acute myocardial infarction (AMI) is unclear. This study investigated the prevalence and impact of CF on the outcomes of patients with AMI. All US adult (≥18 years) hospitalizations for AMI from January 2010 to November 2019 were identified using the Nationwide Readmissions Database. Patients were stratified by readmission at an index or nonindex center. Multivariable models were developed to evaluate factors associated with CF, and independent associations with mortality, complications, and resource utilization. A total of 413,819 patients with AMI requiring nonelective readmission within 30 days of discharge were included for analysis. Of these, 25.4% (n = 104,966) experienced CF. The incidence of CF increased from 2010 to 2019 (nptrend <0.001). After adjustment, patients insured by Medicaid faced higher odds of nonindex readmission. CF was associated with in-hospital mortality (adjusted odds ratio [AOR] 1.09, 95% confidence interval [CI] 1.01 to 1.18), and cardiac (AOR 1.12, 95% CI 1.03 to 1.22), respiratory (AOR 1.14, 95% CI 1.12 to 1.26), and infectious complications (AOR 1.14, 95% CI 1.07 to 1.22). Further, CF was linked to increased odds of nonhome discharge (AOR 1.18, 95% CI 1.11 to 1.24) and an additional ∼$5,000 in per-patient hospitalization costs (95% CI 4,260 to 5,100). Approximately 25% of AMI patients experienced CF, which was independently associated with excess mortality, complications, and expenditures. Given the growing national burden of cardiovascular disease, new efforts are needed to mitigate the significant clinical and financial implications of nonindex readmissions and improve value-based healthcare.