bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of systolic blood pressure on epicardial adipose tissue in patients with chronic coronary artery disease
Authors: Leng S , Teo L , Yew M S , Loong Y T , Raffiee N A S , Wang X M , Ngiam K Y , Lee H K , Huang W M , Vaughan R , Chua T , Tan S Y , Chan M , Baskaran L , Zhong L
Published: October 2024

Objectives

The current study aimed to investigate the impact of systolic blood pressure (SBP) on epicardial adipose tissue (EAT) volume in a large, multi-center cohort of patients with chronic coronary artery disease (CAD).

Methods

We included 879 patients with CAD (mean age: 58±11 years; 294 females; 72% Chinese, 20% Indian/Malay, 8% Others) in the APOLLO study. The EAT volume was measured using non-contrast computed tomography (CT) imaging. The contour of the pericardium was traced from the pulmonary artery bifurcation to the apex of the heart. CT attenuation between -190 and -30 Hounsfield units (HU) was used to select the EAT on every axial slice. The EAT volumes were automatically calculated from 3-dimensional fat voxels at each axial slice, which were then summed to obtain the total EAT volume (Figure 1).

Results

EAT volume was positively correlated with age (r=0.261, P<0.0001). With a one-year increase in age, the EAT volume was found to increase by 1.5 cm3, adjusting for other confounders. The mean EAT volume for males was 8.3 cm3 higher than for females (P=0.015). Patients with hypertension had significantly higher EAT volume (134±51 vs. 114±48 cm3, P<0.0001) compared to those without hypertension. Multivariable analysis adjusted for age, gender and other cardiac risk factors showed that the presence of hypertension (P=0.043) was independently associated with EAT volume. Compared to the highest SBP tertile (≥148 mmHg), those in the lowest SBP tertile (≤132 mmHg) had lower EAT volume (117±52 vs. 128±51 cm3, P=0.007). When examined as a continuous variable, higher SBP was significantly associated with higher EAT volume: for every 10mmHg increase in SBP, EAT volume increased by 2.6 cm3.

Conclusion

The study found a significant association between hypertension and increased EAT volume, emphasizing the importance of managing hypertension to reduce cardiovascular risk.
Are cancer survivors at greater risk of coronary artery disease?
Authors: Soh C , Smith J , Carrington M , Wong J , Marwick T
Published: October 2024

Background

Some cancer survivors are at increased risk of coronary artery disease (CAD), due to shared risk factors, effects of cancer or cancer therapy. Typically an asymptomatic condition, CAD has historically been subject to underdiagnosis, thus risk is compounded for at-risk populations. This study investigates the difference in risk factor status between a survivor group undergoing screening for CAD risk, and a control group without cancer, recruited from the same community.

Methods

1642 participants were recruited from the community in Victoria and Tasmania, Australia, and their cancer status were evaluated. Risk of CAD was identified via the Pooled Cohort Equation (PCE) and participants were stratified into low (<5%), intermediate (5% - 20%) and high risk (>20%) based on their PCE score. A 3:1 propensity matching based on age and sex was performed to match the cohort between cancer survivors and non-cancer participants. Participants’ baseline characteristics were evaluated.

Results

After matching, 651 (median age 66 [IQR 9] years, 70.5% female) non-cancer participants and 217 (median age 66 [IQR 10] years, 70.5% female) cancer survivors were included in the analyses. The prevalence of low and intermediate CAD risk in non-cancer population (38.4% and 57.5%, respectively) and cancer survivors (37.3%, and 54.8%, respectively) were similar (p=0.840 and 0.553, respectively). However, 17 (7.8%) of the cancer survivors were identified as high risk, which was significantly greater than non-cancer population (4.1%, p=0.049). The risk profiles of cancer survivors and the non-cancer population (Table 1) suggest a higher prevalence of lipid abnormalities in survivors.

Conclusions

Cancer survivors have a similar CAD risk profile to control subjects from the same population, but more commonly show lipid abnormalities. Whether this reflects undertreatment in survivors warrants further evaluation.
Long-term validation of AtherosSlerosis CardioVascular Disease (ASCVD) risk score and the role of aspirin for primary Cardiovascular prevention in Korean patients with over ASCVD 20% risk score
Authors: Rha S , Hyun S , Choi B G , Choi S Y , Cha J , Kang J , Chu W , Park S , Choi C U , Park C G
Published: October 2024

Background

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death worldwide. The ASCVD risk score can be a great tool for preventing ASCVD in the future. There is a mediation recommendation depending on calculated risk called United States Prevention Services Task Force (USPSTF) aspirin (ASA) recommendation. However, the validation studies of long-term clinical outcomes in Korean population using the ASCVD risk score and of the effect of ASA in Korean patients using USPSTF recommendation are limited.

Methods

A total of 7,249 patients with any chest pain who underwent coronary spasm provocation tests between January 2004 and December 2021 were enrolled. Patients were divided into four groups, based on the ASCVD risk score: < 5% group (Low Risk, n = 2,534), 5 - 10% group (Borderline Risk, n=1,681), 10 - 20% group (Intermediate Risk, n = 1,896) and ≥ 20% group (High Risk, n = 1,138). The primary endpoint was Major Adverse Cerebral and Cardiovascular Event (MACCE1), including stroke and MACE. The secondary endpoint was MACCE 2, defined as composite of MACE and recurrent angina requiring follow-up coronary angiography (CAG). The third endpoint was the effect of aspirin in patients who have over 20% ASCVD risk.

Results

Long term (10-year) ASCVD risk score was well-validated from the "Low Risk" group to the "High Risk" group by 1.87%, 7.44%, 14.09%, and 30.61%, respectively (P < 0.001). In baseline characteristics, the calculation factors of ASCVD risk score is also well-stratified, showing the more adverse clinical profiles in the "High Risk" group than the "Low Risk" group. In 10-year clinical outcomes, although MACCE1 and MACCE2 showed an increasing trend numerically, stroke was observed to significantly increase according to ASCVD risk score. There was no effect of ASA prescribed in accordance with USPSTF recommendation. The group with the highest rate of 20% or more failed to show the aspirin prevent effect on the occurrence of CV events, but also increased the incidence (MACCE1; HR: 1.647, P-Value: 0.283, 95% CI: 0.662 - 4.100, MACCE2; HR: 1.819, P-Value: 0.025, 95% CI: 1.078 - 3.068).

Conclusion

Long term ASCVD risk score was associated with higher risk of stroke. However, MACCE1 and MACCE2 only showed an increasing trend numerically. Furthermore, the effect of ASA prescribed based on the USPSTF ASA use recommendation statement were not observed in Korean population. Consequently, additional research is needed to ensure the utility of ASCVD risk score and the effect of ASA in high-risk patients to prevent future CV events in Korean population.
The use of allopurinol in prophylaxis against contrast-induced nephropathy in patients undergoing percutaneous coronary intervention
Authors: Mahmoud K , Hasan W , Salah Eldin H , Elramissy D
Published: October 2024

Background

Contrast-induced nephropathy (CIN) is a serious complication after percutaneous coronary intervention (PCI). Inflammation and development of reactive oxygen species are among the postulated mechanisms of CIN. Allopurinol with anti-inflammatory action could be a preventive method of CI-AKI.

Aim of the work

To determine the effect of adding allopurinol to hydration in the prevention of CIN in patients undergoing PCI, with or without hyperuricemia.

Methods

One hundred and seven patients with moderate to high Mehran score undergoing elective PCI were randomly allocated to the allopurinol (n=52) or the control group (n=55). Those in the allopurinol group (hyperuricemic n=25, and normouricemic n= 27) received allopurinol 300 mg one day and one hour before PCI beside intravenous hydration (1 ml/kg/hour) normal saline, a maximum of 100 ml/hour for 12 hours pre and post coronary angiography. Patients in the control group (hyperuricemic n=26 and normouricemic n=29), received the same intravenous hydration only. Serum creatinine and urea were measured before and 48 hours after the procedure while the uric acid level was measured before the procedure only. CIN was defined by a percentage increase in serum creatinine of ≥25% or absolute serum creatinine ≥0.5 mg/dl, 48 hours after PCI.

Results

The mean age of the studied patients was 59.6 ± 9.1 years old, 59% were male. No difference between both groups regarding baseline characteristics or medications. Average Mehran score was 9.0 ± 1.2. CIN was observed in 5 patients in the allopurinol group (9.6%) and 15 patients in the control group (27.3%) (P = 0.017). There was no significant difference between both groups regarding the contrast volume (179.8 ± 68.1 vs. 153.8 ± 57.9 ml, p: 0.052). Hyperuricemia had no significant effect on increasing the incidence of CI-AKI either in patients with or without CKD (p=0.964).

Conclusion

Allopurinol on the top of hydration was found to decrease the incidence of CIN following PCI in patients with moderate to high Mehran score for CIN. The anti-inflammatory action of allopurinol could be the mechanism of this favorable effect, as baseline uric acid didn't affect the results. Further multi-center study with a larger sample size is needed to offer more definite results.
Extracellular vesicle-incorporated long noncoding RNA PUNISHER is increased in coronary artery disease and regulates endothelial cell function
Authors: Hosen D R , Li M E D , Liu M E D , Jansen M E D , Nickenig D R
Published: October 2024

Aims

Long noncoding RNAs (lncRNAs) have emerged as biomarkers and regulators of cardiovascular disease. Circulating lncRNAs can be incorporated into extracellular vesicles (EVs). Our aim was to study the expression pattern of circulating EV-incorporated lncRNAs in patients with and without coronary artery disease (CAD). The regulation of the lncRNA PUNISHER was further assessed as an intercellular messenger in endothelial cell (EC) biology.

Methods and results

Circulating EVs were isolated from the plasma of patients using ultracentrifugation. Electron microscopy, western blot, and NTA were used to determine the size and origin of the EVs. PCR-based human lncRNA array analysis revealed that certain EV-lncRNAs are significantly different in patients with CAD compared to patients without CAD. To validate the lncRNA array results, 60 patients with (n=30) or without (n=30) CAD were prospectively studied. Four atherosclerosis-related lncRNAs (PUNISHER, GAS5, MALAT1, and H19) were quantified in the circulating EVs by using real-time quantitative PCR (RT-qPCR). Among these, PUNISHER (p=0.002) and GAS5 (0.02) were significantly increased in patients with CAD, compared to non-CAD patients. Analysis of RNA degradation revealed that circulating PUNISHER is mainly incorporated within EVs. In vitro, atherosclerotic stimuli consisting of oxLDL or TNF-a treatment caused an upregulation of PUNISHER levels in human coronary artery endothelial cells (HCAEC) and in the corresponding EVs. Labeling of EVs followed by RT-qPCR demonstrated that functional PUNISHER was transported into the recipient ECs, which accelerated cell migration, proliferation, and tube formation. Mechanistically, the RNA-binding protein hnRNPK was identified by an RNA immunoprecipitation (RIP) assay as an interaction partner of PUNISHER, regulating its loading into small EVs. Knockdown of PUNISHER abrogated the EV-mediated effects on EC migration, proliferation, and tube formation. PCR-based gene profiling showed that the expression of VEGF RNA was significantly increased in ECs by treatment with EVs. Protein stability and RNA-immunoprecipitation followed by RT-qPCR analysis indicated that the PUNISHER-hnRNPK axis regulates the stability and binding of VEGFA mRNA to hnRNPK. Knockdown of PUNISHER in EVs abrogated the EV-mediated promotion of VEGFA gene- and protein expression.

Conclusion

The circulating lncRNA PUNISHER is increased in CAD patients. Intercellular transfer of EV-incorporated PUNISHER promotes a pro-angiogenic phenotype via a VEGFA-dependent mechanism.
Early detection of cardiac dysfunction using shear wave imaging: insights into reduced cardiorespiratory fitness in childhood cancer survivors
Authors: Youssef A , Verschueren S , Vanrusselt D , Van Ermengem N , Uyttebroeck A , Hornickx M , Pleysier S , Wouters L , Cools B , D'hooge J , Voigt J U
Published: October 2024

Background

Diastolic dysfunction is thought to be the earliest cardiotoxic sequel after cancer therapy among childhood cancer survivors. Despite many survivors do exhibit reduced cardiorespiratory fitness (CRF) potentially due to cardiotoxicity, current echocardiographic parameters fail to detect hidden diastolic dysfunction early after therapy (1). High frame rate (HFR) shear wave imaging (SWI) is a novel tool that could give insights about myocardial stiffness, which is a key determining factor of diastolic function.

Purpose

We aimed at testing the ability of SWI to detect early alterations in myocardial stiffness among childhood cancer survivors and its relation with the reduced CRF.

Methods

Fifty childhood cancer survivors (mean 20 ±3 years) who received chemo-and/or- radiotherapy (mean time after treatment: 4 ±3 years) and thirty-two matched healthy volunteers (HV) were recruited. Conventional as well as HFR echocardiographic images (ca. 1200 frames/second) were acquired at rest using a modified commercial echocardiography machine. All participants underwent an incremental, symptom-limited cardiopulmonary exercise test on a treadmill measuring peak oxygen consumption (VO2 peak). HFR data were analysed offline. An anatomical M mode was drawn along the ventricular septum, and tissue Doppler acceleration maps were extracted to measure SW velocities after mitral valve closure (MVC) (Figure 1).

Results

Among cancer survivors, left ventricular ejection fraction (LVEF) and global longitudinal strain were significantly lower compared to HV (56 % ±4 vs 59 % ±4, and 17.6 % ±1.6 vs 19.1 % ±1.2, respectively; p <0.001). However, both LVEF and GLS were within the normal range and none of them correlated with the peak VO2 (Figure 2A&B). None of the echocardiographic diastolic parameters (e.g. mitral E, E/e’, left atrial volume or TR jet velocity) showed significant difference between both groups (P > 0.05). The mean SW velocities were significantly higher in cancer survivors compared to HV (3.9 ±0.6 m/s vs 3.2 ±0.3 m/s respectively; p <0.001). Interestingly, SW velocities among cancer survivors showed moderate significant negative correlation with the VO2 peak (r= -0.590, p <0.001) indicating increasing myocardial stiffness as the cardiorespiratory fitness declined (Figure 2C).

Conclusions

Our data indicate that myocardial stiffness in cancer survivors is significantly increased. We hypothesize that this increased stiffness may at least in part explain the significantly reduced cardiorespiratory fitness in this population. Echocardiographic shear wave elastography appears as a promising non-invasive tool for early detection of diastolic dysfunction in follow-up of childhood cancer survivors.Figure 1.Figure 2.
Significant stenosis without thrombus may be the third most common etiology of acute coronary syndrome
Authors: Mori H , Suzuki H , Shinke T
Published: October 2024

Background

Plaque rupture (PR), plaque erosion (PE) and calcified nodule (CN) are known as major etiologies of acute coronary syndrome (ACS). On the other hand, significant stenosis without thrombus (SSWT) can be sometimes observed in culprit plaque of ACS. However, incidence and clinical feature of SSWT in ACS patients are not well known in Japanese.

Method

This is a sub study of TACTICS registry which include ACS patients (n=702) undergoing primary percutaneous coronary intervention (PCI) under optical coherence tomography (OCT) in Japan. Using this registry data, we compared the clinical features and OCT findings of SSWT in ACS patients in comparison with PR, PE and CN. Major adverse cardiac event (MACE) was defined as death, non-fatal myocardial infarction, heart failure, or ischemia-driven revascularization at 1-year.

Results

Plaque rupture (PR: n=411, 61%) and plaque erosion (PE: n=178, 26%) were 2 major etiologies, which was followed by SSWT (n=59, 9%) and calcified nodule (CN: n=28, 4%). Clinical characteristics are shown in table 1. Patients with SSWT was slightly older than PR and PE but younger than CN. Proportion of male was fewer than PR and PE but greater than CN. In terms of traditional coronary risk factors, there were significant differences in prevalences of diabetes, active smoking, and hemodialysis among different etiologies. In SSWT, non-ST elevation myocardial infarction was the main type of ACS followed by unstable angina and ST elevation myocardial infarction (51%, 39% and 10%, respectively), which may be associated with the least CK level and greater TIMI flow. Lesion was less complex with lower proportion of type B2 or C, shorter procedure time, lower proportion of multivessel disease and lower syntax score. OCT findings are shown in table 2. Regarding lipid component and calcification, SSWT showed similar finding as PE. Cholesterol crystal was relatively less as compared to PR and PE. Kaplan-Meier survival curve showing MACE and ischemia driven-TLR are shown in figure 1 and 2. MACE and TLR was the least in SSWT.

Conclusion

SSWT was the third most common etiology of ACS with different feature from PR, PE and CN.
Platelet-large cell ratio predicts no-reflow in patients undergoing primary coronary angioplasty for ST-segment elevation myocardial infarction
Authors: Scridon A , Sus I , Lakatos E K , Demjen Z , Ceamburu A , Fisca C , Cozac D A , Mutu C C , Hadadi L
Published: October 2024

Background

Increased platelet indices have been shown to reflect higher degree of platelet activation and have been related to poorer short- and long-term outcomes in patients presenting with ST-segment elevation myocardial infarction (STEMI).

Purpose

We aimed to evaluate the ability of a validated marker of platelet activation (i.e., the platelet-large cell ratio [P-LCR]) to predict the occurrence of no-reflow in patients undergoing primary percutaneous coronary intervention (pPCI) for STEMI. The ability of P-LCR to predict other markers of thrombotic charge (i.e., use of glycoprotein IIb/IIIa inhibitors and/or thrombus aspiration) was also investigated.

Methods

Use of glycoprotein IIb/IIIa inhibitors and/or thrombus aspiration, occurrence of the ‘no-reflow’ phenomenon and P-LCR values on admission were recorded in 836 consecutive patients treated by pPCI for STEMI. Patients’ demographic data and symptom onset-to-cardiac catheterization laboratory time intervals were also recorded. Correlations between P-LCR values and the presence of thrombotic charge markers were evaluated.

Results

No-reflow occurred in 124 (14.8%) of the study patients; glycoprotein IIb/IIIa inhibitors and thrombus aspiration were used in 228 (27.3%) and in 289 (34.5%) of patients, respectively. Mean P-LCR values were 27.1 ± 7.6%. P-LCR values on admission were significantly higher in patients who presented no-reflow than in those who did not (29.1 ± 5.6% vs. 25.3 ± 5.8%, p = 0.03). Similarly, P-LCR were significantly higher in patients in whom glycoprotein IIb/IIIa inhibitors (29.5 ± 6.1% vs. 25.2 ± 5.3%, p = 0.04) and/or thrombus aspiration (28.4 ± 5.7% vs. 24.8 ± 5.4%, p = 0.03) were used. A P-LCR value ≥26.9% predicted the occurrence of no-reflow with 70.9% sensitivity and 55.4% specificity (p = 0.04).

Conclusions

In the present cohort, P-LCR values on admission predicted the presence of thrombotic charge markers in patients undergoing pPCI for STEMI. Evaluating P-LCR on admission could help identify patients at increased risk of no-reflow, in whom more intensive antiplatelet strategies may be of interest.
Comparison of GRACE and TIMI risk scores in the prediction of in hospital outcome among NSTEMI patients: a single centre study
Authors: Chowdhury M D , Tun-Nessa Malik F , Uddin K , Ahmed N , Badiuzzaman M , Nesaruddin M I R , Banik D , Dutta A , Shahriar Huq T , Habibur Rahman M D
Published: October 2024

Background

Major component of ACS, Non-ST segment elevation myocardial infarction (NSTEMI), has more than twice the incidence compared to ST-segment elevation myocardial infarction (STEMI). GRACE (Global Registry of Acute Coronary Events) and TIMI (Thrombolysis in Myocardial Infarction) risk scores are the two most popular prediction models in ACS due to TIMI’s advantage in its simplicity in clinical application and GRACE’s favorable discriminating power. Nevertheless, limited evidence compared the usefulness of these two major risk scores and their association with in-hospital events.

Purpose

To compare between the predictive ability of GRACE & TIMI risk scores for In hospital outcomes among the NSTEMI patients .

Methods

This prospective observational study was carried out from 8th march 2020 to 7th March 2022. Total 2152 acute NSTEMI patients were included. Both GRACE & TIMI risk score were calculated. For GRACE score, patients who scored ≤108 points were low risk,109-139 points were medium risk, ≥140 points were high risk . For TIMI scores patients with 0-2 scores were low risk , 3-4 scores were medium risk and 5-7 score were High risk. In Hospital outcomes were defined as the in hospital composite events which includes acute left ventricular failure, cardiogenic shock, arrhythmia & mortality.

Results

Among the 2152 patients majority were male (73.5%) with mean age of the study population were 58.33 ± .25 years. Mean Grace score & TIMI score of the study population were 137.81±16.38& 3.29±.97 respectively. Most of the patients were categorized in to Medium risk groups by both GRACE & TIMI risk scores , 70% & 51.3% respectively. However, high risk group percentage were higher in GRACE score group(41.3%) in comparison to TIMI score group(10.3%). GRACE score showed better predictive ability than TIMI score for in-hospital outcomes as evaluated by ROC curve( AUC of GRACE vs TIMI, In hospital ALVF:0.89vs 0.59, P<0.001; Cardiogenic Shock 0.72 vs 0.57, P=0.002; Mortality: 0.75 vs 0.59, P=0.002; arrhythmia 0.72 vs0.63, P=0.003).

Conclusion

GRACE showed better predictive accuracy than TIMI in NSTEMI patients for in-hospital outcomes. The sequential use of TIMI and GRACE scores provide an easy and promising discriminative tool in predicting outcomes in NSTEMI patients , thus improve the identification of high-risk patients.Pic :ROC curve for prediction of ALVFPic: ROC curve for Mortality prediction
Clinical characteristics and outcomes of patients presenting with acute coronary syndromes and suspected plaque erosion
Authors: Di Vito L , Di Giusto F , Bruscoli F , Scalone G , Alfieri M , Panzella F , Delfino D , Silenzi S , Jang I K , Grossi P
Published: October 2024

Background

Plaque erosion (PE) is the second most common pathology of acute coronary events after plaque rupture. PE is characterized by endothelial denudation and formation of neutrophil extracellular traps. Patients with PE may have a different prognosis as compared to those with plaque rupture. Specific clinical and laboratory predictors were validated to suspect PE among acute coronary syndrome (ACS) patients.

Purpose

The objectives of this study were to compare both clinical and laboratory findings, and outcomes of ACS patients with high probability of PE and those with less likely PE.

Methods

Six hundred ninety-six ACS patients were divided into two groups (suspected PE vs less likely PE) based on 5 reported predictors of PE. The predictors were: age <68, anterior ischemia, no diabetes mellitus, hemoglobin >15 g/dL and normal renal function (eGFR> 60 ml/min) as assessed at hospital admission.

Patients with 4 or 5 of these 5 predictors were included in the suspected PE group, while patients with 0 or 1 entered less likely PE group. Baseline clinical features and laboratory analyses at hospital admission were compared between the two groups.

Major adverse cardiac events (MACE), defined as death from any cause, non-fatal myocardial infarction or unplanned revascularization, were compared between the two groups at 20 months after hospital discharge.

Results

Among 696 patients, 283 (41%) composed the suspected PE group, while 413 (59%) entered into less likely PE group.

The suspected PE group had a higher prevalence of current smokers and had a higher BMI. They showed higher values of both LDL cholesterol and triglycerides, while C-reactive protein and fibrinogen levels were significantly lower. The suspected PE group showed a higher frequency of single vessel disease (Table).

The suspected PE group showed a significantly lower rate of MACEs at 20 months (7.4% vs 28.8%, p=0.0001) as well as death from any cause was significantly lower (2.1% vs 24.9%, p=0.0001). The median time from the index ACS episode to recurrent myocardial infarction or unplanned coronary revascularization tended to be longer in the suspected PE group as compared to the less likely PE group (15 months [9-20] vs 9 months [6-13], p=0.062) (Figure).

Conclusions

In a cohort of ACS population, the suspected PE group showed distinctive clinical characteristics with less coronary plaque burden and low grade of systemic inflammation. The suspected PE group had a better prognosis at 20-month follow-up time with a significantly lower rate of death from any cause, and non-fatal coronary events tended to occur later.Table.Baseline characteristicsFigure.Non fatal coronary events
NRF3-mediated mitochondrial superoxide promotes cardiomyocyte apoptosis and impairs cardiac functions by suppressing Pitx2
Authors: Zheng A , Chen Q , Shi Z , Xu X , Yang M , Sun S , Wang L , Wang Y , Xiao Q , Zhang L
Published: October 2024

Background

Myocardial infarction (MI) elicits mitochondria reactive oxygen species (ROS) production and cardiomyocyte apoptosis. Nrf3 (Nuclear factor erythroid 2-related factor 3) has an established role in regulating redox signaling and tissue homeostasis. Herein, we aimed to uncover the exact role and potential mechanism of Nrf3 in injury-induced cardiac remodeling.

Methods

Global (Nrf3-KO) and cardiomyocyte-specific (NRF3△CM) Nrf3 knockout mice were subjected to MI or ischemia/reperfusion (I/R) injury, followed by functional and histopathological analysis. Primary neonatal mice (NMVMs) and rat (NRVMs) ventricular myocytes as well as cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) were used to detect the possible impact of Nrf3 on cardiomyocyte apoptosis and mitochondrial ROS production. Chromatin immunoprecipitation sequencing and immunoprecipitation–mass spectrometry analysis were used to uncover potential targets of Nrf3. MitoPQ administration and cardiomyocyte-specific AAV vector were used to further confirm the in vivo relevance of the identified signal pathways.

Results

Increased level of Nrf3 was observed in cardiomyocytes within border zone of infarcted human heart and murine cardiac tissues post-MI. Both global and cardiomyocyte-specific Nrf3 knockout significantly decreased injury-induced mitochondrial ROS production and cardiomyocyte apoptosis, consequently improving cardiac functions. Additionally, cardiac-specific Nrf3 overexpression reversed the cardiac phenotypes observed in Nrf3-KO mice. Functional studies showed that Nrf3 promoted NMVM, NRVM and hiPSC-CM apoptosis by increasing mitochondrial ROS production. Critically, restoring mitochondrial ROS using MitoParaquat blunted the beneficial effects of Nrf3 deletion on cardiac functions and remodeling. Mechanistically, the cardiac redox regulator paired-like homeodomain transcription factor 2 (Pitx2) was identified as one of the main target genes of Nrf3. Specifically, Nrf3 binds to Pitx2 gene promoter where it increases Pitx2 gene promoter DNA methylation through recruiting heterogeneous nuclear ribonucleoprotein K and DNA-methyltransferase 1 complex, thereby inhibiting Pitx2 expression. Importantly, cardiomyocyte-specific knockdown of Pitx2 blunted the beneficial effects of Nrf3 deletion on cardiac functions and remodeling.

Conclusions

Nrf3 promotes injury-induced cardiomyocyte apoptosis and deteriorates cardiac functions by increasing mitochondrial ROS production via suppressing Pitx2 expression. Targeting Nrf3-Pitx2-mitochondrial ROS signal axis could represent novel therapeutics for treating MI patients.Graphic Abstract
Shear wave speed, dispersion slope and anisotropy evaluation using cardiac shear wave elastography in patients with Fabry disease
Authors: Cafezeiro C , Alencar A C , Pereira F L , Mathias Jr W , Dabarian A L , Chammas M C , Fernandes F
Published: October 2024

Background

Cardiac shear wave imaging has been proposed to investigate left ventricular myocardial alterations non-invasively. Dispersion slope and anisotropy are fundamental properties that have not been studied in Fabry disease (FD) patients yet.

Purpose

The aim of this study was to determine and compare shear wave propagation speed, dispersion slope and fractional anisotropy in FD patients and healthy controls.

Methods

We prospectively included 20 FD patients and 20 healthy controls (HC). Shear wave speed, dispersion slope and fractional anisotropy were measured non-invasively in anteroseptal basal segment using an ultrasound for cardiac shear wave imaging. Echocardiography, electrocardiogram and laboratory evaluations were performed.

Results

Shear wave propagation speed was higher in FD patients than in HC group (1.46 ± 0.12 m/s and 1.36 ± 0.17 m/s, p = 0.03). No difference was found in dispersion slope (11.4 m/s/kHz in FD group and 11.3 m/s/kHz in HC group, p = 0.6). Fractional anisotropy was 0.05 ± 0.04 in FD group and 0.05 ± 0.04 in HC group, p = 0.4.

Conclusion

Shear wave speed was higher in FD patients compared to control group. Dispersion slope and fractional anisotropy in FD group did not reveal significant difference to the control group.
Nomogram-based prediction of MACE in older adults with STEMI
Authors: Soleimani H R , Masoudkabir F , Mehrani M , Ashraf H , Hernandez-Diaz A , Nanna M G , Hakim D , Nelson J , Hosseini K
Published: October 2024

Introduction

Despite the significant progress made in diagnosing and treating patients with ST elevation myocardial infarction (STEMI), high-risk subgroups such as older adults (those over 65 years-old) still face considerable residual risk of major adverse cardiovascular events (MACE) following treatment for their index event. Thus, it is crucial to create accurate, validated, and actionable tools to stratify patients according to their risk of MACE after admission for STEMI.

Purpose

Utilizing clinical data obtained from a registry of patients diagnosed with STEMI, this study aims to develop a nomogram that can reliably predict the likelihood of MACE incidence.

Methods

Using a large electronic single-center registry, all consecutive patients with STEMI, undergoing primary percutaneous coronary intervention (PCI), and aged 65 and above were identified. Demographic, laboratory, clinical and intra-procedural variables were examined. Univariate and multivariate logistic regression analyses were utilized to identify those factors which were independently associated with MACE incidence in the post PCI follow-up period. A nomogram was developed in a training set, and performance metrics such as receiver operating curves (ROC), calibration plots, and decision curve analysis were used for validation in a testing set. Analyses were performed using tidyverse and rms packages in R programming language.

Results

1946 patients were included in the study and split into 70% training and 30% testing sets. Both groups were similar in terms of baseline demographic and clinical characteristics. Mean follow-up period was 17 months. Total MACE incidence in the post PCI follow-up period was 18%. Thirty-eight factors with limited missing information (<5%) were examined for their relationship with MACE incidence and after performing univariate and multivariate analysis 8 were selected for construction of the nomogram: left-ventricular ejection fraction (LVEF), serum creatinine, hemoglobin and fasting blood glucose levels, presence of valvular heart disease, post PCI TIMI flow grade, diameter of the stent placed in the culprit lesion, and presence of shock in the post PCI setting. The area under the curve (AUC) for MACE prediction in post PCI follow-up period showed acceptable discrimination

(c-statistic=73%, 95%CI 71.2% to 76.3%). Calibration plots demonstrated that the nomogram model was well-calibrated, and its predictions were closely aligned with observed outcomes. Additionally, decision curve analysis indicated that the model exhibited strong discriminatory ability in predicting MACE.

Conclusions

A nomogram developed using a combination of laboratory, clinical, and procedural parameters reliably predicts future risk for MACE in older adults following STEMI. Future implementation of this model may identify the highest risk individuals to target more aggressive preventive efforts in a vulnerable cohort of patients.Plot 1Plot 2
Impact of the complexity of percutaneous coronary intervention on clinical outcomes in patients with atrial fibrillation: a real-world study
Authors: Wang Y , Zhang H , Yang Y M
Published: October 2024

Background

Atrial fibrillation (AF) always coexisted with percutaneous coronary intervention (PCI), and complex PCI has increased in recent years. However, limited data exist on clinical outcomes in patients with AF and underwent complex PCI.

Purposes

We aimed to explore the prognosis of patients with AF who had underwent PCI.

Methods

This was a prospective, observational study which enrolled 1132 participants consecutively. Complex PCI was defined as PCI performed to ≥ 3 separate major coronary vessels; ≥3 stents implanted; ≥3 lesions treated; or total stented > length 60 mm. The primary endpoint was defined as major adverse cardiovascular event (MACE) including all-cause death, spontaneous myocardial infarction (MI), stroke, systemic embolism or ischemia-driven revascularization. Major bleeding events were defined according to Thrombolysis in Myocardial Infarction (TIMI) criteria.

Results

A total of 1132 patients who underwent PCI with AF were enrolled. The mean age was 66.6 ±8.9, and 75.1% were male. 320 participants (28.2%) were undergoing complex PCI. During a median follow-up of 1045 days, the primary outcome occurred in 52 of 320 patients (16.2%) in the complex PCI group and 105 of 812 patients (12.9%) in the non-complex PCI group (adjusted hazard ratio: 1.31; 95% confidence interval: 1.08-1.58; P = 0.007), driven by higher rate of MI ( aHR=2.17, 95%CI, 1.00-4.70 and ischemic driven revascularization (aHR=1.86, 95%CI, 1.01-3.45). TIMI major bleeding events were more commonly observed in complex PCI group (aHR=1.15, 95%CI, 1.01-1.31).

Conclusion

The complexity of PCI was an independent risk factor of adverse clinical outcomes, especially in MI, revascularization and TIMI major bleeding events in patients with AF.K-M curves of eventsK-M curves of events
Markers of coagulation and early coronary stent thrombosis
Authors: Galli L , Sator A , Schauer S , Braeu K , Bernhard J , Hengstenberg C , Gangl C , Lang I , Roth C , Berger R , Krychtiuk K , Speidl W
Published: October 2024

Background

Acute stent thrombosis is a rare but deleterious event after percutaneous coronary intervention (PCI). Hemostatic factors such as D-Dimer, fibrinogen, and platelet count have emerged as potential indicators of increased thrombotic risk. However, data regarding the association with early stent thrombosis (ST) is sparse.

Purpose

The aim of this study was to investigate whether markers of coagulation are associated with increased risk of early (< 30 days after PCI) ST.

Methods

Within a prospective single-center registry, we retrospectively analyzed the association between pre-procedural platelet count, plasma levels of fibrinogen and D-Dimer with the occurrence of early ST within 30 days after PCI.

Results

We included 10,714 consecutive patients who underwent percutaneous coronary intervention (PCI) with implantation of drug-eluting stents (DES). Pre-procedural measurements of platelet count, fibrinogen and D-Dimer was available in 6,337, 6,155 and 956 patients, respectively. The number of definite early ST within 30 days was 58 (0.92 %). Pre-procedural platelet count (p<0.05) and plasma levels of fibrinogen (p<0.05) were significantly higher in patients with early ST as compared to patients without ST. Whereas D-Dimer was not associated with early ST, patients in the fifth quintile of platelet count had a significant increased risk for early ST (HR 2.43; 95% CI 1.43 - 4.14; p=0.001) as compared to patients in the lower four quintiles and patients in the fifth quintile of fibrinogen had a significant increased risk for early ST (HR 1.86; 95% CI 1.07 – 3.26; p<0.05) as compared to patients in the lower four quintiles. These associations were independent of clinical risk factors, the presence of acute coronary syndromes and the number of stents.

Conclusions

Pre-procedural platelet count and plasma levels of fibrinogen are associated with the risk of early ST in patients after implantation of DES. Device-level risk factors like stent-type or size and procedure-level risk factors like peri-interventional medication and complications during stent apposition are associated with ST. Platelet count and plasma levels of fibrinogen may be additional patient-level risk factors that have to be taken in account in the development of future personalized strategies to prevent these rare but deleterious complications.
Association between clinical ischemic risk and thrombogenicity phenotype and their prognostic prediction in patients undergoing percutaneous coronary intervention
Authors: Ohn D , Kwon O S , Hwang J Y , Jung Y H
Published: October 2024

Introduction

The CHADS-P2A2RC score has been developed to provide better prognostic precision and improved selection of at-risk patients with coronary artery disease (CAD). The linkage of this clinical ischemic risk with thrombogenicity and their prognostic implication remain still unknown.

Purpose

We investigated the values of thrombogenicity indices according to the CHADS-P2A2RC score and their combined prognostic prediction in CAD patients undergoing percutaneous coronary intervention (PCI).

Methods

In PCI-treated patients (PCI) (n=2,705), clinical ischemic risk was classified with CHADS-P2A2RC score ("high risk": ≥ 4) and thrombogenicity indices were assessed using thromboelastography (TEG). Major adverse cardiovascular events (MACEs: a composite of all-cause death, myocardial infarction, or stroke) and major bleeding were evaluated were monitored for up to 3 years.

Results

Compared with "low/moderate-risk group" (67.7%), "high-risk group" (32.3%) had higher platelet-fibrin clot strength (PFCS: 67.3±7.9 vs. 65.2±7.2 mm; P < 0.001) and lower fibrinolytic activity (clot lysis at 30 min [LY30]: 0.9±2.1% vs. 1.1±2.4%, P < 0.001]. The "high-risk group" showed higher rates of "high PFCS phenotype (≥ 68 mm)" (35.3% vs. 49.7%; P <0.001), MACE (HRadjusted: 1.47; 95% CI: 1.01-2.13; P = 0.045) and all-cause mortality (HRadjusted: 1.87; 95% CI: 1.14-3.07; P = 0.013) than the "low/moderate-risk group", respectively. Among the "low/moderate-risk group", "high MA phenotype" independently predicted MACE (HRadjusted: 1.51; 95% CI: 1.00-2.27; P = 0.048) and all-cause mortality (HRadjusted: 1.90; 95% CI: 1.06-3.4; P = 0.031). Likewise, this phenotype increased the risks of MACE (HRadjusted: 1.47; 95% CI: 1.01-2.13; p = 0.045) and all-cause mortality (HRadjusted: 1.87; 95% CI: 1.14-3.07; p = 0.013) in the "high-risk group" (Table 1 and Figure 1). Prognostic impact of "high MA phenotype" on major bleeding was not significantly different across the risk-group (HRadjusted: 1.02; 95% CI: 0.39-2.72; P = 0.963 in the "low/moderate-risk group" and HRadjusted: 1.08; 95% CI: 0.50-2.34; P = 0.884 in the "high-risk group", respectively).

Conclusion

In PCI-treated patients, CHADS-P2A2RC score was significantly associated with a worse clinical outcome and more thrombogenic profile. Regardless of the ischemic-risk group, the level of clot-strength had an addictive effect on predicting the risk of ischemic event, indicating assessment of thrombogenicity indices using TEG may enhance post-PCI risk stratification for personalized antithrombotic therapy.
Altered clot formation and fibrinolysis in heart transplant recipients
Authors: Bjerre K , Clemmensen T S , Poulsen S H , Hvas A M , Grove E L , Kristensen S D , Eiskjaer H
Published: October 2024

Background

Long-term survival after heart transplantation (HTx) is limited by cardiac allograft vasculopathy (CAV), a frequent accelerated form of coronary artery disease. The pathogenesis remains incompletely understood, but thrombosis may be involved. We aimed to investigate clot formation and fibrinolysis in HTx patients and relate the findings to prognosis.

Methods

This prospective cohort study included 69 patients (median 8.4 years after HTx) with angiographically documented CAV 0 (not significant, n=36), CAV 1 (mild, n=19), and CAV 2-3 (moderate to severe, n=14). Healthy individuals (n=69) served as age- and gender-matched controls. Using a plasma-based fibrin clot formation and lysis assay, we assessed the following clot properties off-aspirin: 1) clot formation reflected by peak absorbance, 2) fibrinolysis measured by clot lysis time, and 3) a combined measure of clot formation and lysis reflected by area under the curve (AUC). Major adverse cardiac events (MACE) included heart failure hospitalization, cardiovascular death, and significant CAV progression.

Results

Median follow-up time was 5.1 (2.1-5.9) years. Five CAV 2-3 patients were excluded as it was not considered safe to interrupt aspirin therapy. Five patients had missing values due to either lysis resistance or severely decreased fibrin formation, and four of these underwent MACE with CAV progression and/or heart failure during follow up. Peak absorbance was significantly higher in HTx patients compared with healthy controls (0.72 vs. 0.50 aggregation units (AU), p<0.0001). Further, a stepwise increment above reference range through CAV groups was seen; CAV 2-3 patients (0.85 ± 0.12 AU) versus CAV 1 patients (0.72 ± 0.17 AU, p<0.05) and CAV 0 patients (0.68 ± 0.27 AU, p=0.06). Clot lysis time was significantly longer in HTx patients compared with healthy controls (1275 vs. 733 seconds, p<0.0001). AUC was significantly increased compared with healthy controls (1399 vs. 547 AU x seconds, p<0.0001). Overall, clot formation and fibrinolysis was not related to MACE.

Conclusion

HTx-patients have increased clot formation and prolonged fibrinolysis compared with healthy controls. Further, HTx-patients have an increased combined measure of these parameters compared with healthy controls, suggesting imbalance between fibrin clot formation and fibrinolysis. None of the measured parameters were related to prognosis.Clot formation and fibrinolysis
Triple-hormone receptor agonist retatrutide significantly improves lipoprotein and apolipoprotein profiles in participants with obesity or overweight
Authors: Nicholls S , Pirro V , Lin Y , Wilson J , Duffin K , Zhen E , Harris C , Thomas M , Hartman M , Coskun T , Milicevic Z , Haupt A , Ruotolo G
Published: October 2024

Background

In a phase 2 study in participants who have obesity or overweight but not type 2 diabetes (T2D) (n=338), retatrutide (RETA), an agonist of GIP, GLP-1 and glucagon receptors, reduced body weight, glycated hemoglobin, triglycerides (TG), LDL-C and VLDL-C.

Purpose

To better understand the effects of RETA on the serum lipid profile we analyzed changes in apolipoprotein levels and distribution and size of lipoprotein particles.

Methods

Adult participants with obesity (BMI ≥30 kg/m2), or overweight (BMI ≥ 27 kg/m2 and < 30 kg/m2) with a weight-related comorbidity, and without T2D were randomized to receive RETA 1, 4, 8, 12 mg or placebo for 48 weeks. Lipids panel (including calculated non-HDL-C), apolipoproteins (apo) and NMR lipoprotein profiles were measured at baseline, 24 and 48 weeks in fasting plasma samples. Data were analyzed using a mixed model for repeated measures after log transformation.

Results

RETA dose-dependently reduced non-HDL-C up to 22.2% and 26.9% and apoB up to 19.6% and 24.2% at 24 and 48 weeks, respectively (Figure). At 48 weeks, RETA reduced TG and apoC-III levels up to 40.6% and 38.0%, respectively. RETA greatly reduced the total number of TG-rich lipoprotein particles (TRLP) and all subfractions of TRLP (large, medium and small) at 48 weeks (Table). Since the reduction in large and medium TRLP was greater than the reduction in small TRLP, the average size of TRLP was smaller following treatment with RETA. RETA reduced the number of total and highly atherogenic small LDL particles (LDLP), while total and small HDL particles (HDLP) were only slightly reduced. The average size of HDLP increased following treatment with RETA. At 48 weeks, the NMR-derived lipoprotein insulin resistance score was dose-dependently decreased by 27.4%, 31.7% and 32.5% with 4 mg, 8 mg and 12 mg, respectively, following RETA treatment.

Conclusions

RETA treatment for 48 weeks dose-dependently reduced levels of non-HDL-C and apoB and the number of total and small LDL particles, suggesting an improvement in atherogenic lipoprotein profile and cardiovascular risk in subjects who have obesity or overweight but not T2D.