Combined Coronary Orbital Atherectomy and Intravascular Lithotripsy for the Treatment of Severely Calcified Coronary Stenoses: The First Case Series

Objective. Severely calcified coronary stenoses remain a significant challenge during contemporary percutaneous coronary intervention (PCI), often requiring advanced therapies to circumvent suboptimal lesion preparation and major adverse cardiac events (MACEs). Recent reports suggest combined coronary atherectomy and intravascular lithotripsy (IVL) may achieve superior preparation of severely calcified coronary stenoses during PCI. We sought to evaluate the safety and utility of combined orbital atherectomy (OA) and IVL for the modification of coronary artery calcification (CAC) prior to drug-eluting stent (DES) implantation in PCI. Methods. We performed a retrospective review of all patients who underwent coronary OA and IVL within a single PCI procedure at our institution. The primary outcome was procedural success, defined as successful DES implantation with a residual percent diameter stenosis of <30% and Thrombolysis in Myocardial Infarction (TIMI) 3 flow following PCI without occurrence of in-hospital MACE (cardiac death, myocardial infarction, or target-vessel revascularization). MACE was additionally assessed at 30 days post intervention. Results. Eight patients underwent combined coronary OA and IVL within a single PCI procedure. The mean percent diameter stenosis prior to intervention was 80.5 ± 8.3%, with a mean calcific arc of 338 ± 42°. Procedural success was achieved in 7 of 8 cases (87.5%). Both in-hospital and 30-day MACE rates were 0%. Conclusion. We report the safe and effective use of combined coronary OA and IVL for the preparation of severely calcified coronary stenoses during PCI. Through their distinct yet complementary mechanisms of action, the combined use of these therapies may achieve superior preparation of severely calcified coronary stenoses during PCI.

J INVASIVE CARDIOL 2022;34(3):E210-E217. Epub 2022 February 18.

Key words: coronary artery disease, percutaneous coronary intervention, PCI, interventional devices

Percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation is a cornerstone for the treatment of complex obstructive coronary stenoses. In several increasingly encountered populations, including those with advanced age, chronic kidney disease (CKD), hypertension, and diabetes, coronary artery calcification (CAC) is common.^1-3 Severely calcified coronary stenoses remain a significant challenge during PCI, often requiring advanced therapies to circumvent suboptimal lesion preparation and adverse events, including stent thrombosis and in-stent restenosis.^4-11 CAC is postulated to lead to these complications by limiting final DES expansion and impairing the stent’s drug elution due to CAC-related polymer damage.^12-16

Coronary intravascular lithotripsy (IVL) has emerged as a potentially transformative therapy for CAC modification prior to DES implantation in PCI.^17-21 Coronary IVL employs an integrated balloon-based catheter to deliver a series of circumferential acoustic pressure waves that microfracture CAC, with a preferential effect on deep calcium and an enhanced efficacy on more severe regions of disease.^22,23 These microfractures have been proposed to increase target-vessel compliance, thereby facilitating DES delivery and improving subsequent DES expansion.^17,19

It has recently been proposed that the combination of a traditional calcium ablative therapy together with the novel mechanism of action of IVL may achieve superior preparation of severely calcified coronary stenoses during PCI.²² Case reports have demonstrated the potential utility of this approach, with the majority of reported cases utilizing rotational atherectomy (Table 1).^24-32 Herein, we report our single-center experience with the novel use of combined coronary orbital atherectomy (OA) and IVL for CAC modification, the first known case series describing this interventional approach.

We conducted this study at Northwestern Memorial Hospital, a large, urban, academic medical center located in Chicago, Illinois. Electronic health records and cardiac catheterization data were retrospectively collected and analyzed for all patients who were admitted to Northwestern Memorial Hospital and underwent PCI with the use of both coronary OA and IVL within a single PCI procedure. Northwestern University’s institutional review board granted a waiver of patient informed consent for data collection.

Due to the lack of commercial availability of a dedicated coronary IVL system in the United States at the time of PCI for all 8 study subjects, the patients underwent coronary IVL with the off-label use of an analogous peripheral IVL system. The decision to perform combined OA and IVL was made intraprocedurally by the primary operator after unsuccessful delivery of intracoronary equipment or suboptimal lesion preparation following initial CAC modification with either coronary OA or IVL alone. Other individual procedural considerations, such as the use of intravascular imaging and access site(s), were at the discretion of the primary operator.

Prior to any intervention, all patients and/or a designated legally authorized representative underwent a thorough informed consent process for the potential off-label use of a peripheral IVL system during PCI. In addition, all patients who were potential candidates for surgical revascularization underwent a formal surgical assessment, and the decision to pursue PCI was based on the outcome of a patient-centered heart team evaluation.

The primary study outcome was procedural success, defined as successful DES implantation with a residual percent diameter stenosis of <30% by visual estimate and Thrombolysis in Myocardial Infarction (TIMI) 3 flow following PCI without occurrence of in-hospital MACE (defined as the composite of cardiac death, myocardial infarction, or target-vessel revascularization). MACE was additionally assessed at 30 days post intervention. Target-vessel revascularization was defined as any repeat revascularization of the target vessel, including the target lesion itself. Myocardial infarction was defined as a creatine kinase-myocardial band (CK-MB) level >3 times the upper limit of normal. CK-MB levels were not routinely measured and were only assessed when clinically indicated.

Principal secondary outcomes included angiographic complications, defined as coronary artery dissection, coronary artery perforation, slow-flow or no-reflow phenomenon, stent thrombosis, in-hospital cerebrovascular accident, and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate to severe bleeding.

Baseline patient and lesion characteristics. From April 2020 through January 2021, a total of 8 patients underwent combined coronary OA and IVL for severely calcified de novo native coronary artery stenoses. Baseline patient characteristics are provided in Table 2. Clinical presentation was stable ischemic heart disease in 6 patients (75%), unstable angina in 1 patient (12.5%), and non-ST–segment myocardial infarction in 1 patient (12.5%). All patients had at least 1 major risk factor for CAC at the time of PCI.

Baseline lesion characteristics by individual patient are provided in Table 3. Target vessels included the right coronary artery (RCA; n = 3), left anterior descending coronary artery (LAD; n = 2), left circumflex coronary artery (LCX; n = 2), and second obtuse marginal coronary artery (OM2; n = 1). One case (patient 1) involved an ostial location, and 1 case (patient 2) involved a chronic total occlusion (CTO). The visually estimated mean percent diameter stenosis by angiography prior to any intervention was 80.5 ± 8.3%. All target lesions met the criteria for concentric circumferential CAC, which was defined as a calcific arc of ≥270°.²²

Procedural characteristics. General procedural characteristics by individual patient are provided in Table 3 and are summarized in Table 4. Primary access was at the operator’s discretion and was via the common femoral artery in 5 cases (62.5%). Contralateral common femoral artery access was also obtained in 1 case (patient 6) as part of a planned strategy of mechanical circulatory support (MCS) during PCI. In this case, an Impella CP (Abiomed, Inc) was utilized. This strategy was chosen to avoid intraprocedural hemodynamic instability given the presence of a large, dominant RCA system that also supplied the entire LCX myocardial territory (Figure 1A).

Coronary OA with the Diamondback 360 Coronary OA System with 1.25 mm Classic Crown (Cardiovascular Systems, Inc) was performed in all patients. No other form of atherectomy was utilized. The speed and total number of OA passes were at the discretion of the primary operator. Coronary IVL with a Shockwave S4 Peripheral IVL System (Shockwave Medical, Inc) was also performed in all patients during the same PCI procedure. The total number of IVL pulses delivered to the target lesion was at the primary operator’s discretion.

The use of both coronary OA and IVL was required in all cases (n = 8) to allow for the delivery of intracoronary equipment (intravascular ultrasound or DES) and/or to allow for complete target-vessel expansion. OA was the initial strategy for CAC modification in 4 cases (50.0%) and IVL was the initial strategy in the remaining 4 cases (50.0%). In all cases in which OA was the primary strategy, difficulty in delivering intracoronary equipment across the target lesion following OA alone necessitated adjunctive IVL. In 3 of the cases in which IVL was the primary strategy, the IVL balloon catheter could not be initially delivered across the target lesion, necessitating the use of OA. However, following OA alone in each of these cases, subsequent difficulty in delivering intracoronary equipment across the target lesion necessitated adjunctive IVL. In the remaining case in which IVL was the primary strategy, a noncompliant balloon demonstrated a residual waist when inflated to high pressure following IVL alone, and therefore adjunctive OA was performed.

Procedural and clinical outcomes. Major procedural outcomes are provided in Table 4 and detailed case studies are provided in Figure 1 and Figure 2. The primary outcome of procedural success was achieved in 7 cases (87.5%). In each of these cases, all target lesions had a residual percent diameter stenosis of 0% by angiography and TIMI 3 flow post intervention.

The single case in which procedural success was not achieved (patient 2) involved a calcified CTO at the bifurcation of the LCX and principal obtuse marginal branch. After the CTO was crossed with antegrade wire escalation, an upfront strategy of IVL was planned. However, the IVL balloon catheter could not initially be delivered across the CTO segment due to severe CAC within the proximal-mid LCX. OA was pursued, but a DES still could not be delivered across the proximal-mid LCX lesion, leading to the decision to proceed with adjunctive IVL. IVL therapy was then successfully delivered, but following removal of the IVL balloon catheter, a non–flow-limiting (TIMI 3) coronary artery dissection was noted within the LCX. DES implantation was subsequently successful within the principal obtuse marginal branch, but then distal wire position was lost and could not be recovered. Six weeks later, the patient returned for a planned PCI of the CTO segment and proximal-mid LCX that was successful, with a postintervention residual percent diameter stenosis of 0% and TIMI 3 flow achieved.

In all 8 cases, there were no coronary artery perforations, slow-flow or no-reflow phenomena, stent thrombosis, in-hospital cerebrovascular accident, or GUSTO moderate to severe bleeding. Emergency use of MCS was not required in any case, and no patient developed intraprocedural hemodynamic or electrical instability. The in-hospital and 30-day MACE rates were both 0%.

This case series demonstrates that coronary OA or IVL alone may be inadequate for the preparation of a subset of severely calcified coronary stenoses, but that these therapies can be safely and effectively combined for the modification of severe CAC during PCI. The combined use of coronary OA and IVL ultimately allowed for successful CAC modification and DES implantation without significant postprocedural residual stenoses in all cases. Furthermore, the combined use of these therapies was safe. The single procedural complication that occurred was well tolerated, and there were no MACEs in-hospital or at 30 days.

The presence of severe CAC remains a significant challenge in contemporary PCI, and a better understanding of its clinicopathology may aid in developing an optimal interventional approach. Two forms of CAC, medial and intimal, are classically recognized and are distinct in their morphologies and pathogeneses.³³ Medial CAC is associated with advanced age, chronic kidney disease, hypertension, and diabetes, and is thought to be the byproduct of a complex interplay between systemic inflammation, serum mineral and hormonal disturbances, and dysregulated gene expression.^34-36 These derangements ultimately lead to the development of an atypical vascular smooth muscle cell phenotype, which causes an organized calcification within the deeper arterial media.^36,37 In contrast, intimal CAC is exclusively associated with atherosclerosis, and is characterized by a punctate and disorganized calcification within the superficial arterial intima.^37,38 Notably, medial and intimal CAC can occur together, and their coexistence may potentiate one another through a positive-feedback loop-like mechanism.³⁷

The impact of CAC on the success of PCI has been demonstrated to be related to clinical features such as location (superficial/intimal vs deep/medial), calcific arc (eccentricity vs concentricity), and thickness.²² In an assessment of 1155 coronary stenoses by intravascular ultrasound, Mintz et al found CAC in 73% of stenoses and noted significant variability in its geographic location, with 48% of CAC only superficial, 28% only deep, and 24% both superficial and deep.³⁹ Subsequent studies have demonstrated that calcific arc and thickness may predict the success of traditional CAC-modifying therapies, with the combination of concentricity and large thickness predicting non-dilatable lesions and final DES underexpansion.^40,41 These collective features may be important considerations when developing a tailored strategy for CAC modification, as the available therapies differ in their mechanisms of action and therefore ability to modify a given CAC phenotype. For example, traditional balloon-based and calcium-ablative therapies primarily act upon superficial/intimal CAC, whereas IVL acts upon both intimal and medial CAC and may be particularly effective on deep calcium.^22,23

From a technical standpoint, CAC presents at least 2 major challenges during PCI. First, CAC may complicate the delivery of intracoronary equipment, thereby increasing the likelihood of suboptimal lesion preparation and DES polymer damage during stent delivery. Second, CAC may impede final DES expansion, thereby increasing the risk of stent thrombosis and in-stent restenosis. In all 8 cases, the use of a single CAC-modifying therapy was inadequate to overcome both of these challenges. In 4 cases, OA alone would not allow for the delivery of intracoronary equipment. Conversely, OA was required for IVL delivery in 4 cases. Nevertheless, the combined use of these therapies ultimately allowed for successful DES implantation with complete final expansion in all cases.

While more data are needed, we speculate that coronary OA and IVL represent CAC-modifying mechanisms that are both complementary and synergistic in the presence of severe CAC. Differential sanding with OA primarily allows for the modification of superficial/intimal CAC, which not only facilitates IVL balloon-catheter delivery, but also may make deeper/medial CAC more accessible to the IVL effect and limit DES polymer damage during stent delivery. The adjunctive circumferential generation of acoustic energy produced by IVL likely disrupts deeper/medial CAC not adequately modified by OA alone, which may be particularly beneficial if OA is run at low speed only. Through their distinct yet complementary mechanisms of action, the combined use of OA and IVL may amplify CAC disruption at multiple levels, thereby maximizing target-vessel compliance to allow for optimal DES delivery and final expansion.

Study limitations. This report has certain limitations inherent to all case series, including its small population, retrospective nature, and lack of a comparator group. Specific limitations include operator discretion in the use of a combined coronary OA and IVL strategy. In addition, OA was occasionally applied when the peripheral IVL balloon catheter would not cross a severely calcified lesion. When dedicated coronary IVL systems with an improved crossability profile become more widely available, the need for adjunctive OA may be reduced.

We report the first case series demonstrating the safe and effective use of combined coronary OA and IVL for the preparation of severely calcified coronary stenoses during PCI. Through their distinct yet complementary mechanisms of action, the use of these CAC-modifying therapies in tandem may achieve superior calcific-lesion preparation prior to DES implantation in comparison with atherectomy alone. Larger studies evaluating the combined use of coronary atherectomy and IVL in the setting of severely calcified coronary stenoses are needed.

Acknowledgments. We thank the patients of Northwestern Memorial Hospital who participated in this retrospective study, as well as their families and caregivers.

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