bluuebunny/crossref_metadata_2025 huggingface dataset:
Current treatment of acute coronary syndromes in cancer patients: the need for improvement
Authors: Carrillo M , Garcia Hernandez N , Hernandez Pineda A H , Leocachin Parra D L , Antezana Castro J F
Published: November 2023

Background

Cancer patients can develop acute coronary syndromes (ACS) due to their oncological therapy exposure or shared risk factors between cancer and cardiovascular disease. Cancer patients have been reported to receive suboptimal treatment in this setting, with lower rates of coronary angiography and or primary percutaneous intervention, despite the clear benefit of these therapies in ACS. This disparity in the care of cancer patients can lead to worse cardiovascular outcomes.

Purpose

To describe the contemporary therapeutic approach in patients with a history of cancer or current cancer presenting with an acute coronary syndrome to a tertiary care cardiology hospital.

Methods

We performed an electronic chart review of patients admitted to the cardiac intensive coronary unit of a tertiary care Cardiology hospital in our city, from May 2021 to February 2023. Patients with a current or historical diagnosis of cancer and acute coronary syndrome (with and without ST segment elevation) were identified. We collected the following information: demographic data, oncological diagnosis, cancer treatment history, ACS type, and ACS management.

Results

Seventy-five patients had diagnosis of current or historical cancer in the selected period. Of them, 40 patients were admitted with diagnosis of acute coronary syndrome. Mean age was 69.8 + 10.0 years. Twenty-one patients (52.5%) had a historical diagnosis of cancer and nineteen patients had diagnosis of current cancer. Of patients with historical cancer the most common type was hematological, followed by prostate and renal cancer. The most common types of active malignancies were prostate, colon, and renal cancer. ST-segment elevation myocardial infarction (STEMI) was the most common type of ACS (27 patients). Notably, only half of the patients presenting with STEMI underwent primary percutaneous coronary intervention, four patients received fibrinolytic treatment, and one third of patients with STEMI did not receive reperfusion therapy. Among patients with STEMI, mean time from symptom onset to reperfusion therapy was 495 minutes. Regarding the 13 patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI), eight underwent an invasive strategy (coronary angiography) in the first 48 hours, of whom six had percutaneous coronary intervention, and one underwent coronary artery bypass graft surgery. Five patients with NSTEMI (38.4%) did not undergo coronary angiography during their hospitalization.

Conclusions

Patients with active or historical cancer presenting with STEMI receive late reperfusion treatment and up to one out of three do not receive reperfusion therapy. An important proportion of cancer patients presenting with NSTEMI do not even undergo invasive strategy. It is imperative to provide optimal care of cancer patients presenting with ACS.
The utility of the HFA-ICOS cardiotoxicity risk assessment tool for HER2-targeted cancer therapies in patients with metastatic breast cancer: from theory to clinical practice
Authors: Leocachin Parra D , Bocardo Galvan J B , Grajales Alvarez R C , Carrillo Estrada M
Published: November 2023

Background

Breast cancer is the most common cancer in women. In developing countries, a considerable proportion of breast cancer diagnoses are made in advanced stages. Nevertheless, the development of targeted therapies, such as trastuzumab and other HER2 targeted agents, has revolutionized the care of these patients, leading to large improvements in disease-free and overall survival. In the other hand, these therapies are associated with cardiac dysfunction. As such, a comprehensive assessment of cardiovascular health before initiation of cancer treatment is fundamental. The HFA-ICOS´s proforma for HER2 targeted therapies is a proposed tool to evaluate the baseline risk of cardiotoxicity in these patients.

Purpose

To evaluate if the HFA-ICOS´s cardiotoxicity risk assessment tool for HER2-targeted cancer therapies allows to properly identify patients with HER2-positive metastatic breast cancer treated with trastuzumab at high risk for cardiotoxicity.

Methods

We performed an electronic chart review of patients with HER2-positive metastatic breast cancer treated with trastuzumab seen at the outpatient oncology clinic from January 2018 to December 2022. We collected the necessary data to apply the HFA-ICOS´s cardiotoxicity risk assessment tool for HER2-targeted cancer therapies, except for cardiac biomarkers. Cardiotoxicity was defined as 10% drop of left ventricular ejection fraction (LVEF) to a value of less than 50%.

Results

Seventy patients were included in our analysis. Mean age was 54.6+12.5 years. Cardiotoxicity was found in twenty-three patients (32%), of which, nine (39.1%) were classified at high risk for cardiotoxicity, twelve patients (52.1%) at medium risk, and two patients (8.6%) at low risk. Among the group with cardiotoxicity there was a higher proportion of older patients, obesity, borderline LVEF at baseline, prior treatment with anthracyclines, and prior exposure to radiotherapy. A high-risk score was more frequent among patients with cardiotoxicity than in those without cardiotoxicity. Most patients were classified with medium risk in both groups. The proportion of patients with low risk was not different in patients with and without cardiotoxicity. None of the variables evaluated was statistically significant.

Conclusions

There was a higher proportion of patients at high risk according to the HFA-ICO´s proforma for HER2 targeted therapies who developed cardiotoxicity in comparison to patients without cardiotoxicity. However, there were no significant differences in patients classified as medium or low risk. Future studies are needed to precise the most adequate method to stratify cardiotoxicity risk in patients with breast cancer exposed to anti-HER2 therapies, in order to establish effective surveillance and a suitable treatment.Table 1.
Vascular and neurological outcomes in patients with atrial fibrillation treated with edoxaban; effects of cancer
Authors: Cheng K , Tu H P T , Scherrer-Crosbie M S C , Cheng K C C , Hsu T Y H
Published: November 2023

Introduction

Data from novel oral anticoagulants (NOACs) trials has shown superior outcomes of NOACs compared to warfarin in vascular and bleeding events in patients with AF, both with and without cancer, however, little discussion has been provided on their effect in congestive heart failure (CHF). NOACs also may have biological benefits in Alzheimer disease (AD). We investigated the impact of edoxaban on vascular and bleeding events, CHF, and AD, in patients with AF, with and without cancer.

Methods

In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, we identified a total of 5683 patients with non-valvular AF (NVAF) treated with edoxaban and matched them for gender and age to 11366 patients treated with warfarin. Subsequently, we similarly matched 703 patients with NVAF and cancer (NVAF-C) treated with edoxaban to 1406 patients treated with warfarin. The crude and adjusted hazard ratios (HRs) were applied for outcome assessments. Outcomes included arterial/venous ischemic events, CHF, Alzheimer disease (AD) , bleeding, acute kidney injury (AKI), and all-cause mortality.Results:Compared to warfarin, edoxaban showed significantly lower adjusted HRs for all-cause mortality (0.37 in NVAF, 0.39 in NVAF with cancer [NVAF-C]), hospitalization for gastrointestinal bleeding (0.74 in NVAF, 0.67 in NVAF-C), and CHF (0.26 in NVAF, 0.31 in NVAF-C) in both NVAF and NVAF-C groups (all p < 0.05). The adjusted HRs of acute myocardial infarction (0.71, p = 0.0051), peripheral artery disease (HR = 0.48, p < 0.001), venous thromboembolism (0.55, p = 0.0003), pulmonary embolism (0.20, p = 0.0002), and AD (0.66, p < 0.001) were also significantly lower for NVAF patients using edoxaban versus warfarin. However, edoxaban was associated with significantly higher adjusted HR of other hospitalized bleeding than warfarin (1.19, p = 0.0016) in NVAF patients but not in NVAF-C patients.

Conclusion

Edoxaban is associated with reduced risks of CHF in both NVAF and NVAF-C patients, and lower incidence of AD in NVAF when comparing to warfarin. These findings further support the use of edoxaban in patients with AF.
Cardiovascular complications of chimeric antigen receptor (CAR)-T cell therapy
Authors: Guerra F , Frangione A , Rrapaj E , Sfredda S , Mancini G , Coretti F , Stronati G , Olivieri A , Dello Russo A
Published: November 2023

Background

Mechanisms of cardiotoxicity during chimeric antigen receptor (CAR)-T cell therapy remain unclear to this day, with the main hypotheses revolving around IL-6 mediated myocardial depression during cytokine release syndrome (CRS), stress-induced or takotsubo cardiomyopathy, and direct toxicity from CAR-T cells. Hereby we present the experience of a regional referral centre for CAR-T therapy and the program developed with a dedicated cardio-oncology centre.

Purpose

To provide preliminary data on cardiovascular-related toxicity of CAR-T therapy in terms of incidence and management.

Methods

All consecutive candidates for CAR-T therapy were prospectively enrolled since the inception of the CAR-T program in our institution (2021). All patients were refractory to at least two lines of immune chemotherapy and had already undergone anthracycline treatment. After conditioning, all patients were treated with autologous CAR-T cells (tisagenlecleucel, Kymriah). Prior to CAR-T cell therapy, all patients underwent baseline cardiac evaluation at our cardio-oncology facility, including a 12-lead ECG, a complete echocardiogram and cardiac biomarkers. The same routine was performed before discharge, after one month. Supplementary evaluations were performed by an on-call cardio-oncology team according to the attending physicians.

Results

Eleven patients (6 males, mean age 60±11 years) underwent CAR-T cell infusion. Over the course of follow-up, six patients (54%) experienced CRS after a median follow-up of 12 days (7-40). Two patients with mild symptoms (Grade I) were managed with non-cardiac-related therapy while three Grade 2 patients had to start cardioprotective drugs (ACE-Is and beta-blockers) for transient left ventricular systolic dysfunction (mean lowest LVEF 44.8±3.7%). One patient experienced a Grade IV CRS due to takotsubo syndrome complicated by cardiogenic shock on day 4 and required high-dose vasopressors and mechanical ventilation. Patients experiencing a CRS had similar demographical characteristics and medical history but standard echocardiogram before CAR-T showed a lower baseline LVEF (54.5±5.6% vs 64.6±6.7%; p=.02) and lower baseline right longitudinal systolic function markers (TAPSE: 19±3 vs. 24±4 mm; p=.02 S': .09±.01 vs .13±.02 m/s; p=.03). Cardiac biomarkers (high-sensitivity Troponin I and NT-proBNP) did not show any significant predictive power at baseline. All CRS patients showed a progressive recovery of ventricular function and survived up to one-year of follow-up.

Conclusions

CAR-T therapy is associated with an increased risk of cardiotoxicity, with up to 36% of all patients requiring unscheduled cardio-oncology evaluation and management both during admission and after discharge. Cardiac adverse events range in degree of severity and should be promptly managed by a dedicated team.
The potentially protective effect of dapagliflozin on the development of cardiotoxicity in cancer patients
Authors: Maragoudakis S , Marketou M , Sideras M , Vittorakis E , Mavroudeas S E , Emiri F , Datseris G , Stratinaki M , Kafkala K
Published: November 2023

Introduction

The clinical trial "DECLARE-TIMI 58" (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), demonstrated that dapagliflozin, a Sodium glucose cotransporter 2 inhibitor, reduces the composite end point of cardiovascular death/hospitalization for heart failure in a broad population of patients with type 2 diabetes mellitus.Chemotherapy is known for its potetial adverse effects on myocardium.We hypothesized that early initiation of treatment with dapagliflozin could prevent cardiotoxicity .

Purpose

We aimed to study if dapagliflozin could exert cardioprotective effects in anthracycline,carfilzomib and trastuzumab-induced cardiotoxicity through the analysis of ejection fraction, global longitudinal strain (GLS) of both left and right ventricle.

Methods

32 diabetic patients who were diagnosed with cancer at our medical center were randomized (16 dapagliflozin;16 placebo). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). Our patients, receiving potentially cardiotoxic treatment: 52% were treated with only trastuzumab, 34% were treated with only anthracycline and 14% with carfilzomib. The primary endpoint was the development of cardiotoxicity after treatment with chemotherapy. Cardiotoxicity was defined as a decrease of LVEF by 5% or more to less than 55% in the presence of symptoms of heart failure or an asymptomatic decrease in LVEF by 10% or more to less than 55%.

Results

In the first trimester of observation compared to baseline, patients treated with dapagliflozin did not show a deterioration of LV GLS [(GLS = −20,2±3,1% vs −19,8±3,1%, p=0,551] .Similarly in the placebo group [(GLS= −23,02±3,6% vs −22,6±3,5%, p=0,572). No significant changes were found in LVEF after treatment with dapagliflozin (57,9±5,6% vs 57,6±6,1%, p=0,733) or the placebo (60,1±5,6% vs 57,8±6,6%, p=0,166).There was a trend in GLS reduction of left ventricle in 2 patients receiving carfilzomib treatment in the placebo group (p=0.058)

Conclusions

At the best of our knowledge, our study is the first to investigate the early prophylactic use of dapagiflozin in the development of non-ischemic cardiomyopathy in patients receiving anthracycline or trastuzumab,carflilzomib therapies. During the first trimester of observation there was no benefit by dapagliflozin administration but 2 of our patients in the placebo group demonstrated reduction in GLS of left ventricle.
Differences in the prevalence of cardiovascular toxicity in a cohort of female breast cancer patients according to the different cardiotoxicity definitions
Authors: Herrera J , Esteban F , Delgado M , Rodriguez A , Ruiz M , Maestre L C , Torres A , Diaz M A , Romo E , Fernandez-Aviles C , Heredia G M , Resua A , Perea J , Mesa D , Pan M
Published: November 2023

Background

The definition of cancer therapy-related cardiac dysfunction (CTRCD) has evolved in the past ten years, as Cardio Oncology has consolidated as a new medical discipline. However, great heterogeneity is noted among the published criteria of the different types of cardiotoxicities by the different scientific societies.

In order to mitigate this variability, a new definition of CTRCD has been recently proposed by the International Cardio-Oncology Society (IC-OS) and endorsed by the latest 2022 ESC Guidelines on cardio-oncology. CTRCD is now classified into different degrees of severity according to symptoms, left ventricular ejection fraction (LVEF) reduction guided by echocardiography and elevation of cardiac biomarkers.

Purpose

we aimed to assess the impact of the new consensus definition of CTRCD in the reclassification of cardiotoxicity in a breast cancer cohort of female patients receiving potentially cardiotoxic therapies (CT) attended in our third-level hospital.

Methods

we retrospectively analyzed and compared the incidence of the different subtypes of CTRCD in a cohort of female breast cancer patients evaluated in our hospital from 2018 to 2021 according to both the previous 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity and the latest 2021 ICOS definition.

Results

a cohort of 193 women with a breast cancer diagnosis and receiving CT was analyzed. Mean age was 58 ± 11 years and 57 % of the patients (110) had a least one cardiovascular risk factor, with no past history of cardiac disease. According to the previous ESC 2016 criteria, 16 patients (8.3%) had cardiac dysfunction associated with cancer treatment whereas with the 2021 IC-OS new definition, a total of 23 women (12%) would have been satisfied the CTRCD criteria. Of Those, 11 were asymptomatic and 7 had severe CTRCD. Overall, this would have translated into a 30% rise in the incidence of patients experiencing any type of cardiotoxicty (p < 0.0001).

Conclusion(s)

by using the new IC-OS criteria for CTRCD, a significant increase in the prevalence of cardiotoxicity was noted in our population, which may translate the higher sensitivity of the proposed criteria to detect clinical or subclinical cardiovascular damage derived from cancer treatment.
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

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 <50% or a reduction in GLS by >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

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) < 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 <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 <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 <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 > 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

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 <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

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

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<0.001), had a higher BMI (25.3 vs 23.9 kg/m2; p<0.001), were more likely to live in a low-middle income country (63.1% vs 38.1%; p<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<0.001), signs of heart failure (27.2% vs 9.2%; p<0.001) and/or an estimated LVEF below 40% (19.9% vs 3.3%; <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

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<200 cells/mm3 (10% vs 4%) or VL>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

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 < 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

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.
Worsening renal function in patients admitted with congestive heart failure: prevalence, risk profile, and hospital readmissions
Authors: Alshammari A , Raiszadeh F , Hughes A , Mccann L , Ionescu N , Kurian D , Devarajan S , Majdalani R , Magdits M , Jha S
Published: November 2023

Introduction

Renal function is often negatively impacted in patients with Congestive Heart Failure (CHF) due to the interplay between the heart and kidneys. Worsening Renal Function (WRF) has been associated with decreased survival, accelerated CHF progression, and higher hospitalization rate. Previous literature has thoroughly documented the effects of CHF on hospital readmissions; however, few studies have examined the impact of WRF on CHF during hospitalization, particularly not in a vulnerable population. Thus, the aim of this study was to determine the prevalence, clinical predictors, and short-term hospital readmissions of WRF among hospitalized CHF patients.

Methods

This was a retrospective chart review utilizing the data of 297 patients hospitalized for CHF from 2019 to 2020, either due to an exacerbation of symptoms or new-onset of disease. The analysis of our study centered around identifying the risk factors and 30-day hospital readmission rates of patients with WRF, defined as an increase in serum creatinine of ≥ 0.3 mg/dL from admission, in comparison to patients who did not develop WRF. The significance between the two groups was measured using Fisher's Exact test, Wilcoxon rank-sum, and chi-square analysis. A risk score calculated from the sum of point values assigned to each independent risk factor was created.

Results

Data shows that 27% of hospitalized CHF patients developed WRF. Patients with WRF had a significantly longer hospital stay and a significantly higher increase in daily Creatinine values. We identified old age, overweight, type 2 diabetes (T2D), chronic kidney disease not on dialysis, and high Furosemide dose (oral and intravenous) as independent risk factors. Other independent risk factors include abnormally high serum levels of ProBNP (≥ 9,000 ng/dL), troponin T ≥ (0.04 ng/mm), and Creatinine (≥ 1.5 mg/dL). Based on this data, a point score reflected that patients with a 6+ risk score were four times more likely to develop WRF than patients with a risk score of 0. There was no association between WRF and higher 30-day readmissions.

Conclusions

WRF is common in hospitalized CHF patients. Although WRF was not associated with an increased 30-day hospital readmission rate, it was associated with longer hospital length of stay and thus increased economic burden. These results highlight the benefits of implementing in-care changes to address the particular risk factors associated with WRF to prevent further progression of renal impairment in hospitalized HF patients. Future directions will incorporate other outcome variables that discern the long-term implications of WRF, including 5-year readmission rates, ESKD, and mortality.
Impact of early stages of CKD with and without proteinuria on cardiac remodelling in UK Biobank cohort
Authors: Naderi H , Yaqoob K , Thomson R , Aksentijevic D , Petersen S E , Yaqoob M , Aung N
Published: November 2023

Background

Chronic kidney disease (CKD) is an established predictor of left atrial (LA) and left ventricular (LV) morphological and functional changes, which translate into excessive cardiovascular morbidity and mortality. However, a focussed study exploring the impact of early stages of CKD defined as stage 1 (eGFR > 90 mL/min per 1.73 m2 + albuminuria) and stage 2 (eGFR 60–89 mL/min per 1.73 m2) with and without proteinuria on cardiac magnetic resonance (CMR) parameters is lacking.

Purpose

In this study, we analysed CMR structural and functional changes in participants with early stages of CKD in the UK Biobank population.

Methods

41,095 participants from the UK Biobank imaging study were categorised into CKD stages. We calculated eGFR using the CKD-EPI 2021 equation and proteinuria was ascertained by the urinary protein creatinine ratio (defined as >30mg/mmol). We sought associations between CKD stages (exposure) and CMR parameters: LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), LV ejection fraction (LVEF), LV global functional index (LVGFI), LV myocardial contractile function (LVMCF), LV mass (LVM), LV mass-to-volume ratio (LVMVR), LV global longitudinal strain (GLS), LV global radial strain (GRS), LV global circumferential strain (GCS), LA maximum volume and left atrial emptying fraction. In the multivariable regression model, we adjusted for covariates including age, sex, ethnicity, height, body mass index, hypertension, diabetes, smoking status, and hyperlipidaemia

Results

Among the participants, 26,779 (65.1%) had normal kidney function, 2,787 (6.8%) stage 1 CKD, 10,534 (25.6%) stage 2 CKD without proteinuria, 689 (1.7%) stage 2 CKD with proteinuria, 241 (0.6%) CKD stage 3A (eGFR 59-45mL/min per 1.73 m2) without proteinuria, 28 (0.1%) stage 3A with proteinuria and 37 (0.1%) with more advanced CKD defined as stages 3B and above. Approximately 8 years after characterisation of CKD stages these participants underwent CMR. Using adjusted multivariable regression models setting normal kidney function as the reference group, the presence of proteinuria in stage 3 CKD was associated with smaller LV volume, lower LVM and more impaired LV function (LVSV beta=-11ml, 95% confidence interval (CI): -5 to -16ml and GLS beta=0.9%, 95% CI: 0.2 to 1.7%).

Conclusions

This study highlights the relationship between proteinuria in the early stages of CKD and cardiac remodelling patterns using CMR. CKD sub-characterisation with presence or absence of proteinuria should be considered for risk stratification.Figure 1
A meta-analysis of high-dose versus low-dose 4-factor prothrombin complex concentrate for reversal of factor Xa inhibitor-associated intracerebral hemorrhage
Authors: Coleman C , Karadenes A , Cassano C , Baker W L
Published: November 2023

Background

Four-factor prothrombin complex concentrate (4FPCC) are often used off-label for treating factor Xa inhibitor-associated major bleeding, including intracerebral hemorrhage (ICH). In addition to debate over 4FPCC’s effectiveness and safety compared with specific reversal agents, questions regarding the optimal 4FPCC dose remain.

Purpose

To evaluate the comparative effectiveness of high-dose versus low-dose 4FPCC for management of factor Xa inhibitor-associated ICH.

Methods

A systematic literature search of electronic databases (PubMed, Embase, and Cochrane) was conducted through January 31, 2023, to identify studies comparing high-dose versus low-dose 4FPCC for reversal of factor Xa inhibitors in individuals with an ICH. The outcomes of interest were hemostatic effectiveness (as defined by the individual study) and thromboembolism. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) individual study comparisons of high- and low-dose 4FPCC were pooled using a random-effects model. Studies were stratified according to whether multivariable adjusted analyses were performed.

Results

Six studies with a total of 447 individuals (high-dose = 254, low-dose = 193) were included. Definition of high-dose 4FPCC included ≥ 30 IU/kg (n=1), ≥ 35 IU/kg (n=3), and 50 IU/kg (n=2). Definition of low-dose 4FPCC 25 IU/kg (n=2), < 30 IU/kg (n=1), and <35 IU/kg (n=3). The overall pooled proportion of hemostatic effectiveness for 4FPCC was 81.4% (95% CI 77.6 to 84.8%) with no evidence of a difference between those receiving high-dose versus low-dose 4FPCC (OR 1.36, 95% CI 0.57-3.28; Figure). In five studies, the pooled proportion of individuals who developed a thrombosis after receiving 4FPCC was 3.1% (95% CI 0 to 15.7%) with no evidence of a difference in odds between high-dose and low-dose (OR 1.23, 95% CI 0.56 to 2.72).

Conclusion

Evidence from mostly small single-center retrospective cohort studies suggests that using high-dose 4FPCC for reversal of factor Xa inhibitor-associated ICH is not associated with differences in the odds of hemostatic effectiveness or thrombosis when compared to the low-dose.Figure.Results of Meta-Analysis