Diffuse Coronary Artery Disease Research Articles

Prognostic value of diffuse high-risk plaque in patients with acute myocardial infarction: a three-vessel optical coherence tomography study

Abstract Background Existing evidence has identified that high-risk plaque (HRP) characterized by a thin-cap fibroatheroma and/or a minimal lumen area ≤ 3.5 mm² were indicative of future cardiovascular events. Diffuse coronary artery disease also contributes to the poor prognosis. Purpose The present study aims to assess the prognostic value of diffuse HRP in patients with acute myocardial infarction (AMI) by using three-vessel optical coherence tomography (OCT). Methods A total of 674 patients with AMI who underwent OCT examination of three major epicardial arteries between January 2017 and December 2018 were consecutively studied. Among 2843 nonculprit lesions detected by OCT, 1375 (48.4%) HRPs were identified and divided into diffuse HRP group (lesion length >20mm, n=443) and focal HRP group (lesion length ≤20mm, n=932). Patients were followed up for a median period of 5 years. Major adverse cardiovascular event (MACE) was defined as the composite of cardiac death, nonculprit lesion-related nonfatal myocardial infarction, and unplanned coronary revascularization. Results The average age of all enrolled patients is 56.7±11.4 years, with 74.9% of male. As compared with focal HRP group, diffuse HRP group had longer lesion length [25.8(23.0,30.8) mm vs. 13.2(9.8,16.1) mm, P<0.001], longer lipid length [18.6(12.3,24.9) mm vs. 7.0(4.5,10.5) mm, P<0.001], and thinner minimal fibrous cap thickness [73.3(53.3,106.7) μm vs. 93.3(60.0,130.0) μm, P<0.001], whereas mean lipid arc was comparable between the two groups. The prevalence of nonculprit plaque rupture (14.2% vs. 7.8%, P<0.001) was significantly higher in diffuse HRP group than that in the focal HRP group. Nonculprit lesions in diffuse HRP group had higher incidence of macrophage accumulation, microvessels, cholesterol crystals, calcification, and layered plaque phenotype than those in focal HRP group (all P<0.001). The incidence of nonculprit lesion-related MACE was 4.7% in diffuse HRP group and 1.7% in focal HRP group [HR: 3.155, 95% confidence interval: 1.579 to 6.301, P=0.002]. Conclusions In patients with AMI, diffuse HRP at nonculprit segment has higher levels of plaque vulnerability and is predictive of future adverse cardiovascular events. Further studies are warranted to investigate the individual treatment strategy of diffuse and focal HRP.Figure 1.Nonculprit plaque vulnerabilityFigure 2.MACE

Impact of the pullback pressure gradient (PPG) on PCI planning and decision-making

Abstract Background Coronary physiology using a distal measurement of fractional flow reserve (FFR) informs about the severity of coronary artery disease (CAD) and, when used for clinical decision-making about revascularisation, is associated with improved outcomes in patients considered for PCI. A second dimension of coronary physiology is available by performing a pullback maneuver, which aids in assessing the presence and location of focal pressure gradients. Yet, the impact of intracoronary physiology guidance with FFR pullbacks on real-time physician decision-making during PCI is not fully known. Methods This prospective study was performed at 25 sites and enrolled patients with at least one epicardial lesion with FFR ≤ 0.80 planned to be treated by PCI. A standardized physiological assessment with FFR pullbacks and Pullback Pressure Gradient (PPG) calculation was performed. Treatment plans were recorded for each lesion based on angiography alone and following FFR pullbacks. The goal of this study was to assess the procedural impact of physiology guidance in stable patients scheduled for PCI. Results Overall, 993 patients (1044 vessels) underwent complete physiological assessment with FFR and PPG. Decision-making during PCI changed in 47.5% (443/1044) after FFR pullbacks. Decision-making during PCI changed in 32.4% (289/890) after FFR pullbacks. PPG use changed revascularisation decisions in 13.9% (138/993) from PCI to CABG (5%; 50/993), from PCI to CABG in 5% (50/993) and to medical management in 8.9% ( 88/993). The frequency of decision changes was significantly higher in patients with diffuse CAD compared to focal cases (24.8% vs. 44.2%, p < 0.001). Among the subset of 855 patients (involving 880 vessels) who underwent PCI, operators modified decision-making regarding stent length in 22.1% of cases (197 out of 880), with these alterations being more prevalent in patients with diffuse CAD (57.2% vs. 46.3%, p = 0.002). Suboptimal Post-PCI result (FFR < 0.88) was more frequent in cases in which PCI strategy was not adapted based on PPG (55.5% vs. 45.6%, p= 0.016) Importantly, there was no significant change in the overall number of stents per patient after FFR pullbacks. Conclusion A standardized coronary physiological assessment impacted PCI decision-making in one-third of the vessels, with a predominant effect in vessels diffusely diseased. The assessment of the distribution of pressure losses along the coronaries modifies the treatment decision and influences PCI strategy in a significant proportion of patients. These findings provide insights into mechanisms by which coronary physiology might improve PCI outcomes.PCI strategy change based on PPGCumulative change of PCI strategy

Mechanisms leading to peri-procedural myocardial infarction in patients with focal versus diffuse coronary artery disease

Abstract Background PMI are characterized by an elevation in cardiac biomarkers, such as troponin, following PCI. Adherence to the 4th UDMIof PMI necessitates not only elevated cardiac biomarkers but also the presence of ECG changes, new loss of viable myocardium, or angiographic findings indicative of a procedural complication. Understanding the mechanisms underlying PMI and their associated factors is of paramount clinical significance. Our goal was to investigate the specific pathways contributing to the occurrence of PMI in stable patients undergoing PCI. Methods This prospective study was performed at 23 sites and enrolled patients with at least one epicardial lesion with an FFR≤0.80 planned to be treated by PCI. Each patient underwent a standardized physiological protocol, including manual FFR pullbacks with PPG calculation for the characterization of CAD patterns. The median PPG value (0.62) was used to divide patients into predominantly focal or diffuse disease. Troponin levels were measured after PCI, and patients exhibiting an elevation exceeding 5 times the upper limit of normal (ULN) were subject to evaluation by an independent clinical events committee. In addition, patients with large troponin elevation (>70 times above the ULN) were adjudicated as PMI as a standalone criterion. The primary objective was to investigate the mechanism leading to PMI in patients with focal versus diffuse CAD. Results Overall, 855 patients were included in this analysis, with 34.5% (295 patients) exhibiting a troponin elevation exceeding 5 times the ULN. Among these cases, 66 (7.7%) were adjudicated as PMI. The prevalence of secondary criteria for PMI was as follows: ECG changes at 7.6% (5/66), new loss of viable myocardium at 0%, side branch occlusion at 18.2% (12/66), and large troponin elevation at 84.8% (56/66). Diffuse disease (PPG < 0.62) was significantly associated with PMI (OR 1.71, 95% CI 1.03 to 2.88, p-value = 0.038). In the overall population, the occurrence of ECG changes after PCI was 0.7% in focal disease compared to 0.8% in diffuse disease (p-value=1.0). Side branch occlusion after PCI was observed in 0.7% in focal disease vs. 2.5% in diffuse disease (p-value=0.04), and large troponin elevation occurred in 4.8% in focal disease vs. 8.5% in diffuse disease (p-value=0.03). Additionally, PPG was significantly associated with the incidence of side branch occlusion (OR 1.71, 95% CI 1.03 to 2.88, p-value=0.038) and large troponin elevation after PCI (OR 1.83, 95% CI 1.06 to 3.22, p-value=0.038). Conclusion The presence of diffuse atherosclerosis, as defined by PPG, was linked to an increased risk of PMI. The mechanisms leading to PMI differed between patients with focal and diffuse disease. Patients with diffuse disease demonstrated a higher incidence of branch occlusion and large troponin elevation following PCI compared to those with focal CAD. Targeting patients with high PPG may improve outcomes after PCI.MACE by PPG

The Role of Inducible Nitric Oxide Synthase in Assessing the Functional Level of Coronary Artery Lesions in Chronic Coronary Syndrome.

Chronic coronary syndrome (CCS) is a long-term manifestation of coronary artery disease, marked by stable but recurring chest pain and myocardial ischemia due to the gradual buildup of atherosclerotic plaques in the coronary arteries. It is a metabolic disorder of coronary arteries characterized by oxidative stress, endothelial dysfunction, inflammation, and hyperlipidemia. The imbalance in oxidative-antioxidative status contributes to stable ischemic heart disease. Oxidative stress involves reactive oxygen and nitrogen species, leading to low-density lipoprotein (LDL) oxidation. Endothelial dysfunction, marked by reduced nitric oxide (NO) bioavailability, is an early onset of CCS, affecting vasodilation, cell proliferation, and inflammatory responses. Enzyme myeloperoxidase (MPO), traditionally considered protective, plays a dual role in initiating and progressing inflammatory diseases. MPO interacts with NO, modulating its catalytic activity. Elevated NO levels inhibit MPO through a reversible complex formation, preventing NO-induced inhibition by inducible nitric oxide synthase (iNOS). MPO also inactivates endothelial nitric oxide synthase (eNOS) and reacts with L-arginine, hindering NO synthesis. The interplay between MPO and NO significantly influences inflammation sites, impacting peroxidation rates and oxidation reactions. Peroxynitrite, a reactive species, contributes to nitration of tyrosine residues and lipid peroxidation. Mechanistic pathways suggest MPO enhances iNOS catalytic activity, influencing CCS development. iNOS, implicated in inflammation and atherosclerosis, is connected to NO regulation. This review analyzes the complex interplay of MPO, iNOS, and NO that affects plaque morphology, oxidative stress, and inflammation, contributing to atherosclerosis progression. Therefore, it is possible that the phenotypes of atherosclerotic plaques, focal and diffuse coronary artery disease, could be defined by the relationship between MPO and iNOS.

Association between 82Rb positron emission tomography-derived regional myocardial blood flow, severity of angiographic coronary artery stenosis, and mortality in patients with chest pain

Impairment in global myocardial flow reserve (MFR) on rubidium-82 (82Rb) positron emission tomography (PET) stress testing predicts cardiovascular events; however, the relationship between regional coronary artery territory myocardial blood flow (MBF) and invasive coronary angiography is unknown. In this study, patients with acute chest pain who were referred for coronary angiography after abnormal PET stress testing were evaluated. Both global and regional coronary territory stress and rest MBF were derived using 82Rb PET. Coronary artery stenosis severity was assessed using quantitative coronary angiography (QCA) performed within 3 months of PET. A total of 189 patients were followed for a median of 4.1 years. The results showed a weak correlation between regional MFR impairment (<1.7) and stenosis severity in the left descending artery (r = −0.20, P = 0.005), left circumflex artery (r = −0.15, P = 0.042), and right coronary artery (r = −0.26, P < 0.001). In addition, a weak correlation was observed between global MFR and stenosis in any vessel, in both binary and continuous analyses. However, impairment in MFR within any territory was associated with increased all-cause mortality in both unadjusted and adjusted analyses. In conclusion, this is the first large-scale study to examine the relationship between regional coronary territory MBF, coronary artery stenosis severity as assessed using QCA, and mortality. Although coronary territory MFR demonstrated a weak correlation with coronary stenosis severity, impairment in per-territory MFR was significantly associated with increased all-cause mortality, suggesting that mechanisms such as diffuse atherosclerosis and/or microvascular disease may be contributing factors.

Influence of Pathophysiological Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes.

Diffuse coronary artery disease (CAD) impacts the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiological CAD patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularisation and procedural outcomes. This prospective, investigator-initiated, single-arm, multicentre study enrolled patients with at least one epicardial lesion with an FFR ≤ 0.80 scheduled for PCI. Manual FFR pullbacks were employed to calculate PPG. The primary outcome of optimal revascularisation was defined as a post-PCI FFR ≥ 0.88. 993 patients with 1044 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, and post-PCI FFR 0.87 ± 0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI 0.61-0.69, p<0.001) and demonstrated excellent predicted capacity for optimal revascularisation (AUC 0.82, 95% CI 0.79-0.84, p<0.001). Conversely, FFR alone did not predict revascularisation outcomes (AUC 0.54, 95% CI 0.50-0.57). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared to those with focal disease (OR 1.71, 95% CI: 1.00-2.97). Pathophysiological CAD patterns distinctly affect the safety and effectiveness of PCI. The PPG showed an excellent predictive capacity for optimal revascularisation and demonstrated added value compared to a FFR measurement.

Comparative Assessment of Treatment Outcomes of Various Myocardial Revascularization Strategies in Patients with Diffuse Coronary Artery Disease

Comparative Assessment of Treatment Outcomes of Various Myocardial Revascularization Strategies in Patients with Diffuse Coronary Artery Disease

Coronary Computed Tomographic Angiography Findings in Diabetic Patients: A tertiary clinic findings

In coronary artery disease, it is important to define the plaque characteristics and the risk factor modifications in diabetic and nou-diabetic patients. In diabetic patients, diffuse atherosclerosis is more frequently seen and acute coronary syndromes are usuaIIy the result of a rupture from an atherosclerotic plaque which is not critically stenotic. For this reason, recognizing early coronary artery atherosclerosis is important for prevention of progression, and complications. In our study, we evaluated diabetic patients with bypass history, coronary stents, and suspected of atherosclerosis by using MDCT. We scanned a total 252 patients with CT angiography. 75 patients with bypass and 26 patients with stents. We found that 40 patients (15%) had 1, 32 patients (12.7%) had 2, 34 patients (13.5%) had 3, 12 patients (4.8%) had 4, 1 patient (4%) had 5 arteries with at least 30% stenosis. In 133 patients, the stenosis was less than 30%. In 151 patients suspected of atherosclerosis without bypass or stent history, mostly soft atherosclerotic plaques were found (115 calcified plaques (74,2%), 124 soft plaques (80%). 68 mixed plaque (43,9%). Of 75 patients with bypass history, 57 (76%) patients had patent bypass grafts without stenosis and 18 (24%) patients had at least one stenotic bypass graft. In 12 of 26 patients with stents, invasive angiography was performed and sensitivity and specificity of coronary CT angiography were 80% and 100% in showing the stenosis. In 252 diabetic patients, the relationship between the LDL levels and plaque types (calcified, mixed, soft) and the severity of the stenosis in the proximal. middle or distal areas of the coronary arteries were not statistically significant. In conclusion, high quality coronary CT angiography permits evaluation of bypass grafts, stent restenosis, and coronary arteries nou-invasively in diabetic patients

Angiography-derived physiological patterns of coronary artery disease: implications with post-stenting physiology and long-term clinical outcomes.

Physiological patterns of coronary artery disease (CAD) have emerged as potential determinants of functional results of percutaneous coronary interventions (PCI) and of vessel-oriented clinical outcomes (VOCE). In this study, we evaluated the impact of angiography-derived physiological patterns of CAD on post-PCI functional results and long-term clinical outcomes. Pre-PCI angiography-derived fractional flow reserve (FFR) virtual pullbacks were quantitatively interpreted and used to determine the physiological patterns of CAD. Suboptimal post-PCI physiology was defined as an angiography-derived FFR value ≤ 0.91. The primary endpoint was the occurrence of VOCE at the longest available follow-up. Six hundred fifteen lesions from 516 patients were stratified into predominantly focal (n = 322, 52.3%) and predominantly diffuse (n = 293, 47.7%). Diffuse pattern of CAD was associated with lower post-PCI angiography-derived FFR values (0.91 ± 0.05 vs. 0.94 ± 0.05; p = 0.001) and larger rate of suboptimal post-PCI physiology (43.0 vs. 22.7%; p = 0.001), as compared to focal CAD. At the median follow-up time of 37months (33-58), post-PCI suboptimal physiology was related to a higher risk of VOCE (16.2% vs. 7.6%; HR: 2.311; 95% CI 1.410-3.794; p = 0.0009), while no significant difference was noted according to baseline physiological pattern. In diffuse disease, the use of intracoronary imaging was associated with a lower incidence of long-term VOCE (5.1% vs 14.8%; HR: 0.313, 95% CI 0.167-0.614, p = 0.030). Suboptimal post-PCI physiology is observed more often in diffusely diseased arteries and it is associated with higher risk of VOCE at follow-up. The use of intravascular imaging might improve clinical outcomes in the setting of diffuse CAD.

Comparison of the Effect of Non-HDL-C/HDL-C Ratio on Coronary Slow Flow with Other Non-Traditional Lipid Markers.

Coronary slow flow (CSF) is a microvascular disease characterized by delayed opacification of the epicardial coronary arteries during angiography. The main pathogenesis of CSF is endothelial dysfunction caused by diffuse atherosclerosis. Dyslipidemia is one of the primary factors raising the risk of atherosclerosis. Compared to conventional lipid profiles, non-traditional lipid profiles more accurately reflect dyslipidemic status. In this work, we compared the non-high density lipoprotein-cholesterol (HDL-C)/HDL-C ratio (NHHR) with other conventional and non-conventional lipid profiles in order to determine its impact on CSF. A total of 9112 subjects who underwent coronary angiography were screened retrospectively, of whom 130 subjects with CSF and 130 subjects with normal CF were included. Multivariate regression analysis was used to identify independent predictors of CSF. Additionally, in order to predict CSF, the diagnostic accuracies of NHHR and other non-traditional lipid profiles were examined. There were significantly higher non-traditional lipid profiles in the CSF group (all p < 0.001). Compared to other non-traditional lipid profiles, NHHR had a stronger association with thrombolysis in myocardial infarction frame count (r = 0.3593, p < 0.0001). In addition to NHHR, non-HDL-C, Castelli's risk index-II, atherogenic index of plasma, plasma glucose, dyslipidemia, smoking, and body mass index were identified as independent predictors of CSF. The ability of NHHR to detect CSF was superior to other non-traditional lipid profiles (area under the curve: 0.785; confidence interval: 0.730-0.840; p < 0.001). NHHR was found to be a potent and reliable predictor of CSF. This indicates that NHHR can be used as a reliable biomarker for risk stratification of CSF.

Coronary artery disease multivessel not amenable to revascularization: contemporary cohort

Severe diffuse coronary artery disease with anatomy that is not amenable to revascularization represents a poorly studied entity, with a poorly defined prognosis and prevalence, associated with high morbidity and mortality, poor quality of life and high hospitalization rates. Due to the limited evidence in this clinical field and the absence of contemporary studies, we decided to explore this line of research, determining epidemiological, clinical and prognostic aspects. Analytical, retrospective observational cohort study, carried out in a National Medical Center. The prevalence of three-vessel coronary artery disease not susceptible to revascularization was 12.2%, the majority were men (66%), over 65 years of age, with a high burden of comorbidities: pharmacological management consisted of beta blockers (91.5 %), antiplatelet aggregation (95.3%) and statins (95.3%): cardiovascular mortality was 9.4%, with myocardial infarction occurring in 10.4%: the predictor variables of mortality were chronic kidney disease, age over 70 years, insufficiency mitral valve. Coronary artery disease of three vessels not susceptible to revascularization continues to be a frequent entity, with a high-risk clinical and anatomical profile, with a better contemporary prognosis despite the multiple gaps in knowledge that limit its understanding and treatment.

NON–RESPONSE TO INCLISIRAN THERAPY IN THREE PATIENTS WITH STATIN INTOLERANCE: A CASE SERIES

Abstract Background Inclisiran is the first silencing–RNA therapy used to reduce LDL–C. It is also recommended in patients with statin intolerance. We describe a case series of three no–responder patients to inclisiran. Case Series 64–year–old man with medical history of type II diabetes mellitus, obesity, hypertension, chronic kidney disease (eGFR 38 ml/min/1.73 m^2), dyslipidemia and statin intolerance. In 2022 the coronary angiography showed diffuse atherosclerosis without significant stenosis. His LDL–c was 115 mg/dl. Rosuvatatin 10 mg was prescribed however it was withdrawn due myalgia. Inclisiran and ezetimibe were prescribed, however one, three and four months later his LDL–C was 96 mg/dl, 114 mg/dl, and 115 mg/dl respectively (Fig 1). Due to the lack of effect, lovastatin 20 mg was added after the third dose of inclisiran, reaching LDL–C levels of 100 mg/dl one month after the initiation of lovastatin. Inclisiran was withdraw (as well as statin due to myalgia) and evolocumab 140 mg was administrated three months later the last dose of inclisiran. Ten days after evolocumab, LDL value was 66 mg/dl. 60–year–old man with hypertension, obesity, and dyslipidemia (LDL 152 mg/dl) with a moderate cardiovascular risk (target LDL–C &amp;lt;70 mg/dl). Patient refused statin therapy because he was scared about myalgia. In October 2021 (first Italian patient out of clinical trial) inclisiran was administrated. However, LDL–C did not change one month after the first and the second dose (147 mg/dl and 134 mg/dl respectively, Fig1). Due to the inefficacy, inclisiran was withdraw and the combination rosuvastatin and ezetimibe 10/10 mg was started with a reduction in LDL–cholesterol levels (51 mg/dl) four months later. However, this treatment was withdrawn due to myalgia in favor of bempedoic acid. One month later LDL–C level was 79 mg/dl. 79–year–old woman with history of coronary revascularization. She was statin and ezetimibe–intolerant, so she was treated with alirocumab 150 mg (LDL–C 89 mg/dl). Since the treatment was ineffective to reach the LDL target values, alirocumab was stopped in favor to inclisiran. However, LDL values increased over the time reaching 103 mg/dl one month after the first dose and 120 mg/dl two months later the second dose (Fig1). Conclusion some patients may be no–responder to inclisiran. A polymorphism of the asialoglycoprotein receptors might be a possible reason. Statin intolerance may also affect inclisiran efficacy.

One-Year Outcomes of Long Coronary Drug-Eluting Stents (≥40 MM) in Patients With Diffuse Coronary Artery Disease: Findings From a Tertiary Care Hospital in North India.

Background and objective Diffuse coronary artery disease (CAD) is associated with extensive involvement of coronary arteries, necessitating the useof long (≥40 mm) drug-elutingstents (DES) based on the lesion length. However, these long DES can lead to complications such as in-stent restenosis (ISR) and stent thrombosis. This study aimed to assess the safety, efficacy, and one-year clinical outcomes of using long DESin patients with diffuse CAD undergoing PCI at a tertiary care hospital in north India. Methodology Patients with diffuse CAD undergoingPCI with longDESbetween January 2017 and June 2022 were included in the study. Baseline characteristics were recorded, and patients were followed up telephonically or in the outpatient department (OPD) at one, three, six, and 12 months following the PCI. The primary endpointwas the target lesion failure (TLF) rate, with secondary endpoints constituting all-cause mortality, major adverse cardiovascular events (MACE), subacute stent thrombosis, and ISR. Results A total of 200 patients were recruited and followed up for one year. The median age of the patients was 58 years (range: 48.25-63 years), and 82% were men. The most frequently stented artery was the left anterior descending (LAD, 48%), followed by the right coronary artery (RCA, 36%). A total of 388 stents (mean: 1.94 ±0.79) were implanted, including both long and short stents. The mean length and diameter of long stents were 43.64 ±3.58 mm and 3 ±0.37 mm, respectively. At the one-year follow-up, patients undergoing PCI with long DES ≥40 mm had an overall TLF rate of 5%, all-cause mortality of 6% (12 patients), MACE of 6% (12 patients), subacute stent thrombosis of 4% (eight patients), and ISR of 1% (two patients).A large proportion of patients (90%) had an uneventful follow-up of up to a year. At the one-year follow-up, all 10 (5%)patients with a primary outcomehad a smallerstent diameterthan those without a primary outcome (2.5 ±0.25 mm vs. 3.03 ±0.35 mm, p=0.015). Conclusions Our results suggest that using extremely long stents (>40 mm) for diffuse coronary lesions is safe, efficacious, and associated with relatively low event rates. In addition, the stent diameter has a substantial correlation with the primary outcome. Further studies with larger sample sizes as well as longer follow-up periods are required to validate our findings.

Synergistic Effect of Transmyocardial Revascularization and Platelet-Rich Plasma on Improving Cardiac Function After Coronary Artery Bypass Grafting.

Background Coronary artery disease (CAD) is a global health burden, contributing to mortality and morbidity. A proportion of patients with CAD suffer from diffuse CAD, where conventional revascularization techniques such as percutaneous coronary intervention and coronary artery bypass grafting (CABG) may be insufficient to adequately restore myocardial perfusion. Transmyocardial revascularization (TMR) uses a laser to create microscopic channels in the myocardium, inducing inflammation, angiogenesis, and neovascularization to improve perfusion to ischemic regions. Platelet-rich plasma (PRP) is an autologous concentrate of platelets that contains a myriad of growth factors and bioactive proteins, which have been shown to promote tissue regeneration and wound healing. The combination of TMR and PRP therapies has been proposed to synergistically enhance myocardial revascularization and functional recovery in patients with advanced CAD undergoing surgical revascularization. Methods This study evaluated the efficacy of combining TMR and PRP with CABG in improving cardiac function in diffuse CAD patients. Fifty-two patients were randomized to CABG alone (n = 16), CABG+TMR (n = 17), CABG+PRP (n = 10), and CABG+TMR+PRP (n = 9). TMR was performed using a holmium:YAG laser to create 10 channels in the inferolateral left ventricular wall. PRP was prepared from autologous whole blood and injected into the myocardium adjacent to the TMR channels. Cardiac function was assessed using speckle-tracking echocardiography preoperatively, postoperatively, and at one-year follow-up. Adverse events, including post-operative atrial fibrillation, acute kidney injury, and readmissions, were also recorded. Statistical analyses were performed to compare outcomes between the treatment groups. Results The CABG+TMR+PRP group showed significantly improved global longitudinal strain (GLS) at one year compared to CABG alone (mean GLS -15.96 vs -12.09, p = 0.02). Post-operative left ventricular ejection fraction trended higher in the TMR+PRP group (57.78%) vs other groups, but not significantly. Post-operative atrial fibrillation was higher in the TMR+PRP group (67% vs 25%, p = 0.04), potentially reflecting increased inflammation. No significant differences were observed in other adverse events. Conclusions The results of this study suggest a synergistic benefit of combining TMR and PRP therapies as an adjunct to CABG in patients with diffuse CAD. The significant improvement in GLS at one year in the TMR+PRP group compared to CABG alone indicates enhanced myocardial remodeling and functional recovery, which may translate to improved long-term outcomes. The higher incidence of postoperative atrial fibrillation in the TMR+PRP group warrants further investigation but may reflect the heightened inflammatory response necessary for angiogenesis and tissue regeneration. Prospective, randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings and optimize treatment protocols. Nonetheless, concomitant TMR+PRP therapy represents a promising approach to augmenting myocardial revascularization and recovery in patients with advanced CAD undergoing surgical revascularization.

Stronger vasoconstriction and weaker vasodilation in mesenteric arteries of Ossabaw than Göttingen minipigs before manifestation of metabolic syndrome

The metabolic syndrome predisposes and contributes to the development and progression of atherosclerosis. The minipig strain “Ossabaw” is characterized by a polygenic predisposition to develop metabolic syndrome and diffuse atherosclerosis in response to a hypercaloric atherogenic diet. The aim of this study was to investigate whether Ossabaw minipigs exhibit an altered vasomotor function even before they develop their diseased phenotype. Mesenteric arteries of adult Ossabaw (n=30) and Göttingen minipigs (n=40), a pig strain without genetic predisposition to a metabolic syndrome, were harvested postmortem, dissected, and mounted on a myograph for isometric force measurements. Maximal vasoconstriction to smooth muscle cell depolarization with potassium chloride (KClmax) was repeatedly induced (twice 0.6×10−1 mol/L and twice 1.2×10−1 mol/L). Cumulative concentration-response curves were determined in response to 1×10−9 -1×10−4 mol/L norepinephrine. Endothelium-dependent and -independent vasodilation were analyzed in response to carbachol and nitroprusside, respectively (1×10−9 - 1×10−4 mol/L, each) after pre-constriction by norepinephrine. The baseline diameter of mesenteric arteries from Ossabaw minipigs was smaller than that from Göttingen minipigs (329±20 vs. 435±11 μm), and mesenteric arteries of Ossabaw minipigs developed a higher baseline force of contraction than mesenteric arteries of Göttingen minipigs (6.2±0.7 vs. 3.6±0.3 mN). The maximal vasoconstrictor response to KCl was comparable between the minipig strains. Vasoconstriction in response to norepinephrine was more pronounced in Ossabaw than in Göttingen minipigs (143±9 vs. 108±6% KClmax). Endothelium-dependent vasodilation (46.4±5.5 vs. 16.0±3.0% of norepinephrine-induced preconstriction) and -independent vasodilation (36.7±4.9 vs. 2.3±0.6% of norepinephrine-induced preconstriction) were less pronounced in Ossabaw than in Göttingen minipigs. Neither the differences in baseline diameter nor in baseline developed force of contraction had any effect on the above data, as analyzed in retrospectively matched subsets of mesenteric arteries with a comparable baseline diameter or a comparable baseline developed force of contraction, respectively. Even before the development of metabolic syndrome, vasomotor function is shifted to more vasoconstriction and less vasodilation in Ossabaw minipigs, suggesting a genetic predisposition for the early development of vascular dysfunction. Thus, Ossabaw minipigs may be a suitable model to reflect the human situation of a heterogeneous, genetically determined primordial risk constellation for vascular dysfunction. This work was supported by the German Research Foundation [SFB 1116 B08 to G.H. and P.K.] and the European COST ACTION in CARDIOPROTECTION [CA16225 to G.H. and IG16225 to G.H. and P.K.]. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Correction to: Intravascular Imaging Findings After PCI in Patients With Focal and Diffuse Coronary Artery Disease.

Correction to: Intravascular Imaging Findings After PCI in Patients With Focal and Diffuse Coronary Artery Disease.

The Role of Coronary Physiology Assessment in the Diagnosis and Treatment of Stable Angina. Dive Inside Recent Findings of Diffuse Coronary Disease Treatment.

Coronary physiology is widely used to assess epicardial coronary lesions in patients with stable angina. Based on the available evidence, physiology plays a crucial role in diagnosing and treating patients. There have been invasive methods for determining cardiac physiology, such as fractional flow reserve and instantaneous wave-free ratio. Still, new non-invasive approaches provide extra anatomical information, such as fractional flow reserve computed tomography (FFR-CT) based on computed tomography and physiology based on angiography. Even though FFR-guided percutaneous coronary intervention (PCI) is clinically beneficial, one-third of patients retain suboptimal FFR after the procedure, associated with severe adverse events, rendering PCI in diffuse coronary artery disease questionable. Using the pullback pressure gradient (PPG), we can analyze the magnitude and extent of pressure losses; a lower value may indicate diffuse disease, while a high value with an abrupt curve may indicate focal disease. Since PCI is not the best option for treating diffuse coronary disease, current strategies focus on conservatively using medical therapy or bypass surgery. It has been demonstrated that patients with diffuse disease of the left anterior descending (LAD) are at a greater risk of developing occlusion of the left internal mammary artery graft than those with focal disease and that maximal medical therapy may be the most effective treatment for these patients.

Endarterectomy may be an effective additional treatment for three diffuse coronary artery disease complicated with diabetes.

In order to evaluate the clinical efficacy of coronary endarterectomy (CE) and coronary artery bypass grafting (CABG) in patients with diabetes complicated with three diffuse coronary artery stenosis. A retrospective analysis was conducted on 460 patients with diabetes mellitus and diffuse three-vessel coronary artery disease who underwent CABG in our department from September 2015 to December 2021. The patients were divided into two groups according to whether they underwent CE: the simple CABG group (group A, n = 254) and the CABG combined CE group (group B, n = 206). The perioperative outcomes, recurrent angina pectoris during 1-year follow-up, and the patency rate of the grafted vessel in coronary CT angiography were compared between the two groups. There was no significant difference in the 30days mortality rate between the two groups (2.3% vs 2.4%, p < 0.05). Group A had a shorter operation time [(3.55 ± 0.59) h versus (4.35 ± 0.65) h], less bypass grafts [(2.72 ± 0.83) versus (3.65 ± 0.72) vessels/case], a lower incidence of perioperative myocardial infarction (7.1% vs 12.6%), and a lower number of patent graft vessels at 1-year follow-up [(2.15 ± 0.42) versus (2.88 ± 0.68) vessels/case] compared with group B (all p < 0.05). Group A had a higher incidence of recurrent angina during follow-up (14.49% vs 6.47%) (p < 0.05). Although there was no significant difference in the incidence of MACCE events between the two groups, the probability of revascularization was higher in group A. Compared with single CABG, combined CE in patients with diabetes mellitus and diffuse three-vessel coronary artery disease can achieve more complete revascularization, reduce the recurrence of angina pectoris and the needing of postoperative revascularization, but the incidence of perioperative myocardial infarction is higher.

Early tirofiban versus heparin for bridging dual antiplatelet therapy in patients undergoing coronary endarterectomy combined with coronary artery bypass grafting: a multicenter randomized controlled trial protocol (the THACE-CABG trial)

BackgroundFor complete revascularization, patients with diffuse coronary artery disease should have a coronary endarterectomy and a coronary artery bypass graft (CE-CABG). Sadly, CE can lead to a lack of endothelium, which raises the risk of thrombotic events. Even though daily dual antiplatelet therapies (DAPT) have been shown to reduce thrombotic events, the risk of perioperative thrombotic events is high during the high-risk period after CE-CABG, and there is no consistent protocol to bridge DAPT. This trial aims to compare safety and efficacy between tirofiban and heparin as DAPT bridging strategies after CE-CABG.MethodsIn phase I, 266 patients undergoing CE-CABG will be randomly assigned to tirofiban and heparin treatment groups to compare the two treatments in terms of the primary safety endpoint, chest tube drainage in the first 24 h. If the phase I trial shows tirofiban non-inferiority, phase II will commence, in which an additional 464 patients will be randomly assigned. All 730 patients will be studied to compare major cardiovascular and cerebrovascular events (MACCEs) between the groups in the first 30 days after surgery.DiscussionGiven the possible benefits of tirofiban administration after CE-CABG, this trial has the potential to advance the field of adult coronary heart surgery.Trial registrationchictr.org.cn, ChiCTR2200055697. Registered 6 January 2022. https://www.chictr.org.cn/com/25/showproj.aspx?proj=149451. Current version: 20,220,620.

One-year outcomes after off-pump coronary artery bypass grafting in diffuse coronary atherosclerosis

One-year outcomes after off-pump coronary artery bypass grafting in diffuse coronary atherosclerosis