Assessment of Plaque Characteristics by Contrast-Enhanced Ultrasound and Stent Restenosis following Carotid Artery Stenting: A Retrospective Study.

Background and objective: carotid artery stenosis contributes significantly to ischemic strokes, with management options including carotid endarterectomy (CEA) and carotid artery stenting (CAS) ischemic stroke risk can be reduced. Controversies persist regarding their efficacy and factors influencing complications, and understanding the relationship between atherosclerotic plaque characteristics and stent restenosis after CAS is crucial. Methods: we conducted a retrospective study involving 221 patients who underwent CAS for symptomatic or asymptomatic carotid artery stenosis. Comprehensive assessments of plaque morphology were performed using contrast-enhanced ultrasound (CEUS) before CAS. Patient demographics, including smoking status and diabetes, were also recorded. Stent restenosis was diagnosed using various imaging modalities, including ultrasound, angiography, and digital subtraction angiography (DSA). Results: plaque analysis using CEUS revealed a significant association between plaque grade and restenosis incidence (p < 0.001), particularly with grade 0 (11.1%) and grade 2 plaques (66.7%). Smoking was notably associated with plaque vascularization and restenosis (p < 0.001), while diabetes did not significantly impact plaque characteristics or restenosis risk (p > 0.05). The mean duration of restenosis was 17.67 months. Stenting was the most frequent treatment modality for restenosis (70.6%). However, no significant relationship was found between restenosis type and plaque morphology (p = 0.268). Furthermore, while no clear relationship was observed between plaque morphology and the type of restenosis, our findings underscored the importance of plaque characterization in predicting post-CAS outcomes. Conclusions: this study highlights the utility of CEUS in predicting stent restenosis following CAS. There was a significant association between stent restenosis within 12-24 months after the carotid stenting procedure and an elevated grade of plaque vascularization. Moreover, one of the main factors possibly determining the grade of plaque vascularization was smoking. Further research is warranted to elucidate the underlying mechanisms and refine risk stratification in this patient population.

Assessment of atherosclerotic plaque morphology using contrast-enhanced ultrasound and its impact on primary cardiovascular events following simultaneous carotid endarterectomy and coronary artery bypass grafting.

OBJECTIVE: The incidence of stroke after on-pump cardiac surgery during the perioperative period can affect up to 2% of patients, and is frequently linked to carotid artery disease. Notably, in patients with significant unilateral carotid artery stenosis of 80%-99%, the risk of stroke reaches 4%. Among individuals undergoing coronary artery bypass grafting (CABG), 3% to 10% exhibit significant carotid artery stenosis. To mitigate the risk of stroke and mortality, patients can undergo either simultaneous or staged carotid endarterectomy and CABG. The aim of this study was to assess whether early postoperative complications, including stroke, following simultaneous CABG/CAE procedures, correlate with morphological attributes of carotid plaque, assessed via contrast-enhanced ultrasound. METHODS: A single centre retrospective analysis was performed including 62 patients who underwent simultaneous CABG/CEA between 2019 and 2022. Our study excluded patients who underwent staged carotid endarterectomy and CABG procedures, off-pump CABG, or those necessitating urgent CABG. Our analysis focused on patients meeting elective CABG criteria, diagnosed with symptomatic triple-vessel or left main trunk coronary artery disease (CAD), alongside asymptomatic carotid stenosis (a. carotis internae) exceeding 70% or symptomatic ipsilateral carotid stenosis surpassing 50%. The extent of contralateral carotid artery stenosis was not taken into account. Prior to the CEA/CABG procedure, each patient underwent contrast-enhanced ultrasound to assess atherosclerotic lesions, which were classified using Nakamura et al.'s classification. Among the patients, 37.1% exhibited no neovascularisation within the atherosclerotic plaque, 56.5% showed insignificant neovascularisation, and 6.5% displayed notable neovascularization within the plaque. Our study aimed to establish a connection between the degree of plaque vascularisation identified through contrast-enhanced ultrasound and subsequent postoperative complications. RESULTS: Upon evaluating postoperative complications occurring within 30 days after the surgery and the plaque morphology identified through contrast-enhanced ultrasound, a statistically significant correlation was observed between a higher grade of plaque vascularisation and the occurrence of ischaemic stroke (r = 0.329, p = .008). Monte Carlo calculations of the Chi-square test indicated a significant association between a higher grade of plaque vascularisation and the presence of peripheral artery disease (χ2 = 15.175, lls = 2, p = .003). CONCLUSION: Within 30 days of surgery, a significant correlation exists between the occurrence of ischaemic stroke following carotid endarterectomy subsequent to CABG and the presence of a higher grade plaque vascularisation as identified by contrast-enhanced ultrasound.

The Effect of Platelet Activity, ABCB1 Genetic Polymorphism, and Renal Function on the Development of Ticagrelor-Related Dyspnea in Patients with Acute Coronary Syndrome.

Purpose: The aim of this study was to determine the effect of ABCB1 genetic polymorphism and renal function on the occurrence of ticagrelor-related dyspnea. Patients and Methods: A total of 299 patients with acute with type 1, 2, or 3 myocardial infarction (with and without ST-segment elevation), who underwent coronary angiography and PTCA with stent implantation and were treated with antiplatelet drugs (ticagrelor and aspirin), were enrolled in this prospective study. For all enrolled patient's platelet aggregation (induction with high-sensitivity adenosine diphosphate, ADP HS) testing was performed using a MULTIPLATE® analyzer. Venous blood was also collected for genotyping. Results: Patients experiencing ticagrelor-related dyspnea had lower ADP HS value (ADP HS ≤ 19.5 U; OR = 2.254; P = 0.009), higher creatinine concentration (>90 µmol/l; OR = 3.414; P = 0.019), and lower GFR value (<60 mL/min/1.73 m2; OR = 2.211; P = 0.035). ABCB1 T allele was associated with ticagrelor-related dyspnea (OR = 2.550; P = 0.04). Conclusion: Ticagrelor-related dyspnea was found to be related to low platelet aggregation, increased plasma creatinine concentration, decreased GFR, and ABCB1 T allele. Carriers of the ABCB1 T allele had a higher plasma creatinine concentration that could be associated with an inhibitory effect of ticagrelor on P-glycoprotein function.

The Impact of Polymorphisms in ATP-Binding Cassette Transporter Genes on Anthracycline-Induced Early Cardiotoxicity in Patients with Breast Cancer.

BACKGROUND: Cardiac side effects associated with anthracycline-based treatment may seriously compromise the prognosis of patients with breast cancer (BC). Evidence shows that genes that operate in drug metabolism can influence the risk of anthracycline-induced cardiotoxicity (AIC). ATP-binding cassette (ABC) transporters could serve as one of the potential biomarkers for AIC risk stratification. We aimed to determine the link between single-nucleotide polymorphisms (SNPs) in several ABC genes (ABCB1 rs1045642, ABCC1 rs4148350, ABCC1 rs3743527) and cardiotoxicity. METHODS: The study included 71 patients with BC, who were treated with doxorubicin-based chemotherapy. Two-dimensional echocardiography and speckle-tracking echocardiography were performed. AIC was defined as a new decrease of 10 percentage points in the left ventricular ejection fraction (LVEF). SNPs in ABCB1 and ABCC1 genes were evaluated using real-time PCR. RESULTS: After a cumulative dose of 236.70 mg/m2 of doxorubicin, 28.2% patients met the criteria of AIC. Patients who developed AIC had a larger impairment in left ventricular systolic function compared to those who did not develop AIC (LVEF: 50.20 ± 2.38% vs. 55.41 ± 1.13%, p < 0.001; global longitudinal strain: -17.03 ± 0.52% vs. -18.40 ± 0.88%, p < 0.001). The ABCC1 rs4148350 TG genotype was associated with higher rates of cardiotoxicity (TG vs. GG OR = 8.000, 95% CI = 1.405-45.547, p = 0.019). CONCLUSIONS: The study showed that ABCC1 rs4148350 is associated with AIC and could be a potential biomarker to assess the risk of treatment side effects in patients with BC.

Relationships of Whole-Heart Myocardial Mechanics and Cardiac Morphometrics by Transthoracic Echocardiography with Main Prognostic Factors of Heart Failure in Non-Ischemic Dilated Cardiomyopathy.

BACKGROUND: there are many prognostic factors of heart failure (HF) based on their evaluation from imaging, to laboratory tests. In clinical practice, it is crucial to use widely available, cheap, and easy-to-use prognostic factors, such as left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, 6 min walk test (6MWT), B-type natriuretic peptide (BNP), etc. We sought to evaluate the relationships between whole-heart myocardial mechanics and cardiac morphometrics with the main commonly used prognostic factors of HF in patients with non-ischemic dilated cardiomyopathy (NIDCM). METHODS AND RESULTS: two-dimensional (2D) echocardiography for myocardial mechanics (global longitudinal, radial, and circumferential strains of the left ventricle; right ventricular longitudinal strain; strain values of reservoir, conduit, and contraction function of both atria) and cardiac morphometric (diameters and volumes of both atria and ventricles) parameters were performed, and the HF main traditional prognostic factors were identified. We assessed 109 patients (68.8% male; 49.7 ± 10.5 years) with newly diagnosed NIDCM. Myocardial mechanics and morphometrics were weakly correlated with the patient's age, gender, and smoking (R = 0.2, p < 0.05). Stronger relationships were observed with NYHA class, 6MWT, and BNP (the strongest correlations were with LVEF: R = -0.499, R 0.462, R = -0.461, p < 0.001, respectively). There were moderately strong correlations with LVEF and other whole-heart myocardial mechanics or morphometrics. Moreover, LVEF with global regurgitation volume (GRV) and right ventricle free wall longitudinal strain (RVFWLS) were the most usually detected parameters in multivariate analysis to be associated with changes in HF prognostic factors. CONCLUSIONS: in NIDCM patients, the main prognostic factors of HF are correlated with whole-heart myocardial mechanics and morphometrics. However, LVEF, GRV, and RVFWLS are the most usually found 2D echocardiographic factors associated with changes in HF prognostic factors.

Instantaneous wave free ratio value impact on left internal mammary artery graft patency.

OBJECTIVES: To assess whether instantaneous wave - free ratio (iFR) value is associated with left internal mammary artery (LIMA) graft failure at 12 months follow-up post coronary artery bypass graft (CABG). BACKGROUND: Data suggests bypass to a non-significant left anterior descending artery (LAD) lesion due to visual over-estimation may lead to LIMA graft failure. Implementing iFR may result in better arterial graft patency. METHODS: In iCABG (iFR guided CABG) study patients planned to undergo an isolated CABG procedure was prospectively enrolled and iFR was performed for LAD. Coronary computed tomography angiography was performed at 2 and 12 months follow-up. The primary endpoint of this study was to determine the rate of LIMA graft occlusion or hypoperfusion at 2 and 12-months follow-up. We considered a composite secondary endpoint of Major adverse cardiovascular and cerebrovascular event (MACCE) as a secondary outcome. RESULTS: In total 69 patients were included with no differences regarding age, sex and risk factors. At 2 months, 50 of LIMAs with pre-CABG iFR median 0.855 (0.785 - 0.892) were patent. Hypoperfusion was found in 8 LIMAs (median iFR 0.88 (0.842 - 0.90)). While, 7 LIMAs (median iFR 0.91 (0.88 - 0.96)) were occluded (p = 0.04). At 12 months, when iFR of LAD was >0.85: just 12 (31.6% out of all patent LIMAS) grafts were patent and 24 (100.0% out of all hypoperfused/occluded) grafts were hypoperfused or occluded (p < 0.001). In terms of MACCE, no difference (p = 1.0) was found between all 3 groups divided according to iFR value. CONCLUSIONS: Instantaneous wave - free ratio value above 0.85 in LAD is a powerful tool predicting LIMA graft failure at 1-year follow up period.

Subthreshold High-Frequency Electrical Field Stimulation Induces VEGF Expression in Cardiomyocytes.

Subthreshold electrical stimulation (SES) has been shown to induce an improvement of angiogenesis in ischemic and nonischemic skeletal muscles, mediated by increased VEGF expression. VEGF plays a key role in physiological and pathological angiogenesis. Cardiomyocytes possess the ability to synthesize and secrete VEGF. Thus, we thought to investigate the effect of SES on VEGF regulation in cultured neonatal rat ventricular myocytes (NRVMs), in the aim to reveal new techniques for therapeutic angiogenesis in ischemic heart disease. Cell cultures of NRVMs were electrically stimulated with field strengths below the myocyte depolarization threshold (0.5 V/cm with 1 ms bipolar impulse duration). Frequencies ranging from 5 Hz up to 25, 50, and 99 Hz were applied over a period of 48 h. The expression of VEGF and its receptor KDR was determined with Western blot and ELISA. To reveal the biological activity of the secreted VEGF amount, cultured human coronary artery endothelial cells (HCAECs) were treated with the cell culture supernatant of NRVMs exposed to SES. A dominant effect of SES was observed at 25 Hz. Within this particular frequency the VEGF protein amount in the cytoplasm as well as in the cell culture supernatant increased significantly. In parallel, the protein expression of the KDR receptor decreased in a significant manner. Moreover, cell culture supernatant of NRVMs exposed to SES augmented the growth of HCAECs. Cardiomyocytes respond to SES with an increase in biologically active VEGF expression that promotes cell proliferation of HCAECs. This mechanism may provide new approaches to develop therapeutic angiogenesis in the ischemic heart.

Decreased plasminogen activator inhibitor and tissue metalloproteinase inhibitor expression may promote increased metalloproteinase activity with increasing duration of human atrial fibrillation.

INTRODUCTION: Atrial fibrosis has been shown to concur with the persistence of atrial fibrillation (AF) and is only incompletely reversible, thus counteracting attempts to restore and maintain sinus rhythm (SR). Besides the angiotensin system, the matrix metalloproteinases (MMP) play a major role in the pathogenesis of fibrosis. Thus, the present study investigated changes of the MMP system during the development of human AF. METHODS AND RESULTS: Right atrial appendages of 146 patients were excised during heart surgery and grouped according to rhythm (SR vs AF) and AF duration. Hydroxyproline as a surrogate for collagen content and morphometrically determined collagen content increased significantly from SR (14.3 +/- 7.7%) to chronic permanent AF (CAF) of 6-24 months (21.2 +/- 9.2%, P = 0.02), and CAF of > 60 months (25.3 +/- 4.7%, P < 0.01). From SR to paroxysmal and chronic persistent AF (CPAF) and to CAF MMP-2 and MMP-9 activity rose, while their mRNA and protein levels were not altered significantly. Plasminogen activator inhibitor (PAI), an inhibitor of a potent activator of many MMPs, was significantly decreased with increasing duration of AF. In parallel, the mRNA levels of the tissue inhibitors of MMPs TIMP-1 and -2 decreased significantly. CONCLUSION: Human atrial fibrogenesis is enhanced with increasing duration of AF: a longer AF duration is associated with elevated atrial interstitial MMP activity, but decreased PAI and TIMP expression.

Simultaneous transesophageal cardioversion and echocardiography: feasibility and safety.

BACKGROUND: Transesophageal echocardiography (TEE) is routinely used to exclude atrial thrombus prior to cardioversion of atrial fibrillation (AF). Because the TEE probe lies adjacent to the atria, cardioversion using an electrode attached to the TEE probe should allow for immediate low-energy transesophageal cardioversion. OBJECTIVE: The purpose of this study was to evaluate a cardioversion electrode sheath that can be affixed to conventional TEE probes for simultaneous thrombus exclusion and cardioversion of AF. METHODS: A thin electrode was integrated into a latex or polyurethane sheath covering a conventional TEE probe. TEE thrombus exclusion and biphasic transesophageal cardioversion using a step-up protocol were performed during deep sedation. Esophagoscopy was performed immediately after cardioversion and after 1 week. RESULTS: TEE was performed in 27 patients. One patient showed left atrial thrombi. Transesophageal cardioversion was successful in 25 of the remaining 26 patients. Mean atrial cardioversion threshold was 63 +/- 48 J. Transesophageal cardioversion restored sinus rhythm in two patients with unsuccessful transthoracic cardioversion. Transesophageal cardioversion in deep sedation was well tolerated. Esophagoscopy revealed slight mucosal damage in three patients at the site of shock application; two of these patients showed signs of gastroesophageal reflux disease. Mucosal damage unrelated to the site of shock delivery was noted in three patients. CONCLUSION: Atrial thrombus exclusion and transesophageal cardioversion of AF via a disposable cardioversion sheath offers the opportunity to perform transesophageal cardioversion and TEE thrombus exclusion during one sedation. It may not be suitable for use in patients with gastroesophageal reflux disease. Transesophageal cardioversion may establish sinus rhythm in selected patients refractory to transthoracic cardioversion.

Imaging of the coronary venous system: retrograde coronary sinus angiography versus venous phase coronary angiograms.

BACKGROUND: Left ventricular lead implantation for cardiac resynchronization therapy (CRT) usually requires a pre- or intraprocedural occlusion contrast venography of the coronary sinus (CS) in order to identify tributaries to the lateral wall. As many patients undergo a preprocedural coronary angiogram, we investigated the diagnostic accuracy of venous phase imaging of the CS in patients prior to CRT implantation. The aim of this study was to assess the quality of venous phase coronary sinus angiography. METHODS: In 24 CRT patients retrograde occlusion venography and venous phase coronary sinus angiography obtained during coronary angiography were compared with respect to image quality, vessel diameters and the ability to identify a coronary sinus side branch suitable for left ventricular lead placement. RESULTS: Suitable target vessels for left ventricular lead implantation were identified in all patients irrespective of the method (retrograde occlusion venography or venous phase coronary sinus angiography). There was a high concordance in vessel diameters between venous phase and retrograde angiography. Visibility was superior in retrograde venography. CONCLUSIONS: In heart failure patients who are scheduled for coronary angiograms venous phase coronary sinus angiography is a time-saving and easy to perform alternative imaging modality. Radiation exposure and the amount of contrast medium needed is reduced as compared to coronary sinus occlusion angiography. The information obtained thereby may be used to plan subsequent CRT implantation without the need for retrograde coronary sinus angiography.