bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of oral anticoagulants on the incidence of dementia in patients with atrial fibrillation: a systematic review and meta-analysis
Authors: Latif F , Nasir M M , Meer K K , Farhan S H , Cheema H A , Khan A B , Umer M , Rehman W U , Ahmad A , Khan M A , Almas T , Mactaggart S , Nashwan A J , Ahmed R , Dani S S
Published: October 2024

Background

Atrial fibrillation (AF) is a common cardiac arrhythmia, with dementia being an increasingly recognised complication of this. Treatment with oral anticoagulant (OAC) therapy may be protective in developing this complication.

Purpose

This meta-analysis aims to investigate the validity of this hypothesis, whilst additionally exploring the effect of specific OAC medication subtypes on the incidence of dementia.

Methods

A comprehensive search of MEDLINE and Embase for relevant studies reporting the efficacy of OAC therapy for the incidence of dementia in patients with AF was conducted from its inception until March 2023. This included observational studies that reported odds ratio, risk ratio and hazard ratio for adult AF patients. Studies including patients with prior OAC use or prior history of dementia were excluded. Statistical analysis was performed using a random-effects model to calculate the pooled hazard ratio and their corresponding 95% confidence interval for all outcomes. Subgroup analyses were also performed according to the study design, presence of observational window, and prior history of stroke in patients.

Results

A total of 13 studies were included in the study. Although the heterogeneity was high in all comparisons, we demonstrated that OAC usage lowered the risk of developing dementia in AF patients when compared to the non-OAC cohort. Looking more specifically at medication subtypes, direct oral anticoagulants (DOACs) and vitamin K agonists (VKA) were both effective in reducing the likelihood of AF patients developing dementia when compared to non-OAC treatments.

Conclusion

Our meta-analysis confirms that administration of OAC and its subtypes (VKA and DOAC) are effective pharmacotherapies in managing dementia in patients with AF. These findings have important clinical implications for the management of AF patients and highlight the need for further investigation of the protective effects of OAC therapy on cognitive decline. Future research should explore the long-term effects of OAC therapy on cognitive function in AF patients.
Direct oral anticoagulants or warfarin in patients with left ventricular thrombus: a meta-analysis of randomized clinical trials
Authors: Maqsood M , Zhang R , Bangalore S
Published: October 2024

Background/Introduction

There are limited randomized controlled trials (RCTs) data on the use of direct oral anticoagulants (DOAC) versus warfarin in patients with left ventricular (LV) thrombus. Current AHA and ESC guidelines recommend oral anti-coagulants (either DOAC or warfarin) for 3 to 6 months without any preference.

Purpose

We aimed to compare outcomes with DOACs versus warfarin in patients with LV thrombus.

Methods

A comprehensive literature search was performed from inception to 02/01/2024 of the PubMed database. RCTs of adult patients comparing DOAC to warfarin were evaluated for mortality, major bleeding, stroke, and LV thrombus resolution. Meta-analytic Odds ratio (OR) with 95% confidence intervals (CI) were calculated using DerSimonian-Laird method.

Results

From 100 studies, four RCTs with 188 subjects (95 DOAC and 93 warfarin) were included with mean age of 53.4 years, 69.5% males, and mean follow up 5.03 months. There was no difference in mortality (OR= 0.67 [95% CI 0.15-3.06]; p=0.60; I2=0%; 3 trials), stroke (OR= 0.46 [95% CI 0.09-2.44]; p=0.37; I2=0%; 4 trials), major bleeding (OR= 0.43 [95% CI 0.12-1.55]; p=0.20; I2=0%; 4 trials), and LV thrombus resolution (OR= 1.33 [95% CI 0.45-3.95]; p=0.61; I2=0%; 2 trials) with use of DOAC compared to warfarin (Figure Panel A to D). Overall, there was no evidence of publication bias using either funnel plot or eggers test (p > 0.05).

Conclusions

In this meta-analysis of 4 RCTs, there was similar efficacy and safety of DOAC and warfarin in patients with LV thrombus. However, the evidence is limited by small sample size with lesser precision in the estimates. Future large-scale trials are needed to confirm these findings.
Edoxaban for stroke prevention in routine practice patients with atrial fibrillation with and without atherosclerotic disease: a post-hoc sub-study of ETNA-AF-Europe
Authors: De Vries T A C , De Groot J R , Hemels M E W , Komen J J , Steffel J , Weiss T , De Asmundis C , Kirchhof P , De Caterina R
Published: October 2024

Background

Patients with atrial fibrillation (AF) and concomitant coronary and peripheral artery disease (CAD and/or PAD) have an increased risk of adverse health events compared to those without such atherosclerotic disease. The annual risks of major adverse cardiovascular outcomes for these patients treated with edoxaban in routine clinical practice remain uncertain.

Purpose

To determine the clinical characteristics and rates of key adverse events over multiple years of follow-up in patients with and without atherosclerotic disease (defined as CAD and/or PAD).

Methods

This is a post-hoc sub-study of ETNA-AF-Europe, a multinational, prospective cohort study on unselected patients with AF treated with edoxaban. In total, 13,164 (97%) of the 13,632 patients who provided informed consent were included in this substudy. The included patients were followed for a total of 48 months. Data were collected at baseline and yearly thereafter (±2 months). The present analysis compared baseline clinical characteristics (n [%] or mean [SD]) and clinical outcomes (events per 100 patient-years [%/year] with 95% confidence intervals [95% CI]) by CAD/PAD status at baseline.

Results

Of the 13,164 patients included in the analysis, 2973 had CAD and/or PAD (n=2762 CAD only). Patients with atherosclerotic disease were older (75.3 years vs 73.2 years), had higher CHA2DS2-VASc scores (3.8 vs 3.0) and HAS-BLED scores (2.8 vs 2.4), and more frequently received the reduced dose of 30 mg edoxaban than those without CAD/PAD (30.2% vs 21.0%) (Table). Cardiovascular comorbidities were in general more prevalent in those with atherosclerotic disease vs those without.

Rates of stroke or systemic embolism (0.89%/year, 95%-CI 0.72–1.09 vs 0.59%/year, 95%-CI 0.52–0.68), myocardial infarction (0.73%/year, 95%-CI 0.58–0.92 vs 0.25%/year, 95%-CI 0.20–0.30), and cardiovascular (1.56%/year, 95%-CI 1.33–1.83 vs 0.85%/year, 95%-CI 0.76–0.95) as well as all-cause death (5.96%/year, 95%-CI 5.50–6.46 vs 3.56%/year, 95%-CI 3.37–3.77) were higher for patients with CAD/PAD vs those without such atherosclerotic disease (Figure).

Conclusion

Annual rates of thromboembolic and bleeding events were low for AF patients treated with edoxaban in routine practice. The higher rates of thrombotic and bleeding events in patients with CAD/PAD are most likely caused by differences in baseline intrinsic risks. Nonetheless, these differences, particularly the threefold higher rate of myocardial infarction, warrants further investigation.Baseline Characteristics
Characterisation of the pharmacokinetic and pharmacodynamic relationship of milvexian in total knee replacement patients
Authors: Zhou W , Bozenhardt E , Merali S , Zannikos P , Back H , Ajavon-Hartmann A , Strony J , Plotnikov A , Chintala M , Goyal N , Samtani M
Published: October 2024

Background

Milvexian, an oral factor XIa inhibitor, is currently being evaluated in patients at risk for thrombotic events due to atrial fibrillation, ischaemic stroke, or acute coronary syndrome. The exposure-response relationship between clinical efficacy and safety endpoints and milvexian pharmacokinetic (PK) metrics was recently submitted as a separate publication. Characterisation of the relationship between the coagulation pharmacodynamic (PD) markers versus milvexian PK metrics at the patient level has yet to be reported.

Purpose

This analysis characterised the relationship between the coagulation biomarkers, activated partial thromboplastin time (aPTT) and prothrombin time (PT), and milvexian systemic exposure in patients undergoing total knee replacement (TKR) evaluated in the AXIOMATIC-TKR study.

Methods

A population pharmacokinetic (PopPK) model was previously developed and characterised the PK of milvexian in TKR patients well. The PK/PD relationships between observed aPTT and PT versus PopPK model estimated time-matched milvexian plasma concentrations via nonlinear mixed effects modeling. The relationship between key clinical safety endpoints (e.g., any bleeding or clinically relevant non-major bleeding) and individual PD marker change (e.g., aPTT ratio to baseline) was also explored.

Results

The aPTT increased with increasing plasma concentration of milvexian over the range of doses evaluated in the study (25mg QD to 200mg BID). An Emax type of model reasonably characterised the PK/PD relationship between the aPTT and model predicted time-matched milvexian plasma concentration, which is consistent with previously observed relationships in healthy volunteers. No change was observed in PT with increased milvexian exposure. No obvious relationship was identified between any (including clinically relevant non-major) bleeding and aPTT ratio to baseline.

Conclusions

Increased milvexian exposure is directly correlated with aPTT prolongation over the range of doses evaluated in the TKR study. There was no obvious relationship between any (including clinically relevant non-major) bleeding and aPTT ratio. The PK/PD relationship of aPTT without a parallel relationship in PT distinguishes milvexian, a FXIa inhibitor, from previously studied FXa inhibitors. These analyses were a complementary component in dose selection for the milvexian Phase 3 program.

Figure 1. PK/PD relationship between aPTT (left) and PT (right) and estimated time-matched plasma concentration (AXIOMATIC-TKR study)
Comparative effects of different antiplatelet strategies in carriers of CYP2C19 loss-of-function alleles: a network meta-analysis
Authors: Galli M , Occhipinti G , Benenati S , Laborante R , Ortega-Paz L , Franchi F , D'amario D , Frati G , Biondi-Zoccai G , Sciarretta S , Angiolillo D J
Published: October 2024

Background

Carriers of cytochrome 2C19 (CYP2C19) loss of function (LoF) alleles treated with clopidogrel have impaired drug metabolism resulting in reduced active metabolite levels, high platelet reactivity (HPR), and an increased risk of thrombotic events. Several alternative antiplatelet therapies have been proposed to overcome HPR in these patients, but their comparative effects remain poorly explored.

Purpose

To assess the comparative effects of different alternative antiplatelet agents in carriers of CYP2C19 LoF alleles undergoing percutaneous coronary interventions (PCI).

Methods

Randomized controlled trials (RCTs) comparing different oral antiplatelet therapies in carriers of CYP2C19 LoF alleles undergoing PCI were included. A frequentist network meta-analysis was conducted to estimate mean difference (MD) or odds ratios (OR) and 95% confidence intervals (CI). The primary outcome was platelet reactivity assessed by VerifyNow and reported as P2Y12 reaction unit (PRU). The secondary outcome was the rate of HPR as defined in each trial. Standard-dose of clopidogrel (75 mg daily) was used as reference treatment. Antiplatelet strategies were ranked according to P-scores, ranging between 0 (poor performance) and 1 (good performance).

Results

A total of 13 RCTs testing 6 alternative strategies (i.e., clopidogrel 150 mg, prasugrel 3.75 mg, 5 mg, and 10 mg, ticagrelor 90 mg bid, and adjunctive cilostazol 100 mg bid) were included in the network. Compared with standard-dose clopidogrel, the greatest reduction in PRU was observed with prasugrel 10 mg (MD -128.61; 95% CI -145.09; -111.49) and ticagrelor 90 mg bid (MD -125.61; 95% CI -170.66; -80.56), followed by prasugrel 5 mg (MD -118.03; 95% CI -143.15; -92.92) and prasugrel 3.75 mg (MD -73.00; 95% CI -108.97; -37.03). High-dose clopidogrel was associated with a modest (MD -32.11; 95% CI -51.33; -12.90) and adjunctive cilostazol with a non-significant (MD -44.11; 95% CI -98.05; -9.82) reduction in PRU compared with standard-dose clopidogrel (Figure 1). Rates of HPR were reduced with all treatments compared with standard-dose clopidogrel. Ranking of treatments for the primary endpoint showed that standard-dose prasugrel ranked as the best treatment (P-score=0.884), followed by ticagrelor (P-score=0.835), low-dose prasugrel (0.767), very-low dose prasugrel (P-score=0.474), cilostazol (P-score=0.306), high-dose clopidogrel (P-score=0.224), and standard-dose clopidogrel (P-score=0.009) (Figure 2).

Conclusion

Among carriers of CYP2C19 LoF alleles undergoing PCI, standard-dose prasugrel or ticagrelor are most effective in reducing platelet reactivity, followed by reduced-dose of prasugrel, while double-dose clopidogrel and adjunctive cilostazol showed only modest effects. The clinical implications of these pharmacodynamically effective strategies warrant further investigation.
A novel formula to assess the QT interval in ventricular paced rhythm
Authors: Almasri A , Werner C , Gieres C , Ukena C , Boehm M , Abdin A
Published: October 2024

Background

QT interval measurement in the presence of right ventricular pacing (RVP) represents a clinical challenge due to altered ventricular activation resulting in a prolonged QT-interval. The aim of this study is to compare the QT interval in patients before and after ventricular pacing to develop a new formula for QT interval assessment in patients with RVP.

Methods and results

All patients presenting to our pacemaker clinic with single- or dual chamber device were included in this prospective observational study. Inclusion criteria were no permanent right ventricular stimulation, an intrinsic QRS interval of <120 ms, and ventricular rate >35 bpm and <150 bpm. Three 12-lead electrocardiograms were recorded for each patient: during intrinsic rhythm and 2 following an atrial paced and a ventricular paced QRS at the same rate. The intrinsic QRS and QT time/JT time (QTi/JTi) were measured during intrinsic and subsequent RVP. To obtain the formula, all measurements were performed on 100 patients (mean age 74 ± 11.3, male 33%) (RV apical lead 30% and non-apical lead 70%). Based on our measurements, a new formula QT (non-paced) = 139.23 + 0.55 xQT (paced) was derived. A population of 482 individuals (mean age 75.5±13.2 years (SD), 64% male) with permanent RV pacing were used as a validation group. The intrinsic QRS and QT time were measured during SR and subsequent RVP. To assess the relationship between the predicted QT with RVP and the measured QT without RVP, linear correlations analyses were performed. Our formula had a strong correlation with the irrespective QT without RVP (r=0.50)

Conclusion

We proposed a new simple formula to accurately estimate QT during RVP. This formula can be easily utilized in clinical practice.

Figure 1: MAD characteristic value via plots stands for Median Absolute Difference (i.e. by how many ms the prediction is estimated on average).

Figure 2: "Forest Plot" illustrates the correlation coefficients in the form of a forest plot. The dot r represents r and the bars the 95% confidence intervalsMAD characteristic value via plots standForest Plot" illustrates the correlation
Pretreatment with dual antiplatelet therapy in acute myocardial infarction
Authors: Motovska Z , Hlinomaz 0 , Kala P , Benesova K , Mrozek J , Hromadka M , Muzafarova T , Precek J , Matejka J , Tomasov P , Bis J , Cervinka P , Vodzinska A , Hrabos V , Jarkovsky J
Published: October 2024

Background

Combined antithrombotic therapy prevents thrombus progression and its components embolization, and thus, it has an essential role in coronary microcirculation (re)perfusion in acute myocardial infarction (AMI). Pretreatment with P2Y12 inhibitors, on top of aspirin, before primary angioplasty has not been satisfactorily studied in STEMI.

Purpose

To investigate the impact of combined antiplatelet therapy on-treatment on the outcome of patients with STEMI.

Methods

Patients who suffered STEMI during the 7 years (1/2016-12/2022) were included. The analysis is based on population data from the National Health Information System (NHIS). Information on AMIs from the Intervention Module of the Registry of Cardiovascular Operations and Interventions was combined with prescription data from the Registry of Reimbursed Health Services 6 months before MI and identification of deceased patients from the Registry of Death Records. Data from the NHIS covers almost 100% of all cases in the population. Standard descriptive statistics and test were applied in the analysis. Multivariate logistic regression adjusted for clinical and procedural characteristics was adopted to analyze the influence of pretreatment on the risk of 1) out-of-hospital cardiac arrest (OHCA), 2) clinical condition at admission – need of mechanical ventilation and circulatory instability (Killip III,IV), 3) initial TIMI flow through the infarct-related coronary artery (IRA ), and 4) short term mortality.

Results

The study sample consisted of data from 40,383 STEMIs of which 1,601 patients were on dual antiplatelet therapy (DAPT) with aspirin plus iP2Y12 lasting 1 to 6 months before the event occurred. Patients on chronic oral anticoagulation (N 2101) were excluded. Patients on DAPT versus those without antiplatelet therapy or on aspirin at a daily dose of 100 mg were older, had higher comorbidity rates, and were at higher risk of mortality (Table).

The multivariate logistic regression analysis showed that patients on DAPT at the time of MI onset and lasting for at least one month had a higher likelihood of preserved perfusion through the IRA (Odds ratio and 95% Confidence interval, OR (95% CI) 1. 193 (1.074; 1.326), p=0.001). However, the DAPT pretreatment did not reduce the risk of OHCA, the need for mechanical ventilation, or initial circulatory destabilization. It did not positively affect the prognosis of the patients (Figure ).

Conclusion

The significant benefit of the DAPT pretreatment on the preservation of infarct-related coronary artery flow did not translate into a positive effect on the prognosis of STEMI patients.
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

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

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

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 <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

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

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

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

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

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=<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.
Impact of atrial fibrillation on cardiac autonomic function in elderly patients
Authors: Haemmerle P , Schier J , Rizas K , Schlageter V , Aeschbacher S , Krisai P , Coslovsky M , Reichlin T , Moschovitis G , Conen D , Sticherling C , Osswald S , Bauer A , Kuehne M , Meyer-Zurn C
Published: October 2024

Introduction

Cardiac autonomic dysfunction has been linked to an increased risk of mortality (1), stroke and silent brain lesions (2) and cognitive impairment (3) in patients with atrial fibrillation (AF). However, the impact of AF on cardiac autonomic function is poorly understood.

Purpose

We aimed to explore the impact of AF on cardiac autonomic function by comparing AF patients with a matched control cohort without AF.

Methods

We enrolled patients with and without AF from two ongoing, prospective, multicenter cohort studies (Swiss-AF Cohort and Swiss-AF Control) if they had a high-resolution 16-lead resting ECG recording in sinus rhythm for a duration of 5 minutes at baseline visit. Cardiac autonomic function was quantified by periodic repolarization dynamics (PRD), a marker of repolarization instability associated with sympathetic activity. PRD was quantified by means of wavelet analysis, as validated previously (4). Cardiac autonomic dysfunction was defined present if PRD exceeded the established cut-off of 10.0 deg2 (5). We built multivariable adjusted linear and logistic regression models to explore the association of AF with PRD and cardiac autonomic dysfunction.

Results

We included 2077 patients, 1113 (54%) from the AF cohort and 964 (46%) from the matched non-AF cohort. Baseline characteristics were well balanced between the groups (mean age 71 vs. 73 years in patients with and without AF, mean CHA2DS2-VASc score 3.0 vs. 3.5, female sex 31.3% vs. 36.6%). The median PRD was 18.2 deg2 (IQR 9.9-25.4) in patients with AF and 15.8 deg2 (IQR 8.1 -23.0) in patients without AF (p<0.001, Figure). 832 (75%) of the AF patients suffered from cardiac autonomic dysfunction, vs. 656 (68%) of the non-AF patients (p<0.001). Multivariable adjusted linear regression analysis revealed an independent association of AF with continuous levels of PRD (beta-coefficient -1.57, 95% CI -2.64 - -0.488, p=0.004). Further, AF was independently associated with the presence of cardiac autonomic dysfunction (Odds Ratio 1.48, 95% CI 1.18-1.87, p<0.001, Table).

Conclusion

In this cross-sectional analysis of a patient population with and without AF, AF was independently associated with increased PRD values, reflecting sympathetic predominance, and with the presence of cardiac autonomic dysfunction. These findings implicate a relevant role of AF in the development of cardiac autonomic dysfunction in elderly patients.Figure
Shared care in heart failure management is linked with physical and mental health by perceived control in patient-caregiver dyads
Authors: Chung M L , Moser D K
Published: October 2024

Background

Patients with heart failure (HF) and their family caregivers have interdependent relationships in managing HF. Shared care within dyads refers to interpersonal interactions characterized by exchanging care and support in chronic illness management. High levels of shared care improve patients’ health outcomes, but it is unclear if shared care is equally beneficial for caregivers. Also unknown is how shared care contributes to the outcomes of both dyad members. We propose that perceived control may be critical in the link between shared care and health status for dyads. Thus, the purpose of this study was to determine whether perceived control over one’s health mediates the association between shared care and physical and mental health in patients with HF and their caregivers.

Method

Patients with HF and their primary caregivers (N=151 dyads) completed questionnaires in this cross-sectional study. Shared care, perceived control over one’s own health, and health status were assessed using the three subscales of the Shared Care Instrument (i.e., communication, decision-making, and reciprocity), the Cardiac Attitudes Scale-Revised, and the Medical Outcomes Study Health Survey-36, physical and mental health scales, respectively. A series of actor-partner interdependence models with mediation dyadic analyses were conducted.

Results

Patients with HF (mean age 60.3 Years, 64% male) and their caregivers (mean age 56.6 years, 75% female) reported similar levels of communication and reciprocity in shared care, but patients reported higher scores of decision-making in shared care than their caregivers (P < .001). Perceived control over one’s own health significantly mediated the association between communication and physical health (indirect actor effect = .1487; 95% CI: 0.0478 to 0.2759) and between communication and mental health (indirect actor effect = .1650; 95% CI: 0.0454 to 0.3260) for patients, not caregivers (Figures A1 & A2). Similarly, perceived control significantly mediated the association between reciprocity and physical and mental health for patients, not caregivers (Figures B1 & B2). Perceived control mediated the association of decision-making with physical health and mental health for caregivers, not patients (Figures C1 & C2).

Conclusion

Higher levels of communication and reciprocity increased patients’ perceived control, ultimately improving their physical and mental health, whereas caregivers’ decision-making improved their health by enhancing their perceived control over their health. The different patterns of shared care are linked to the health of patients and caregivers by enhancing perceived control over one’s health.Figure A & BFigure C