bluuebunny/crossref_metadata_2025_split huggingface dataset:
iRight4Me: individualisation of P2Y12 inihibitors in the realworld practice - an interim report
Authors: Makhnoon S M , Amirruddin S N A , Syed S S I , Sim S H W , Lim S L L , Chang G C , Kristanto W K , Ng R N , Liew L N , Teo V T , Tan D 
Published: October 2024

Abstract

Background
The uptake of CYP2C19 testing has been limited, as clinicians opined majority of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary interventions (PCI) should receive Ticagrelor per international guidelines. Remaining minority with high bleeding risk (HBR) would be on Clopidogrel from the outset. We set out to study how clinicians’ knowledge of CYP2C19 phenotype affects choice of P2Y12 inhibitors, and thus real-world clinical outcomes for ACS patients. We report the interim findings of bleeding at 6 months in the Ticagrelor-loaded subgroup.

Methods
Patients eligible for escalation or de-escalation were recruited into the study and tested for CYP2C19 polymorphism. CYP2C19 phenotype results and recommendations were revealed to outpatient clinicians, giving them the choice to keep or switch P2Y12 inhibitors. Bleeding outcomes were prospectively tracked and adjudicated by independent study team members.

Results
A total of 740 patients who have completed 6 months from index admission for ACS were used for this analysis. Overall adjudicated MACCE and bleeding rates were 3.46% (n = 27) and 12.7% (n=95) respectively. CYP2C19 Non-LoF (Loss-of-Function) patients who were de-escalated to Clopidogrel were least likely to bleed (Fig 1). Ticagrelor-only patients experienced almost twice the risk of bleeding than those who were de-escalated to Clopidogrel, regardless of phenotype status (15.1% vs 7.8%, Cox HR, p = 0.042). High bleeding risk (HBR) factors did not explain for differences in bleeding. The non-LoF patients on Ticagrelor (n = 173) experienced more than 2-fold risk of bleeding compared to those de-escalated to Clopidogrel (n = 71), adjusted HR 0.389, p = 0.059. MACCE rates were similar between these two groups at 2.41% for Non-LoF continued on Ticagrelor (n = 164) and 2.44% for Non-LoF switched to Clopidogrel (n = 81) respectively.

Conclusion
Our interim analysis shows that Ticagrelor is associated with significantly higher rates of bleeding which could be mitigated by de-escalation to Clopidogrel. Non-LoF patients who have been de-escalated to Clopidogrel could be at much lower risk of bleeding, without losing out on MACCE outcomes. CYP2C19 phenotype status has the potential to add more precision to decision-making. We expect to report final results of 1000 patients at the end of 12 months to fully assess the impact of phenotype-guided de-escalation on bleeding and MACCE.
Limited visibility and uptake of the clopidogrel pharmacogenomic guidelines among cardiologists
Authors: Venetucci L , Dello Russo C , Akintola A , Keavney B , Gagliardi D , Ramlogan R , Pirmohamed M 
Published: October 2024

Abstract

Background
Clopidogrel is an antiplatelet agent widely utilised in the treatment of acute coronary syndromes and following coronary interventions. Clopidogrel is a prodrug activated in the liver, mostly by cytochrome P450 2C19 that is encoded by a gene (CYP2C19). Variability in CYPC2C19 affects enzymatic activity and leads to variability in the activation and efficacy of clopidogrel. In 2011, the Clinical Pharmacogenetics Implementation Consortium (CPIC) produced the first set of detailed guidelines on the use of genetic testing to guide the clinical utilization of clopidogrel. Updates on these guidelines were published in 2013 and 2022. However, pre-prescription genetic testing is seldom performed.

Purpose
To establish whether these pharmacogenomics guidelines have visibility within the cardiovascular (CVD)community and have been incorporated into CVD guidelines.

Methods
(i) We examine the impact of the CPIC Clopidogrel guidelines released in 2013 and 2022 by looking at the citation patterns in CVD journals indexed in PubMed. (ii) We reviewed the guidelines released by the European Society of Cardiology and the American College of Cardiology on the management of coronary interventions and coronary artery disease over the last 15 years to establish whether CPIC guidelines are making any impact on practice.

Results
The CPIC 2022 guidelines were cited by 88 articles (49 journals) of which 13 citations (14.7%) appear in CVD journals. None of these citations are in the five major journals in which CVD guideline statements are most frequently published (Nature Review Cardiology, European Heart Journal, Circulation, Journal of the American College of Cardiology, and Journal of the American Medical Association - Cardiology). The 2013 guideline received 366 citations (183 PubMed journals). Of these, 47 were in cardiology journals (12.8%), but only 4 citations were in one of the same five major cardiology journals (2 in Nature Review Cardiology, 1 in Circulation and 1 in JAMA Cardiology). Of the 14 guidelines published by the ESC and ACC over the last 14 years, none cited the CPIC clopidogrel guidelines. Only 6 out of the 14 guidelines mentioned that the efficacy of clopidogrel was modulated by genetic factors but none of them included details or practical implications.

Conclusion(s)
Whilst sufficient time has not yet elapsed for the 2022 CPIC guidelines to have an impact on the specialist literature, the 2013 guidelines have had limited visibility within the CVD community. Undoubtedly, given the potential contribution of PGx, discussions on its uptakes are ongoing thus far, without resolution. Some considerations of clopidogrel genetics are diffusing into the specialty; however, from the citation evidence, it appears that CPIC clopidogrel guidelines of any vintage have had limited impact in terms of adoption and/or endorsement by cardiologists.
Potential use of pharmacogenetics in cardiology: genome-wide association studies of amiodarone-induced thyroid disorders
Authors: Rand S , Tragante V , Sorensen E , Ostrowski S R , Pedersen O B , Olesen M S , Bundgaard H , Ghouse J 
Published: October 2024

Abstract

Background
Amiodarone is a commonly prescribed antiarrhythmic drug used to manage supraventricular and ventricular arrhythmias. The use of amiodarone is associated with a broad range of adverse effects, including amiodarone-induced hypothyroidism (AIH) or amiodarone-induced thyrotoxicosis (AIT) (1). Both conditions are linked with increased mortality and have no known reliable risk predictors (2).

Purpose
We investigated the genetic underpinnings of amiodarone-induced thyroid disorders, and the clinical validity and utility of screening for genetic variants.

Methods
We conducted the first genome-wide association studies (GWAS) of AIH and AIT using data from three large biobanks. We compared the AUCs for SNPs identified through the above GWAS with polygenic risk scores for both hypo- and hyperthyroidism. Finally, we tested the clinical validity and utility of screening for risk variants.

Results
We found two risk loci for AIH. The lead variant at the first locus, rs1443438, was intronic to FOXE1 (OR 0.39, MAF = 35%, P = 1.59 × 10-42). The other lead variant, rs2209796, was located 93 kb upstream to FOXA2 (OR 0.56, MAF = 29%, P = 2.64 × 10-15: Figure 1). For AIT, we found one risk locus. The lead variant, rs2268803, was intronic to CAPZB (OR 1.81, MAF = 42%, P = 2.43 × 10-8: Figure 1). Next, we added GWAS SNPs or polygenic risk scores to risk prediction models consisting of age, sex and 4 principal components (PCs), and compared AUC estimates between risk models. Using GWAS SNPs, we found that the AIT variant increased the AUC with 6% (95%CI 1.1 – 10.3, AUC: 0.72) and 9% (95%CI 6.2 – 11.2, AUC: 0.75) for AIH, compared to the benchmark model. Both GWAS SNP models were superior to polygenic risk scores in terms of AUC (P for difference &lt;0.05). The positive and negative predictive value (PPV and NPV) for the AIT-variant was 14.6% and 95.7%, respectively. For the AIH-variants combined, we found a PPV of 17% and a NPV of 95%.

Conclusions
Common genetic variants are associated with both amiodarone-induced hypo- and hyperthyroidism and are at this point, superior to polygenic risk scores in predicting amiodarone-induced thyroid disorders. These findings add to the potentials of pharmacogenetics in cardiology.
Figure 1. Double Manhattan plot of amiodarone induced thyroid disorders.
The Y-axis is the negative log10 of the P-value for each single nucleotide polymorphism. The X-axis is the chromosome, with positions on each chromosome ranging from lower to higher (left to right). The dotted line marks the threshold for genome-wide significance. Amiodoarone-induced hypothyroidism at the top, and amiodarone-induced thyrotoxicosis at the bottom.Figure 1
Impact of allogenic Fecal Microbiota Transplantation (FMT) on lipid parameters in patients with metabolic syndrome (MetS): a meta-analysis
Authors: Wang L , Zhang L , Zhang Y , Li J P 
Published: October 2024

Abstract

Background
Metabolic Syndrome (MetS) has long been considered a formidable global health concern, and impaired lipid metabolism has been one of its crucial clinical manifestations. Fecal Microbiota Transplantation (FMT) has emerged as a potential therapeutic strategy for MetS, nevertheless, prior meta-analyses have not only yielded conflicting outcomes, but as well predominantly centered on glycemic parameters, leaving the potential impact of FMT on lipid metabolism remained unexplored.

Purpose
This meta-analysis systematically assessed the influence of allogenic FMT on lipid parameters in MetS patients, unraveling its potential as an innovative therapeutic modality for MetS.

Methods
A meta-analysis was performed to explore the impact of allogenic FMT on lipid parameters (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TCHO] and triglycerides [TG]) in patients with MetS. Terms regarding FMT and metabolic syndrome were searched in PubMed/Medline, EMBASE, Web of Science, the Cochrane Library, and Scopus from the inception of the databases until 31 August 2023. Ten randomized controlled trials (RCTs) were included and mean difference (MD) of parameters were pooled using a fixed effects model. Subgroup analyses according to follow-up durations were performed, and this study was registered in PROSPERO.

Results
A total of 532 patients in 10 studies were included. Patients undergoing allogenic FMT manifested significantly higher HDL-c level compared with control group (receiving placebo or autologous FMT, pooled MD 0.06 [95% CI: 0.02, 0.10]), and the result remained consistent in the subgroup with 4 to 6 weeks of follow-up (MD 0.07 [95% CI: 0.02, 0.10]). Though overall pooled result did not manifest a significant LDL lowering effect (MD -0.08 [95% CI: -0.21, 0.05]), in subgroup analyses, a significantly lowered LDL level was observed at 12 weeks of follow-up (MD -0.34 [95% CI: -0.60, -0.08]). No significant difference was observed between allogenic FMT and control group concerning TCHO ant TG levels regardless of lengths of follow-up.

Conclusions
An overall higher level of HDL-C and lowered LDL-C at 12 weeks of follow-up was observed in MetS patients receiving allogenic FMT. The results indicated that gut microbiota from lean, healthy donors may display a beneficial effect on modulating lipid metabolism in patients with MetS. Allogenic FMT manifested promising therapeutic impact and could serve as a viable intervention for MetS patients. Future large-scale RCTs are required for further validation.
Patient control preferences prior to discharge after cardiac surgery
Authors: Wynne R , Mctier L , Rowe C , Abbs M , Kerr D 
Published: October 2024

Abstract

Background
The impact of patient preferences and participation in the acute recovery period prior to discharge after cardiac surgery is not well understood. Although there is a plethora of literature describing pre and post discharge interventions to support patients’ recovery there is minimal evidence demonstrating the effectiveness of specific interventions that optimise recovery or patient preferences for participation in decision making related to this period of transition from hospital to home.

Purpose
The aim of this study was to explore patient preferences for participation in discharge planning.

Methods
This study took place in a major metropolitan hospital in Victoria, Australia with a population base of over 1 million people that provides over 100,000 episodes of care and approximately 850 cardiothoracic procedures annually. We recruited consecutive adult patients, able to understand and speak English who were being discharged home after cardiac surgery. Prior to discharge, a Registered Nurse conducted a semi-structured interview following patient consent where patients were asked to complete the 5 item Control Preferences Scale (CPS) in relation to 3 discharge planning questions. With each question patients were asked to rate their preferred and actual role in the decision-making process. The CPS has 5 cards each portraying a role in treatment decision making; active (1-2), collaborative (3) or passive (4-5) participation to determine what level of control patients’ desire in relation to their care.

Results
From 196 patients undergoing cardiac surgery 63 (32.1%) were eligible and agreed to participate. When asked about making plans for discharge 9 (14.3%) patients’ preference was to have an active role in this process, 25 (39.7%) preferred a collaborative approach and 29 (46.1%) a passive approach. Patients perceived their actual role was active (n = 10, 15.9%), collaborative (n = 17, 27.0%) or passive (n = 36, 57.1%). When asked about deciding when to go home 9 (14.3%) patients’ preference was to have an active role in this process, 18 (28.6%) preferred a collaborative approach and 36 (57.1%) preferred a passive approach. Patients perceived their actual role was active (n = 8, 12.7%), collaborative (n = 13, 20.6%) or passive (n = 42, 66.6%). When asked about their preferred role in deciding where they go when discharged 21 (33.4%) patients’ preference was to have an active role in this process, 19 (30.2%) preferred a collaborative approach and 23 (36.5%) a passive approach. Patients perceived their actual role was passive (n = 24, 38.1%), collaborative (n = 16, 25.4%) or passive (n = 23, 36.5%).

Conclusion
Patient preferences for control were congruous with their perceived experience of involvement in decision making which indicates patients’ preference for control is taken into account by clinicians managing the discharge planning process in this setting.
Peer support interventions improve disease self-management after coronary heart disease diagnosis: a systematic review and meta-analysis
Authors: Weddell J , Shi W , Redfern J , Buckley T , Gallagher R 
Published: October 2024

Abstract

Background
Patients with coronary heart disease (CHD) diagnoses often experience impacts on patient-reported outcomes (quality of life, depression, disease self-management and self-efficacy) at a time when secondary prevention is required. Peer support has proven benefits for these issues in many chronic conditions but synthesis of the evidence in CHD populations has not been undertaken.

Purpose
In this systematic review and meta-analysis, we aimed to explore the impact of peer support interventions on health-related quality of life, depression, anxiety, self-management and self-efficacy in CHD.

Methods
Electronic databases were searched from inception to November 2023 (MEDLINE, Embase, PsycINFO, CINAHL, Scopus, PubMed [non-MEDLINE], Web of Science, and the Cochrane Central Register of Controlled Trials). Randomised controlled trials (RCTs) evaluating peer support interventions (that enable experience sharing and/or support by others with the same condition) in populations with diagnosed CHD were eligible for inclusion. Risk of bias was assessed using the Cochrane risk of bias tool. Meta-analyses were undertaken in RevMan Version: 7.4.0 using the inverse variance method and a random effects model.

Results
In total, 16 papers reporting 14 unique RCTs were included. The total sample (n=1793) was 65% male with a mean age of 54.5±13.0 years. The diagnosis of the samples varied between studies, including coronary artery bypass graft(s), first time or newly diagnosed myocardial infarction and percutaneous coronary intervention. By 6-months follow-up, peer support interventions demonstrated no statistically significant improvements in health-related quality of life (SMD -0.38, 95% CI -1.84, 1.08), depression (SMD -0.09, 95% CI -0.26, 0.08) and anxiety (SMD -0.85, 95% CI -1.83, 0.14). Whereas, improvements occurred in disease self-management (SMD 1.49, 95% CI 0.66, 2.32) and self-efficacy in both short term (by 6-months, SMD 0.57, 95% CI 0.37, 0.77) and longer term (6-12 months, SMD 0.67, 95% CI 0.29, 1.05). Peer support interventions varied widely in format and several studies were of poor quality.

Conclusion
Peer support interventions benefit patient-reported outcomes of disease self-management and self-efficacy up to 6 and 12 months, but not for other patient reported outcomes after CHD diagnosis. More exploration is needed of content, delivery and focus of peer support interventions to maximise effectiveness for CHD secondary prevention.
Cognitive and physical fatigue: the experience and consequences of brain fog after spontaneous coronary artery dissection, a qualitative study
Authors: Weddell J , Rogerson M C , Gallagher R , Hesselson S , Iismaa S E , Graham R M , Jackson A C , Redfern J , Buckley T , Murphy B M 
Published: October 2024

Abstract

Background
Mild cognitive impairment (often subjectively referred to as "brain fog") and cognitive fatigue are common sequelae after acute coronary syndrome. However, little is known about the nature and impact of these experiences in spontaneous coronary artery dissection (SCAD) survivors.

Purpose
To understand if and how brain fog and cognitive fatigue are experienced following SCAD.

Methods
Participants were recruited from a larger SCAD genetics study database and were considered eligible if they had experienced SCAD within 12 months. Seven semi-structured online focus groups, with the primary aim of exploring psychosocial impacts of SCAD, were conducted between December 2021 and January 2022. Each focus group lasted for 1 hour 30 minutes and were led by investigators extensively experienced in qualitative research and cardiac rehabilitation. Interviews were digitally recorded, transcribed verbatim, and thematically analysed using Braun and Clark’s reflexive approach.

Results
Participants (n=30) had a mean age of 52.2±9.5 years and mostly female (n=27, 90%), partnered (n=27, 90%) and employed (n=27, 90%). Four main themes were identified: experiences of brain fog, perceived causes of brain fog, impacts of brain fog and coping with brain fog. Experiences of brain fog included memory lapses, difficulty concentrating and impaired judgement. Perceived causes of brain fog included medication, sleep deprivation and tiredness, and menopause and hormonal changes. The impacts of brain fog included rumination, changes in self-perception, disruption to hobbies and pastimes, and limitations at work. Coping mechanisms used for these challenges included reminders, setting expectations, being one's own advocate, making lifestyle adjustments, and support from peers.

Conclusion
Brain fog is commonly experienced by SCAD survivors and present challenges to normal life after SCAD. The impacts on daily life are varied, including those relating to self-perception and capacity to work. SCAD survivors reported difficulty understanding causes and found their own path to coping. Clinicians should be aware of these experiences as they are ideally placed to assist patients with these challenges.
Cardiovascular disease history as a predictor for adverse outcomes in frail older adults admitted to acute geriatric settings: 12-month outcomes from an Australian frailty registry
Authors: Mcdonagh J , Lindley R , Byth K , John R , Ferguson C 
Published: October 2024

Abstract

Introduction
Frailty is common in older adults with cardiovascular disease (CVD), with prevalence between 25-62% (1). The incidence of CVD increases with age, yet the outcomes of frail older adults with a history of CVD who present to acute geriatric settings, is not well understood.

Purpose
To report the association of CVD and rehospitalisation and/or mortality at 12 months in a cohort of frail older adults enrolled in an Australian frailty registry.

Methods
A convenience sample of participants enrolled in the frailty registry, with 12-month follow-up completed. The frailty registry is a prospective cohort study of adults admitted to the rehabilitation and aged care departments at two Australian hospitals. Frailty was assessed using the Clinical Frailty Scale (CFS), a score of 1-4 is ‘non-frail’, 5-6 is ‘mild-moderately frail’ and 7-9 is ‘severely frail’ (2). For this study, ‘CVD’ was defined as having a history of either heart failure, stroke, or atrial fibrillation. The cumulative incidence of first rehospitalisation and/or death during the first 12 months post discharge was estimated using one minus the Kaplan-Meier estimate of the survival function. Association between CVD (history of CVD, and type of CVD condition) and the composite endpoint were analysed. Adjusted Hazard Ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox models incorporating variables of interest and potential confounders.

Results
A total of 592 participants were included, median age was 82 years, 59% (n= 349) were female. The majority were frail with 50% (n= 295) classified as mild-moderately frail and 21% (n= 123) classified as severely frail. Almost half (45%, n= 265) had a history of CVD. The incidence of frailty (CFS score ≥5, mild-severely frail) was higher in those with CVD compared to those without CVD (76% vs 66%). A history of CVD was significantly associated with higher rate of first readmission or death within 12 months, compared to no history of CVD (p=0.017) (Figure 1). Of the three CVD conditions, heart failure was the only independent predictor of the composite endpoint (HR 1.60 [CI 1.14 -2.24], p=0.007). A CFS score of mild-moderately frail (HR 1.51 [CI 1.18 - 1.93, p=0.001) and severely frail were also independent predictors of the composite endpoint (HR 1.83 [CI 1.35- 2.48], p=&lt;0.001) (Table 1).

Conclusions
A history of CVD has a significant impact on adverse outcomes in frail older adults admitted to acute geriatric settings. Frailty according to the CFS was independently predictive of rehospitalisation and mortality in this cohort. Heart failure was the only independent predictor of the composite endpoint. These findings underscore the importance of identifying and addressing CVD and in the context of frailty, emphasising the need for targeted interventions to improve outcomes in this vulnerable population.Figure 1.Table 1.