bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequential assessment of cardiac function after CART therapy in accordance with the grade of CRS
Authors: Sunayama I , Min K , Orihara Y , Yoshihara S , Yoshihara K , Matsumoto Y , Nishimura K , Naito Y , Goda A , Tamaki H , Higasa S , Asakura M , Ishihara M 
Published: October 2022

Abstract

Introduction
As Chimeric Antigen Receptor T-cell (CAR-T) therapy gains its clinical advantage in the management of diffuse large B cell lymphoma (DLBCL), accumulating evidence shows that it often accompanies cardiac dysfunction. Previous retrospective studies indicated the potential involvement of cytokine release syndrome (CRS) in cardiac dysfunction after CAR-T therapy, but no prospective study has reported the time course of cardiac dysfunction. Moreover, the relationship between the severity of CRS and cardiac dysfunction after CAR-T therapy remains unclear.

Purpose
The objectives of this study are to prospectively examine the sequential changes in cardiac markers overtime after CAR-T therapy and to clarify the association between the grade of CRS and cardiac markers.

Methods
In this prospective observational study, 30 DLBCL patients who underwent CAR-T therapy from July 2020 to March 2022 were enrolled. Before and after the treatment, the level of cardiac biomarkers and echocardiographic index were sequentially collected. We classified all patients into two groups according to the severity of CRS after CAR-T therapy, namely low-CRS group (CRS &lt;2) and high-CRS group (CRS ≥2). Cardiac biomarkers and echocardiographic parameters were further analyzed in both groups.

Results
The average age of participants was 59.6 years, and 9 patients (30%) were female. The average duration of DLBCL was 2.7 years. The CRS showed its peak severity on day 3. The number of patients in low- and high-CRS group was 13 and 17, respectively and tocilizumab was administrated for 46% and 71% of the patients in low- and high-CRS group, respectively. At the baseline before CAR-T therapy, there were no significant differences in cardiac parameters between the two groups. During the follow-up, sequential measurements of cardiac biomarkers revealed that high-CRS group showed significantly higher NT-proBNP level compared to that of low-CRS group (NT-proBNP; 90pg/ml vs. 623pg/ml, p=0.0001, respectively) and both had their peak on day 3, whereas troponin T level did not show any differences. Likewise, sequential measurements of echocardiographic parameters revealed that high-CRS group showed significantly increased E/A compared to low-CRS group on day 7 (E/A; 0.77 vs. 0.90, p=0.021, respectively), but not in the later phase. The parameters for systolic function including GLS and EF and parameters for diastolic function such as E/e' and LAVI did not alter among the two groups throughout the follow-up.

Conclusion
In the patients who underwent CAR-T therapy for DLBCL, the elevation of NT-proBNP level and increase in E/A was transiently observed within a week and correlated with the severity of CRS.

Funding Acknowledgement
Type of funding sources: None.
Use of emgliflozine in cardiotoxicity treatment. EMPACARD-treatment registry. Six-months follow-up
Authors: Daniele A J , Gregorietti V , Costa D , Lopez-Fernandez T 
Published: October 2022

Abstract

Background
Despite improvements in cancer management, cancer treatment related cardiac dysfunction (CTRCD) is a growing medical problem that impact cancer patients' prognosis, especially when it leads to early interruptions of effective anticancer therapies. Heart failure (HF) therapies are recommended in patients who develop symptomatic CTRCD or asymptomatic decrease in left ventricular ejection fraction (LVEF). However, the beneficial effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors was not prospectively tested in patients with cancer and CTRCD

Purpose
EMPACARD-treatment is a prospective registry aiming at evaluating the usefulness of empagliflozin on left ventricular remodelling in patients with metastatic breast cancer and refractory CTRCD.

Methods
Metastatic breast cancer patients, who develop refractory CTRCD during or after anthracycline chemotherapy and/or HER2 targeted therapies were prospectively included in our study and treated with empagliflozin 10mg/day on top of their current HF therapies. Refractory CTRCD was defined as symptomatic HF in patients treated with optimal doses of neurohormonal HF therapies, including sacubitril/valsartan. Clinical and echocardiographic variables were analysed to determine the potential benefits of empagliflozin on left ventricular remodelling (LVEF and left ventricular diastolic diameter (LVDD)), NT-proBNP levels, NHYA class and 6 minutes walking test (6MWT). The median follow-up was 6 months.
Continuous variables were summarized as medians with interquartile ranges (IQR) and compared with Wilcoxon's test for paired samples. Categorical values were expressed as percentages and compared with the chi-squared test. Statistical significance was considered with a p-value of less than 0.05. All analyses were performed with R version 4.1.1.

Results
19 metastatic breast cancer patients were included. Baseline characteristics and HF treatments are described in table 1. One patient received a heart transplant, and there were no deaths. At 6 months follow up LVEF significantly improved from 30% (IQR 27.5–32) to 38% (IQR (33.5–39), (p&lt;0.001), NT-proBNP decreased from 1342 pg/ml (IQR (977–1756) to 784 pg/ml (IQR 641–1099.5) (p&lt;0.0001), and similar improvements were observed in LVDD and 6MWT (Table 2). NYHA functional class improved in 95% of patients from class III to I or II at 6 months follow-up (p&lt;0.003).

Conclusions
Guideline-based HF therapy, including empagliflozin improves LV remodelling in patients with cancer and refractory CTRCD. Empagliflozin might be a promising treatment option in patients with refractory CTRCD

Funding Acknowledgement
Type of funding sources: None.
HFA-ICOS cardiovascular toxicity risk score validation in CARDIOTOX registry
Authors: Rivero Santana B , Caro Codon J , Juarez Olmos V , Martinez Monzonis A , Zatarain-Nicolas E , Moliner P , Cadenas Chamorro R , Severo Sanchez A , Valbuena Lopez S , Zamora Aunon P , Gomez Prieto P , Gonzalez Juanatey J R , Lopez-Sendon J , Lopez De Sa E , Lopez-Fernandez T 
Published: October 2022

Abstract

Background
Cancer therapy-related cardiovascular toxicity (CTox) is a growing medical problem and baseline cardiovascular (CV) risk assessment is recommended in all patients scheduled to receive potentially cardiotoxic cancer therapy. Based on literature review, the Heart Failure Association (HFA) Cardio-Oncology working group and the International Cardio-Oncology Society (ICOS) proposed a risk score to predict CTox but, it has not been validated.

Purpose
To validate the HFA-ICOS anthracycline risk assessment score in the CARDIOTOX registry cohort (NCT02039622).

Methods
The CARDIOTOX registry is a prospective multicenter study aiming at identifying factors related with CTox and assessing the utility of clinical, biochemical, and echo parameters for the early detection of CV disease during and after cancer therapy. A total of 1324 adult patients were prospectively included from April 2012 to October 2017. Data was collected at baseline, 3 weeks and 3, 6, 12, 18 and 24 months after initiation of treatment. Clinical follow-up was extended until January 2020. All patients receiving anthracycline chemotherapy were stratified according to HFA-ICOS risk score and Kaplan-Meier survival curves were analyzed to estimate the risk of all-cause mortality and anthracycline chemotherapy-related CV complications defined by HFA-ICOS risk score (left ventricular dysfunction (LVD), heart failure (HF) and arrhythmias).

Results
A total of 1066 patients were included in the analysis. Baseline characteristics are summarized in table 1. 571 patients (53.6%) meet low, 333 (31.2%) medium, 152 (14.3%) high and 10 (0.9%) very-high HFA-ICOS CTox risk criteria. 197 patients (18.4%) died of any cause during follow-up. CV death occurred in 4 patients (2%), all caused by HF. Any degree of CTox was identified in 519 (48.7%) patients during the 110 months follow-up (73 (6.8%) developed clinical HF/HF hospitalization, 29 (2.7%) asymptomatic LVEF &lt;50%; 27 (2.5%) clinically relevant arrhythmias and 390 (36.6%) an asymptomatic increase in cardiac biomarkers or a relative decrease in GLS&gt;15%). Figures 1A and 1B showed the cumulative mortality rate and CTox rate during follow-up. CTox and all-cause mortality rates increased significantly according to the estimated baseline HFA-ICOS score.

Conclusions
HFA-ICOS risk score categorizes patients according to their risk of developing anthracycline chemotherapy-related CTox, showing a good ability to predict both all-cause mortality and CTox.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III (PI13/00559).
Prognostic impact of coronary artery calcifications in patients with newly diagnosed prostate cancer
Authors: Stoedkilde-Joergensen N , Bugge Tinggaard A , Winther S , Ejlersen J A , Boettcher M 
Published: October 2022

Abstract

Background
Patients diagnosed with prostate cancer (PCa) are known to be at increased risk of cardiovascular events. Because of the ageing population and better cancer treatment, the number of these patients is increasing. A prostate-specific membrane antigen positron emission tomography (PSMA-PET) is guideline recommended as part of the diagnostic workup. This scan includes a non-ECG-gated computed tomography (CT) of the thorax, allowing assessment of coronary artery calcifications (CAC). It is not well-established, whether estimation of CAC based on this CT scan can identify patients with increased risk of major adverse cardiac events (MACE) and thus possibly improve therapy and prognosis.

Purpose
This study aims to assess CAC and evaluate whether high calcium scores predict the risk of MACE in patients newly diagnosed with PCa.

Methods
We identified 634 consecutive patients diagnosed with PCa and undergoing PSMA-PET from 2016 to 2019 in an area of 300.000 residents. In total, 63 patients were excluded due to prior revascularization. The remaining 571 patients (mean age 69.9±6.7 years) were included. Patients were followed until June 2021 or until an event occurred (mean follow-up 962±372 days). We used a standard cardiac CT software to assess CAC. Information on MACE defined as all-cause mortality, stroke and myocardial infarction were obtained from electronic patient files. We divided patients into five groups based on their coronary artery calcium score (CACS): 0–10, 11–99, 100–399, 400–999, and + 1000. Cox regression analysis was used to compute the hazard ratios (HR) for MACE with CACS 0–10 as reference while adjusting for age, hypertension diabetes, and treatment with aspirin and statins.

Results
We found a significantly increasing risk of MACE with increasing CACS after adjustment for risk factors. For CACS 100–399 (n=136): HR 2.10 (95% CI: 0.98–4.51, p=0.056), for CACS 400–999 (n=79): HR of 2.99 (95% CI: 1.35–6.59, p=0.007) and for CACS +1000 (n=150): HR 3.06 (95% CI: 1.37–6.85, p=0.006) (Figure 1). Cardiovascular disease prevention treatment with statins and aspirin was 53% and 16% in patients with CACS 400–999 and 52% and 19% in patients with CACS + 1000.

Conclusion
In patients with PCa, estimating coronary calcium score based on non-ECG-gated CT scans, which are performed as part of the diagnostic workup, predicts the occurrence of MACE. In the patient group with the highest CAC, a four-year event rate of 24% was found. In combination with the finding of infrequent use of statin and aspirin, this emphasizes the possibility of early detection of high CAC in patients with PCa and illustrates the potential for more extensive use of preventive treatment. Future studies should investigate the effect of preventive treatment being initiated in patients with PCa and high CAC.

Funding Acknowledgement
Type of funding sources: None.
Pregnancy outcomes in women with Ebstein's anomaly: data from the EORP Registry of Pregnancy and Cardiac Disease (ROPAC)
Authors: Van Der Zande J A , Tutarel O , Ramlakhan K P , Johson M R , Hall R , Roos-Hesselink J W 
Published: October 2022

Abstract

Background
Ebstein's anomaly is a rare congenital cardiac condition characterized by displacement of the posterior and septal leaflets of the tricuspid valve towards the apex of the right ventricle. The ESC Guidelines for the management of cardiovascular diseases during pregnancy categorize women with uncomplicated Ebstein's anomaly as modified World Health Organization (mWHO) risk class II. However, data regarding pregnancy outcomes in women with Ebstein's anomaly are scarce.

Purpose
To evaluate the maternal and perinatal risks of pregnancy in women with Ebstein's anomaly.

Methods
All patients with Ebstein's anomaly who had been included in the Registry of Pregnancy and Cardiac Disease (ROPAC), which is an international, prospective, observational registry of pregnant women with underlying cardiac disease (n=5739), were evaluated. The primary outcome was the occurrence of a major adverse cardiac event, defined as maternal mortality, heart failure, arrhythmia, thromboembolic events or endocarditis. The secondary outcomes were obstetric and perinatal outcomes and the influence of pregnancy on tricuspid valve regurgitation.

Results
Thirty-six hospitals in 22 countries enrolled 81 women with Ebstein's anomaly (mean age 29.7 years, 46.9% nulliparous). Seven (8.6%) women had a history of tricuspid valve repair and a further eight (9.9%) of tricuspid replacement. Most women (67.9%) were in NYHA class I. At least one major adverse cardiac event occurred in 8 (9.9%) pregnancies, including heart failure (n=6), supraventricular arrhythmia (n=3) and thromboembolic events (n=2). There was no maternal death. Almost half of the women underwent a Caesarean section (49%) and preterm delivery occurred in 24.7%. Neonatal mortality was 2.5% and four (4.9%) infants had neonatal congenital heart disease. Serial echocardiographic data pre- and postpregnancy were available in 14 women. There was no clear deterioration in tricuspid regurgitation (see Picture 1).

Conclusion
Although mortality was zero, in 10% of the pregnant women with Ebstein's anomaly a major adverse cardiac event occurred, most frequently heart failure or arrhythmia. Therefore, women with Ebstein's anomaly should be categorized as mWHO risk class II at least, but perhaps more correctly as II–III. Preconception counseling is crucial, so that women are aware of the potential risks of maternal morbidity, preterm delivery and congenital heart disease and the need for careful monitoring during pregnancy.

Funding Acknowledgement
Type of funding sources: None.
A nationwide cohort study on the impact of gestational diabetes on future cardiovascular events
Authors: Bullough S , Lip G Y H , Fauchier G , Herbert J , Sharp A , Bisson A , Ducluzeau P H , Fauchier L 
Published: October 2022

Abstract

Background
The link between hypertensive disease in pregnancy and future cardiovascular events is well established, as is the increased risk of developing type 2 diabetes mellitus after gestational diabetes (GDM). What is less well understood is the impact of GDM on future cardiovascular events. The literature is conflicting although suggestive that the risk of cardiovascular events with a history of GDM is 2 fold higher.

Purpose
Using the largest cohort to date and utilising robust data acquisition procedures and follow up we assessed the prognostic value of GDM for future cardiovascular events.

Methods
All female patients discharged from French hospitals in 2013 with at least 5 years of subsequent follow-up were identified. Those with a previous major adverse cardiovascular event, history of hypertensive disease, pre-existing diabetes or under the age of 18 years old were excluded. They were grouped depending on their history of GDM. After propensity score matching, patients with GDM were matched 1:1 with patients with no GDM. Hazard ratios for cardiovascular events during follow-up were adjusted by age at baseline.

Results
A total of, 1,738,101 women were included in the analysis, leaving 1,141,743 women (mean age 52.2, SD 19.7) once exclusion criteria were applied: 6998 (0.6%) had a history of GDM and the mean follow-up was 5.1 years (SD 1.3 years). Those with a history of GDM had a lower risk of new onset heart failure (HF) (hazard ratio [HR] 0.66, 95% confidence interval [CI]: 0.45–0.98) and all-cause death (HR 0.61, 95% CI 0.47–0.79). There was no significant difference in risk for myocardial infarction (HR 0.88, 95% CI 0.38–2.03), ischaemic stroke (HR 0.94, 95% CI 0.55–1.63), new onset atrial fibrillation (AF) (HR 0.61, 95% CI 0.33–1.11), cardiovascular death (HR 1.25, 95% CI 0.47–3.36) and major cardiovascular events (i.e. in-hospital cardiovascular death, myocardial infarction, ischaemic stroke or new-onset HF (MACE-HF)) (HR 0.75, 95% CI 0.56–1.01).

Conclusions
In a large contemporary analysis of female patient seen in French hospitals and utilising a robust data set we present the largest population analysis of the association between GDM and future cardiovascular events. Those with a history of GDM do not have a higher risk of myocardial infarction, ischaemic stroke, new onset AF, cardiovascular death or MACE-HF. Contrary to what is widely thought, a history of GDM confers a lower risk of new onset HF and all-cause death when compared to those women with no history of GDM.

Funding Acknowledgement
Type of funding sources: None.
A prediction model for aberrant cardiac remodelling in women after preeclampsia; Queen of Hearts study
Authors: Mohseni-Alsalhi Z , Janssen E B N J , Delmarque J , Van Kuijk S M J , Spaanderman M E A , Ghossein-Doha C 
Published: October 2022

Abstract

Background
Preeclampsia, a hypertensive pregnancy disorder, is strongly associated with aberrant left ventricular remodelling up to ten years after delivery and heart failure later in life. To detect occult cardiac abnormalities, echocardiography is necessary but not feasible for all these women. A prediction model for aberrant cardiac remodelling to be used in primary care may guide towards intensified follow-up for those at risk or tempered follow-up for low-risk individuals.

Purpose
To develop a prediction model for aberrant left ventricular remodelling in former pregnant women weighing their complicated pregnancy.

Methods
In this large cohort study, we included women (aged ≥18 years) with a history of preeclampsia or normotensive pregnancy at a postpartum interval of 6 months until 30 years. Comprehensive cardiovascular assessment was performed, including echocardiography, 30-minutes blood pressure measurements and circulating biomarkers. The procedures were in accordance with institutional guidelines and adhered to the principles of the Declaration of Helsinki. Aberrant cardiac remodelling based on echocardiography was defined as either left ventricular concentric remodelling or left ventricular hypertrophy. A prediction model based on clinical and circulating markers was developed using univariable and multivariable logistic regression with backward elimination. Internal validation was performed using Heuristic shrinkage factor. Performance of the final model was evaluated in terms of discrimination by the area under the receiver operating characteristic (AUC-ROC) curve.

Results
We included 1466 women, of which 93 (6.3%) with left ventricular concentric remodelling and/or left ventricular hypertrophy (mean ± SD age, 43±10 years) and 1373 (93.7%) without left ventricular concentric remodelling and/or left ventricular hypertrophy (40±8 years). The final prediction model was based on the predictors age, waist circumference, systolic blood pressure, Homeostatic Model Assessment of Insulin Resistance (HOMAIR), and preeclampsia (y/n) (Table 1). After internal validation, this prediction model showed a good discriminative ability of AUC-ROC-curve 0.71 (95% CI 0.661–0.758) (Figure 1).

Conclusion
We developed a good-performing prediction model for aberrant cardiac remodelling in former pregnant women based on five conventional variables that could contribute to risk-guided follow-up after preeclampsia aiming at intensifying follow-up for those at risk and tempered follow-up for low-risk women.

Funding Acknowledgement
Type of funding sources: None.
Outcomes in pregnant women with valvular heart disease from sub Saharan Africa transferred to a developed nation. A distinct care model
Authors: Ferreira V , Garcia Bras P , Castelo A , Santos A , Viveiros A , Ilhao Moreira R , Machado A I , Alves M , Cruz Ferreira R 
Published: October 2022

Abstract

Background
Pregnant women with valvular heart disease (VHD) in African countries still bear a disproportionate burden of maternal morbidity and mortality, due to the reduced accessibility to health care and the scarcity of skilled professionals. It is unclear if outcomes would be improved by care-delivery model changes.

Purpose
We performed a clinical audit of African pregnant women with VHD who were transferred for their care from five countries to our cardio-obstetrics unit, during a twenty-year period, through a memorandum of agreement of international cooperation.

Methods
A retrospective analysis of 81 pregnancies (P) in 45 African women with VHD (median age 24, IQR 22–29 years) from 2001 to 2020. The main outcome measures were major maternal complications and perinatal outcome.

Results
History of rheumatic heart disease was determined in 74.1% of the P. Most women were in NHYA I or II before P (79.0%), 43.2% had previous cardiac medication and 60.5% were anticoagulated (33.3% with acenocoumarol and 27.2% with warfarin). 59.3% of P had at least one valvular prosthesis, including 38 mechanical prosthetic valve (MPV) and 10 biological valves. 22.2% had prior surgical or percutaneous VHD correction, excluding prosthesis implantation. At baseline, impaired left ventricular ejection fraction was found in 12.3%. Previous arrhythmic event, stroke or infectious endocarditis were found in 12.3%, 8.6% and 6.2% of P, respectively.
During P, deterioration in NYHA functional class occurred in 42.0% and 9.9% required initiation or intensified cardiac medication. For MPV, 51% maintained a vitamin K antagonist, 15.7% used LMWH from 6 to 12th weeks and 9.8% used LMWH throughout P. Valve thrombosis occurred in 4 women (4.9% of P), with one maternal death in a patient with double MPV.
Hemorrhagic complications happened in 8.6% of P, all anticoagulated, in immediate postpartum or puerperal period. The 81 P resulted in 56 live births (69.1%), with a medium birth weight of 3026±471g. Delivery by caesarean section was performed in 28.3% of newborns. The incidence of miscarriage was 23.5% and fetal malformations occurred in 14.8%, with warfarin embryopathy in 4 cases. In univariate analysis, the presence of valvular protheses (p=0.001), and anticoagulation (p=0.001) were related to unsuccessful P. In multivariate analysis, VKA therapy was the unique independent predictor of unsuccessful P (p=0.048).

Conclusion
With the multidisciplinary care provided, pregnancy was relatively well tolerated and successful for women transferred from sub–Saharan Africa. However, the presence of a valvular prothesis is associated with unsuccessful pregnancy even in a developed nation. Efforts other than the implantation of a MPV should be pursued vigorously in sub Saharan Africa.

Funding Acknowledgement
Type of funding sources: None.