Transplantation Outcomes in Hepatitis C Virus-Positive Donor Hearts After Circulatory Death.

Although the use of hepatitis C virus (HCV)-positive hearts has been shown to be safe and effective among donors with donation after brain death (DBD), it remains unknown whether such organs recovered after circulatory death (DCD) have similar outcomes. In contradistinction to recovery from DBD using cold static organ storage, DCD procurement processes typically use normothermic-perfusion transport strategies that necessitate the use of a large volume of donor blood and involve exposure to temperatures oscillating between cold to dominantly normothermic conditions. We performed a retrospective analysis of United Network for Organ Sharing (UNOS) registry data in the United States and found that clinical outcomes do not differ with respect to rates of treated allograft rejection, early and 1-year survival. Ideally, the organ-recovery source should not result in a bias in organ-offer acceptance from HCV-positive donors, although long-term outcome data are yet unavailable.

Global consumption patterns of combination hypertension medication: An analysis of pharmaceutical sales data from 2010-2021.

Hypertension is the most significant risk factor for cardiovascular disease and mortality worldwide, affecting 1.3 billion adults. Global disparities in hypertension control are widening with low- and middle-income countries (LMIC) having the fastest growing rates of hypertension and low rates of control. Treatment for hypertension can be challenging, with multiple drug classes and dosing schedules. Combination antihypertensives have been suggested as a solution for their efficacy and potential to improve adherence. Global consumption of combination and non-combination antihypertensives across 75 countries and 2 regions from 2010 to 2021 was estimated using the IQVIA MIDAS database on pharmaceutical sales. Consumption rates were standardized using Standard Units (SUs) and analysed by high-income (HIC), upper-middle income (UMIC), and LMIC income classification. Global median consumption rate of all antihypertensives per 1000 inhabitants per day increased from 184.78 SUs in 2010 to 325.6 SUs in 2021, with HICs consistently having the highest rates. Median consumption rates of combination and non-combination antihypertensives increased across all country income groups but combination drugs were consumed at a lower rate and proportion. LMICs consumed a higher percentage of combination antihypertensives relative to non-combination (45.5%) than UMICs (24.3%) and HICs (24.4%) in 2021. While combination antihypertensives may be preferred for their potential for increased adherence and effectiveness, their global uptake is inconsistent. HICs consume less combination medication relative to non-combination, despite higher overall consumption rates of antihypertensives. LMICs show increasing use of combination medications, indicating a shift towards their use.

Excess Risk of Mortality and Hospitalization in Patients with Heart Failure According to Age and Comorbidity - A Nationwide Register Study.

Background: Heart failure (HF) is associated with increased risk of death and a hospitalization, but for patients initiating guideline directed medical therapy, it is unknown how high these risks are compared to the general population - and how this may vary depending on age and comorbidity. Methods: In this retrospective cohort study, we identified patients diagnosed with HF in the period 2011-2017, surviving the initial 120 days after diagnosis. Patients who were on angiotensin converting enzyme inhibitor (ACEi)/ angiotensin receptor blocker (ARB) and beta-blocker were included and matched to 5 non-HF individuals from the background population each based on age and sex. We assessed the 5-year risk of all-cause death, HF and non-HF hospitalization according to sex and age and baseline comorbidity. Results: We included 35,367 patients with HF and 176,835 matched non-HF individuals. Patients with HF had a five-year excess risk (absolute risk difference) of death of 13% (31% [for HF] - 18% [for non-HF]), of HF hospitalization of 17% and of non-HF hospitalization of 24%. Excess risk of death increased with increasing age, whereas the relative risk decreased - for women in their twenties, the excess risk was 7%, risk ratio 7.2, while the excess risk was 18%, risk ratio 1.5 for women in their eighties. Having HF as a 60-year old man was associated with a five-year risk of death similar to a 75-year old man without HF. Further, HF was associated with an excess risk of non-HF hospitalization, ranging from 8% for patients >85 years to 30% for patients <30 years. Conclusion: Regardless of age, sex and comorbidity, HF was associated with excess risk of mortality and non-HF hospitalizations, but the relative risk ratio diminishes sharply with advancing age, which may influence allocation of resources for medical care across populations.

Excess long-term risk of adverse outcomes in heart failure patients with high and low levels of NT-proBNP: A 7-year follow-up study (NorthStar Trial).

Background: This study investigated excess risk in patients with heart failure with reduced left ventricular ejection fraction (HFrEF) with or without elevated levels of NT-proBNP (N-terminal pro-brain natriuretic peptide). Methods: Patients with HFrEF from the NorthStar cohort (n = 1120) were matched on age, sex, and presence of AF (atrial fibrillation/flutter) to five controls without HFrEF from The Danish National Patient Registries. Patients were compared with controls before and after stratification according to baseline NT-proBNP levels, with cutoffs defined as

Temporal trends in infection-related hospitalizations among patients with heart failure: A Danish nationwide study from 1997 to 2017.

BACKGROUND: Despite improved survival, hospitalization is still common among patients with heart failure (HF). OBJECTIVE: This study aimed to examine temporal trends in infection-related hospitalization among HF patients and compare it to temporal trends in the risk of HF hospitalization and death. METHODS: Using Danish nationwide registers, we included all patients aged 18 to 100 years, with HF diagnosed between January 1, 1997 and December 31, 2017, resulting in a total population of 147.737 patients. The outcomes of interest were primarily infection-related hospitalization and HF hospitalization and secondarily all-cause mortality. The Aalen Johansen's estimator was used to estimate 5-year absolute risks for the primary outcomes. Additionally, cox analysis was used for adjusted analyses. RESULTS: The population had a median age of 74 [64, 82] years and 57.6 % were males. Patients with HF had a higher risk of infection over time 16.4 % (95% CI 16.0-16.8) in 1997 to 2001 vs 24.5% (95% CI 24.0-24.9) in 2012 to 2017. In contrast, they had a lower risk of HF hospitalization 26.5% (95% CI 26.1-27.0) in 1997 to 2001 vs 23.2% (95% CI 22.8-23.7) in 2012 to 2017. The risk of infection stratified by infection type showed similar trends for all infection types and marked the risk of pneumonia infection as the most significant in all subintervals. CONCLUSION: In the period from 1997 to 2017, we observed patients with HF had an increased risk of infection-related hospitalization, driven by pneumonia infections. In contrast, the risk of HF hospitalization decreased over time.

Umbilical Cord pH Levels and Neonatal Morbidity and Mortality.

Importance: Umbilical cord pH (UC-pH) level is an important objective indicator of intrapartum fetal hypoxia and is used to predict neonatal morbidity and mortality. A UC-pH value of less than 7.00 is often defined as a threshold for severe acidosis, but existing evidence is divergent and largely based on UC-pH measurements from selected populations; consequently, the results are challenging to interpret. Objective: To investigate the association between UC-pH levels and the risk of adverse neonatal outcomes in a national setting with universal UC-pH measurement. Design, Setting, and Participants: This national, population-based cohort study included all liveborn, singleton, full-term infants without malformations born in Denmark from January 1, 2012, to December 31, 2018. Data were analyzed from January 1, 2023, to March 1, 2024. Exposure: Umbilical cord pH level categorized as less than 7.00, 7.00 to 7.09, 7.10 to 7.19 and 7.20 to 7.50 (reference group). Main Outcomes and Measures: The primary outcome was a composite of severe adverse neonatal outcomes: neonatal death, therapeutic hypothermia, mechanical ventilation, treatment with inhaled nitric oxide, or seizures. Secondary outcomes were individual components of the primary outcome, Apgar score, respiratory outcomes, and hypoglycemia. Data are presented as adjusted risk ratios (ARRs) with 95% CIs. Results: Among the 340 431 infants included, mean (SD) gestational age was 39.9 (1.6) weeks; mean (SD) birth weight was 3561 (480) g; and 51.3% were male. Umbilical cord pH of less than 7.20 was observed more often among infants with a gestational age of 40 or 41 weeks (31.6%-33.6% compared with 18.2%-20.2% at a gestational age of 39 weeks) and among male infants (53.9%-55.4% vs 44.6%-46.1% among female infants). Compared with the pH reference group (576 of 253 540 [0.2%]), the risk for the primary outcome was increased for the groups with UC-pH levels of less than 7.00 (171 of 1743 [9.8%]), 7.00 to 7.09 (101 of 11 904 [0.8%]), and 7.10 to 7.19 (259 of 73 244 [0.4%]). Comparable patterns were observed for the individual outcomes, except for neonatal death, which was only increased in the group with UC-pH levels of less than 7.10. The risk of treatment with continuous positive airway pressure was increased when UC-pH levels were less than 7.20, and the risk of hypoglycemia was 21.5% if UC-pH levels were less than 7.10. Conclusions and Relevance: In this cohort study of 340 431 newborn infants, results support and extend previous studies indicating a higher risk of adverse outcomes even at UC-pH levels above 7.00. The threshold for more intensive observation and treatment may be reconsidered.

Pyrometallurgical Approach to Extracting Valuable Metals from a Combination of Diverse Li-Ion Batteries' Black Mass.

Li-ion batteries (LIBs) are widely used nowadays. Because of their limited lifetimes and resource constraints in manufacturing them, it is essential to develop effective recycling routes to recover their valuable elements. This study focuses on the pyrometallurgical recycling of black mass (BM) from a mixture of different LIBs. In this study, the high-temperature behavior of two types of mixed BM is initially examined. Subsequently, the effect of mechanical activation on the BM reduction kinetics is investigated. Finally, hematite is added to the BM to first be reduced by the excess graphite in the BM and second to form an Fe-based alloy containing Co and Ni. This study demonstrates that mechanical activation does not necessarily affect the kinetics of BM high-temperature behavior. Furthermore, it demonstrates that alloy-making by the addition of hematite is a successful method to simultaneously utilize the graphite in the BM and recover Co and Ni, regardless of the LIB type.

Incidence of clinical outcomes in heart failure patients with and without advanced chronic kidney disease.

AIMS: Chronic kidney disease (CKD) is a well-established risk factor for heart failure (HF); however, patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 have been systematically excluded from clinical trials. This study investigated the incidence of HF and kidney outcomes in HF patients with and without advanced CKD, that is, eGFR < 30. METHODS: From nationwide registries, HF patients were identified from 2014 to 2018 and categorized into three groups according to baseline eGFR (eGFR ≥ 60, 60 > eGFR ≥ 30 and eGFR < 30). The incidence of primary outcomes (all-cause mortality, HF hospitalization, end-stage kidney disease and sustained 50% eGFR decline) was estimated using cumulative incidence functions. RESULTS: Of the 21 959 HF patients included, the median age was 73.9 years, and 30% of patients had an eGFR between 30 and 60 and 7% had an eGFR < 30. The 4 year incidence of all-cause mortality was highest for patients with eGFR < 30 (28.3% for patients with eGFR ≥ 60, 51.6% for patients with 60 > eGFR ≥ 30 and 72.2% for patients with eGFR < 30). The 4 year incidence of HF hospitalization was comparable between the groups (25.8%, 29.8% and 26.1% for patients with eGFR ≥ 60, 60 > eGFR ≥ 30 and eGFR < 30, respectively). For patients with eGFR < 30, kidney outcomes were four times more often the first event than patients with eGFR > 30 (4 year incidence of kidney outcome as the first event was 5.0% for eGFR ≥ 60, 4.8% for 60 > eGFR ≥ 30 and 20.1% for eGFR < 30). CONCLUSIONS: Patients with advanced CKD had a higher incidence of mortality and poorer kidney outcomes than those without advanced CKD, but a similar incidence of HF hospitalizations.

Age-specific mortality trends in heart failure over 25 years: a retrospective Danish nationwide cohort study.

BACKGROUND: Despite advances in heart failure care reducing mortality in clinical trials, it remains unclear whether real-life cohorts have had similar improvements in life expectancy across the age spectrum. We aimed to investigate how mortality trends changed in patients with heart failure over the past 25 years, stratified by age groups. METHODS: Using Danish nationwide registries, we identified patients with new-onset heart failure aged 18-95 years. The 5-year all-cause mortality risk and the absolute risk difference of mortality between patients with heart failure and age-matched and sex-matched heart failure-free controls were assessed using Kaplan-Meier estimates and multivariable Cox regression models. Mortality trends were analysed across five calendar periods (1996-2000, 2001-05, 2006-10, 2011-15, and 2016-20) and three age groups (<65 years, 65-79 years, and ≥80 years). FINDINGS: 194 997 patients with heart failure were included. Mortality significantly decreased from 1996-2000 (66% [95% CI 65·5-66·4]) to 2016-20 (43% [42·1-43·4]), with similar results shown in all age groups (<65 years: 35% [33·9-36·1] to 15% [14·6-16·3]; 65-79 years: 64% [63·1-64·5] to 39% [37·6-39·6]; and ≥80 years: 84% [83·1-84·3] to 73% [71·7-73·9]). Adjusted mortality rates supported these associations. The absolute risk difference declined notably in younger age groups (<65 years: 29·9% [28·8-31·0] to 12·7% [12·0-13·4] and 65-79 years: 41·1% [40·3-41·9] to 25·1% [24·4-25·8]), remaining relatively stable in those aged 80 years or older (30·6% [29·9-31·3] to 28% [27·2-28·8]). INTERPRETATION: Over 25 years, there has been a consistent decrease in mortality among patients with heart failure across age groups, albeit less prominently in patients aged 80 years or older. Further insight is needed to identify effective strategies for improving disease burden in older patients with heart failure. FUNDING: None. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Modifiable risk factors and risk of myocardial infarction in offspring with parental disease.

AIMS: Children of patients with early-onset myocardial infarction (MI) are at increased risk, but the importance of concordant versus discordant parent-offspring risk factor profiles on MI risk is largely unknown. We quantified the long-term absolute risk of MI according to shared risk factors in adulthood. METHODS: We sampled data on familial predisposed offspring and their parents from the Framingham Heart Study. Early MI was defined as a history of parental MI onset before age 55 in men or 65 in women. Individuals were matched 3:1 with non-predisposed offspring. Cardiovascular risk factors included obesity, smoking, hypertension, high cholesterol, and diabetes. We estimated the absolute 20-year incidence of MI using the Aalen-Johansen estimator. RESULTS: At age 40, the 20-year risk of MI varied by cholesterol level (high cholesterol 25.7% [95% confidence interval 11.2%; 40.2%] vs. non-high cholesterol 3.4% [0.5; 6.4]) among predisposed individuals and this difference was greater than in controls (high cholesterol 9.3% [1.5; 17.0] vs. non-high cholesterol 2.5% [1.1; 3.8]). Similar results were observed for prevalent hypertension (26.7% [10.8; 42.5] vs. 4.0% [0.9; 7.1] in predisposed vs. 10.8% [3.2; 18.3] and 2.1% [0.8; 3.4] in controls). Among offspring without risk factors, parental risk factors carried a residual impact on 20-year MI risk in offspring (0% [0; 11.6] for 0-1 parental risk factors versus 3.3% [0; 9.8] for ≥2 parent risk factors at age 40, versus 2.9% [0; 8.4] and 8.5% [0; 19.8] at age 50 years). CONCLUSION: Children of patients with early-onset MI have low absolute risks of MI in the absence of midlife cardiovascular risk factors, especially if the parent also had a low risk factor burden prior to MI.

Children of patients with early-onset myocardial infarction (MI) are at a higher risk of disease themselves. Cardiovascular risk factor control is important to lower the risk of disease, but little is known about how the offspring's risk differs based on risk factor controls. Using multi-generational data from the Framingham Heart Study, we observed that adult children of people with early-onset MI have low absolute 20-year risk of developing an MI if they do not have any cardiovascular risk factors, especially if the parent also had low risk factor burden prior to MI, suggesting that close surveillance for risk factor development in offspring is warranted. In offspring of parents with early-onset MI who did not have any risk factors, the number of risk factors in the parent seemed to slightly impact the risk of MI. Improved clarity of the interplay between risk factors in parents and offspring can help medical doctors provide accurate guidance in terms of preventing the development of MI. Our findings suggest that in the absence of risk factors, assessment of the parents' risk factors burden may be helpful for further risk stratification.

Cardiomyopathy in First-Degree Relatives of Patients Presenting With Acute Myocarditis: Prevalence and Prognostic Significance.

BACKGROUND: Acute myocarditis has been genetically linked to dilated cardiomyopathy (DCM), but the clinical significance remains uncertain. We investigated the prevalence and long-term prognosis of DCM and heart failure (HF) among unselected patients hospitalized with acute myocarditis and their first-degree relatives compared with an age- and sex-matched cohort. METHODS: This was an observational study utilizing the Danish nationwide registries, where all patients with a first-time myocarditis diagnosis from 1995 to 2018 were identified and matched (on birth year and sex) with 10 controls from the general population. RESULTS: Totally 3176 patients with acute myocarditis and 31 760 controls were included (median age, 49.8 [Q1-Q3, 32.5-70.2] years; 35.6% female). At baseline, patients with myocarditis had a higher prevalence of DCM (7 [0.2%] versus 8 [0.0%]) and HF (336 [10.6%] versus 695 [2.2%]) than controls; P<0.0001 for both. Patients with myocarditis more often had siblings with DCM (12 [0.4%] versus 17 [0.05%]) or HF (36 [1.1%] versus 89 [0.3%]); P<0.0001, odds ratios 7.09 (3.38-14.85) and 2.92 (1.25-6.80), respectively, whereas parental DCM and HF did not differ among patients with myocarditis and controls. Patients with myocarditis had greater 20-year incidence of DCM, HF, and all-cause mortality (0.5% [0.3%-0.9%], 15% [13%-17%], and 47% [44%-50%]) compared with controls (0.06% [0.03%-0.11%], 6.8% [6.4%-7.3%], and 34% [33%-35%]; P<0.0001). Having a first-degree relative with DCM or HF was associated with increased long-term mortality among the patients with myocarditis (hazard ratio, 1.40 [1.11-1.77]) but not among the controls (hazard ratio, 0.90 [0.81-1.01]; Pdifference=0.0008). CONCLUSIONS: Acute myocarditis aggregates with DCM within families, where it carries a worsened prognosis. A differential association between parents and siblings (with sibling preponderance) could suggest that additional environmental factors are important for myocarditis development even in predisposed individuals.

Use of medical therapy and risk of clinical events according to frailty in heart failure patients - A real-life cohort study.

AIMS: Although recent randomized clinical trials have demonstrated the advantages of heart failure (HF) therapy in both frail and not frail patients, there is insufficient information on the use of HF therapy based on frailty status in a real-world setting. The aim was to examine how frailty status in HF patients associates with use of HF therapy and with clinical outcomes. METHODS AND RESULTS: Patients with new-onset HF between 2014 and 2021 were identified using the nationwide Danish registers. Patients across the entire range of ejection fraction were included. The associations between frailty status (using the Hospital Frailty Risk Score) and use of HF therapy and clinical outcomes (all-cause mortality, HF hospitalization, and non-HF hospitalization) were evaluated using multivariable-adjusted Cox models adjusting for age, sex, diagnostic setting, calendar year, comorbidities, pharmacotherapy, and socioeconomic status. Of 35 999 participants (mean age 69.1 years), 68% were not frail, 26% were moderately frail, and 6% were severely frail. The use of HF therapy was significantly lower in frailer patients. The hazard ratio (HR) for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation was 0.74 (95% confidence interval 0.70-0.77) and 0.48 (0.43-0.53) for moderate frailty and severe frailty, respectively. For beta-blockers, the corresponding HRs were 0.74 (0.71-0.78) and 0.51 (0.46-0.56), respectively, and for mineralocorticoid receptor antagonists, 0.83 (0.80-0.87) and 0.58 (0.53-0.64), respectively. The prevalence of death and non-HF hospitalization increased with frailty status. The HR for death was 1.55 (1.47-1.63) and 2.32 (2.16-2.49) for moderate and severe frailty, respectively, and the HR for non-HF hospitalization was 1.37 (1.32-1.41) and 1.82 (1.72-1.92), respectively. The association between frailty status and HF hospitalization was not significant (HR 1.08 [1.02-1.14] and 1.08 [0.97-1.20], respectively). CONCLUSION: In real-world HF patients, frailty was associated with lower HF therapy use and with a higher incidence of clinical outcomes including mortality and non-HF hospitalization.

Temporal Trends in the Initiation of Dialysis Among Patients With Heart Failure With or Without Diabetes: A Nationwide Study From 2002 to 2016.

BACKGROUND: The incidence and distribution of acute and chronic dialysis among patients with heart failure (HF), stratified by diabetes, remain uncertain. We hypothesized that with improved survival and rising comorbidities, the demand for dialysis would increase over time. METHODS AND RESULTS: Patients with incident HF, aged 18 to 100 years, between 2002 and 2016, were identified using Danish nationwide registers. Primary outcomes included acute and chronic dialysis initiation, HF-related hospitalization, and all-cause mortality. These outcomes were assessed in 2002 to 2006, 2007 to 2011, and 2012 to 2016, stratified by diabetes. We calculated incidence rates (IRs) per 1000 person-years and hazard ratios (HR) using multivariable Cox regression. Of 115 533 patients with HF, 2734 patients received acute dialysis and 1193 patients received chronic dialysis. The IR was 8.0 per 1000 and 3.5 per 1000 person-years for acute and chronic dialysis, respectively. Acute dialysis rates increased significantly among patients with diabetes over time, while no significant changes occurred in those without diabetes, chronic dialysis, HF-related hospitalization, or overall mortality. Diabetes was associated with significantly higher HRs of acute and chronic dialysis, respectively, compared with patients without diabetes (HR, 2.07 [95% CI, 1.80-2.39] and 2.93 [95% CI, 2.40-3.58] in 2002 to 2006; HR, 2.45 [95% CI, 2.14-2.80] and 2.86 [95% CI, 2.32-3.52] in 2007 to 2011; and 2.69 [95% CI, 2.33-3.10] and 3.30 [95% CI, 2.69-4.06] in 2012 to 2016). CONCLUSIONS: The IR of acute and chronic dialysis remained low compared with HF-related hospitalizations and mortality. Acute dialysis rates increased significantly over time, contrasting no significant trends in other outcomes. Diabetes exhibited over 2-fold increased rates of the outcomes. These findings emphasize the importance of continued monitoring and renal care in patients with HF, especially with diabetes, to optimize outcomes and prevent adverse events.

Clinical Trajectories and Long-Term Outcomes of Alcoholic Versus Other Forms of Dilated Cardiomyopathy.

BACKGROUND: Alcoholic cardiomyopathy (ACM) is a form of dilated cardiomyopathy (DCM) occurring secondary to long-standing heavy alcohol use and is associated with poor outcomes, but the cause-specific risks are insufficiently understood. METHOD: Between 1997 and 2018, we identified all patients with a first diagnosis of ACM or DCM. The cumulative incidence of different causes of hospitalisation and mortality in the two groups was calculated using the Fine-Gray and Kaplan-Meier methods. RESULTS: A Total of 1,237 patients with ACM (mean age 56.3±10.1 years, 89% men) and 17,211 individuals with DCM (mean age 63.6±13.8 years, 71% men) were identified. Diabetes (10% vs 15%), hypertension (22% vs 31%), and stroke (8% vs 10%) were less common in ACM than DCM, whereas obstructive lung disease (15% vs 12%) and liver disease (17% vs 2%) were more prevalent (p<0.05). Cumulative 5-year mortality was 49% in ACM vs 33% in DCM, p<0.0001, multivariable adjusted hazards ratio 2.11 (95% confidence interval 1.97-2.26). The distribution of causes of death was similar in ACM and DCM, with the predominance of cardiovascular causes in both groups (42% in ACM vs 44% in DCM). 5-year cumulative incidence of heart failure hospitalisations (48% vs 54%) and any somatic cause (59% vs 65%) were also similar in ACM vs DCM. At 1 year, the use of beta blockers (55% vs 80%) and implantable cardioverter defibrillators (3% vs 14%) were significantly less often used in ACM vs DCM. CONCLUSIONS: Patients with ACM had similar cardiovascular risks and hospitalisation patterns as other forms of DCM, but lower use of guideline-directed cardiovascular therapies and greater mortality.

Long-term cardiovascular events, graft failure, and mortality in kidney transplant recipients.

BACKGROUND: Kidney transplant recipients are at increased risks of cardiovascular events, but contemporary risk estimates are sparse. Using the Danish nationwide administrative databases, we quantified 1- and 5-year risks of cardiovascular disease and kidney failure among all first-time kidney transplant recipients (2005-2018) and age- and sex-matched controls (1:10 ratio). METHODS: Cumulative 1- and 5-year incidence of cardiovascular events (myocardial infarction, stroke, or heart failure), kidney failure (re-transplantation or need for dialysis >30 days post-transplant), and mortality following transplantation were calculated until maximally Dec 31, 2018. RESULTS: A total of 2,565 kidney transplant recipients (median age 50.5 [25-75th percentile 40.2-60.7] years, 37 % females) and 25,650 controls were included. 1-year cumulative incidence of myocardial infarction, stroke, or heart failure was 2.6 % (95 % confidence interval 1.9 %-3.2 %) among kidney transplant recipients versus 0.5 % (0.4 %-0.5 %) in controls. Cumulative 5-year risk estimates for the same endpoints were 8.3 % (7.1 %-9.5 %) for the transplant patients, and 2.6 % (2.3 %-2.8 %) among controls, respectively. For the kidney transplant cohort, cumulative mortality was 2.2 % (1.7 %-2.8 %) and 10.3 % (9.0 %-11.6 %) at 1- and 5 years, respectively, versus 0.5 % (0.4 %-0.6 %) and 3.0 % (2.7 %-3.2 %) for controls. The cumulative incidence of dialysis and re-transplantation was 6.1 % (5.2 %-7.1 %) at 1 year and 16.3 % (14.7 %-17.9 %) at 5 years, respectively. CONCLUSIONS: Despite the benefits of transplantation, kidney transplant recipients continue to have significant long-term cardiovascular disease, end-stage kidney disease, and mortality risks even with contemporary medical management. Better cardiovascular preventive strategies are warranted to improve prognosis in this segment of patients.

Integrated omics analysis of coronary artery calcifications and myocardial infarction: the Framingham Heart Study.

Gene function can be described using various measures. We integrated association studies of three types of omics data to provide insights into the pathophysiology of subclinical coronary disease and myocardial infarction (MI). Using multivariable regression models, we associated: (1) single nucleotide polymorphism, (2) DNA methylation, and (3) gene expression with coronary artery calcification (CAC) scores and MI. Among 3106 participants of the Framingham Heart Study, 65 (2.1%) had prevalent MI and 60 (1.9%) had incident MI, median CAC value was 67.8 [IQR 10.8, 274.9], and 1403 (45.2%) had CAC scores > 0 (prevalent CAC). Prevalent CAC was associated with AHRR (linked to smoking) and EXOC3 (affecting platelet function and promoting hemostasis). CAC score was associated with VWA1 (extracellular matrix protein associated with cartilage structure in endomysium). For prevalent MI we identified FYTTD1 (down-regulated in familial hypercholesterolemia) and PINK1 (linked to cardiac tissue homeostasis and ischemia-reperfusion injury). Incident MI was associated with IRX3 (enhancing browning of white adipose tissue) and STXBP3 (controlling trafficking of glucose transporter type 4 to plasma). Using an integrative trans-omics approach, we identified both putatively novel and known candidate genes associated with CAC and MI. Replication of findings is warranted.

Outcomes of untreated subclinical antibody-mediated rejection after heart transplantation.

Subclinical antibody-mediated rejection (AMR) is represented by histopathological and/or immunopathological manifestations in the absence of significant cardiac allograft dysfunction. Treatment remains uncertain as there is a lack of data on asymptomatic heart transplant (HT) recipients (HTR) with a positive cardiac biopsy. We sought to determine the impact of untreated subclinical biopsy-proven AMR, regardless of circulating donor-specific antigen (DSA) expression, when diagnosed on surveillance biopsies in the first year after HT. This retrospective case control study evaluated 260 HTR between May 2004 and February 2021. These comprised 231 controls and 29 patients with untreated subclinical AMR. The mortality event rate was higher in controls (2.63 events per 100 person-years) compared to the scAMR Group (1.71 events per 100 person-years), a difference that did not reach statistical significance (hazard ratio 0.66, CI: 0.18-2.36). The combined event rate of cardiac allograft vasculopathy (CAV), graft dysfunction, or mortality was higher in the subclinical AMR group (5.60 events per 100 person-years) than in controls (3.89 events per 100 person-years) but did not reach statistical significance (hazard ratio 1.63, CI: 0.07-40.09). Our results suggest that subclinical AMR diagnosed in the first year after HT on surveillance biopsy is not associated with decreased survival. This may sway the management of subclinical AMR towards a more conservative approach in transplant-capable institutions that currently prioritize treatment, though prospective, randomized studies of such a management strategy are required.

Correction: Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography.

[This corrects the article DOI: 10.1371/journal.pone.0208645.].

Initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to level of frailty in people with type 2 diabetes and cardiovascular disease in Denmark: a cross-sectional, nationwide study.

BACKGROUND: Whether frailty influences the initiation of two cardioprotective diabetes drug therapies (ie, SGLT2 inhibitors and GLP-1 receptor agonists) in people with type 2 diabetes and cardiovascular disease is unknown. We aimed to assess rates of initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to frailty in people with type 2 diabetes and cardiovascular disease. METHODS: For this cross-sectional, nationwide study, all people with type 2 diabetes and cardiovascular disease in Denmark between Jan 1, 2015, and Dec 31, 2021, from six Danish health-data registers were identified. People younger than 40 years, with end-stage renal disease, with registered contraindications to SGLT2 inhibitors or GLP-1 receptor agonists, or with previous use of either drug therapy were excluded. The Hospital Frailty Risk Score was used to categorise people as either non-frail, moderately frail, or severely frail. Cox proportional hazards models were used to analyse the association between frailty and initiation of an SGLT2 inhibitor or a GLP-1 receptor agonist. FINDINGS: Of 119 390 people with type 2 diabetes and cardiovascular disease, 103 790 were included. Median follow-up time was 4·5 years (IQR 2·7-6·1) and median age across the three frailty groups was 71 years (64-79). 65 959 (63·6%) of 103 790 people were male and 37 831 (36·5%) were female. At index date, 66 910 (64·5%) people were non-frail, 29 250 (28·2%) were moderately frail, and 7630 (7·4%) were severely frail. Frailty was associated with a significantly lower probability of initiating therapy with an SGLT2 inhibitor or a GLP-1 receptor agonist than in people who were non-frail (moderately frail hazard ratio 0·91, 95% CI 0·88-0·94, p<0·0001; severely frail 0·75, 0·70-0·80, p<0·0001). This association persisted after adjustment for age, sex, socioeconomic status, year of inclusion, duration of type 2 diabetes, duration of cardiovascular disease, polypharmacy, and comorbidity. INTERPRETATION: In people with type 2 diabetes and cardiovascular disease in Denmark, frailty was associated with a significantly lower probability of SGLT2-inhibitor or GLP-1 receptor-agonist initiation, despite their benefits. Formulating clear and updated guidelines on the use of SGLT2 inhibitors and GLP-1 receptor agonists in people who are frail with type 2 diabetes and cardiovascular disease should be a priority. FUNDING: Department of Cardiology, Herlev and Gentofte University Hospital. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.