bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diastolic function assessment with left atrial strain in long-term survivors of childhood acute lymphoblastic leukemia
Authors: Fernandez-Aviles Irache C , Gonzalez Manzanares R , Heredia Campos G , Resua Collazo A , Castillo Dominguez J C 
Published: November 2023

Abstract

Background
Survivors of childhood cancer might be at increased risk of diastolic dysfunction at follow-up due to cardiotoxic treatment exposure. Although diastolic function assessment is challenging in this relatively young population, left atrial strain might provide a novel insight into this evaluation.

Purpose
To examine diastolic function in a cohort of long-term survivors of childhood acute lymphoblastic leukemia survivors using left atrial strain and conventional echocardiographic parameters.

Methods
Long-term survivors who were diagnosed at a single center between 1985-2015 and a control group of healthy siblings were recruited. Conventional diastolic function parameters and strain were compared, the latter measured during the three atrial phases: reservoir (PALS), conduit (LACS) and contraction (PACS). Inverse probability of treatment weighting was used to account for differences between the groups.

Results
90 survivors (24.6±9.7 years, time since diagnosis 18 [11-26] years) and 58 controls were analyzed. PALS and LACS were significantly reduced compared to the control group: 46.4±11.2 vs 52.1±11.7 (p=0.003) and 32.5±8.8 vs 38.2±9.3 (p=0.003), respectively (figure 1B). Conventional diastolic parameters and PACS were similar between the groups (figure 1A). The reductions in PALS and LACS were associated to cardiotoxic treatment exposure in age and sex adjusted analysis (≥ moderate risk, low risk, controls): 45.4±10.5, 49.5±12.9, 52.1±11.7 (padj=0.003) and 31.7±9.0, 35.2±7.5, 38.2±9.3 (padj=0.001), respectively (figure 2).

Conclusions
Long-term childhood leukemia survivors showed a subtle impairment in diastolic function that was detected using atrial strain but not with conventional measurements. This impairment was more pronounced in those with higher cardiotoxic treatment exposure.Figure 1Figure 2
Characteristics and outcome of chest pain among patients with and without a history of cancer
Authors: Faierstein K , Tal-Ben Ishay R T B I , Raphael R R , Peretz Y P , Fourey D F , Shilo N S , Mayan H M , Maor E M 
Published: November 2023

Abstract

Background
Progress in medical oncology has led to remarkable contributions and prolonged life expectancy among cancer patients. Despite the improved prognosis, cancer treatment is associated with adverse cardiovascular outcomes in the oncologic population. This study aims to investigate the clinical characteristics and outcomes of cancer survivors presenting to the emergency department with chest pain.

Methods
We included consecutive adult patients (18 years and older) who presented at a large tertiary medical center, with chest pain between 2007 and 2022 and were hospitalized for further investigation. All-cause mortality and cancer data were available for all patients from national registries. Patients with active cancer were excluded. Patients were divided into two groups; (1) past cancer (defined as no oncologic therapy in the previous 6 months) and (2) no cancer history. A binary logistics regression model was used to identify patients diagnosed with non-ST-segment elevation myocardial infarction (NSTEMI), pulmonary embolism, new-onset atrial fibrillation, or death within 30 days of presentation.

Results
Final study population included 37,633 patients with a median age of 65 (IQR, 55-75), of whom 13,089 (34.8%) were women. There were 1807 (5%) patients with a history of cancer and 35,829 (95%) with no oncologic background. Patients with a cancer history were older (65 vs. 64, p&lt;0.001) and were less likely to be men (50% vs. 66%, P&lt;0.001). Univariate binary logistic regression demonstrated that cancer survivors were almost three times more likely to meet the study end-point and to have a cardiovascular diagnosis during hospitalization (OR 2.55, 95% CI 2.24-2.91, p&lt;0.001). The association was consistent in a multivariate model (OR 1.7, 95% CI 1.46-1.96, p&lt;0.001) and was more pronounced among females. During a median follow-up of 5.8 years (IQR, 2.4-8.1), 6,987 patients died. Kaplan-Meier survival analysis demonstrated that cancer survivors were more likely to die during follow-up (7.2% vs. 2.2%, respectively, log-rank P&lt;0.001). A propensity score matching model demonstrated that cancer survivors were twice more likely to meet the study end-point of in-hospital cardiovascular diagnosis or mortality within 30 days (17% vs. 8%, p&lt;0.001).

Conclusions
Among patients hospitalized with chest pain, those with an oncologic background are twice more likely to have a cardiovascular diagnosis that can explain their symptoms. In addition, these patients are at risk for short and long-term mortality. Our results support including a history of cancer in risk stratification models of patients presenting with chest pain.Kaplan-Meier curve by oncologic historyCardiovascular endpoints (log. scale)
Risk prediction model of cardiotoxicity in breast cancer patients; the multicenter prospective CHECK HEART-BC (comprehensive heart imaging to evaluate cardiac damage linked with chemotherapy in breast
Authors: Terui Y , Nochioka K , Ota H , Tada H , Sato H , Miyata S , Toyoda S , Shimojima M , Izumiya Y , Kitai T , Yasuda S , Sugimura K 
Published: November 2023

Abstract

Background
Cardiotoxicity due to cancer therapy has been emerging as an important issue along with the improvement in prognosis of breast cancer patients. Although the usefulness of global longitudinal strain and biomarker analysis was previously reported separately, there are few studies based on systematic evaluation of cardiotoxicity. Furthermore, large prospective cohort studies regarding cardiotoxicity and its prediction in breast cancer patients were also limited.

Purpose
Multicenter prospective study was performed to reveal the current characteristics of cardiotoxicity and develop a robust prediction model for cardiotoxicity using systematic evaluation of cardiac function.

Methods and results
Breast cancer patients who were scheduled for neoadjuvant and/or adjuvant chemotherapy were prospectively screened at the 25 participating institutions from August 2017 and March 2020. As a study protocol, follow-up visits were planned every 3 months from pre-treatment to 12 months after chemotherapy (median follow-up of 366 days). To evaluate their cardiac function, echocardiography, high-sensitive cardiac troponin, natriuretic peptide, and 12-lead ECG were acquired at every follow-up visit. cardiotoxicity was defined as a reduction in LVEF &gt;10% point from baseline and to a value &lt;53% in LVEF.

Results
542 chemotherapy-naïve patients were included for analysis from 25 institutions. cardiotoxicity developed in 46 (8.5%) during follow-up period. The HEART2 score based on pre-treatment data (model A) was composed of 6 variables including heart rate &gt;64 bpm, LV end-systolic volume index &gt;36.0 mL/m2, treatment with anthracycline, with radiation, with trastuzumab, and TAPSE &lt;26 mm. The receiver-operating characteristic (ROC) curve showed acceptable accuracy (an area under curve (AUC) 0.74 [95%confidence interval 0.66-0.81], P&lt;0.01). Furthermore, the ROC curve of the HEART2 score adding variables of 3 months after chemotherapy (model B) (difference in heart rate from pre-treatment, LV end-systolic volume index &gt;42.0 mL/m2) showed a greater AUC than the model based on only pre-treatment data (AUC 0.81 [95%confidence interval 0.73-0.90], P&lt;0.01). No patient with low-risk group in the HEART2 score based on variables of pre-treatment and 3 months after chemotherapy developed cardiotoxicity, while 28.1% developed cardiotoxicity in patients with high-risk group in both models.

Conclusions
CHECK HEART-BC study revealed current clinical characteristics of cardiotoxicity and developed the HEART2 score which showed good accuracy and consistency. The HEART2 score can provide an efficient and effective strategy for early detection of cardiotoxicity.The HEART2 scoreThe combination of model A and B
Long-term and real-life incidence of cancer therapy-related cardiovascular toxicity in patients with breast cancer: a swedish cohort study
Authors: Mallios P , Hubbert L , Karlstrom P , Papakonstantinou A , Bergh J , Hedayati E 
Published: November 2023

Abstract

Background
Cancer treatment and cancer itself increase the risk for cardiovascular disease (CVD) which in its turn contributes to cancer therapy-related cardiovascular toxicity (CTR-CVT). The aim of this study was to evaluate the long-term risk and predictors of CTR-CVT as well as all-cause mortality in women diagnosed with early breast cancer (BC) who were candidates for adjuvant chemotherapy.

Methods
Data from 433 women aged 18-60 years who were diagnosed with lymph node-positive BC between 1998-2002 and were eligible for adjuvant chemotherapy, were collected from Swedish health registers and medical records. For this study CTR-CVT was defined as hypertension (HT), coronary artery disease (CAD), heart failure (HF) or atrial fibrillation (AF) after the diagnosis of BC. Follow-up was from the date of BC diagnosis until November 30, 2021, or death. The incidence of CTR-CVT and all-cause mortality were calculated and hazard ratios (HR) for various factors associated with CTR-CVT were determined.

Results
The median age of the study population was 50 years (interquartile range (IQR) 32 years). A total of 910 CTR-CVT events were diagnosed in 311 women with a median of 19.3 years of follow-up (IQR 15.3 years). The proportions of CTR-CVT events were as follows: HT 281 (64%); CAD 198 (46%); HF 206 (47%); and AF 225 (51%). The cumulative incidence of CTR-CVT was 71.8% and 50% of all 433 patients developed CTR-CVT within 11.7 years of BC diagnosis (standard deviation (SD) 0.57, 95% confidence interval (CI) 10.6-12.9). Age was a risk factor for CTR-CVT. Treatment with anthracyclines increased the risk for HF (p=0.001; HR 2.0; 95%CI 1.4-2.8), CAD (p= 0.002; HR 1.7; 95% CI 1.2-2.4), and AF (p=0.013; HR 1.5; 95%CI 1.0-2.0). At the end of the 24-year study period, 227 of the 433 women were alive and the total cumulative mortality was 47.6%. Chemotherapy (anthracyclines or other agent) and older age at the time of BC diagnosis were associated with higher mortality rate.

Conclusions
In this cohort study the incidence of CTR-CVT and all-cause mortality after BC diagnosis and treatment was high, particularly in older patients and those receiving anthracyclines. This finding together with the time to onset of CTR-CVT, supports the current cardio-oncology guidelines recommending initial risk stratification, cardiovascular monitoring during treatment, followed by long-term annual screening for cardiovascular risk factors and CTR-CVT among BC survivors.Incidence CTR-CVTSurvival rate
The Dutch Cardio-Oncology cohort: Incidence of cardiovascular disease predisposes to a higher cancer mortality rate
Authors: Koop Y , Yousif L , De Boer R A , Bots M , Meijers W , Vaartjes C H 
Published: November 2023

Abstract

Background
Cardiovascular disease (CVD) and cancer are the two leading causes of death worldwide. The relationship between the two diseases is complex and multi-factorial, with both diseases sharing risk factors and influencing each other's pathogenesis and progression. Given this interaction and the high prevalence of both CVD and cancer, it is crucial to understand the impact of CVD incidence on cancer mortality and to evaluate which CVD patients are at highest risk. This study aims to evaluate which patients with incidence cardiovascular disease have a higher risk of malignancy-related mortality, stratified for type of cardiovascular disease and compared to the general population without cardiovascular diseases.

Methods
We performed a national population-based cohort study with incidence CVD patients, in the Netherlands between January 2000 and December 2005. A control group was selected from the entire Dutch population using a genetic matching algorithm, which consists of the closest match for age and sex, and a propensity scores for country of birth. Both CVD and control patients were older than 18 years and did not have current diagnosis or a history of CVD and malignancies in the 5 years before inclusion. Mortality data were evaluated after data linkage of national registries from Dutch Hospital Data and Statistics Netherlands until December 2020. Cox proportional hazard models were performed to evaluate mortality risk.

Results
A total of 2 240 879 participants were included with a mean follow-up of 12 years (sd 7.6), of which 738 666 developed CVD. Mean age was 70.5 years (sd 14.8) for CVD patients and 66.4 years (sd 15.9) for control patients. Amongst CVD patients, 492 551 (66.7%) died within follow-up, in 90 982 (12.3%) malignacies were the primary cause. For control patients, this was 641 117 (42.7%) and 169 180 (11.3%), respectively. Correcting for follow-up time, malignancy-related mortality incidence rates per 1000 person years were 118 for patients with CVD and 84 for control patients. The hazard of malignancy-related mortality was significantly higher in CVD patients compared to control patients (HR 1.42, 95% CI 1.41 – 1.43). The patients most at risk were those with venous diseases (i.e. phlebitis, venous embolism and thrombosis; HR 2.28 95% CI (2.20 – 2.36) and peripheral artery disease (HR 1.89, 95% CI 1.81 – 1.94). The incidence rate of malignancy related mortality was highest in patients with heart failure, with an incidence of 258 per 1000 person-years.

Conclusions
This is the first in depth study evaluating malignancy-related mortality in patients with newly developed CVD. Results show that CVD predisposes to a higher cancer mortality rate, especially in patients with venous and peripheral artery diseases. The interaction between CVD and cancer underlines the need to develop strategies for early detection and effective management of both diseases in this population.
Effects on reduction of morbidity and mortality in ACHD population of childbearing age as a result of ESC Guidelines
Authors: Metwaly S , Lennie V 
Published: November 2023

Abstract

Introduction
Cardiovascular disease remains the leading cause of maternal death during pregnancy and peripartum period. ACHD is a rising cause for maternal cardiovascular complications. Several studies demonstrated the beneficial role of systematic maternal cardiovascular risk assessment culminating in the European Society of Cardiology guidelines in 2018 endorsing the use of the modified World Health Organization (mWHO) classification to stratify maternal risk and further guide surveillance and management of women with underlying cardiac conditions.

Purpose
In this study we aim to reduce maternal cardiovascular morbidity risks by actively implementing recommendations from the 2018 ESC guidelines for the management of cardiovascular diseases in women with ACHD in childbearing age in Grampian region, Scotland.

Methods
We identified women of childbearing age (n = 204) in the ACHD population of NHS Grampian (n = 594). We initially calculated baseline percentage of ACHD women who had pre-pregnancy counselling, documented mWHO risk assessment and, if applicable, contraception advice and pregnancy rate. This population has been prospectively followed up during the period from 2020 to 2022 and ESC guidelines were implemented. By the end of the follow up period we assessed the changes in the pregnancy rate in ACHD women.

Results
Overall, the population of ACHD women of childbearing age in Grampian region has significantly grown (expanded) during the study period (from n = 204 to n = 230) and the vast majority (90.5%) of these patients are diagnosed with mWHO class I (38.3%, ESC mild ACHD) or mWHO class II / class II-III (52.2%, ESC moderate ACHD). There has been an increase in the percentage of women reviewed in Transition Clinic compared to baseline (44.7% versus 27.8%, respectively), a clearer documentation of mWHO pregnancy risk (31.6% versus 7.3%) and an increase in contraceptives use, especially in moderate and severe ACHD patients compared to baseline (65.2% versus 57.1%, respectively). This resulted in an overall reduction of the numbers of pregnancy in ACHD women compared to baseline (7.9% versus 40.1%, respectively), especially in women with ESC moderate and severe ACHD (Table 1) with consequent reduction in hospital admissions and morbidity.

Conclusions
Implementing risk stratification tools (mWHO pregnancy risk stratification) and systematic pre-pregnancy counselling with contraceptive advice (all key recommendations from the ESC guidelines) reduce the rate of high-risk pregnancy in ACHD women. This translates to an improvement in survival rates and lower morbidity in ACHD women. Further follow up is required to ensure the consistency of this finding.
Pregnancy and cardiac maternal outcomes in women with inherited cardiomyopathy: interest of the new CARPREG II risk score
Authors: Wallet T , Legrand L , Isnard R , Gandjbakhch E , Pousset F , Proukhnitzky J , Dommergues M , Nizard J , Charron P 
Published: November 2023

Abstract

Introduction
Inherited cardiomyopathies are rare but at high risk of cardiac maternal morbidity and mortality during pregnancy and post-partum. However data for risk stratification remains scarce. The new CARPREG II index score emerged to better predict prognosis in pregnancies with heart disease. Still, role of this score in inherited cardiomyopathies is unclear.

Objective
To describe characteristics and cardiac maternal outcomes in patients with inherited cardiomyopathy during pregnancy, and to evaluate the interest of the various index scores in this population.

Methods
In this retrospective monocentric study, 90 pregnancies of 74 patients were included (mean age 32 ± 5 years), with 28 dilated cardiomyopathies (DCM), 46 hypertrophic cardiomyopathies, 11 arrhythmogenic right ventricular cardiomyopathies and 5 left ventricular non compaction, excluding peri partum cardiomyopathies.

Results
A cardiac maternal complication was observed for 18 (20%) pregnancies, mainly driven by arrythmia and heart failure, and with 3 cardiovascular deaths. 43 (48 %) presented fetal or neo natal complications, with 18 premature delivery and 3 fetal or neonatal death. Median CARPREG II score was 2 [0;3], higher in the DCM subgroup. CARPREG II was significantly associated with the onset of cardiac maternal complication (p&lt; 0.05 for all) and seemed to show a better performance for risk stratification than previous scores (Area under curve of ROC: 0.782 for CARPREG II, AUC 0.755 and 0.697 for CARPREG and mWHO respectively). Prior hospitalization for heart failure, left ventricular dysfunction, multiple line treatments, cardiac symptoms prior to pregnancy and late pregnancy assessment were associated with cardiac complications (p &lt; 0.05 for all)

Conclusion
Pregnancy in women with inherited cardiomyopathy remains at high risk of maternal cardiovascular major events. Late pregnancy assessment and initial severity of cardiomyopathy were found associated with cardiac prognosis. The new CARPREG II score appeared as the most efficient for cardiac risk stratification in this population.
A non-coding SCN5A variant that reduces sodium channel function in hiPSC-derived cardiomyocytes is significantly enriched in Brugada syndrome patients from Thailand
Authors: Walsh R , Mauleekoonphairoj J , Mengarelli I , Verkerk A , Bosada F , Van Duijvenboden K , Poovorawan Y , Wongcharoen W , Sutjaporn B , Wandee P , Christoffels V , Wilde A , Nademanee K , Bezzina C , Khongphatthanayothin A 
Published: November 2023

Abstract

Background/Introduction
Brugada syndrome (BrS) is an inherited arrhythmia condition that can cause sudden cardiac death. Rare coding and common non-coding genetic variation in the Nav1.5 cardiac sodium channel-encoding SCN5A gene is robustly associated with BrS, but the role of rare and low frequency non-coding variants remains unexplored. BrS is several times more prevalent in Southeast Asia compared to other populations, indicating ancestry-specific genetic risk factors remain to be discovered.

Purpose
To identify and characterise novel genetic risk factors in BrS patients from Southeast Asia.

Methods
We performed genome sequencing in 231 BrS probands from Thailand and 500 population-matched controls to identify novel disease associated variants across the entire SCN5A locus. The candidate variant was engineered into human induced pluripotent stem cells (hiPSCs) by CRISPR-Cas9 and its effect was evaluated by single cell electrophysiology analysis on hiPSC-derived cardiomyocytes.

Results
We identified a rare (absent in gnomAD), non-coding variant in a regulatory element of the SCN5A gene (GRCh38:3-38580380-A-C) that was significantly enriched in cases (3.9%) vs controls (0.2%) (OR=20.2[2.5-160.6], p=2e-04). Transcription factor motif scanning analysis suggested the variant is likely to disrupt a Mef2 site that is conserved across species (Figure 1) – the MEF2 family of transcription factors play a critical role in cardiac transcriptional regulation. In hiPSC-derived cardiomyocytes, a significant reduction of peak Nav1.5-mediated sodium-current (INa) density (30% decrease at -20mV, p=8e-03), without changes in gating properties, was observed in cardiomyocytes carrying the variant in heterozygosity compared to isogenic controls (Figure 2). The variant also significantly reduced luciferase activity of the candidate regulatory element in HEK cells in the presence of cardiac transcription factors (Tbx5, Gata4, Mef2A, Mef2D).

Conclusion
A novel, non-coding variant in an SCN5A enhancer region is associated with BrS and was functionally validated using single cell electrophysiology in hiPSC-derived cardiomyocytes. This variant is found in ∼1 in every 25 BrS patients from Thailand and therefore may at least partially explain the increased prevalence of BrS in this region. Our study highlights the importance of research in understudied populations to understand the genetic aetiology of disease in diverse ancestries and to identify novel disease risk factors.