bluuebunny/crossref_metadata_2025 huggingface dataset:
Amiodarone and the risk for pulmonary fibrosis. A Danish nationwide study
Authors: Al-Abbasi B , Haxha S , Storgaard A , Kober L , Gislason G , Torp-Pedersen C H , Bang C
Published: November 2023

Background

Amiodarone may cause pulmonary fibrosis. However, very few studies have investigated this possible association. This study will evaluate whether amiodarone is associated with pulmonary fibrosis, and furthermore, if there is an exposure-response relationship.

Method and results

Using Danish national patient registries, we conducted an observational population-based study. Individuals diagnosed with pulmonary fibrosis were identified between 1996 and 2020 using ICD codes and then included in a nested case-control study, where cases were matched with 5 controls.

The exposure to amiodarone was defined by dispensed amiodarone recipes from the national prescription registry. Cox regression analysis was used to derive the crude hazard ratio (HR) and the confidence interval (CI). The analyses were also adjusted and stratified for pre-specified comorbidities to derive multivariate Hazard ratio. Furthermore, we analysed the outcome in respect to amiodarone exposure time (<3 months, 3-6 months, 6-12 months, 1-3 years, 3-5 years, over 5 years) and also in respect to the cumulative dosage.

A total of 27 948 cases diagnosed with pulmonary fibrosis over the 24 years period of study in Danish population were matched with 139 740 controls. The average age was 69 years and 45% was females.

We found that amiodarone treatment was associated with significant risk of pulmonary fibrosis (HR: 4.20, 95%CI: [3.83-4.60], p<0.001). After adjusting for comorbidities including hypertension, diabetes mellitus, asthma, chronic obstructive pulmonary disease, ischemic heart disease, heart failure, stroke, any cancer, liver failure, chronic kidney disease, and alcohol, the association remained significant (HR:2.55, 95%CI: [2.30-2.82], p<0.001) (Figure 1), and its remained also significant after excluding COPD patients from the population (HR: 3.93, 95%CI: [3.50-4.40], p<0.001). Finally, the treatment exposure relationship, 0-3 months (HR:2.34, 95%CI [1.82-3.02], p<0.001), and over 5 years (HR: 5.90, 95%CI [4.56-7.65], p<0.001) (figure 2), and dose response relationship, 0-18gm (HR: 2.48, 95%CI: [1.93-3.18], p<0.001), 120-240gm (HR: 4.34, 95%CI: [3.46-5.45], p<0.001), and over 840gm (HR: 7.06, 95%CI: [3.08-16.15], p<0.001) (figure 3).

Conclusion

Amiodarone use was found associated with an independent incident pulmonary fibrosis, 4-fold crude risk and with a more than 2-fold hazard already within the first 3 months of treatment. The association showed also a dose- and duration relationship, where larger doses and longer treatment were associated with higher hazard of pulmonary fibrosis.
Optimal adherence threshold to non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation to reduce the risk of thromboembolism and death
Authors: Grymonprez M , Steurbaut S , Capiau A , Vauterin D , Van Vaerenbergh F , Mehuys E , Boussery K , De Backer T L , Lahousse L
Published: November 2023

Background

Poor adherence to non-vitamin K antagonist oral anticoagulants (NOACs) may raise thromboembolic risks in patients with atrial fibrillation (AF). However, the minimal adherence to maintain the protective effects of NOACs is currently unknown.

Purpose

To investigate thresholds of NOAC adherence in association with thromboembolic and mortality risks.

Methods

Using two Belgian nationwide healthcare databases, AF patients ≥45 years old with ≥1 NOAC prescription claim between January 1st, 2013 and January 1st, 2019 were identified. Patients were followed from NOAC initiation until the first occurrence of the investigated outcome, treatment discontinuation (>60-day supply gap), switch to VKAs, death, emigration or end of the study period. Adherence was measured using the proportion of days covered (PDC) after one year of treatment. Inverse probability weighted Cox regression (adjusting for 39 confounding covariates) was used to investigate outcomes (identified using International Classification of Diseases-coded hospital discharge diagnoses and medical procedure codes) between NOAC users with a one-year PDC of 100% (reference group) and NOAC users with lower PDCs.

Results

A total of 92,111 newly-treated AF patients were included during a mean follow-up of 2.7 ± 1.4 years (250,750 person-years of on-treatment follow-up). The proportions of persistent NOAC users with a PDC of 100%, 95-99%, 90-94%, 85-89%, 80-84% and <80% after one year of treatment were 62.7%, 17.4%, 9.5%, 5.1%, 2.8% and 2.5%, respectively. Compared to NOAC users with a one-year PDC of 100%, significantly higher risks of stroke or systemic embolism were observed among NOAC users with PDCs of 85-89% (adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) (1.19-1.54)), 80-84% (aHR 1.31, 95%CI (1.08-1.58)) and <80% (aHR 1.64, 95%CI (1.34-2.01)), while no significant differences were observed among NOAC users with one-year PDCs of 95-99% (aHR 1.02, 95%CI (0.94-1.12)) or 90-94% (aHR 1.06, 95%CI (0.95-1.18)) after multivariable adjustment. Significantly higher risks of all-cause mortality (aHR 1.09, 95%CI (1.01-1.17) and major or clinically relevant non-major bleeding (aHR 1.10, 95%CI (1.04-1.16) were observed with decreasing levels of NOAC adherence, starting from NOAC users with a one-year PDC of 90-94% versus 100%. Findings were similar with once-daily and twice-daily dosed NOACs.

Conclusion

Lower adherence to NOAC treatment is associated with increased risks of thromboembolism, all-cause mortality and bleeding. For adequate stroke prevention in AF, the optimal adherence threshold to NOAC treatment should be at least 90%, irrespective of the dosing regimen of NOACs.Figure 1
Outcomes with oral anticoagulation resumption or discontinuation after an anticoagulation-related event in patients with atrial fibrillation
Authors: Denas G , Gennaro N , Ferroni E , Zorzi M , Pagliani L , Pengo V
Published: November 2023

Background

There are uncertainties on the resumption of anticoagulation therapy in patients with non-valvular atrial fibrillation who experience a thrombotic or haemorrhagic event while on oral anticoagulation.

Purpose

We assessed the cumulative incidence of recurrent stroke, major bleeding and all-cause mortality associated with restarting antithrombotic treatment, after stroke or major bleeding during anticoagulation therapy for atrial fibrillation.

Methods

We included anticoagulated patients with atrial fibrillation that were discharged (2013-2020) from hospital for stroke, intracranial haemorrhage (ICH), and major bleeding. To adjust for competing risk of death and reduce confounding, we started the follow up after 120-days blanking period, counting events in patients resuming oral anticoagulation versus those that did not. Risks of all-cause mortality, thromboembolism, intracranial haemorrhage, and major bleeding were estimated with multivariable Cox proportional hazard models and propensity score to adjust for differences in baseline characteristics.

Results

1029 patients (mean age 77 years) were included in the final cohort: 23% were ischemic stroke, 18% were ICH, and 59% major bleeding; of these, 77% resumed anticoagulation. Among patients with stroke as the index event (92% resumed anticoagulation) the cumulative incidence of events was significantly lower in patients resuming therapy (HR 0.2, 95%CI 0.1-0.4, p<0.01). In patients with ICH (64% resumed therapy) the cumulative incidence of events was lower in patients resuming anticoagulation (HR 0.4, 95%CI 0.2-0.7, p<0.01). Same was true for patients with major bleeding, with patients resuming therapy (76%), experiencing fewer events (HR 0.5, 95%CI 0.2-0.7, p<0.01). In the multivariable analysis considering age, sex and propensity score as covariates, resumption of anticoagulation significantly reduced the cumulative event rate (HR 0.5, 95%CI 0.4-0.6, p<0.01).

Conclusion

In patients with atrial fibrillation who experienced an anticoagulation-related event, resuming oral anticoagulation was associated with better outcomes for all-cause mortality and subsequent events as compared with patients who did not resume treatment.Stacked Area Charts and Cox regression
Predicting thrombus outcome during anticoagulation for left ventricular thrombus
Authors: Yang Q , Liang Y A N , Zhu J U N , Quan X I N
Published: November 2023

Background

Up to 22% of embolizations have been linked to left ventricular (LV) thrombosis. Oral anticoagulation (OAC) for at least 3 months is recommended for patients with LV thrombus, according to guidelines. The purpose of this study was to predict the resolution of thrombus in patients with LV thrombus who were taking OAC for 3 months.

Methods

We enrolled patients prospectively from 2020 to 2022 and retrospectively from 2013 to 2019 at a national center of cardiovascular diseases in China. Patients with a history of LV thrombus < 3 months were included. Eligible patients were administered OAC and scheduled for 3 months of follow-up visits. The primary efficacy outcome was the rate of thrombus resolution at 3 months. Safety outcomes and major cardiovascular adverse events were collected. The hazard ratio (HR) and 95% confidence intervals (CIs) were estimated with adjustment for covariates using Cox regression models.

Results

We identified a total of 380 eligible patients. The median age was 53 (41, 63) years and 310 (81.6%) patients were male. The main underlying etiologies were dilated cardiomyopathy (51.6%). 204 (53.7%) patients received non-vitamin K antagonist oral anticoagulants (NOACs) while the rest were on warfarin within 3 months. In multivariable analysis, patients with NOACs had a higher likelihood of thrombus resolution than those taking warfarin (HR 1.39, 95% CI 1.08 – 1.79, P = 0.011). Lower LV ejection fraction levels and smaller diameter or thickness of thrombi were also the dominant predictors of thrombus resolution followed by a faster heart rate, a higher white blood cell count, therapy of diuretics, beta-blocker, and parental anticoagulation during hospitalization (eight variables, all P < 0.05). At 3 months, 29 patients (7.6%) suffered major cardiovascular adverse events, including 26 emboli and 3 deaths. One patient (0.3%) experienced an ISTH major bleeding.

Conclusions

Patients with systemic anticoagulation and positive treatment for heart failure achieved a greater rate of thrombus resolution at 3 months. The option of oral anticoagulation might be favorable NOACs, and further randomized controlled studies are warranted to explore.Forest plot of multivariable analysis.
Comparison of baseline characteristics and outcomes of on-label full dose (20mg) and off-label reduced dose (15mg) rivaroxaban in patients with atrial fibrillation in Asian elderly patients
Authors: Kim J Y , Kim J , Park S J , Park K M , Kim J S , On Y K
Published: November 2023

Introduction

In ROCKET-AF trial, rivaroxaban 20mg was on label dose and dose reduction criteria for rivaroxaban is creatinine clearance (CrCl) less than 50ml/min. Some Asian countries using reduced doses label compared with other global regions according to the J-ROCKET trial.

Purpose

The aim of this study was to assess the patients characteristic and outcomes of on-label full dose rivaroxaban and off-label reduced dose rivaroxaban in Asian elderly patients.

Methods

This study is a multi-center, prospective, non-interventional observational study to evaluate the efficacy and safety of rivaroxaban in atrial fibrillation patients older than 65 years old with or without renal impairment.

Results

A total of 1098 patients (mean age 72.8±5.8 years, 691[62.9%] males) was included and 265 patients received on label full does (20mg) rivaroxaban and 560 patients received off label reduced dose (15mg) rivaroxaban. Off label group showed older, more female patients, lower body weight, impaired CrCl and higher CHADS-VASc score. There showed no significant differences between two groups in major and minor bleeding, stroke and net-clinical outcomes.

Conclusions

Physicians prefer to prescribe off-label reduced dose rivaroxaban in patients with older and frail patients in Asia real world practice. There showed no differences in outcomes in these patients. Off label 15mg of rivaroxaban might be consider in specific populations.
Comparison of Antithrombotic Regimens after Left Atrial Appendage Occlusion: A Systematic Review and Network Meta-analysis
Authors: Carvalho P E P , Gewehr D M , Miyawaki I A , Nogueira A , Felix N , Nascimento B R , Garot P , Darmon A , Mazzone P , Preda A , Kubrusly L F , Cardoso R
Published: November 2023

Background

The optimal antithrombotic therapy following left atrial appendage occlusion (LAAO) in patients with non-valvular atrial fibrillation (AF) remains uncertain.

Purpose

This network meta-analysis aimed to compare the efficacy and safety of various antithrombotic strategies after LAAO.

Methods

We conducted a comprehensive search of MEDLINE, Cochrane, Embase, and ClinicalTrials.gov databases for studies that reported outcomes after LAAO, stratified by the antithrombotic therapies administered at discharge. Direct oral anticoagulants (DOACs), vitamin-K antagonists (VKAs), single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), DOAC plus SAPT, VKA plus SAPT, and no antithrombotic therapy were analyzed. We performed a frequentist random-effects model network meta-analysis to estimate the odds ratio (OR) with 95% confidence intervals (CI) for each strategy. The surface under the cumulative ranking curve (SUCRA) P-scores provided a ranking of treatments. Quality assessment and risk of bias were conducted in accordance with Cochrane recommendations.

Results

We included 39 studies comprising 10,573 patients with non-valvular AF. As shown in Figure 1, in the network comparison, DAPT (OR 0.33; 95% CI 0.14-0.73), DOAC (OR 0.31; 95% CI 0.11-0.84), DOAC plus SAPT (OR 0.15; 95% CI 0.03-0.68), and VKA (OR 0.29; 95% CI 0.10-0.87) were superior to no therapy in preventing device-related thrombosis (DRT). There was no significant difference between the therapies analyzed in terms of major bleeding (Figure 2). In the SUCRA analysis, DOAC plus SAPT had the highest probability of being the best strategy for preventing DRT, followed by VKA and DOAC monotherapies, respectively. DOAC monotherapy was associated with the lowest probability of major bleeding, followed by DOAC plus SAPT and VKA as monotherapy, respectively.

Conclusion

In patients with non-valvular AF undergoing LAAO, post-discharge therapy with DOAC as monotherapy reduces the incidence of DRT compared with no therapy and is associated with a lower probability of major bleeding compared with other therapies.Figure 1.DRTFigure 2.Major bleeding
Repeat coronary revascularization in high-risk patients treated with ticagrelor monotherapy after PCI: Insights from the randomized TWILIGHT trial
Authors: Spirito A , Baber U , Sartori S , Moliterno D J , Kastrati A , Collier T , Gibson C M , Vogel B , Angiolillo D J , Pocock S , Cohen D J , Escaned J , Sardella G , Dangas G , Mehran R
Published: November 2023

Background

Repeat revascularization after percutaneous coronary intervention (PCI) remains a major concern, even though its impact on mortality is limited. The effect of ticagrelor monotherapy vs. standard dual antiplatelet therapy (DAPT) on this outcome is unclear.

Aim

To assess the impact of ticagrelor monotherapy vs. DAPT on repeat revascularization after PCI.

Methods

In the TWILIGHT trial, high-risk patients who were event-free and adherent to a ticagrelor-based DAPT for 3 months after PCI were randomized to ticagrelor plus aspirin or ticagrelor plus placebo for 12 additional months. In this post-hoc analysis, the primary endpoint was repeat revascularization due to recurrent or persistent symptomatic myocardial ischemia. Secondary endpoints included target lesion revascularization (TLR), target vessel revascularization (TVR) and major adverse cardiac and cerebrovascular events (MACCE) and net adverse clinical events (NACE) (Figure). All endpoints were adjudicated and assessed at 12 months after randomization in the per-protocol population.

Results

Among 6,759 patients, ticagrelor monotherapy and ticagrelor plus aspirin were associated with a similar risk of repeat revascularization (7.1% vs 6.7%, HR 1.07, 95% CI 0.89-1.29), TLR, TVR and MACCE (Figure), while NACE was lower with ticagrelor monotherapy.

Conclusion

In high-risk patients undergoing PCI, ticagrelor monotherapy after 3 months of ticagrelor plus aspirin was associated with similar rates of recurrent coronary revascularization and MACCE and a lower risk of NACE compared with continued DAPT.
Long-term outcomes of beta-blocker use in elderly patients without left ventricular systolic dysfunction after percutaneous coronary intervention for acute myocardial infarction
Authors: Choe J C , Lee S H , Ahn J H , Park J S , Lee H W , Oh J H , Choe J H , Lee H C , Cha K S , Jeong M H
Published: November 2023

Background

The use of beta-blocker for elderly patients without left ventricular systolic dysfunction (LVSD) after percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) was uncertain. Additionally, limited data was available on long-term outcomes of beta-blocker use in elderly patients who have undergone PCI for acute MI and without LVSD.

Purpose

We aimed to investigate the long-term clinical benefit of beta-blocker use in elderly patients underwent PCI for acute MI and without LVSD.

Methods

Among 13104 patients with acute MI who have undergone PCI in a nationwide, prospective, and real-world registry, 2566 elderly (defined as ≥70 years) patients without LVSD (defined as EF <50%) were included. 2063 patients were prescribed with beta-blocker, and 503 patients were not. The major adverse cardiac events (MACE; cardiac death, recurrent MI, any revascularization, readmission due to heart failure [HF], stroke, or definite/probable stent thrombosis [ST]) and the components of MACE were compared in multivariable Cox regression, propensity score (PS) matched, and underwent PS-adjusted analyses.

Results

During a median follow-up of 998 days, MACE, all-cause death, and cardiac death occurred in 560 patients (21.8%), 374 patients (14.6%), and 224 patients (8.7%), respectively. The beta-blocker group had significantly lower rates of MACE (entire: 20.9% vs. 25.4%, hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.58-0.76, p=0.03; PS-matched: n=986, 20.3% vs. 25.8%, HR 0.69, 95% CI 0.61-0.78, p<0.001), all-cause death (entire: 12.9% vs. 21.5%, HR 0.55, 95% CI 0.44-0.69, p<0.001; PS-matched: 11.8% vs. 20.9%, HR 0.58, 95% CI 0.47-0.72, p<0.001), and cardiac death (entire: 7.7% vs. 13.1%, HR 0.54, 95% CI 0.41-0.72, p<0.001; PS-matched: 7.3% vs. 13.5%, HR 0.57, 95% CI 0.43-0.79, p<0.001) than the no beta-blocker group. There were no significant differences in the risks of recurrent MI, any revascularization, readmission due to HF, stroke, and definite/probable ST between the groups. The lower risk of MACE in the beta-blocker group than in the no beta-blocker group was consistently observed in the subgroup analyses. In patients ≥80 years, beta-blocker versus no beta-blocker groups showed the reduced rates of MACE, all-cause death, cardiac death, recurrent MI, any revascularization, readmission due to HF, stroke, and definite/probable ST, but insignificantly.

Conclusions

We showed that from nationwide registry, the use of beta-blocker was associated with improved long-term clinical outcomes compared to the no use of beta-blocker in elderly patients without LVSD after PCI for acute MI.outcomes
Genome-wide association study of amidoarone-induced hypothyroidism
Authors: Rand S , Olesen M S , Ostrowski S R , Sorensen E , Pedersen O B , Bundgaard H , Ghouse J
Published: November 2023

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 across several organ systems. As many as 10-20% of all patients treated with amiodarone develop thyroid dysfunction, most commonly amiodarone induced hypothyroidism (AIH). (1)

Purpose

We examined if AIH may have a genetic predisposition.

Methods

We conducted the first genome-wide association study of AIH using data from a large biobank. Cases were defined as individuals who within one year of amiodarone initiation were given a diagnosis of hypothyroidism or treated with thyroid hormone replacement. Controls were defined as individuals who were continuously treated with amiodarone, without any history of hypothyroidism. Odds Ratios (ORs) and 95% confidence intervals (CIs) were computed using logistic mixed model regression.

Results

In total, we identified 339 cases of AIH and 2,296 amiodarone-treated controls (Table 1). We found two risk loci, residing at chromosome 9q22.33 and 20p11.21. The lead variant at the first locus, rs9696968-G, was an intron variant located in PTCSC2 (OR: 2.32; 95% CI 1.91 – 2.83, P = 8.17 × 10-18). The other lead variant, rs1543443-A, was located 82 kb upstream to FOXA2 and was at borderline genome-wide significance (OR 1.77, 95% CI 1.44 – 2.19, P = 5.19 × 10-8; Figure 1). The locus in PTCSC2 is a top hit in thyroid cancer (OR 1.69) and hypothyroidism (OR 1.3). (2) FOXA2, a critical transcription factor, is recognized in mice for its role during development, in regulation of mature tissues, and once mutated also involved in cancer. (3)

Conclusions

We found two risk loci located in PTCSC2 and FOXA2 that were significantly associated with AIH, but replication is needed in order to confirm these associations. Indeed, it seems that individuals with genetic susceptibility to hypothyroidism are more likely to develop AIH, hence the PTCSC2 locus is a known high impact rick locus for hypothyroidism. These findings add to the potentials of pharmacogenetics in cardiology.

Cases are individuals with hypothyroidism within one year after initiation of amiodarone therapy. Controls are disease free individuals who are continuously taking amiodarone.

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). Each novel locus is presented in red color. The dotted line marks the threshold for genome-wide significance.Table 1.Characteristics of study group.Figure 1.Manhattan plot of amiodarone induced hypothyroidism.
Finasteride effectively attenuates the impairments of left ventricular function and cardiac sympathovagal balance in both aging and obese male rats via reducing systemic oxidative stress
Authors: Apaijai N , Pintana H , Saengmearnuparp T , Chattipakorn S C , Chattipakorn N
Published: November 2023

Background

Cardiovascular diseases are commonly found in the elderly and obese population manifested by left ventricular (LV) dysfunction and impaired cardiac sympathovagal balance. Finasteride (FIN), a 5-alpha reductase inhibitor (5-ARI), is a universal prescription for patients with benign prostatic hyperplasia (BPH). Since BPH is commonly found in obesity and aging, it is essential to investigate whether FIN could have an impact on the LV function and cardiac sympathovagal balance in either elderly or obese conditions.

Purpose

We tested the hypothesis that impaired LV function and cardiac sympathovagal balance are observed in aging and obese conditions, and FIN improves these parameters through a reduction of systemic oxidative stress in both aging and obese male rats.

Methods

Twenty-four male Wistar rats (aged 8 weeks old) were randomly divided into 3 groups (n=8/group) to receive one of the followings: 1) normal diet (ND) feeding, 2) ND feeding with D-galactose injection (150 mg/kg/day, subcutaneous injection, 18 weeks) for creating an aging model, and 3) HFD feeding for 18 weeks for creating an obesity model. At week 13, rats in each group were divided into 2 subgroups (n=4/subgroup) and received either a vehicle (drinking water) or FIN (5 mg/kg/day) via oral gavage. At the end of treatment, echocardiography was performed to assess LV function, and the heart rate variability (HRV) was determined to quantify cardiac sympathovagal balance. The blood was collected, and serum was used to determine serum malondialdehyde (MDA) levels as a marker of systemic oxidative stress.

Results

At week 13, D-galactose injection successfully induced aging as indicated by increasing cardiac p53 protein expression. HFD also caused obesity in those rats as indicated by increased body weight and visceral fat weight. LV dysfunction (as indicated by reduced %LVEF and %LVFS) and cardiac sympathovalgal imbalance (as indicated by an increased LF/HF ratio) were observed in both models (Figure 1A-C). This functional impairment was associated with an increased MDA levels (Figure 1D). Treatment with FIN successfully reduced cardiac sympathovagal imbalance in both models (Figure 1C); however, an improvement of LV function was found only in aging rats-treated with FIN (Figure 1A, B). Consistent with a reduction of cardiac sympathovagal imbalance, FIN decreased systemic oxidative stress in both models (Figure 1D).

Conclusions

FIN effectively improved cardiac sympathovagal balance in rats under both aging and obese conditions. However, FIN reduced LV dysfunction only in aging rats. Interestingly, FIN did not affect these cardiac parameters in normal healthy rats. These findings suggest the cardioprotective potential of FIN in both aging and obese populations.
Statin use is associated with a lower risk of mortality in patients with malignant breast cancer treated with anthracyclines. A global federated health database analysis
Authors: Bucci T , Gue Y , Dobson R , Palmieri C , Pignatelli P , Cross M , Lip G Y H
Published: November 2023

Introduction

Anthracyclines (ANT are a key component in the treatment of early breast cancer but are associated with an enhanced oxidative stress which is associated with f short- and long-term adverse events. Statins are a well-known class of lipid lowering agent with anti-inflammatory properties that could potentially counteract ANT toxicity in cancer patients.

Purpose

To assess the potential therapeutic benefit of statins among malignant breast cancer patients treated with ANT.

Methods

Retrospective study utilizing a global federated health research network (TriNetX). Patients with malignant breast cancer (ICD code C50) treated with ANT were categorized in two groups: statin users (at least 1 month before the ANT treatment); and non-statin users. The primary outcome was the 5-year risk of all-cause death. Secondary outcomes were the intra-treatment (within 6 months), post-treatment (6 months-1 year) and long-term (1 year-5 years) risk of-all cause death. A further sensitivity analysis was done to assess the risk differences between hydrophilic (rosuvastatin and pravastatin) and lipophilic (atorvastatin, simvastatin, lovastatin) statins. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM).

Results

Amongst the 36,770 patients with breast cancer identified (mean age 60±12.6 years, 98.6% female): 6,616 (17.9%) were statin users and 30,154 (81.1%) were non-statin users. Statins users were older and had more cardiovascular risk factors. After PSM, the 5-year risk of all-cause death was significantly lower in statin users (HR 0.72, 95%CI 0.63-0.83) compared to non-statins users. Analyzing the different time frames, the lowest risk of all-cause death was observed in the early period after the ATN treatment (Figure 1). The 5-year all-cause death was reduced in both the hydrophilic (HR: 0.69, 95%CI 0.58-0.83) and lipophilic statins (HR 0.72, 95%CI 0.65-0.79), when compared to non-statins users (Figure 2), with no significant differences between these two statin types (p=0.496).

Conclusion

Statin use was associated with a reduced risk of all-cause death in breast cancer patients treated with ATN. Further studies are needed to clarify the mechanism(s) by which statins counteract the ATN toxicity.
Mortality, cardiovascular disease and long covid at 3 months in individuals hospitalized with covid-19- a whf study
Authors: Sliwa Hahnle K , Nikhare K , Singh K , Raspail L , Banerjee A , Pinto F , Narula J , Pineiro D , Perel P , Prabhakaran D
Published: November 2023

Background

COVID-19 pandemic presents a number of unpredictable and long-lasting challenges. Understanding the short- and long-term effects of COVID-19 infection is crucial for better planning of preventive and management strategies for future pandemics. This study aims to determine short- and long-term clinical sequelae among COVID-19 hospitalized patients across low-middle-, upper-middle and high-income countries.

Methods

This global, multi-centre, prospective cohort study across 16 countries aimed to recruit 3300 patients hospitalized with COVID-19. We evaluated persistent long COVID symptoms, re-admissions, death, cardiovascular disease complications, new onset hypertension or diabetes, reinfection with COVID-19, vaccination, quality of life and costs at 1, 3, 6, 9-12-months post-hospital discharge using a standardized questionnaire over the phone. We are reporting interim descriptive analysis including demographic characteristics and short-term (3-month) clinical sequelae among COVID-19 hospitalized patients.

Results

We present baseline characteristics and follow-up data for 1,474 patients at the 3 months visit after hospital discharge. The patients were predominantly Asian (97%), male (55%) with a mean age (SD) of 56 (19.6) years and from low- and middle-income (82%), upper middle-income (4%) and high-income (14%) countries. 60% of the patients had received 2 doses of COVID-19 vaccination. 92% patients had fever and 90% had cough when admitted to hospital. More than one-third of patients (38%) reported at least one long COVID-19 symptom. Most commonly reported long COVID-19 symptoms were fatigue (22%), memory impairment, concentration, or decision-making (15%), and feeling more anxious (11%). Nearly half of the patients reported mild fatigue (46%) and 8% had severe fatigue. Less than 1% of patients reported loss of smell or taste. Most commonly reported post-discharge complications (new onset illnesses) were pulmonary embolism (8%), kidney involvement (2%) and new onset hypertension (1%). A quarter of patients reported problems in self-care, and 7%-12% patients reported pain or mobility issues or anxiety/depression. At 3-month follow-up, 3% of the patients had died and the most common causes of death were sudden cardiac arrest (33%), liver dysfunction/end stage renal disease (31%) and stroke or respiratory illness (13%).

Conclusions

Three months after hospitalized COVID-19, our interim analysis revealed a 3-month mortality rate of 3% mostly due to sudden cardiac arrest, liver dysfunction, stroke and respiratory diseases (relatively higher compared to studies from other regions). Patients commonly reported persistent symptoms, such as fatigue, memory/concentration impairment, and anxiety. Further, long-term follow-up data will guide health policies to prevent and manage long COVID sequelae worldwide.Table 1Figure 1
Educational intervention to improve self-care behaviours for heart failure patients who develop renal insufficiency
Authors: Al Kalaldeh M
Published: November 2023

Background

Renal insufficiency is common in adults with heart failure. Promoting heart failure self-care behaviours contributes to avoid poor prognosis of acute kidney injury.

Aims

To introduce a nurse-led educational program for patients with heart failure who suffer from acute kidney injury and asses its impact on patients' perception and self-care behaviours.

Methods

In this pretest-posttest interventional study, patients were assessed for their perception and self-care behaviours before and after enrolling in an educational program.

Results

Among fifty patients, ages means were 51.16 years old (SD=5.35). Based on New York Heart Association (NYHA), 62% of patients had class II and IV symptoms, and 76 % had mild to moderate decrease in estimated Glomerular Filtration Rate. In the pre-education assessment, moderate deficits were present in both perception and self-care behaviours. After delivery of self-care education, patients demonstrated an improvement in perception (t: 3.65, df: 49, SE: 0.34, p<0.001, CI: 0.61-2.19), and self-care behaviours (t: 8.66, df: 49, SE: 1.05, p<0.001, CI: 7.02-11.18). In multivariate analysis, the educational program explained 68.1% of the variation in posttest self-care behaviours scores.

Conclusion

Education on self-care behaviour improved the perception and self-care of patients with heart failure who suffer from evolving acute kidney injury.
Health care professionals most relevant phrases used in a digital medical translation tool in 24-7 communication with minority speaking heart surgery patients during hospitalization
Authors: Lie I , Rokeness S , Hasle C H , Johannsen N , Skredsvik K , Nes L S
Published: November 2023

Background/Introduction

Health care professionals’ communications with hospitalized minority speaking heart patients are even in 2023 still frequently limited to non-verbal language, notes from informal caregivers and "google translate" in situations where interpreters are not available. Health care based digital solutions aiding translation may help improve health care professionals’ assessment, information about and treatment of minority speaking patients, and there is an urgent need for innovative research into this area.

Purpose

To describe the most relevant phrases used by health care professionals’ in a digital, medical translation tool for 24-7 communication with minority speaking heart surgery patients during hospitalization.

Methods

A digital medical translation tool was customized using the internationally recognized ABCDE (Airway, Breathing, Circulation, Disability, Exposure) systematic approach to assess and treat, in addition with the pre-operative surgical safety checklist employed as a framework. Health care professionals’ use of phrases in the digital tool when communicating with the minority speaking heart surgery patient’s during their clinical hospital pathway (Figure 1) were then counted, categorized, and finally linked to health care professionals’ actions.

Results

Fifty-five health care professionals (i.e. registered nurses, intensive care nurses, operating room nurses, anaesthesia nurses and physiotherapists) were during 60 shifts with 24-7 follow-up of five minority speaking heart surgery patients using a total of 410 phrases from the digital medical translation tool. The phrases were categorized and counted into the ten most common categories (Figure 2): 1. Pain (e. g. are you in pain?), 2. Nutrition (e. g. are you hungry?), 3. Respiration (e.g. breathe in), 4. Mobilisation (e.g. you have to get up and stand), 5. Psychological support (e.g. the surgery went well), 6. Safe surgery (e.g. do you have any teeth that are loose?), 7. Medications (e.g. pain relievers), 8. Communication (e.g. just answer "yes" or "no"), 9. Examination (e.g. you are going to have an x-ray examination), 10. Circulation (e.g. do you feel dizzy?). Health care professionals’ actions (i.e. assessment, information and reassurance, and instructions) were categorized and related to these phrases.

Conclusions

A health care based digital medical translation tool can aid in communication with minority speaking patients in situations when interpreters are not available. This study shows how health care professionals’ use of such a translation tool when communicating with minority speaking heart surgery patients during hospitalization can employ phrases and categories 24-7 to improve patients’ healthcare.Fig.1 Clinical pathwayFig.2 HCP communication
Novel PVC detection algorithm in an implantable cardiac monitor for longitudinal risk monitoring
Authors: Dukes J , Marmerstein J , Kondama Reddy R , Whittington H
Published: November 2023

Background

Guideline therapy is recommended in patients with frequent premature ventricular contractions (PVCs). Longitudinal monitoring of the PVC burden can effectively guide treatment options, stratify patient risk, and manage HF progression. Implantable cardiac monitors (ICMs) may provide a suitable long-term diagnostic tool to monitor PVC burden and guide clinical therapy.

Objective

Quantify the performance of a novel QRS morphology and timing-based PVC detection algorithm as implemented for an ICM.

Methods

The algorithm utilizes self-adapting timing-based ectopy detection and dynamic measures of QRS morphology to identify unifocal and multifocal PVCs. The training dataset consisted of 200 sECG episodes recorded in implanted BIOMONITOR (BM) devices, collected from 48 patients. The algorithm was then evaluated on 227 sixty-second duration sECG episodes from 79 BM patients in the CERTITUDE registry. Each beat was adjudicated as normal, PVC, or PAC by at least two clinical experts. In a total of 22,433 beats, 756 true PVCs were assessed (3.4% PVC prevalence). Overall, patient averaged, and generalized estimating equation (GEE) estimates for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated, as well as patient-specific PVC burden (PVCs/Total Beats).

Results

Patient-averaged PVC detection sensitivity was 73.8%, with a PPV of 89.2%, specificity of 99.6%, and NPV of 99.1%. Using a GEE model to adjust for multiple episodes per patient, the algorithm achieved detection sensitivity of 66.6±9.8% (95% CI) and PPV of 86.6±6.5%, with specificity of 99.5±0.4% and NPV of 99.0±0.5%. The main reasons for missed PVC detections were morphological similarities to normal beats, insufficient prematurity, or lack of a compensatory pause. Additionally, the algorithm faithfully represented the PVC burden, with a median difference of -0.24% between the PVC burden calculated by the detection algorithm and the adjudicated burden. Algorithm burden was highly correlated with the true PVC burden for each patient, with a Pearson correlation coefficient of 0.80 (p < 0.0001).

Conclusions

The PVC detection algorithm was highly specific, achieving a specificity of 99.6% and a sensitivity of 73.8%, and accurately representing the overall PVC burden for each patient. This PVC detection algorithm would provide a valuable clinical diagnostic marker to monitor PVC burden trends to guide therapy as well as assess the longitudinal risk of HF. Measurement of PVC burden combined with the 5.5-year longevity of the BIOMONITOR ICM could provide an innovative approach to optimize clinical management of patients.Example PVCs detected by the algorithm
Examining the real-world up-titration of heart failure therapy and treatment related factors limiting optimisation in Irish nurse-led heart failure clinics
Authors: Lehane M , Farrell C , Burke E , Nugent C , Molloy A , Aherne J , Corrigan R , Howley C , Mcnally C , Murphy C , Fall S , Maher S , Thorpe R , Mcgovern N , Caples N
Published: November 2023

Introduction

The potential of guideline-directed heart failure therapy to reduce mortality and morbidity in HF patients is tremendous however real-world data indicates sub-optimal up-titration to target doses. Challenges to optimisation include patient-related factors, treatment related factors and service-related factors. The observational QUALIFY Study reported a prescription rate of 87.8% for ACEI's/ARB's, 86.9% for Beta-blockers and 70.3% for MRA's.

Purpose

To examine the real-world pattern of up-titration and maximisation of four pillars of HF therapy to maximum doses in Irish Nurse-led HF Clinics in comparison to recent observational/registry studies and to highlight the main treatment related factors limiting optimisation.

Methods

A cross sectional prospective audit over a 3-month period was carried out in 18 HF centres in Ireland. Ethical approval was sought and granted in all centres. Patients included in the audit were those with HFrEF that achieved optimal tolerated dose of betablocker, ARNI/ACE-I, MRA and SGLT2I during the period of the audit.

Results

The audit included 648 participants, 499 (77%) male and 147 (23%) female (2 unknown). Average age of male was 68.5 years old and female was 68.7 years old.

The rate of prescription for ARNI and ACEi/ARB was 93.8% (n=608), 65% (n=420) of patients were prescribed ARNI, ACEi were prescribed for 147 (22.6%) and ARB’s for 41 (6.3%) patients respectively. Hypotension was a limiting factor in 22.4% (n=146) of cases.

Over 608 (93.6%) patients received a beta-blocker to maximum tolerated dose and 6% (n=40) did not receive a beta-blocker. Hypotension was a limiting factor for 77 (11.8%) patients, followed by fatigue in 15 (2.3%) of patients.

84% of patients received an MRA and 97 (14.9%) patients did not received an MRA. Hyperkalaemia was a limiting factor in 51 cases (7.8%), followed by chronic kidney disease in 32 cases (4.9%) and hyponatraemia in 6 cases (0.9%).

Only 13.2% (n=86) of patients did not receive an SGLT2 and 86.8% were prescribed an SGLT2. Urinary tract infection was reported in 13 cases (2%), CKD preluded prescription in 7 patients (1%) and fungal infection occurred in 3 cases (0.4%).

Conclusion

A strong commitment to optimising heart failure therapy is evident in Irish nurse-led clinics. Prescription rates for patients optimised were 93.8% for ARNI/ACE/ARB, 93.6% for BB, 84% for MRA and 86.8% for SGLT2. This has surpassed target doses seen in observation studies. Future audits will examine the impact of nurse prescribing on the achievement of optimal target doses.
Allied health professional-physician collaboration to enhance guideline-directed medical therapy of heart failure: expanding therapeutic opportunities
Authors: Khaykin Y , Pirbaglou M , Yang J , Gao-Kang J , Giuria J , Pandher M , Garber D , Dell E , Shamiss Y
Published: November 2023

Background

Guideline-directed medical therapy (GDMT) is the cornerstone of treatment for heart failure patients with reduced ejection fraction (HFrEF). Optimization of GDMT at a targeted allied professional medication titration clinic represents a key opportunity to provide greater access to care and further refine patient care models, leading to improvements in clinical outcomes.

Purpose

To evaluate the effectiveness of an allied health practitioner optimization clinic model in HFrEF as indicated by changes in rates of triple and quadruple GDMT therapy (see associated table).

Methods

Qualified patients were either: proactively screened from clinic lists, having demonstrated a diagnosis of heart failure, reduced ejection fraction, and not receiving triple or quadruple therapy, or were physician-referred after initial optimization during 2021-2022. Participants subsequently underwent medication review and optimization by an allied health professional, involving introduction, up-titration, down-titration, or withdrawal of medications across relevant medication classes as tolerated.

Results

52 (78.8% male) patients with a mean age of 70.3 (11.4) years and mean ejection fraction of 30.1 (6.7) percent underwent medication optimization. Along with HFrEF, all patients exhibited cardio-metabolic multi-morbidity (2-3 cardio-metabolic diagnoses), including hypertension (59.6%), dyslipidemia (71.2%), coronary artery disease (61.5%), atrial fibrillation (42.3%), and type 2 diabetes (21.2%). Pre-optimization prescription rates ranged from: 53.8% for ACEi/ARB, 30.8% for ARNI, 80.8% for beta-blockers, 59.6% for MRA, 40.4% for diuretics, and 13.5% for SGLT2i. Medication review and optimization spanned an average of 2.8 (1-7) meetings, and lead to an average of 1.9 (range 0-4) medication changes. Among 49 patients considered for ARNI optimization, there were 43 (87.7%) successful introductions and progressive dose adjustments, including 12 (27.9%) dose adjustments among those already prescribed. Additional changes involved optimizations in: beta-blockers (5 introductions, 5 dose-changes), MRA (8 introductions, 4 dose-changes, 2 withdrawals), diuretics (1 introduction, 7 dose-changes, 2 withdrawals), and SGLT2i (17 introductions). Collaboration between allied health professionals and physicians in optimization demonstrated significant improvements in rates of triple (42.3% vs 63.5%, P= 0.003) and quadruple (5.8% vs 26.9%, P= 0.001) therapy post-optimization.

Discussion

A Collaborative approach to medication optimization increased the use of GDMT in ambulatory patients with HFrEF. Collaboration presents both clinicians and health systems with greater opportunities to improve healthcare access, therapeutic inertia, and disease management.Pre-post Changes in GDMT Rates
Improving frequency and appropriateness of direct oral anticoagulant (DOAC) prescribing for af through integrated pharmacy-led care
Authors: Turner E , Stirling K , Donley M
Published: November 2023

Background

Anticoagulants for stroke-risk reduction in atrial fibrillation (AF) are underutilised and international literature shows 10-25% of patients on a direct oral anticoagulant (DOAC) for AF are prescribed an inappropriate dose, increasing the risk of stroke and bleeding. NHS England targets are for 90% high-risk AF patients to be prescribed anticoagulation by 2029.

Purpose

A new pharmacy-led integrated care model was developed to improve the frequency and quality of prescribing and monitoring of DOACs for AF in line with national guidance. This abstract describes the results when this model of care was rolled out across a large UK city.

Methods

The integrated model of care was designed to provide a multi-pronged approach and empower primary care pharmacy teams to prescribe and manage DOACs for AF. The model includes an education and training programme, a weekly specialist-run virtual clinical discussion service, a 48-hour turn around advice and guidance service and a clinical tool that identifies and makes recommendations for patients on an unlicensed dose of a DOAC.

Results

16,594 patients are included on the city’s AF register. From April-November 2022, an additional 1,339 (8%) patients were anticoagulated. An increase from 76.3% to 84.3% of patients on the AF register. Dosing as per manufacturers Summary of Product Characteristics (SmPC) improved for all DOACs. In April 2022 an incorrect dose was prescribed for 10%, 15% and 12% of patients respectively on apixaban, edoxaban and rivaroxaban. In November 2022 incorrect dosing reduced across the board to 7%, 8% and 7% of patients respectively. 914 patients prescribed an inappropriate dose had their dose adjusted to meet SmPC recommendations based on relevant characteristics (renal function, age, weight, serum creatinine, interacting medicines). Monitoring according to local guidelines also increased. Experience of staff was overwhelmingly positive and demonstrated growth in knowledge, skills, and activity amongst primary care pharmacy teams. Rapid access to specialist support allowed patients to be managed close to home.

Conclusions

This integrated care model improves frequency and appropriateness of DOAC prescribing for patients with AF. The model results in incorrect dosing lower than any described in international literature. The service model is sustainable and scalable, grows cross-sector clinical leadership and develops relationships between primary and secondary care. The next steps are to roll this model out across a large region.