Calcified Plaque

Evan Shlofmitz; Nowera Zafar; Nauman Khalid

Calcified Plaque

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Continuing Education Activity

Coronary artery calcification is frequently encountered during percutaneous coronary intervention (PCI). Calcified plaque poses numerous challenges to successful percutaneous coronary intervention. Stent delivery and optimal stent expansion become more difficult with a calcified plaque. Procedural complications and long-term adverse outcomes are worse and closely correlated with increasing severity of coronary artery calcification. This activity reviews the etiology, presentation, evaluation, and management of calcified plaque lesions and reviews the role of the interprofessional team in evaluating, diagnosing, and managing the condition.

Objectives:

Describe the evaluation of calcified plaque in coronary vessels.
Summarize the treatment of calcified plaques in coronary vessels and the unique challenges they present.
Review the prognosis of patients with calcified plaques in coronary vessels.
Outline interprofessional team strategies for improving care coordination and communication to improve outcomes for patients with calcified plaque lesions in their coronary arteries.

Introduction

Etiology

Risk factors associated with coronary artery calcification include advanced age, diabetes, kidney disease, and smoking increasing prevalence.[3][4]

Epidemiology

Severe coronary artery calcification is present in approximately 6 to 20% of all patients treated with PCI.[5]

Histopathology

A calcified nodule (CN) is an eruptive accumulation of small nodular calcifications with a thick calcified plate and overlying thrombus that correlate with an acute coronary syndrome.[6] Calcified nodules are present in approximately 4% of lesions and are best visualized with optical coherence tomography (OCT) in vivo.[6]

History and Physical

A comprehensive history can elucidate risk factors associated with increased coronary artery calcification (CAC). In patients with multiple risk factors for CAC undergoing coronary angiography, a high clinical suspicion should be present and intravascular imaging should be used as needed for further characterization.

Evaluation

Severe coronary artery calcification has been classically defined angiographically as the presence of radiopacities appreciated without cardiac motion before the injection of contrast, which involves both sides of an arterial wall, with calcification length of greater than or equal to 15 mm and extend at least partially into a target lesion.[7] By intravascular ultrasound (IVUS), severe coronary artery calcification is defined by the presence of an arc of calcium greater than or equal to 270 degrees on at least one cross-sectional plane. By angiography alone, coronary artery calcium is significantly underappreciated and underrecognized.[8] Intravascular imaging modalities including IVUS and OCT allow for improved detection and characterization of the presence and severity of coronary artery calcification.[9][10]

Treatment / Management

The treatment of calcified lesions during PCI is dependent on the severity of calcium. An OCT-based scoring system, known as the calcium-volume index or rule of 5's, helps to stratify the likelihood a calcified plaque would correlate with stent under-expansion if not treated with a lesion preparation strategy. Calcified lesions involving an arc of calcium more than 50% of the vessel (greater than 180 degrees), with a thickness exceeding 0.5mm and over 5 mm in length, are most strongly associated with stent under-expansion and should be treated with atherectomy when appropriate.[11] Calcified lesions with a mild to moderate degree of calcification can be treated with cutting, scoring, or sculpting balloons and often do not require atherectomy. Severely calcified lesions, however, are best managed with adjunctive atherectomy in advance of stent implantation. Not only does atherectomy improve the likelihood of successful stent delivery, but atherectomy modifies the plaque morphology of the lesion, facilitating adequate stent expansion by increasing the possibility of calcium fracture.[12] Maximizing stent expansion can help to reduce the likelihood of in-stent restenosis.

The two primary atheroablative modalities for lesion preparation of severely calcified lesions before stent implantation include rotational atherectomy (RA) and orbital atherectomy (OA). Rotational atherectomy was developed by David Auth and has been in clinical use since 1988.[13] RA uses differential cutting, is available in diameters ranging from 1.25 to 2.50 mm can rotate at speeds often ranging from 150000 to 200,000 rpm. The PREPARE-CALC trial demonstrated that target lesion revascularization, stent thrombosis, and target vessel failure were low and not significantly different between the traditional angioplasty and RA groups with contemporary drug-eluting stents.[14][15]

Orbital atherectomy is a newer modality that utilizes an eccentrically mounted, diamond-coated crown that orbits bi-directionally.[16] Coronary orbital atherectomy is available with a single 1.25mm burr and can orbit at either low speed (80000 rpm) or high speed (120000 rpm).[17] The ORBIT II trial compared orbital atherectomy with historical controls and found OA to be safe, feasible, and associated with a low rate of adverse ischemic events.[18] A real-world multicenter, all-comers registry of patients treated with orbital atherectomy confirmed these findings.[19]

A new tool for lesion preparation of severely calcified coronary plaque is intravascular lithotripsy (IVL), which incorporates emitters that release sonic pressure waves to modify calcified plaque and fracture calcium.[20] Excimer-laser coronary atherectomy (ELCA) can be used to facilitate the treatment of under-expanded stents due to stent implantation within the heavily calcified plaque.[21][22][21] Following stent implantation in a calcified plaque, routine intravascular imaging can be used to confirm the achievement of adequate stent expansion.[23]

Differential Diagnosis

Intravascular imaging modalities allow for the characterization of plaque and can detect calcified plaque with increased sensitivity than with angiography alone.[24] Intravascular imaging with IVUS or OCT at times has limitations in its ability to differentiate predominantly calcified plaque from lipid-rich plaque due to the often heterogeneous nature of the disease.[25] Near-infrared spectroscopy (NIRS) is an intravascular imaging modality that can detect lipid-rich plaque (LRP), helping to distinguish LRP from calcified plaque.[26] Calcium may deposit in different cardiovascular structures, including within coronary arteries, myocardium, and pericardium.[27]

Pertinent Studies and Ongoing Trials

The Evaluation of Treatment Strategies for Severe Calcific Coronary Arteries: Orbital Atherectomy vs. Conventional Angioplasty Technique Prior to Implantation of Drug-Eluting Stents: The ECLIPSE Trial (ECLIPSE) [ClinicalTrials.gov Identifier: NCT03108456] is an ongoing randomized clinical trial that will be the largest to date evaluating the treatment of severely calcified lesions with PCI. The ECLIPSE trial is comparing orbital atherectomy versus conventional angioplasty prior to stent implantation and plans to enroll an estimated 2000 patients.

Prognosis

Calcified coronary artery lesions are associated with worse outcomes both periprocedural and long-term when treated with percutaneous coronary interventions.[5][28] At the time of PCI, calcified lesions have correlations with an increased likelihood of unsuccessful stent delivery as well as worse stent expansion compared with a non-calcified lesion.[1] The stent under-expansion commonly associated with calcified lesions is directly associated with higher rates of restenosis.[29]

Complications

Percutaneous coronary revascularization of coronary artery calcification correlates with increased procedural complications and worse long-term outcomes. Stent under-expansion is a common complication of PCI of a heavily calcified plaque without adequate lesion preparation.[30]

Deterrence and Patient Education

Risk factors for calcified lesions include increasing age and diabetes, smoking, peripheral vascular disease, chronic kidney disease, and hemodialysis.

Enhancing Healthcare Team Outcomes

Recognition of calcified plaque is essential during PCI to optimize stent implantation. Calcified plaque is best assessed and characterized by intravascular imaging modalities. Stent under-expansion is a frequent complication of PCI in severely calcified plaque and correlates with high rates of in-stent restenosis. Severe coronary artery calcification frequently warrants lesion preparation to facilitate optimal stent expansion.

After PCI, management involving an interprofessional team that includes the vascular surgeon, the primary care provider, and nurse practitioner, as well as specialty trained nursing and pharmacy, should participate in optimizing patient care following the procedure to enhance patient outcomes. Communication between these professionals will improve the coordination of care. Specialty trained nurses in cardiology, intensive care, and rehabilitation may be involved.

In the aftermath, the primary care physician, nursing, and pharmacy can collaboratively educate the patient on limiting the risk factors for CAD include cessation of smoking, participating in regular exercise, eating a healthy diet, and maintaining optimal body weight. [Level 5]

Details

References

[1]

Barbato E, Shlofmitz E, Milkas A, Shlofmitz R, Azzalini L, Colombo A. State of the art: evolving concepts in the treatment of heavily calcified and undilatable coronary stenoses - from debulking to plaque modification, a 40-year-long journey. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2017 Aug 25:13(6):696-705. doi: 10.4244/EIJ-D-17-00473. Epub [PubMed PMID: 28844031]

[2]

Mattesini A, Di Mario C. Calcium: A predictor of interventional treatment failure across all fields of cardiovascular medicine. International journal of cardiology. 2017 Mar 15:231():97-98. doi: 10.1016/j.ijcard.2017.01.054. Epub 2017 Jan 10 [PubMed PMID: 28096040]

[3]

Madhavan MV, Tarigopula M, Mintz GS, Maehara A, Stone GW, Généreux P. Coronary artery calcification: pathogenesis and prognostic implications. Journal of the American College of Cardiology. 2014 May 6:63(17):1703-14. doi: 10.1016/j.jacc.2014.01.017. Epub 2014 Feb 12 [PubMed PMID: 24530667]

[4]

Castagna MT, Mintz GS, Ohlmann P, Kotani J, Maehara A, Gevorkian N, Cheneau E, Stabile E, Ajani AE, Suddath WO, Kent KM, Satler LF, Pichard AD, Weissman NJ. Incidence, location, magnitude, and clinical correlates of saphenous vein graft calcification: an intravascular ultrasound and angiographic study. Circulation. 2005 Mar 8:111(9):1148-52 [PubMed PMID: 15723972]

[5]

Généreux P, Madhavan MV, Mintz GS, Maehara A, Palmerini T, Lasalle L, Xu K, McAndrew T, Kirtane A, Lansky AJ, Brener SJ, Mehran R, Stone GW. Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes. Pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) TRIALS. Journal of the American College of Cardiology. 2014 May 13:63(18):1845-54. doi: 10.1016/j.jacc.2014.01.034. Epub 2014 Feb 19 [PubMed PMID: 24561145]

[6]

Lee T, Mintz GS, Matsumura M, Zhang W, Cao Y, Usui E, Kanaji Y, Murai T, Yonetsu T, Kakuta T, Maehara A. Prevalence, Predictors, and Clinical Presentation of a Calcified Nodule as Assessed by Optical Coherence Tomography. JACC. Cardiovascular imaging. 2017 Aug:10(8):883-891. doi: 10.1016/j.jcmg.2017.05.013. Epub [PubMed PMID: 28797410]

[7]

Lee MS, Anose BM, Martinsen BJ, Lee AC, Shlofmitz RA, Chambers JW. Orbital atherectomy treatment of severely calcified native coronary lesions in patients with prior coronary artery bypass grafting: Acute and one-year outcomes from the ORBIT II trial. Cardiovascular revascularization medicine : including molecular interventions. 2018 Jul:19(5 Pt A):498-502. doi: 10.1016/j.carrev.2017.10.009. Epub 2017 Nov 5 [PubMed PMID: 29117920]

[8]

Mintz GS, Popma JJ, Pichard AD, Kent KM, Satler LF, Chuang YC, Ditrano CJ, Leon MB. Patterns of calcification in coronary artery disease. A statistical analysis of intravascular ultrasound and coronary angiography in 1155 lesions. Circulation. 1995 Apr 1:91(7):1959-65 [PubMed PMID: 7895353]

[9]

Wang X, Matsumura M, Mintz GS, Lee T, Zhang W, Cao Y, Fujino A, Lin Y, Usui E, Kanaji Y, Murai T, Yonetsu T, Kakuta T, Maehara A. In Vivo Calcium Detection by Comparing Optical Coherence Tomography, Intravascular Ultrasound, and Angiography. JACC. Cardiovascular imaging. 2017 Aug:10(8):869-879. doi: 10.1016/j.jcmg.2017.05.014. Epub [PubMed PMID: 28797408]

[10]

Shlofmitz E, Kuku KO, Waksman R, Garcia-Garcia HM. Intravascular ultrasound-guided drug-eluting stent implantation. Minerva cardioangiologica. 2019 Aug:67(4):306-317. doi: 10.23736/S0026-4725.19.04895-3. Epub 2019 Mar 4 [PubMed PMID: 30845795]

[11]

Fujino A, Mintz GS, Matsumura M, Lee T, Kim SY, Hoshino M, Usui E, Yonetsu T, Haag ES, Shlofmitz RA, Kakuta T, Maehara A. A new optical coherence tomography-based calcium scoring system to predict stent underexpansion. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2018 Apr 6:13(18):e2182-e2189. doi: 10.4244/EIJ-D-17-00962. Epub 2018 Apr 6 [PubMed PMID: 29400655]

[12]

Fujino A, Mintz GS, Lee T, Hoshino M, Usui E, Kanaji Y, Murai T, Yonetsu T, Matsumura M, Ali ZA, Jeremias A, Moses JW, Shlofmitz RA, Kakuta T, Maehara A. Predictors of Calcium Fracture Derived From Balloon Angioplasty and its Effect on Stent Expansion Assessed by Optical Coherence Tomography. JACC. Cardiovascular interventions. 2018 May 28:11(10):1015-1017. doi: 10.1016/j.jcin.2018.02.004. Epub [PubMed PMID: 29798768]

[13]

Valdes PJ, Nagalli S, Diaz MA. Rotational Atherectomy. StatPearls. 2023 Jan:(): [PubMed PMID: 29763091]

[14]

Abdel-Wahab M, Toelg R, Byrne RA, Geist V, El-Mawardy M, Allali A, Rheude T, Robinson DR, Abdelghani M, Sulimov DS, Kastrati A, Richardt G. High-Speed Rotational Atherectomy Versus Modified Balloons Prior to Drug-Eluting Stent Implantation in Severely Calcified Coronary Lesions. Circulation. Cardiovascular interventions. 2018 Oct:11(10):e007415. doi: 10.1161/CIRCINTERVENTIONS.118.007415. Epub [PubMed PMID: 30354632]

[15]

Wilensky RL, Selzer F, Johnston J, Laskey WK, Klugherz BD, Block P, Cohen H, Detre K, Williams DO. Relation of percutaneous coronary intervention of complex lesions to clinical outcomes (from the NHLBI Dynamic Registry). The American journal of cardiology. 2002 Aug 1:90(3):216-21 [PubMed PMID: 12127606]

Level 2 (mid-level) evidence

[16]

Shlofmitz E, Shlofmitz R, Lee MS. Orbital Atherectomy: A Comprehensive Review. Interventional cardiology clinics. 2019 Apr:8(2):161-171. doi: 10.1016/j.iccl.2018.11.006. Epub 2019 Jan 30 [PubMed PMID: 30832940]

[17]

Shlofmitz E, Martinsen BJ, Lee M, Rao SV, Généreux P, Higgins J, Chambers JW, Kirtane AJ, Brilakis ES, Kandzari DE, Sharma SK, Shlofmitz R. Orbital atherectomy for the treatment of severely calcified coronary lesions: evidence, technique, and best practices. Expert review of medical devices. 2017 Nov:14(11):867-879. doi: 10.1080/17434440.2017.1384695. Epub 2017 Oct 4 [PubMed PMID: 28945162]

[18]

Lee M, Généreux P, Shlofmitz R, Phillipson D, Anose BM, Martinsen BJ, Himmelstein SI, Chambers JW. Orbital atherectomy for treating de novo, severely calcified coronary lesions: 3-year results of the pivotal ORBIT II trial. Cardiovascular revascularization medicine : including molecular interventions. 2017 Jun:18(4):261-264. doi: 10.1016/j.carrev.2017.01.011. Epub 2017 Jan 23 [PubMed PMID: 28162989]

[19]

Lee MS, Shlofmitz E, Goldberg A, Shlofmitz R. Multicenter Registry of Real-World Patients With Severely Calcified Coronary Lesions Undergoing Orbital Atherectomy: 1-Year Outcomes. The Journal of invasive cardiology. 2018 Apr:30(4):121-124 [PubMed PMID: 29610442]

[20]

Brinton TJ, Ali ZA, Hill JM, Meredith IT, Maehara A, Illindala U, Lansky A, Götberg M, Van Mieghem NM, Whitbourn R, Fajadet J, Di Mario C. Feasibility of Shockwave Coronary Intravascular Lithotripsy for the Treatment of Calcified Coronary Stenoses. Circulation. 2019 Feb 5:139(6):834-836. doi: 10.1161/CIRCULATIONAHA.118.036531. Epub [PubMed PMID: 30715944]

Level 2 (mid-level) evidence

[21]

Yin D, Maehara A, Mezzafonte S, Moses JW, Mintz GS, Shlofmitz RA. Excimer Laser Angioplasty-Facilitated Fracturing of Napkin-Ring Peri-Stent Calcium in a Chronically Underexpanded Stent: Documentation by Optical Coherence Tomography. JACC. Cardiovascular interventions. 2015 Jul:8(8):e137-e139. doi: 10.1016/j.jcin.2015.02.018. Epub [PubMed PMID: 26205458]

[22]

Cook SL, Eigler NL, Shefer A, Goldenberg T, Forrester JS, Litvack F. Percutaneous excimer laser coronary angioplasty of lesions not ideal for balloon angioplasty. Circulation. 1991 Aug:84(2):632-43 [PubMed PMID: 1860207]

[23]

Shlofmitz E, Chen Y, Dheendsa A, Khalid N. Comment on "Modern-Day Nationwide Utilization of Intravascular Ultrasound and Its Impact on the Outcomes of Percutaneous Coronary Intervention With Coronary Atherectomy in the United States". Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. 2019 Oct:38(10):2799-2800. doi: 10.1002/jum.14963. Epub 2019 Feb 4 [PubMed PMID: 30719743]

Level 3 (low-level) evidence

[24]

Shlofmitz E, Kerndt CC, Parekh A, Khalid N. Intravascular Ultrasound. StatPearls. 2023 Jan:(): [PubMed PMID: 30725704]

[25]

Parviz Y, Shlofmitz E, Fall KN, Konigstein M, Maehara A, Jeremias A, Shlofmitz RA, Mintz GS, Ali ZA. Utility of intracoronary imaging in the cardiac catheterization laboratory: comprehensive evaluation with intravascular ultrasound and optical coherence tomography. British medical bulletin. 2018 Mar 1:125(1):79-90. doi: 10.1093/bmb/ldx049. Epub [PubMed PMID: 29360941]

[26]

Waksman R, Torguson R, Spad MA, Garcia-Garcia H, Ware J, Wang R, Madden S, Shah P, Muller J. The Lipid-Rich Plaque Study of vulnerable plaques and vulnerable patients: Study design and rationale. American heart journal. 2017 Oct:192():98-104. doi: 10.1016/j.ahj.2017.02.010. Epub 2017 Feb 16 [PubMed PMID: 28938968]

[27]

Khalid N, Hussain K, Shlofmitz E. Pericardial Calcification. StatPearls. 2023 Jan:(): [PubMed PMID: 30855926]

[28]

Ertelt K, Généreux P, Mintz GS, Reiss GR, Kirtane AJ, Madhavan MV, Fahy M, Williams MR, Brener SJ, Mehran R, Stone GW. Impact of the severity of coronary artery calcification on clinical events in patients undergoing coronary artery bypass grafting (from the Acute Catheterization and Urgent Intervention Triage Strategy Trial). The American journal of cardiology. 2013 Dec 1:112(11):1730-7. doi: 10.1016/j.amjcard.2013.07.038. Epub 2013 Sep 5 [PubMed PMID: 24012035]

[29]

Song HG, Kang SJ, Ahn JM, Kim WJ, Lee JY, Park DW, Lee SW, Kim YH, Lee CW, Park SW, Park SJ. Intravascular ultrasound assessment of optimal stent area to prevent in-stent restenosis after zotarolimus-, everolimus-, and sirolimus-eluting stent implantation. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions. 2014 May 1:83(6):873-8. doi: 10.1002/ccd.24560. Epub 2013 Nov 9 [PubMed PMID: 22815193]

[30]

Dong P, Bezerra HG, Wilson DL, Gu L. Impact of Calcium Quantifications on Stent Expansions. Journal of biomechanical engineering. 2019 Feb 1:141(2):0210101-8. doi: 10.1115/1.4042013. Epub [PubMed PMID: 30453326]