The plaque hypothesis: understanding mechanisms of plaque progression and destabilization, and implications for clinical management.

PURPOSE OF REVIEW: Major adverse cardiac events (MACE) typically arise from nonflow-limiting coronary artery disease and not from flow-limiting obstructions that cause ischemia. This review elaborates the current understanding of the mechanism(s) for plaque development, progression, and destabilization and how identification of these high-risk features can optimally inform clinical management. RECENT FINDINGS: Advanced invasive and noninvasive coronary imaging and computational postprocessing enhance an understanding of pathobiologic/pathophysiologic features of coronary artery plaques prone to destabilization and MACE. Early investigations of high-risk plaques focused on anatomic and biochemical characteristics (large plaque burden, severe luminal obstruction, thin cap fibroatheroma morphology, and large lipid pool), but more recent studies underscore that additional factors, particularly biomechanical factors [low endothelial shear stress (ESS), high ESS gradient, plaque structural stress, and axial plaque stress], provide the critical incremental stimulus acting on the anatomic substrate to provoke plaque destabilization. These destabilizing features are often located in areas distant from the flow-limiting obstruction or may exist in plaques without any flow limitation. Identification of these high-risk, synergistic plaque features enable identification of plaques prone to destabilize regardless of the presence or absence of a severe obstruction (Plaque Hypothesis). SUMMARY: Local plaque topography, hemodynamic patterns, and internal plaque constituents constitute high-risk features that may be located along the entire course of the coronary plaque, including both flow-limiting and nonflow-limiting regions. For coronary interventions to have optimal clinical impact, it will be critical to direct their application to the plaque area(s) at highest risk.

Multimodality imaging results of TAP versus novel modified TAP stenting in coronary bifurcation: From bench testing to first-in-man investigation.

OBJECTIVES: We investigated the results of T and small protrusion (TAP) versus a novel modification of TAP (mTAP) stenting by multimodality imaging in bench testing and in patients with coronary bifurcation lesions (CBL). BACKGROUND: TAP stenting is a suboptimal technique for bailout side branch (SB) stenting. METHODS: In a bench model, optical coherence tomography (OCT), microscopic examinations (ME), and computational fluid dynamics (CFD) were performed after TAP and mTAP stenting. In 20 patients with CBL, 80 intravascular ultrasound (IVUS) examinations were performed during mTAP stenting in which the SB stent was pulled-back to indent the inflated main vessel (MV) balloon and deployed while deflating it. For TAP stenting, the tip of the SB stent was positioned in the MV and deployed. RESULTS: In bench testing, OCT showed neocarina length (NL) was shorter and minimum stent area (MSA) was larger after mTAP versus TAP stenting (2.84 ± 0.70 vs. 4.80 ± 020 mm; 6.75 ± 1.50 vs. 4.5 ± 2.2 mm2 ; respectively; p < 0.05). By ME, NL was shorter and shear rate trended lower after mTAP versus TAP stenting. In patients, IVUS showed MSA was larger after versus before mTAP stenting (6.32 ± 0.58 vs. 5.21 ± 0.56 mm2 ; p < 0.01); NL was 1.43 ± 0.22 mm with SB ostium coverage. The Seattle Angina questionnaire (SAQ) score was higher at 6 months versus baseline (85 ± 4.0 vs. 48 ± 6.0, respectively; p < 0.001). CONCLUSIONS: This multimodality imaging study showed, for the first time, mTAP stenting resulted in larger stent area and shorter neocarina than TAP stenting in bench testing. In patients with CBL, mTAP stenting led to larger stent area, short neocarina with complete SB ostium coverage, and improved the SAQ score at follow-up.

A new intravascular ultrasound-guided stenting strategy compared with angiography on stent expansion and procedural outcomes in patients with positive lesion remodeling.

OBJECTIVES: We investigated the role of a new intravascular ultrasound (IVUS)-guided stenting strategy versus angiography on optimal stent expansion (OSE) and procedural outcomes in patients with positive lesion remodeling. BACKGROUND: There are no IVUS criteria on how to achieve OSE. METHODS: A total of 100 patients were assigned to a new IVUS-guided stenting strategy (IVUS group) versus angiography-guided stenting (Angio group). In the IVUS group, among patients with positive lesion remodeling, defined as a remodeling ratio (RR; lesion external elastic membrane (EEM) area/distal reference EEM area) >1.05, the stent was expanded with a balloon sized to the distal reference EEM diameter. In the Angio group, the stent was expanded by visual estimation. In both groups, IVUS was performed after postdilation. RESULTS: Minimum stent area (MSA) and stent volume index were significantly larger in the IVUS versus Angio group (7.1 ± 1.9 vs. 5.9 ± 1.5 mm2 , and 8.7 ± 2.1 vs. 7.5 ± 1.8 mm3 /mm, respectively; p < .01). The percentages of OSE, defined as an MSA ≥5.4 mm2 , MSA ≥90% of distal reference lumen area (DRLA), or MSA > DRLA, were significantly higher in the IVUS versus Angio group (80 vs. 56%, 78 vs. 54%, and 71 vs. 38%, respectively; p < .01). Stent underexpansion, malapposition, and residual reference segment stenosis were significantly higher in the Angio versus IVUS group (44 vs. 12%, 16 vs. 4%, and 12 vs. 0%, respectively; p < .05). In the IVUS group, owing to positive remodeling, there was no incidence of dissection or perforation. CONCLUSIONS: This new strategy of IVUS-guided stenting in patients with positive lesion remodeling, compared with angiography, significantly increased stent expansion and decreased stent underexpansion, malapposition, and residual reference segment stenosis with no complications.

Preemptive percutaneous coronary intervention for coronary artery disease: identification of the appropriate high-risk lesion.

PURPOSE OF REVIEW: Management of patients with coronary artery disease (CAD) has been based on identification of a coronary obstruction causing ischemia and performing a revascularization procedure to reduce that ischemia, with the goal of thereby preventing subsequent major adverse cardiac events (MACEs) in that vascular territory. Recent investigations demonstrate that preemptive percutaneous coronary intervention (PCI) of nonculprit coronary lesions (NCLs) that may not cause ischemia in patients with ST-segment elevation myocardial infarction (STEMI) reduces MACE. In this review, we focus on preemptive PCI, discuss its mechanistic benefits and speculate on its potential value for other coronary syndromes. RECENT FINDINGS: The COMPLETE trial in STEMI patients treated with primary PCI demonstrated that preemptive PCI of NCL obstructions, which may not cause ischemia, but often exhibit high-risk OCT plaque characteristics, reduced cardiovascular death or nonfatal myocardial infarction. Reduction in MACE from preemptive PCI of NCL was similar for lesions confirmed to cause ischemia (fractional flow reserve <0.80) and for lesions that were only visually assessed to have luminal obstruction at least 70%.The ISCHEMIA trial in patients with stable CAD and moderate/severe ischemia demonstrated that MACE risk increased progressively with more extensive atherosclerosis, but that performing PCI of ischemia-producing lesions did not reduce MACE. Adverse cardiac events likely originated in high-risk plaque areas not treated with PCI. SUMMARY: In STEMI patients, preemptive PCI of high-risk NCL that may not cause ischemia improves long-term MACE. In stable CAD patients, MACE increases as the atherosclerotic burden increases, but PCI of the ischemia-producing lesion itself does not improve outcomes compared with optimal medical therapy. Adverse events likely originate in high-risk plaque areas that are distinct from ischemia-producing obstructions. Identification of highest-risk atherosclerotic lesions responsible for future MACE may provide an opportunity for preemptive PCI in patients with a variety of coronary syndromes.

Spatial patterns of high-risk biomechanical metrics in plaques with abnormal vs. normal physiological flow indices.

BACKGROUND: Plaques associated with abnormally low physiological flow reserve indices are appropriate for percutaneous coronary intervention (PCI). However, recent trials demonstrate that PCI of ischemia-producing lesions does not reduce major adverse cardiac events (MACE). Low endothelial shear stress (ESS) or high ESS gradient (ESSG) are associated with MACE wherever they occur along the plaque. This study aims to determine the presence of high-risk ESS metrics in obstructive coronary plaques with high-risk (<0.80) vs. borderline-risk (0.80-0.89) vs. normal Instantaneous Wave-free Ratio (iFR) (>0.89). METHODS: We included 50 coronary arteries (50 patients) with variable iFR values who underwent coronary angiography and optical coherence tomography (OCT), followed by 3D reconstruction and computational fluid dynamics calculations of ESS/ESSG. The cohort was divided into 3 groups: iFR < 0.80, iFR 0.80-0.89, and iFR > 0.89. Spatial distribution of ESS metrics was reported along the course of each plaque, and high-risk ESS metrics and their location were compared among the 3 iFR subgroups. RESULTS: High-risk ESS features (Minimal ESS, Maximum ESSG) were similarly distributed along the course of the atherosclerotic plaque in the three iFR subgroups, both in absolute value and in location: Min ESS: 0.5 ± 0.3 vs. 0.4 ± 0.2 vs. 0.4 ± 0.2 Pa respectively (p = 0.60); Max ESSG any direction: 13.7 ± 9.4 vs. 10.4 ± 10.6 vs. 10.0 ± 7.8 Pa/mm respectively (p = 0.30). ESS metrics were spatially located up to ≥18 mm from the plaque minimal luminal area (MLA) in both directions. CONCLUSION: High-risk ESS metrics are similarly observed in plaques with normal or abnormal iFR, both in absolute value and spatial location in reference to the MLA. Utilizing iFR to identify plaques likely to cause MACE would miss the majority of plaques mechanistically at high-risk to destabilize and cause future adverse cardiac events.

Association between sleep duration and hypertension incidence: Systematic review and meta-analysis of cohort studies.

AIM: Sleep duration has been suggested to be associated with hypertension (HTN). However, evidence of the nature of the relationship and its direction has been inconsistent. Therefore, we performed a meta-analysis to assess the relationship between sleep duration and risk of HTN incidence, and to distinguish more susceptible populations. METHODS: PubMed, Embase, Scopus, Web of Science, and ProQuest were searched from January 2000 to May 2023 for cohort studies comparing short and long sleep durations with 7-8 hours of sleep for the risk of HTN incidence. Random-effect model (the DerSimonian-Laird method) was applied to pool risk ratios (RR) and 95% confidence interval (CI). RESULTS: We included sixteen studies ranging from 2.4 to 18 years of follow-up duration evaluating HTN incidence in 1,044,035 people. Short sleep duration was significantly associated with a higher risk of developing HTN (HR: 1.07, 95% CI: 1.06-1.09). The association was stronger when the sleep duration was less than 5 hours (HR: 1.11, 95% CI: 1.08-1.14). In contrast to males, females (HR: 1.07, 95% CI: 1.04-1.09) were more vulnerable to developing HTN due to short sleep duration. No significant difference between different follow-up durations and age subgroups was observed. Long sleep duration was not associated with an increased incidence of HTN. CONCLUSION: Short sleep duration was associated with higher risk of HTN incidence, however, there was no association between long sleep duration and incidence of HTN. These findings highlight the importance of implementing target-specific preventive and interventional strategies for vulnerable populations with short sleep duration to reduce the risk of HTN.

Comprehensive biomechanical and anatomical atherosclerotic plaque metrics predict major adverse cardiovascular events: A new tool for clinical decision making.

BACKGROUND AND AIMS: Anatomical imaging alone of coronary atherosclerotic plaques is insufficient to identify risk of future adverse events and guide management of non-culprit lesions. Low endothelial shear stress (ESS) and high plaque structural stress (PSS) are associated with events, but individually their predictive value is insufficient for risk prediction. We determined whether combining multiple complementary, biomechanical and anatomical plaque characteristics improves outcome prediction sufficiently to inform clinical decision-making. METHODS: We examined baseline ESS, ESS gradient (ESSG), PSS, and PSS heterogeneity index (HI), and plaque burden in 22 lesions that developed subsequent events and 64 control lesions that remained quiescent from the PROSPECT study. RESULTS: 86 fibroatheromas were analysed from 67 patients. Lesions with events showed higher PSS HI (0.32 vs. 0.24, p<0.001), lower local ESS (0.56Pa vs. 0.91Pa, p = 0.007), and higher ESSG (3.82 Pa/mm vs. 1.96 Pa/mm, p = 0.007), while high PSS HI (hazard ratio [HR] 3.9, p = 0.006), high ESSG (HR 3.4, p = 0.007) and plaque burden>70 % (HR 2.6, p = 0.02) were independent outcome predictors in multivariate analysis. Combining low ESS, high ESSG, and high PSS HI gave both high positive predictive value (80 %), which increased further combined with plaque burden>70 %, and negative predictive value (81.6 %). Low ESS, high ESSG, and high PSS HI co-localised spatially within 1 mm in lesions with events, and importantly, this cluster was distant from the minimum lumen area site. CONCLUSIONS: Combining complementary biomechanical and anatomical metrics significantly improves risk-stratification of individual coronary lesions. If confirmed from larger prospective studies, our results may inform targeted revascularisation vs. conservative management strategies.

Comparative Analysis of PCI Strategies in Aortic Stenosis Patients Undergoing TAVI: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been increasingly used in patients with severe aortic stenosis (AS). Since coronary artery disease (CAD) is common among these patients, it is crucial to choose the best method and timing of revascularization. This study aims to compare different timing strategies of percutaneous coronary intervention (PCI) in patients with severe AS undergoing TAVI to clarify whether PCI timing affects the patients' outcomes or not. METHODS: A frequentist network meta-analysis was conducted comparing three different revascularization strategies in patients with CAD undergoing TAVI. The 30-day all-cause mortality, in-hospital mortality, all-cause mortality at 1 year, 30-day rates of myocardial infarction (MI), stroke, and major bleeding, and the need for pacemaker implantation at 6 months were analyzed in this study. RESULTS: Our meta-analysis revealed that PCI during TAVI had higher 30-day mortality (RR = 2.46, 95% CI = 1.40-4.32) and in-hospital mortality (RR = 1.70, 95% CI = [1.08-2.69]) compared to no PCI. Post-TAVI PCI was associated with higher 1-year mortality compared to other strategies. While no significant differences in major bleeding or stroke were observed, PCI during TAVI versus no PCI (RR = 3.63, 95% CI = 1.27-10.43) showed a higher rate of 30-day MI. CONCLUSION: Our findings suggest that among patients with severe AS and CAD undergoing TAVI, PCI concomitantly with TAVI seems to be associated with worse 30-day outcomes compared with no PCI. PCI after TAVI demonstrated an increased risk of 1-year mortality compared to alternative strategies. Choosing a timing strategy should be individualized based on patient characteristics and procedural considerations.

Comparative effectiveness of ultrathin vs. standard strut drug-eluting stents: insights from a large-scale meta-analysis with extended follow-up.

BACKGROUND: Newer generation ultrathin strut stents are associated with less incidence of target lesion failure (TLF) in patients undergoing percutaneous coronary intervention (PCI) in the short term. However, its long-term effect on different cardiovascular outcomes remains unknown. OBJECTIVES: We aim to identify the effects of newer-generation ultrathin-strut stents vs. standard thickness second-generation drug-eluting stents (DES) on long-term outcomes of revascularization in coronary artery disease. METHODS: We searched PubMed, Web of Science, Cochrane Library databases, and Scopus for randomized controlled trials (RCTs) and registries that compare newer-generation ultrathin-strut (< 70 mm) with thicker strut (> 70 mm) DES to evaluate cardioprotective effects over a period of up to 5 years. Primary outcome was TLF, a composite of cardiac death, target vessel myocardial infarction (TVMI) or target lesion revascularization (TLR). Secondary outcomes included the components of TLF, stent thrombosis (ST), and all-cause death were pooled as the standardized mean difference between the two groups from baseline to endpoint. RESULTS: We included 19 RCTs and two prospective registries (103,101 patients) in this analysis. The overall effect on the primary outcome was in favor of second-generation ultrathin struts stents in terms of TLF at ≥ 1 year, ≥ 2 years, and ≥ 3 years (P value = 0.01, 95% CI [0.75, 0.96]), P value = 0.003, 95% CI [0.77, 0.95]), P value = 0.007, 95% CI [0.76, 0.96]), respectively. However, there was no reported benefit in terms of TLF when we compared the two groups at ≥ 5 years (P value = 0.21), 95% CI [0.85, 1.04]). Some of the reported components of the primary and secondary outcomes, such as TLR, target vessel revascularization (TVR), and TVMI, showed the same pattern as the TLF outcome. CONCLUSION: Ultrathin-strut DES showed a beneficial effect over thicker strut stents for up to 3 years. However, at the 5-year follow-up, the ultrathin strut did not differ in terms of TLF, TLR, TVR, and TVMI compared with standard-thickness DES, with similar risks of patient-oriented composite endpoint (POCE), MI, ST, cardiac death, and all-cause mortality.

Trends in Transcatheter Versus Surgical Aortic Valve Replacement Outcomes in Patients With Low-Surgical Risk: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Limited data exist on long-term outcomes after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). This meta-analysis aims to elucidate outcome trends following TAVR versus SAVR in patients with severe aortic stenosis and low-surgical risk. METHODS AND RESULTS: A systematic search was conducted in PubMed, Embase, Scopus, and the Cochrane Library databases from inception until May 2024, to identify studies comparing TAVR versus SAVR in patients with low-surgical risk (Society of Thoracic Surgeons predicted risk of mortality score <4%). The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, stroke, disabling stroke, rehospitalization, myocardial infarction, aortic valve reintervention, permanent pacemaker implantation, and new-onset atrial fibrillation. Binary random-effects models were used to compare the risk of each outcome across various follow-up intervals and the risk of bias was assessed using the Cochrane Collaboration's Risk of Bias-2 tool. The meta-analysis included 6 randomized trials including 4682 patients. TAVR was associated with a lower risk of all-cause mortality than SAVR in the 30-day (hazard ratio [HR: 0.45] [95% CI: 0.26-0.77], I2: 0%) and 30-day to 1-year (HR: 0.55 [95% CI: 0.37-0.81], I2: 16%) follow-ups. However, the risk of all-cause mortality was similar during >1-year follow-ups. TAVR was associated with a significantly lower risk of cardiovascular mortality, disabling stroke, rehospitalization, new-onset atrial fibrillation, and a higher risk of permanent pacemaker implantation compared with SAVR during the 30-day follow-up. CONCLUSIONS: TAVR was associated with a lower risk of all-cause mortality within the first year of post-procedural follow-up compared with SAVR. However, the risk of all-cause mortality was similar in >1-year follow-ups.

Enhanced stent imaging improves the diagnosis of stent underexpansion and optimizes stent deployment.

OBJECTIVES: To investigate the clinical value and diagnostic accuracy of enhanced stent imaging (ESI) as compared with quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). BACKGROUND: ESI is an image acquisition and processing angiography-based software that improves visualization and provides measurements of deployed stents. METHODS: A total of 40 consecutive patients (42 stents) were studied. Stent deployment was evaluated sequentially and independently by angiography, ESI, and IVUS. Following each imaging modality, the operator determined the necessity of postdilation unrelated to the other modalities. Stent diameters were measured off-line by QCA, ESI, and IVUS at several sites along the deployed stent and compared. RESULTS: Following stent deployment and based solely on angiography, the operator decided to postdilate seven of the 42 stents (16.7%). This decision was not changed after reviewing the ESI images of these seven stents. Of the 35 stents not requiring postdilation based on angiography alone, ESI influenced the operator to change the decision and postdilate 10 of 35 stents (28.6%). The ESI-based measurements had better correlation with IVUS (r = 0.721, P < 0.0001) than did QCA with IVUS (r = 0.563, P < 0.0001). Bland-Altman analysis showed a trend towards better agreement between ESI and IVUS than between QCA and IVUS (mean differences = 0.038 vs. 0.121; P = 0.19, respectively). CONCLUSIONS: ESI is an easy to use modality that enhances stent visualization, helps in the decision making process whether to postdilate the stent, and provides estimation of stent expansion with better correlations than QCA when compared to IVUS. © 2012 Wiley Periodicals, Inc.

Volumetric intravascular ultrasound assessment of mechanisms and results of stent expansion in heart transplant patients.

BACKGROUND: Percutaneous coronary intervention with stent placement for the treatment of patients with cardiac allograft vasculopathy is common, but data regarding stent behavior in this setting is lacking. OBJECTIVES: We investigated mechanisms and potential differences in stent expansion among transplant patients vs. patients with native coronary artery atherosclerotic disease ("controls"). METHODS: We compared pre- and poststent intravascular ultrasound in 12 transplant patients (17 lesions) and 33 control patients (34 lesions) matched according to age (60.1 ± 9.2 years), diabetes mellitus, and lesion location. Planar and volumetric analysis was conducted for every 1 mm at the lesion site as well as the first 5 mm proximal and distal to the stent edge. Focal stent expansion was defined as minimum stent area (MSA) divided by mean reference lumen area. Diffuse stent expansion was defined as mean stent area divided by mean reference lumen area. RESULTS: Transplant patients had more plaque than "controls" prestenting, but similar MSA and focal and diffuse stent expansion afterwards. The increase in mean lumen area correlated with the increase in mean vessel area in both groups, transplant (R = 0.64, P = 0.008) and controls (R = 0.70, P < 0.0001), but correlated inversely with changes in mean plaque area only in the transplant group (R = 0.55, P = 0.027). There were no differences in calcification between the two groups and no axial plaque distribution from the lesion into the reference segments in either group. CONCLUSIONS: The mechanism of stent expansion in transplant vasculopathy appears to be similar to de novo atherosclerosis-i.e., mainly vessel expansion to achieve similar acute results.

Association between insomnia and the incidence of myocardial infarction: A systematic review and meta-analysis.

BACKGROUND: Insomnia has been closely associated with cardiovascular disease (CVD) including myocardial infarction (MI). Our study aims to assess the eligibility of insomnia as a potential risk factor for MI. METHODS: PubMed, Scopus, and Web of Science were searched using terms; such as "Insomnia" and "MI." Only observational controlled studies with data on the incidence of MI among insomniacs were included. Revman software version 5.4 was used for the analysis. RESULTS: Our pooled analysis showed a significant association between insomnia and the incidence of MI compared with noninsomniacs (relative risk [RR] = 1.69, 95% confidence interval [CI] = 1.41-2.02, p < .00001). Per sleep duration, we detected the highest association between ≤5 h of sleep, and MI incidence compared to 7-8 h of sleep (RR = 1.56, 95% CI = 1.41-1.73). Disorders of initiating and maintaining sleep were associated with increased MI incidence (RR = 1.13, 95% CI = 1.04-1.23, p = .003). However, subgroup analysis of nonrestorative sleep and daytime dysfunction showed an insignificant association with MI among both groups (RR = 1.06, 95% CI = 0.91-1.23, p = .46). Analysis of age, follow-up duration, sex, and comorbidities showed a significant association in insomniacs. CONCLUSION: Insomnia and ≤5 h of sleep are highly associated with increased incidence of MI; an association comparable to that of other MI risk factors and as such, it should be considered as a risk factor for MI and to be incorporated into MI prevention guidelines.

Endothelial shear stress computed from coronary computed tomography angiography: A direct comparison to intravascular ultrasound.

INTRODUCTION: Intravascular ultrasound (IVUS) studies have shown that biomechanical variables, particularly endothelial shear stress (ESS), add synergistic prognostic insight when combined with anatomic high-risk plaque features. Non-invasive risk assessment of coronary plaques with coronary computed tomography angiography (CCTA) would be helpful to enable broad population risk-screening. AIM: To compare the accuracy of ESS computation of local ESS metrics by CCTA vs IVUS imaging. METHODS: We analyzed 59 patients from a registry of patients who underwent both IVUS and CCTA for suspected CAD. CCTA images were acquired using either a 64- or 256-slice scanner. Lumen, vessel, and plaque areas were segmented from both IVUS and CCTA (59 arteries, 686 3-mm segments). Images were co-registered and used to generate a 3-D arterial reconstruction, and local ESS distribution was assessed by computational fluid dynamics (CFD) and reported in consecutive 3-mm segments. RESULTS: Anatomical plaque characteristics (vessel, lumen, plaque area and minimal luminal area [MLA] per artery) were correlated when measured with IVUS and CCTA: 12.7 â€‹± â€‹4.3 vs 10.7 â€‹± â€‹4.5 â€‹mm2, r â€‹= â€‹0.63; 6.8 â€‹± â€‹2.7 vs 5.6 â€‹± â€‹2.7 â€‹mm2, r â€‹= â€‹0.43; 5.9 â€‹± â€‹2.9 vs 5.1 â€‹± â€‹3.2 â€‹mm2, r â€‹= â€‹0.52; 4.5 â€‹± â€‹1.3 vs 4.1 â€‹± â€‹1.5 â€‹mm2, r â€‹= â€‹0.67 respectively. ESS metrics of local minimal, maximal, and average ESS were also moderately correlated when measured with IVUS and CCTA (2.0 â€‹± â€‹1.4 vs 2.5 â€‹± â€‹2.6 â€‹Pa, r â€‹= â€‹0.28; 3.3 â€‹± â€‹1.6 vs 4.2 â€‹± â€‹3.6 â€‹Pa, r â€‹= â€‹0.42; 2.6 â€‹± â€‹1.5 vs 3.3 â€‹± â€‹3.0 â€‹Pa, r â€‹= â€‹0.35, respectively). CCTA-based computation accurately identified the spatial localization of local ESS heterogeneity compared to IVUS, with Bland-Altman analyses indicating that the absolute ESS differences between the two CCTA methods were pathobiologically minor. CONCLUSION: Local ESS evaluation by CCTA is possible and similar to IVUS; and is useful for identifying local flow patterns that are relevant to plaque development, progression, and destabilization.

Anthracyclines and the risk of arrhythmias: A systematic review and meta-analysis.

BACKGROUND: There have been controversial findings from recent studies regarding anthracyclines use and the subsequent risk of arrhythmias. This study aimed to evaluate the existing evidence of the risk of arrhythmias in patients treated with anthracyclines. METHODS: PubMed, Scopus, and Web of Science databases were searched up to April 2022 using keywords such as "anthracycline" and "arrhythmia." Dichotomous data were presented as relative risk (RR) and confidence interval (CI), while continuous data were presented as mean difference (MD) and CI. Revman software version 5.4 was used for the analysis. RESULTS: Thirteen studies were included with a total of 26891 subjects. Pooled analysis showed that anthracyclines therapy was significantly associated with a higher risk of arrhythmia (RR: 1.58; 95% CI: 1.41-1.76; P < .00001), ST segment and T wave abnormalities (RR: 1.73, 95% CI: 1.18-2.55, P = .005), conduction abnormalities and AV block (RR = 1.86, 95% CI = 1.06-3.25, P = .03), and tachycardia (RR: 1.736, 95% CI: 1.11-2.69, P = .02). Further analyses of the associations between anthracyclines and atrial flutter (RR = 1.30, 95% CI = 0.29-5.89, P = .74), atrial ectopic beats (RR: 1.27, 95% CI: 0.78-2.05, P = .34), and ventricular ectopic beats (RR: 0.93, 95% CI: 0.53-1.65, P = .81) showed no statistically significant results. Higher doses of anthracycline were associated with a higher risk of arrhythmias (RR: 1.49; 95% CI: 1.08-2.05; P = .02) compared to the lower doses (RR: 1.36; 95% CI: 1.00-1.85; P = .05). Newer generations of Anthracycline maintained the arrhythmogenic properties of previous generations, such as Doxorubicin. CONCLUSION: Anthracyclines therapy was significantly associated with an increased risk of arrhythmias. Accordingly, Patients treated with anthracyclines should be screened for ECG abnormalities and these drugs should be avoided in patients susceptible to arrhythmia. The potential benefit of the administration of prophylactic anti-fibrotic and anti-arrhythmic drugs should also be explored.

The role of endothelial shear stress, shear stress gradient, and plaque topography in plaque erosion.

BACKGROUND AND AIMS: Plaque erosion is a common underlying cause of acute coronary syndromes. The role of endothelial shear stress (ESS) and endothelial shear stress gradient (ESSG) in plaque erosion remains unknown. We aimed to determine the role of ESS metrics and maximum plaque slope steepness in plaques with erosion versus stable plaques. METHODS: This analysis included 46 patients/plaques from TOTAL and COMPLETE trials and Brigham and Women's Hospital's database who underwent angiography and OCT. Plaques were divided into those with erosion (n = 24) and matched stable coronary plaques (n = 22). Angiographic views were used to generate a 3-D arterial reconstruction, with centerlines merged from angiography and OCT pullback. Local ESS metrics were assessed by computational fluid dynamics. Among plaque erosions, the up- and down-slope (Δ lumen area/frame) was calculated for each culprit plaque. RESULTS: Compared with stable plaque controls, plaques with an erosion were associated with higher max ESS (8.3 ± 4.8 vs. 5.0 ± 1.9 Pa, p = 0.02) and max ESSG any direction (9.2 ± 7.5 vs. 4.3 ± 3.11 Pa/mm, p = 0.005). Proximal erosion was associated with a steeper plaque upslope while distal erosion with a steeper plaque downslope. Max ESS and Max ESSG any direction were independent factors in the development of plaque erosion (OR 1.32, 95%CI 1.06-1.65, p = 0.014; OR 1.22, 95% CI 1.03-1.45, p = 0.009, respectively). CONCLUSIONS: In plaques with similar luminal stenosis, plaque erosion was strongly associated with higher ESS, ESS gradients, and plaque slope as compared with stable plaques. These data support that ESS and slope metrics play a key role in the development of plaque erosion and may help prognosticate individual plaques at risk for future erosion.

Relationship between biomarkers and subsequent clinical and angiographic restenosis after paclitaxel-eluting stents for treatment of STEMI: a HORIZONS-AMI substudy.

Drug-eluting stents (DES) reduce the incidence of in-stent restenosis (ISR) after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Whether the use of biomarkers might be of utility to identify patients who remain at risk for DES ISR after primary PCI has never been examined. A total of 26 biomarkers were measured at enrollment and 30 days and analyzed at a central core laboratory in 501 STEMI patients from the HORIZONS-AMI trial. All patients underwent primary PCI with the TAXUS paclitaxel-eluting stent (PES), were scheduled for routine angiographic follow-up at 13 months, and were followed for 3 years. Mean in-stent late-loss was 0.28 ± 0.57 mm, and target lesion revascularization (TLR) at 3 years occurred in 9.1 % of patients. Low levels of interleukin-6 (IL-6) and placental growth factor (PLGF) at admission were associated with both higher in-stent late loss and ischemia-driven TLR. Additionally, low admission levels of cardiotrophin-1 (CT-1) were associated with higher rates of ischemia-driven TLR. At 30-day follow-up lower values of IL-1ra (IL-1ra), matrix metalloproteinase 9 (MMP9), and myeloperoxidase (MPO), and a decline relative to admission in IL-1ra, monocyte chemotactic protein-1 (MCP-1), and MMP9 were associated with higher in-stent late loss. Low values of IL-6 at 30 days were also associated with ischemia-driven TLR. After multivariate adjustment, only MPO at 30 days and a decline of MCP-1 between admission and 30 days were associated with in-stent late loss, and only CT-1 was associated with TLR. MPO at 30 days and a decline of MCP-1 between admission and 30 days were independently associated with in-stent late loss, and CT-1 was associated with TLR. Additional studies to confirm and validate the utility of these biomarkers are warranted.

Impact of baseline thrombocytopenia on the early and late outcomes after ST-elevation myocardial infarction treated with primary angioplasty: analysis from the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial.

BACKGROUND: Thrombocytopenia (TP) is a common abnormality in patients presenting with acute coronary syndrome. Whether baseline TP has any influence on the outcome of patients treated with primary angioplasty for acute myocardial infarction is unknown. METHODS: We sought to detect the impact of baseline TP on the early and late outcomes of patients with ST-elevation myocardial infarction in the HORIZONS-AMI trial that included a protocol of immediate angiography and primary percutaneous coronary intervention. RESULTS: Baseline TP was found in 4.2% of patients and was associated with a higher incidence of cardiovascular mortality, major bleeding, and major cardiovascular events at short- and long-term follow-up. The 30-day rates of death, major bleeding, major cardiac events, and major cardiac events plus major bleeding were 6.2%, 11.9%, 9.6%, and 18.5% in the TP group, respectively, compared with 2.1%, 7%, 5.2%, and 10.8% in those without TP (P < .05 for all). Similarly, event rates at 2 years were 11.3%, 12.7%, 24.7%, and 30.8% compared with 5.1%, 7.9%, 18.5%, and 23.3% (P < .05). By multivariate analysis, baseline TP was an independent predictor of 30-day net adverse clinical events but not of any 2-year events. CONCLUSIONS: We found that baseline TP in patients with ST-elevation myocardial infarction undergoing routine angiography and primary percutaneous coronary intervention is strongly associated with early adverse events and is a maker of late events, related to both ischemia and bleeding.

The role of far-field intravascular ultrasound in transcatheter aortic valve replacement.

Precise and accurate characterization of the aortic valve complex is a vital step in the procedure planning for transcatheter aortic valve replacement (TAVR). Far-field intravascular ultrasound (IVUS) is a novel technology that can be utilized to assess aortic valve annulus and predict paravalvular leak, with comparable results to multi-detector computed tomography-the current gold standard in the preprocedural planning in TAVR. Far-field IVUS carries the advantage of minimal contrast use and lower radiation exposure. In this commentary, we describe two cases of far-field IVUS use during TAVR procedures and review its role as a complementary tool to current the imaging modalities used in TAVR.

Reviewing imaging modalities for the assessment of plaque erosion.

Plaque rupture followed by intracoronary thrombus formation is recognized as the most common pathophysiological mechanism in acute coronary syndromes (ACS). The second most common underlying substrate for ACS is plaque erosion whose hallmark is thrombus formation without cap disruption. Invasive and non-invasive methods have emerged as a promising tool for evaluation of plaque features that either predict or detect plaque erosion. Optical coherence tomography (OCT), high-definition intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and near-infrared autofluorescence (NIRF) have been used to study plaque erosion. The detection of plaque erosion in the clinical setting, mainly facilitated by OCT, has shed light upon the complex pathophysiology underlying ACS not related to plaque rupture. Coronary computed tomography angiography (CCTA), which is to date the most commonly used non-invasive technique for coronary plaque evaluation, may also have a role in the evaluation of patients predisposed to erosion. Also, computational models enabling quantification of endothelial shear stress may pave the way to new research in coronary plaque pathophysiology. This review focuses on the recent imaging techniques for the evaluation of plaque erosion including invasive and non-invasive assessment.