Identification and treatment of calcified nodules in percutaneous coronary intervention.

Calcified nodules in the coronary arteries: systematic review on incidence and percutaneous coronary intervention outcomes.

Case presentation : A 56-year-old man presented to the hospital with chest pain and a non–ST-segment elevation myocardial infarction. Thrombotic plaque rupture in the left anterior descending coronary artery was treated with an everolimus-eluting stent. After stent deployment, angiography demonstrated the presence of a hazy opacity at the distal edge of the stent, and there was concern about a possible edge dissection. Optical coherence tomography (OCT) imaging of the opacity showed residual thrombus and no dissection. Subsequent aspiration thrombectomy and balloon dilation effectively treated the lesion without deployment of an additional stent. OCT is an intravascular imaging modality that utilizes near-infrared light to generate cross-sectional blood vessel images. OCT is similar to intravascular ultrasound (IVUS), and both OCT and IVUS provide information about intravascular anatomy that far exceeds the level of detail obtained from conventional contrast cineangiography. With the use of light rather than ultrasound reflectance, OCT generates in vivo images of coronary arteries and deployed stents with up to 10 to 15 μm of spatial resolution compared with the 100- to 200-μm resolution of IVUS. Although the spatial resolution of OCT is markedly superior to that of IVUS, near-infrared light does not penetrate tissue as effectively as sound, and therefore OCT imaging depths range from 1 to 3 mm into the vessel wall, whereas IVUS imaging depths range from 4 to 10 mm (Table). Additionally, near-infrared light is scattered by red blood cells, and therefore OCT imaging requires transient blood clearing during image acquisition. View this table: Table. Comparison of FD-OCT and IVUS The speed of light was initially a central challenge to developing a “clinically friendly” OCT system. Light travels too quickly for direct measurement of differential reflectance caused by vascular structures, and the original time delay OCT (TD-OCT) systems utilized a moving reference mirror to calibrate reflected light waves for image …

To provide a summary of prevalence, pathogenesis, and treatment of coronary calcified nodules (CNs). CNs are most frequently detected at the sites of hinge motion of severely calcified lesions such as in the middle segment of right coronary artery and left main coronary bifurcation. On histopathology, CNs exhibit two distinctive morphologies: eruptive and non-eruptive. Eruptive CNs, which have a disrupted fibrous cap with adherent thrombi, are biologically active. Non-eruptive CNs, which have an intact fibrous cap without thrombi, are biologically inactive, representing either healed eruptive CNs or protrusion of calcium due to plaque progression. Recent studies using optical coherence tomography (OCT) have shown a difference in the mechanism of stent failure in the two subtypes, demonstrating early reappearance of eruptive CNs in the stent (at ~ 6months) as a unique mechanism of stent failure that does not seem to be preventable by simply achieving adequate stent expansion. The cause of CN reappearance in stent is not known and could be due to acute or subacute intrusion or continued growth of the CN. Whether modification of CN is needed, the most effective calcium modification modality and effectiveness of stent implantation in eruptive CNs has not been elucidated. In this review, we discuss pathogenesis of CNs and how intravascular imaging can help diagnose and manage patients with CNs. We also discuss medical and transcatheter therapies beyond conventional stent implantation for effective treatment of eruptive CNs that warrant testing in prospective studies.

Percutaneous coronary intervention has been developed for patients with coronary artery disease. Calcified lesions are recognized as an unsolved issue where many clinical devices have evolved and some disappeared. Understanding intracoronary imaging of the calcified lesions can help operators to make decisions during the procedure. There are several potential stories of progression of calcification, although a precise mechanism of progression of calcification remains unknown. In the process of a large calcification, it is histologically believed that lipid is replaced by calcification. This process can be observed by intracoronary imaging devices, i.e., intravascular ultrasound and optical coherence tomography. Calcified nodule is a unique type of calcifications. Among the calcified lesions, especially calcified nodule has serious clinical outcomes such as target lesion revascularization (TLR) with stent under-expansion. Additionally, in-stent calcified nodule is a distinctive type of restenosis pattern after stenting to calcified nodule, leading to malignant cycle of repeated TLR. Recently, calcified nodule is divided into two types based on the surface irregularity: (1) eruptive and (2) non-eruptive calcified nodule. Eruptive calcified nodule has higher rate of target vessel revascularization than non-eruptive calcified nodule despite greater stent expansion in eruptive calcified nodule. It is thought that there are differences of component such as the amount of fibrin and the size of calcific nodules between both, although it is common for both to include calcific nodules and fibrin. Histopathological understanding calcified nodule can be helpful to choose the treatment devices during the procedure in the area where there is no correct answer.

BackgroundCalcified plaque is thought to adversely impact outcomes after percutaneous coronary intervention (PCI). This study sought to evaluate the impact of nodular calcification in patients with acute coronary syndrome treated with primary percutaneous coronary intervention.MethodsUsing optical coherence tomography (OCT), 500 culprit plaques with calcification were analyzed from 495 acute coronary syndrome (ACS) patients on whom PCI was performed. Based on morphology, we classified calcification into two subtypes: nodular calcification and non-nodular calcification. Nodular calcification was defined as protruding mass with an irregular surface, high backscattering, and signal attenuation while non-nodular calcification was defined as an area with low backscattering heterogeneous region with a well-delineated border without protrusion into the lumen on OCT.ResultsCalcified culprit plaques were divided into nodular calcification group (n = 238) and non-nodular calcification group (n = 262). Patients with nodular calcification were older (p < 0.001) and had lower left ventricular ejection fraction (p = 0.006) compared to patients with non-nodular calcification. Minimum stent area (5.0 (3.9, 6.3) mm2 vs. 5.4 (4.2, 6.7) mm2, p = 0.011) and stent expansion (70 (62.7, 81.8) % vs. 75 (65.2, 86.6) %, p = 0.004) were significantly smaller in the nodular calcification group than in the non-nodular calcification group. Stent under-expansion was most frequent (p = 0.003) in the nodular calcification group.ConclusionThis study demonstrate that the presence of nodular calcification is associated with a smaller minimum stent area and a higher incidence of stent under-expansion. Lesions with nodular calcification may be at risk of stent under-expansion.

Orbital atherectomy versus balloon angioplasty before drug-eluting stent implantation in severely calcified lesions eligible for both treatment strategies (ECLIPSE): a multicentre, open-label, randomised trial.

Background Calcified nodule (CN) is a distinct plaque phenotype, characterized as protruding nodular calcification penetrating lumen surface with the attached thrombus. Recent studies revealed that a risk of repeat revascularization after PCI was substantially elevated in patients with coronary artery disease (CAD) attributable to CN. Furthermore, pathohistological studies have elucidated mechanistic insights into the formulation and progression of CN, suggesting that it is formulated by the fracture of sheet calcification at its adjacent segment. Purpose To elucidate the association of calcified plaque volume at CN and adjacent lesions with TLR risks in CAD patients receiving PCI by using IVUS imaging. Methods This multicenter study analyzed IVUS imaging at culprit segment was conducted in 204 CAD patients attributable to de novo CN receiving PCI. The calc grade was assigned at each 1-mm cross-sectional frame of CN and culprit segment, respectively (no calc=0, 1-89°=1, 90-179°=2, 180-269°=3, 270-360°=4). Calcium Volume Index (CVI) at both CN and adjacent zone were calculated (Figure; Calcification volume index at CN zone = the sum of calcium scores at CN・averaged lesion slices of CN / CN lesion slices, Calcification volume index at adjacent zone = the sum of calcium scores at adjacent zone・averaged lesion slices of adjacent zone / adjacent zone slices). Predictors of TLR were analyzed by multivariate Cox hazard model. Results CN was successfully treated by DES (82%) and DCB (18%). 34% and 8.3% of subjects required rotablator and orbital atherectomy, respectively. Consequently, final lumen area after PCI was 7.2 ± 0.4 mm2. During the 2.8-year observational period (interquartile range: 2.4 to 3.2 years), TLR was required in 63 patients (30.9%) of study population. CVI at CN and adjacent zone were 9.9 ± 0.4 and 7.0 ± 0.7, respectively. On multivariate analysis, hemodialysis, final lumen area, CVI at both CN and adjacent zone predicted TLR (Figure). Recurrent TLR (two or more TLRs) was found in 23.3% patients who suffered from TLR. Of note, even among patients who required TLR, CVIs at both zones were significantly higher in patients with recurrent TLR than those without (Figure). Conclusion CAD subjects caused by CN exhibited a considerably high-risk TLRs. Our findings underscore that calcification severity at both CN and adjacent segment predicted TLR and is associated with repeated TLR.methodsResults

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.

Acute coronary syndrome includes unstable angina, acute myocardial infarction, and sudden coronary death. In individuals with sudden coronary death, 50–60% displays acute coronary thrombus at the culprit site, while the remaining cases demonstrate a stable coronary plaques with greater than 75% cross-sectional area luminal narrowing, with or without chronic total occlusion or healed myocardial infarction. Three different causes of coronary thrombus have been shown, i.e., plaque rupture, plaque erosion, and calcified nodule. Plaque rupture (PR) is the most common cause of coronary thrombus, which shows a disrupted fibrous cap and an underlying necrotic core in contact with the flowing blood and a luminal thrombus. The second most common cause of thrombosis is plaque erosion. Plaque erosions show an absence of endothelium with an underlying abundance of smooth muscle cells in a proteoglycan-collagen-rich matrix. The least frequent cause of coronary thrombosis is calcified nodule which occurs in highly calcified arteries. Calcified nodule demonstrates a disrupted fibrous cap due to fragments of calcified spicules typically surrounded by fibrin and an overlying platelet-rich thrombus. Calcified nodules are usually eccentric and usually have an overlying nonocclusive thrombus. The precursor lesion of rupture is a vulnerable plaque which demonstrates all the features of rupture, but there is an intact fibrous cap, and the necrotic core is usually smaller than that observed in ruptures. Erosive plaques mostly show an underlying fibroatheroma or pathologic intimal thickening, while calcified nodules demonstrate a highly calcified plaque in a heavily calcified coronary artery.

Background: Among calcified lesions, nodular calcium is the most challenging subset to deal with during percutaneous coronary intervention (PCI), as there are limited options available for its modification. This study was done to assess the safety, efficacy and impact of coronary intravascular lithotripsy (IVL) on calcified nodule (CN) using optical coherence tomography (OCT). Methods: A total of 17 patients with 40 CN undergoing PCI using coronary intravascular lithotripsy were prospectively enrolled in the study. OCT parameters studied were pre-IVL minimum lumen area (MLA), calcium (Ca) score, number of CN, proximal and distal reference diameter, post-IVL gain in MLA, calcium fracture, major dissection, post-PCI minimum stent area (MSA), stent expansion, apposition, edge dissection and spherical index at CN. Spherical index was calculated by dividing the shortest and longest diameter at CN after stent placement. The primary safety endpoint was freedom from major adverse cardiovascular events (death, MI and target vessel revascularization) during hospitalisation and at 30 days. Primary efficacy endpoints were gain in MLA after stent placement and stent expansion. Results: Pre-IVL mean MLA at CN was 3.87±2.25mm 2 , Ca score was 3.94±0.24, Ca arc 190.59±54.02 o , Ca depth 0.97±0.31mm, Ca length 22.73±9.87mm and CN height-1.04±0.30 mm. All 17 (100%) patients developed Ca fractures, post-IVL MLA at CN was 5.20±2.31mm 2 , CN height 0.83±0.19mm and luminal gain at CN was 0.76 ± 1.71mm 2 . 10 (58.8%) patients developed fractures at base of CN and rest developed fractures at apex. Patients with fractures at base showed decrease in luminal area after IVL due to luminal shift of nodule, but all these patients had good stent expansion, likely due to Ca softening. Post-IVL OCT showed minor dissections in 5 (29.4%) and major in 3 (17.6%) patients. There was no perforation, slow flow or abrupt vessel closure. Stent expansion and MSA at CN was 107.12 ± 18.98% and 8.57±2.54 mm 2 respectively with spherical index of 0.83±0.12. All patients were free of MACE during hospitalization and at 30 days. Conclusion: Coronary intravascular lithotripsy is safe and effective for modification of coronary calcified nodules during percutaneous coronary intervention.

Our aim was to compare stenosis severity and plaque content between STEMI culprit lesions with intact fibrous cap (IFC) and those with plaque rupture (PR) in a prospective study. We evaluated 93 patients undergoing OCT and thrombectomy as part of a prospective substudy of the TOTAL (ThrOmbecTomy versus PCI ALone) trial. Culprit lesion morphology was assessable by OCT in 70/93 (75.3%). IFC was found in 31 (44.3%), PR in 34 (48.6%) and calcified nodule in five (7.1%) patients. Following thrombectomy, OCT demonstrated similar lumen area stenosis in IFC (79.3%) and PR (79.6%) (p=0.88). Lumen area stenosis <50% was observed in none of the patients with PR and in one patient with IFC. IFC had fewer quadrants with lipid plaque as compared to PR (28.16±15.02 vs. 39.12±14.23, p=0.004). However, in both lesion types, lipid was the predominant plaque type (83.9 vs. 63.7% of diseased quadrants). In a prospective study of STEMI patients treated with thrombectomy, mild residual stenoses were uncommon in IFC lesions. Although lipid content was lower than in PR lesions, lipid composed the majority of the diseased segments in IFC.

Impact of ultrasound reverberation in calcified coronary arteries: Intravascular ultrasound study

A Combined Optical Coherence Tomography and Intravascular Ultrasound Study on Plaque Rupture, Plaque Erosion, and Calcified Nodule in Patients With ST-Segment Elevation Myocardial Infarction: Incidence, Morphologic Characteristics, and Outcomes After Percutaneous Coronary Intervention.

Evidence of prognostic factors for stent failure after drug-eluting stent implantation for calcified nodules (CNs) is limited. We aimed to clarify the prognostic risk factors associated with stent failure among patients who underwent drug-eluting stent implantation for CN lesions using optical coherence tomography (OCT). This retrospective, multicentre, observational study included 108 consecutive patients with CNs who underwent OCT-guided percutaneous coronary intervention (PCI). To evaluate the quality of CNs, we measured their signal intensity and analysed the degree of signal attenuation. All CN lesions were divided into dark or bright CNs according to the half width of signal attenuation, greater or lower than 332, respectively. During the median follow-up period of 523 days, 25 patients (23.1%) experienced target lesion revascularisation (TLR). The 5-year cumulative incidence of TLR was 32.6%. Multivariable Cox regression analysis revealed that younger age, haemodialysis, eruptive CNs, dark CNs assessed by pre-PCI OCT, disrupted fibrous tissue protrusions, and irregular protrusions assessed by post-PCI OCT were independently associated with TLR. The prevalence of in-stent CNs (IS-CNs) observed at follow-up OCT was significantly higher in the TLR group than in the non-TLR group. Factors such as younger age, haemodialysis, eruptive CNs, dark CNs, disrupted fibrous tissue, or irregular protrusions were independently related to TLR in patients with CNs. The high prevalence of IS-CNs might indicate that the main cause of stent failure implanted in CN lesions could be the recurrence of CN progression in the stented segment.

Calcified nodule (CN) is a phenotypic feature of calcified plaques which causes acute coronary syndrome (ACS). Recent studies reported that culprit lesions harboring CN has been shown to increase a risk of repeat revascularization after percutaneous coronary intervention (PCI) with the implantation of newer-generation drug-eluting stent (DES) or debulking device. Mechanistically, a re-protrusion of CN into the lumen has been considered as an important cause associated with repeat revascularization after PCI. These observations suggest the need for additional therapeutic approach to mitigate a risk of repeat revascularization at CN lesions. Here we report a case who received the implantation of one covered stent due to coronary artery perforation after stent implantation at coronary lesion exhibiting CN. This case is unique in terms of preventing restenosis by using covered stent which could physically hinder protrusion of CN through the stent strut. A 79-year-old man presented to the emergency department with his prolonged chest pain. Although he had a history of hypertension and adrenal hypertrophy, he was not taking any medication prior to his admission. He was diagnosed as ST-segment elevation myocardial infarction. Emergent coronary angiography revealed one severe stenosis in the middle segment of his right coronary artery (RCA). Primary PCI was performed under the guidance of intravascular ultrasound (IVUS) imaging. IVUS imaging prior to PCI revealed a protruding shape of calcification and its irregular surface at his culprit lesion, suggesting the presence of a CN. Following one DES implantation, coronary artery perforation occurred at the segment receiving DES implantation. We implanted one covered stent for the coronary artery perforation. This procedure resulted in successfully sealing coronary artery perforation. Seven months later, follow-up coronary angiography and optical coherence tomography (OCT) imaging were conducted to evaluate his RCA. Any in-stent restenosis (ISR) was not observed. Furthermore, OCT imaging elucidated a small amount of neointimal proliferation without any re-protruding feature of CN through the segment receiving a covered stent. Of note, he did not experience any clinically-driven target lesion revascularization (TLR) for 2 years after PCI. Our case indicates the use of covered stent as an effective approach to physically hinder the re-protrusion of calcification tissues into the lumen, potentially mitigating a risk of ISR.