Definition and Characterization of Coronary Calcification: History
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Please note this is an old version of this entry, which may differ significantly from the current revision.
Contributor:
Natthapon Angsubhakorn
,
Nicolas Kang
,
Colleen Fearon
,
Chol Techorueangwiwat
,
Pooja Swamy
,
Emmanouil S. Brilakis
,
Aditya S. Bharadwaj

Coronary artery calcification is increasingly prevalent in our patient population. It significantly limits the procedural success of percutaneous coronary intervention and is associated with a higher risk of adverse cardiovascular events both in the short-term and long-term. 

  • coronary artery calcification
  • intravascular imaging
  • percutaneous coronary intervention

1. Introduction

The prevalence of moderate to severe calcification in coronary lesions being treated with percutaneous coronary intervention (PCI) is between 18 to 24%, according to recent meta-analyses and multiethnic registries [1][2][3]. Advanced age, diabetes mellitus, hypertension, hyperlipidemia, smoking, and chronic kidney disease are associated with coronary calcification [4]. Due to increasing age and comorbidities of patients undergoing PCI, the prevalence of severely calcified coronary lesions is increasing [5]. Severe coronary calcification is independently associated with increased major adverse cardiac events following PCI [2][5]. In addition to long-term adverse outcomes, treatment of calcified coronary lesions also poses significant technical challenges. It is associated with an increased likelihood of procedural failure (such as balloon uncrossability or stent under-expansion), complications (such as coronary dissection, coronary perforation, or balloon rupture), and periprocedural mortality and morbidity [5][6]. The periprocedural assessment of the extent and thickness of coronary calcium is critical for calcium modification planning [7][8]. There are many technologies available to modify severely calcified plaques, such as non-compliant (NC) balloons, rotational, orbital and laser atherectomy, and intravascular lithotripsy (IVL) [9]. Each of these modalities of calcium modification has advantages and disadvantages. The contemporary algorithm for treating severely calcified lesions with a preference for one device over the other is changing, especially with the advent of IVL. The selected relevant clinical trials that support their clinical use, as depicted in Table 1. 
Table 1. Relevant clinical trials for the treatment of coronary calcification.
Study Study Arms Relevant Endpoint(s) Outcomes/Results * Conclusions
Cutting Balloon Angioplasty
GRT [10] CBA vs. PTCA Binary restenosis after 6 months CBA: 31.4%
PTCA: 30.4%
p = NS		 No reduction in restenosis with CBA after 6 months.
REDUCE (unpublished) CBA vs. PTCA Binary restenosis after 6 months CBA: 32.7%
PTCA: 25.5%
p = NS		 No reduction in restenosis with CBA after 6 months.
RESCUT [11] CBA vs. PTCA for ISR Binary restenosis after 7 months CBA: 29.8%
PTCA: 31.4%
p = NS		 No reduction in recurrent ISR with CBA after 7 months.
CBA before DES [12] CBA before DES vs. BA Minimum stent CSA (mm2), Acute lumen gain (mm2) CBA:6.26 ± 0.4, 3.74 ± 0.38
BA:5.03 ± 0.33, 2.44 ± 0.29
p = 0.031, 0.015		 CBA achieved larger lumen CSA and larger lumen gain compared to BA.
Mechanisms of Acute Lumen Gain Following Cutting Balloon Angioplasty in Calcified and Noncalcified Lesions [13] CBA vs. BA in calcified and non-calcified group ΔEEM CSA (mm2), ΔP + M CSA (mm2), Δlumen CSA (mm2) Calcified lesions:
CBA: 1.4 ± 1.7, −2.3 ± 1.9, 3.7 ± 1.5
BA: 1.2 ± 1.2, −1.8 ± 1.9, 3.0 ± 1.5
p = NS, NS, 0.05
Non-calcified lesions:
CBA: 1.0 ± 1.8, −2.9 ± 2.1, 3.9 ± 1.9
BA: 1.6 ± 1.8, −2.0 ± 1.9, 3.6 ± 1.6
p = NS(0.11), 0.03, NS		 In calcified lesions, CBA achieves a larger lumen gain vs. BA.
In noncalcified lesions, there is larger plaque reduction with CBA but no difference in lumen gain vs. BA.
Scoring Balloon Angioplasty
Intimal disruption and cobalt-chromium DES [14] SBA vs. BA Stent expansion, lumen eccentricity,
intimal disruption frequency, extent		 SBA: 68%, 0.94, 68%, 122°
BA: 62.1%, 0.80, 0.8, 65°
p = 0.017, 0.18, 0.035, 0.035		 SBA achieved increased stent expansion with similar lumen eccentricity when compared with BA. SBA had more frequent and extensive intimal disruption when compared with BA.
Predilatation with SBA vs. NC [15] SBA vs. NC Stent expansion (mm), in-stent late loss after 1 year (mm) SBA: 70.7 ± 11.2, 0.71 ± 0.63
NC: 69.1 ± 11.1, 0.23 ± 0.52
p = NS, 0.03		 SBA achieved decreased in-stent late loss when compared to NC after 1 year. There was no difference in stent expansion between SBA and NC groups.
Rotational Atherectomy
ERBAC [16] RA vs. ELCA vs. PTCA Procedural success ∑, TVR after 6 months RA: 89%, 42.4%
ELCA: 77%, 46%
PTCA: 80%, 31.9%
p = 0.0019, 0.013		 RA achieved superior procedural success when compared with ELCA and PTCA, but both RA and ELCA had unfavorable late outcomes when compared with PTCA.
COBRA [17] RA vs. PTCA Binary restenosis after 6 months RA: 49%
PTCA: 51%
p = 0.35		 RA did not reduce restenosis after 6 months when compared with PTCA.
DART [18] RA vs. PTCA in small vessels (2–3 mm) TVF after 12 months RA: 30.5%
PTCA: 31.2%
p = 0.98		 RA did not reduce TVF after 12 months when compared with PTCA.
STRATAS [19] Aggressive RA (B/A 0.7–0.9) with PTCA (<1 bar) vs. routine RA (B/A < 0.7) with PTCA (4 bar) Binary restenosis after 6 months Aggressive: 58%
Routine: 52%
p = NS		 Aggressive RA debulking did not reduce restenosis after 6 months when compared with routine RA debulking.
CARAT [20] Aggressive RA (B/A > 0.7) vs. Routine RA (B/A = 0.7) MACE after 6 months Aggressive: 36.3%
Routine: 32.7%
p = NS		 Aggressive RA debulking did not reduce MACE after 6 months compared with routine RA debulking.
ROOSTER [21] RA (B/A = 0.7) vs. PTCA for diffuse ISR with IVUS guidance TLR after 9 months RA: 32%
PTCA: 45%
p = 0.04		 RA achieved less TLR after 9 months compared with PTCA in diffuse ISR.
ARTIST [22] RA (B/A = 0.7) vs. PTCA for diffuse ISR with IVUS guidance in a subset MACE after 6 months RA: 80%
PTCA: 91%
p = 0.0052		 PTCA achieved a lower MACE when compared to RA in diffuse ISR.
ROTAXUS [23] RA with DES vs. DES Late lumen loss (mm) after 9 months RA with DES: 0.31 ± 0.52
DES: 0.44 ± 0.58
p = 0.04		 RA before DES achieved increased late lumen loss when compared to DES alone.
Prepare-CALC [24] RA vs. modified CSA Successful stent delivery and expansion, late lumen loss (mm) after 9 months RA: 98%, 0.22 ± 0.41
CSA: 81%, 0.16 ± 0.40
p = 0.001, 0.21		 RA achieved greater success at stent delivery and expansion than CSA and had similar late lumen loss rates after 9 months.
Orbital Atherectomy
ORBIT I [25] OA single arm Device success ∫
Procedural success ∬
TLR, MACE after 6 months		 Device success: 98%
Procedural success: 94%
TLR, MACE (6 months): 2%, 8%		 OA successfully facilitated stent delivery with a low cumulative TLR and MACE after 6 months.
ORBIT II [26] OA single arm Safety endpoint Ω (95% CI)
Efficacy endpoint Ψ (95% CI)		 Safety endpoint: 89.6% (86.7–92.5%)
Efficacy endpoint: 88.9% (85.5–91.6%)		 OA significantly exceeded the primary safety and efficacy endpoints of 83% and 82% respectively. OA also improved in-hospital and 30-day outcomes compared to historic controls with severe CAC.
Laser Atherectomy
LAVA [27] ELCA vs. PTCA in native vessels or SVG MACE after 6 months ELCA: 28.9%
PTCA: 23.5%
p = 0.55		 ELCA did not reduce MACE after 6 months compared with PTCA in native vessels or SVG.
AMRO [28] ELCA vs. PTCA in native vessels MACE after 6 months ELCA: 33.3%
PTCA: 29.9%
p = 0.55		 ELCA did not reduce MACE after 6 months compared with PTCA in native vessels.
Intravascular Lithotripsy
DISRUPT CAD I [29] Coronary IVL single arm Safety endpoint Ω Effectiveness endpoint Ψ Safety endpoint: 95%
Effectiveness endpoint: 98.5%		 Coronary IVL safely and effectively aided stent placement with minimal perioperative complications.
DISRUPT CAD II [30] Coronary IVL single arm Safety endpoint Ω Effectiveness endpoint Ψ
Calcium fractures measured by OCT
Mean stent expansion		 Safety endpoint: 100%
Effectiveness endpoint: 94.2%
Calcium fractures: 67.4%
Mean stent expansion: 101.7%		 Coronary IVL safely and effectively aided stent placement with minimal perioperative complications.
OCT demonstrated that calcium fractures were an underlying mechanism for IVL.
Coronary IVL allowed for excellent stent expansion.
DISRUPT CAD III [31] Coronary IVL single arm Safety endpoint Ω (lower-bound of 95% CI)
Effectiveness endpoint Ψ (lower-bound of 95% CI)		 Safety endpoint: 92.2% (89.9%, p = 0.0001)
Effectiveness endpoint: 92.4% (90.2%, p = 0.0001)		 Coronary IVL safely and successfully assisted with stent delivery. The lower bounds of the 95% CI for the safety and effectiveness endpoints exceeded the performance goal of 84.4% and 83.4%, respectively.
DISRUPT CAD IV [32] Coronary IVL single arm Safety endpoint Ω: CAD IV cohort vs. propensity matched historical IVL control group
Effectiveness endpoint Ψ: CAD IV cohort vs. propensity matched historical IVL control group		 Safety endpoint: 93.8% vs. 91.2%, p = 0.008
Effectiveness endpoint: 93.8% vs. 91.6%, p = 0.007		 Coronary IVL safely and effectively aided stent placement with minimal perioperative complications.
The results from coronary IVL in the Japanese CAD IV cohort were non-inferior to those from a study of patients treated with IVL in the USA and Europe.
Abbreviations: ΔEEM, change in external elastic membrane; ΔP + M, change in plaque plus media; Δlumen, change in lumen or acute lumen gain; B/A, burr/artery ratio; BA, balloon angioplasty; BMS, bare-metal stent; CABG, coronary artery bypass surgery; CAC, coronary artery calcification; CBA, cutting balloon angioplasty; CI, confidence interval; CSA, cross-sectional area; DES, drug-eluting stent; ELCA, excimer laser coronary angioplasty; ISR, in-stent restenosis; IVL, intravascular lithotripsy; IVUS, intravascular ultrasound; MACE, major adverse cardiac events; MI, myocardial infarction; NS, nonsignificant; NC, noncompliant balloon; OA, orbital atherectomy; OCT, optical coherence tomography; PTCA, percutaneous transluminal coronary angioplasty; PTRA, percutaneous transluminal rotational atherectomy; RA, rotational atherectomy; SBA, scoring balloon angioplasty; SVG, saphenous vein graft; TVF, target vessel failure; TVR, target vessel revascularization. * In order of relevant endpoints; ∑ Diameter stenosis < 50%, absence of death, non-Q-wave MI, or CABG; ∫ Residual stenosis < 50% without device malfunction; ∬ <20% residual stenosis; Ω 30-day freedom from MACE; Ψ residual stenosis < 50% without in-hospital MACE.

2. Definition and Characterization of Coronary Calcification

Several imaging modalities can identify and characterize calcified coronary lesions, including coronary angiography, coronary CT angiography, and intravascular imaging [33]. Coronary CT angiography has emerged as a useful non-invasive tool to identify coronary calcium and plan coronary interventions. Measurement of coronary artery calcium score can be used to stratify cardiovascular risk as it is a powerful predictor of atherosclerotic cardiovascular disease [5]. Coronary angiography generally demonstrates severely calcified lesions as radiopacities without cardiac motion before contrast injection, frequently visible on both sides of the arterial lumen (tram-track). Intravascular ultrasound (IVUS) enables full-thickness visualization of the coronary artery wall, allowing a detailed evaluation of calcified lesions and deposits within deeper layers of the coronary artery wall. Calcium appears as a bright, hyperechoic arch with acoustic shadowing. Optical coherence tomography (OCT) uses infrared light to create even higher resolution images, with a particular advantage in accurate visualization of calcium thickness. Calcium appears as low-intensity signal areas with well-delineated borders.
The 2021 American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) guidelines recommend using intracoronary imaging for procedural guidance in complex coronary artery stenting cases (class 2a recommendation, level of evidence B) [8]. Both OCT and IVUS can identify, localize, and quantify coronary artery calcium, allowing a comprehensive pre-PCI assessment of coronary calcium patterns and severity to predict successful stent expansion. Three essential OCT-derived parameters of coronary calcification predicted stent underexpansion, including an arc of calcium ≥ 180°, calcium length > 5 mm, and calcium thickness ≥ 0.5 mm [34]. On IVUS, the length of superficial calcium > 270° (≥5 mm), circumferential 360° calcium, a calcified nodule, and a small caliber vessel (<3.5 mm) predicted stent underexpansion [35]. Calcium scoring systems were developed to identify lesions that may require calcium modification. An OCT-based calcium score of ≥4 or an IVUS-based calcium score of ≥2 was associated with a significantly higher risk of stent underexpansion and indicates the need for calcium modification [34][35]. Table 2 shows a simplified system to categorize calcified coronary lesion severity into mild/moderate/severe, based on the presence of high-risk features on intravascular imaging [36].
Table 2. Classification of calcified coronary lesion severity based on intravascular imaging.
Severity OCT-Based Calcium Score
  • Calcium Arc of >180° (2 Points), 90–180° (1 Point)
  • Calcium Length of >5 mm (1 Point)
  • Calcium Thickness of >0.5 mm (1 Point)
 IVUS-Based Calcium Score
  • Length of Calcium (>270°) of >5 mm (1 Point)
  • Presence of 360° Circumferential Calcium (1 Point)
  • Vessel Diameter of ≤3.5 mm (1 Point)
  • Presence of a Calcified Nodule (1 Point)
Mild to moderate 0–3 0–1
Severe ≥4 ≥2
Abbreviations: IVUS, intravascular ultrasound; OCT, optical coherence tomography.

This entry is adapted from the peer-reviewed paper 10.3390/jpm12101638

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