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We described a rare case of acute ischemic stroke due to calcified cerebral emboli from calcified carotid plaque (CCP). Radiological examinations revealed that the CCP had an irregular configuration containing a calcified nodule and scattered spotty calcifications, and a large calcified plate. The patient underwent carotid endarterectomy to prevent embolic recurrence. Histopathological examination confirmed the presence of an erupted plaque with a disrupted fibrous cap. Calcified nodular protrusion and spotty calcifications in CCP are predictive of a high risk of embolic stroke with plaque rupture. Thus, careful treatment strategies are crucial to prevent the CCP-related embolic recurrence. [ABSTRACT FROM AUTHOR]

Calcified nodules (CNs) are among the most challenging lesions to treat in contemporary percutaneous coronary intervention. CNs may be divided into 2 subtypes, eruptive and noneruptive, which have distinct histopathological and prognostic features. An eruptive CN is a biologically active lesion with a disrupted fibrous cap and possibly adherent thrombus, whereas a noneruptive CN has an intact fibrous cap and no adherent thrombus. The use of intravascular imaging may allow differentiation between the 2 subtypes, thus potentially guiding treatment strategy. Compared with noneruptive CNs, eruptive CNs are more likely to be deformable, resulting in better stent expansion, but are paradoxically associated with worse clinical outcomes, in part because of their frequent initial presentation as an acute coronary syndrome and subsequent reprotrusion of the CN into the vessel lumen through the stent struts. Pending the results of ongoing studies, a tailored therapeutic approach based on the distinct features of the different CNs may be of value. [Display omitted] • Calcified nodules are among the most challenging lesions to treat with contemporary percutaneous coronary intervention. • There are 2 subtypes of calcified nodules, eruptive and noneruptive, which have distinct histopathological and prognostic features. • The use of intravascular imaging enables differentiation of the 2 subtypes of calcified nodules in daily practice, which may help determine the optimal treatment strategy. • Pending the results of ongoing studies, a tailored therapeutic approach based on the distinct features of the different calcified nodules may be recommended. [ABSTRACT FROM AUTHOR]

Background: Calcified nodules (CN) have been linked to unfavorable clinical outcomes. However, there is a lack of systematic studies on non-culprit lesions with CN in patients with acute coronary syndromes (ACS). This study aims to investigate the frequency, distribution, predictors, and outcomes of CN in non-culprit lesions among ACS patients. Methods: We included 376 ACS patients who received successful stent placement in their culprit lesions. Intravascular ultrasound (IVUS) was performed to evaluate non-culprit lesions in left main arteries and all three coronary arteries (CA). CN was defined as accumulations of small nodular calcium deposits exhibiting a convex shape protruding into the lumen. Results: CNs was identified in 16.9% (121 of 712) per artery and 26.9% (101 of 376) per patient. They were predominantly located at the mid portion of the right coronary artery (26.3%) and the bifurcation site (59.9%). Patients with CN were older (63.57 ± 8.43 vs. 57.98 ± 7.15, p < 0.001) and had a higher prevalence of diabetes mellitus (55.4% vs. 42.2%, p = 0.022). However, there were no significant differences in baseline characteristics observed after propensity score matching (PSM). Multivariate analysis revealed that CN were independently associated with major adverse cardiovascular events (MACE) both before and after PSM (hazard ratio (HR): 0.341, 95% confidence interval (95% CI): 0.140-0.829, p = 0.018; HR: 0.275, 95% CI: 0.108-0.703, p = 0.007, respectively). During the observational period of 19.35 ± 10.59 months, the occurrence of MACE was significantly lower in patients with CN before and after PSM (5.9% vs. 16.7%, p = 0.046; 4.0% vs. 18.1%, p = 0.011; respectively). Conclusions: CN in non-culprit lesions with ACS patients was prevalent and caused fewer adverse clinical outcomes. [ABSTRACT FROM AUTHOR]

The process of coronary calcification represents one of the numerous pathophysiological mechanisms involved in the atherosclerosis continuum. Optical coherence tomography (OCT) represents an ideal imaging modality to assess plaque components, especially calcium. Different calcification patterns have been contemporarily described in both early stages and advanced atherosclerosis. Microcalcifications and spotty calcifications correlate positively with macrophage burden and inflammatory markers and are more frequently found in the superficial layers of ruptured plaques in acute coronary syndrome patients. More compact, extensive calcification may reflect a later stage of the disease and was traditionally associated with plaque stability. Nevertheless, a small number of culprit coronary lesions demonstrates the presence of dense calcified plaques. The purpose of the current paper is to review the most recent OCT data on coronary calcification and the interrelation between calcification pattern and plaque vulnerability. How different calcified plaques influence treatment strategies and associated prognostic implications is of great interest.

The concept of lifetime management has not been discussed in the field of percutaneous coronary intervention (PCI), because the durability of drug-eluting stent (DES) is considered to be long enough for most patients. Furthermore, even if in-stent restenosis occurs, the treatment for in-stent restenosis is simple in most cases. On the other hand, the long-term clinical outcomes after DES implantation are worse in severely calcified coronary lesions than in non-calcified lesions. Moreover, the treatment for in-stent calcified restenosis or restenosis due to stent underexpansion is not simple. The concept of lifetime management of severely calcified lesions may be necessary like that of aortic stenosis. Recently, several algorithms have been published in PCI to severely calcified lesions, partly because of the emergence of IVL. These algorithms focus on the selection of cracking and debulking devices for the preparation of stenting. However, the optimal stent expansion does not guarantee the long-term patency, when the target lesion includes calcified nodules. Stent restenosis due to calcified nodules is difficult to manage. In this review article, we propose the algorithm for severely calcified lesions focused on the shape of calcification. We do not need to hesitate stenting when multiple cracks on circumferential calcification are observed by intravascular imaging devices. However, DCB may be an option as final device in some situations, when lifetime management of severely calcified lesions is considered. [ABSTRACT FROM AUTHOR]

Milia-like idiopathic calcinosis cutis (MICC) and subepidermal calcified nodule (SCN) are described as different entities under the heading of idiopathic calcinosis cutis. Although there are some clinical differences, they share many features. Whereas MICC lesions are located mostly on the extremities and rarely on the face, SCN manifests itself mostly on the face, rarely on the extremities. Milia-like idiopathic calcinosis cutis almost always presents with multiple lesions, whereas SCN shows mainly solitary and rarely multiple lesions. Association with Down syndrome (DS) has been reported in up to two-third of the cases with MICC, but not in SCN. We herein present a 5-months-old girl without DS, manifesting a 2mm solitary, white hard papule surrounded by erythema, located on the finger. Histopathologic findings revealed the presence of dermal calcium deposits. When a solitary papular lesion of idiopathic calcinosis is seen in a child, especially if not associated with DS, it is difficult to differentiate MICC from SCN. We believe that these entities may represent variants of the same pathology and it may be more appropriate to designate a solitary lesion as SCN, regardless of its location.

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. [ABSTRACT FROM AUTHOR]

Abstract Background Calcified nodule (CN) is a type of potentially vulnerable plaque. Its formation mechanism remains unknown. This study was to assess serum marker and computed tomography angiography (CTA) characteristics of CN validated by intravascular ultrasound (IVUS). Methods Patients who underwent coronary CTA followed by invasive coronary angiography and IVUS were retrospectively analyzed. Serum levels of alkaline phosphatase (ALP), gamma-glutamyltransferase, and calcium were collected. Results IVUS detected 128 de novo calcified lesions in 79 patients with coronary artery disease (CAD). CNs were identified in 11.4% (9/79) of patients and 9.4% (12/128) of lesions. Compared with patients with non-nodular calcified plaques, CN patients had higher serum level of ALP (82.00 vs 65.00 U/L, P = 0.022) and total plaque volume (673.00 vs 467.50 mm3, P = 0.021). Multivariable analyses revealed that serum ALP level and total plaque volume were independently associated with the prevalence of CN in CAD patients with calcified plaques. At lesion level, the CN group had a higher frequency of moderate to heavy calcification on angiography (75.00% vs 40.52%, P = 0.017). In terms of CTA characteristics, plaques with CN had a more severe diameter stenosis (79.00% vs 63.00%, P = 0.007), higher plaque burden (85.40% vs 77.05%, P = 0.005), total plaque density (398.00 vs 283.50 HU, P = 0.008), but lower lipid percentage (14.65% vs 19.75%, P = 0.010) and fiber percentage (17.90% vs 25.65%, P = 0.011). Mean plaque burden is an independent predictor of the prevalence of CN in calcified plaques (odds ratio = 1.102, 95% confidence interval: 1.025–1.185, P = 0.009). The AUC is 0.753 (95% confidence interval: 0.615–0.890, P = 0.004). When using 84.85% as the best cutoff value, the diagnostic sensitivity and specificity of mean plaque burden for predicting the presence of CN within calcified plaques were 66.7% and 80.2%, respectively. Conclusions CN had different CTA imaging features from non-nodular coronary calcification. The presence of a CN was associated with a higher serum ALP level and plaque burden.

Whether an eruptive or noneruptive target lesion calcified nodule (CN) portends worse acute and long-term clinical outcomes after stenting has not been established. The authors sought to compare acute and long-term clinical outcomes in eruptive CN vs noneruptive CN morphology. Using optical coherence tomography, an eruptive CN was defined as an accumulation of small calcium fragments protruding and disrupting the overlying fibrous cap, typically with small amount of thrombus. A noneruptive CN was defined as an accumulation of small calcium fragments with a smooth intact fibrous cap without an overlying thrombus. The primary endpoint was target lesion failure (TLF) including cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization in patients with ≥6-month follow-up. Among 3,231 patients with evaluable pre- and postintervention OCT, 236 patients had lesions with CNs (7.3%). After eliminating 4 secondary lesions and 6 patients without ≥6-month follow-up, 126 (54.8%) lesions with eruptive CNs and 104 (45.2%) lesions with noneruptive CNs formed the current report. Compared with noneruptive CNs, eruptive CNs were independently associated with greater stent expansion (89.2% ± 18.7% vs. 81.5% ± 18.9%; P = 0.003) after adjusting for morphologic and procedural factors. At 2 years, eruptive CNs trended toward more TLF compared with noneruptive CNs (Kaplan-Meier estimates, 19.8% vs 12.5%; P = 0.11) and significantly more target lesion revascularization (18.3% vs 9.6%; P = 0.04). In the adjusted model, eruptive CNs were independently associated with 2-year TLF (HR: 2.07; 95% CI: 1.01-4.50; P = 0.048). Compared with noneruptive CN morphology, lesions with an eruptive CN appearance on optical coherence tomography had a worse poststent long-term clinical outcome despite better acute stent expansion. [Display omitted] [ABSTRACT FROM AUTHOR]

Optical coherence tomography (OCT) is an intravascular imaging technique that uses near-infrared light. OCT provides high-resolution cross-sectional images of coronary arteries and enables tissue characterization of atherosclerotic plaques. OCT can identify plaque rupture, plaque erosion, and calcified nodule in culprit lesions of acute coronary syndrome. OCT can also detect important morphologic features of vulnerable plaques such as thin fibrous caps, large lipid cores, macrophages accumulation, intraplaque microvasculature, cholesterol crystals, healed plaques, and intraplaque hemorrhage. [ABSTRACT FROM AUTHOR]

Background: Despite the increase in the number of patients with peripheral artery disease (PAD), the pathophysiology is not fully elucidated. Recently, angioscopy with a 0.48-megapixel equivalent resolution camera became available for patients with PAD. We aimed to compare the plaque component between native stenosis and occlusion in the femoropopliteal artery using this modality. Materials and Methods: Thirty-two consecutive patients who underwent endovascular treatment for native femoropopliteal artery disease with angioscopy were studied. The major angioscopic classifications of each lesion were defined as follows: atheromatous plaque (AP) was defined as luminal narrowing without any protrusion, calcified nodule (CN) was defined as a protruding bump with surface irregularity, a mainly reddish thrombus was defined as organizing thrombus (OG), and organized thrombus (OD) was defined by more than half of the thrombus showing a whitish intima-like appearance. Results: A total of 34 lesions (stenosis, n=18; occlusion, n=16) from 32 patients were included. All stenotic lesions showed AP or CN (n=8 [44%], n=10 [56%], respectively), whereas all occluded lesions showed OG or OD (n=5 [31%], n=11 [69%], respectively), which amounted to a statistically significant difference (p<0.001). In occluded lesions, stiff wires (>3 g) were required to cross all lesions classified as OD, whereas this was not always necessary for lesions classified as OG (11 [100%] of 11, 1 [25%] of 5, respectively; p=0.04). Yellow color plaques were observed to a similar degree in all angioscopic classifications. Major adverse limb events, defined as amputation and any reintervention at 12 months, were highly variable, depending on the angioscopic findings, and tended to be more frequently observed in CN and OD (13% in AP, 40% in CN, 0% in OT, and 36% in OD, p=0.25). Conclusion: Angioscopy revealed varying components in stenosis and occlusion with different degrees of clinical impact. This may provide new information on the pathophysiology of PAD. [ABSTRACT FROM AUTHOR]

Although coronary artery perforation can be a fatal complication during percutaneous coronary intervention, it is rarely observed in in-stent restenotic lesions. We present a case with coronary artery perforation after balloon dilatation for a recurrent in-stent restenotic lesion with calcified nodule inside the double-layered stents that were previously implanted. (Level of Difficulty: Advanced.)

Subepidermal calcified nodules are an uncommon subtype of idiopathic calcinosis cutis. Morphologically, this entity typically present as a single, well-circumscribed, white-yellow nodule. Based on clinical appearance alone, subepidermal calcified nodules are frequently misdiagnosed and often requires histological confirmation. We describe two cases of subepidermal calcified nodules presenting atypically as cutaneous horns. Subepidermal calcified nodules presenting as a cutaneous horn has rarely been reported; on review, there are fewer than 10 such cases have been described within the past 30 years. The cases described here illustrate the clinical variety and should increase awareness of subepidermal calcified nodules presented. [ABSTRACT FROM AUTHOR]

Background: Calcified nodule (CN) is a type of potentially vulnerable plaque. Its formation mechanism remains unknown. This study was to assess serum marker and computed tomography angiography (CTA) characteristics of CN validated by intravascular ultrasound (IVUS).Methods: Patients who underwent coronary CTA followed by invasive coronary angiography and IVUS were retrospectively analyzed. Serum levels of alkaline phosphatase (ALP), gamma-glutamyltransferase, and calcium were collected.Results: IVUS detected 128 de novo calcified lesions in 79 patients with coronary artery disease (CAD). CNs were identified in 11.4% (9/79) of patients and 9.4% (12/128) of lesions. Compared with patients with non-nodular calcified plaques, CN patients had higher serum level of ALP (82.00 vs 65.00 U/L, P = 0.022) and total plaque volume (673.00 vs 467.50 mm3, P = 0.021). Multivariable analyses revealed that serum ALP level and total plaque volume were independently associated with the prevalence of CN in CAD patients with calcified plaques. At lesion level, the CN group had a higher frequency of moderate to heavy calcification on angiography (75.00% vs 40.52%, P = 0.017). In terms of CTA characteristics, plaques with CN had a more severe diameter stenosis (79.00% vs 63.00%, P = 0.007), higher plaque burden (85.40% vs 77.05%, P = 0.005), total plaque density (398.00 vs 283.50 HU, P = 0.008), but lower lipid percentage (14.65% vs 19.75%, P = 0.010) and fiber percentage (17.90% vs 25.65%, P = 0.011). Mean plaque burden is an independent predictor of the prevalence of CN in calcified plaques (odds ratio = 1.102, 95% confidence interval: 1.025-1.185, P = 0.009). The AUC is 0.753 (95% confidence interval: 0.615-0.890, P = 0.004). When using 84.85% as the best cutoff value, the diagnostic sensitivity and specificity of mean plaque burden for predicting the presence of CN within calcified plaques were 66.7% and 80.2%, respectively.Conclusions: CN had different CTA imaging features from non-nodular coronary calcification. The presence of a CN was associated with a higher serum ALP level and plaque burden. [ABSTRACT FROM AUTHOR]

Optical coherence tomography (OCT) has become the best imaging tool to assess calcified plaque and nodule. However, every OCT pullback has numerous images, and artificial analysis requires too much time and energy. Thus, it is unsuitable for clinical application. This study aimed to develop and validate an automatic assessment of calcified plaque and nodule by OCT using deep-learning model. The OCT images of calcified plaque and nodule were labeled by two expert readers based on the consensus. A deep-learning model with a MultiScale and MultiTask u-net network (MS-MT u-net) was developed. Then, with the ground truth labeled by expert readers as reference, the diagnostic accuracy and agreement of the model was validated. For the pixelwise evaluation of calcified plaque, the model had a high performance with precision (93.95%), recall (88.95%), and F1 score (91.38%). For the lesion-level evaluation of calcified plaque, the quantitative metrics by the model excellently correlated with the ground truth (calcium score, r = 0.90, p < 0.01; calcified volume, r = 0.99, p < 0.01). For calcified nodules, the model showed excellent diagnostic performance including sensitivity (91.7%), specificity (89.3%), and accuracy (91.0%). We developed a novel deep-learning model to identify the attributes of calcified plaque and nodule. This model provided excellent diagnostic accuracy and agreement with the ground truth, thereby reducing the subjectivity of manual measurements and substantially saving time. These findings can help practitioners efficiently adopt appropriate therapeutic strategies to treat calcified lesions. [ABSTRACT FROM AUTHOR]

Coronary artery calcification is frequently observed in coronary artery disease (CAD) patients with end-stage renal disease (ESRD). Calcified nodule (CN) is recognized as one of the vulnerable plaque characteristics responsible for acute coronary syndrome (ACS). Although CN is a cause of ACS in only 10%, its prevalence may be higher in elderly patients and/or ESRD. The aim of this study is to investigate incidence, clinical characteristics, and prognostic impact of CN in CAD patients with ESRD on dialysis. A total of 51 vessels from 49 CAD patients with ESRD on dialysis were enrolled in this study. CN was defined as a high-backscattering mass protruding into the lumen with a strong signal attenuation and an irregular surface by optical coherence tomography. Incidence, clinical characteristics and prognosis of patients with CN were studied. Major adverse cardiac events (MACE) were defined as a composite of all-cause death, non-fatal myocardial infarction, target vessel revascularization (TVR) and stroke. CNs were observed in 30 vessels from 29 patients (59.2%). Duration of dialysis was significantly longer in CN group than in non-CN group (P = 0.03). Overall, all-cause death, cardiac death, TVR and MACE occurred in 7 (14.3%), 3 (6.1%), 11 (22.4%) and 16 (32.7%) patients during follow-up (median 826 days), respectively. Kaplan–Meier survival analysis revealed that MACE-free survival was significantly lower in patients with CN compared with those without CN (Log-rank, P = 0.036). In conclusion, CN was observed in about 60% of the CAD patients with ESRD and was associated with duration of dialysis and worse prognosis. [ABSTRACT FROM AUTHOR]

Objectives: Endovascular therapy (EVT) for calcified nodules in patients with peripheral artery disease (PAD) remains challenging in achieving favorable outcomes. This study aims to investigate the effectiveness of orbital atherectomy (OA) for calcified nodules using an IM catheter to precisely control the device and achieve optimal engagement with the target lesion., Methods: We performed EVT for a calcified nodule in the right common femoral artery using an OA. Due to the large vessel size, controlling the OA to effectively engage the lesion was challenging. To overcome this, we utilized an IM catheter to guide the OA toward the target lesion., Results: The use of the IM catheter successfully directed the OA to the calcified lesion, resulting in significant lumen enlargement. The procedure was completed without any complications, and the OA achieved effective debulking of the calcified nodule., Conclusions: The combination of OA and IM catheter facilitated effective contact with the target lesion, improving the performance of the debulking device. This approach may enhance the management of calcified lesions in large-diameter arteries during EVT, potentially leading to better clinical outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Calcified nodule (CN) is a high-risk phenotype of coronary artery calcification that causes in-stent restenosis frequently. Stent thrombosis (ST) is a critical complication following percutaneous coronary intervention, and its onset is associated with severely calcified lesions. However, the association between CN and ST remains unclear. Moreover, while reprotrusion of CNs through the stent strut is not uncommon immediately after stenting, the risk of ST associated with this acute reprotrusion of CNs is not well recognized. We present a case of a 70-year-old female who developed acute ST following reprotrusion of a CN in the left main coronary artery. After the successful stenting to a large CN, a prominent acute protrusion occurred, followed by the acute occlusion of the implanted stent due to massive thrombus formation. This case highlights the importance of careful monitoring for thrombus formation even after good stent expansion, especially when large acute reprotrusion of CNs is observed., (© 2024 Wiley Periodicals LLC.)

Background: Non-eruptive calcium nodules (CNs) are commonly seen in heavily calcified coronary artery disease. They are the most difficult subset for modification, and may result in stent damage, malapposition and under-expansion. There are only limited options available for non-eruptive CN modification. Intravascular lithotripsy (IVL) is being explored as a potentially safe and effective modality in these lesions., Aims: This study aimed to investigate the safety and efficacy of the use of IVL for the modification of non-eruptive CNs. The study also explored the OCT features of calcium nodule modification by IVL., Methods: This is a single-center, prospective, observational study in which patients with angiographic heavy calcification and non-eruptive CN on OCT and undergoing PCI were enrolled. The primary safety endpoint was freedom from perforation, no-reflow/slow flow, flow-limiting dissection after IVL therapy, and major adverse cardiac events (MACE) during hospitalization and at 30 days. MACE was defined as a composite of cardiac death, myocardial infarction (MI), and ischemia-driven target lesion revascularization (TLR). The primary efficacy endpoint was procedural success, defined as residual diameter stenosis of <30% on angiography and stent expansion of more than 80% as assessed by OCT., Results: A total of 21 patients with 54 non-eruptive CNs undergoing PCI were prospectively enrolled in the study. Before IVL, OCT revealed a mean calcium score of 3.7 ± 0.5 and a mean MLA at CN of 3.9 ± 2.1 mm 2 . Following IVL, OCT revealed calcium fractures in 40 out of 54 (74.1%) CNs with an average of 1.05 ± 0.72 fractures per CN. Fractures were predominantly observed at the base of the CN (80%). Post IVL, the mean MLA at CN increased to 4.9 ± 2.3 mm 2 . After PCI, the mean MSA at the CN was 7.9 ± 2.5 mm 2 . Optimal stent expansion (stent expansion >80%) at the CN was achieved in 85.71% of patients. All patients remained free from MACE during hospitalization and at the 30-day follow-up. At 1-year follow-up, all-cause death had occurred in 3 (14.3%) patients., Conclusions: This single-arm study demonstrated the safety, efficacy, and utility of the IVL in a subset of patients with non-eruptive calcified nodules. In this study, minimal procedural complications, excellent lesion modifications, and favorable 30-day and 1-year outcomes were observed., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

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.

Abstract Background The interventional treatment of calcified lesions with severe tortuosity in the left anterior descending artery (LAD) was challenging and the report of rotational atherectomy with mother-and-child technique has been scarce. Case presentation An 84-year-old woman was hospitalized for non-ST-segment acute coronary syndrome. Coronary angiography revealed a calcified nodule in the LAD. During rotational atherectomy of the calcified and tortuous lesion in the proximal LAD, eccentric cutting due to wire bias nearly caused perforation. The burr seemed to protrude from the contrast media during angiography. Intravascular ultrasound imaging revealed that extremely eccentric ablation almost reached the adventitia. We successfully ablated the distal calcified nodule by preventing proximal overcutting of the tortuous lesion with support from a guide extension catheter, i.e., the mother-and-child technique, followed by the deployment of the drug-eluting stent. The patient was discharged without chest symptoms and no symptom recurred during 12-month follow-up. Conclusion This case demonstrated that safe ablation of a calcified nodule located distal to a tortuous and calcified lesion in the proximal LAD with the mother-and-child technique.

[Display omitted] [ABSTRACT FROM AUTHOR]

A 75-year-old female patient on hemodialysis presented with non–ST-segment elevation myocardial infarction. After successful primary percutaneous coronary intervention, in-stent restenosis (ISR) occurred 3 consecutive times. Intravascular imaging assessment during the repeated percutaneous coronary intervention indicated that the ISR was not associated with neointimal hyperplasia but was mainly attributed to a calcified nodule, which protruded into the lumen. We applied excimer laser catheter ablation to avoid another ISR. (Level of Difficulty: Intermediate.)

Recent advances in intravascular imaging techniques have made it possible to assess the culprit lesions of acute coronary syndrome (ACS) in the clinical setting. Intravascular ultrasound (IVUS) is the most commonly used intravascular imaging technique that provides cross-sectional images of coronary arteries. IVUS can assess plaque burden and vessel remodeling. Optical coherence tomography (OCT) is a high-resolution (10 μm) intravascular imaging technique that uses near-infrared light. OCT can identify key features of atheroma, such as lipid core and thin fibrous cap. Near-infrared spectroscopy (NIRS) can detect lipid composition by analyzing the near-infrared absorption properties of coronary plaques. NIRS provides a chemogram of the coronary artery wall, which allows for specific quantification of lipid accumulation. These intravascular imaging techniques can depict histological features of plaque rupture, plaque erosion, and calcified nodule in ACS culprit lesions. However, no single imaging technique is perfect and each has its respective strengths and limitations. In this review, we summarize the implications of combined use of multiple intravascular imaging techniques to assess the pathology of ACS and guide lesion-specific treatment.

Calcified nodules (CNs) cause in-stent restenosis (ISR) frequently. Although reprotrusion of CNs through stent struts is one of the mechanisms of ISR, the process of this phenomenon has not been understood. Furthermore, little is known about stent fracture (SF) occurring at the site of CNs. We are presenting a case of an 82-year-old male who developed early ISR due to the combination of an in-stent CN and SF in the hinged right coronary artery. The process of progression of the in-stent CN was recorded sequentially with angiography and intravascular ultrasound (IVUS). IVUS from the fulcrum of hinge motion revealed the repetitive protruding movement of the CN into the stent lumen., (© 2024 Wiley Periodicals LLC.)

The process of coronary calcification represents one of the numerous pathophysiological mechanisms involved in the atherosclerosis continuum. Optical coherence tomography (OCT) represents an ideal imaging modality to assess plaque components, especially calcium. Different calcification patterns have been contemporarily described in both early stages and advanced atherosclerosis. Microcalcifications and spotty calcifications correlate positively with macrophage burden and inflammatory markers and are more frequently found in the superficial layers of ruptured plaques in acute coronary syndrome patients. More compact, extensive calcification may reflect a later stage of the disease and was traditionally associated with plaque stability. Nevertheless, a small number of culprit coronary lesions demonstrates the presence of dense calcified plaques. The purpose of the current paper is to review the most recent OCT data on coronary calcification and the interrelation between calcification pattern and plaque vulnerability. How different calcified plaques influence treatment strategies and associated prognostic implications is of great interest.

Culprit lesions of acute coronary syndrome (ACS) could be classified as plaque rupture (PR), erosion, or calcified nodule (CN). We aimed to determine the relationship among clinical characteristics, morphological plaque features, and long-term prognosis in ACS. Patients with ACS, who underwent pre-intervention optical coherence tomography between April 2013 and July 2018 were retrospectively enrolled, and classified into the three groups based on the culprit lesion morphology. In the 436 patients enrolled, incidences of PR, erosion, and CN in ACS culprit lesions were 46.1, 39.9, and 14.0%, respectively. Plaque erosion was more frequent in men aged < 60 years and CN was more frequent in older adults in both sexes (≥ 80 years) (P < 0.001). Patients with CN had a higher incidence of hemodialysis treatment (P < 0.001) and diabetes (P = 0.003). Multivariate analysis revealed that ST elevation myocardial infarction (STEMI) (P = 0.049) and presence of thin-cap fibroatheroma (TCFA) at the culprit lesion were independently associated with PR; in younger patients (< 60 year), preserved left ventricular ejection fraction and lower incidence of TCFA were correlated with plaque erosion; and older age, non-STEMI, or unstable angina pectoris, higher serum brain natriuretic peptide levels, and lower incidence of TCFA were independently associated with CN. Multivariable analysis revealed that CN (odds ratio [OR] 1.990, P = 0.005), male sex (OR 2.012, P = 0.004), and older age (OR 1.036, P < 0.001) were independently associated with future adverse events during a median follow-up of 757 days. Different patient characteristics and morphological features were associated with the type of culprit lesion in patients with ACS. [ABSTRACT FROM AUTHOR]

Background: The interventional treatment of calcified lesions with severe tortuosity in the left anterior descending artery (LAD) was challenging and the report of rotational atherectomy with mother-and-child technique has been scarce.Case Presentation: An 84-year-old woman was hospitalized for non-ST-segment acute coronary syndrome. Coronary angiography revealed a calcified nodule in the LAD. During rotational atherectomy of the calcified and tortuous lesion in the proximal LAD, eccentric cutting due to wire bias nearly caused perforation. The burr seemed to protrude from the contrast media during angiography. Intravascular ultrasound imaging revealed that extremely eccentric ablation almost reached the adventitia. We successfully ablated the distal calcified nodule by preventing proximal overcutting of the tortuous lesion with support from a guide extension catheter, i.e., the mother-and-child technique, followed by the deployment of the drug-eluting stent. The patient was discharged without chest symptoms and no symptom recurred during 12-month follow-up.Conclusion: This case demonstrated that safe ablation of a calcified nodule located distal to a tortuous and calcified lesion in the proximal LAD with the mother-and-child technique. [ABSTRACT FROM AUTHOR]

This study sought to investigate the ability of combined near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS) to differentiate plaque rupture (PR), plaque erosion (PE), or calcified nodule (CN) in acute myocardial infarction (AMI). Most acute coronary syndromes occur from coronary thrombosis based on PR, PE, or CN. In vivo differentiation among PR, PE, and CN is a major challenge for intravascular imaging. The study enrolled 244 patients with AMI who had a de novo culprit lesion in a native coronary artery. The culprit lesions were assessed by both NIRS-IVUS and optical coherence tomography (OCT). Maximum lipid core burden index in 4 mm (maxLCBI 4mm) was measured by NIRS. Plaque cavity and convex calcium was detected by IVUS. The OCT diagnosis of PR (n = 175), PE (n = 44), and CN (n = 25) was used as a reference standard. In the development cohort, IVUS-detected plaque cavity showed a high specificity (100%) and intermediate sensitivity (62%) for identifying OCT-PR. IVUS-detected convex calcium showed a high sensitivity (93%) and specificity (100%) for identifying OCT-CN. NIRS-measured maxLCBI 4mm was largest in OCT-PR (705 [interquartile range (IQR): 545 to 854]), followed by OCT-CN (355 [IQR: 303 to 478]) and OCT-PE (300 [IQR: 126 to 357]) (p < 0.001). The optimal cutoff value of maxLCBI 4mm was 426 for differentiating between OCT-PR and -PE; 328 for differentiating between OCT-PE and -CN; and 579 for differentiating between OCT-PR and -CN. In the validation cohort, the NIRS-IVUS classification algorithm using plaque cavity, convex calcium, and maxLCBI 4mm showed a sensitivity and specificity of 97% and 96% for identifying OCT-PR, 93% and 99% for OCT-PE, and 100% and 99% for OCT-CN, respectively. By evaluating plaque cavity, convex calcium, and maxLCBI 4mm , NIRS-IVUS can accurately differentiate PR, PE, and CN. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Coronary angiography (CAG) is the standard modality for assessing coronary stenosis; however, it has limitations in assessing coronary plaque morphology. Optical coherence tomography (OCT) is a high-resolution (10-20 μm) light-based intravascular imaging technique that can identify more detailed coronary plaque morphology compared to other intravascular imaging modalities. OCT is remarkable for characterizing fibrous, fibrocalcific, and lipid-rich plaques. The capabilities of OCT are well suited for discriminating three types of unstable plaque morphologies underlying coronary thrombosis, such as plaque rupture, erosion, and calcified nodules. The high resolution of OCT makes it possible to identify important features of vulnerable plaques, such as thin-cap (<65 μm thick) fibroatheroma, macrophages, vasa vasorum, and cholesterol crystals.Areas covered: This review summarizes the clinical impact of OCT and its efficacy in identifying plaque components and morphological features associated with plaque vulnerability.Expertopinion: The unique properties of OCT as a tool for investigating high-risk lesions have greatly contributed to a better understanding of plaque vulnerability. Consequently, OCT has led to significant changes in medical treatment and percutaneous coronary intervention strategies for acute coronary syndrome. Further development and investigation of OCT are necessary to better predict and manage acute coronary events in the future. [ABSTRACT FROM AUTHOR]

Background: Calcified nodule (CN) has a unique plaque morphology, in which an area of nodular calcification causes disruption of the fibrous cap with overlying luminal thrombus. CN is reported to be the least frequent cause of acute coronary thrombosis, and the pathogenesis of CN has not been well studied.Objectives: The purpose of this study is to provide a comprehensive morphologic assessment of the CN in addition to providing an evolutionary perspective as to how CN causes acute coronary thrombosis in patients with acute coronary syndromes.Methods: A total of 26 consecutive CN lesions from 25 subjects from our autopsy registry were evaluated. Detailed morphometric analysis was performed to understand the plaque characteristics of CN and nodular calcification.Results: The mean age was 70 years, with a high prevalence of diabetes and chronic kidney disease. CNs were equally distributed between men and women, with 61.5% of CNs found in the right coronary artery (n = 16), mainly within its mid-portion (56%). All CNs demonstrated surface nonocclusive luminal thrombus, consisting of multiple nodular fragments of calcification, protruding and disrupting the overlying fibrous cap, with evidence of endothelial cell loss. The degree of circumferential sheet calcification was significantly less in the culprit section (89° [interquartile range: 54° to 177°]) than in the adjacent proximal (206° [interquartile range: 157° to 269°], p = 0.0034) and distal (240° [interquartile range: 178° to 333°], p = 0.0004) sections. Polarized picrosirius red staining showed the presence of necrotic core calcium at culprit sites of CNs, whereas collagen calcium was more prevalent at the proximal and distal regions of CNs.Conclusions: Our study suggests that fibrous cap disruption in CN with overlying thrombosis is initiated through the fragmentation of necrotic core calcifications, which is flanked-proximally and distally-by hard, collagen-rich calcification in coronary arteries, which are susceptible to mechanical stress. [ABSTRACT FROM AUTHOR]

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Calcified nodule (CN) is an eruptive calcified mass causing acute coronary syndrome (ACS). Since coronary calcification is associated with an elevated cardiac event's risk, ACS attributable to CN may exhibit worse clinical outcome following percutaneous coronary intervention (PCI). We retrospectively analyzed 657 ACS patients receiving PCI with newer-generation drug-eluting stent (DES) implantation under intravascular ultrasound (IVUS) guidance. CN was defined as (1) protruding calcification with its irregular surface and (2) the presence of calcification at adjacent proximal and distal segments. The primary endpoint was a composite of major adverse cardiac event [MACE = cardiac death + ACS recurrence + target lesion revascularization (TLR)]. CN was identified in 5.3% (=35/657) of the study subjects. CN patients were more likely to have coronary risk factors including hypertension (p = 0.005), chronic kidney disease (p < 0.001), maintenance hemodialysis (p < 0.001) and a history of PCI (p < 0.001). During the observational period (median = 1304 days), CN was associated with an increased risk of MACE (HR = 7.68, 95%CI = 4.61–12.80, p < 0.001), ACS recurrence (HR = 12.32, 95%CI = 6.05–25.11, p < 0.001) and TLR (HR = 10.48, 95%CI = 5.80–18.94, p < 0.001). These cardiac risks related to CN were consistently observed by Cox proportional hazards model (MACE: p < 0.001, ACS recurrence: p < 0.001, TLR: p < 0.001) and a propensity score–matched cohort analysis (MACE: p = 0.002, ACS recurrence: p = 0.01, TLR: p = 0.005). Of note, over 80% of TLR at the CN lesion was driven by its re-appearance within the implanted DES. ACS patients attributable to CN have an increased risk of ACS recurrence and TLR, mainly driven by the continuous growth and protrusion of the calcified mass. Image 1 • Acute coronary syndrome (ACS) patients attributable to calcified nodule (CN) exhibited significant heightened risk of adverse cardiac events compared to those without. • In ACS patients attributable to calcified nodule, recurrence of ACS occurred mainly due to in-stent restenosis. • Over 80% of in-stent restenosis at lesions containing CN exhibited its re-appearance within the implanted stent.. • Our findings suggest the need for additional therapeutic approach to modify CN in ACS subjects.. [ABSTRACT FROM AUTHOR]

Background: Calcified nodules (CN) have been linked to unfavorable clinical outcomes. However, there is a lack of systematic studies on non-culprit lesions with CN in patients with acute coronary syndromes (ACS). This study aims to investigate the frequency, distribution, predictors, and outcomes of CN in non-culprit lesions among ACS patients., Methods: We included 376 ACS patients who received successful stent placement in their culprit lesions. Intravascular ultrasound (IVUS) was performed to evaluate non-culprit lesions in left main arteries and all three coronary arteries (CA). CN was defined as accumulations of small nodular calcium deposits exhibiting a convex shape protruding into the lumen., Results: CNs was identified in 16.9% (121 of 712) per artery and 26.9% (101 of 376) per patient. They were predominantly located at the mid portion of the right coronary artery (26.3%) and the bifurcation site (59.9%). Patients with CN were older (63.57 ± 8.43 vs. 57.98 ± 7.15, p < 0.001) and had a higher prevalence of diabetes mellitus (55.4% vs. 42.2%, p = 0.022). However, there were no significant differences in baseline characteristics observed after propensity score matching (PSM). Multivariate analysis revealed that CN were independently associated with major adverse cardiovascular events (MACE) both before and after PSM (hazard ratio (HR): 0.341, 95% confidence interval (95% CI): 0.140-0.829, p = 0.018; HR: 0.275, 95% CI: 0.108-0.703, p = 0.007, respectively). During the observational period of 19.35 ± 10.59 months, the occurrence of MACE was significantly lower in patients with CN before and after PSM (5.9% vs. 16.7%, p = 0.046; 4.0% vs. 18.1%, p = 0.011; respectively)., Conclusions: CN in non-culprit lesions with ACS patients was prevalent and caused fewer adverse clinical outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Background Dialysis is an independent risk factor for in‐stent restenosis (ISR) after stent implantation in coronary arteries. However, the characteristics of ISR in patients undergoing dialysis remain unclear, as there are no histological studies evaluating the causes of this condition. The aim of the present study was to investigate the causes of ISR between patients who are undergoing dialysis and those who are not by evaluating tissues obtained from ISR lesions using directional coronary atherectomy. Methods and Results A total of 29 ISR lesions from 29 patients included in a multicenter directional coronary atherectomy registry of 128 patients were selected for analysis and divided into a dialysis group (n=8) and a nondialysis group (n=21). Histopathological evaluation demonstrated that an in‐stent calcified nodule was a major histological characteristic of ISR lesions in the dialysis group and the prevalence of an in‐stent calcified nodule was significantly higher in the dialysis group compared with the nondialysis group (75% versus 5%, respectively; P

Stenting for severely calcified lesions has a higher risk of stent restenosis or stent failure than stenting for lesions without calcification, and stenting for complex lesions including ostial or bifurcation lesions sometimes causes plaque shift which leads to side branch occlusion. A calcified nodule (CN) is considered one of the culprits for stable angina or acute coronary syndrome. However, the optimal strategy for this lesion is not well clarified. We report a patient who presented stable angina with a CN at the ostial left circumflex artery. In this case, pretreatment with excimer laser coronary atherectomy (ELCA) and scoring balloon dilatation followed by drug-coated balloon (DCB) dilatation successfully prevented plaque shift caused by stenting in the acute phase. In addition, it also maintained the patency in the late phase. Furthermore, we observed the CN lesions at preprocedural, postprocedural, and late phase by optical coherence tomography. ELCA, which has a unique debulking technique, and scoring balloon dilatation followed by DCB dilatation might offer an alternative treatment for ostial CN lesions instead of stenting. 〈 Learning objective: The optimal strategy for severely calcified lesions with calcified nodule is controversial because the prevalence of calcified nodule is rare and stent failure is more common in calcified lesions. In particular, regarding a calcified nodule located in ostial left circumflex coronary artery lesion, excimer laser coronary atherectomy and scoring balloon dilatation followed by drug-coated balloon may give an alternative treatment to avoid stenting.〉 [ABSTRACT FROM AUTHOR]

Distinct clinical characteristics have been demonstrated in patients with plaque erosion as compared with those with plaque rupture. We reasoned that greater physical activity might influence the onset of plaque erosion. In total, 97 consecutive patients with non ST-segment elevation acute coronary syndrome (ACS) who underwent optical coherence tomography (OCT) imaging of the culprit lesion were enrolled. OCT-determined culprit plaque characteristics were plaque erosion (18.6%), calcified plaque (26.8%), plaque rupture (32.0%) and other (22.7%). The physical activity evaluated by estimated metabolic equivalents (METs) at ACS onset was significantly greater in the plaque erosion group than in the plaque rupture group (3.3 ± 1.7 vs. 2.1 ± 1.0, p = 0.011). The rate of ACS onset outdoors was the highest (61.1%) in the plaque erosion group. The combination of greater physical activity (> 3 METs), outdoor onset and higher body mass index (> 25.1 kg/m2) had a significant odds ratio for the incidence of plaque erosion (odds ratio 15.0, 95% confidence interval 3.81 to 59.0, p < 0.001). Plaque erosion was associated with greater physical activity at the onset. This finding may help to further clarify the pathogenesis of ACS Impact of physical exertion on the incidence of plaque erosion. NSTE-ACS, non ST-segment elevation acute coronary syndrome. [ABSTRACT FROM AUTHOR]

Solitary calcified nodule-related carpal tunnel syndrome (CTS) is rare and easy to be misdiagnosed owing to the high incidence of primary CTS. Release of the transverse carpal ligament without removal of the mass leads to persistence of the symptoms and subsequent complications like wasting of the thenar muscles. Here, we report two cases of solitary calcified nodule-related CTS and discuss the role of ultrasound in preventing misdiagnosis. Both patients reported persistent numbness over the lateral side of their palm and weakness of the right wrist with thenar muscle atrophy. One patient had undergone transverse carpal ligament release 2 years previously, and the other had received a local injection of lidocaine at the clinic. Neither patient experienced symptom relief. X-ray revealed a similar finding of nodule lesions in front of the capitate–hamate region. Solitary calcified nodule-related CTS was diagnosed, and the patients underwent nodule removal with/without transverse ligament release. The first patient was a typical case of misdiagnosed solitary calcified nodule-related CTS. The second patient had a definitive clinical sonographic diagnosis before surgery. The accurate diagnosis of secondary CTS is paramount for performing effective surgery. Thus, ultrasonography is an easy, convenient, safe, and effective method in screening for secondary CTS.

In-stent restenosis with neoatherosclerosis has been known as the predictor of target lesion revascularization (TLR) after percutaneous coronary intervention. However, the impact of in-stent calcification (ISC) alone on clinical outcomes remains unknown since neoatherosclerosis by optical coherence tomography includes in-stent lipid and calcification. We aimed to assess the effect of ISC on clinical outcomes and clinical differences among different types of ISC. We included 126 lesions that underwent optical coherence tomography-guided percutaneous coronary intervention and divided those into the ISC group (n = 38) and the non-ISC group (n = 88) according to the presence of ISC. The cumulative incidence of clinically driven TLR (CD-TLR) was compared between the ISC and non-ISC groups. The impact of in-stent calcified nodule and nodular calcification on CD-TLR was evaluated using the Cox hazard model. The incidence of CD-TLR was significantly higher in the ISC group than in the non-ISC group (p = 0.004). In the multivariate Cox hazard model, ISC was significantly associated with CD-TLR (hazard ratio [HR] 3.58, 95% confidence interval [CI] 1.33 to 9.65, p = 0.01). In-stent calcified nodule/nodular calcification and in-stent nodular calcification alone were also the factors significantly associated with CD-TLR (HR 3.34, 95%CI 1.15 to 9.65, p = 0.03 and HR 5.21, 95%CI 1.82 to 14.91, p = 0.002, respectively). ISC without in-stent calcified nodule/nodular calcification, which was defined as in-stent smooth calcification, was not associated with CD-TLR. In conclusion, ISC was associated with a higher rate of CD-TLR. The types of calcifications that led to a high rate of CD-TLR were in-stent calcified nodule/nodular calcification and in-stent nodular calcification alone but not in-stent smooth calcification. In-stent calcified nodule and nodular calcification should be paid more attention., Competing Interests: Declaration of competing interest Dr. Jinnouchi has received speaking honoraria from Abbott Vascular, Boston Scientific, Terumo and NIPRO. Dr. Sakakura has received speaking honoraria from Abbott Vascular, Boston Scientific, Medtronic Cardiovascular, Terumo, OrbusNeich, Japan Lifeline, Kaneka, and NIPRO; served as a proctor for Rotablator for Boston Scientific; and served as a consultant for Abbott Vascular and Boston Scientific. Prof. Fujita has served as a consultant for Mehergen Group Holdings, Inc. The remaining authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Percutaneous coronary intervention (PCI) of calcified coronary arteries is associated with poor outcomes. Poorly modified calcified lesion hinders the stent delivery, disrupts drug-carrying polymer, impairs drug elution kinetics and results in under-expanded stent (UES). UES is the most common cause of acute stent thrombosis and in-stent restenosis after PCI of calcified lesions. Angiography has poor sensitivity for recognition and quantification of coronary calcium, thereby mandating the use of intravascular imaging. Intravascular imaging, like intravascular ultrasound and optical coherence tomography, has the potential to accurately identify and quantify the coronary calcium and to guide appropriate modification device before stent placement. Available options for the modification of calcified plaque include modified balloons (cutting balloon, scoring balloon and high-pressure balloon), atherectomy devices (rotational atherectomy and orbital atherectomy) and laser atherectomy. Coronary intravascular lithotripsy (IVL) is the newest addition to the tool box for calcified plaque modification. It produces the acoustic shockwaves, which interact with the coronary calcium to cause multiplanar fractures. These calcium fractures increase the vessel compliance and result in desirable minimum stent areas. Coronary IVL has established its safety and efficacy for calcified lesion in series of Disrupt CAD trials. Its advantages over atherectomy devices include ease of use on workhorse wire, ability to modify deep calcium, no debris embolization causing slow flow or no-flow and minimal thermal injury. It is showing promising results in modification of difficult calcified lesion subsets such as calcified nodule, calcified left main bifurcation lesions and chronic total occlusion. In this review, authors will summarize the mechanism of action for IVL, its role in contemporary practice, evidence available for its use, its advantages over atherectomy devices and its imaging insight in different calcified lesion scenarios.