Cellular crosstalk in atherosclerotic plaque microenvironment

Coronary artery disease and acute coronary syndromes are accountable for significant morbidity and mortality, despite the preventive measures and technological advancements in their management. Thus, it is mandatory to further explore the pathophysiology in order to provide tailored and more effective therapies, since acute coronary syndrome pathogenesis is more varied than previously assumed. It consists of plaque rupture, plaque erosion, and calcified nodules. The advancement of vascular imaging tools has been critical in this regard, redefining the epidemiology of each mechanism. When it comes to acute coronary syndrome management, the presence of ruptured plaques almost always necessitates emergent reperfusion, whereas the presence of plaque erosions may indicate the possibility of conservative management with potent antiplatelet and anti-atherosclerotic medications. Calcified nodules, on the other hand, are an uncommon phenomenon that has largely gone unexplored in terms of the best management plan. Future studies should further establish the importance of detecting the underlying mechanism and the role of various treatment plans in each of these distinct entities.

Pathophysiology of Acute Coronary Syndromes—Diagnostic and Treatment Considerations

BACKGROUND
A recent meta-analysis of randomized control trials demonstrated a significantly higher risk of major amputation in patients treated with drug-coated balloons (DCBs) compared with standard treatment, especially in high-dose paclitaxel-coated DCBs. Distal particulate embolization after DCB use was considered a potential cause of the higher incidence of major amputation. The current study aimed to histologically and biologically compare biologic drug effect and distal particulate embolization in 3 DCBs (a high-dose paclitaxel-coated DCB [IN.PACT Admiral] and 2 low-dose paclitaxel-coated DCBs [Ranger and Lutonix]).


METHODS AND RESULTS
The DCBs were inflated in the healthy descending aortas of 18 rabbits, followed by euthanasia 28 days after the procedure. The treated descending aorta and distal skeletal muscles were histopathologically evaluated, and paclitaxel concentrations were measured. The paclitaxel concentration of the treated lesion was highest for Ranger, followed by IN.PACT and Lutonix (Ranger vs IN.PACT vs Lutonix: 1089 [745-2170] pmol/mg vs 638 [160-2075] pmol/mg vs 25 [10-304] pmol/mg, respectively; p<0.0001). In the histopathological evaluation, the angle of severe medial smooth muscle cell loss was largest for Ranger followed by IN.PACT and Lutonix (12.8 [8.0-20.4] degree vs 1.4 [1.2-5.2] degree vs 0.8 [0.5-2.5] degree, respectively), with significant differences for Ranger vs IN.PACT (p=0.007) and Ranger vs Lutonix (p=0.002). However, paclitaxel concentrations of distal skeletal muscles were lowest for Lutonix, followed by Ranger and IN.PACT (12 [1-58] pmol/mg vs 15 [13-21] pmol/mg vs 42 [19-108] pmol/mg, respectively, p<0.0001). The numbers of arteries with downstream DCB effects were highest for IN.PACT, followed by Ranger and Lutonix (Ranger vs IN.PACT vs Lutonix, 3 [3-4] vs 4 [3-7] vs 2 [1-2], respectively), which was consistent with the measured tissue paclitaxel concentrations.


CONCLUSION
These findings suggest that Ranger demonstrates the strongest paclitaxel effect, as well as the second-best effect regarding distal particulate embolization, making it a good treatment option for patients with peripheral artery disease among the 3 DCBs evaluated in the current study. Further clinical head-to-head comparisons with larger numbers of patients are needed to explore which DCB is the most effective and safe treatment option.Clinical Impact:The findings of the current preclinical study suggests that Ranger demonstrates the strongest paclitaxel effect, as well as the second-best effect regarding distal particulate embolization making it a good treatment for patients with intermittent claudication and chronic limb-threatening ischemia.

Differences in Biologic Drug Effects and Distal Particulate Embolization in Three Paclitaxel-Coated Balloons for Femoropopliteal Lesions in a Rabbit Model.

Effect of solid surface curvature and wall heat loss on the downward flame spread along the edge of thin PMMA sheets

The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is an independent risk index for cardiovascular events. This study aimed to evaluate the association between TG/HDL-C ratio and coronary plaque characteristics as seen on coronary computed tomography angiography (CCTA) and the corresponding increase in the likelihood of cardiovascular events. A total of 935 patients who underwent CCTA for suspected coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined based on three characteristics: positive remodeling, low-density plaques, and spotty calcification. Significant stenosis was defined as luminal narrowing of >70%. Patients with a higher TG/HDL-C ratio showed significantly greater prevalence of HRP and significant stenosis than patients with low TG/HDL-C ratios (p < 0.01). Multivariate logistic analysis demonstrated that the TG/HDL-C ratio was significantly associated with the presence of HRP (p < 0.01) but not with significant coronary stenosis (p = 0.24). During the median follow-up period of 4.1 years, 26 cardiovascular events including cardiovascular death and acute coronary syndrome occurred. The highest TG/HDL-C tertile was associated with cardiovascular events, with the lowest TG/HDL-C tertile as the reference (hazard ratio, 3.75; 95% confidence interval, 1.04–13.50). A high TG/HDL-C ratio is associated with the presence of CCTA-verified HRP, which can lead to cardiovascular events in patients with suspected CAD.

/pdf/the-association-of-triglyceride-to-high-density-lipoprotein-1sw3hwyg.pdf

The Association of Triglyceride to High-Density Lipoprotein Cholesterol Ratio with High-Risk Coronary Plaque Characteristics Determined by CT Angiography and Its Risk of Coronary Heart Disease

AIMS
Coronary vasospasm is associated with acute coronary syndrome (ACS) and may persist during primary percutaneous coronary intervention (PCI). We aimed to elucidate the incidence, morphological characteristics, and prognostic impact of residual vasospasm in plaque rupture (PR) and plaque erosion (PE) lesions using optical coherence tomography (OCT).


METHODS
We enrolled 142 patients with ACS who underwent OCT-guided primary PCI. All patients received intracoronary vasodilators before OCT examination. Residual vasospasm was identified as intimal gathering and categorised as polygonal- or wavy- patterned depending on the luminal shape. A wavy pattern was defined as a curved intimal surface line. A polygonal pattern was defined as a lumen with multiple angles. The incidence of major cardiovascular events, defined as death, non-fatal myocardial infarction, stroke, and any revascularization, within 1-year of PCI was identified.


RESULTS
The prevalence of residual vasospasm in PR and PE was 15.1% (13 of 86) and 21.4% (12 of 56), respectively. Wavy pattern was the major shape of the residual vasospasm. Polygonal-patterned lumen was more frequently observed in PR than in PE (38.5 vs. 8.3 %). The polygonal-patterned lumens had significantly larger lipid arcs (257.9 vs. 78.0 °; P＜0.01), and significantly smaller areas (1.27 vs. 1.88 mm2; P=0.05) than wavy patterned lumens. Residual vasospasm had a prognostic impact on PR but not PE at 1-year of successful primary PCI.


CONCLUSION
Considerable proportion of ACS including both PR and PE had residual vasospasm with variable morphological feature and different prognostic impact.

Assessment of Residual Vasospasm in Patients with Plaque Rupture or Plaque Erosion using Optical Coherence Tomography.

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Assessment of Residual Vasospasm in Patients with Plaque Rupture or Plaque Erosion using Optical Coherence Tomography.