bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating time in therapeutic range in post-acute myocardial infarction patients with left ventricular thrombus treated with vitamin K antagonist
Authors: Leow A S T , Teo Y N , Teo Y H , Goh F Q , Ho J S Y , Tan B Y Q , Yeo L L L , Li T Y W , Lee E C Y , Wong R C C , Chai P , Yeo T C , Chan M Y Y , Sia C H
Published: November 2023

Background

The standard of care for the treatment of post-acute myocardial infarction (AMI) patients with left ventricular (LV) thrombus is oral anticoagulation with vitamin K antagonist (VKA). Due to the narrow therapeutic range of VKA, patients require frequent monitoring. Adequacy of anticoagulation can be assessed by time in therapeutic range (TTR). This study aimed to evaluate the clinical characteristics and outcomes of post-AMI patients with LV thrombus treated with VKA, stratified by anticoagulation adequacy in terms of TTR ≥70% vs. TTR <70%.

Methods

Among 3000 consecutive echocardiogram results containing the keyword "thrombus" from December 2013 to August 2017, we identified 87 post-AMI patients complicated by LV thrombus and treated with VKA oral anticoagulation. Demographics, treatment including TTR, and outcome measures were analysed.

Results

The cohort was followed up for a median of 4.3 years (IQR 3.6 – 5.3). Patients with and without adequate anticoagulation had no significant differences in terms of age (p = 0.859), gender (p = 0.438), co-morbidities, LV ejection fraction (p = 0.638). A majority of post-AMI patients with LV thrombus treated with VKA had inadequate anticoagulation, as only 25.3% (n = 22) had TTR ≥70%. SAMe-TT2R2 score, a clinical predictor score for adequacy of anticoagulation, was high in the study cohort (median 4, IQR 3 – 5), with no significant difference between the two groups (p = 0.907). On multivariable analysis, TTR <70% was significantly associated with higher incidence of combined outcomes (presence of bleeding, stroke, or mortality) (HR 2.91 [95% CI 1.01 – 8.39], p = 0.048). Patients with TTR <70% had a higher cumulative incidence of bleeding events while on anticoagulation (p = 0.036), and a higher cumulative incidence of overall stroke on Kaplan-Meier analysis, but did not achieve statistical significance (p = 0.077). Patients with TTR <70% had a significantly higher cumulative incidence of combined outcomes (both while on anticoagulation and overall) compared to those with TTR ≥70% (p = 0.026, p = 0.017).

Conclusion

LV thrombus patients treated with inadequate VKA anticoagulation of TTR <70% had overall poorer outcomes compared to TTR ≥70%. Further studies are needed to evaluate anticoagulation adequacy in this population.
The effect of DOAC-Stop on lupus anticoagulant testing in patients with pulmonary embolism receiving direct oral anticoagulants
Authors: Klepczyk A , Zabczyk M , Papuga-Szela E , Undas A , Wypasek E
Published: November 2023

Background

Direct oral anticoagulants (DOACs) are widely used as first-line treatment for pulmonary embolism (PE) but may cause false positive lupus anticoagulant (LA) based on prolongation diluted Russell's viper venom time (dRVVT) or activated partial thromboplastin time (aPTT). Exclusion of antiphospholipid syndrome is recommended in PE patients since this disease requires warfarin, not DOACs.

Aims

We evaluated whether the use of DOAC-Stop, an agent reversing in vitro effects of DOACs, allows for reliable LA testing in PE patients on DOACs.

Methods

We assessed 172 consecutive PE patients aged 48 ± 14 years (50.6 % women) screened for antiphospholipid syndrome according to ISTH guidelines. Blood was collected 1–24 h since intake of a DOAC, i.e. rivaroxaban (n=81, 47.1%), dabigatran (n=53, 30.8%) and apixaban (n=38, 22.1%). LA testing was performed after DOAC-Stop (Haematex Research, Hornsby, Australia) treatment. Positive LA was reported when the normalized (patient/standard plasma clotting time) LA screening and screening (LA1)/confirmation (LA2) ratios exceeded 1.2.

Results

In screening tests after DOAC-Stop use, the dRVVT remained prolonged in 9 (5.2%) patients including 4 (44.5%) on apixaban, 3 (33.3%) on rivaroxaban and 2 (22.2%) on dabigatran, while the dRVVT LA1/LA2 ratio was abnormal in 7 (4.1%) subjects: 3 (42.9%) were on apixaban, 3 (42.9%) on rivaroxaban and 1 (14.2%) on dabigatran. In 2 (22,2%) patients the dRVVT LA1/LA2 ratio exceeded 2. The aPTT-LA screening test remained prolonged in 8 (4.6%) patients including 4 (50.0%) on apixaban, 2 (25.0%) on rivaroxaban and 2 (25.0%) on dabigatran, while the aPTT LA1A/LA2A ratio was abnormal in 5 (2.9%) patients: 3 (60.0%) on apixaban, 1 (20.0%) on rivaroxaban and 1 (20.0%) on dabigatran). In 1 (12.5%) patients the aPTT LA1/LA2 ratio exceeded 2.

Antiphospholipid syndrome with the presence of LA was diagnosed in 7 (87.5%) patients. False positive LA had 1 (0.6%) patients after the DOAC-Stop use.

Conclusion(s)

To our knowledge, this is the largest cohort of PE patients on DOACs evaluated for LA, with use of DOAC-Stop, showing reliability of such approach in the real-life setting, with <1% of patients with false positive LA.
Pattern of dual antiplatelet use and 12-month outcomes stratified by bleeding and ischemic risk in acute coronary syndrome patients undergoing percutaneous coronary intervention
Authors: Yan B , Lai A , Sun H , Tam T K , Tan G M
Published: November 2023

Background

There is a need to understand real-world antiplatelet usage in different risk group patients to provide insights into personalised approach to acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).

Purpose

We aimed to evaluate patterns and outcomes of antiplatelet therapy use in ACS patients undergoing PCI according to their bleeding and ischemic risks.

Methods

We retrospectively analysed 3,577 consecutive ACS patients who underwent urgent or emergent PCI from 16 hospitals in between Jan 2016 to Dec 2020. Patients were stratified according to their (i) bleeding risk using PRECISE-DAPT score ≥25 as high (HBR) and <25 as low bleeding risk (LBR) and further by (ii) ischemic risk if any one of the following: diffuse multi-vessel disease, chronic kidney disease, ≥3 stents implanted or lesions treated, total stented length >60mm, chronic total occlusion and history of STEMI is present as high ischemic risk (HIR) or absent as low ischemic risk (LIR). Pattern of dual-antiplatelet (aspirin plus clopidogrel or ticagrelor) use and 12-month outcomes including major bleeding, recurrent MI and cardiovascular (CV) death were compared between HBR, LBR, HIR and LIR groups. Independent predictors of antiplatelet therapy use and clinical events were identified using multi-variate analysis.

Results

Of 3,577 patients, 25.6% (n=914) are HBR and 74.4% (n=2663) LBR. 86.5% (793/914) of HBR patients also had HIR. Overall usage of aspirin plus clopidogrel was 48.4% and ticagrelor 48.3%. Usage of ticagrelor was significantly higher in LBR (54.0%) compared to HBR (31.8%) patients (p<0.01) but not significantly different between HIR (30.4%) and LIR (41.3%) patients (p=NS). HBR was an independent predictor against ticagrelor use with odds ratio of 0.48 (95% confidence interval 0.38 to 0.60). Aspirin plus ticagrelor compared to aspirin plus clopidogrel was associated with significantly lower recurrent MI rates in both HBR (9.3% vs. 22.7%) and LBR (3.0% vs. 6.0%, both p<0.01) patients, higher bleeding risk in HBR (1.7% vs. 0.5%, p<0.01) but not in LBR (0.6% vs 0.9%, p=NS) and no significant differences in CV death rates in both HBR (3.4% vs. 5.3%) and LBR (1.0% vs. 0.9%, both p=NS) at 12-months.

Conclusions

In our cohort of ACS patients undergoing PCI, a quarter have HBR of which majority also have HIR. Patients’ bleeding risk was a stronger determinant of dual-antiplatelet therapy choice than ischemic risk. Aspirin and ticagrelor was associated with significantly lower recurrent MI rates irrespective of bleeding risk but high major bleeding rates in HBR but not LBR patients. Our results support personalised approach to dual-antiplatelet therapy use based on bleeding risk.
Are heart failure patients with mildly reduced ejection fraction treated according to current international guidelines?
Authors: Schupp T , Pumpe K P , Abel N A , Reinhardt M R , Schmitt A S , Weidner K W , Akin I A , Behnes M B
Published: November 2023

Objective

This study aims to investigate the guideline adherence and prognostic role of guideline recommended heart failure (HF) therapies in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF).

Background

Limited data regarding the guideline adherence and prognostic impact of different pharmacotherapies in patients with HFmrEF is available.

Methods

A large retrospective study was used including all consecutive hospitalized patients with HFmrEF (i.e., left ventricular ejection fraction (LVEF) 41 – 49%) from 2016 to 2022 according to current European guidelines. The prescription rates and the prognostic role of angiotensin-converting enzyme and receptor blockers (ACEi/ARB), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), sodium glucose linked transporter 2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitor"(ARNi) was assessed. The primary endpoint was the first heart-failure related re-hospitalization at 3 years. Secondary endpoints comprised amongst others cardiovascular re-hospitalization. Kaplan-Meier, uni- and multivariable Cox regression analyses were applied for statistics.

Results

775 consecutive patients with HFmrEF surviving index hospitalization were included. Of those, 73% were discharged on ACEi/ARB, followed by BB (26%), 14% MRA, whereas only minor part was treated with SGLT2i (3%). In HFmrEF patients, no prognostic impact of BB (10% vs. 7%; log rank p=0.218; HR=1.474; 95% CI 0.792-2.742; p=0.220), ACEi/ARB (9% vs. 10%; log rank p=0.444; HR=0.822; 95% CI 0.497-1.359; p=0.445), SGLT2i (8% vs. 9%; log rank p=0.821; HR=0.851; 95% CI 0.209-3.470; p=0.445), MRA (8% vs. 9%; log rank p=0.748; HR=0.892; 95% CI 0.443-1.794; p=0.748) regarding the risk of heart-failure related re-hospitalization at 3 years was observed. In line, these pharmacotherapies were not associated with the risk of cardiovascular re-hospitalization.

Conclusions

In patients hospitalized with HFmrEF between 2016 and 2022, only infrequent treatment with guideline recommended HF therapies was observed, whereas non of the current HF therapies was associated with the risk of heart-failure related rehospitalization.
The clinical implementation of a de-escalation strategy using CYP2C19 genotyping in patients with an acute coronary syndrome: insights from the FORCE-ACS registry
Authors: Azzahhafi J , Van Den Broek W W A , Chan Pin Yin D R P P , Ten Berg J M
Published: November 2023

Background

Current guidelines recommend prasugrel and ticagrelor in patients undergoing percutaneous coronary intervention (PCI), however these potent P2Y12-inhibitors are associated with a higher bleeding risk when compared to clopidogrel. The CYP2C19 gene influences the efficacy of clopidogrel, with carriers of loss-of-function alleles having a higher risk for major adverse cardiovascular events. A genotype-guided strategy whereby noncarriers are treated with clopidogrel has been shown to reduce bleeding without increasing the risk of major adverse cardiovascular events and to be cost-effective. Currently, there are no practical guidelines for implementing a genotype-guided strategy and there are still operational issues regarding the usage of buccal swabs or venous blood samples.

Purpose

The study aimed to assess the feasibility of a CYP2C19 genotype-guided de-escalation strategy in acute coronary syndrome (ACS) patients treated with dual antiplatelet therapy and to evaluate the de-escalation rate.

Methods

ACS patients receiving genotype-guided antiplatelet therapy from August 2021 onwards were eligible. Genotyping was done using buccal swabs in a point-of-care (POC) device or by venous blood samples in the lab. Genotyping results were entered into the EHR. Attending physicians received automatic notifications to change antiplatelet therapy based on genotyping results, but subsequent management was at their discretion. The primary endpoint is maintenance therapy with P2Y12 inhibitors, with secondary endpoints being therapy changes, and time until genotype results. Therapy changes based on genotyping method were assessed using the Chi-square and Mann-Witney U test.

Results

In total, 1,530 patients with suspected ACS were included in the FORCE-ACS registry from June 2021 to January 2023. A CYP2C19 genotype test was performed in 738 ticagrelor treated patients and 260 (35%) patients carried a CYP2C19 LoF-allele. The median time to genetic test result was 6.2 hours, with 84.6% of results known within 24 hours for POCT and 15.4% for blood analysis. Of all 478 CYP2C19 LoF-allele noncarriers eligible for de-escalation, 433 (90.4%) patients were successfully de-escalated from ticagrelor to clopidogrel. De-escalation to clopidogrel occurred within 24 hours in 70.9% of patients and within 48 hours in 93.1%. The time to de-escalation was significantly lower in patients analyzed using POCT (25.4 hours) compared to blood analysis (58.9 hours).

Conclusion

The implementation of routine genotyping is feasible and de-escalation rates to clopidogrel in non-carriers are acceptable. The quicker time-to-results and de-escalation highlights the potential benefits of using POC testing.Overview of genotype-guided strategy
The inflammatory proteome and risk of atrial fibrillation: genetic insights into causal relevance
Authors: Camm C J F , Casadei B , Hopewell J C
Published: November 2023

Background

Cardiac and systemic inflammation have been associated with a higher risk of atrial fibrillation (AF) in both animal models and human studies. Causality, however, has been questioned due to inconsistent efficacy of anti-inflammatory treatments in preventing incident or recurrent AF, and potentially confounding associations with AF risk factors such as ischaemic heart disease. Inflammatory processes are highly complex and involve a large number of proteins, but the individual relevance and causal role of these for AF remains unclear.

Purpose

To explore the nature of the relationship between the inflammatory proteome and risk of AF.

Methods

Associations between 26 inflammatory proteins and AF were assessed in a two-sample Mendelian randomization (MR) framework, with primary MR causal estimates with AF estimated among 339,214 White British UK Biobank (UKB) participants (AF cases=30,630). MR analyses for each inflammatory protein included independent variants previously associated with the relevant protein at genome-wide significance (p<5x10-8) across the genome (trans-protein quantitative trait loci [pQTLs]), or restricted to at least 50kb from the closest upstream gene and 50 kb downstream from the target gene (cis-pQTLs). Sensitivity analyses to assess potential pleiotropy were conducted (MR-Egger, weighted median, and weighted mode). Associations passing multiple testing threshold (p<0.002) in UKB were further validated in meta-analyses with independent datasets including over 50,000 AF cases (FinnGen and AFGen). Research undertaken using UKB application 14568.

Results

This inflammatory protein-wide study identified three proteins that have support for causal associations with AF. Genetically-predicted levels of IL6R, CD40, and Chitinase-3-like protein 1 (YKL40) each showed a negative association with risk of AF, with up to a 5% lower AF risk per standard deviation higher genetically-predicted levels of these proteins (Figure 1). These findings were further confirmed in meta-analysis with data from AFGen and FinnGen. No evidence of pleiotropy was identified, and results were also confirmed in cis-pQTL analyses, which were fully consistent with the trans-pQTL analyses (Table 1). Analyses stratified by various baseline characteristics highlighted stronger causal estimates in those with higher levels of C-reactive protein (with interaction p-values <0.001).

Conclusions

Genetic approaches support the relevance of lifelong differences in the inflammatory proteome for AF, and causal relationships between specific inflammatory markers and risk of AF. Greater soluble IL6R and CD40 as measured in proteomic analyses are both associated with lower levels of inflammation. As previous work indicates that genetically upregulated CD40 and IL6R are similarly associated with a lower risk of ischemic stroke, the risk-benefit of directly targeting these pathways needs further consideration.Figure 1Table 1
CYP2C19 genotype prevalence and association with recurrent myocardial infarction in British-South Asians treated with clopidogrel
Authors: Magavern E F , Jacobs B , Warren H , Finocchiaro G , Finer S , Van Heel D A , Smedley D , Caulfield M J
Published: November 2023

Background

Pharmacogenomics examines how genes and drugs interact to explain some of the inter-individual variability in response to medications. CYP2C19 is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Although the European Society of Cardiology and National Institute for Care Excellence recommend ticagrelor (a non CYP2C19 dependent P2Y12 antagonist) as the antiplatelet agent of choice, clopidogrel remains widely prescribed for acute coronary syndrome and myocardial infarction. CYP2C19 poor metabolizers are known to be more common in Asian ancestry but very few studies have looked specifically at South Asian populations or linked metabolizer diplotypes with clinical efficacy data in this population. The outcome studies on which clopidogrel was licensed for efficacy and safety did not include significant South Asian representation. Furthermore, South Asians are known to have a higher prevalence of cardio-metabolic disease compared with European ancestry populations.

Methods

We studied the Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants to look at prevalence of CYP2C19 metabolizer genotypes and correlate these with recurrent myocardial infarction risk for those who had been prescribed clopidogrel in primary care. Multivariable regression was used to test for association between known CYP2C19 diptotypes and recurrent myocardial infarction in those prescribed clopidogrel, controlling for known CVD risk factors, percutaneous coronary intervention, age, and gender.

Results

Genes & Health cohort participants (N = 44,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss of function allele. The prevalence of poor metabolizers carrying 2 CYP2C19 loss of function alleles is 13%, which is higher than in previously studied European (2.4%) and Central/South Asian populations (8.2%). This is primarily due to the *2 LOF allele present in 56% of the population. 69% of the cohort who were diagnosed with an acute MI were prescribed clopidogrel. The presence of the poor metabolizer diplotype is significantly associated with higher risk of recurrent MI, or failed secondary prevention on clopidogrel in this population, OR 3.1 (p = 0.02), with some subsequent ischemic events already described in this young cohort (Acute MI prescribed clopidogrel N = 697, Recurrent MI in this group N=39).

Conclusions

A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry. In absence of genotype guided prescribing, maximal adherence to guidelines recommending non CYP2C19 dependent P2Y12 anti-platelet therapy is likely to be disproportionately beneficial in this ethnic cohort.Risk of recurrent MICentral illustration
Xanthine oxidase inhibitors withdrawal syndrome
Authors: Kuwabara M , Nakai M , Sumida Y , Kodama T
Published: November 2023

Background

In humans, uric acid is the final metabolite of adenosine triphosphate, an energy source. Xanthine oxidase (XO) contributes to urate metabolism, and XO inhibitors (XOI) suppress the production of uric acid and could store ATP. However, recent studies showed that discontinuation of XOI may lead to ATP depletion and increased death as a withdrawal syndrome. We examined whether the XOI withdrawal syndrome actually occurs.

Methods

This study retrospectively analyzed the Japanese Registry Of All cardiac and vascular Diseases (JROAD) database, which included 8,927,858 patients out of 9,825,635 data from April 2014 to March 2020, excluding 330,847 patients younger than 20 years and 566,930 patients older than 90 years. Of these, 356,405 were hospitalized patients with cardiovascular disease who were receiving uric acid-lowering drugs, and 315,388 were on XOI (41,017 were on other uric acid-lowering medications)(Fig). The XOI adherents were divided into the following four groups, and the number of deaths and mortality rates for each were identified as follows.

Results

(1) Those who were on the drug at admission and continued the drug at discharge: 219,020 cases, of which 59 deaths (0.03%). (2) 89,035 patients were discharged from the hospital on the medication they were on at the time of admission, of which 17,663 died (19.84%). (3) 7,241 patients who were not on any medication at admission (medication was given during hospitalization) and continued on medication at discharge, including 11 deaths (0.15%). (4) No medication at admission (medication was given during hospitalization) and stopped at discharge: 92 cases, of which 11 deaths (11.96%).

Continuous medication group: 226,261 cases, including (1) and (3), of which 70 deaths, (0.03%). Withdrawal group: 89,127 cases, including (2) and (4), of which 17,674 deaths (19.8%). The number of deaths in the withdrawal group was 620 times higher than that in the continuation group (p<0.001).

Conclusion

XOI withdrawal syndrome is detected in our study. However, some of the deaths in the XOI discontinuation group were due to the fact that other medications were also discontinued, which indicate impossible to determine a direct causal relationship between XOI withdrawal and death. Further studies are needed to check the relationship between XOI withdrawal and death in other algorithms.Fig. Flow-chart of the study
Sex differences in incidence of self-reported adverse drug reactions after percutaneous coronary intervention
Authors: Pettersen T , Schjott J , Allore H , Bendz B , Borregaard B , Fridlund B , Hadjistavropoulos H D , Larsen A I , Nordrehaug J E , Rasmussen T B , Rotevatn S , Valaker I , Wentzel-Larsen T , Norekval T M
Published: November 2023

Background

Despite experiencing adverse drug reactions (ADRs) more often than men, the proportion of women participating in clinical drug trials is low. Thus, evidence for sex differences in the incidence of ADRs is limited.

Aim

To determine sex differences in incidence of self-reported ADRs after percutaneous coronary intervention (PCI). Further, to determine whether receiving information about ADRs is associated with sex.

Methods

CONCARDPCI is a prospective multicentre cohort study (N=3417) conducted at seven referral PCI centres in two Nordic countries. Clinical data were collected from patients’ medical records. Socio-demographic characteristics were obtained by self-report after PCI. Two questions from the Heart Continuity of Care Questionnaire (HCCQ) were used to determine if information about potential ADRs was received before hospital discharge. De novo created questions were used to determine if patients reported ADRs from prescribed therapy. Questionnaires were distributed two- (T1), six- (T2), and twelve months (T3) after hospital discharge to assess the incidence of self-reported ADRs in a longitudinal perspective. Logistic regression was utilised to scrutinize the aims, reported as odds ratios (ORs) with 95% confidence intervals (CIs).

Results

Patients were predominantly male (78%), with a mean age of 65 years (SD 11). Female patients were older (68, SD 10). Acute coronary syndrome was the most frequent cause of admission for PCI (62%). At T1, 2656 of the included patients responded to the questions from the HCCQ. Of these, 1019 patients (39%) reported being informed of potential ADRs from prescribed therapy, 1075 patients (42%) reported not having been informed, 511 patients (20%) reported ‘Hard to decide’, and 51 (2%) reported ‘Not applicable’. Patients reporting ‘Hard to decide’ or ‘Not applicable’ were excluded from further analysis. Women were less likely to receive information than men (OR 0.58, CI 0.45 – 0.75, p<0.001). For the total study population, 42%, 49% and 40% reported ADRs at T1-T3 respectively. After adjusting for sociodemographic and clinical variables, the incidence of self-reported ADRs were significantly higher in women compared to men at T1 (OR 1.71, CI 1.36 – 2.15, p<0.001), T2 (OR 1.89, CI 1.49 – 2.38, p<0.001), and T3 (OR 1.79, CI 1.40 – 2.28, p<0.001).

Conclusion

Women report significantly more ADRs from prescribed therapy than men after PCI. However, they are less likely to receive information about potential ADRs compared to men. Efforts to improve communication on ADRs and gender equity should be a priority.
Nurse-driven protocol for the management and follow-up of subclinical atrial fibrillation episodes in pacemaker patients
Authors: Iglesias J A , Benezet Mazuecos J , Lozano A , Crosa J , Miracle A , Esteban I , Elosegui C , Illescas C
Published: November 2023

Background

Atrial high-rate episodes (AHREs) compatible with atrial fibrillation (AF) detected in pacemakers are associated with an increased risk of stroke. Nurses trained in pacemaker (PM) follow-up can detect theses AHREs during patient’ scheduled visits and provide the best care option to the patients.

Purpose

To evaluate a nurse protocol applied in these patients focused on a) identifying those with AHREs and taking into account the timing of these events and their duration, and b) provide the best care and follow-up then after.

Methods and Results

To create our protocol, we evaluated PM patients without a previous history of AF and classified the incidence of AHREs into 3 groups: >5 minutes to 24 hours; >24 hours and patients who are in clinical AF (documented on ECG) at the time of the visit. We also evaluate the time elapsed since PM implantation (£ 3 months vs > 3 months) and the type of atrial electrode fixation (active vs passive). In a prior study we analyzed 110 patients with AHREs >5 minutes and <24 hours (56% male, age 75 ± 9 years, mean CHA2DS2VACS scores of 3.5 ± 1.5). After 24 ± 9 months, 40 patients (36.4%) presented AHREs, and CT images showed ischemic brain lesions in 26 of them (23.6%). The presence of AHREs at 3 months was more frequent in patients with a recent MP implantation (17% vs 4.5%) and with a significant relationship with the type of active fixation of the electrode. The presence of ischemic lesions on CT was related to the detection of AHREs during follow-up, but not with AHREs in the first 3 months. Therefore, we designed a dedicated protocol for follow-up in these patients (AHREs >5 minutes and <24 hours) after PM implantation with repetitive follow-up visits assessing the evolution of AHREs. In cases of >24 hours and those with ECG documented AF, Guidelines recommendations were followed.

Conclusions

In PM patients, the presence of AHREs might be related to serious clinical complications. On the other hand, AHREs occur regularly during the first 3 months after PM implantation, maybe related to the procedure itself and the use of active fixation for the atrial lead. AHREs in this period may not be related to major complications and individual risk should be carefully assessed before starting anticoagulation. A dedicated protocol for closer follow-up visits in these patients might help to identify those at risk and prevent clinical events.
Co-production of a structured integrated post pulmonary embolism care model (Attend-PE)
Authors: Hojen A A , Lindegaard S F , Larsen T B , Johnsen S P , Rolving N
Published: November 2023

Background

More than half of patients with pulmonary embolism (PE) develop persistent functional limitation and experience lower quality of life (1). To mitigate long-term complications, the European Society of Cardiology clinical guidelines on PE management recommends an integrated model for patient care after PE. However, there is currently no consensus on what such an optimal follow-up strategy should include, and high-quality evidence to provide guidance is lacking (1,2).

Purpose

To describe the co-production of a structured model for PE follow-up.

Methods

This study is part of the project - A structured Integrated post PE care model (Attend-PE) aimed at developing and testing the effectiveness of a structured, integrated and patient-centred follow-up care model for patients with PE in Denmark.

The co-production of the Attend-PE model was conducted from October 2021 till June 2022, featuring user-centred and participatory design techniques. This methodology was combined with a structural stepwise approach based on Intervention Mapping, to ensure the developed model was founded on evidence and theory (3).

Results

In accordance with the Intervention Mapping protocol, a national panel of stakeholders was formed, and a needs assessment was conducted. The needs assessment comprised a mapping of PE follow-up at all main sites treating PE in Denmark (18 hospitals), based on a co-design process with patients and health care professionals inspired by the patient journey method. To supplement this, a literature search was conducted to identify further knowledge concerning the follow-up care needs and preferences of patients with PE, as well as the optimal clinical management of PE follow-up. Based on this, the overall goal and performance objectives of a structured follow-up care model were formulated, laying the foundation for co-production workshops. In two full-day workshops, patient representatives and healthcare professionals, as well as experts in the field of PE, developed the components, scope, and sequence of the Attend-PE model. Subsequently, the structure and organization of the follow-up model were refined during online workshops, and a working group produced patient education material.

The Attend-PE model (Figure 1), outlines a systematic strategy for post-PE in-hospital follow-up, involving patient education, the content and frequency of individual follow-up consultations, and the application of patient reported outcome measures to actively assess physical and psychological well-being. This model supports an individualized post-hospitalization follow-up care plan tailored to the patient's specific needs.

Conclusion(s)

The co-production process was successful in developing a structured follow-up model for patients with PE which was based on patients’ needs and preferences, as well as the clinical experience and perspectives of healthcare providers, and was in line with current clinical guidelines.Attend-PE model
The effectiveness of high-intensity interval training compared to moderate-intensity continuous training in patients with heart failure: a systematic review and meta-analysis
Authors: Okamura M , Shimizu M , Yamamoto S , Nishie K , Konishi M
Published: November 2023

Background/Introduction

Cardiac rehabilitation including exercise therapy is beneficial for improving exercise tolerance, physical function, quality of life (QOL), and life expectancy in patients with heart failure. High-intensity interval training (HIIT) has attracted attention as a new training modality in heart failure, whereas moderate-intensity continuous aerobic training (MCT) is recommended as the main training modality to improve exercise tolerance. However, the effects of HIIT in patients with heart failure remain controversial.

Purpose

This systematic review and meta-analysis aimed to examine the effectiveness of HIIT compared to MCT on exercise tolerance in patients with heart failure.

Methods

We searched for studies published up to 4 March 2022 in EMBASE, MEDLINE via Ovid SP, PubMed, and the Cochrane Library via Wiley Online Library with no limitations on data, language, or publication status. We included randomised controlled trials comparing the effectiveness of HIIT and MCT on peak oxygen uptake (VO2), as a measure of exercise tolerance, aerobic threshold (AT) VO2, ventilatory equivalent of carbon dioxide (VE/VCO2), and QOL. We pooled the data on peak VO2, compared HIIT to MCT, and conducted a sub-analysis if there was heterogeneity in the result.

Results

We identified 15 randomised controlled trials with 557 patients from a total of 23,272 records. Our meta-analysis showed that participants who underwent HIIT achieved a significantly higher peak VO2 than those who underwent MCT (mean difference 1.46 ml/kg/min, 95% confidence interval 0.39 to 2.53; I2 = 65.7%; very low-quality evidence) (Figure 1). Participants who underwent HIIT had no statistically significant difference in AT VO2, VE/VCO2, and QOL compared to those who underwent MCT. The meta-regression analysis, conducted as a sub-analysis to explore possible causes of heterogeneity, revealed that the effect size of HIIT compared to MCT was inversely associated with body mass index (r = -0.508, p = 0.028, 95% confidence interval -0.95 to -0.07) (Figure 2).

Conclusions

Our systematic review showed that HIIT achieved a higher peak VO2 than MCT in patients with heart failure. In addition, HIIT may be more effective in improving exercise tolerance in patients with low body mass index.
Individual tailored physical training in patients with postural orthostatic tachycardia syndrome after COVID-19 - a feasibility study
Authors: Svensson A , Svensson-Raskh A , Stahlberg M , Bruchfeld J , Holmstroem L , Fedorowski A , Nygren-Bonnier M
Published: November 2023

Background

A significant proportion of patients with COVID-19 have developed persistent symptoms, described as post-acute COVID-19 syndrome (PACS ). A specific PACS variant is the postural orthostatic tachycardia syndrome (POTS). POTS is a cardiovascular autonomic dysfunction characterized by an excessive increase in heart rate in standing, deconditioning and low quality of life. Studies that have evaluated the effect and feasibility of individual tailored physical training in POTS associated with COVID-19 are sparse.

Purpose

To evaluate the effects and feasibility of individualized exercise on physical and psychological function in patients with POTS after COVID-19.

Method

Patients with POTS + PACS were enrolled between Dec 2021 and Dec 2022. The intervention consisted of individually tailored training, including endurance and muscle-strengthening exercises with a gradual progression of time, dose and position. The training was based on the study subject's heart rate and/or self-estimated exertion using BORG RPE. The intervention lasted 12 weeks. Progression of the exercise was halted if the study subject described increased symptoms >24h after the last exercise session. Measurements were carried out at baseline and after intervention: 6-minute walking test (6MWT), Active Standing Test (AST) and self-assessment of symptoms through forms; Malmö POTS scale (MaPS), Vanderbilt Orthostaic Symptom Score (VOSS), Fatigue Severity Scale (FSS) health-related quality of life (EQ-5D-5L), anxiety (GAD) and depression (PHQ-9). Physical activity and time in different positions (lying, sitting, standing and walking) were measured using accelerometers (ActivPAL). Recruitment rate, compliance and adverse events was registered as feasibility.

Results

A total of 24 patients were enrolled and 23 patients completed the intervention (19 women; mean age, 40.9 years (SD 10.7). No severe adverse events occurred however some of the patients described symptoms as post exertion malaise (PEM). After the intervention, patients demonstrated improvement in physical (6MWT, p<0.005) and psychological functions (PHQ-9, p<0.001), less symptoms related to POTS (MaPS p<0.01, VOSS p<0.02, FSS p<0.045) and improved HrQoL (EQ-5D p<0.001) (Table 1). The primary outcome, time spent in upright position increased by 1.5h/day i.e. by 49% (Figure 1).

Conclusion

In patients with COVID-19-related POTS, an individually tailored training seem to contribute to increased time in upright position, reduction of POTS-specific symptoms and improved functions. The intervention seems to be feasible in terms of recruitment, compliance and safety. Further studies are needed to verify these results and compare disease progression with and without intervention.Table 1Figure 1
Quantification of heart failure decompensation through mixed digital methodology
Authors: Romano L , Curcio A , Scalzi G , Malizia B , Festa M , Indolfi C
Published: November 2023

Background

While natriuretic peptides (NPs) quantification and echocardiographic assessments are recommended for diagnosis of heart failure (HF), yet electrocardiographic determinants of cardiac rhythm alterations predisposing to sudden cardiac death (SCD) are lacking. Premature ventricular contractions (PVCs) are common in HF. In some patients, PVCs are triggered by the same mechanism that gives rise to ventricular tachycardia (VT). Appropriate clinical evaluation is important in these patients. Currently, smartwatches are becoming particularly popular to enhance health monitoring.

Purpose

The aims of this study were: to evaluate the feasibility and reliability of the clinical use of a smartwatch, to detect main features of QRS-complex (width, voltage), and to correlate PVCs with VT originating in different aetiologies of HF.

Methods

From November ‘22 to February ’23, 53 patients admitted to the Division of Cardiology of our academic hospital underwent standard ECG and smartwatch-based lead I acquisitions. Concordance between the two technologies was assessed by Cohen κ coefficient. Bland-Altman method for analysis of measurement agreement was used for comparison.

Results

Clinical characteristics of the subjects included in this study are described in the Table. All patients had diagnosis of acute or chronic HF and had PVCs (N= 47) and/or VT (N=3). Sustained and non-sustained VT were more common in patients with HF and reduced ejection fraction. In 7 cases we detected PVCs with the same standard ECG’s morphology and axis during recording ECG with the smartwatch. The Cohen κ coefficients for the measurement of the voltage and width of QRS complex were 0.833 (95% CI, 0.725-0.936) and 0.869 (95% CI, 0.747- 0.956), respectively; voltage and width of PVCs were 0.860 (95% CI, 0.579-1.00) and 0.822 (95% CI, 0.429-1.00), respectively. Concordance was found between the smartwatch ECG and standard ECG for QRS width (bias, −0.05; SD, 0.395; lower limit, −0.821; and upper limit, 0.727), for QRS voltage (bias, −0.004; SD, 0.034; lower limit, −0.073; and upper limit, 0.062), for PVC width (bias, −0.7; SD, 2.167; lower limit, −4.372; and upper limit, 4.12), PVC voltage (bias, −0.02; SD, 0.07; lower limit, -0.112; and upper limit, 0.162) using the Bland-Altman analysis.

Conclusions

Smartwatch can accurately measure QRS width and voltage and reproducibly detect PVCs compared with standard ECG. Valid correlation indices and good concordance between the two methods were observed using digitally-assessed lead I. These data could be of great interest due to the widespread diffusion of wearable devices; the smartwatch could be helpful especially when frequent monitoring of VT becomes necessary. Currently available smartwatches display, in this regard, an implementation for PVCs detection.
Artificial intelligence-based identification of left ventricular systolic dysfunction from 12-lead electrocardiograms: External validation and advanced application of an existing model
Authors: Koenig S , Hohenstein S , Nitsche A , Pellissier V , Leiner J , Stellmacher L , Hindricks G , Bollmann A
Published: November 2023

Background

The diagnostic application of artificial intelligence (AI)-based models to detect cardiovascular diseases from electrocardiograms (ECG) evolves and some promising results were reported. However, most published algorithms lack external validation.

Purpose

Aim of this study was to validate an existing, open-source algorithm for the detection of left ventricular systolic dysfunction (LVSD) from 12-lead ECGs.

Methods

Patients with digitalized data pairs of 12-lead ECGs and echocardiography (at intervals of ≤7 days) were retrospectively selected from the Heart Center Leipzig ECG and electronic medical records databases. A previously developed AI-based model was applied to ECGs and calculated probabilities for LVSD. Area under the receiver operating characteristic curve (AUROC) was computed overall and in cohorts stratified for baseline and ECG characteristics. Repeated echocardiography studies recorded ≥3 months after index diagnostics were used for follow-up (FU) analysis.

Results

At baseline, 42,291 ECG-echocardiography pairs were analyzed and AUROC for LVSD detection was 0.88. Corresponding sensitivity and specificity were 82% and 77% for the optimal LVSD-probability cutoff based on Youden’s J. AUROCs were lower in ECG-subgroups with tachycardia, atrial fibrillation and wide QRS complex. In patients without LVSD at baseline and available FU, model-generated high probability for LVSD was associated with a 4-fold increased risk of developing LVSD during FU.

Conclusion

We provide the external validation of an existing AI-based ECG-analyzing model for the detection of LVSD with excellent and robust performance metrics. The association of false positive LVSD screenings at baseline with a deterioration of ventricular function during FU is hypothesis-generating and deserves further research.
Ultra-short heart rate variability over 15 seconds is associated with increased long-term risk of cardiovascular disease
Authors: Orini M , Van Duijvenboden S , Young W J , Ramirez J , Jones A R , Tinker A , Munroe P B , Lambiase P D
Published: November 2023

Background

Heart rate variability (HRV) is an established cardiac autonomic marker with prognostic value, whose application at scale is limited by the fact it requires relatively long ECG recordings (≥ 5-min). Ultra-short HRV (usHRV) is derived from much shorter recordings and can be measured at scale using standard and wearable ECGs, but its association with cardiovascular events is undetermined.

Purpose

(1) To validate usHRV measured using 15-second ECGs and (2) To investigate association with multiple outcomes in individuals without cardiovascular disease.

Methods

Data from the National Survey for Health and Development (N=1,337) was used to assess the agreement between usHRV and standard HRV (which requires ≥5-minute ECGs). Participants from the first visit of the UK Biobank study (2009-2013), without cardiovascular disease and with an ECG (N=51,628, 64% male, median age 58) were recruited to assess association of usHRV with outcomes. Exposures included usHRV time-domain indices RMSSD and SDSD, which measure fast heart rate variations related to cardiac vagal modulation, and usHRV spectral index PHF, which is related to respiratory sinus arrhythmia. Outcomes included incident atrial fibrillation (AF), major adverse cardiovascular events (MACE), stroke and mortality.

Results

HRV indices RMSSD and SDSD measured in 15-second ECGs showed excellent agreement (median correlation coefficient ≥0.84 and narrow limits of agreement in Bland-Altman analyses, Fig. 1) with indices measured from 6-minute ECGs, while PHF showed good agreement (median correlation coefficient 0.70 and small positive bias). In the UK Biobank, after a median follow-up of 11.5 (11.4-11.7) years, incidence of AF, MACE, stroke, and mortality was 3.8%, 3.9%, 1.7% and 4.3%, respectively. An inverse linear association was found between usHRV and AF and stroke, with hazard ratios between 1.07 and 1.13 for a standard deviation decrease in RMSSD, SDSD and PHF, p<0.05. Non-linear cox regressions (Fig. 2) showed that the association of RMSSD (and SDSD) with MACE and mortality was U-shaped with individuals in the bottom quintiles of usHRV indices showing increased risk with respect to those in the third quintile (hazard ratios between 1.16 and 1.29, p<0.05).

Conclusions

Cardiac autonomic dysfunction measured with usHRV from 15-second ECGs is associated with increased risk of AF, MACE, stroke, and mortality in individuals without cardiovascular disease. usHRV can be measured from both standard clinical ECGs and novel wearable devices and may have a role to monitor autonomic function at scale and improve understanding and prevention of cardiovascular disease.Fig1: 6-min vs 15-sec HRVFig2: usHRV association with outcomes
Usefulness of CineECG method in identification of P-wave morphology variants in an elderly epidemiologic cohort
Authors: Baturova M , Van Dam P , Johnson L S B , Smith G , Platonov P
Published: November 2023

Background

Biphasic P waves in inferior leads categorizes interatrial block (IAB) into partial or advanced subtypes. P-wave morphology is highly variable, and visual assessment of P-wave morphology is subjective, especially in case of low-amplitude P waves. CineECG is a non-subjective approach which is not sensitive to signal amplitude, and which can also calculate terminal P-wave angle.

Purpose

To assess the relationship between P-wave morphology in inferior ECG leads, categorization of the IAB subtypes and terminal P-wave angle using CineECG in an elderly epidemiologic cohort.

Methods

We included participants with sinus rhythm on an ECG collected 2002-2006 in the general-population based Malmö Preventative Project (n=983, age 70±5 years, 38% females). ECGs were digitally processed using the Glasgow algorithm. IAB was defined as a P-wave ≥120 ms and classified regarding as partial (pIAB, P waves affected in none [pIAB-0] or only 1 inferior lead III [p-IAB-1]) or advanced (aIAB, P waves affected in leads III and aVF [aIAB-2] or all 3 inferior leads [aIAB-3, typical aIAB]). All ECGs were also processed using CineECG. The vectorcardiogram was computed from the 12 lead ECG and a generic model of the atria and torso, with average body build and heart orientation. We used the terminal P-wave angle as the variable which describes the direction of the terminal part of P wave in the frontal plane (Figure).

Results

IAB was documented in 413 (42%) subjects: 344 (35%) had pIAB (199 (20%) with pIAB-0; 145 (15%) with pIAB-1) and 60 (6.5%) had aIAB (45 (5%) with aIAB-2 and 15 (1.5%) with aIAB-3 or typical aIAB). P wave morphology could not be categorized by these definitions in 9 subjects. Terminal P wave angle correlated with P wave morphology (Spearman’s r=0.127, p<0.001) and progressively increased with increase of P wave morphology class from pIAB-0 to aIAB-3 (Figure, Table).

Conclusion

Morphology variants of IAB can be classified depending on the degree of the terminal P wave angle which correlates with the order and number of bipolar inferior leads. CineECG provides an instrument for 3D quantification of the terminal atrial depolarization direction which can be used to detect IAB in an earlier stage.Figure.Atrial depolarisarion and IAB.