bluuebunny/crossref_metadata_2025 huggingface dataset:
C-reactive protein compared to procalcitonin in guiding of anti-microbial stoppage in patients with septic shock
Authors: Abdelrahman Ehab Ahmed , Abdelazeem Ehab Said , Heikal Amr Tarek , Ibrahim Ibrahim Emad Fawzy Rezk
Published: September 2024

Background

One of the greatest and most effective strategies to decrease the likelihood of discovering antibiotic-resistant bacteria in patients receiving critical care is to shorten the duration of antibiotic therapy.

Objectives

To assess the utility of procalcitonin compared to traditional inflammation markers like C-reactive protein in an antimicrobial stoppage in patients with septic shock.

Methods

This was a comparative, prospective, randomized, observer-blind clinical experiment conducted on 60 septic patients hospitalized in intensive care units at Benha University hospitals between May 2021 and May 2022. Groups for PCT and CRP patients were separated. The full clinical history, co-morbidities that were related, and patient history were recorded. The baseline PCT and CRP values were determined on days 4, 7, 10, and 14. They were contrasted with sepsis ratings obtained from the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sepsis-related Organ Failure Assessment (SOFA). Days 4, 7, and 10 were used to evaluate the antibiotic's efficacy.

Results

There was no correlation between CRP levels and APACHE II and SOFA scores on days 1, 4, and 7, but on days 7 and 10, PCT levels were strongly linked with both (P < 0.05). PCT was linked to lower antibacterial exposure (23.3% of PCT participants ceased taking antibiotics on day 4, compared to 6.6% of CRP participants; P = 0.07). After 10 days, 30% of the PCT group and 70% of the CRP group kept up their antimicrobial regimen (P = 0.0001).

Conclusion

Procalcitonin dramatically reduced the duration of antimicrobial treatment. Procalcitonin use has reduced hospital expenses, complications of extended hospital stay, side effects of excessive antibiotic use, and hence, the mortality rate in septic patients.
Finerenone in heart failure and chronic kidney disease with type 2 diabetes: FINE-HEART pooled analysis of cardiovascular, kidney and mortality outcomes
Authors: Vaduganathan Muthiah , Filippatos Gerasimos , Claggett Brian L. , Desai Akshay S. , Jhund Pardeep S. , Henderson Alasdair , Brinker Meike , Kolkhof Peter , Schloemer Patrick , Lay-Flurrie James , Viswanathan Prabhakar , Lam Carolyn S. P. , Senni Michele , Shah Sanjiv J. , Voors Adriaan A. , Zannad Faiez , Rossing Peter , Ruilope Luis M. , Anker Stefan D. , Pitt Bertram , Agarwal Rajiv , McMurray John J. V. , Solomon Scott D.
Published: September 2024

Cardiovascular-kidney-metabolic syndrome is an emerging entity that connects cardiovascular diseases, chronic kidney disease and diabetes. The non-steroidal mineralocorticoid receptor antagonist finerenone has been studied in three prospective randomized clinical trials of patients with cardiovascular-kidney-metabolic syndrome: FIDELIO-DKD, FIGARO-DKD and FINEARTS-HF. In light of the strong epidemiological overlap and shared mechanistic drivers of clinical outcomes across cardiovascular-kidney-metabolic syndrome, we summarize the efficacy and safety of finerenone on cardiovascular, kidney and mortality outcomes in this pre-specified participant-level pooled analysis. The three trials included 18,991 participants (mean age 67 ± 10 years; 35% women). During 2.9 years of median follow-up, the primary outcome of cardiovascular death occurred in 421 (4.4%) participants assigned to finerenone and 471 (5.0%) participants assigned to placebo (hazard ratio (HR): 0.89; 95% confidence interval (CI): 0.78–1.01; P = 0.076). Death from any cause occurred in 1,042 (11.0%) participants in the finerenone arm and in 1,136 (12.0%) participants in the placebo arm (HR: 0.91; 95% CI: 0.84–0.99; P = 0.027). Finerenone further reduced the risk of hospitalization from heart failure (HR: 0.83; 95% CI: 0.75–0.92; P < 0.001) and the composite kidney outcome (HR: 0.80; 95% CI: 0.72–0.90; P < 0.001). While in this pooled analysis the reduction in cardiovascular death was not statistically significant, finerenone reduced the risks for deaths of any cause, cardiovascular events and kidney outcomes. PROSPERO identifier: CRD42024570467.
Construction of amide-bonded supramolecular multifunctional fillers towards boosted self-healing, thermal conductivity and dielectric properties
Authors: Yao Junlong , Fu Zongqiang , Yang Huan , Gao Lin , Jiang Xueliang , Nie Wei , Sun Zhengguang , Lu Haolan , Lin Meiyun , Xu Jinglou
Published: September 2024

The two modified fillers effectively improved the self-healing efficiency, dielectric properties and thermal conductivity of the supramolecular composites by forming a synergistic effect of amide bonds.
Research on interval prediction method of railway freight based on big data and TCN‐BiLSTM‐QR
Authors: Feng Chenyang , Lei Yang
Published: September 2024

With the rapid development of logistics, the categories of goods and the frequencies of train transportation in railway freight have increased significantly. The volatility and uncertainty of railway freight transportation have become even greater. Accurately predicting railway freight volume in the medium to long term has become increasingly challenging. On the basis of traditional prediction models, this paper introduces the concepts of interval and probability prediction, and proposes a temporal convolutional network (TCN)‐bi‐directional long short‐term memory (BiLSTM) interval prediction method for medium and long‐term railway freight volume. The method uses grey relational analysis for data dimensionality reduction and feature extraction, and TCN, BiLSTM, and quantile regression for modelling. Through a case study of freight transportation on the Shuohuang Railway, the results show that the TCN‐BiLSTM model achieves higher accuracy in point prediction and better performance in interval prediction compared to other general prediction models. The interval prediction can provide references for freight volume fluctuations in periods with significant volatility, which can assist railway transportation companies in better scheduling and planning based on such information.
Comparative analyses of publicness in urban squares within a diversifying metropolis
Authors: Istrate Aura-Luciana , Mitchell Annie , Russell Paula , Murphy Sadhbh
Published: September 2024

Ensuring publicness and accommodating more diverse human activity in urban public spaces is necessary. This research analyses the relationship between human activities, ownership, and physical features encouraging or discouraging use within the city centre of Dublin (Ireland), a diversifying metropolis experiencing dereliction. Four urban squares were assessed through fieldwork, including direct observation and behavioural mapping. Results indicate that publicness and features encouraging or discouraging use are not directly associated with site ownership. Nor was the presence of nature and landscaping determined by ownership, though it generated microclimates that promoted a higher mix of activities. Implications of going beyond formal definitions of ownership for publicness placed under broader sustainability agendas and recommendations for urban design practice are derived.
Coordination between water relations strategy and carbon investment in leaf and stem in six fruit tree species
Authors: Piña Ismael , Garrido-Salinas Marco , Seguel Oscar , Opazo Ismael , Faúndez-Urbina Carlos , Verdugo-Vásquez Nicolás , Villalobos-Soublett Emilio
Published: September 2024

The water relation strategy is a key issue in climate change. Given the difficulty of determining water relations strategy, there is a need for simple traits with a solid theoretical basis to estimate it. Traits associated with resource allocation patterns along a ‘fast-slow’ plant economics spectrum are particularly compelling, reflecting trade-offs between growth rate and carbon allocation. Avocado (Persea americana), fig tree (Ficus carica), mandarin (Citrus reticulata), olive (Olea europaea), pomegranate (Punica granatum), and grapevine (Vitis vinifera) were characterised in terms of iso-anisohydric strategy through stomatal behaviour, water potential at the turgor loss point (TLP), and hydroscape area. Additionally, the association of these metrics with leaf mass per area (LMA) and wood density (WDen) was explored. We observed high coordination between LMA and WDen, and both traits were related to metrics of water relation strategy. More anisohydric species tended to invest more carbon per unit leaf area or unit stem volume, which has implications for hydraulic efficiency and water stress tolerance. WDen and TLP were the most powerful traits in estimating the water relation strategy for six fruit species. These traits are easy to measure, time-cost efficient, and appear central to coordinating multiple traits and behaviours along the water relations strategies.
Estimating Additive Interaction in Two-Stage Individual Participant Data Meta-Analysis
Authors: Basten Maartje , van Tuijl Lonneke A , Pan Kuan-Yu , Hoogendoorn Adriaan W , Lamers Femke , Ranchor Adelita V , Dekker Joost , Frank Philipp , Galenkamp Henrike , Knol Mirjam J , Noisel Nolwenn , Payette Yves , Sund Erik R , Zwinderman Aeilko H , Portengen Lützen , Geerlings Mirjam I
Published: September 2024

Individual participant data (IPD) meta-analysis provides important opportunities to study interaction and effect modification for which individual studies often lack power. While previous meta-analyses have commonly focused on multiplicative interaction, additive interaction holds greater relevance for public health and may in certain contexts better reflect biological interaction. Methodological literature on interaction in IPD meta-analysis does not cover additive interaction for models including binary or time-to-event outcomes. We aimed to describe how the Relative Excess Risk due to Interaction (RERI) and other measures of additive interaction or effect modification can be validly estimated within two-stage IPD meta-analysis. First, we explain why direct pooling of study-level RERI estimates may lead to invalid results. Next, we propose a three-step procedure to estimate additive interaction: 1) estimate effects of both exposures and their product term on the outcome within each individual study; 2) pool study-specific estimates using multivariate meta-analysis; 3) estimate an overall RERI and 95% confidence interval based on the pooled effect estimates. We illustrate this procedure by investigating interaction between depression and smoking and risk of smoking-related cancers using data from the PSYchosocial factors and Cancer (PSY-CA) consortium. We discuss implications of this procedure, including the application in meta-analysis based on published data.
Effects of acetic acid fermentation product and its components on defense signaling in rice
Authors: Abe Koharu , Mori Manae , Nakayama Akira
Published: September 2024

Acetic acid fermentation product made from isomalto-oligosaccharide as the main raw material is composed of isomalto-oligosaccharide and acetic acid. In this paper, we have shown that the fermentation product enhanced the expression of disease resistance genes in rice, and that its main functional component was acetic acid. It has been reported so far that acetic acid enhances the jasmonic acid signaling pathway, while the role of isomalto-oligosaccharide in plant defense signaling remains unclear. In this study, we demonstrated the possibility that isomalto-oligosaccharide shifted part of the jasmonic acid signaling pathway, which is enhanced by acetic acid, to the salicylic acid signaling pathway, which is the other major defense pathway. Furthermore, glucose, a constituent monosaccharide of isomalto-oligosaccharide, and a disaccharide maltose had little effect on the signaling pathway, but a trisaccharide maltotriose tended to have a similar effect to isomalto-oligosaccharide on the defense signaling pathway.
Noradrenergic modulation of saccades in Parkinson’s disease
Authors: Orlando Isabella F , Hezemans Frank H , Ye Rong , Murley Alexander G , Holland Negin , Regenthal Ralf , Barker Roger A , Williams-Gray Caroline H , Passamonti Luca , Robbins Trevor W , Rowe James B , O’Callaghan Claire
Published: September 2024

Noradrenaline is a powerful modulator of cognitive processes, including action decisions underlying saccadic control. Changes in saccadic eye movements are common across neurodegenerative diseases of ageing, including Parkinson’s disease. With growing interest in noradrenergic treatment potential for non-motor symptoms in Parkinson’s disease, the temporal precision of oculomotor function is advantageous to assess the effects of this modulation. Here, we studied the effect of 40 mg atomoxetine, a noradrenaline reuptake inhibitor, in 19 people with idiopathic Parkinson’s disease using a single dose, randomized double-blind, crossover, placebo-controlled design. Twenty-five healthy adult participants completed the assessments to provide normative data. Participants performed prosaccade and antisaccade tasks. The latency, velocity and accuracy of saccades, and resting pupil diameter, were measured. Increased pupil diameter on the drug confirmed its expected effect on the locus coeruleus ascending arousal system. Atomoxetine altered key aspects of saccade performance: prosaccade latencies were faster and the saccadic main sequence was normalized. These changes were accompanied by increased antisaccade error rates on the drug. Together, these findings suggest a shift in the speed-accuracy trade-off for visuomotor decisions in response to noradrenergic treatment. Our results provide new evidence to substantiate a role for noradrenergic modulation of saccades, and based on known circuitry, we advance the hypothesis that this reflects modulation at the level of the locus coeruleus–superior colliculus pathway. Given the potential for noradrenergic treatment of non-motor symptoms of Parkinson’s disease and related conditions, the oculomotor system can support the assessment of cognitive effects without limb-motor confounds on task performance.
Graph neural network based phishing account detection in Ethereum
Authors: Ratra Siftee , Ghosh Mohona , Baliyan Niyati , Rashmitha Mohan Jinka , Singh Sanjana
Published: September 2024

In recent years, the widespread adoption of Ethereum-based transactions, such as cryptocurrencies and blockchain technologies, have revolutionized the way financial transactions are conducted. These decentralized and transparent systems offer numerous advantages, including enhanced security, immutability, and reduced transaction costs. However, alongside their benefits, Ethereum-based transactions have also attracted the attention of malicious actors seeking to exploit unsuspecting users through phishing scams. Phishing scams have thus become frequent in this scenario. Therefore, it is required to implement an effective and reliable phishing scam detection method. In this paper, we present the implementation of a highly efficient detection method by carrying out a graph-like data network formation, over which we then apply models that are based on graph neural networks like Magnet Link Prediction and Graph AutoEncoder Pathfinder Discovery Network Algorithm (GAE_PDNA). This helps in extracting useful information from the nodes of the graph. After relevant embeddings have been obtained, the classification of the phishing account is performed using AdaBoost classifier that helps in complex decision-making and detects the accounts related to the phishing scams. Our best model attains a precision of 0.99 and an F1 score of 0.99.

Highlights
Do DanGer-SHOCK-like patients benefit from VA-ECMO treatment in infarct-related cardiogenic shock? results of an individual patient data meta-analysis
Authors: Zeymer Uwe , Freund Anne , Hochadel Matthias , Ostadal Petr , Belohlavek Jan , Massberg Steffen , Brunner Stefan , Flather Marcus , Adlam David , Hassager Christian , Moeller Jacob E , Schneider Steffen , Desch Steffen , Thiele Holger
Published: September 2024

Aims

In a recent meta-analysis of randomized controlled trials, routine use of veno-arterial ECMO (VA-ECMO) did not improve outcomes in patients with acute myocardial infarction-related cardiogenic shock (AMI-CS), while a microaxial flow pump reduced mortality in a selected group of patients with AMI-CS in the DanGer-Shock trial.

Methods and results

Individual patient data of patients included in four randomized clinical trials investigating the routine use of VA-ECMO in AMI-CS were centrally analysed. For the purpose of this sub-analysis, DanGer-Shock-like patients were analysed (STEMI only, presumed low likelihood of brain injury). The primary endpoint was 180-day all-cause mortality. A total of 202 patients (106 randomized to VA-ECMO and 96 to control) were included. There were no differences in baseline characteristics, angiographic and interventional features between the two groups. Mortality after 6 months was numerically lower with VA-ECMO between the groups [45% in VA-ECMO group vs. 51% in control group; hazard ratio, 0.84; 95% confidence interval (CI), 0.56–1.26], while major bleeding (OR, 2.24; 95% CI, 1.08–4.64) and peripheral vascular complications (OR, 3.65; 95% CI, 1.15–11.56) were increased with the use of VA-ECMO.

Conclusion

In this exploratory subgroup analysis in patients with CS, STEMI, and a low likelihood of brain injury, there was no mortality benefit with the routine use of VA-ECMO. However, as indicated by the large confidence intervals, the statistical power was limited to draw definite conclusions.
Challenges in diagnosis and management of aortobronchial fistula: a case report
Authors: Abaydi Mohamed Hamza , Dhimene Safae , Ech-chenbouli Amine , El Boussaadani Badre , Raissuni Zainab
Published: September 2024

Background

Aortobronchial fistulas (ABFs) are rare but potentially life-threatening conditions, often presenting with haemoptysis. They can develop following various thoracic aortic conditions or procedures.

Case Presentation

A 70-year-old patient with a history of descending aorta replacement and ischaemic stroke presented with chest pain and upper gastrointestinal bleeding. Imaging revealed a fistula between the aortic prosthesis and the lung, along with other cardiovascular abnormalities. Despite the indication for anticoagulant therapy, tranexamic acid was initiated due to bleeding risk. The patient showed clinical improvement with tranexamic acid treatment but experienced recurrence of bleeding after discontinuation. Endovascular treatment for the contained rupture at the proximal stent anastomosis was indicated.

Discussion

Haemoptysis is the primary symptom of ABFs, often recurring until the fistula enlarges. Postoperative aortic fistulas into the airways are uncommon and can occur years after surgery. Thoracic endovascular aortic repair has become the primary treatment for high-risk patients with thoracic aortic disease. Various diagnostic modalities can visualize a fistula tract, but practical visualization is rare. Untreated ABFs invariably lead to death.

Conclusion

This case highlights the challenges in diagnosing and managing ABFs, emphasizing the need for a multidisciplinary approach and regular follow-up. Patient education and prompt reporting of symptoms are essential. Early intervention upon suspicion of recurrence is crucial for optimizing patient outcomes.
Blood culture-negative Haemophilus endocarditis with large vegetation and the role of bronchoalveolar lavage: a case report
Authors: Pant Samaksha , Colombier Sébastien , Lambert Nadège , Delay Dominique , Girod Grégoire
Published: September 2024

Background

Blood culture-negative endocarditis (BCNE) is a significant condition associated with cardiac vegetation. It often occurs alongside sepsis, auto-immune diseases, or malignancies, posing a risk of vegetation and embolization. Notable pathogens include Haemophilus species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species.

Case summary

A 60-year-old white male Belgian patient presented with worsening dyspnoea. His recent medical history included chronic infections over the past 6 months. Transthoracic echocardiography revealed severe aortic stenosis with an 18 × 12 mm vegetation. Despite normal inflammatory markers and negative blood tests, 18F-fluorodeoxyglucose positron emission tomography with computed tomography excluded malignancy but identified multiple bilateral septic lung emboli. Sputum cultures and tuberculosis polymerase chain reaction (PCR) were negative. Facing the high risk of cardiac embolization and the need for aortic valve replacement, surgery was scheduled with an intraoperative bronchoalveolar lavage (BAL) to investigate the lung lesions. Intraoperative findings confirmed valvular lesions, and a biological aortic valve was successfully implanted. The post-operative course was uneventful. Aortic valve cultures and eubacterial PCR results were negative, but BAL cultures were positive for Haemophilus influenzae, indicating a chronic infection. The patient showed favourable progress at 6 months post-surgery with ongoing antibiotherapy.

Discussion

This case illustrates a rare BCNE associated with large vegetation and symptomatic H. influenzae chronic respiratory tract colonization (CRTC). For BCNE cases with negative sputum cultures and suspected bacterial CRTC, we recommend performing BAL cultures for accurate diagnosis.
Effects of beta-blockers on quality of life and well-being in patients with myocardial infarction and preserved left ventricular function—a prespecified substudy from REDUCE-AMI
Authors: Mars Katarina , Humphries Sophia , Leissner Philip , Jonsson Martin , Karlström Patric , Lauermann Jörg , Alfredsson Joakim , Kellerth Thomas , Ravn-Fischer Annica , Erlinge David , Lindahl Bertil , Yndigegn Troels , Jernberg Tomas , Held Claes , Olsson Erik M G , Hofmann Robin
Published: September 2024

Aims

In the Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction (REDUCE-AMI) study, long-term beta-blocker use in patients after acute myocardial infarction (AMI) with preserved left ventricular ejection fraction demonstrated no effect on death or cardiovascular outcomes. The aim of this prespecified substudy was to investigate effects of beta-blockers on self-reported quality of life and well-being.

Methods and results

From this parallel-group, open-label, registry-based randomized clinical trial, EQ-5D, and World Health Organization well-being index-5 (WHO-5) questionnaires were obtained at 6–10 weeks and 11–13 months after AMI in 4080 and 806 patients, respectively. We report results from intention-to-treat and on-treatment analyses for the overall population and relevant subgroups using Wilcoxon rank sum test and adjusted ordinal regression analyses. Of the 4080 individuals reporting EQ-5D (median age 64 years, 22% female), 2023 were randomized to beta-blockers. The main outcome, median EQ-5D index score, was 0.94 [interquartile range (IQR) 0.88, 0.97] in the beta-blocker group, and 0.94 (IQR 0.88, 0.97) in the no-beta-blocker group 6–10 weeks after AMI, OR 1.00 [95% CI 0.89–1.13; P > 0.9]. After 11–13 months, results remained unchanged. Findings were robust in on-treatment analyses and across relevant subgroups. Secondary outcomes, EQ-VAS and WHO-5 index score, confirmed these results.

Conclusion

Among patients after AMI with preserved left ventricular ejection fraction, self-reported quality of life and well-being was not significantly different in individuals randomized to routine long-term beta-blocker therapy as compared to individuals with no beta-blocker use. These results appear consistent regardless of adherence to randomized treatment and across subgroups which emphasizes the need for a careful individual risk-benefit evaluation prior to initiation of beta-blocker treatment.
The incidence of atrial fibrillation detected by implantable loop recorders: a comparison between patients with and without embolic stroke of undetermined source
Authors: Chousou Panagiota A , Chattopadhyay Rahul K , Matthews Gareth , Clark Allan , Vassiliou Vassilios S , Pugh Peter J
Published: September 2024

Aims

Stroke is the most debilitating outcome of atrial fibrillation (AF). The use of implantable loop recorders increases the detection of AF episodes among patients with embolic stroke of undetermined source. The significance of device-detected AF, or subclinical AF, is unknown. This study aimed to compare the incidence of AF detected by implantable loop recorder in patients with and without embolic stroke of undetermined source.

Methods and results

We retrospectively studied all patients without known AF who were referred to our institution for implantable loop recorder implantation following embolic stroke of undetermined source, syncope, or palpitations from March 2009 to November 2019. The primary endpoint was any detection of AF or atrial flutter by implantable loop recorder. Seven hundred and fifty patients were included and followed up for a mean duration of 731 days (SD 443). An implantable loop recorder was implanted following embolic stroke of undetermined source in 323 and for assessment of syncope, palpitations, or another reason in 427 patients. The incidence of AF was significantly (P < 0.001) higher among patients with embolic stroke of undetermined source compared with the non-embolic stroke of undetermined source group; 48.6% vs. 13.8% (for any duration of AF) and 32.2% vs. 12.4% (for AF lasting ≥30 s) both P < 0.001. Kaplan–Meier analysis showed significantly higher incidence of AF for incremental durations of AF up to >5.5 h, but not >24 h. This was driven by longest AF durations of <6 min and between 5.5 h and 24 h, suggesting a bimodal distribution. In a multivariable Cox regression analysis, embolic stroke of undetermined source independently conferred an almost 5-fold increase in the hazard for any duration of AF.

Conclusion

The incidence of AF is significantly higher amongst embolic stroke of undetermined source vs. non-embolic stroke of undetermined source patients monitored constantly by an implantable loop recorder. A high number of embolic stroke of undetermined source survivors have short-duration AF episodes. Further work is needed to determine the optimal treatment strategy of these AF episodes in embolic stroke of undetermined source.
A decade of follow-up: atrial fibrillation, pulmonary pressure, and the progression of tricuspid regurgitation
Authors: Loutati Ranel , Katz Asaf , Segev Amit , Kuperstein Rafael , Sabbag Avi , Maor Elad
Published: September 2024

Background and aims

Long-term data on atrial fibrillation (AF) impact on tricuspid regurgitation (TR) progression and its relation to pulmonary pressure are scant. We investigated this association in a study spanning over a decade.

Methods and results

Adults with echocardiographic evaluation before 2014, free of significant TR, were included. Patients were dichotomized by baseline AF, followed by stratification according to systolic pulmonary artery pressure (sPAP). The development of new significant TR and its impact on mortality were studied. Study population included 21 502 patients (median age 65, 40% female), 13% had baseline AF. During a median follow-up of 12 years, 11% developed significant TR. Compared with patients free of AF, patients with baseline AF were 3.5 and 1.3 times more likely to develop significant TR in univariate and multivariate models, respectively (95% CI 3.27–3.91, 1.18–1.44, P < 0.001 for both). The risk of TR progression was higher in patients with permanent AF and those treated with rate control strategy (hazard ratio 1.95 and 2.01, respectively; P < 0.001 for both). The association of AF with TR progression was sPAP-related, being more pronounced among patients with normal sPAP than among those with elevated sPAP (HR 1.5 vs. 1.18; P for interaction <0.001). TR progression was independently linked to a two-fold higher mortality risk, consistent regardless of baseline AF (P < 0.001).

Conclusion

AF is an independent predictor of TR progression, especially in patients with normal sPAP. Subsequent research on strategies to prevent TR progression in this patient population is warranted.
Infective endocarditis with or without congenital heart disease: clinical features and outcomes
Authors: Havers-Borgersen Eva , Østergaard Lauge , Holgersson Christine Kjærsgaard , Stahl Anna , Schmidt Michael Rahbek , Smerup Morten , Køber Lars , Fosbøl Emil L
Published: September 2024

Background and Aims

Patients with congenital heart disease (CHD) form a high-risk subgroup for infective endocarditis (IE), necessitating tailored prevention and treatment strategies. However, comprehensive nationwide data comparing IE characteristics and outcomes in patients with and without CHD, including children, are sparse. This study aims to address this gap in knowledge.

Methods

Using Danish nationwide registries, all patients with IE from 1977 to 2021 were identified and stratified on whether they had a diagnosis of CHD, regardless of its complexity. Characteristics prior to and during admission as well as associated outcomes (i.e. in-hospital mortality, 1-year mortality, and 10-year mortality, and IE recurrence) were compared between groups.

Results

In total, 14 040 patients with IE were identified, including 895 (6.4%) with CHD. Patients with vs. without CHD were younger at the time of IE diagnosis (median age 38.8 vs. 70.7 years), less comorbid, and more frequently underwent cardiac surgery during admission (35.7% vs. 23.0%, P < .001). Notably, 76% of patients with IE < 18 years of age had CHD. The IE-related bacteraemia differed between groups: Streptococci (29.9%) were the most common in patients with CHD, and Staphylococcus aureus (29.9%) in patients without CHD. Patients with CHD had a significantly lower cumulative incidence of in-hospital mortality (5.7% vs. 17.0%, P < .001) and 1-year mortality (9.9% vs. 31.8%, P < .001) compared with those without CHD. The 10-year cumulative incidence of IE recurrence was similar between groups (13.0% and 13.9%, P = .61).

Conclusions

Patients with CHD who develop IE exhibit distinct characteristics and improved long-term outcomes compared with patients without CHD. Notably, the majority of children and adolescents with IE have underlying CHD.
Semaglutide and blood pressure: an individual patient data meta-analysis
Authors: Kennedy Cormac , Hayes Peter , Cicero Arrigo F G , Dobner Stephan , Le Roux Carel W , McEvoy John W , Zgaga Lina , Hennessy Martina
Published: September 2024

Background and Aims

Randomized clinical trials (RCTs) assessing semaglutide reported reductions of systolic blood pressure (SBP) in trial populations with baseline blood pressure in the normotensive range. This study aimed to determine whether this SBP reduction is greater in hypertensive groups.

Methods

Individual patient data (IPD) from three RCTs examining the effect of semaglutide 2.4 mg on body weight over 68 weeks were included. Trial participants were categorized according to a hypertension diagnosis, treatment or baseline measurement (HTN), baseline SBP > 130 mmHg (HTN130) or >140 mmHg (HTN140), and those with apparent resistant hypertension (RH). The primary analysis compared the in-trial change in SBP in the semaglutide and placebo arms. Alterations of anti-hypertensive medications were quantified by treatment intensity score and compared between arms. These analyses were performed using analysis of covariance.

Results

Overall, 3136 participants were included. The difference in SBP change between the treatment (n = 2109) and placebo (n = 1027) groups was −4.95 mmHg [95% confidence interval (CI) −5.86 to −4.05] overall. This difference was −4.78 mmHg (95% CI −5.97 to −3.59) for HTN, −4.93 mmHg (95% CI −6.75 to −3.11) for HTN130, −4.09 mmHg (95% CI −7.12 to −1.06) for HTN140, and −3.16 mmHg (95% CI −8.69–2.37) for RH. Reduction in SBP was mediated substantially by weight loss. The anti-hypertensive treatment intensity score decreased for those on semaglutide compared to placebo (−0.51; 95% CI −0.71 to −0.32).

Conclusions

This IPD analysis of three large RCTs found blood pressure reductions with semaglutide in participants with hypertension that were similar to those seen in all trial participants. This finding may in part be due to concurrent reductions to anti-hypertensive medications. These results suggest that semaglutide is a useful adjunctive treatment for patients with hypertension and obesity.
Strain surveillance during chemotherapy to improve cardiovascular outcomes: the SUCCOUR-MRI trial
Authors: Marwick Thomas H , Dewar Elizabeth , Nolan Mark , Shirazi Mitra , Dias Peter , Wright Leah , Fitzgerald Ben , Kearney Leighton , Srivastava Piyush , Atherton John , Negishi Kazuaki , Sverdlov Aaron L , Wahi Sudhir , Otton James , Selvanayagam Joseph , Thomas Liza , Thavendiranathan Paaladinesh
Published: September 2024

Background and Aims

The detection of cancer therapy-related cardiac dysfunction (CTRCD) by reduction of left ventricular ejection fraction (LVEF) during chemotherapy usually triggers the initiation of cardioprotective therapy. This study addressed whether the same approach should be applied to patients with worsening of global longitudinal strain (GLS) without attaining thresholds of LVEF.

Methods

Strain surveillance during chemotherapy for improving cardiovascular outcomes (SUCCOUR-MRI) was a prospective multicentre randomized controlled trial involving 14 sites. Of 355 patients receiving anthracyclines with normal baseline LVEF, 333 patients (age 59 ± 13 years, 79% women) with at least one other CTRCD risk factor, able to undergo magnetic resonance imaging (MRI), GLS, and three-dimensional echocardiography were tracked over 12 months. A total of 105 patients (age 59 ± 13 years, 75% women, 69% breast cancer) developing GLS-CTRCD (>12% relative reduction of GLS without a change in LVEF) were randomized to cardioprotection with neurohormonal antagonists vs. usual care. The primary endpoint was 12-month change in MRI-LVEF; the secondary endpoint was MRI-LVEF-defined CTRCD.

Results

During follow-up, two patients died, and two developed heart failure. Most patients were randomized at 3 months (62%). Median doses of angiotensin inhibition/blockade and beta-blockade were 75% and 50% of respective targets; 21 (43%) had side-effects attributed to cardioprotection. Due to a smaller LVEF change from baseline with cardioprotection than usual care (−2.5 ± 5.4% vs. −5.6 ± 5.9%, P = .009), follow-up LVEF was higher after cardioprotection (59 ± 5% vs. 55 ± 6%, P < .0001). After adjustment for baseline LVEF, the mean (95% confidence interval) difference in the change in LVEF between the two groups was −3.6% (−1.8% to −5.5%, P < .001). After cardioprotection, 1/49 patients developed 12-month LVEF-CTRCD, compared to 6/56 in usual care (P = .075). Global longitudinal strain improved at 3 months post-randomization in the cardioprotection group, with little change with usual care.

Conclusions

In patients with isolated GLS reduction after anthracyclines, cardioprotection is associated with better preservation of 12-month MRI-LVEF compared with usual care.
Intensive early and sustained lowering of non–high-density lipoprotein cholesterol after myocardial infarction and prognosis: the SWEDEHEART registry
Authors: Schubert Jessica , Leosdottir Margrét , Lindahl Bertil , Westerbergh Johan , Melhus Håkan , Modica Angelo , Cater Nilo , Brinck Jonas , Ray Kausik K , Hagström Emil
Published: September 2024

Background and Aims

Non–HDL-C provides an estimate of lipid-associated risk and is a secondary treatment target after myocardial infarction (MI). The aim was to study the relationship between non–HDL-C levels after MI and risk of adverse outcomes.

Methods

From the SWEDEHEART registry, 56 262 patients with MI were included. Outcomes were major adverse cardiovascular event (MACE: death, MI, and ischaemic stroke), death, and non-fatal MI. Non–HDL-C was assessed at admission, 2 months, and 1 year. Target achievement (<2.2 mmol/L) of non–HDL-C, timing thereof, and outcomes were assessed.

Results

During median follow-up of 5.4 years, 9549 had MACE, 5427 died, and 3946 had MI. Long-term hazard ratio (HR) for MACE in the lowest vs. the highest quartile of achieved non–HDL-C at 1 year was 0.76 [95% confidence interval (CI) 0.71–0.81]. Short-term results were consistent also when assessing non–HDL-C levels at 2 months, including early events up to 1 year (HR 0.80, 95% CI 0.68–0.92). Similar results were observed for all outcomes. Patients achieving both early and sustained targets had lowest risk of outcomes (HR 0.80, 95% CI 0.74–0.86) vs. patients achieving target early or late (HR for both 0.86, 95% CI 0.79–0.93).

Conclusions

The lowest achieved levels both at 2 months and at 1 year of non–HDL-C were associated with better outcome. The lowest risk was observed when target was achieved within 2 months of MI and sustained thereafter. These findings challenge the current stepwise approach for cholesterol lowering after MI, which inevitably results in delaying goal attainment and possible harm.
Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy
Authors: Garcia-Pavia Pablo , Oręziak Artur , Masri Ahmad , Barriales-Villa Roberto , Abraham Theodore P , Owens Anjali T , Jensen Morten K , Wojakowski Wojciech , Seidler Tim , Hagege Albert , Lakdawala Neal K , Wang Andrew , Wheeler Matthew T , Choudhury Lubna , Balaratnam Ganesh , Shah Ashish , Fox Shawna , Hegde Sheila M , Olivotto Iacopo
Published: September 2024

Background and Aims

Long-term safety and efficacy of mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM) are unknown. MAVA-LTE (NCT03723655) is an ongoing, 5-year, open-label extension study designed to evaluate the long-term effects of mavacamten.

Methods

Participants from EXPLORER-HCM (NCT03470545) could enrol in MAVA-LTE upon study completion.

Results

At the latest data cut-off, 211 (91.3%) of the 231 patients originally enrolled in MAVA-LTE still received mavacamten. Median (range) time on study was 166.1 (6.0–228.1) weeks; 185 (80.1%) and 99 (42.9%) patients had completed the Week 156 and 180 visits, respectively. Sustained reductions from baseline to Week 180 occurred in left ventricular outflow tract gradients [mean (standard deviation): resting, −40.3 (32.7) mmHg; Valsalva, −55.3 (33.7) mmHg], N-terminal pro B-type natriuretic peptide [median (interquartile range): −562 (−1162.5, −209) ng/L], and EQ-5D-5L score [mean (standard deviation): 0.09 (0.17)]. Mean left ventricular ejection fraction (LVEF) decreased from 73.9% (baseline) to 66.6% (Week 24) and 63.9% (Week 180). At Week 180, 74 (77.9%) of the 95 patients improved by at least one New York Heart Association class from baseline. Over 739 patient-years exposure, 20 patients (8.7%; exposure-adjusted incidence: 2.77/100 patient-years) experienced 22 transient reductions in LVEF to <50% resulting in temporary treatment interruption (all recovered LVEF of ≥50%). Five (2.2%) patients died (all considered unrelated to mavacamten).

Conclusions

Long-term mavacamten treatment resulted in sustained improvements in cardiac function and symptoms in patients with obstructive HCM, with no new safety concerns identified. Transient, reversible reductions in LVEF were observed in a small proportion of patients during long-term follow-up.
Glycoprotein IIb/IIIa inhibitors in acute myocardial infarction and angiographic microvascular obstruction: the REVERSE-FLOW trial
Authors: Eitel Ingo , Saraei Roza , Jurczyk Dominik , Fach Andreas , Hambrecht Rainer , Wienbergen Harm , Frerker Christian , Schmidt Tobias , Allali Abdelhakim , Joost Alexander , Marquetand Christoph , Kurz Thomas , Haaf Philip , Fahrni Gregor , Mueller Christian , Desch Steffen , Thiele Holger , Stiermaier Thomas
Published: September 2024

Background and Aims

Glycoprotein (GP) IIb/IIIa inhibitors are recommended in acute myocardial infarction (AMI) for bailout treatment in case of angiographic microvascular obstruction (MVO), also termed no-reflow phenomenon, after percutaneous coronary intervention (PCI) with, however, lacking evidence (class IIa, level C).

Methods

The investigator-initiated, international, multicentre REVERSE-FLOW trial randomized 120 patients with AMI and thrombolysis in myocardial infarction flow grade ≤ 2 after primary PCI to optimal medical therapy with or without GP IIb/IIIa inhibitor. The primary endpoint was infarct size [percentage of left ventricular (LV) mass assessed by cardiac magnetic resonance (CMR). Secondary endpoints included CMR-derived MVO and 30-day adverse clinical events. The trial is registered with ClinicalTrials.gov: NCT02739711.

Results

The population was predominantly male (76.7%) with a median age of 66 years and ST-elevation myocardial infarction in 73.3% of patients. Clinical and angiographic characteristics were well balanced between the cohorts. Patients in the treatment group (n = 62) received eptifibatide (n = 41) or tirofiban (n = 21). Infarct size assessed by CMR imaging was similar in both study groups [25.4% of LV mass (%LV) vs. 25.2%LV; P = .386]. However, the number of patients with evidence of CMR-derived MVO (74.5% vs. 92.2%; P = .017) and the extent of MVO (2.1%LV vs. 3.4%LV; P = .025) were significantly reduced in the GP IIb/IIIa inhibitor group compared with controls. Thirty-day outcome showed an increased bleeding risk after GP IIb/IIIa inhibitor administration restricted to non–life-threatening bleedings (22.6% vs. 6.9%; P = .016) without differences in all-cause mortality (4.8% vs. 3.4%; P = .703).

Conclusions

Bailout GP IIb/IIIa inhibition in AMI patients with angiographic MVO failed to reduce the primary endpoint infarct size but decreased CMR-derived MVO and led to an increase in non-fatal bleeding events.
Long-term effect of biodegradable vs. durable polymer everolimus-eluting stents on neoatherosclerosis in ST-segment elevation myocardial infarction: the CONNECT trial
Authors: Taniwaki Masanori , Häner Jonas Dominik , Kakizaki Ryota , Ohno Yohei , Yahagi Kazuyuki , Higuchi Yoshiharu , Siontis George C M , Ando Kenji , Stortecky Stefan , Suzuki Nobuaki , Morf Laura , Watanabe Naoki , Lanz Jonas , Ueki Yasushi , Otsuka Tatsuhiko , Biccirè Flavio Giuseppe , Sakurada Masami , Losdat Sylvain , Räber Lorenz
Published: September 2024

Background and Aims

Neoatherosclerosis is a leading cause of late (>1 year) stent failure following drug-eluting stent implantation. The role of biodegradable (BP) vs. durable polymer (DP) drug-eluting stents on long-term occurrence of neoatherosclerosis remains unclear. Superiority of biodegradable against durable polymer current generation thin-strut everolimus-eluting stent (EES) was tested by assessing the frequency of neoatherosclerosis 3 years after primary percutaneous coronary intervention (pPCI) among patients with ST-segment elevation myocardial infarction (STEMI).

Methods

The randomized controlled, multicentre (Japan and Switzerland) CONNECT trial (NCT03440801) randomly (1:1) assigned 239 STEMI patients to pPCI with BP-EES or DP-EES. The primary endpoint was the frequency of neoatherosclerosis assessed by optical coherence tomography (OCT) at 3 years. Neoatherosclerosis was defined as fibroatheroma or fibrocalcific plaque or macrophage accumulation within the neointima.

Results

Among 239 STEMI patients randomized, 236 received pPCI with stent implantation (119 BP-EES; 117 DP-EES). A total of 178 patients (75%; 88 in the BP-EES group and 90 in the DP-EES group) underwent OCT assessment at 3 years. Neoatherosclerosis did not differ between the BP-EES (11.4%) and DP-EES (13.3%; odds ratio 0.83, 95% confidence interval 0.33–2.04, P = .69). There were no differences in the frequency of fibroatheroma (BP-EES 9.1% vs. DP-EES 11.1%, P = .66) or macrophage accumulation (BP-EES 4.5% vs. DP-EES 3.3%, P = .68), and no fibrocalcific neoatherosclerosis was observed. Rates of target lesion failure did not differ between groups (BP-EES 5.9% vs. DP-EES 6.0%, P = .97).

Conclusions

The use of BP-EES for primary PCI in patients presenting with STEMI was not superior to DP-EES regarding frequency of neoatherosclerosis at 3 years.
Cardiac biomarkers and effects of aficamten in obstructive hypertrophic cardiomyopathy: the SEQUOIA-HCM trial
Authors: Coats Caroline J , Masri Ahmad , Barriales-Villa Roberto , Abraham Theodore P , Brinkley Douglas Marshall , Claggett Brian L , Hagege Albert , Hegde Sheila M , Ho Carolyn Y , Kulac Ian J , Lee Matthew M Y , Maron Martin S , Olivotto Iacopo , Owens Anjali T , Solomon Scott D , Tfelt-Hansen Jacob , Watkins Hugh , Jacoby Daniel L , Heitner Stephen B , Kupfer Stuart , Malik Fady I , Meng Lisa , Wohltman Amy , Januzzi James L
Published: September 2024

Background and Aims

The role of biomarker testing in the management of obstructive hypertrophic cardiomyopathy is not well defined. This pre-specified analysis of SEQUOIA-HCM (NCT05186818) sought to define the associations between clinical characteristics and baseline concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI), and to evaluate the effect of treatment with aficamten on biomarker concentrations.

Methods

Cardiac biomarkers were measured at baseline and serially throughout the study. Regression analyses determined predictors of baseline NT-proBNP and hs-cTnI concentrations, and evaluated whether early changes in these biomarkers relate to later changes in left ventricular outflow tract gradient (LVOT-G), other echocardiographic measures, health status, and functional capacity.

Results

Baseline concentration of NT-proBNP was associated with LVOT-G and measures of diastolic function, while hs-cTnI was associated with left ventricular thickness. Within 8 weeks of treatment with aficamten, NT-proBNP was reduced by 79% (95% confidence interval 76%–83%, P < .001) and hs-cTnI by 41% (95% confidence interval 32%–49%, P < .001); both biomarkers reverted to baseline after washout. Reductions in NT-proBNP and hs-cTnI by 24 weeks were strongly associated with a lowering of LVOT-G, improvement in health status, and increased peak oxygen uptake. N-Terminal pro-B-type natriuretic peptide reduction strongly correlated with the majority of improvements in exercise capacity. Furthermore, the change in NT-proBNP by Week 2 was associated with the 24-week change in key endpoints.

Conclusions

N-Terminal pro-B-type natriuretic peptide and hs-cTnI concentrations are associated with key variables in obstructive hypertrophic cardiomyopathy. Serial measurement of NT-proBNP and hs-cTnI appears to reflect clinical response to aficamten therapy.