bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac CARE study: How the ESC Cardio-Oncology guidelines fo 2022 affect the study population
Authors: Loganath K , Dweck M , Henriksen P 
Published: November 2023

Abstract

Introduction
The new 2022 ESC Guidelines in Cardio-Oncology focused on cancer therapy-related cardiac dysfunction (CT-RCD), with the formal introduction of biomarkers in the classification and risk stratification of CTR-CD in addition to structural imaging . We here, investigated how these changes affect the classification of patients in the Cardiac CARE study and the value of high sensitivity troponin I (hSTrop-I).

Methods
The Cardiac CARE study prospectively recruited 191 patients who underwent anthracycline therapy for breast cancer or non-Hodgkin’s lymphoma. All patients underwent regular hSTrop-I levels throughout their anthracycline therapy as well as a baseline and 6-month cardiac magnetic resonance scans including assessment of left ventricular ejection fraction and global longitudinal strain.
A post-hoc analysis assessed the association between hSTrop-I and the development of cardiac dysfunction (defined as a reduction in left ventricular ejection fraction &lt;50% or a reduction in GLS by &gt;15%) using logistic regression with data corrected for age and gender. In addition, receiver operator curves (ROC) were drawn and area under the curve (AUC) analysis was performed to assess the value of hSTrop-I as an addition to the classification model. Finally, to compare our data with the new guidelines, a confusion matrix was performed.

Results
11 patients were diagnosed as having cardiotoxicity in the Cardiac CARE study but using the 2022 ESC guidelines in Cardio-Oncology, 53 patients were re-classified into the ‘asymptomatic mild cardiotoxicity’ group (95% CI of 0.5162 and 0.6823; kappa value 0.157). Using a logistic regression model, a difference in hSTrop-I measured at the first cycle of anthracycline therapy had an odds ratio of 1.37 (95% CI 0.37-5.10) which when corrected for age dropped to 1.18 (95% CI of 0.28-5.01) and with combined age and sex correction, fell further, to 0.83 (95% CI of 0.12 and 5.56). A ROC analysis looking at the performance of hSTrop-I at predicting cardiac dysfunction demonstrated an area under the curve of 0.605 and when corrected for age and sex, was 0.640.

Conclusion
The addition of cardiac biomarkers to the new classification, significantly reclassified 53 of 191 (27.7%) of patients who were previously normal, to having asymptomatic mild cancer therapy-related cardiac dysfunction, mostly due to the inclusion of hSTrop I. HSTrop-I prior to anthracycline treatment was not a robust predictor of the development of anthracycline-induced cardiotoxicity in our cohort of patients. Of note, the Cardiac CARE patients are a low-risk group of patients and follow-up data is limited to 6 months.
Implementing artificial intelligence-based cardio-obstetric screening in a diverse patient population: a prospective study
Authors: Adedinsewo D , Morales-Lara A C , Hardway H , Johnson P W , Young K A , Douglass E J , Butler Tobah Y S , Rose C H , Burnette D P , Attia Z I , Lopez-Jimenez F , Friedman P A , Carter R E , Noseworthy P A 
Published: November 2023

Abstract

Background
Cardiomyopathy is a leading cause of pregnancy-related mortality and represents the number one cause of death in the late postpartum period.

Purpose
The goal of this study was to prospectively evaluate the effectiveness of an artificial intelligence-based electrocardiogram (AI-ECG) and a point-of-care artificial intelligence-enhanced digital stethoscope for cardiomyopathy screening among pregnant and postpartum women.

Methods
We conducted a single-arm prospective study of pregnant and postpartum women (up to 12 months following delivery) enrolled at three sites between October 2021 and October 2022. Study participants completed a standard 12-lead ECG, ECG + phonocardiogram recordings with a digital stethoscope, a demographic questionnaire, and a transthoracic echocardiogram (TTE) within a 24-hour period. Diagnostic performance of the AI-ECG and digital stethoscope for cardiomyopathy detection, defined as left ventricular ejection fraction (LVEF) &lt; 45%, was evaluated using the area under the curve (AUC) and standard measures of diagnostic performance.

Results
We included 100 consecutive pregnant and postpartum women who provided informed consent and had at least one ECG recorded, completed the questionnaire, and had an echocardiogram performed. All participants self-identified as female, and 41% were recruited from a federally qualified health center. The median age of participants was 31 years (Q1: 27, Q3: 34). Thirty-eight percent identified as non-Hispanic White, 32% as non-Hispanic Black, 21% as Hispanic or Latino, 6% as Asian, and 3% as Other (1 Native Hawaiian and 2 multiracial). Five percent (5/100) had LVEF &lt;45%. The 12-lead AI-ECG model demonstrated close to perfect discrimination (accuracy 99%; AUC 1.00, sensitivity 100%) for detection of cardiomyopathy with 1 false positive screen (LVEF 49%), Figure 1A. The digital stethoscope (angled position) had an AUC of 0.99 (95% CI: 0.97, 1.00) for detection of LVEF &lt;45%. Sensitivity, specificity, positive predictive value, and negative predictive value for the digital stethoscope were 60%, 98%, 60% and 98%, respectively for detection of LVEF &lt;45% (Figure 1B & 1C).

Conclusions
In this small prospective study, we found that 5% of pregnant and postpartum women had cardiomyopathy, a potentially life-threatening condition, and that a rapid, inexpensive, ubiquitous, massively scalable point-of-care test - the ECG - showed promising results, identifying it with an AUC &gt; 0.98 with the application of artificial intelligence.Figure 1
Mendelian randomization of the cardiovascular disease-related proteome identifies novel drug targets for gestational hypertension and preeclampsia
Authors: Schuermans A , Truong B , Ardissino M , Slob E A W , Gray K J , Yan Q , Burgess S , Natarajan P , Honigberg M C 
Published: November 2023

Abstract

Introduction
Hypertensive disorders of pregnancy (HDPs; including preeclampsia/eclampsia and gestational hypertension) are a leading cause of maternal and neonatal morbidity and mortality worldwide, and women with HDPs have increased long-term risk for cardiovascular morbidity and mortality.

Purpose
Here, we leveraged Mendelian randomization (MR) to identify novel therapeutic targets for gestational hypertension and preeclampsia/eclampsia and HDP-associated cardiovascular disease.

Methods
Genetic instruments were constructed for 90 proteins that were measured using the Olink CVD-I assay, chosen due to their previous associations with cardiovascular disease. We only included cis-protein quantitative trait loci (cis-pQTLs; variants at P≤5x10-4 within 200kb of the protein-encoding region) to minimize potential horizontal pleiotropy. Cis-pQTLs were clumped at R²≤0.4, based on previous literature. Primary analyses used the inverse-variance weighted method adjusted for residual correlation between variants. We performed multiple sensitivity analyses, including clumping at different R² thresholds, using different MR methods, and testing for opposite direction of effects. Proteins robust to sensitivity analyses were selected for phenome-wide association studies (PheWAS) to investigate potential non-HDP-related effects.

Results
Seventy-five of 90 proteins had at least one valid cis-pQTL. We identified ten proteins associated with either gestational hypertension (CCL4, CD40, ECP, Galectin-3, KIM-1, MMP-12, NT-proBNP, and ST2) or preeclampsia/eclampsia (cystatin B, ECP, HSP27, and ST2) with a false discovery rate &lt;0.05 (Figure 1). Four proteins (CD40, ECP, galectin-3, NT-proBNP) were robust to sensitivity analyses for gestational hypertension, while three proteins (cystatin B, ECP, HSP27) were robust for preeclampsia/eclampsia (Figure 2). PheWAS of genetic instruments suggested that non-HDP-related (i.e., "off-target") effects would predominantly be beneficial for ECP (three beneficial vs. one adverse non-HDP-related associations), galectin-3 (thirty-one vs. seven), and HSP27 (ten vs. two).

Conclusions
We identified putative causal associations of six cardiovascular disease-related proteins with gestational hypertension and/or preeclampsia/eclampsia. These findings call for further investigation into the preventive and therapeutic potential of these proteins.Figure 1Figure 2
Effect of successful bariatric surgery on maternal cardiovascular outcomes
Authors: Mustafa A , Wei C , Khan S , Grovu R , Rizvi T , Behuria S , Lee S , Lafferty J , Weinberg M 
Published: November 2023

Abstract

Background
Obesity is a common comorbidity and is prevalent in at least 20% of pregnant women. Its prevalence is increasing at an alarming rate and is associated with worse pregnancy outcomes. With increasing obesity, more females are considering bariatric surgery (BS) as a form of weight-loss.

Purpose
The purpose of the study is to evaluate the effect of successful bariatric surgery (sBS) on maternal cardiovascular outcomes.

Methods
Pregnant females were sampled from the National Inpatient Sample Database (2016-2018). Demographics and comorbidities were collected using ICD-10 and DRG codes. Pregnant patients were stratified into three groups – morbidly obese, overweight/obese, and sBS. Individuals with a history of BS and not currently morbidly obese or overweight/obese were included in the sBS group. The primary outcome was a composite and was defined as major adverse cardiovascular events (MACE; Table 1). Secondary outcomes included pre-eclampsia (preE), gestational diabetes (GDM), and length of hospital stay (LOS). Patients with concurrent history of BS and overweight/obese/morbidly obese were excluded. To address confounding factors, sBS patients were matched 1:1 with morbidly obese and overweight/obese patients by 15 variables (Table 1). Binary logistic regression analyses were performed to assess for association between sBS and cardiac outcomes.

Results
Out of 207,511 patients included, 5,517 were sBS, 132,483 were overweight/obese, and 69,511 were morbidly obese. Compared to the sBS group (0.1%), MACE was higher in morbidly obese (0.7%) and overweight/obese patients (0.3%). Additionally, morbidly obese patients had higher acute heart failure, peripartum cardiomyopathy, acute pulmonary edema, preE, GDM, and longer LOS than sBS patients. Overweight/obese had more preE and GDM than the sBS cohort (Table 1).
After 1:1 matching, MACE was more prevalent in morbidly obese patients (OR:6.69 [1.99-22.52]; p=0.002) and overweight/obese patients (OR:6.5 [1.5-28.9; p=0.01) when compared to sBS group. Both morbidly obese and overweight/obese groups were associated with increased preE (OR:3.0 and 2.1 respectively), GDM (OR:3.2 and 2.3 respectively), LOS (Coefficient:3.4 and 3.3 respectively; Figure 1).

Conclusion
Despite longstanding effects of obesity, sBS patients had better cardiovascular outcomes, even after matching for pre-existing cardiac conditions. A reduction in weight leads to decreased circulatory volume and improved cardiac output, resulting in lower risk of acute pulmonary edema, peripartum cardiomyopathy, and acute heart failure. The decrease in systemic inflammation and endothelial dysfunction likely led to a reduction in preE. Although pregnancy after bariatric surgery requires multidisciplinary management due to specific nutritional needs, the significant reduction in MACE highlights the importance of considering it as an option if conventional weight loss measures fail.Table 1Figure 1
Diuretic use in pregnancy: data from the ESC Registry of Pregnancy and Cardiac disease (ROPAC)
Authors: Van Der Zande J A , Greutmann M , Tobler D , Ramlakhan K P , Cornette J M J , Hall R , Johnson M R , Roos-Hesselink J W 
Published: November 2023

Abstract

Background
Data on diuretic use during pregnancy are limited and show varying results. Therefore, it remains unsure whether they can be safely used.

Purpose
Our study aims to evaluate the perinatal outcomes after in-utero diuretic exposure.

Methods
The Registry of Pregnancy and Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with structural heart disease. Outcomes were compared between women who used diuretics during pregnancy versus those who did not. Multivariable regression analysis was used to assess the impact of diuretic use on the occurrence of congenital abnormalities and fetal growth, after adjustment for potential confounders.

Results
Diuretics were used in 382 (6.7%) of the 5739 ROPAC pregnancies, most often furosemide (n=332, 86%). Women who used diuretics during pregnancy, compared to those without, were older (30.9 vs 29.4 years; p&lt;0.001), had a higher BMI (25.3 vs 23.9 kg/m2; p&lt;0.001), were more likely to live in a low-middle income country (63.1% vs 38.1%; p&lt;0.001), and more likely to have chronic hypertension (9.9% vs 6.4%; p=0.007), atrial fibrillation/flutter (7.1% vs 1.5%; p&lt;0.001), signs of heart failure (27.2% vs 9.2%; p&lt;0.001) and/or an estimated LVEF below 40% (19.9% vs 3.3%; &lt;0.001). Diuretic use during the first trimester was not independently associated with fetal or neonatal congenital abnormalities (OR 1.30; 95% CI 0.66-2.55). After adjustment for confounders, diuretic use during pregnancy was not independently associated with small for gestational age (OR 1.36; 95% CI 0.97-1.91).

Conclusions
Based on our data, diuretics can be used safely during pregnancy and discontinuation of diuretics prior or during pregnancy in women with appropriate indication seems not to be necessary. However, for treatment of systemic hypertension, alternative antihypertensive agents with more safety data regarding perinatal outcomes, such as labetalol or nifedipine, are preferred.
Higher subclinical cardiac fibrosis in South African youth with HIV: results from the CTAAC-heart study
Authors: Jao J , Zar H J , Kahts M , Jermy S , Nyathi M , Asafu-Agyei N , Legbedze J , Carkeek E , Mautsa T , Bonner L B , Mccomsey G A , Feinstein M , Kurland I J , Myer L B , Ntusi N 
Published: November 2023

Abstract

Background
Few data exist on cardiac fibrosis and inflammation in youth with HIV, particularly in sub-Saharan Africa.

Purpose
Our objective was to assess the association between HIV status and cardiovascular magnetic resonance (CMR) measures of subclinical cardiac fibrosis, inflammation, and function.

Methods
We performed CMR on a cross-section of youth in South Africa: youth with perinatally acquired HIV (YPHIV), youth with non-perinatally acquired HIV (YNPHIV), and HIV-seronegative youth (YHIV-). Subclinical fibrosis [late gadolinium enhancement (LGE) mass and fraction, extracellular volume (ECV)], inflammation [native T1 and T2 mapping], and cardiac function (cine, strain, and strain rate) were assessed. CD4, viral load (VL), and fasting glucose, insulin [for Homeostatic Model Assessment-Insulin Resistance (HOMA)] and lipids were obtained. Unadjusted and adjusted quantile regression models were used to assess the association between HIV status and CMR outcomes. In sub-group analyses of youth with HIV, we additionally adjusted for HIV factors.

Results
Of 464 youth, 287 were YPHIV, 87 YNPHIV, and 90 YHIV-. YNPHIV were older with a higher proportion self-identifying as female than YPHIV and YHIV- (median age 20 vs 18 and 17 years; 85% vs 50% and 49%, respectively). YPHIV had lower body surface area (1.6 vs 1.7 and 1.7m2) and a higher proportion with prior TB disease (70% vs. 20% vs 8%) compared to YNPHIV and YHIV-. Tobacco use, HOMA, total cholesterol, and low-density lipoproteins were similar between groups. Among youth with HIV, YPHIV had a higher proportion with CD4&lt;200 cells/mm3 (10% vs 4%) or VL&gt;50 copies/mL (39% vs 13%) but lower proportion on integrase inhibitors (33% vs 84%). LGE mass (0.13 vs 0.12 vs 0.07g respectively) and fraction (0.3% vs 0.3% vs. 0.2% respectively) were higher in YPHIV and YNPHIV than YHIV-; native T1 was highest in YNPHIV compared to YPHIV and YHIV- (Table). In adjusted analyses, compared to YHIV-, median LGE mass was higher in YPHIV and YNPHIV (β:0.06, p=0.01 for YPHIV, β:0.05, p=0.03 for YNPHIV) and LGE% was higher in YPHIV (β:0.14, p=0.02); native T1 and ECV did not differ between groups in adjusted analyses. Among youth with HIV, CMR outcomes did not differ significantly for persons with perinatal vs non-perinatal HIV. Findings did not vary in analyses restricted to females.

Conclusion
In one of the largest studies of CMR among youth with HIV in sub-Saharan Africa, we found that despite their young age, YPHIV and YNPHIV appear to have higher subclinical cardiac fibrosis than YHIV- and healthy adults in South Africa. Youth with HIV may benefit from early screening and long-term monitoring for cardiovascular disease.TableFigure
Prolonged fibrinolysis time is a risk factor for mortality in patients with chronic kidney disease - a propensity score matched analysis
Authors: Berger M , Speer T , Lysaja K , Fliser D , Marx N , Schuett K 
Published: November 2023

Abstract

Purpose
To investigate the role of fibrinolysis time and clot structure on cardiovascular mortality of patients with chronic kidney disease.

Methods
Clot characteristics were measured in 56 propensity score matched patients (i.e. based on gender, BMI, presence of CAD, presence of CVD and CKD stage) by a modified ROTEM assay with the addition of 175 ng/ml of tPA from the Care4HOMe study.

Results
In total 462 patients with CKD stage II-IV were included in the Care4HOMe study. Patients with cardiovascular death differed significantly from patients without cardiovascular mortality with respect to presence of cardiovascular disease (CVD), presence of coronary artery disease (CAD) and CKD stage (all p &lt; 0.001). Therefore, to assess clot characteristics in a less confounded environment we propensity score matched patients with and without cardiovascular death in a 1:1 ratio. After matching a total of 56 patients with similar baseline characteristics remained. Interestingly, clot-formation time (CFT) and maximal lysis (ML) were significantly altered in patients that suffered cardiovascular death (CFT Event-free: 150±172sec; CFT CV-death: 80±61sec p = 0.035; ML Event-free: 30±61%; ML CV-death: 10±81% p = 0.021). To assess the prognostic importance of both parameters we stratified CFT and ML based on the median and calculated Kaplan-Meier curves and performed a Cox-proportional hazard regression analysis. Combined assessment revealed that a ML lower than the median significantly increased the cardiovascular mortality risk (HR 3.7 95%CI 1.3 – 10.3, p = 0.009; Log-rank 0.0059) while the stratified-CFT remained insignificant (HR 0.99 95%CI 0.99 – 1.00, p = 0.28, Log-rank p = 0.79). Additional C-statistic demonstrated that the predictive value of ML with respect to cardiovascular mortality in CKD patients was comparable to established CKD mortality predictors including Cystatin-C plasma levels and Urine Albumin/Creatine Ratio (UACR) (ML 0.69, 95%CI 0.53-0.86; CystatinC 0.70, 95%CI 0.51 – 0.80; UACR 0.70, 95%CI 0.56-0.84).

Conclusions
Prolonged fibrinolysis time may be an important prognostic parameter that links atherothrombotic risk to cardiovascular mortality in patients with chronic kidney disease.Maximum Lysis
Biomarker-based clinical subphenotypes of cardiac surgery associated acute kidney injury and their association with in-hospital treatments and outcomes: a data-driven cluster analysis
Authors: Huang X H , Zeng J T , Su X T , Zheng Z 
Published: November 2023

Abstract

Background
Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI) is a prevalent and detrimental complication after cardiac surgery. Its etiology, pathophysiology, and clinical features are often obscure and heterogenous, with varying prognosis and therapeutic requirements. Cluster analysis has been increasingly used to profile complex diseases, but no prior studies have applied it to the CSA-AKI population.

Purpose
We aim to employ an unsupervised, data-driven cluster analysis approach utilizing routinely available and previously reported perioperative biomarkers to identify CSA-AKI subphenotypes that exhibit varying treatment requirements and in-hospital outcomes.

Methods
Patients diagnosed with CSA-AKI in accordance with the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, who underwent coronary bypass grafting surgery in a single institution and had comprehensive perioperative data, were included (n=7 796). Cluster analysis based on 12 routinely available perioperative biomarkers was performed to partition CSA-AKI subphenotypes. Treatment requirements for vasoactive supports, diuretics, and dialysis, as well as AKI duration and in-hospital mortality rates, were compared among the identified subphenotypes.

Results
Three distinct clusters of patients with CSA-AKI were identified with different clinical characteristics, treatment needs, and in-hospital outcomes. Cluster 1(n=2 452, 31.5%) was characterized by normal NT-proBNP level, less comorbidities, predominantly isolated surgery, and better prognosis. Cluster 3 (n=1 060, 13.6%) was distinguished by extremely inflammatory states (significantly higher hsCRP level), more comorbidities, more complex surgery, and worse prognosis. Cluster 2 (n=4 284, 55.0%) was considered the intermediate cluster. CSA-AKI patients in cluster 3 exhibited significantly higher in-hospital mortality rate, longer AKI duration and hospital stay, and increased requirements for vasoactive supports, diuretics, and dialysis compared with the other two clusters. Notably, according to the current KDIGO criteria, 87.4% of cluster 3 patients are classified as only stage 1.

Conclusions
Three clinical subphenotypes of CSA-AKI were identified based on routine perioperative biomarkers, which demonstrated varying treatment requirements and in-hospital outcomes. This cluster analysis augments the current severity-based staging system for general AKI, providing additional risk stratification and treatment implications that are more tailored to cardiac surgery patients.