bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective effects of nicotinamide mononucleotide on radiation-related cardiac injury
Authors: Wang Z , Zhao X , Zhou Z , Wang F , Zhang X , Tse G , Li G , Liu Y , Liu T
Published: November 2023

Background

Radiation therapy for cancer treatment can cause damage to the heart. There are numerous possible mechanisms related to radiation-related cardiac dysfunction, among which increased oxidative stress is an important factor. However, the detailed mechanisms remain unclear and effective treatments on radiation-related cardiac dysfunction are still lacking. Nicotinamide mononucleotide (NMN), the most direct precursor of nicotinamide adenine dinucleotide (NAD+), can effectively reduce reactive oxygen species (ROS) production and thus could be a candidate to alleviate radiation-induced damage. However, the protective effects and the underlying mechanisms of NMN on radiation-related cardiac injury remain to be elucidated. Therefore, this study was designed to identify the mechanisms of radiation-related cardiac injury and investigate the protective actions of NMN.

Methods

Wild-type c57 mice were divided into radiation exposure (7.2Gy radiation) and non-exposure groups. Wild-type C57BL6/J mice supplied with NMN for 12 months before radiation. Echocardiography to detect mice cardiac function. Epicardial electrical mapping technique to detect electrical conduction in the heart. Non-targeted metabolomics was used to detect cardiac different metabolites. In parallel, we observed the effect of radiation on survival and mitochondrial function (ROS production and ATP content) of H9C2 cells with or without NMN.

Results

In the radiation exposure group, echocardiography showed that the left ventricular ejection fraction (LVEF) and fractional shortening (FS) were reduced, whilst epicardial mapping demonstrated slowed conduction velocity and change in the direction of propagation. Non-targeted metabolomics showed the different metabolites between the radiation group and the control group were mainly in nucleotide and amino acid metabolism. Metabolic pathway enrichment analysis showed that different metabolites were implicated in the metabolism of pyrimidine, folate, arginine and proline, and tryptophan. Mice with NMN before radiation showed reduced mechanical and electrical dysfunction, with non-targeted metabolomic results showed NMN rescued the radiation-induced down-regulation of 1-(4-aminobutyl)urea, 4-aminobenzoic acid, 3-hydroxyanthranilic acid, which ultimately exerted cardioprotective effects. We also found that radiation can reduce the survival, increase ROS production, and reduce ATP content of H9C2 cells in vitro, and these harmful effects can be partially reversed by NMN.

Conclusion

The mechanical and electrical dysfunction caused by radiation were associated with altered nucleotide and amino acid metabolism in the myocardium, and these harmful effects could be partially mitigated by NMN supplement.
The use of high sensitivity troponin T as a biomarker of anthracycline cardiotoxicity
Authors: Bannister C , Tam To B , Patel T , Yap R , Cannata A , Bromage D , Mcdonagh T
Published: November 2023

Introduction

Anthracyclines are a highly effective class of chemotherapy used to treat a wide variety of malignancies. Their use is complicated by the development of cancer therapy-related cardiac dysfunction (CT-RCD), defined broadly as the development of left ventricular systolic dysfunction following cancer treatment. Troponin, a well-established marker of myocardial necrosis and early myocardial injury following anthracycline chemotherapy, may predict the subsequent development of CT-RCD. It is not known, however, at what timepoint troponin should be measured, or if there is a clinically relevant threshold that best predicts the development of CT-RCD.

Purpose

1. To investigate if high sensitivity troponin T (hsTnT) accurately predicts the development of anthracycline CT-RCD

2. To establish the best timepoint at which hsTnT should be measured to predict CT-RCD

3. To establish the most clinically relevant hsTnT concentration to predict CT-RCD

Methods

In 2020 we introduced a clinical pathway for outpatients receiving anthracycline chemotherapy at our Institution. As part of this pathway, hsTnT concentrations are measured at baseline (pre-chemotherapy) and prior to each anthracycline cycle. In this study, we performed a prospective audit of outpatients receiving anthracycline chemotherapy for the treatment of breast or haematological malignancies. Troponin concentrations prior to each chemotherapy cycle were assessed and ROC curve analyses were performed to determine the most accurate timepoint and threshold to predict CT-RCD. CT-RCD was defined as a drop in the left ventricular ejection fraction (LVEF) of >10% from baseline to a value of <50%.

Results

118 outpatients were treated with anthracycline chemotherapy between August 2020 and May 2022. 64 patients (54%) were treated for breast cancer and 54 (46%) for haematological malignancies. The mean age was 54±15yrs, with 71% females. At baseline, 27 (23%) of patients had a diagnosis of hypertension, 16 (14%) diabetes, 28 (24%) smoking history, 10 (8%) chronic kidney disease and 31 (26%) obesity. The median cumulative dose was 360mg/m² for Epirubicin and 300mg/m² for Doxorubicin. The baseline mean LVEF was 60.5±4%. 97/118 (82%) of patients had a follow up echocardiogram. 11/97 (11%) of patients developed CT-RCD. Mean hsTnT concentrations rose incrementally as the cumulative dose of anthracycline increased (Fig 1). Baseline hsTnT concentration was the most accurate predictor of subsequent CT-RCD (AUC 0.75), with a 75% sensitivity and 80% specificity for predicting CT-RCD if the baseline hsTnT concentration was ≥10.5ng/L. In addition, the baseline mean hsTnT concentration was significantly higher in patients with CT-RCD vs. those with no CT-RCD, P=0.0008 (Fig 2).

Conclusions

High sensitivity troponin T concentrations appear to be clinically useful in predicting subsequent CT-RCD, with the most accurate point of measurement being at baseline, prior to chemotherapy commencing.
Pregnancy associated hypertensive disorders and risk of cardiovascular disease: a mendelian randomisation study
Authors: Tschiderer L , Van Der Schouw Y T , Onland-Moret N C , Bloemenkamp K W M , Seekircher L , Burgess S , Willeit P , Peters S A E
Published: November 2023

Background

Pregnancy associated hypertensive disorders including pre-eclampsia/eclampsia and gestational hypertension have been related to unfavourable maternal cardiovascular risk factor profiles and a significantly higher risk to develop maternal cardiovascular disease (CVD) events in observational studies. However, whether these associations are causal is not yet fully understood.

Purpose

We conducted a Mendelian Randomisation study to investigate whether genetic liability to pre-eclampsia/eclampsia and gestational hypertension is related to cardiovascular risk factors and the risk of experiencing CVD outcomes.

Methods

We analysed individual-participant data of women and men from the UK Biobank. The rationale for also analysing men was to study the role of genetic liability to pre-eclampsia/eclampsia and gestational hypertension in CVD risk without experiencing the underlying phenotype. We studied a range of CVD outcomes including myocardial infarction, stroke (including subtypes), and combined CVD endpoints. Furthermore, we analysed a set of blood pressure-, lipid-, liver-, and kidney-related cardiovascular risk factors. To study the genetic association with pre-eclampsia/eclampsia and gestational hypertension we used effect sizes and standard errors from a large-scale genome-wide association study. For the genetic associations with cardiovascular risk factors and CVD outcomes, we used individual-participant data from the UK Biobank. We applied Mendelian Randomisation analysis using inverse variance weighted regression in our primary analysis and implemented additional regression methods as sensitivity analyses.

Results

We included 264,160 women and 223,043 men from the UK Biobank with available genetic data. Mean age at baseline was 56.5 (standard deviation 8.1) and 56.7 (8.2) years in women and men, respectively. Of all women and men, 44.3% and 50.9% had a history of hypertension and mean age at hypertension was 50.0 (10.8) and 51.2 (9.1) years, respectively. Genetically proxied pre-eclampsia/eclampsia and gestational hypertension were related to a higher risk of CVD in both sexes, with odds ratios of 1.20 (1.01, 1.43) and 1.22 (1.10, 1.36) in women and 1.29 (1.08, 1.53) and 1.28 (1.16, 1.42) in men, respectively. The relations were more pronounced for ischaemic than for haemorrhagic outcomes. Furthermore, genetically proxied pre-eclampsia/eclampsia and gestational hypertension were associated with higher levels of systolic and diastolic blood pressure and earlier age at hypertension in both women and men.

Conclusion

Genetic liability to pregnancy associated hypertensive disorders including pre-eclampsia/eclampsia and gestational hypertension is associated with higher CVD risk, implying biological mechanisms relating to these disorders are causally related to CVD risk in both women and men.
Reverse remodelling of right ventricle induced by pregnancy
Authors: Machado Araujo J , Ferreira A F , Azevedo M J , Saraiva F , Machado A P , Sousa C , Sampaio-Maia B , Leite-Moreira A , Ramalho C , Santos M , Falcao-Pires I
Published: November 2023

Introduction

During pregnancy, the cardiovascular (CV) system is exposed to haemodynamic overload and is required to meet the increased demands of the growing foetus. Many studies have focused on left ventricular remodelling, overlooking right cardiac chamber changes.

Aim

To characterize the right cardiac reverse remodelling (RR) through echocardiography during pregnancy and postpartum.

Methods

This prospective cohort study included volunteer pregnant women (healthy and women with CV risk factors - obese and/or hypertensive and/or with gestational diabetes) recruited at two tertiary centres from 2019 to 2021. Women were evaluated by transthoracic echocardiography at the 3rd trimester [PT3, 30-35 weeks, peak of cardiac remodelling] of pregnancy and 6 months after delivery [PP2] (RR). Wilcoxon test was used to compare values between PT3 and PP2.

Results

We included 130 pregnant women with a median age of 33 years, 42% had CV risk factors. RV volume reduced significantly from PT3 to PP2 (33.9 mL to 30.5 mL, p=0.015). Similar significant regression of RA area was observed (13.6 cm2 to 13.1 cm2, p=0.045). Regarding systolic function of the RV, a significant increase in fractional area change (FAC) was reported from PT3 to PP2 (47.4% to 49.4%, p=0.019), while the opposite progression was found for tricuspid annular plane systolic excursion (TAPSE, 24.6 mm to 23.4 mm, p<0.001) and S' tricuspid wave (14.2 cm/s to 12.7 cm/s, p<0.001). In terms of myocardial deformation, a significant increase of RV global longitudinal strain (GLS) (-23% to -25%, p=0.016) and RA (34% to 37%, p=0.026) from the pre- to the postpartum period. Regarding the changes in diastolic function, E/A tricuspid ratio increased significantly after delivery (1.3 to 1.7, p<0.001), mostly due to a decrease of A wave velocity (38 cm/s to 29 cm/s, p<0.001), while no significant difference was found in E/e’ from PT3 to PP2 (3.8 to 3.7, p=0.140). No differences were observed in pulmonary vascular resistance and pulmonary artery systolic pressure (1.3 woods in both and 18 mmHg in both, respectively).

Conclusion

We report a significative regression of right chambers size up to 6 months after delivery. Pregnancy significantly impacts right systolic function as assessed by decreased FAC and strain analysis with a compensatory increase of TAPSE. Right diastolic function reflects pregnancy adaptation to volume overload as observed by the augmented velocity of atrial contraction.
Impact of coronary flow reserve on the mortality and major adverse cardiac and cerebrovascular event in hemodialysis patients, regardless of diabetes
Authors: Umemoto N , Oshima S , Takemoto K , Takikawa S , Itou R , Sakakibara S , Sumino M , Murohara T
Published: November 2023

Background

Ischemic heart disease (IHD) is still a major problem not only in general patients but also in regular hemodialysis (HD) patients. We have reported about prognostic value of coronary flow reserve (CFR) derived from N13-ammonia PET in HD population for all-cause mortality and major adverse cardiac event (MACE) in prior studies. We investigated the impact of diabetes and low CFR on the mortality in HD population.

Methods

A total 1,027 HD patients who undergone 13N-ammonia PET for suspected IHD were enrolled. We divided them into four groups according to CFR (cut off value = 2.0) and whether DM or not. We collected and evaluated their all-cause mortality, cardiovascular (CV) mortality and MACE, and analyzed using Kaplan-Meier methods and uni/multivariate cox regression model.

Results

The number of DM with better CFR group was 194, DM with worse CFR was 244, non-DM with better CFR was 361 and non-DM with worse CFR was 221. We found 285 case of all-cause mortality, 121 case of CV mortality, 164 case of CV mortality and 424 case of MACCE. Whether DM or not, CFR predicts HD patients’ prognosis precisely (See figure). Furthermore, multivariate Cox regression model showed CFR (continuous value) was an independent predictor for all-cause mortality (hazard ratio (HR); 0.774, 95% confidential interval (CI) 0.606-0.979, p value=0.037) and MACCE (HR0.769, 95%CI0.630-0.932, p=0.009) in DM and HD population. Furthermore, CFR predicted all-cause mortality (HR0.731, 95%CI 0.569-0.940, p=0.015) and non-CV death (HR0.636, 95%CI0.451-0.896, p=0.010) in non-DM and HD population.

Conclusion

The HD patients with DM and low CFR had worst prognosis in all-cause mortality, CV death, non-CV death and MACCE.
Renal insufficiency increases the risk of left ventricular remodeling
Authors: Li Q , Liu J , Kang Y , Lu X Z , Sheng S H , Chen S Q , Tan N , Chen J Y , Liu Y
Published: November 2023

Background

Renal insufficiency (RI) is a common disease and associated with heart failure (HF). Left ventricular remodeling (LVR) is a vital process in the progression of HF. However, few studies investigate the relationship between RI and LVR.

Methods

We included 4,973 consecutive patients undergoing coronary angiography (CAG) from January 2007 to December 2018 at Guangdong Provincial People's Hospital (NCT04407936). RI was defined as estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2. LVR was defined as: 1) left ventricular ejection fraction (LVEF) decreased by ≥ 10% from baseline, or 2) a follow-up measurement of LVEF < 40%. Univariate and multivariate logistical regressions were used to assess the association between RI and LVR.

Results

Of the 4,973 patients (61.8 ± 10.5 years, female 30.8%) included in the study. The patients who developed LVR have lower eGFR (73.7 ± 24.2 vs. 78.4 ± 24.2 ml/min/1.73m2, p<0.001). Among the 3,568 (60.6%) patients with RI, 526 (14.7%) had LVR. After adjusting for confounding, multivariate logistic regression showed that RI was associated with a significantly higher risk of LVR (mild RI: OR: 1.23, 95%CI 1.00-1.51, P=0.050; moderate RI: OR: 1.48, 95%CI 1.15-1.92, P = 0.003; severe RI: OR: 1.50, 95%CI 0.91-2.40, P = 0.096). In addition, LVR patients had higher all-cause mortality compared to non-LVR patients (18.1% vs. 9.3%).

Conclusions

Worse renal function increases the risk of decrease in left ventricular systolic function, and severe renal function insufficiency increases the risk of decreased left ventricular systolic function as high as 80% in patients following coronary angiography.Central Illustration
Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation on chronic haemodialysis: a systematic review and meta-analysis of randomised controlled trials
Authors: Navalha D D P , Felix N S , Nogueira A K S , Clemente M R C , Fernandes G C
Published: November 2023

Background

Patients with atrial fibrillation (AF) and end-stage renal disease on chronic haemodialysis (HD) are at risk for thromboembolic and bleeding events. The safety and efficacy of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in this population remains unclear.

Purpose

This systematic review and meta-analysis aimed to compare DOACs with VKAs in patients with AF on chronic HD with regards to cardiovascular mortality, all-cause mortality, ischaemic or uncertain type of stroke, and major or life-threatening bleeding.

Methods

We systematically searched PubMed, EMBASE, and Cochrane Library for randomised controlled trials (RCTs) comparing DOACs with VKAs in patients with AF on chronic HD from inception to February 2023 in accordance with PRISMA guidelines. Statistical analyses were performed using Review Manager 5.4.1. Heterogeneity was evaluated using I2 statistics. We performed the data extraction following the intention-to-treat principle.

Results

We selected three RCTs including 341 patients, of whom 176 (51.6%) were randomised to DOACs. Follow-up ranged from 174 days to 3.38 years. There was no significant difference between groups in terms of cardiovascular mortality (RR 1.35; 95% CI 0.71–2.60; p=0.36; I2=0%; Fig. 1A), all-cause mortality (RR 0.99; 95% CI 0.76–1.30; p=0.96; I2=11%; Fig. 1B), ischaemic or uncertain type of stroke (RR 0.52; 95% CI 0.18–1.48; p=0.22; I2=0%; Fig. 2A), or major or life-threatening bleeding (RR 0.69; 95% CI 0.42–1.14; p=0.15; I2=20%; Fig. 2B), with an overall low between-study heterogeneity.

Conclusion

In this meta-analysis, no significant difference was observed between DOACs and VKAs in cardiovascular mortality, all-cause mortality, ischaemic or uncertain type of stroke, nor major or life-threatening bleeding in patients with AF on chronic HD.Figure 1Figure 2
Predictability of noninvasive liver fibrosis score for cardiac events in patients with nonalcoholic fatty liver disease
Authors: Shibata N , Ito T , Toyoda H , Tanaka A , Morita Y , Kanzaki Y , Watanabe N , Yoshioka N , Morishima I
Published: November 2023

Background

Patients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of cardiac events. Although the severity of liver fibrosis is related to worsening prognosis in patients with NAFLD, it is unclear whether the noninvasive liver fibrosis score has a predictive value for cardiac events.

Purpose

To investigate the relationship between noninvasive liver fibrosis score and the future risk of cardiac events.

Methods

Among 13,368 patients with NAFLD diagnosed using ultrasonography, 4,071 patients were evaluated. Liver fibrosis was assessed and divided into three groups based on the Fibrosis-4 (FIB4) index (cut-off value of 1.30 and 2.67) and NAFLD fibrosis score (NFS) (cut-off values of -1.455 and 0.676), respectively. The primary outcome of this study was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease.

Results

The median age of the evaluated patients was 61 [52–69] years, and 2,201 [54.1%] were male. After a median follow-up period of 6.6 years, 179 (4.4%) patients experienced MACE. Kaplan–Meier survival analysis demonstrated that MACE increased progressively with theFIB4 index (log-rank, p < 0.001) and NFS (log-rank, p < 0.001). Multivariable analysis showed that the higher the FIB4 index, the higher the risk for MACE (compared to the group [reference] with low FIB4 index values, hazard ratio [HR] was 1.860 for the group with intermediate FIB4 index values [95% confidence interval (CI), 1.326–2.610; p<0.001] and 3.325 for the group with high FIB4 index values [95% CI, 2.017–5.479; p<0.001]), and the higher the NFS, the higher the risk for MACE (compared to the group [reference] with low NFSvalues, HR was 1.938 for the group with intermediate NFS values [95% CI, 1.391–2.699; p<0.001] and 3.492 for the group with high NFSvalues [95% CI, 1.997–6.105; p<0.001]).

Conclusions

The FIB4 index and NFS impacted the predictability of MACE in patients with NAFLD.Kaplan–Meier analysis for MACE
Fully automated quantitative stress perfusion cardiac MRI to assess myocardial perfusion in adult patients with convalescent Kawasaki disease and coronary aneurysms: an age and sex-matched analysis
Authors: Cheng K , Bolland M , De Silva R
Published: November 2023

Introduction

Coronary aneurysms are a well-documented complication of childhood Kawasaki disease. They may persist into adulthood predisposing to impaired myocardial blood flow, symptoms, and adverse cardiovascular events. Preliminary reports suggest that Kawasaki disease may also be associated with coronary microvascular dysfunction. The effect of coronary involvement from Kawasaki disease on myocardial perfusion in convalescent asymptomatic adults has not been studied using fully automated inline quantitative perfusion MRI (CMR).

Purpose

To assess the effect of coronary artery abnormalities on quantitative myocardial perfusion in adult patients with convalescent Kawasaki disease compared to an age and sex-matched control cohort.

Methods

Retrospective single centre cohort analysis of adult patients with convalescent Kawasaki disease who have undergone fully automated inline quantitative myocardial stress perfusion CMR. All patients had coronary involvement during their acute childhood illness. An age and sex-matched group (n=14) with normal CMRs was selected for comparison. Rest MBF was corrected for heart rate by dividing by the scan heart rate and multiplying by the mean resting heart rate among all subjects. A per-vessel analysis was performed using a linear mixed effects model with pairwise comparisons to assess the effect of coronary abnormalities (normal, aneurysmal with or without thrombosis, revascularised) on myocardial perfusion reserve (MPR).

Results

28 patients were included (14 Kawasaki; 14 controls). All patients in the Kawasaki cohort had assessment of coronary anatomy either by CT (93%) or invasive (7%) coronary angiography. A total of 84 vessels were analysed. Mean age and sex were well matched (Kawasaki: 27±6.2 years; 13 males : 1 female vs. controls: 27±6.4 years; 13 males : 1 female). In patients with Kawasaki disease, thrombosed aneurysmal arteries were associated with a significantly impaired MPR compared to normal (mean Δ: -0.817; P=0.003) and aneurysmal (mean Δ: -0.957; P<0.001) arteries. MPR in aneurysmal and revascularised arteries were not significantly different from normal arteries in patients with Kawasaki disease. There was no significant difference in MPR between normal coronary arteries in patients with Kawasaki compared to controls.

Conclusions

Thrombosis in coronary aneurysms was associated with a significant impairment of myocardial perfusion in adult patients with convalescent Kawasaki disease. There was no significant reduction in perfusion in territories supplied by normal or aneurysmal arteries which does not support coronary microvascular dysfunction in these patients. Further studies are needed to confirm these preliminary findings.
Cross-sectional analysis of demographic and clinical characteristics of patients using icosapent ethyl
Authors: Nelson J , Toth P , Soran H , Ganda O , Hannachi H , Wong N , Abrahamson D , Hartman J , Philip S
Published: November 2023

Background/Introduction

Icosapent ethyl (IPE) is an ethyl ester of eicosapentaenoic acid first approved in 2012 in the United States for the treatment of severe hypertriglyceridemia (triglyceride [TG] levels ≥500 mg/dL).1 Following results from the global REDUCE-IT trial in 2019 in which IPE substantially reduced the risk of cardiovascular (CV) events,2 IPE was approved in European countries and the United States to reduce the risk of CV events in adults treated with statins who have elevated TG levels (≥150 mg/dL) and established CV disease (CVD) or diabetes mellitus (DM) with additional risk factors for CVD.1,3 An estimated 3 million American adults are eligible to receive IPE for primary and secondary CVD prevention.4

Purpose

Provide the first descriptive study of demographic and clinical characteristics of US patients taking IPE.

Methods

A database with electronic medical records of >89 million patients from 56 US health care organizations was used to identify those taking IPE, defined as those for whom at least 2 IPE prescriptions were documented (ie, on 2 separate dates). No specific date range or exclusion criteria were applied. Patient demographic information, prior/existing conditions, prior/concomitant medications, and laboratory data were retrieved.

Results

As of January 19, 2023, a total of 40,408 patients taking IPE were identified; they had a mean (SD) age of 60.3 years (12.9) and a body mass index of 31.9 kg/m2 (6.07). Most patients started taking IPE after January 1, 2019 (72.8%), were men (60.5%), White (75.2%), non-Hispanic or Latino (73.1%), and from the southern (46.0%) or northeastern (34.0%) United States (Table). In line with the indication of IPE, 65.3% had prior atherosclerotic CVD or DM and at least 1 risk factor. Common prior or existing conditions associated with those indicated for IPE treatment were DM (41.0%), coronary artery disease (30.2%), prior myocardial infarction (11.0%), prior stroke (7.4%), and severe hypertriglyceridemia (8.1%); hypertension (68.4%) and obesity (40.9%) were common comorbidities. Mean (SD; median) TG level in the 3 months before IPE initiation was 422 mg/dL (506; 300). Treatment with statins was very high (71.8%), and common other concomitant medications included anticoagulants (53.3%), antidiabetic agents (52.3%), and antiplatelets (46.0%; Table). Fibrates were used by 26.0% of patients taking IPE any time on or before IPE initiation.

Conclusion(s)

Patients using IPE commonly had a history of CVD, DM, or both, took statins, and had elevated levels of TG, thereby meeting the indication for IPE treatment. The high baseline TG levels in this population suggest that IPE is underutilized.
Early repeat ablation strategy in atrial fibrillation patients is associated with lower recurrence rates
Authors: Toennesen J
Published: November 2023

Introduction

Atrial fibrillation (AF) ablation at early stages of AF improves the ablation outcomes in de novo ablations. Whether this is true in repeat ablations is unknown. Therefore, data pertaining the impact of early repeat ablation on AF recurrence in large, unselected cohorts is highly warranted.

Purpose

To examine AF recurrence after repeat ablation by time from recurrent AF to repeat ablation.

Method

Using Danish nationwide registries, all Danish patients above 18 years who underwent repeat AF ablation from January1st 2010 to December31st 2018 were identified and included at the date of repeat ablation. Exposure of interest was time from recurrent AF after de novo ablation to repeat ablation. The primary outcome was recurrent AF, defined from using a composite endpoint comprising claimed prescriptions of AAD, hospital admissions due to AF, re-ablation, or electrical cardioversions. The cumulative incidence of recurrent AF by time from recurrent AF to repeat ablation at 5-year follow-up after a blanking period of 90 days, was estimated using the Aalen-Johansen estimator, taking death as a competing risk into account. The Hazard Ratios of recurrent AF by time from recurrent AF to repeat ablation were examined using Cox models adjusted for sex, age, procedure-year, heart failure, ischemic heart disease, chronic obstructive pulmonary disease, and hypertension. Sub-group analysis of the impact of procedural year and AF-type (paroxysmal vs persistent) were made.

Results

The study cohort consisted of 2,704 patients. Median age [IQR] was 63 [55, 68] in the early ablation group (repeat ablation within 0.5 year after recurrent AF) and 65 [58, 70] in the late ablation group (repeat ablation at least 0.5 year after recurrent AF). It was predominately males and paroxysmal AF patients accounted for 62% and 59% in early vs late repeat ablations. Patient characteristics regarding left atrium size, left ventricular ejection fraction, and body mass index were relatively similar. Prior use of amiodarone was slightly higher in the early ablation group, while use of class 1C antiarrhythmics was highest in the late ablation group.

A total of 1,625 (60%) patients had recurrent AF within 5 years after the blanking period. The mean follow-up time was 874 days.

The cumulative incidence (95% CI) of recurrent AF was 54.8% (52.4%, 57.2%) and 67.3% (64.5%, 70.2%) in the early and late repeat ablation groups respectively. (Figure 1)

The HR (95% CI) for the late repeat ablation group was 1.25 (1.10, 1.41) with the early repeat ablation group as reference. (Figure 2)

Conclusion

Among 2,704 patients undergoing repeat AF ablations from 2010-2018, we found that early repeat ablation was associated with significantly lower recurrence rates. Therefore, early repeat ablation could potentially provide substantial benefits and improve outcomes, indicating repeat ablation as first-line therapy might be ideal.
Baseline characteristics and outcomes of extended oral anticoagulant treatment in patients with venous thrombosis: a retrospective cohort study in France
Authors: Chaves J , Pesce G , Gusto G , Quignot N , Khachatryan A , Subash R , Mokgokong R
Published: November 2023

Background

Guidelines recommend anticoagulant (AC) extended treatment for patients with unprovoked VTE or VTE provoked by permanent risk factors (ESC 2019, CHEST 2021). A recent observational study has shown that apixaban extended treatment (>6 months) vs no extended treatment in patients with venous thromboembolism (VTE), regardless of risk factors, is associated with decreased risk of recurrent VTE (rVTE), with no increase in major bleeding. A better safety profile for patients receiving apixaban vs those receiving vitamin K antagonists (VKAs) was also observed.

Purpose

To describe characteristics of patients with VTE receiving AC extended treatment (>6months) vs those receiving acute treatment only (<6 months). Outcomes among patients receiving extended treatment with apixaban and VKAs were also reported.

Methods

The presence of risk factors were assessed in a nationwide retrospective cohort study of AC treatment-naïve adult patients (identified via the French national health data system: SNDS) with VTE, who were prescribed VKAs or apixaban from 2013 to 2018. Descriptive statistics for patients receiving AC extended treatment vs those receiving only acute treatment are presented. Risk of bleeding (based on principal diagnoses of hospital stays), rVTE (based on principal diagnosis of hospital stays and specified procedures), and all-cause mortality were assessed 18 months following the initiation of extended treatment using inverse probability treatment weighted (IPTW) analysis to balance baseline socio-demographic and clinical characteristics.

Results

21,215 VTE patients who initiated AC treatment were included: 10,775 VKAs (41.5% acute vs 58.5% extended treatment) and 10,440 apixaban (44.5% acute vs and 55.5% extended treatment). A higher proportion of apixaban and VKA patients with permanent risk factors (apixaban: 57.7%; VKAs: 57.7%) or unprovoked VTE (apixaban: 56.8%; VKAs: 59.7%) received extended treatment vs acute treatment only. Table 1 shows the adverse clinical outcomes assessed during extended treatment in IPTW balanced cohorts. Compared to patients treated with VKAs (n=6151), patients treated with apixaban (n=5682) had lower rates of rVTE (1.89 vs 2.84 per 100 person-years), bleeding (1.11 vs 1.69 per 100 person-years) and all-cause mortality (2.70 vs 6.74 per 100 person-years).

Conclusions

A slightly higher proportions of patients with permanent VTE risk factors and unprovoked VTE received extended treatment compared to acute treatment. Consistent with guidelines, there persists a need to increase these rates when clinically indicated to improve patient outcomes. Clinical event rates were numerically lower for apixaban compared to VKAs, which suggests clinical benefit for apixaban. However, more robust confirmatory analyses are required.
Risk and benefits of baseline antiplatelet therapy in 58,598 patients with atrial fibrillation randomized to NOACs vs warfarin
Authors: Patel S , Palazzolo M G , Antman E M , Braunwald E , Carnicelli A P , Connolly S J , Granger C B , Patel M R , Wallentin L , Ruff C T , Giugliano R P
Published: November 2023

Background

The efficacy and safety of NOAC versus warfarin (W) may differ in AF pts receiving antiplatelet therapy (APT) at baseline. Moreover, prior individual trial-specific analyses examining the treatment effect of NOAC vs. W as a function of APT are underpowered for interaction testing.

Purpose

We evaluated outcomes by randomized anticoagulant stratified by baseline APT in a pooled individual pt-level meta-analysis of 4 pivotal RCTs of NOAC vs. W in AF: RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48.

Methods

Pts were stratified by use of APT vs. no APT at baseline. Pts randomized to low-dose NOAC not globally approved (edoxaban 30/15 mg or dabigatran 110 mg) were excluded. The primary efficacy and safety outcomes were stroke/systemic embolic events (S/SEE) and major bleeding, respectively; ischemic stroke (IS), intracranial hemorrhage (ICH), major GI bleeding and all-cause mortality (ACM) were secondary outcomes. Each outcome was assessed by randomized treatment using a Cox model stratified by trial with adjustment for age, sex, weight, CrCl, smoking status, HTN, DM, CAD, prior MI, PAD, and prior stroke. Interaction testing was performed by APT at baseline.

Results

Of 58,598 pts, 19,774 (34%) were on APT at baseline (92% aspirin only, 5% P2Y12 only, 3% DAPT). Pts treated with APT had greater prevalence of CAD (41% vs. 24%), prior MI (22% vs. 11%), and PAD (6% vs. 4%) (p<0.001 for each). Reflective of these baseline differences, the annualized event rate for each outcome was higher in the APT vs. no APT group (Figure). The treatment effect (HR) of NOAC vs. W for all 6 clinical outcomes was consistent irrespective of baseline APT (p-interaction [aHR] for each = NS; Figure). However, the absolute risk reduction (ARR) for NOAC vs. W differed for ICH and major GI bleeding as a function of baseline APT (Figure). Specifically, for ICH, a greater absolute benefit was seen with NOAC vs. W in those on APT at baseline (ARR 0.6% vs. 0.3%; p-int = 0.007). Conversely, for major GI bleeding, NOAC vs. W was associated with greater absolute risk in those on APT (ARR -0.6% vs. -0.2%; p-int = 0.04).

Conclusions

The treatment effect of NOAC vs. W is consistent irrespective of APT at baseline for S/SEE, major bleeding, and ACM. Given higher rates of bleeding in AF pts treated with both APT and anticoagulation, concomitant APT should be avoided when possible. In pts requiring concomitant APT, NOAC instead of W should be considered owing to greater absolute safety benefit for ICH, which should be weighed against individual patient-specific risk factors for GI bleeding.
Comparative effectiveness and safety of apixaban and low-molecular weight heparin among patients with venous thromboembolism and active cancer in an extended treatment setting
Authors: Cohen A T , Dhamane A D , Liu X , Han S , Stellhorn R , Zhang Q , Singh R , Wang J , Luo X
Published: November 2023

Background

The 2020 European Society of Cardiology guidelines recommend extended anticoagulant (AC) treatment among patients with VTE and with progressive or persistent risk factors (such as cancer) as they are at a high risk of a recurrent VTE episode.

Purpose

The study evaluated the risk of recurrent VTE and major bleeding (MB) among patients with VTE and active cancer prescribed apixaban or LMWH (reference) for ≥3 months.

Methods

This retrospective study included patients ≥18 years with VTE who initiated apixaban or LMWH within 30 days following the first VTE event using a large administrative claims database, representing ≥140 million patients enrolled in US health plans. Data from July 1, 2016, through April 30, 2022, was used. Patients were required to have ≥3 months of continuous enrollment (CE) and ≥3 months of continuous primary AC treatment following the date of apixaban/LMWH initiation. The end of 3 months of primary treatment was designated as index date. The follow-up period was from the day after the index date until the earliest of disenrollment, discontinuation of index anticoagulant, switch to another anticoagulant, or the end of the study period. The MB and recurrent VTE outcomes were evaluated and compared in the follow-up period. Inverse-probability treatment weighting (IPTW) was used to balance the treatment cohorts on relevant demographic and clinical characteristics including VTE and cancer-related variables. Incidence rate for the outcomes were calculated per 100 person-years. Cox proportional hazard models were used to evaluate the adjusted risk of recurrent VTE and MB reported as hazard ratios (HR) along with 95% confidence interval (CI).

Results

After the eligibility criteria was met, the study included 13,527 apixaban and 2,914 LMWH treated patients with VTE and active cancer. Post IPTW, the treatment cohorts were balanced on baseline patient characteristics (Figure 1). In the follow-up period, the incidence rates (IR) per 100 person-years for recurrent VTE and MB were lower for apixaban than LMWH among patients with VTE and active cancer (Figure 2). Apixaban patients had a lower risk of recurrent VTE (HR: 0.42; 95% CI: 0.34–0.53) and MB (HR: 0.50; 95% CI: 0.41–0.61) when compared to LMWH (Figure 2).

Conclusion

In this observational cohort analysis of patients with VTE and active cancer, extended anticoagulation treatment of ≥3 months with apixaban was associated with a lower risk of recurrent VTE and MB compared with LMWH. Additional research is required to confirm these findings.Figure 1Figure 2
DNA methylation of ADAMTS7 gene promoter in direct oral anticoagulant-induced bleeding in patients with atrial fibrillation
Authors: Atzemian N , Ragia G , Thomopoulos T , Tsaliki V , Kolios G , Chalikias G , Trikas A , Tziakas D , Manolopoulos V G
Published: November 2023

Introduction

Direct Oral Anticoagulants (DOACs) are recommended as first-line treatment in atrial fibrillation (AF) patients. Despite their benefits and effectiveness, several patients experience bleeding events. No studies have addressed how epigenetic modifications may affect DOAC treatment. To fill this gap, we are conducting a study aiming to follow in time changes of DNA methylation patterns in naïve AF patients starting DOAC therapy. Herein, we present our findings regarding DNA methylation analysis of ADAM Metallopeptidase with Thrombospondin Type 1 Motif 7 (ADAMTS7), a protease that acts on the cardiovascular system.

Methods

A total of 76 AF patients treated with dabigatran, rivaroxaban, or apixaban and 22 non-AF controls were included. Genomic DNA has been isolated at baseline (t0, controls and patients), and for patients at 7 (t1) and 28 (t2) days of DOAC treatment. Blood genomic DNA was isolated and bisulfite converted prior to methylation analysis. Promoter DNA methylation of ADAMTS7 was analyzed with qMSP-PCR.

Results

In our study, no major bleeding or thrombotic events were recorded. A total of 16 minor bleeding events occurred. The percentage of ADAMTS7 methylation at baseline did not differ between patients and controls (16,8% vs. 14,8%, p=0,138). In patient cohort, DOAC therapy did not alter ADAMTS7 methylation at different timepoints (16,8% at t0, 15,7% at t1 and 14,3% at t2, p=0,293 from t0 to t1, p=0,06 from t0 to t2 and p=0,205 from t0 to t1). When patients were categorized into experiencing bleeding events (cases) or not (controls), ADAMTS7 was demethylated from t0 to t2 (-3,7% in cases vs. -1.2% in controls, p=0.015) and from t1 to t2 (-2,1% in cases vs. -1,1% in controls, p=0.034). In adjusted regression analysis, bleeding was associated with ADAMTS7 demethylation (β=-2,973, 95%CI -5,481, -0,466, p=0,021).

Conclusion

This is the first study of DNA methylation on DOACs. Our findings suggest that the methylation of the promoter of ADAMTS7 is reduced when DOAC-related bleeding occurs, increasing its expression levels, and may subsequently promote hemostasis and endothelium remodeling through different pathways.
SLCO1B1*5 is protective against non-senile cataracts in cohort prescribed statins: analysis in a British-South Asian cohort
Authors: Magavern E F , Van Heel D A , Smedley D , Caulfield M J
Published: November 2023

Background

Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The SLCO1B1*5 reduced function variant is known to increase systemic exposure to statins. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity.

Methods

The Genes & Health cohort consists of UK participants of Bangladeshi and Pakistani ancestry. SLCO1B1*5 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B1*5 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not.

Results

Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5-0.9, p 0.007)).

Conclusions

Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.Study results overview
Impact of qualified nursing education on self-care and disease knowledge in heart failure patients
Authors: Ayed S
Published: November 2023

Purpose

Guidelines on management of heart failure patients support intensive patient education on self-care. To evaluate the short and long-term impact of a structured education by a qualified heart failure nurse on patient´s self-care and disease knowledge.

Methods

131 patients (66±12 years) hospitalized for heart failure participated in a structured one hour education program by a heart failure nurse. Patients completed a questionnaire consisting of 15 questions, nine of the European Heart Failure Self-Care Behaviour Scale (EHFScB-9) and additionally six questions on the patient´s disease knowledge 1 day before, 6 months and 12 months after the education course. Possible responses ranged from 1 (complete agreement) to 5 (complete disagreement). Clinical events during the 12 months follow-up period were determined. Factors predicting with potential impact on the teaching effect were evaluated. Seven patients refused further participation during follow-up, 13 patients were lost during follow-up, and one patient was excluded from the study due to progressive dementia.

Results

Nine patients died during the study and 33 patients had recurrent hospitalization for heart failure. EHFScB-9 scale improved from 24.0±7.2 at baseline to 17.0±7.4 (p<0.001) at 6 months, and 17.2±6.1 (p<0.001 vs. baseline) after 12 months. Concerning the disease knowledge score, it improved from 17.9±5.3 at baseline to 12.1±4.3 (p<0.05) at 6 months follow-up, and to 12.0±5.5 (p<0.05) at 12 months after education. Scores to individual questions prior to education ranged from 1.2±0.8 on adherence to the medication protocol to 2.7±1.4 on everyday weighting habits. Greatest improvement after education were obtained on reaction to weight gains (-1.9±1.3), daily weight control (-1.6±1.4) and knowledge on the reason of patient’s heart failure (-1.6±1.2). The NYHA-classification improved from 2.8±0.8 before teaching to 2.2±0.7 (p<0.001) at 12-months follow-up. No predictor of an insufficient teaching effect could be defined. Patients with a clinical event (death, recurrent hospitalization) had a combined EHFScB-9 and disease knowledge score of 32.6±8.1vs. 28.9±9.9 in those patients without a clinical event. Patients with more than one hospitalization due to acute decompensated heart failure during the follow-up period express insignificant improvement of the combined EHFScB-9 and disease knowledge score immediately after the education session.

Conclusions

A qualified nurse education program improves self-care behaviour and patient´s disease knowledge with a persisting effect at 6 and 12 months follow-up. There are no patient characteristics which preclude the implementation of an educational session.
Association of clinical outcomes and the use of telemetry monitors in patients with advanced heart failure
Authors: Saffi M , Silva Cruz R , Rodrigues Ilha V , Severgnini Eugenio C , Machado Pires Lemos D , Regina Da Luz K , Fantin S , Pereira De Souza L , Rejane Rabelo-Silva E
Published: November 2023

Background

Telemetry is a remote technology transmitted by radio frequency that sends patients' electrocardiographic signals in real-time, through a Bluetooth wireless network to a monitor located in a cardiovascular intensive care unit (ICU). This device is indicated for patients admitted in hospital clinical units that need monitoring (24 hours) for previous history or risk of developing cardiac arrhythmias. Patients with advanced heart failure often receive inotropic/antiarrhythmic drugs in the cardiovascular ICU. When clinically stable, this type of patient can be discharged from the cardiovascular ICU and monitored remotely in hospital clinical units using telemetry.

Purpose

We aimed o evaluate the clinical profile of patients with telemetry and to associate those with advanced heart failure who receive inotropic/antiarrhythmic drugs with unfavorable composite outcomes (death or cardiac arrhythmia).

Methods

Retrospective cohort study. Telemetry records were collected by nurses from the cardiovascular intensive care unit of a public university hospital. The study period was from January 2020 to May 2022. All the procedures in this study were in accordance with the Helsinki Declaration and approved by the Institutional Ethics Committee.

Results

In a sample of 703 patients, the mean (±SD) age was 63.4 ± 14.4 years, predominantly male 452 (64.3%). The median stay of the monitored patients was 4 (2-7) days. Among the monitored patients, regarding telemetry indications, patients diagnosed with advanced heart failure who receive inotropic/antiarrhythmic drugs had a prevalence rate of 12.8%. Of these, 32 (35.6%) had at least 1 complication, identified by telemetry, related significantly to unfavorable composite outcomes (P<0.001). All these patients who had the event identification through telemetry received immediate assistance by the cardiovascular intensive care team.

Conclusion

The use of telemetry in patients with advanced heart failure who receive inotropic/antiarrhythmic drugs admitted to hospital clinical units was associated significantly with unfavorable composite outcomes. The early detection of clinical outcomes might be useful in decision-making and in reducing major complications.