Left Anterior Descending Research Articles

Understanding the impact of heart failure treatment on cancer growth

Abstract Background Heart failure (HF) is associated with systemic alterations that extend beyond the cardiovascular system. The dysregulation of physiological pathways induced by HF, encompassing inflammatory or neurohormonal pathways, may foster an environment conducive to cancer growth and the spead of metastases. It is unknown whether these alterations are attenuated when HF is treated, and whether certain therapies for HF may yield more significant effects than others. Purpose This study aims to investigate whether myocardial infarction (MI)-induced left ventricular (LV) dysfunction promotes breast cancer growth and triggers the development of lung metastases. Additionally, it compares the potential impact of different therapeutic strategies for LV dysfunction on cancer development. Methods Myocardial infarction (MI) was induced in 11-week-old female BALB/c mice by ligation of the left anterior descending (LAD) coronary artery, leading to LV dysfunction and significant dilation within four weeks. Starting 2 weeks after surgery, mice with ejection fraction (EF) < 40% received daily oral gavage of vehicle or one of three drugs: carvedilol (10 mg/kg), enalapril (20 mg/kg), or empagliflozin (15 mg/kg). Four weeks post-surgery, 2x105 4T1 metastatic breast cancer cells were injected into the 4th mammary fat pad. Tumor volume was measured every two days, starting eight days after injection. Weekly echocardiographic assessments monitored cardiac function until the end of the experiment. Tumors were excised on day 22 after injection. Mice were euthanised on day 28 for post-mortem analysis. MCM2 proliferation staining was performed on lung tissue to quantify metastases. Results Among the HF treatments, only empagliflozin (n=11) induced a significant decrease in both left ventricular end-diastolic and end-systolic volume (Fig. 1.A; p=0.0043; Fig. 1.B; p=0.0186) compared to the vehicle group (n=11). Tumor weight and volume (Fig. 1.C-D) were not different in the HF/vehicle group (n=15) and the sham-operated group (n=13). Carvedilol (n=14) led to a small reduction in tumor weight (Fig. 1.C; p=0.1264), while empagliflozin (n=11) exhibited a significant reduction in both tumor weight (Fig. 1.C; p=0.0306) and volume (Fig. 1.D; p=0.0268). In addition, carvedilol (n=13) significantly reduced lung metastases (Fig. 1.E; p=0.0347) compared to the HF/vehicle group (n=13). Enalapril (n=10) and empagliflozin (n=9) did not significantly impact the development of lung metastases. Conclusion Despite the absence of increased cancer growth post-MI, our findings indicate that specific treatments for HF—namely, carvedilol and empagliflozin—attenuate cancer growth post-MI. Furthermore, carvedilol demonstrated potential in reducing metastatic spread. Additional research is required to uncover the underlying mechanisms both in the presence and absence of HF, and to explore the molecular impact that HF treatments have on various stages of cancer progression.Figure 1

Fibroblast-specific deletion of ERBB4 impairs cardiac regeneration in neonatal mice

Abstract Background Scarless regeneration of the neonatal mammalian heart is a remarkable but poorly understood process. Previous studies have shown that paracrine actions of neuregulin-1 (NRG1) are indispensable to stimulate cardiomyocyte proliferation in the injured neonatal heart, and are mediated by activation of the ERBB4 receptor. It remains unclear, however, whether NRG1 also contributes to other steps of neonatal cardiac regeneration, e.g. to the control of collagen synthesis by fibroblasts, hence contributing to scarless healing. Purpose To study temporal evolution of the infarct size during 21 days after myocardial infarction (MI) in neonatal fibroblast-specific Erbb4 knock-out (KO) and wild type (WT) mice. We hypothesized that scarless healing would be completed within 21 days in WT mice, and incomplete in KO mice. Methods Fibroblast-specific hemizygous Erbb4 KO (FB-Erbb4-KO) mice were generated (Erbb4F/+ Col1a2-Cre+, C57BL/6 background), because fibroblast-specific nullizygous Erbb4 KO were not viable. Validation of the KO was performed both on RNA (qPCR) and protein (western blot) level. MI was induced in one-day old FB-Erbb4-KO and WT littermates of both sexes by permanent ligation of the left anterior descending (LAD) coronary artery under hypothermic anaesthesia. Pups from both groups were euthanized at 4 (WT, n=9; KO, n=11), 7 (WT, n=12; KO, n=4), 10 (WT, n=11; KO, n=7) and 21 (WT, n=16; KO, n=8) days post-MI. Following dissection, hearts were formalin-fixed and paraffin embedded for histopathological evaluation. Transverse sections were cut at 4 distinct locations from the ligation site to the apex and stained with Masson’s Trichrome for infarct scar measurement. Genotyping was performed post-mortem and unblinded after data analysis. Results Both the transgenic mice model and the LAD ligation technique were successfully validated. No significant differences in the initial infarct scar size were observed between WT and FB-Erbb4-KO mice 4 days post-MI (p=0.6556). 7-days post-MI the infarct scar size was 6-fold smaller compared to 4 days post-MI in both FB-Erbb4-KO and WT mice, with a trend towards a larger infarct scar size in the FB-Erbb4-KO group compared to WT (p=0.0989). At day 10 post-MI, infarct scar size in the FB-Erbb4-KO group was significantly larger (p=0.0499) compared to WT. At 21 days post-MI, the infarct size had almost completely disappeared in the WT group, but remained clearly present in the FB-Erbb4-KO group (Fig. 1, p=0.0099). Infarct scar sizes at all timepoints are graphically shown in Fig. 2. Conclusion Fibroblast-specific deletion of the ERBB4 receptor causes incomplete resolution of the infarct scar in murine neonates 21 days after MI. While the initial infarct scar size 4 days after injury is the same, impaired scar resolution becomes progressively more evident towards day 21 post-MI. These findings indicate that scarless healing of the neonatal mammalian heart requires NRG1/ERBB4 signalling in fibroblasts.Fig. 1Fig. 2

Fractalkine Inhibition in Acute Myocardial Infarction leads to reduced intramyocardial haemorrhage

Abstract Background The fractalkine receptor CX3CR1 has been linked to the development of microvascular obstruction (MVO) in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). Pre-clinical studies have demonstrated a reduction in infarct size, inflammation and intramyocardial haemorrhage (IMH) with inhibition of CX3CR1. Purpose The FRACTAL study is a phase IIa, pilot, randomized, 2-arm parallel group, placebo-controlled, double blinded, multi-centre trial. In addition to assessing the safety and tolerability of the fractalkine inhibitor KAND567 in STEMI patients, a subgroup exploratory analysis was performed. We investigated into the translation of MRI and blood samples characteristics between the two groups. Methods Patients with an anterior STEMI who had an occluded proximal to mid left anterior descending (LAD) artery were recruited. These patients had to present within 5 hours of the onset of their chest pain. They were subsequently randomised on a 1:1 basis to receive either KAND567 or placebo. Patients then underwent an MRI at day 3, and subsequently a comparator at 3 months. Additionally, throughout the period of their follow-up, patients would regularly undergo blood sampling to assess multiple parameters. Results Of the 71 patients recruited into the study, 29 patients in the KAND567 arm and 28 patients in the placebo arm received both MRIs. The KAND567 arm had shown a similar troponin rise at day 1 compared to placebo (4357 vs 4286). Baseline MRI demonstrated an identical infarct size between both arms. The presence and absence of IMH was then analysed defining IMH+ as presence of IMH and IMH- as IMH absence. The presence of IMH in patients showed a larger infarct size. The infarct size of IMH+ were the same between KAND567 and placebo, which was a similar finding in the IMH- arm too. However, when compared to day 90 MRI demonstrated a numerically smaller infarct size in the KAND567 group with a smaller percentage of IMH. This was consistent with a lower rate of IMH in the KAND567 arm too, when compared between the groups (35.5% vs 55.2%; p=0.15) (see table below). This seemed to be related to the smaller distribution IMH+, as the IMH+ infarcts were much larger in both arms, whilst overall infarct size in IMH subgroup were identical. Conclusion KAND567 appears to prevent the transition from IMH- to IMH+, while it doesn’t change infarct size in the respective subgroups of IMH+ or IMH-.MRI Comparator Table

Effect of antiretroviral treatment on myocardial work and arterial function of treatment-naive patients with HIV

Abstract Background/Aim HIV infection is related with cardiovascular adverse events. We investigated the effects of antiretroviral treatment in myocardial and vascular function of newly diagnosed patients with HIV. Patients and methods A total of 70 newly diagnosed HIV patients (41.2±8.7 years old, 87 % male) were enrolled. Patients were randomized to the newer integrase inhibitor Dolutegravir or to the older protease inhibitor Darunavir/Cobicistat. We measured at baseline and 12 months posttreatment: (a) Left Ventricular (LV) Global Longitudinal Strain (GLS), (b) LV Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW), Global Work Efficiency (GWE), (c) Coronary Flow Reserve (CFR) of Left Anterior Descending Artery. At baseline, we compared the HIV patients with 35 healthy matched controls. Results At baseline patients with HIV had impaired myocardial function, endothelial function and endothelial glycocalyx compared with healthy controls. Twelve months after intervention HIV patients improved myocardial function, as assessed by GLS, GWI, GCW, GWW and GWE (p<0.05). Moreover, twelve months after intervention HIV patients improved endothelial function, as evaluated by an increase in CFR and a decrease in PBR5-25 (p<0.05). Response to therapy was similar between the two groups of treatment. Nevertheless, in HIV patients 12 months post treatment myocardial, endothelial function and endothelial glycocaylyx was impaired in comparison with healthy controls. Conclusions Treatment with antiretroviral therapy partially improves myocardial and arterial function 12 months post treatment.

Evaluating the role of pericoronary adipose tissue on coronary artery disease: insights from CCTA on risk assessment, vascular stenosis, and plaque characteristics.

Pericoronary adipose tissue (PCAT) plays a significant role in the occurrence and progression of coronary artery disease (CAD). This study investigates the relationship between PCAT and CAD, focusing on the occurrence of the disease, the severity of vascular narrowing, and the characteristics of arterial plaques. We analyzed a cohort of 152 individuals with CAD and 55 individuals with non-coronary artery disease (N-CAD). Participants underwent both coronary computed tomography angiography (CCTA) and digital subtraction angiography (DSA). Utilizing United Imaging software for artificial intelligence delineation, we measured the fat attenuation index (FAI) and volume of PCAT in the left anterior descending (LAD), left circumflex (LCX), and right coronary arteries (RCA). Our findings demonstrate that while CCTA is effective in diagnosing CAD compared to DSA, its diagnostic power for individual coronary arteries remains limited. Further analysis revealed that the FAI of the RCA and the overall PCAT volume independently influenced CAD (OR: 1.057, 95% CI: 1.002 to 1.116; OR: 0.967, 95% CI: 0.936 to 0.999). FAI showed a significant independent effect on RCA stenosis (OR: 1.041, 95% CI: 1.003 to 1.081), while the fat volume of the LAD had a significant independent effect on LAD stenosis (OR: 0.884, 95% CI: 0.809 to 0.965). A higher FAI and a lower fat volume were significantly correlated with more severe vascular stenosis percentages in all three arteries (p < 0.05), except for the fat volume and stenosis of the LCX. Moreover, we found the significant differences in the fat volume of the LCX between different plaque types (H = 8.869, p = 0.012), with calcified plaques consistently exhibiting the lowest fat volume across all three arteries. Finally, the likelihood ratio test confirmed that incorporating the PCAT fat volume parameter of LAD significantly improved the diagnostic ability of CCTA for both CAD (p = 0.01543) and LAD stenosis (p = 0.001585). The quantification of PCAT has potential application value in the comprehensive assessment of CAD. It is recommended that cardiology and radiology departments consider incorporating PCAT into the assessment criteria for patients suspected of having CAD.

Tilianin suppresses NLRP3 inflammasome activation in myocardial ischemia/reperfusion injury via inhibition of TLR4/NF-κB and NEK7/NLRP3.

Tilianin, a flavonoid compound derived from Dracocephalum moldavica L., is recognized for its diverse biological functionalities, in particular alleviating myocardial ischemia-reperfusion injury (MIRI). There is ample evidence suggesting that the NLRP3 inflammasome has a significant impact on the development of MIRI. In this study, rats undergoing the ligation and subsequent release of the left anterior descending (LAD) coronary artery and H9c2 cardiomyocytes subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were used to investigate the effects of tilianin on NLRP3 inflammasome and its anti-MIRI mechanisms. Upon reperfusion, the rats were intraperitoneally injected with tilianin at doses of 3, 10, 30mg/kg. H9c2 cells were treated with tilianin at concentrations of 10, 30, and 50μg/mL. Echocardiography, TTC staining and TUNEL staining demonstrated that tilianin remarkably improved cardiac function and mitigated myocardial damage in MIRI rats. Additionally, notable inflammatory response reduction by tilianin was evidenced by subsequent hematatoxylin-eosin (HE) staining, inflammatory cytokines assay, and quantitative proteomics. Further western blotting analysis and immunofluorescence staining showed tilianin decreased the levels of TLR4, p-NF-κB, NLRP3, and ASC in MIRI rats and H9c2 cells exposed to OGD/R, alongside a significant reduction in cleaved gasdermin D, mature IL-1β and IL-18. Molecular docking, cellular thermal shift assay (CETSA) and co-immunoprecipitation (co-IP) assay revealed that tilianin impeded the interaction between NLRP3 and NEK7. Taken together, tilianin protects cardiomyocytes from MIRI by suppressing NLRP3 inflammasome through the inhibition of the TLR4/NF-κB signaling pathway and the disruption of the NEK7/NLRP3 interface. These findings underscore the potential of tilianin as a promising therapeutic candidate for MIRI.

Successful Management of Inferior Wall STEMI in a Patient with Obstructive Three-Vessel Disease, Diabetes Mellitus, and Hypertension: A Case Report

We report the case of a 67-year-old female with a complex medical history, including poorly controlled Type 2 diabetes mellitus, hypertension and recent inferior wall ST-segment elevation myocardial infarction (STEMI). She presented with generalized body aches, arm numbness and vomiting. Coronary angiography revealed severe three-vessel coronary artery disease including a 100% thrombotic occlusion of the right coronary artery (RCA). The patient underwent successful percutaneous coronary intervention (PCI) to both the distal and most-proximal RCA, followed by recommendations for further intervention on the left circumflex (LCx) and left anterior descending (LAD) arteries. This case highlights the challenges and successful management strategies in patients with multivessel coronary artery disease, comorbid diabetes and hypertension.

Clinical and Angiographic Characteristics of Coronary Heart Disease Patients at RS Jantung Jakarta

Coronary Heart Disease (CHD) is a cardiovascular disease that impairs perfusion to the myocardium. Coronary Computed Tomography Angiography (CCTA) and Invasive Coronary Angiography (ICA) or commonly known as coronary catheterization are two possible modalities to visualize the coronary vessels in CHD patients. However, both of the modalities have their own advantages and disadvantages. This study aims to describe details of the stenosis severity frequencies in both modalities with the characteristics of these CHD patients at RS Jantung Jakarta. This study uses an observational descriptive method to assess the frequency distribution of stenosis severity in CHD patients that have completed CCTA and ICA examination at RS Jantung Jakarta with 369 patients, 1.476 coronary vessels, and 807 stenotic lesions in total. Sampling method of this study is consecutive sampling. Majority of CHD patients in this study were ≥60 years old and have obesity. Majority of the patients on this study reach the blood pressure target. Most of the patients have only one vessel with significant stenosis. Most vessel affected was LAD (Left Anterior Descending Artery). There’s 71.4% of the coronary vessels detected as severe stenosis on CCTA examination but only 50.4% of the coronary vessels detected as severe stenosis on ICA examination. It can’t be denied that although CT coronary angiography has high potential, it still can’t replace coronary catheterization (invasive coronary angiography) as the gold standard in determining the degree of coronary artery stenosis in CHD patients due to its limitation.

Ostial left main disease tackled with a percutaneous coronary intervention using a second-generation drug-eluting stent: A case report

Abstract: The hospital emergency admitted a middle-aged male who had previously undergone stenting in the left anterior descending (LAD) and right coronary arteries due to severe central chest pain radiating to both arms. A two-dimensional color Doppler echocardiogram showed septal hypokinesia, and coronary angiography showed a 70% ostial left main (LM) stenosis. The LAD coronary artery had a patent stent, but the mid-right coronary artery had a totally occluded stent. The chest pain increased during coronary angiography, and the patient consented to percutaneous coronary intervention (PCI) with a second-generation drug-eluting stent. The patient was discharged in a stable condition. The evolution and the current approach of PCI compared to coronary artery bypass grafting surgery for LM coronary disease based on randomized trials are discussed.

Utility of the AngelMed Guardian System in myocardial bridging: a case report

BackgroundMyocardial bridging (MB) is a known congenital anomaly in which a segment of the coronary artery transverses from the epicardium through the myocardium. MB may clinically manifest as recurrent angina, acute coronary syndrome, ventricular dysrhythmia, and even sudden cardiac death. On electrocardiogram (EKG), MB can present with findings consistent with significant ST-segment changes. The AngelMed Guardian System (the Guardian device) was developed in an effort to optimize the time from the onset of myocardial ischemia to intervention. The device analyzes myocardial electrical changes and alerts the patient to seek emergent medical evaluation if an acute ST-segment deviation is detected. We describe the first documented case of the Guardian device detecting acute ST-segment changes secondary to myocardial bridging.Case PresentationA 50-year-old male, with a history of percutaneous coronary intervention of the proximal left anterior descending (LAD) artery, presented to his cardiologist’s office with reports of recurrent, atypical chest pain. The Guardian device was implanted. One month after implantation, the patient experienced chest pain and was alerted by the Guardian device to seek emergent medical evaluation. Initial EKG and high-sensitivity troponins were negative for acute ischemia. Guardian device interrogation revealed significant ST depressions, encouraging further ischemic evaluation. The exercise myocardial perfusion imaging revealed an apical reversible defect. Left heart catheterization revealed a large segment of mid-LAD MB with the patient’s previous LAD stent noted to be widely patent along with no evidence of new obstructive coronary disease. Following the identification of the MB, medication regimen adjusted and the patient denied recurrence of chest pain or Guardian alerts.ConclusionsWe describe the first documented case of the Guardian device detecting acute ST-segment changes that were secondary to myocardial bridging. The Guardian device appropriately documented an ischemic event not appreciated with initial EKG or troponin testing. With the assistance of the Guardian device, we were able to rapidly identify MB as the cause for the ischemic EKG changes and subsequent abnormal stress test, optimize medical management, and prevent recurrent atypical chest pain along with office and hospital visits.

Qingxin Jieyu Granule alleviates myocardial infarction through inhibiting neutrophil extracellular traps via activating ANXA1/FPR2 axis

BackgroundMyocardial infarction (MI), representing the most severe manifestation of coronary artery disease (CAD), stands as a primary concern in the prevention and management of cardiovascular diseases. Clinical evidence demonstrates that Qingxin Jieyu Granule (QXJYG) is efficacious in treatment of MI patients. However, the mechanisms underlying its therapeutic effects remain to be elucidated. PurposeThis study aimed to evaluate the effects of QXJYG on MI and investigate its underlying mechanisms. Materials and methodsThe MI model in rats was developed through ligating the left anterior descending (LAD) artery. The effect of QXJYG on cardiac function impairment in MI rats was assessed by echocardiography, while the improvement of cardiomyocyte morphology and myocardial fibrosis after treatment with QXJYG was evaluated through hematoxylin-eosin (H&E) staining and Masson staining. The chemical constituents of QXJYG in blood were identified by using the UPLC-Q-TOF/MS technique. Furthermore, the molecular mechanism underlying the QXJYG therapeutic effect in MI was postulated based on the disease gene-drug target network analysis. Other technical methods such as ELISA, immunohistochemical staining, Western Blot analysis and application of pharmacological inhibitors were employed to verify the effectiveness of QXJYG in treating MI and explore its potential molecular targets. ResultsThe cardiac function in experimental rats post-MI was significantly impaired, as evidenced by an enlarged infarction area, disordered arrangement of cardiomyocytes, and aggravated myocardial fibrosis. QXJYG treatment significantly enhanced the cardiac function and reduced the pathological damage of the cardiac tissue in MI rats. Through the network pharmacology analysis, we identified that FPR2 might be a potential target of QXJYG in its cardiac protection role. QXJYG markedly downregulated the level of neutrophil extracellular traps (NETs) in MI rats, specifically manifested as a significant reduction in the Histone-DNA level and expression of myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) proteins. Furthermore, QXJYG upregulated the levels of ANXA1 and FPR2 proteins in MI rats. The level of FPR2 was markedly reduced in MI rats upon administration of WRW4, a specific inhibitor of FPR2, which was associated with exacerbated MI injury and an elevated level of NETs. When WRW4 was co-administered with QXJYG, the cardioprotective effects of QXJYG on MI were significantly diminished. However, the addition of DNase I did not result in significant changes of the outcomes in MI rats after QXJYG intervention. ConclusionQXJYG treatment alleviates cardiac tissue injury in MI rats by inhibiting NETs through activating the ANXA1/FPR2 axis. The findings extend our understanding of the therapeutic effectiveness of QXJYG and offer a scientific foundation for the clinical utilization of QXJYG.

Improved diagnostic accuracy of vessel-specific myocardial ischemia by coronary computed tomography angiography (CCTA)

BackgroundDiscrepancies between stenosis severity assessed at coronary computed tomography angiography (CCTA) and ischemia might depend on vessel type. Coronary plaque features are associated with ischemia. Thus, we evaluated the vessel-specific correlation of CCTA-derived diameter stenosis (DS) and invasive fractional flow reserve (FFR) and explored whether integrating morphological plaque features stratified by vessel might increase the predictive yield in identifying vessel-specific ischemia. MethodsObservational cohort study including patients undergoing CCTA for suspected coronary artery disease, with at least one vessel with DS ​≥ ​50 ​% at CCTA, undergoing invasive coronary angiography and FFR. Plaque analysis was performed using validated semi-automated software. Coronary vessels were stratified in left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA). Per vessel independent predictors of ischemia among CCTA-derived anatomical and morphologic plaque features were tested at univariable and multivariable logistic regression analysis. The best cut-off to predict ischemia was determined by Youden's index. Ischemia was defined by FFR≤0.80. ResultsThe study population consisted of 192 patients, of whom 224 vessels (61 ​% LAD, 19 ​% LCX, 20 ​% RCA) had lesions with DS ​≥ ​50 ​% interrogated by FFR. Despite similar DS, the rate of FFR≤0.80 was higher in the LAD compared to LCX and RCA (67.2 ​% vs 43.2 ​% and 44.2 ​%, respectively, p ​= ​0.018). A significant correlation between DS and FFR was observed only in LAD (p ​= ​0.003). At multivariable analysis stratified by vessel, the vessel-specific independent predictors of positive FFR were percent atheroma volume (threshold>17 ​%) for LAD, non-calcified plaque volume (threshold >130 ​mm3) for LCX, and lumen volume (threshold <844 ​mm3) for RCA. Integrating DS and vessel-specific morphological plaque features significantly increased the predictive yield for ischemia compared to DS alone (AUC ranging from 0.51 to 0.63 to 0.76–0.80). ConclusionsIntegrating DS and vessel-specific morphological plaque features significantly increased the predictive yield for vessel-specific ischemia compared to DS alone, potentially improving patients’ referral to the catheterization laboratory.

Ling gui shen fu decoction ameliorates cardiac injury in ischemic heart disease rats by regulating ANP32A/HIF2α/HMGB1 signal route

Purpose: To investigate the effect of ling gui shen fu decoction (LGSFD) on cardiac injury and cardiomyocyte apoptosis in rats with ischemic heart disease (IHD), and to elucidate the underlying molecular mechanism. Methods: An IHD rat model was established by performing coronary artery occlusion surgery on the left anterior descending (LAD) of rats. The rats were assigned equally to 5 groups: sham-operated group (sham group), IHD group, IHD + perindopril group, IHD + low- dose LGSFD group (IHD + LGSFD-L group), and IHD + high-dose LGSFD group (IHD+LGSFD-H group). The LGSFD was given via gavage. A hypoxia-induced cardiomyocyte model was established by subjecting H9C2 cells to hypoxia. Then, LGSFD-containing serum or blank serum was used to treat the hypoxic rat cardiomyocytes (H9C2). The severity of cardiac injury and extent of apoptotic changes in cardiomyocytes was determined using hematoxylin-eosin (H&amp;E) staining and TUNEL staining, while immunoblotting was used to measure the protein expressions of ANP32A, p-AKT, AKT, HIF-2α, p-mTOR, mTOR and HMGB1. Results: The cardiac injury of rats in the LGSFD groups was significantly reversed, relative to the IHD group (p &lt; 0.05). Moreover, LGSFD reduced the level of apoptosis in hypoxia- induced H9C2 cells and upregulated the concentrations of ANP32A, p-AKT, HIF-2α and p-mTOR. However, the expression levels of HMGB1 were decreased in the heart tissues of IHD rats and hypoxic H9C2 cells. Silencing of ANP32A with ANP32A siRNA (siANP32A) down- regulated ANP32A, p-AKT, HIF-2α and p-mTOR, but up-regulated apoptosis and expression levels of HMGB1 in hypoxic H9C2 cells. Conclusion: LGSFD ameliorates cardiac injury in IHD rats by inhibiting cardiomyocyte apoptosis via the ANP32A/HIF-2α/HMGB1 axis. Further investigations are recommended into the specific mechanism of LGSFD effect using clinical samples, in order to facilitate its clinical development.

An Anomalous Right Coronary Artery Draining into the Left Ventricle Through a Fistula

Background: Of the three main epicardial coronary arteries, the right coronary artery, left anterior descending artery, and the left circumflex artery, there are many variables between individuals regarding arterial course, distribution of side branches, and termination points. The term ‘Coronary Artery Anomaly’ (CAA) is reserved for congenital alterations in origin or course of the epicardial arteries that occur in less than 1% of the population. While the majority are asymptomatic, such anomalies can significantly increase the risk of myocardial ischemia and sudden cardiac death. With the increasing use of Coronary Computed Tomography Angiography (CCTA), the rate of detection of anomalous coronary arteries is increasing every year. The concurrent presence of a coronary cameral fistula further escalates clinical complexity requiring a multidisciplinary approach to management. Case Report: A 61-year-old female with a past medical history of hypertension, hypothyroidism, migraine, Non-Sustained Ventricular Tachycardia (NSVT), and Supraventricular Tachycardia (SVT), presented to the emergency department with chest pain and palpitations. Coronary angiography was performed revealing a large Right Coronary Artery (RCA) with a proximal branch giving rise to the Left Circumflex Artery (LCX), with an additional branch supplying the Left Anterior Descending (LAD) territory. The RCA and LCX arteries terminated distally in the left ventricular cavity forming a coronary cameral fistula. No flow-limiting stenosis was observed. Intervention versus medical management was discussed with a multidisciplinary team, and the decision was made to proceed with medical management. The patient’s symptoms improved with the medical management. Conclusion: A thorough diagnostic evaluation and a multidisciplinary approach in managing rare coronary anomalies are critical. Medical management, risk factor modification, and regular follow-up are essential components of long-term care for patients with complex coronary artery anomalies.

Infliximab in the Treatment of a Giant Coronary Aneurysm in Behçet's Disease.

Behçet's disease (BD) is a rare, multisystemic inflammatory disorder with a diverse range of manifestations, primarily affecting the mucocutaneous and ocular systems. While vascular involvement is less frequent it can be severe, with coronary aneurysms being particularly rare. We report a 28-year-old male with BD who developed a giant anterior interventricular artery aneurysm. The patient, initially managed with azathioprine and colchicine, presented with acute chest pain and elevated cardiac markers. Imaging revealed a coronary aneurysm measuring 5.03 cm. Due to the inflammatory nature of the aneurysm surgical intervention was initially deferred, and the patient was treated with corticosteroids and cyclophosphamide. Despite these treatments, recurrent symptoms prompted the initiation of infliximab therapy. Administered at 5 mg/kg at weeks 0, 2 and 6, with subsequent doses every two months, infliximab led to a significant reduction in aneurysm size to 3.73 cm. This case highlights the effectiveness of infliximab in managing giant coronary aneurysms associated with BD, demonstrating its potential as a treatment option for severe vascular complications in BD. The substantial reduction in aneurysm size following infliximab therapy underscores the need for further investigation into its role in treating such rare but serious manifestations of BD. A giant coronary aneurysm is a rare complication of Behçet's disease.Infliximab effectively reduced the aneurysm size.Imaging shows a substantial decrease in aneurysm size after infliximab treatment.

Cardiomyocyte-derived C-type natriuretic peptide diminishes myocardial ischaemic injury by promoting revascularisation and limiting fibrotic burden

BackgroundC-type natriuretic peptide (CNP) is a significant player in the maintenance of cardiac and vascular homeostasis regulating local blood flow, platelet and leukocyte activation, heart structure and function, angiogenesis and metabolic balance. Since such processes are perturbed in myocardial infarction (MI), we explored the role of cardiomyocyte-derived CNP, and pharmacological administration of the peptide, in offsetting the pathological consequences of MI. MethodsWild type (WT) and cardiomyocyte-restricted CNP null (cmCNP-/-) mice were subjected to left anterior descending coronary artery (LADCA) ligation and acute effects on infarct size and longer-term outcomes of cardiac repair explored. Heart structure and function were assessed by combined echocardiographic and molecular analyses. Pharmacological administration of CNP (0.2 mg/kg/day; s.c.) was utilized to assess therapeutic potential. ResultsCompared to WT littermates, cmCNP-/- mice had a modestly increased infarct size following LADCA ligation but without significant deterioration of cardiac structural and functional indices. However, cmCNP-/- animals exhibited overtly worse heart morphology and contractility 6 weeks following MI, with particularly deleterious reductions in left ventricular ejection fraction, dilatation, fibrosis and revascularization. This phenotype was largely recapitulated in animals with global deletion of natriuretic peptide receptor (NPR)-C (NPR-C-/-). Pharmacological administration of CNP rescued the deleterious pathology in WT and cmCNP-/-, but not NPR-C-/-, animals. Conclusions and implicationsCardiomyocytes synthesize and release CNP as an intrinsic protective mechanism in response to MI that reduces cardiac structural and functional deficits; these salutary actions are primarily NPR-C-dependent. Pharmacological targeting of CNP may represent a new therapeutic option for MI.

Percutaneous Coronary Intervention Versus Robotic Coronary Bypass for Left Anterior Descending Artery Chronic Total Occlusion

BackgroundBoth percutaneous coronary interventions (PCIs) and robotic-assisted coronary artery bypass (CAB) offer viable options for left anterior descending (LAD) chronic total occlusion (CTO) revascularization. Our study aims to compare long-term clinical outcomes associated with these 2 strategies. MethodsIn this retrospective study, we analyzed data from 273 patients diagnosed with LAD CTO who underwent either PCI (n = 129) or CAB (n = 144) at a single institution. Long-term follow-up was available for 96 PCI and 125 CAB patients. We employed Kaplan-Meier curves and the log-rank test to conduct cumulative survival analyses free of major adverse cardiovascular events (MACE), cumulative survival, survival free of myocardial infarction, and repeat revascularization. ResultsIn the study cohort, patients who underwent PCI exhibited a higher prevalence of comorbidities including diabetes (48.9% vs 24.6%; P < .001), lower ejection fraction (44 ± 14 vs 52 ± 10; P < .001), prior heart failure (36.6% vs 22.2%; P = .02), and prior bypass surgery (16% vs 0, P < .001). PCI to non-LAD vessels was performed as part of initial complete revascularization in 40.3% of PCI and 40.6% of CAB patients. Upon a median 3.4 years of follow-up, CAB patients had significantly higher rates of survival free of MACE compared to PCI patients (unadjusted hazard ratio, 2.39; 95% CI, 1.13-5.03). Although PCI patients had similar unadjusted mortality, they experienced higher myocardial infarction and repeat revascularizations compared to CAB. However, the risk of repeat revascularization was attenuated after adjusting for prior bypass, diabetes, and ejection fraction. ConclusionsAmong patients with LAD CTO, those undergoing robotic-assisted CAB had a higher 5-year overall survival free of MACE compared to those who underwent PCI. This discrepancy in outcomes can be attributed in part to the greater burden of comorbidities among PCI patients.

TCT-438 Long-Term Efficacy of Drug-Coated Balloon Treatment for De Novo Left Anterior Descending Artery Disease

TCT-438 Long-Term Efficacy of Drug-Coated Balloon Treatment for De Novo Left Anterior Descending Artery Disease

TCT-400 In-Hospital Outcome of Antegrade Dissection Reentry in Left Anterior Descending Artery Chronic Total Occlusions: Patient Data Pooled Analysis of 4 Multicenter Registries

TCT-400 In-Hospital Outcome of Antegrade Dissection Reentry in Left Anterior Descending Artery Chronic Total Occlusions: Patient Data Pooled Analysis of 4 Multicenter Registries

IMPACT OF LESION COMPLEXITY ON PCI SUCCESS IN LAD DISEASE: A RETROSPECTIVE STUDY

Coronary artery disease (CAD) involving the left anterior descending (LAD) artery is a major cause of morbidity and mortality globally. The prognosis of patients with coronary artery disease depends on the extent of at-risk myocardium. LAD comparatively supplies a large percentage of the left ventricle compared to RCA or LCX. The principal indication of percutaneous coronary intervention is to improve the quality of life in patients with angina refractory to medications. There are many advancements in PCI techniques for better management of challenging lesions due to physiological, anatomical, or functional difficulties. Some of the complex lesions include ostial lesions, bifurcating lesions, calcified lesions, and chronic total occlusions. However, as lesion complexity plays a significant role in procedural success and long-term outcomes, complex lesions are often associated with increased rates of restenosis, adverse events, and procedural challenges Objective: This study aims to evaluate the impact of lesion complexity on PCI success in patients with LAD disease. Methods: This retrospective cohort study was conducted from January 1, 2021, to December 31, 2023, at a tertiary cardiovascular center. A total of 216 participants who had PCI to LAD lesions done were included. Lesion complexity was assessed using the SYNTAX score and categorised into low, intermediate, and high complexity groups. The primary outcome was restenosis at 12 months, defined as ≥50% luminal narrowing in patients requiring repeat angiography due to any indication. Secondary outcomes included procedural success, major adverse cardiac events (MACE), and rates of stent thrombosis. Data were analysed using SPSS version 24.0, with statistical significance set at p &lt; 0.05. Results: Among the 216 participants, 72% were male, and the mean age was 61.4 ± 9.8 years. Restenosis occurred in 13.9% of participants, with higher rates observed in patients with high-complexity lesions (24.5%) compared to low-complexity lesions (7.7%) (p = 0.02). Procedural success was achieved in 92.6% of cases, though it decreased with increasing lesion complexity (97.8% for low, 93.4% for intermediate, and 85.7% for high-complexity groups). MACE occurred in 4.6% of participants, with stent thrombosis noted in 2.7%. Conclusion: Lesion complexity significantly influences PCI success and restenosis rates in LAD disease. Patients with higher complexity lesions experience worse outcomes, necessitating individualised treatment strategies to optimise procedural success.