bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality and major adverse cardiac events in women with breast cancer receiving radiotherapy: a 10-year cohort study of patients and population controls
Authors: Jacobs J , L'hoyes W , Lauwens L , Weltens C , Voigt J U , Wildiers H , Neven P , Herrmann J , Thijs L , Staessen J , Janssens S , Van Aelst L
Published: October 2022

Background

Treatment for breast cancer (BC) frequently involves radiotherapy. Guidelines recommend screening for cardiac adverse events starting 10 years after radiotherapy. The rationale for recommending this interval is unclear and informed the objective of this study.

Objectives

Study cardiovascular event rates in the first decade following curative radiotherapy for breast cancer, the time frame before guidelines recommend screening.

Methods

We performed a monocentric, retrospective study enrolling all women with unilateral BC in 2007–2008, who received radiotherapy as part of their curative treatment. We compared event rates during 10 years follow-up with an age and risk factor-matched control population (FLEMENGHO population).

Results

We included 1095 BC patients (median age 55y, IQR: 47–66y). Two hundred and eighteen (19.9%) women died. Cancer and cardiovascular mortality accounted for 107 (49.1%) and 22 (10.1%) deaths, respectively. The incidence of coronary artery disease was similar compared to age and risk-matched women [risk ratio 0.75 (95% CI 0.48–1.18)], yet heart failure (HF) [risk ratio 1.97 (95% CI 1.19–3.25)] and atrial fibrillation or flutter (AF) (risk ratio 1.82 (95% CI 1.07–3.08) occurred more often. Age [HR 1.040 (95% CI 1.012–1.069)], tumor grade [HR 1.646 (95% CI 1.103–2.458)], and neo-adjuvant treatment setting [HR 3.079 (95% CI 1.432–6.620)] were risk factors for mortality; hormonal therapy [HR 0.007 (95% CI 0.001–0.042)] proved protective. Risk factors for MACE were mean heart dose [HR 1.079 (95% CI 1.012–1.151], hormonal therapy, history of cardiovascular disease [HR 2.771 (95% CI 1.253–6.126)], and Mayo Clinic Cardiotoxicity Risk Score [HR 2.547 (95% CI 1.538–4.217)]. While mean heart dose [HR 1.141 (95% CI 1.017–1.282)] and cardiovascular history [HR 3.374 (95% CI 1.259–9.043] clearly associated with new onset HF, only a trend towards higher AF burden with increasing mean heart dose could be observed.

Conclusions

Ten-year mortality following curative treatment for unilateral BC was mainly cancer-related. HF and AF constituted significantly increased risks in the first decade following irradiation. Mean heart dose, pre-existing cardiovascular diseases, and Mayo Clinic Cardiotoxicity Risk Score were risk factors for early cardiac mortality and adverse events and should guide early dedicated cardio-oncological follow-up.

Funding Acknowledgement

Type of funding sources: None.
Coronary calcification is independently associated with major adverse cardiovascular events in men with recurrent prostate cancer while aortic calcification is not
Authors: Som A , Shaikh P , Deng A , Deych E , Zhang K
Published: October 2022

Background

Cardiovascular disease is an important cause of morbidity and mortality in men with prostate cancer. Coronary and aortic calcification have been associated with major adverse cardiovascular events (MACE) in the general population, and are readily seen on staging cancer positron emission tomography (PET)/computed tomography (CT) scans. The utility of vascular calcification on non-gated CT for cardiovascular risk assessment in men with prostate cancer is not known.

Purpose

We determined the association between coronary and aortic calcification on non-gated CT imaging and MACE in men with prostate cancer.

Methods

We studied 354 men who underwent indium-111 capromab pendetide PET/CT for recurrent prostate cancer at our institution between 2012–2016. Clinical data were obtained from the medical record. Coronary and aortic calcification were qualitatively assessed using a standardized scoring system. The primary outcome of MACE included myocardial infarction, stroke, coronary and/or peripheral revascularization, heart failure hospitalization, and all-cause mortality.

Results

Over 5 years of follow-up, 63 patients (18%) met the primary outcome. Vascular calcification was common in this cohort (median 68 years of age), with 214 patients (60%) having coronary calcification and 296 patients (84%) having aortic calcification. Older patients had greater coronary and aortic calcification, and also higher rate of MACE. In adjusted models for age and diabetes, coronary calcification was associated with higher rate of MACE (hazard ratio [HR] 2.1, interquartile range [IQR] 1.1–4.0, p=0.02) while aortic calcification was not (HR 2.7, IQR 0.8–9.0, p=0.12). Undifferentiated vascular calcification was not associated with MACE (p=0.24).

Conclusions

Coronary calcification on non-gated CT scan is independently associated with MACE in men with recurrent prostate cancer while aortic calcification is not. The presence of coronary calcification should be included in staging PET/CT reports, and this information should prompt implementation of cardiovascular risk modification strategies.

Funding Acknowledgement

Type of funding sources: Private hospital(s). Main funding source(s): This study was supported by the Mentors in Medicine Program, Department of Internal Medicine, Washington University School of Medicine.
Association between immune checkpoint inhibitors and vascular endothelial growth factor targeted therapy with cardiovascular events
Authors: Drobni Z , Gong J , Raghu V , Zafar A , Gongora C , Quinaglia T , Suero-Abreu G , Gilman H , Gao X , Sullivan R , Merkely B , Reynolds K , Neilan T
Published: October 2022

Background

The use of immune checkpoint inhibitors (ICI) has been associated with a 3-fold higher risk for cardiovascular events as compared to cancer patients who did not receive ICI. Therapies targeting vascular endothelial growth factor (VEGF) have also been associated with a wide range of cardiovascular events. The combination use of ICIs and VEGF inhibitors is currently approved as a treatment for patients with renal-cell carcinoma, hepatocellular carcinoma, non-small cell lung cancer, and endometrial cancer. Data are lacking whether the combination of ICIs and VEGF-targeted therapy is associated with an additional increase in cardiovascular events.

Purpose

To evaluate whether the combination use of ICI and VEGF targeted therapies are associated with a higher risk of cardiovascular events as compared to ICI therapy alone, we performed a retrospective matched case-control study.

Methods

Cases received both ICI and VEGF-targeted therapy (n=157), and control patients (n=157) only received ICI therapy. The primary outcome was a composite of cardiovascular events (myocardial infarction, coronary revascularization, ischemic stroke, deep venous thrombosis, and pulmonary embolism). Patients were censored at time of first event or at last date of follow up. Cox proportional hazard regression analysis was performed to calculate hazard ratio (HR) with 95% confidence interval (CI), counting only the first cardiovascular event.

Results

Baseline characteristics for the cases and controls are shown in Table 1. Overall cases (combination ICI and VEGF inhibitor) and controls (ICI alone) were not different with respect to age, type of cancer, and a prior history of any cardiovascular event. Cases received more ICI cycles as compared to controls (median of 7 [4–17] cycles vs. 4 [2–10] cycles, P<0.001). Cases also had a longer follow-up time (334 [127–663] days vs. 201 [60–564] days, P=0.008) as compared to the control group. As compared to ICI alone, a similar risk for a composite cardiovascular event was observed in those who received both ICI and VEGF-targeted therapy (HR, 0.70 [95% CI, 0.39–1.25]; P=0.23, Table 1). In total, 21/157 patients had a composite cardiovascular event among the cases, who received the combination of ICI and VEGF inhibitor (9 DVT, one MI, 9 PE, two ischemic strokes) as compared to 25/157 among the controls, who received ICI alone (14 DVT, 3 MI, 7 PE, one ischemic stroke). The median time to event was not different between the two groups (126 [98–260] days vs. 145 [28–205] days, P=0.47).

Conclusion

We found that among 157 patients who received a combination of ICI and VEGF-targeted therapy and 157 matched control patients who only received ICI therapy, the risk for cardiovascular events was not different between the two groups.

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding.
Basal characteristics of the prospective spanish immunotherapy registry of cardiovascular toxicity: SIR-CVT
Authors: Zatarain-Nicolas E , Perez-Ramirez S , De Castro J , Martin-Garcia A , Del Barco E , Mesa Rubio D , De La Haba J , Martinez Monzonis M A , Aguin Losada S , Lozano Palencia T , Martinez-Banaclocha N , Gomez-Rubin M C , Cortez-Castedo P , Martin P , Lopez-Fernandez T
Published: October 2022

Background

The immune checkpoint inhibitors (ICI) have improved the prognosis of many cancers in the last years but concerning cardiovascular toxicity (CVtox) have been reported. Nowadays, specific surveillance protocols are lacking, and early diagnosis of toxicity may be challenging.

Purpose

To characterize the cardiovascular (CV) effects of immunotherapy and to seek for the mechanisms of CVtox of ICI in a protocolize surveillance program of cardio-oncology.

Methods

A multicentre national registry was developed by a research consortium of scientific societies of Cardiology and Oncology (SEC and SEOM) and the cardiovascular research centre (CNIC) in Spain (Figure 1). A total of 18 hospitals participate in recruiting since Q4 2021. A follow-up protocol was stablished with clinical, electrocardiographic (EKG), echocardiography, cardiac magnetic resonance (CMR) and laboratory assessment, including cardiac biomarkers, inflammatory panel and the expression of miR-721, a specific myocarditis biomarker. Toxicity management is performed at each institution following international guidelines.

Results

53 patients were currently included. Median age was 68 [59, 75] years-old, 79% were male. 83% had at least 1 CV-risk factor (75% smoking history, 20% diabetes mellitus, 50% hyperlipemia, 57% hypertension, 19% chronic kidney injury) and up to34% had previous CV disease. 93% had at least one dose of COVID19 vaccine. Dyspnoea was referred by 23% of patients, 28% have abnormal EKG findings and one-third (33%) abnormal cardiac biomarkers (median Troponin I-hs 5.30 [2.60, 11.00]; NT-proBNP 199 [68, 736]). Mean LVEF (60% [56.15, 66.78]) and GLS (−18 [−19.75, −16]) were within the normal range but 26% showed LGE at baseline. Cancer characteristics are summarized in Table 1.

Conclusion

Real-world SIR-CVT patients show a high CV risk profile and frequent pre-existing CV diseases before ICI treatment. The prospective follow-up of this cohort will help to develop personalized surveillance protocols according to baseline CVtox risk and to define different grades of cardiotoxicity.

Funding Acknowledgement

Type of funding sources: None.
The importance of cancer in the prediction of embolic and hemorrhagic risk in patients with atrial fibrillation
Authors: Lizancos Castro A , Raposeiras Roubin S , Abu-Assi Alnakeeb E , Dominguez Erquicia P , Parada Barcia J A , Ledo Pineiro A , Noriega Caro V , Gonzalez Garcia A , Iglesias Otero C
Published: October 2022

Introduction

Cancer is a prevalent disease and is associated with a two-fold greater risk of developing cardiovascular disease. Atrial fibrillation (AF) is a common cardiovascular comorbidity among oncologic patients and the co-occurrence of these two represents several clinical challenges. Many cancers interact with the coagulation system and the representation of this population in clinical trials with cardiovascular drugs is scarce. Thus the impact of cancer regarding clinical outcomes in patients with AF is unclear.

Purpose

The aim of this study was to assess how cancer influences the prediction ability of embolic and hemorrhagic risk in patients with AF.

Methods

The study population comprised 16,056 patients from a Spanish health area diagnosed with AF between 2014 and 2018 of whom 1,137 (7.1%) had a history of cancer. During a median follow-up of 4.9 years we assessed the relationship between cancer and bleeding and embolic events by competing risk analysis considering death a competing risk.

Results

After adjusting for age, sex, CHA2DS2-VASC score, HAS-BLED score and anticoagulation therapy, cancer was not associated with a higher risk of embolic events (sHR 0.73, 95% CI 0.41–1.26; p=0.256). Neither was an association between an increased rate of embolic events and cancer detected, overall (sHR 0.73, 95% CI 0.41–1.26), regarding active cancer, or any subgroup of cancer. However, cancer was associated with an increased risk of bleeding specifically in patients with active cancer (sHR 1.42, 95% CI 1.20–1.67) or prior radiotherapy (sHR 1.40, 95% CI 1.19–1.65). Both CHA2DS2-VASC and HAS-BLED scores showed a suboptimal performance to predict embolic and bleeding risk in non-anticoagulated patients with active cancer (c-statistic <0.50). Discrimination and calibration ability of ATRIA and HEMORR2HAGES bleeding risk scores was also poor in patients with cancer (c-statistic <0.6 and Brier score >0.1). Moreover, the ratio between the increase in bleeding and decrease in embolic events in anticoagulated patients was similar in those with and without cancer (5.6 vs 7.8 bleeding events, p<0.001).

Conclusion

Cancer was associated with an increased risk of bleeding but not an increased risk of embolic events. Neither the CHA2DS2-VASC nor the HAS-BLED scores showed a good performance for predicting embolic and hemorrhagic events in AF patients with active cancer. The embolic-hemorrhagic ratio profile of anticoagulation was similar in patients with and without cancer, and parallel to cancer-free patients, anticoagulation significantly reduced embolic events while increasing bleeding risk in oncological patients.

Funding Acknowledgement

Type of funding sources: None.
Effect of 1st line treatment on aortic inflammation as assessed by 18 FDG PET/CT in patients with Hodgkin and non-Hodgkin lymphoma
Authors: Solomou E , Terentes-Printzios D , Kafouris P , Pouli A , Sioni A , Giannouli S , Metaxas M , Angelopoulou M , Ioakimidis N , Aggeli C , Voulgarelis M , Tousoulis D , Tsioufis C , Anagnostopoulos C D , Vlachopoulos C
Published: October 2022

Background

Despite advances in the treatment of oncology patients, therapy-related side effects may lead to premature morbidity among cancer survivors. Inflammatory activation that has been linked to cardiovascular disease is particularly crucial for the pathogenesis of both Hodgkin (HL) and non-Hodgkin lymphoma (NHL).

Objectives

To assess the vascular effects of chemotherapy in patients with HL and NHL by 18-Fluorodeoxyglucose (FDG PET/CT) and to investigate possible interactions with systemic inflammation as assessed by circulating inflammatory markers.

Methods

Between July 2015 and July 2019, sixty-five consecutive patients (37 males, mean age 56±17.8 years) with histologically confirmed new diagnosis of either HL (n=33) or NHL (n=32), were prospectively studied. PET/CT imaging was performed at baseline, at an interim phase and after 1st line treatment. Aortic FDG uptake was assessed by measuring global aortic TBR. Serum interleukin-6 (IL6) and interleukin-1b (IL1b) were measured at each phase for all patients and served as circulating inflammatory markers.

Results

Patients with HL demonstrated significant reduction in aortic TBR after 1st line treatment (aortic TBRbaseline=1.98, aorticTBR3rdscan=1.75, p=0.001, F=8.335), which remained significant after adjustment for 10-year cardiovascular risk (Framingham risk score), dyslipidemia, hypertension and diabetes (p=0.002, F=7.664). In contrast, patients with NHL did not demonstrate a significant aortic inflammation response (aortic TBRbaseline = 2.13, aorticTBR3rd scan=2.015, p=0.596, F=0.527), Figure 1. Regarding inflammatory markers, after 1st line treatment IL6 levels were reduced significantly in both HL and NHL groups (IL6baseline HL=3.25, IL6 post 1st line treatment HL=0.448, p=0.00; IL6baseline NHL=0.475, IL6 post 1st line treatment NHL=0.144, p=0.001); IL1b levels did not change significantly in either group, Table 1.

Conclusions

We demonstrate for the first time that aortic inflammation as assessed by 18-FDG PET-CT is reduced in HL patients after 1st line treatment but not in NHL patients. These findings imply that different pathophysiological pathways and different therapies might affect the arterial bed in different ways in lymphoma patients. Further, a strong potential role of molecular imaging in cardio-oncology emerges, offering valuable information on disease prognosis and progression with a single examination.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Hellenic Society of Hypertension
High risk of cardiovascular disease in curatively treated patients with oesophageal cancer: a Danish cohort study
Authors: Soendergaard M , Nordsmark M , Nielsen K M , Valentin J B , Johnsen S P , Poulsen S H
Published: October 2022

Background

The cardiovascular disease (CVD) burden among patients with oesophageal cancer (EC) treated with curative intent is unclear.

Purpose

To determine CVD incidence and all-cause mortality in patients with EC.

Material and methods

Danish national health registries were used to identify patients diagnosed with primary EC between 2008 and 2018. Each EC patient was matched with ten individuals from the general population. The primary endpoint was a CVD hospital contact (CVD-HC), either admission or outpatient contact. Secondary endpoints were all-cause mortality and five specific CVD endpoints evaluated separately: atrial fibrillation, ischemic heart disease, heart failure, perimyocarditis, and venous thromboembolism. Using registries, all endpoints were assessed up to ten years following the EC diagnosis.

Results

The study included 1,525 patients with EC matched to 15,250 individuals from the general population. Patients with EC had a post-diagnosis one-year adjusted hazard ratio (HR) of CVD-HCs of 6.1 (95% CI: 5.6 to 6.8) compared with the general population. During the next nine years, the risk of CVD-HC was comparable between the two cohorts with an adjusted HR of 1.0 (95% CI: 0.9 to 1.3) (Figure 1). Patients with EC, particularly those with prevalent CVD (29%) had a high risk of ischemic heart disease with a one-year HR of 6.2 (95% CI: 3.7 to 10.4). The risk of venous thromboembolism and atrial fibrillation was 14-fold and four-fold elevated within the first year after EC diagnosis compared to the general population. After EC diagnosis, all-cause mortality was, as expected, increased in patients with EC compared with the general population. However, prevalent CVD among patients with EC did not appear to be associated with higher all-cause mortality.

Conclusion

CVD morbidity was transiently increased in the first year following EC diagnosis compared with the general population. All-cause mortality risks were high but did not appear to be affected by prevalent CVD. The very high risk of CVD in curatively treated patients with EC calls for healthcare initiatives to advance preventive and post-treatment strategies.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): The Danish Cancer SocietyCarpenter Jorgen Holm and Wife Elisa F. Hansen's Memorial Scholarship
Clinical and pathologic features of out-of-hospital cardiac arrest in pregnancy: insights from a state-wide registry
Authors: Paratz E , Rowe S , Van Heusden A , Thompson T , Morgan N , Smith K , James P , Pflaumer A , Connell V , Semsarian C , Ingles J , Parsons S , Stub D , Zentner D , La Gerche A
Published: October 2022

Background

Cardiovascular disease is the most common cause of indirect maternal mortality worldwide, and cardiac arrest occurs in up to 1 in 12,000 pregnancies.

Objective

To define rates, clinical and pathologic factors of out-of-hospital cardiac arrest (OHCA) in pregnant and post-partum females.

Methods

A prospective state-wide cardiac arrest registry combining ambulance, hospital and forensic data captured all OHCAs from 2019–2021. Clinical and pathological details for pregnant patients were identified.

Results

1,482 OHCAs occurred, including 376 females of child-bearing age of whom eight were pregnant or post-partum. OHCA incidence was lower in pregnant females compared to non-pregnant females of child-bearing age (5.2 OHCAs per 100,000 pregnant females vs 23.1 per 100,000 females of child-bearing age, p<0.0001). Seven patients (87.5%) died, with five (62.5%) having a cardiac cause of OHCA (unascertained = 2, cardiomyopathy = 2 (1 hypertrophic), ischemic heart disease = 1). Two patients had pre-existing cardiac risk factors, but none had a cardiac diagnosis pre-arrest. Compared to in-hospital cardiac arrests (IHCAs) in pregnancy, OHCAs are more likely to have a cardiac cause (odds ratio 3.81) and lower maternal survival (odds ratio 0.09).

Conclusion

Maternal OHCA affects approximately 1 in 20,000 pregnancies with high maternal mortality rates. OHCA occurs at one-quarter the rate in non-pregnant females of child-bearing age. Approximately two-thirds of maternal OHCAs had an underlying cardiac cause, but low rates of cardiac diagnosis pre-arrest. OHCAs differ markedly from IHCAs in pregnant females, requiring ongoing evaluation as to specific causes and preventability.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): NHMRC, NHF
Gestational diabetes, preeclampsia and the maternal heart
Authors: Thiru S , Ansari F , Cubbon R , Forbes K , Chowdhary A , Jex N , Kotha S , Morley L , Xue H , Kellman P , Greenwood J P , Plein S , Everett T , Scott E , Levelt E
Published: October 2022

Background

Gestational diabetes mellitus (GDM) and preeclampsia (pE) are both associated with an increased risk of cardiovascular mortality and morbidity, including an increased risk of developing heart failure in later life. Both conditions are increasing in prevalence; GDM affects up to 12% and pE affects 3–5% of pregnancies worldwide. Compromised cardiac energy production is an important contributor to most forms of heart disease. The changes in myocardial energetics in GDM and pE have not been characterised previously.

Purpose

We sought to assess if women with GDM and women with pE in the third trimester of pregnancy exhibit adverse cardiac alterations in myocardial energetics, function or tissue characteristics.

Methods

Thirty-eight healthy pregnant (HP) women, thirty women with GDM and fifteen women with pE were recruited, matched for age and ethnicity. Participants underwent phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance for assessment of myocardial energetics (phosphocreatine to ATP ratio (PCr/ATP)), tissue characteristics, biventricular volumes and ejection fractions, left ventricular (LV) mass, global longitudinal strain (GLS) and mitral in-flow E/A ratio.

Results

The biochemical characteristics and multiparametric MR results are given in Table 1.

The women in the GDM and the pE groups had higher body-mass index. There was a stepwise increase in the systolic and diastolic BP from the HP to the GDM to the pE group. There was no difference in NTproBNP concentrations between the groups. The gestational weight gain was higher in women with GDM and pE compared to the HP group.

The women in the GDM and the pE groups showed similar reductions in myocardial PCr/ATP ratios compared to HP group (Figure 1a), accompanied by lower LV end-diastolic volumes and higher LV mass (Figure 1b) and enhanced LV concentricity in both groups (Figure 1c). While LV ejection fractions were similar across the groups, the GLS was reduced in women with GDM and in women with pE (Figure 1d).

Conclusions

We show here for the first time that despite no prior diagnosis of diabetes or hypertension, women with GDM or pE manifest impaired myocardial contractility and higher LV mass, associated with reductions in myocardial energetics. These findings may aid our understanding of the long-term cardiovascular risks associated with these conditions.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Wellcome Trust
Hypertensive disorders in pregnancy increase subsequent risk of ischaemic cardiovascular events: genetic evidence from a Mendelian randomisation study
Authors: Rayes B , Ardissino M , Slob E , Johnson M , Ng F S
Published: October 2022

Background

Hypertensive disorders in pregnancy are major causes of maternal and foetal morbidity and have also been associated with long-term maternal risk of cardiovascular diseases. Whilst many retrospective and prospective cohort studies have explored this relationship, it is difficult to make causal inferences from observational studies due to potential residual confounding and bias. Leveraging genetic data predisposing to exposures and outcomes in instrumental variable analysis, Mendelian randomisation (MR) can provide valuable information for causal inference. The aim of this study is to use MR to investigate the relationship between hypertensive disorders in pregnancy and cardiovascular diseases.

Methods

Uncorrelated single nucleotide polymorphisms (SNPs) were selected as instrumental variables from the FinnGen consortium summary statistics for the exposures of any hypertensive disorder in pregnancy, and its two subgroups of gestational hypertension, and pre-eclampsia or eclampsia. Genetic association estimates for outcomes were extracted from GWAS studies of 122,733 for coronary artery disease, 34,217 cases for ischaemic stroke, 47,309 cases for heart failure and 60,620 cases for atrial fibrillation. All studies included patients predominantly of European ancestry. Primary analysis was conducted using inverse-variance weighted MR.

Results

Hypertensive disorders in pregnancy were associated with increased risk of coronary artery disease (odds ratio (OR) 1.24; 95% confidence interval (CI) 1.08–1.43; p=0.002); and this association was evident for both gestational hypertension (OR= 1.08; 95% CI: 1.00–1.17; p=0.040) and pre- or eclampsia (OR=1.06; 95% CI: 1.01–1.12; p=0.030). Hypertensive disorders in pregnancy were also associated with increased risk of ischaemic stroke (OR=1.27; 95% CI: 1.12–1.44; p=2.87x10–4). Neither gestational hypertension nor pre-eclampsia were independently associated with increased risk of ischaemic stroke, though effect estimates were consistent in direction. No associations were noted between the three hypertensive disorders in pregnancy and the outcomes of heart failure or atrial fibrillation.

Conclusions

Our findings provide genetic evidence that supports a likely causal association between hypertension in pregnancy and increased risk of coronary artery disease and stroke. This is consistent with observational evidence and supports the classification of hypertensive disorders in pregnancy as risk factors for cardiovascular disease.

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council GEPSI 946647 for EAWSBritish Heart Foundation RG/16/3/32175 for FSN
Feasibility of a longitudinal statistical atlas model to study aortic growth in congenital heart disease
Authors: Sophocleous F , Bone A , Shearn A I U , Nieves Velasco Forte M , Bruse J L , Caputo M , Biglino G
Published: October 2022

Background

Studying anatomical shape progression over time is of utmost importance to refine our understanding of clinically relevant processes. These include vascular remodelling, such as aortic dilation, which is particularly important in some congenital heart defects (CHD).

Purpose

A novel methodological framework for analysing three-dimensional (3D) shape changes over time (“growth”) has been applied for the first time in a CHD scenario, i.e., bicuspid aortic valve (BAV) disease, the most common CHD.

Methods

Three-dimensional aortic shapes (n=94) reconstructed as surface meshes from cardiovascular magnetic resonance imaging (MRI) data represented the input for a longitudinal shape atlas model, using multiple scans over time (n=2–4 scans per patient). This model relies on diffeomorphic transformations in the absence of point-to-point correspondence, and on the correct combination of initialization, estimation, and registration parameters.

Results

We computed the 3D shape trajectory of an average disease progression over time in our cohort (Picture 1, grey to blue shapes), as well as time-dependent parameters, geometric variations and the average shape of the population (Picture 1, red shape). Results cover a spatiotemporal spectrum of visual and numerical information that can be further used to investigate clinical associations and stratify patients, as such capturing aortic remodelling in the presence of BAV aortopathy.

Conclusion

This proof-of-concept study demonstrates the feasibility of applying advanced statistical shape models to track disease progression and stratify patients with CHD.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): British Heart Foundation and NIHR BRC
Prediction model for hypertension after preeclampsia in initially normotensive women; the Queen of Hearts cohort
Authors: Hooijschuur M , Janssen B N J , Mulder E G , Kroon A A , Meijers J M J , Van Bussel B C T , Van Kuijk S M J , Spaanderman M E A , Ghossein-Doha C
Published: October 2022

Background

Timely detection and treatment of hypertension prevents cardiovascular diseases. Formerly preeclamptic women are at increased risk for hypertension, but targeted and structural follow-up of these women is lacking.

Purpose

To develop a prediction model for the development of hypertension in the decade following preeclampsia in women who were initially normotensive shortly after pregnancy.

Methods

In this longitudinal cohort study, formerly preeclamptic women were invited twice for a cardiovascular assessment. The first visit took place at a median interval of 10 months after delivery and a second visit 10 years later as part of the Queen of Hearts cohort study on early detection of heart failure among young women with a history of preeclampsia (ClinicalTrials.gov Identifier NCT02347540). Normotensive women at the first visit were divided in two groups whether or not they had developed hypertension during visit 2. Hypertension was defined as SBP ≥130 mmHg and/or DBP ≥80 mmhg and/or use of antihypertensive medication. We developed a prediction model using multivariable logistic regression analysis. The model was internally validated with bootstrapping techniques.

Results

Of the 259 women, 185 (71%) were normotensive at first visit of which 49 (26%) had developed hypertension at the second visit. The prediction model, based on birth weight centile, mean arterial pressure, total cholesterol, left ventricular mass index and left ventricular ejection fraction, had a good to excellent discriminative ability of AUC-ROC-curve 0.82 (95% CI 0.75–0.89) with an optimism corrected AUC of 0.80. Sensitivity and specificity of our model to predict yearly 10% risk to develop hypertension was 98% and 65% respectively and positive- and negative-predictive values were 50% and 99% respectively.

Conclusions

Based on five easily available variables, we developed a good-to-excellent performing predictive tool to identify incident hypertension following preeclampsia in women that were normotensive shortly after pregnancy.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): This work was partially supported by funding of de Nederlandse Hartstichting (Dutch Heart Foundation, grant number: 2013T084, Queen of Hearts study)
Endothelial glycocalyx improvement after six months and one-year of antiretroviral therapy in treatment naive patients with human immunodeficiency virus
Authors: Triantafyllidi H , Fragkou P , Birmpa D , Benas D , Thymis I , Kostelli G , Schoinas A , Protopapas K , Kavvatha D , Antoniadou A , Papadopoulos A , Ikonomidis I
Published: October 2022

Background

Chronic inflammation induced by Human Immunodeficiency Virus (HIV) plays a key role in the development of early cardiovascular (CV) disease. The impact of currently recommended first line antiretroviral therapy (ART) on CV risk early after treatment initiation is still under investigation. We aimed to explore any treatment-induced changes in endothelial function through endothelial glycocalyx measurement (EG) in treatment naïve HIV patients' one year post HIV treatment initiation by different ART agents.

Methods

We estimated endothelial function by endothelial glycocalyx integrity measurement in 58 recently diagnosed and treatment naïve HIV patients (mean age=38+10 years, 91% males, 61% smokers) at baseline and at 1-year post ART initiation (integrase or protease inhibitors). Increased perfusion boundary region (PBR) of the sublingual arterial microvessels (ranged from 5–25 micrometers) using Sideview Darkfield imaging (Microscan, Glycocheck) was measured as a non-invasive accurate index of reduced EG thickness.

Results

From a total population of 54 HIV patients, 35 patients were randomly treated by the newer integrase inhibitor Dolutegravir (Group A, mean age = 37±10 years, 89% males, 54% smokers) while 22 patients by the older protease inhibitor Darunavir/Cobicistat (Group B, mean age = 38±10 years, 95% males, 74% smokers). No differences were found between groups regarding age, weight, lipid profile (LDL-C, HDL-C, triglycerides), office (SBP, DBP) and central (cBP) blood pressure. We found that weight (76±14 vs. 81±16 kg, p<0.001), SBP (125±12 vs. 130±14 mmHg, p=0.003) and cBP (116±12 vs. 121±12 mmHg, p=0.001) were increased in the entire HIV population, at 1 year post-treatment. At 6 months evaluation, PBR5–25 was decreased in the entire HIV population and Group A (2.18±0.3 μm vs. 2.05±0.3 μm, p=0.01 and 2.19±0.3 μm vs. 2.02±0.3 μm, p=0.02, respectively). However, at 1-year post treatment evaluation, PBR5–25 was decreased in all groups, total HIV population, Group A and Group B (2.18±0.3 μm vs. 1.96±0.3 μm, p<0.001, 2.19±0.3 μm vs. 1.93±0.3 μm, p=0.003 and 2.17±0.3 vs. 1.99±0.3, p=0.04, respectively).

Conclusions

Endothelial function, estimated by endothelial glycocalyx integrity, is improved in newly diagnosed and treatment naïve HIV patients, evaluated at 6 and 12 months post-treatment initiation by integrase or protease inhibitors despite weight and blood pressure increase.

Funding Acknowledgement

Type of funding sources: None.
Comparison of CT acquired valvular calcification scores in hemodialysis vs peritoneal dialysis patients undergoing open heart surgery
Authors: Kanaan C , Layoun H , Kondoleon N , Mirzai S , Fadel R , Schold J , Arrigain S , Mehdi A M , Taliercio J T , Unai S , Kapadia S , Harb S , Nakhoul G
Published: October 2022

Background

Several factors have been identified as independent risk factors for cardiac valvular calcification (CVC), including but not limited to age, inflammatory conditions, loss of calcification inhibitors, and dysregulated bone mineral metabolism. However, data is scarce regarding which dialysis modality portends more severe CVC.

Purpose

Our aim was to compare the degree of valvular calcification in hemodialysis (HD) and peritoneal dialysis (PD) patients prior to open heart surgery (OHS) using a computed CT calcium score.

Methods

Dialysis patients who underwent OHS at our institution from 2009–2019 who had a pre-surgical cardiac CT were grouped according to duration of dialysis modality prior to their surgical date. There were two study cohorts to evaluate outcomes of interest: mitral and aortic calcification. We included the first surgical record per patient for patients undergoing isolated CABG, or CABG+valve surgery (repair or replacement), or valve-only surgery (repair or replacement). To evaluate mitral calcification, we excluded any patients undergoing any mitral valve surgery (repair or replacement). We also excluded patients with a history of mitral valve repair/replacement. To evaluate aortic calcification, we excluded any patients undergoing any aortic valve surgery (repair or replacement). We also excluded patients with a history of aortic valve repair/replacement. Mitral annular and aortic valvular calcification were assessed using the Agatston score. Logistic regression was performed to test for the association of PD and HD cumulative dialysis duration with presence of valvular calcification.

Results

A total of 296 patients met inclusion criteria for at least one of the strata in our study. Of those, 214 met inclusion for the mitral strata, and 166 met criteria for the aortic strata (Table 1). In the logistic regression model for the mitral strata, age and female sex were associated with higher odds of presence of mitral calcification (Figure 1). Cumulative years on PD and cumulative years on HD were not significantly associated with presence of mitral calcification. In the logistic regression model for the aortic strata, age was associated with higher odds of presence of aortic calcification, while female sex was associated with lower odds (Figure 1). Cumulative years on PD and cumulative years on HD were not significantly associated with presence of aortic calcification.

Conclusion

Presence of mitral and aortic calcification for patients undergoing OHS was not significantly associated with cumulative length of PD or HD after adjusting for age and gender, suggesting that there may be more factors at play in the progression of valvular calcification in end stage renal disease patients than what was previously thought.

Funding Acknowledgement

Type of funding sources: None.
Mesenchymal stromal cell therapy with early tacrolimus withdrawal prevents left atrial remodelling in renal transplant recipients: an analysis of the TRITON trial
Authors: Meucci M C , Reinders M E J , Groeneweg K E , Bezstarosti S , Ajmone Marsan N , Bax J J , De Fijter J W , Delgado V
Published: October 2022

Background

After renal transplantation, there is a need for immunosuppressive regimens that effectively prevent allograft rejection, while minimizing cardiovascular side effects. The TRITON study is the first randomized clinical trial that tested a strategy with autologous bone marrow derived mesenchymal stromal cell (MSC) therapy and complete withdrawal of calcineurin inhibitors (CNIs). The combination of MSC therapy and CNIs discontinuation was associated with improved blood pression control and regression of left ventricular hypertrophy. Nevertheless, the impact of this immunosuppressive strategy on left atrial (LA) structural and functional remodelling, which has been proven as an independent predictor of cardiovascular outcomes, has not been investigated.

Purpose

To assess the effects of MSC therapy combined with CNIs withdrawal on longitudinal changes of LA structure and function, evaluated by two-dimensional transthoracic echocardiography.

Methods

The TRITON trial randomized renal transplant recipients to MSC therapy – infused at week 6 and 7 after transplantation, with complete withdrawal at week 8 of tacrolimus (MSC group) – or standard tacrolimus dose (control group). Patients who underwent transthoracic echocardiography with speckle-tracking analysis at week 4 and 24 after renal transplantation were included in this sub-analysis. Changes in echocardiographic variables between 4 and 24 weeks post-transplantation were evaluated and compared between randomization arms using an analysis of covariance model, adjusted for baseline variable.

Results

54 patients (MSC group =27; control group =27) were included. Between 4 and 24 weeks after transplantation, an increase in indexed minimal LA volume (LAVImin) was observed in the control group, whereas in the MSC group there were no changes in LAVImin over the time, leading to a significant difference between groups (p=0.021). Moreover, patients randomized to MSC therapy showed a benefit in LA function, assessed by a significant interaction between changes in LA emptying fraction (LAEF) and LA reservoir strain and the treatment group (p=0.012 and p=0.027, respectively) (Table 1).

The association between changes in LA structural and functional parameters and the randomization arm remained significant after adjustment for changes in systolic blood pressure, diastolic blood pressure and estimated glomerular filtration rate over the time (Figure 1).

Conclusion

The combination of MSC therapy and early CNIs withdrawal prevents LA structural and functional remodelling in the first six months after renal transplantation. MSC therapy appears a promising approach in renal transplant recipient, effective in the prevention of graft rejection, while exerting potential cardioprotective effects.

Funding Acknowledgement

Type of funding sources: None.
Baseline cardiovascular risk in subjects with type 2 diabetes and chronic kidney disease from the FLOW trial
Authors: Mahaffey K W , Baeres F M M , Bakris G , Bosch-Traberg H , Gislum M , Lawson J , Mann J F E , Mersebach H , Perkovic V , Rossing P , Tuttle K , Pratley R
Published: October 2022

Background

Patients with chronic kidney disease and type 2 diabetes (T2D) have a high risk of progression to kidney failure as well as cardiovascular (CV) events. It is established that glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and reduce body weight. Some CV outcomes trials have shown that GLP-1RAs reduce CV risk in people with T2D at high CV risk; for example, the SUSTAIN 6 trial demonstrated that the GLP-1RA semaglutide significantly lowered the rate of major CV events (CV death, non-fatal myocardial infarction and non-fatal stroke) versus placebo. Some trials have also indicated that GLP-1RAs reduce albuminuria and estimated glomerular filtration rate (eGFR) decline. Based on these previous results indicating potential kidney-protective effects, the FLOW trial (NCT03819153) is evaluating once-weekly, subcutaneous semaglutide 1.0 mg versus placebo on kidney- and CV-related outcomes in participants with T2D. We describe the baseline characteristics and the calculated CV risk of this patient population using the atherosclerotic CV disease (ASCVD) and second manifestations of arterial disease (SMART) risk calculators.

Methods

FLOW is an ongoing, multicentre, randomised, double-blind, parallel-group, event-driven, phase 3b trial, with participants randomised 1:1 to semaglutide or placebo, each in addition to standard of care. Recruitment is complete and 3,535 participants with T2D, an eGFR ≥25–≤75 mL/min/1.73 m2, and urine albumin-to-creatinine ratio ≥100–≤5,000 mg/g have been enrolled. The primary endpoint is time to first occurrence of a kidney composite that includes ≥50% persistent eGFR reduction, kidney failure (persistent eGFR <15 mL/min/1.73 m2 or initiation of chronic dialysis or kidney transplantation), and kidney-related death, or CV death. Key secondary outcomes include time to first occurrence of CV death, myocardial infarction or stroke.

Results

The baseline clinical characteristics and demographics are shown (Table 1). Median age was 68 years, 30% were female, mean diabetes duration was 17 years, and 98% had a history of hypertension. Overall, 52% of participants had a previous CV event. The calculated 10-year risk for ASCVD events in those without prior ASCVD was 31% in males and 18% in females, and in those with previous CV events was 37–56% in males and 35–53% in females depending on the type of CV disease reported in the calculator (Table 2).

Conclusions

The FLOW trial has completed enrolment. Based on the ASCVD and SMART risk calculators, the enrolled population has a substantial risk for adverse CV outcomes. Event ascertainment is ongoing, and the FLOW trial will provide evidence for the potential of semaglutide to improve kidney and CV outcomes in the T2D population.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Novo Nordisk
Assessment of left atrial function and diastolic dysfunction in patients with Becker muscular dystrophy
Authors: Gegenava T , Van De Velde N , Koeks Z , Spitali P , Verschuuren J J G M , Delgado V , Bax J , Niks E H , Ajmone-Marsan N
Published: October 2022

Background

Becker muscular dystrophy (BMD) is frequently characterized by myocardial involvement1 but little is known about the prevalence of left ventricular (LV) diastolic dysfunction (DD) in these patients, particularly when using more recently proposed measure of left atrial (LA) function.

Purpose

Purpose of our study was to assess LVDD in patients with BMD using the currently recommended echocardiographic multiparametric approach and adding LA reservoir strain as advanced measure of LVDD.

Methods

A total of 33 BMD patients (38±13 years) were analyzed including standard and advanced echocardiography at the time of their first visit and at 24 months follow-up. A control group consisted of 20 age- and gender-matched healthy subjects.

Results

18% of BMD patients showed an e'lateral <10, 0% an E/e' >14, 22% a LAVI >34ml/m2 and 11% a tricuspid velocity >2.8m/s. When applying the currently recommended multiparametric approach, 83% of BMD patients showed normal DD and 17% showed indeterminate LV diastolic dysfunction (50% positive parameters); no BMD patient had >50% positive DD parameters for confirmed DD. LA reservoir strain was significantly lower in BMD patients as compared to controls (28±10% vs. 42±11%; p<0.001) (Figure), while LA indexed volume (LAVI) was not (26±19 ml/m2 vs. 21±6 ml/m2; p=0.142). When using the reported median value of LA reservoir strain (47%) for normal subjects with comparable age2, 31 (94%) BMD patients had impaired LA strain, but when using the cut-off value of <19% for increased LV filling pressure, 6 (18%) patients showed affected LA reservoir strain. Patients with more impaired six minute walk test (6MWT), defined as in the 1st tertile (1st tertile 0–309m; 2nd tertile 310–523m; 3rd tertile >523m) had significantly lower LA reservoir strain (1st tertile, 22±6% vs. 2nd tertile, 29±14% vs. 3rd tertile, 33±5%; p=0.022). LA reservoir strain tended to deteriorate at 1 year follow-up but not significantly (from 29±10% to 26±12%; p=0.200).

Conclusions

LVDD is not highly prevalent in BMD patients but LA dysfunction as assessed by LA reservoir strain is reduced and may improve detection of myocardial involvement in these patients, also over time.

Funding Acknowledgement

Type of funding sources: None.