Left Anterior Descending Research Articles

The Impact of Different Revascularization Strategies Implemented in Acute Myocardial Infarction on the Recovery of Left Ventricular Functional and Deformational Parameters

Background: Despite well-established therapeutic techniques, such as direct revascularization through percutaneous coronary intervention (PCI), acute myocardial infarction (AMI) remains a leading cause of mortality and morbidity. Objectives: To determine if two-dimensional speckle tracking echocardiography (STE) deformation parameters and the early recovery of left ventricular (LV) functions are affected by the timing of PCI in AMI. Methods: A total of 200 cases with newly-onset acute myocardial infarction (AMI) who had a baseline left ventricular ejection fraction (LVEF) higher than 40% and received effective therapy with percutaneous coronary intervention (PCI) were included in this investigation. cases were categorized as either ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI). cases were grouped into four groups according to the time between presentation and PCI. Using standard echocardiography and two-dimensional (2D) ST-elevation STE, individuals were re-evaluated three months later to find out if remodeling had taken place or if the LV function had returned. Results: Of the 200 AMI patients, including 140 males (70%), improvement in global longitudinal strain (GLS) and harmed longitudinal strain (HLS) were better in STEMI and NSTEMI patients received urgent revascularization with PCI (groups I and III) versus patients with pharmacoinvasive strategy or routine invasive strategy (Groups II and IV) (P < 0.05) while there was an insignificant difference between group I and III (P = 0.79). Of the 200 patients, 47 patients (23.5%) presented signs of LV remodeling at 3 months follow up. Age, smoking history, hypertension, dyslipidemia, Killip class, peak creatine phosphokinase - MB level, baseline left ventricular end diastolic volume (LVEDV), HLS, and harmed longitudinal strain rate (HLSR) were all factors that were found to be significantly associated with left ventricular remodeling (P<0.05) in the univariate logistic regression analysis. The following factors were identified as independent predictors of left ventricular remodeling in multivariate logistic regression analysis: damaged left ventricular ejection fraction (EF) and end-systolic volume, peak troponin I, Killip class, culprit left anterior descending (LAD), 2 and 3-vessel coronary artery disease (CAD), and wall motion score index (WMSI). Conclusion: Earlier PCI in AMI helps earlier improvement in myocardial strain parameters. HLS and HLSR are excellent predictors for LV remodeling and may do better than global parameters.

Overcoming Challenges in Kabul, Afghanistan: Successful Management of Mid-Portion Left Anterior Descending Artery Ellis Class 3 Coronary Artery Perforation, Complicated by Cardiac Tamponade and Concurrent Cardiac Arrest

Overcoming Challenges in Kabul, Afghanistan: Successful Management of Mid-Portion Left Anterior Descending Artery Ellis Class 3 Coronary Artery Perforation, Complicated by Cardiac Tamponade and Concurrent Cardiac Arrest

An In Vivo Model of Estrogen Supplementation Concerning the Expression of Ca2+-Dependent Exchangers and Mortality, Vitality and Survival After Myocardial Infarction in Ovariectomized Rats

Background: Ischemic-reperfusion damage of cardiomyocytes due to myocardial infarction (MI) often leads to the death of an individual. Premenopausal women have been observed to have a significantly lower risk of cardiovascular disease (CVD) than men of the same age. In menopausal women, this trend is significantly reversed, and the risk of CVD increases up to 10-fold. Estrogens affect the development and function of the heart muscle, and as they decrease, the risk and poor prognosis of CVD increase. This study is focused on the effects of estrogen supplementation on morbidity, vitality, and NCX1 expression after MI on a model system. Methods: In this study, female Sprague Dawley rats (n = 58), which were divided into three experimental groups (NN—control group, non-supplemented; OVX-N—ovariectomized, non-supplemented; OVX-S—ovariectomized, supplemented), received left thoracotomy in the fourth intercostal space. The left anterior descendent coronary artery was ligated 2 mm from its origin with an 8.0 suture. An immunohistological analysis as well as an RT-PCR analysis of NCX1 expression were performed. Results: A higher survival rate was recorded in the OVX-N group (86%) in comparison with the OVX-S group (53%) (p < 0.05). In addition, higher NCX1 expression 7 days/14 days after MI in the OVX-S group in comparison with the NN and OVX-N (p < 0.001 and p < 0.05) groups was recorded. Seven days after MI, a significantly higher expression (p < 0.005) of mRNA NCX1 in the OVX-N group was also recorded in comparison with the NN group. Conclusions: This study provides a comprehensive description of the effect of estrogen supplementation on NCX1 expression and overall vitality in ovariectomized rats that survived MI.

The risk factors for in-stent restenosis following drug-eluting stent implantation in end-stage renal disease patients receiving renal replacement therapy

Abstract Background Chronic renal disease is a recognized risk factor for in-stent restenosis (ISR) following percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). However, the specific risk of ISR among individuals with end-stage renal disease (ESRD) remains unclear or insufficiently studied. Purpose It is imperative to identify the risk factors associated with ISR among patients with ESRD and coronary artery disease following the implantation of DES. This identification is crucial for generating evidence-based strategies aimed at preventing ISR. Methods ESRD patients undergoing renal replacement therapy with concomitant coronary artery disease who underwent PCI with their initial DES implantation at our hospital between January 2013 and December 2022 were included in the study cohort. Clinical data, laboratory test results, and PCI specifics were compared between patients with and without ISR. Univariate and multivariate analyses utilizing Cox proportional hazard regression were employed to identify independent risk factors for DES-ISR. Results Among the 321 patients with ESRD who underwent PCI with DES implantation, totaling 874.5 patient-years of follow-up, 53 cases of ISR occurred during this period, yielding an incidence rate of 6.1 per 100 patient-years. Several baseline characteristics, angiographic findings, and procedural details were found to elevate the risk of ISR significantly. These included underlying diabetes mellitus, peripheral artery disease (PAD), high serum parathyroid hormone levels, LDL-C levels, acute coronary syndrome as the clinical presentation, the presence of triple vessel disease, duration of dual antiplatelet therapy less than 1 year, target lesion involving the left main (LM) or left anterior descending (LAD) artery, target vessel size less than 3 mm, ostial lesion, bifurcation lesion, number of stents implanted equal to or more than 3, and stent size less than 3 mm. In the multivariate Cox proportional hazard model, bifurcation lesion (HR 14.70, 95% CI 4.66-46.38), PCI of LM or LAD (HR 5.29, 95% CI 1.14-24.60), target vessel size less than 3 mm (HR 4.10, 95% CI 1.77-9.50), PAD (HR 3.92, 95% CI 1.52-10.08), and ostial lesion (HR 2.92, 95% CI 1.16-7.38) were identified as independent risk factors for ISR (all p-values < 0.05). Conclusions Among ESRD patients with coronary artery disease, bifurcation lesion, PCI involving the LM or LAD, target vessel size less than 3 mm, PAD, and ostial lesion are identified as independent risk factors for ISR. These findings hold significance in enhancing risk stratification and decision-making concerning treatment planning for this population.Univariate analysis risk factors for ISR

Prognostic significance of coexistent coronary artery disease in patients undergoing transcatheter aortic valve implantation for aortic stenosis

Abstract Background The optimal management of coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) is uncertain. As TAVI expands into lower risk cohorts with longer life expectancies there is increasing need to determine the prognostic significance of coexistent CAD and identify which lesions may benefit from revascularisation. Purpose To evaluate the prognostic significance of coexistent CAD in patients with AS undergoing TAVI stratified according to myocardial territories at risk. Methods Using a retrospective, single-centre, observational registry, patients undergoing TAVI for severe AS between 2015 and 2020 were included. CAD was angiographically determined using computed tomography or invasive coronary angiography. CAD was stratified into 1) low-risk: <70% stenosis in all major epicardial coronary arteries or <50% in the left main (LM); 2) intermediate-risk: ≥70% stenosis in one or two arteries, except the proximal left anterior descending (LAD) and LM; 3) high-risk: ≥70% stenosis in the proximal LAD, ≥70% stenosis in 3 arteries or LM stenosis ≥50%. Patients with previous CABG were categorised as high-risk if: ≥70% stenosis of 3 coronary grafts or graft supplying a proximally stenosed LAD; and intermediate-risk if: ≥70% stenosis of 1 or 2 non-LAD grafts. Baseline characteristics and procedural outcomes were compared between the 3 cohorts, with the impact of CAD on outcomes evaluated after adjustment for demographics and comorbidities. Results 1805 patients were included; median age 84 (79-88), 51% male sex, median logistic Euroscore 13 (8-21). 1281 (71%), 384 (21%) and 140 (8%) patients were characterised as low-, intermediate- and high-risk coronary anatomy respectively. High risk patients were older than the other groups, however, did not have the highest prevalence of comorbidities (Table 1). Other than pacemaker implantation (9% vs 12% vs 6%, p=0.04), there were no differences in procedural complications or in-hospital mortality between groups (Table 1). At a median follow-up of 3.5 (2.3-4.8) years, 920 patients (51%) died, 292 (16%) had hospitalisation for heart failure (HHF) and 565 patients (31%) had a major adverse coronary event (MACE); defined as either myocardial infarction, HHF or cardiovascular death. Coronary anatomical stratification was associated with MACE (Log rank p<0.001) (Figure 1). After multivariate adjustment, high-risk anatomy was associated with all-cause mortality (hazard ratio (HR): 1.34, 95% confidence interval (CI): 1.06-1.68, p=0.013), HHF (HR: 1.49, 95% CI: 1.01-2.21, p=0.046) and MACE (HR: 1.68, 95% CI: 1.27-2.21, p<0.001). Conclusions Whilst the presence of CAD does not impact TAVI procedural safety, untreated high-risk coronary anatomy is associated with future adverse events and may warrant intensive medical therapy and/or revascularisation.

Incremental role of Cardio-Ankle Vascular Index in predicting ischemic threshold in patients with suspected coronary artery disease

Abstract Background The Cardio-Ankle Vascular Index (CAVI) quantifies arterial stiffness and has emerged as a potential biomarker for cardiovascular disease and its associated risk factors. This study explores the prognostic utility of CAVI in predicting myocardial ischemia in patients with suspected coronary artery disease (CAD). Additionally, it examines the relationship between global longitudinal strain (GLS) and the wall motion score index (WMSI) during both rest and stress echocardiography. Methods We conducted a retrospective analysis of patients with suspected CAD who underwent CAVI measurement and stress echocardiography within a three-month window. Coronary angiography was utilized to evaluate anatomical stenosis (>50%). We used multivariate analysis to identify predictors of the ischemic threshold. Results In our cohort of 127 patients (average age 61.4 ± 9.1, 78% male), the prevalence of hypertension, dyslipidemia, and diabetes was 76%, 68% and 47% of patients, respectively. Prior coronary intervention and a history of myocardial infarction were showed significant prevalence at 33% and 9%, respectively. CAD distribution included absence in 15%, left main (LM) disease in 8%, proximal left anterior descending (LAD) artery disease in 38%, mid-to-distal LAD disease in 50%, left circumflex artery disease in 46%, and right coronary artery disease in 57%. A robust correlation between GLS and WMSI was observed both at rest and during peak stress (r=0.68 and r=0.57, p<0.001, respectively). High CAVI (≥8.5), resting GLS in the LAD(<-15.5%), and peak GLS during stress (<-15.3%) emerged as significant ischemic threshold predictors in multivariate analysis (AUC = 0.82, p<0.0001). Conclusion The correlation between WMSI and GLS provides valuable insights into cardiac mechanics. These findings underscore the clinical relevance of incorporating CAVI, GLS, and WMSI into routine assessments for patients with suspected CAD to enhance prognostic stratification.ROC for final predictive model

Residual ischemia location after STEMI by CMR and association with non-culprit coronary artery disease

Abstract Background Many ST-segment elevation myocardial infarction (STEMI) patients present with non-culprit coronary artery disease. In cases with incomplete revascularization, stress cardiac magnetic resonance (sCMR) could help detect and locate residual ischemia. Purpose We aim to evaluate the usefulness of sCMR to detect and locate residual ischemia in STEMI patients after discharge and correlate the findings with angiographical non-culprit coronary lesions, if any. Methods Reperfused, stable STEMI patients submitted to undergo sCMR within the first year after STEMI were included in the cohort. Index coronary angiography was revised, culprit and non-culprit coronary artery disease were registered, and significant stenoses were defined as ≥50% by visual assessment. Residual ischemia on sCMR (by first-pass vasodilator stress perfusion) was analysed and categorized as either absent or present in anterior, lateral, and inferior territories. Unrevascularized non-culprit coronary lesions were correlated with territories with residual ischemia on sCMR and lesions in subsequent coronary angiography. A p-value <0.05 was considered statistically significant. Results The study group was made up of 234 patients who underwent sCMR within the first year after STEMI (mean age 58.95±11.85 years, 78.2% male, 48.7% anterior infarction). Residual ischemia by sCMR was noted in 63 (26.9%) patients. In the 95 patients (40.6%) who underwent complete revascularization during index admission, residual ischemia by sCMR was seldom detected (n=14, 14.7%) and distributed on anterior (n=8), lateral (n=3) and inferior (n=4) territories. More than half of the cohort (n=139, 59.4%) depicted unrevascularized non-culprit coronary lesions, and residual ischemia was detected in 49 (35.3%) patients. Non-culprit lesions on left anterior descendent artery (n=62) associated with ischemia in 38.7% of cases (n=24), most commonly in the anterior territory (n=17, 70.8%). Similar findings were noted for lesions on circumflex artery (n=66), which depicted residual ischemia in 34.8% (n=23) of cases and most frequently in the lateral territory (n=13, 56.5%); and lesions in right coronary artery (n=45), which depicted residual ischemia in 42.2% (n=19) of cases, most commonly in the inferior territory (n=13, 68.4%). Significant coronary stenosis was found in most patients who underwent subsequent coronary angiography after residual ischemia detection (41 out of 47, 87.2%). Conclusions One third of STEMI patients with incomplete revascularization and non-culprit coronary artery disease depict residual ischemia on sCMR, the location of which generally correlates with index coronary anatomy and significant stenosis in subsequent coronary angiography. Residual ischemia is infrequent in patients with complete revascularization, but not inexistent. sCMR should be considered in selected STEMI patients according to coronary anatomy and/or symptoms to guide therapy.Stress CMR and ischemia location

Complete vs culprit-lesion-only myocardial revascularization in patients with out-of-hospital cardiac arrest: insights from the multicentric "Lombardia CARe" registry

Abstract Background Out-of-hospital Cardiac Arrest (OHCA) is a potentially devastating complication of patients with Myocardial Infarction (MI). Multivessel Disease (MVD) is a frequent occurrence in this setting, being present in nearly half patients undergoing Coronary Angiography (CAG). We previously reported that, in case of MI complicated by OHCA and evidence of MVD, a complete myocardial revascularization, as compared to culprit-lesion-only revascularization, was associated with an improved 1-year survival and favorable neurological outcomes. We aimed to validate and confirm these results on a multicentric scale with a larger patient cohort. Methods This is a multicentric, prospective, observational study. We considered all the consecutive patients with OHCA and MI enrolled in the Lombardia CARe Registry from January 1st 2015 to December 31st 2022 who underwent CAG in 6 centers in Northen Italy. Results A total of 623 patients were included; of these, 403 underwent CAG. Median age was 64 years, and about 80% had no previous history of ischemic heart disease. Median ejection fraction (EF) at presentation was 40%. MVD was present in 186 (46.1%) patients and was subsequently treated with either complete (32.3%) or incomplete (67.7%) coronary revascularization. Left anterior descendent (LAD) artery was the culprit lesion in almost 1/3 of patients. The 1-year survival rate was 78.3% in the complete revascularization group and 42.9% in the culprit-lesion-only revascularization group (p-value < 0.001). After correction for factors that were predictors on univariate analysis, complete revascularization strategy was independently associated with a reduced risk of death [HR: 0.27 (95% CI: 0.01 to 0.739; p = 0.01] and death or unfavorable neurological outcome [HR: 0.23 (95% CI: 0.08 to 0.67); p = 0.007]. Conclusions Complete revascularization strategy was confirmed to be associated with an improvement of 1-year survival and with a good neurological outcome in patients resuscitated from OHCA. These results highlight the independent impact on survival of a complete coronary intervention strategy in patients with OHCA plus MVD.

The utility of angiography-derived fractional flow reserve in predicting graft occlusions prior to bypass surgery

Abstract Background Occurrence of graft occlusion following coronary artery bypass graft (CABG) surgery has been linked to the presence of native coronary artery competitive flow (1). Despite its routine use in guiding revascularization, coronary angiography lacks sensitivity for assessing coronary stenosis significance. Data regarding the use of pressure-derived fractional flow reserve (FFR) to assess the hemodynamic significance of coronary stenoses prior to CABG are inconclusive (2) and the penetration of FFR in clinical routine is limited for various reasons (3). Different systems have been developed to predict FFR based on coronary angiographic images, eliminating pressure wires or hyperemic agents (4). Preliminary data demonstrated a high concordance between off-site angiography-derived FFR and pressure wire–based FFR (5-7). However, the use of this technique prior to CABG is not well studied. Purpose This study aims to correlate pre-CABG angiography-derived FFR with graft occlusion. Secondary endpoint is the correlation between the presence of at least one occluded bypass graft and overall mortality. Methods Retrospective study of patients undergoing CABG in whom a follow-up angiogram has been performed. Angiography-based FFR was calculated with a dedicated software (vFFR, CAAS 8.2 Workstation, Pie Medical Imaging), obtaining each major native coronary vessel before CABG. Post-CABG angiograms were conducted at least 6 weeks post-surgery to exclude graft-failures due to technical factors and thrombosis. Results From 2005 and 2014, 204 patients underwent pre-CABG angiography, with post-CABG angiograms at a median of 3.85 years [IQR 1.33-8.80] post-surgery. In total, 125 patients had to be excluded due to inadequate angiogram quality for vFFR assessment (outdated imaging system, improper vessel angles, vessel overlap, insufficient contrast). Consequently, 79 patients were suitable for pre-CABG vFFR analysis, including 132 grafted vessels (93 arterial and 39 saphenous grafts). The median patient age was 68 years [IQR 58-72] and mean time for clinical follow-up was 9.9±3.6 years. Vessels analyzed using vFFR were left anterior descending (LAD) (n=60, 45.5%), left circumflex (LCX) (n=39, 29.5%), ramus intermedius (RIM) (n=8, 6.1%) and right coronary artery (RCA) (n=25, 18.9%). Mean pre-CABG vFFR was 0.59±0.15. To predict graft occlusion, a vFFR cut-off value of 0.745 with an area under the curve (AUC) of 0.847 (95%CI 0.752–0.942) had a specificity of 0.722 and a sensitivity of 0.902 (Figure A). There was no difference in overall-mortality when comparing patients with at least one occluded bypass graft to those without (57.1% vs. 57.9%, p=0.949, Figure B). Conclusions vFFR can be used as a noninvasive tool to predict graft patency in patients undergoing CABG with acceptable sensitivity and specificity. Bypass graft occlusion did not correlate with overall-survival in this cohort.

How to predict myocardial injury in patients with large ischaemic burden identified during stress echocardiography?

Abstract Background/Introduction Stress echocardiography (SE) is well established diagnostic tool in coronary artery disease (CAD) with broadly agreed consensus for the indications and protocols. There is, however, no clear non-invasive SE parameter in identifying high risk features in patients with large burden of inducible regional wall motion abnormalities (RWMA) that would require prompt treatment or urgent admission. Purpose To identify high risk features during SE associated with myocardial injury following a positive SE with large amount of RWMA. Methods All consecutive patients referred for SE from June 2019 to November 2022 to diagnose coronary artery disease were assessed for inducible RWMAs using a hybrid protocol (low dose Dobutamine and exercise on supine bike with 3 min increments of workload of 25W). Those with ≥4/17 segments of inducible RWMAs underwent measurement of Troponin level 1 hour after the test termination. Somatometric characteristics, risks factors, symptoms, haemodynamic pre- and during SE and results of subsequent coronary angiography were recorded. Results 631 patients were referred for assessment of CAD. 87 patients had ≥4/17 inducible RWMAs out of 152 patients with positive SE. 61/87 who had Troponin measurements were included in the analysis. Mean age was 65 ± 13 yo, 61% were male. There was high prevalence of known CAD (77%) and cardiovascular risks factors as hypertension (59%) and hyperlipidaemia (61%). The median exercise time was 9 minutes, 46% developed chest pain (CP), 49% - ECG changes, 39% - left ventricular (LV) dilatation and 74% - reduction in LVEF. Troponin was positive in 25/61 patients. Invasive coronary angiography confirmed clinical CAD in 51/61 patients. 5 patients had either normal angiogram or non-obstructive CAD, 5 patients were awaiting diagnostic test. The severity of CAD appears to be associated with magnitude of Troponin release (1 vessel disease - 16.5 ng/L, 2 vessels disease - 39.9 ng/L, 3 vessels disease – 58.2 ng/L). All patients (6/61) with higher troponin values (>90ng/L) had multivessel disease involving the left anterior descending (LAD) artery. Interestingly, 2/5 patients without CAD had elevated Troponin suggesting possible ongoing myopathic process. The only non-invasive SE parameters that were significantly related to troponin increase were recovery time (P=0.001) and exercise time (P<0.05) whereas symptoms, BP response and LVEF reduction showed a trend which did not achieve significance. Conclusions In patient with positive SE with large burden of inducible RWMAs prolonged recovery time and low threshold for ischaemia appear to be the most reliable characteristic to identify patients with potential myocardial injury and should be used as a triaging tool for admission or early invasive assessment.

Predictive ability and prognostic correlation of global longitudinal strain in patients with negative dipyridamole stress echocardiography by wall motion criteria

Abstract Background Dipyridamole stress echocardiography (DSE) is an established technique to detect coronary artery disease (CAD) and for risk stratification. Speckle Tracking Echocardiography (STE), as an objective and quantitative evaluation of ventricular function, may add incremental value to conventional stress echo analysis. Purpose To assess the prognostic value of rest (Rest-GLS) and peak (Peak-GLS) stress global longitudinal strain (GLS) in patients with suspected CAD and negative DSE according to wall motion index (WMI) criteria. Methods We retrospectively enrolled patients who underwent DSE at our centre for suspected CAD, with normal WMI. Strain Reserve was calculated as Rest GLS – Peak-GLS (Delta-GLS). We also collected data regarding other conventional parameters such as coronary flow reserve (CFR) of left anterior descending (LAD), left ventricle contractile reserve (LVCR), delta left ventricular ejection fraction (Delta-LVEF), heart rate response (HRR). Our primary endpoint was a composite of all-cause death and coronary revascularization. Receiver operating characteristic (ROC) curves were used to compare the predictive ability of the parameters. Adjusted logistic regression analyses were used to assess associations, also modelled as a restricted cubic spline. Results A total of 355 patients were included in the analysis (median age 68.2, IQR 58.2-75.2, 38.0% female). At follow-up, 58 patients met the primary endpoint. Figure 1 shows the ROC curves of different DSE parameters. Delta-GLS and Peak-GLS showed high predictive ability of composite endpoint events (area under the curve [AUC] 0.87, 95% Confidence Interval [CI] 0.82-0.92, AUC, 0.85, 95% CI 0.79-0.91, respectively), which was significantly higher compared with other DSE parameters, included Basal-GLS (P for difference for all < 0.001). After adjustments for age, previous CAD, sex, and diabetes, reducing values of Rest-GLS, Peak-GLS and Delta-GLS were significantly associated with higher odds of experiencing composite endpoint events (Basal-GLS, odds ratio [OR] 1.13, 95% CI 1.04-1.24; Peak-GLS, OR 1.45, 95% CI 1.32-1.63; Delta-GLS, OR 1.73, 95% CI 1.50-2.04). Plotting the results of the logistic regression analysis on a restricted cubic spline, reducing values of Peak-GLS and Delta-GLS showed a linear increase for the risk of adverse events, while Rest-GLS showed a plateau for lower values. Conclusion The use of GLS parameters in DSE can help to better stratify the risk for the patients since they are associated with adverse cardiovascular events.Figure 1Figure 2

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.

Distal solution for an (un)conventional radial artery complication: a Case Report

Abstract Background The European Society of Cardiology (ESC) guidelines recommend transradial access (TRA) for coronary angiography due to its advantages, including lower mortality and bleeding complications. Arterial pseudoaneurysms are rare but challenging complications of TRA, occurring in 0.009%-0.05% of procedures. Non-surgical management, especially in cases with large (&amp;gt;1 mm) necks or late discovery, can be difficult due to the limited effectiveness of echo-guided compression and risks of echo-guided thrombin injection, like thrombin embolization leading to necrosis. Case Summary An 82-year-old underwent successful non-surgical management of a large-neck pseudoaneurysm following TRA for a primary percutaneous coronary intervention (PCI) of the left anterior descending (LAD) artery. Clinical examination revealed a pulsatile mass at the puncture site, diagnosed via ultrasound as a pseudoaneurysm with a &amp;gt;1 mm neck. Through distal radial access (DRA), an initial 5Fr sheath was upsized to 8Fr based on ultrasound findings, achieving complete pseudoaneurysm exclusion. Follow-ups confirmed pseudoaneurysm sealing and radial artery patency. Discussion This case illustrates an effective non-surgical approach to managing large-neck pseudoaneurysms post-TRA, utilizing an upsized sheath technique. It underscores the importance of innovative non-surgical strategies in complex cases, providing a safe and effective alternative to traditional management methods.

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.