Geographic access to cardiac rehabilitation and cardiovascular disease outcomes: A study of rural United States counties.

Prior studies have examined rural-urban disparities in access to cardiac rehabilitation (CR). However, few have examined the relationship between disparate access to CR and cardiovascular disease outcomes in rural areas. In this analysis of 1975 nonmetro United States counties, we investigated the relationship between number of hospitals with CR and Medicare-population hospitalization rates (per 1000 adults ≥65 years) and county-population mortality rates (per 100,000 adults ≥18 years) due to coronary heart disease (CHD), heart failure (HF), or stroke, using multivariable linear-regression-modeling adjusting for socio-demographic and comorbid conditions. Median CHD hospitalization (13.0 vs. 12.2), HF hospitalization (16.1 vs. 13.3), HF death (114.2 vs. 110.9), stroke hospitalization (12.0 vs. 10.9), and stroke death (39.6 vs. 37.1) rates were higher in nonmetro counties without versus with a CR facility (p-values< 0.001). There were inverse correlations between number of hospitals with CR and CHD (r= -0.161), HF (r= -0.261) and stroke (r= -0.237) hospitalization rates, and stroke mortality (r= -0.144) rates (p-values< 0.001). After adjustment, as the number of hospitals with CR increased, there were decreases in hospitalization rates of 1.78 for CHD, 7.20 for HF, and 2.43 for stroke, per 1000 in the population (p-values < 0.001) and decreases in stroke deaths of 9.17 per 100,000 in the population (p= 0.02). Access to hospitals with CR in US nonmetro counties is inversely related to CHD, HF, and stroke hospitalization, and stroke mortality. Our findings call for reducing barriers to CR in nonmetro communities and further exploring the relationship between CR and stroke outcomes.

Time to Dementia Diagnosis Among Veterans with Comorbid Insomnia and Depressive Episodes.

Background: Older adults with heart failure are at elevated risk of Alzheimer's disease and related dementias (AD/ADRD). Research suggests that insomnia and depressive episodes contribute somewhat dissociable impacts on risk for AD/ADRD in this patient population, although the temporal ordering of effects is unknown. Objective: This study examined time to dementia diagnosis among patients with comorbid insomnia and/or depressive episodes in an epidemiological sample. Methods: Secondary data analyses were conducted using a cohort study of 203,819 Veterans with a primary admission diagnosis of heart failure in 129 VA Medical Centers. Results: Patients with diagnoses of both insomnia and depressive episodes had the shortest time to a dementia diagnosis at both 1-year (Hazard ratio = 1.43, 95% CI [1.36, 1.51]) and 3-year follow-up time points (Hazard ratio = 1.40, 95% CI [1.34, 1.47]) versus patients with one or neither comorbidity. Conclusions: Individuals with both comorbidities had the shortest time to dementia onset. Screening for these comorbidities may help to identify patients at elevated risk of dementia who could benefit from enhanced monitoring or early intervention strategies for more rapid detection and management of dementia symptoms.

Artificial intelligence approaches for phenotyping heart failure in U.S. Veterans Health Administration electronic health record.

AIMS: Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD-code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients. METHODS AND RESULTS: The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP-HF) and non-HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF-related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP-HF as cases (PPV, 0.86; sensitivity, 0.86). From the 'HF ICD-code universe', we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54). CONCLUSIONS: These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.

Identification and outcomes of KDIGO-defined chronic kidney disease in 1.4 million U.S. Veterans with heart failure.

AIMS: According to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline, the definition of chronic kidney disease (CKD) requires the presence of abnormal kidney structure or function for >3 months with implications for health. CKD in patients with heart failure (HF) has not been defined using this definition, and less is known about the true health implications of CKD in these patients. The objective of the current study was to identify patients with HF who met KDIGO criteria for CKD and examine their outcomes. METHODS AND RESULTS: Of the 1 419 729 Veterans with HF not receiving kidney replacement therapy, 828 744 had data on ≥2 ambulatory serum creatinine >90 days apart. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (n = 185 821) or urinary albumin-to-creatinine ratio (uACR) >30 mg/g (n = 32 730) present twice >3 months apart. Normal kidney function (NKF) was defined as eGFR ≥60 ml/min/1.73 m2, present for >3 months, without any uACR >30 mg/g (n = 365 963). Patients with eGFR <60 ml/min/1.73 m2 were categorized into four stages: 45-59 (n = 72 606), 30-44 (n = 74 812), 15-29 (n = 32 077), and <15 (n = 6326) ml/min/1.73 m2. Five-year all-cause mortality occurred in 40.4%, 57.8%, 65.6%, 73.3%, 69.7%, and 47.5% of patients with NKF, four eGFR stages, and uACR >30mg/g (albuminuria), respectively. Compared with NKF, hazard ratios (HR) (95% confidence intervals [CI]) for all-cause mortality associated with the four eGFR stages and albuminuria were 1.63 (1.62-1.65), 2.00 (1.98-2.02), 2.49 (2.45-2.52), 2.28 (2.21-2.35), and 1.22 (1.20-1.24), respectively. Respective age-adjusted HRs (95% CIs) were 1.13 (1.12-1.14), 1.36 (1.34-1.37), 1.87 (1.84-1.89), 2.24 (2.18-2.31) and 1.19 (1.17-1.21), and multivariable-adjusted HRs (95% CIs) were 1.11 (1.10-1.12), 1.24 (1.22-1.25), 1.46 (1.43-1.48), 1.42 (1.38-1.47), and 1.13 (1.11-1.16). Similar patterns were observed for associations with hospitalizations. CONCLUSION: Data needed to define CKD using KDIGO criteria were available in six out of ten patients, and CKD could be defined in seven out of ten patients with data. HF patients with KDIGO-defined CKD had higher risks for poor outcomes, most of which was not explained by abnormal kidney structure or function. Future studies need to examine whether CKD defined using a single eGFR is characteristically and prognostically different from CKD defined using KDIGO criteria.

Clinical Outcomes After Acute Coronary Syndromes or Revascularization Among People Living With HIV: A Systematic Review and Meta-Analysis.

Importance: Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately. Objective: To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group. Data Sources: Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023. Study Selection: Included studies met the following criteria: patients living with HIV and HIV-negative comparator group included, patients presenting with ACS or undergoing PCI included, and longitudinal follow-up data collected after the initial event. Data Extraction and Synthesis: Data extraction was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Clinical outcome data were pooled using a random-effects model meta-analysis. Main Outcome and Measures: The following clinical outcomes were studied: all-cause mortality, major adverse cardiovascular events, cardiovascular death, recurrent ACS, stroke, new heart failure, total lesion revascularization, and total vessel revascularization. The maximally adjusted relative risk (RR) of clinical outcomes on follow-up comparing patients living with HIV with patients in control groups was taken as the main outcome measure. Results: A total of 15 studies including 9499 patients living with HIV (pooled proportion [range], 76.4% [64.3%-100%] male; pooled mean [range] age, 56.2 [47.0-63.0] years) and 1 531 117 patients without HIV in a control group (pooled proportion [range], 61.7% [59.7%-100%] male; pooled mean [range] age, 67.7 [42.0-69.4] years) were included; both populations were predominantly male, but patients living with HIV were younger by approximately 11 years. Patients living with HIV were also significantly more likely to be current smokers (pooled proportion [range], 59.1% [24.0%-75.0%] smokers vs 42.8% [26.0%-64.1%] smokers) and engage in illicit drug use (pooled proportion [range], 31.2% [2.0%-33.7%] drug use vs 6.8% [0%-11.5%] drug use) and had higher triglyceride (pooled mean [range], 233 [167-268] vs 171 [148-220] mg/dL) and lower high-density lipoprotein-cholesterol (pooled mean [range], 40 [26-43] vs 46 [29-46] mg/dL) levels. Populations with and without HIV were followed up for a pooled mean (range) of 16.2 (3.0-60.8) months and 11.9 (3.0-60.8) months, respectively. On postdischarge follow-up, patients living with HIV had lower prevalence of statin (pooled proportion [range], 53.3% [45.8%-96.1%] vs 59.9% [58.4%-99.0%]) and ß-blocker (pooled proportion [range], 54.0% [51.3%-90.0%] vs 60.6% [59.6%-93.6%]) prescriptions compared with those in the control group, but these differences were not statistically significant. There was a significantly increased risk among patients living with HIV vs those without HIV for all-cause mortality (RR, 1.64; 95% CI, 1.32-2.04), major adverse cardiovascular events (RR, 1.11; 95% CI, 1.01-1.22), recurrent ACS (RR, 1.83; 95% CI, 1.12-2.97), and admissions for new heart failure (RR, 3.39; 95% CI, 1.73-6.62). Conclusions and Relevance: These findings suggest the need for attention toward secondary prevention strategies to address poor outcomes of cardiovascular disease among patients living with HIV.

Rare genetic variation in VE-PTP is associated with central serous chorioretinopathy, venous dysfunction and glaucoma.

Central serous chorioretinopathy (CSC) is a fluid maculopathy whose etiology is not well understood. Abnormal choroidal veins in CSC patients have been shown to have similarities with varicose veins. To identify potential mechanisms, we analyzed genotype data from 1,477 CSC patients and 455,449 controls in FinnGen. We identified an association for a low-frequency (AF=0.5%) missense variant (rs113791087) in the gene encoding vascular endothelial protein tyrosine phosphatase (VE-PTP) (OR=2.85, P=4.5×10-9). This was confirmed in a meta-analysis of 2,452 CSC patients and 865,767 controls from 4 studies (OR=3.06, P=7.4×10-15). Rs113791087 was associated with a 56% higher prevalence of retinal abnormalities (35.3% vs 22.6%, P=8.0×10-4) in 708 UK Biobank participants and, surprisingly, with varicose veins (OR=1.31, P=2.3×10-11) and glaucoma (OR=0.82, P=6.9×10-9). Predicted loss-of-function variants in VEPTP, though rare in number, were associated with CSC in All of Us (OR=17.10, P=0.018). These findings highlight the significance of VE-PTP in diverse ocular and systemic vascular diseases.

A multi-ancestry GWAS of Fuchs corneal dystrophy highlights the contributions of laminins, collagen, and endothelial cell regulation.

Fuchs endothelial corneal dystrophy (FECD) is a leading indication for corneal transplantation, but its molecular etiology remains poorly understood. We performed genome-wide association studies (GWAS) of FECD in the Million Veteran Program followed by multi-ancestry meta-analysis with the previous largest FECD GWAS, for a total of 3970 cases and 333,794 controls. We confirm the previous four loci, and identify eight novel loci: SSBP3, THSD7A, LAMB1, PIDD1, RORA, HS3ST3B1, LAMA5, and COL18A1. We further confirm the TCF4 locus in GWAS for admixed African and Hispanic/Latino ancestries and show an enrichment of European-ancestry haplotypes at TCF4 in FECD cases. Among the novel associations are low frequency missense variants in laminin genes LAMA5 and LAMB1 which, together with previously reported LAMC1, form laminin-511 (LM511). AlphaFold 2 protein modeling, validated through homology, suggests that mutations at LAMA5 and LAMB1 may destabilize LM511 by altering inter-domain interactions or extracellular matrix binding. Finally, phenome-wide association scans and colocalization analyses suggest that the TCF4 CTG18.1 trinucleotide repeat expansion leads to dysregulation of ion transport in the corneal endothelium and has pleiotropic effects on renal function.

Real-World Efficacy and Safety of Universal 8-Week Glecaprevir/Pibrentasvir for Treatment-Naïve Patients from a Nationwide HCV Registry in Taiwan.

INTRODUCTION: Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). METHODS: The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. RESULTS: A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. CONCLUSION: Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

Impact of Prior COVID-19 Infections on Cardiac Rehabilitation Completion Rates and Outcomes.

PURPOSE: This is a retrospective cohort study designed to evaluate the impact of having a prior COVID-19 infection on cardiac rehabilitation (CR) completion rates and outcomes. METHODS: Participants enrolled into the CR program from June 1, 2020, to March 30, 2022. They completed both physical and mental health assessments prior to enrollment and upon completion of the program. The cohort was divided into (-) COVID and (+) COVID based on whether they self-reported a prior COVID-19 infection. Outcome measures included General Anxiety Disorder-7, Patient Health Questionnaire-9, Mental Composite Score (Short Form Health Survey-36), Physical Composite Score (Short Form Health Survey-36), and exercise capacity (reported in METs). Program completion rates and outcome measures were compared between (-) COVID and (+) COVID cohorts. RESULTS: A total of 806 participants were enrolled in the study. Program completion rates were 58.7% in the (-) COVID group and 67.2% in the (+) COVID group ( P = .072). African Americans ( P = .017), diabetics ( P = .017), and current smokers ( P = .003) were less likely to complete the program. Both (-) COVID and (+) COVID groups showed significant improvement in all outcome measures after completing the CR program. However, there was no difference in outcomes between groups. CONCLUSIONS: Having a prior COVID-19 infection did not negatively impact the mental and physical health benefits obtained by completing the CR program, regardless of the American Association of Cardiovascular and Pulmonary Rehabilitation risk category.

Factors Associated With Early Palliative Care Among Patients With Heart Failure.

Background: Heart failure (HF) is a progressive, life-limiting illness for which palliative care (PC) is considered standard of care. Among patients that do receive PC, consultation tends to occur late in the illness course. Objective: Our primary aim was to examine patient factors associated with receiving PC in HF. Secondarily, we sought to determine factors associated with early PC encounters. Design: This was a retrospective cohort study of U.S. Veterans with prior hospitalization who died between January 1, 2011 and December 31, 2020. Setting/Subjects: Subjects were Veterans with HF who died with a prior admission to a Veterans Affairs hospital in the United States. Measurements: We calculated the time from PC encounter to death. We characterized HF patients who died without PC, with late PC (≤90 days before death), and with early PC (>90 days before death). Results: We identified 232,079 Veterans with a mean age of (76.5 ± 10.7) years. Within the cohort, 56.5% (n = 131,122) of Veterans died with no PC, 22.5% (n = 52,114) had PC <90 days before death, and 21.0% (n = 48,843) had PC >90 days before death. Veterans who died without PC tended to be younger with fewer comorbidities. Conclusions: While more than 20% of HF patients in our cohort had PC well in advance of death, more than half died without PC. PC involvement seemed to be driven by comorbidities rather than HF. Effective collaboration with Cardiology is needed to identify patients who would benefit from earlier PC involvement.

Lower odds of successful community discharge after medical hospitalization for Veterans with schizophrenia: A retrospective cohort study of national data.

Medical comorbidity, particularly cardiovascular diseases, contributes to high rates of hospital admission and early mortality in people with schizophrenia. The 30 days following hospital discharge represents a critical period for mitigating adverse outcomes. This study examined the odds of successful community discharge among Veterans with schizophrenia compared to those with major affective disorders and those without serious mental illness (SMI) after a heart failure hospital admission. Data for Veterans hospitalized for heart failure were obtained from the Veterans Health Administration (VHA) and Centers for Medicare & Medicaid Services between 2011 and 2019. Psychiatric diagnoses and medical comorbidities were assessed in the year prior to hospitalization. Successful community discharge was defined as remaining in the community without hospital readmission, death, or hospice for 30 days after hospital discharge. Logistic regression analyses adjusting for relevant factors were used to examine whether individuals with a schizophrenia diagnosis showed lower odds of successful community discharge versus both comparison groups. Out of 309,750 total Veterans in the sample, 7377 (2.4%) had schizophrenia or schizoaffective disorder and 32,472 (10.5%) had major affective disorders (bipolar disorder or recurrent major depressive disorder). Results from adjusted logistic regression analyses demonstrated significantly lower odds of successful community discharge for Veterans with schizophrenia compared to the non-SMI (Odds Ratio [OR]: 0.63; 95% Confidence Interval [CI]: 0.60, 0.66) and major affective disorders (OR: 0.65, 95%; CI: 0.62, 0.69) groups. Intervention efforts should target the transition from hospital to home in the subgroup of Veterans with schizophrenia.

Serious mental illness is associated with elevated risk of hospital readmission in veterans with heart failure.

OBJECTIVE: Adults with serious mental illness (SMI) have high rates of cardiovascular disease, particularly heart failure, which contribute to premature mortality. The aims were to examine 90- and 365-day all-cause medical or surgical hospital readmission in Veterans with SMI discharged from a heart failure hospitalization. The exploratory aim was to evaluate 180-day post-discharge engagement in cardiac rehabilitation, an effective intervention for heart failure. METHODS: This study used administrative data from the Veterans Health Administration (VHA) and Centers for Medicare & Medicaid Services between 2011 and 2019. SMI status and medical comorbidity were assessed in the year prior to hospitalization. Cox proportional hazards models (competing risk of death) were used to evaluate the relationship between SMI status and outcomes. Models were adjusted for VHA hospital site, demographics, and medical characteristics. RESULTS: The sample comprised 189,767 Veterans of which 23,671 (12.5%) had SMI. Compared to those without SMI, Veterans with SMI had significantly higher readmission rates at 90 (16.1% vs. 13.9%) and 365 (42.6% vs. 37.1%) days. After adjustment, risk of readmission remained significant (90 days: HR: 1.07, 95% CI: 1.03, 1.11; 365 days: HR: 1.10, 95% CI: 1.07, 1.12). SMI status was not significantly associated with 180-day cardiac rehabilitation engagement (HR: 0.98, 95% CI: 0.91, 1.07). CONCLUSIONS: Veterans with SMI and heart failure have higher 90- and 365-day hospital readmission rates even after adjustment. There were no differences in cardiac rehabilitation engagement based on SMI status. Future work should consider a broader range of post-discharge interventions to understand contributors to readmission.

Adversities in childhood and young adulthood and incident cardiovascular diseases: a prospective cohort study.

Background: Much remains unknown regarding the associations of adversities in childhood and adulthood with incident cardiovascular diseases (CVD). We aimed to examine the independent and cumulative relations of adversities in childhood and adulthood with incident CVD and whether these associations can be mitigated by adopting a healthy lifestyle later in life. Methods: We included 136,073 men and women [38-72 years at baseline] free of diagnosed CVD at baseline who responded to surveys on adversities in childhood and adulthood in the United Kingdom Biobank prospective cohort. They were recruited between 2006 and 2010 and were followed-up until 28 January 2021. Adversities included physical abuse, emotional abuse, sexual abuse, emotional neglect, and physical neglect. Participants were categorised into four groups according to the exposure periods, which were no adversity, childhood adversity only, adulthood adversity only, and cumulative adversity (both childhood and adulthood). The primary outcomes included incident fatal and non-fatal CVD events. The modifiable lifestyle factors were smoking, physical activity, diet, sleeping, social or leisure activities, and friend or family visits. Findings: We identified 16,415 (10.71/1000 person-year) incident CVD during a median follow-up of 11.8 years. Compared with participants with no adversity, CVD incidence increased by 11% in those with childhood adversity only (adjusted hazard ratio [HR]: 1.11 [95% CI 1.06-1.17], p < 0.001), 4% in those with adulthood adversity only (1.04 [1.00-1.09], p = 0.05), and 21% in those with cumulative adversity (1.21 [1.16-1.26], p < 0.001). Analysis of interactions showed that adulthood adversity amplified the childhood adversity-CVD association (p for interaction = 0.03). Compared with the participants with one or fewer ideal lifestyle factors, those with more than four ideal factors had a 25%-36% lower risk of CVD across the three adversity groups. Interpretation: Our findings suggested that childhood adversities were associated with an increased risk of CVD which can be magnified by adulthood adversities and substantially mitigated by adopting a healthy lifestyle later in life. Funding: The National Natural Science Foundation of China and Guangzhou Foundation for Basic and Applied Basic Research.

An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan.

BACKGROUND: Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. METHODS: 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. RESULTS: Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2-4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3-4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2-4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2-4 abnormalities (p < 0.01). CONCLUSIONS: Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care.

Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program.

BACKGROUND/AIMS: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1-3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. METHODS: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. RESULTS: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. CONCLUSION: Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Clinical predictors of right ventricular dysfunction and association with adverse outcomes in peripartum cardiomyopathy.

AIMS: We sought to identify factors associated with right ventricular (RV) dysfunction and elevated pulmonary artery systolic pressure (PASP) and association with adverse outcomes in peripartum cardiomyopathy (PPCM). METHODS AND RESULTS: We conducted a multi-centre cohort study to identify subjects with PPCM with the following criteria: left ventricular ejection fraction (LVEF) < 40%, development of heart failure within the last month of pregnancy or 5 months of delivery, and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included a composite of (i) major adverse events (need for extracorporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation, or death) or (ii) recurrent heart failure hospitalization. RV function was obtained from echocardiogram reports. In total, 229 women (1993-2017) met criteria for PPCM. Mean age was 32.4 ± 6.8 years, 28% were of African descent, 50 (22%) had RV dysfunction, and 38 (17%) had PASP ≥ 30 mmHg. After a median follow-up of 3.4 years (interquartile range 1.0-8.8), 58 (25%) experienced the composite outcome of adverse events. African descent, family history of cardiomyopathy, LVEF, and PASP were significant predictors of RV dysfunction. Using Cox proportional hazards models, we found that women with RV dysfunction were three times more likely to experience the adverse composite outcome: hazard ratio 3.21 (95% confidence interval: 1.11-9.28), P = 0.03, in a multivariable model adjusting for age, race, body mass index, preeclampsia, hypertension, diabetes, kidney disease, and LVEF. Women with PASP ≥ 30 mmHg had a lower probability of survival free from adverse events (log-rank P = 0.04). CONCLUSIONS: African descent and family history of cardiomyopathy were significant predictors of RV dysfunction. RV dysfunction and elevated PASP were significantly associated with a composite of major adverse cardiac events. This at-risk group may prompt closer monitoring or early referral for advanced therapies.

Proprotein convertase subtilisn/kexin type 9 inhibitors and small interfering RNA therapy for cardiovascular risk reduction: A systematic review and meta-analysis.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear. OBJECTIVE: The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials. METHODS: Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic. RESULTS: In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p<0.01) and Alirocumab reduced LDL-c by -46.35% (95% CI: -51.75, -41.13, p<0.01). Inclisiran 284mg reduced LDL-c by -54.83% (95% CI: -59.04, -50.62, p = 0.05) and Inclisiran 300mg reduced LDL-c by -43.11% (95% CI: -52.42, -33.80, p = 0.01). After a median of 8 months (IQR 6-15), Evolocumab reduced the risk of myocardial infarction (MI), OR 0.72 (95% CI: 0.64, 0.81, p<0.01), coronary revascularization, 0.77 (95% CI: 0.70, 0.84, p<0.01), stroke, 0.79 (95% CI: 0.66, 0.94, p = 0.01) and overall MACE 0.85 (95% CI: 0.80, 0.89, p<0.01). Alirocumab reduced MI, 0.57 (0.38, 0.86, p = 0.01), cardiovascular mortality 0.35 (95% CI: 0.16, 0.77, p = 0.01), all-cause mortality 0.60 (95% CI: 0.43, 0.84, p<0.01), and overall MACE 0.35 (0.16, 0.77, p = 0.01). CONCLUSION: PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.

Trends in Palliative Care Utilization in Deceased Veterans With Heart Failure.

Background: Specialist-level palliative care in the final days does not allow time to alleviate symptoms and suffering. This analysis examined the change in the time from initial specialty-level palliative care to death among Veterans with heart failure. Methods: This retrospective cohort study examined Veterans with a diagnosis of heart failure (HF) who died between 2011 and 2021. We examined the decedents from each year as a separate cohort. The primary outcome was time from specialty-level palliative care (SPC) encounter to death in the year death occurred. Results: Of the cohort (n = 232,079), 56.5% did not receive SPC. Specialist-level palliative care >90 days before death more than doubled from 10.1% (2011) to 26.2% (2021), and Specialist-level palliative care in the last day of life was cut from 2.5% to 0.9%. Conclusion: For Veterans with HF, specialist-level palliative care moved earlier in the disease course and has a substantial growth opportunity.