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Intravascular lithotripsy for treatment of calcific coronary lesions in ST elevation myocardial infarction

To describe the utility and safety of intravascular lithotripsy (IVL) in the setting of primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI).


| INTRODUCTION
Primary PCI is increasingly performed in older and more co-morbid patients, 1,2 with more calcified and complex coronary artery disease.
Angiographic coronary artery calcium (CAC) is frequent in target lesions in STEMI, 3 associated with worsened epicardial flow, a poorer response to fibrinolytic therapy, and is an independent risk factor for increased cardiovascular major adverse events (MACE). 4 Existing tools for calcium modification have limitations in STEMI which may restrict their use. Repeated high pressure balloon dilatation in a thrombotic lesion can cause distal embolization. Although data are scarce on the use of rotational atherectomy in STEMI, it is relatively contraindicated due to the risk of no-reflow caused by embolization of atheromatous debris. This risk is likely to be greater in the highly thrombotic milieu of STEMI, where the microvasculature may already be congested.
There is also a risk of increased platelet activation by the heat generated by the rapidly rotating burr. Perhaps as a consequence, the use of rotational atherectomy is low in non ST elevation myocardial infarction (NSTEMI) and STEMI-0.7% in a pooled analysis of the HORIZONS-AMI and ACUITY trials. 3 Coronary intravascular lithotripsy (IVL; Shockwave Medical, CA, USA) is an emerging treatment modality for vascular calcium that may offer advantages over existing therapies. IVL has been shown to be safe and effective in patients with calcific disease requiring revascularization for stable clinical syndromes. 5 Coronary calcium is a major risk factor for stent underexpansion and subsequent stent failure, 3,[6][7][8] In addition to facilitating optimal stent expansion in de-novo lesions, 5 IVL has demonstrated utility in the management of under-expanded stents due to coronary calcification, 9 and may be of particular use in this subset of patients presenting with STEMI. As a balloon-based therapy, IVL has a reduced learning curve compared to other calcium modification techniques, and with the potential for low complication rates, may have an advantage over these existing tools.. 5 Here we present the first description of procedural characteristics and safety outcomes following IVL use in STEMI.

| Study design and patient population
We performed a retrospective analysis of all patients in whom IVL was used during primary PCI at six UK sites between June 2018 and September 2020. Inclusion criteria were presentation fulfilling criteria for STEMI (chest discomfort or other symptoms suggestive of ischemia and ST segment elevation in at least two contiguous ECG leads) and the use of IVL in the culprit lesion during the primary PCI. All patients received IVL as part of standard care, with therapy administered as per the manufacturer's recommendations.

| Procedure
Interventional strategy was determined by anatomy and operator preference. Antithrombotic therapy was prescribed according to current guidelines.

| Endpoints
The primary safety endpoint was procedural complications and inhospital major adverse cardiac events (MACE), defined as all-cause death, non-fatal myocardial infarction (MI) or target vessel revascularization (TVR). 10

| Definitions
An undilated lesion was defined as a lesion which failed to yield despite high pressure (>18 atm) inflation of a non-compliant (NC) balloon sized 1:1 to the vessel. Severe angiographic calcification was defined as radiopacities seen before contrast injection, appearing to involve both sides of the arterial lumen on angiography. Concentric calcium was defined as >270 calcium arc seen on intracoronary imaging. Thrombolysis in Myocardial Infarction (TIMI) criteria was used to describe coronary flow, and has been defined previously. 11 No reflow (TIMI 0-1) was defined as a persistent reduction in coronary flow in the absence of dissection, spasm, stenosis or thrombus of the epicardial vessel. 12 Stent expansion was defined as the minimum stent area (MSA) divided by the distal reference area, expressed as a percentage.
Stent underexpansion was defined as stent expansion <90%. Target lesion revascularization (TLR) was defined as repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. 10 Bleeding was defined as BARC Type 3 bleeding. 13 Significant bystander lesions were defined as major epicardial arteries with >70% angiographic stenosis.

| Statistical analysis
Continuous data are expressed as a mean ± SD, categorical data are expressed as total number and percentage unless otherwise stated.

T A B L E 1 Patient characteristics
We identified 72 eligible patients, over a 2 year period, representing 1% of total STEMI procedures undertaken across the six sites. The total annual STEMI number of the sites is 3,328, the total annual number of PCIs 11,912, and the total annual number of IVL cases 503.
Patient characteristics are shown in Table 1.
Procedural characteristics are shown in Table 2

| DISCUSSION
This retrospective analysis describes the procedural characteristics and safety outcomes in patients treated with IVL during STEMI.
Although STEMI is most commonly caused by rupture of thin capped lipid rich plaque, in 8% of STEMI the culprit lesion is an eroded calcified nodule. As CAC increases with age, 21 the incidence of calcification (54%) within all STEMIs 19 and eroded calcific nodules are also likely to increase.
Dealing with CAC in the context of STEMI may carry a higher risk of procedural complications and, if CAC is inadequately treated, a higher risk of stent failure. Existing technologies such as high pressure balloon inflation, scoring or cutting balloons and rotational atherectomy are associated with increased rates of slow/no reflow, severe dissection and perforation. This may translate to a reluctance to modify calcium within STEMI and explain the low use of these technologies. We hypothesize that these risks may be reduced with IVL, due to the low pressure inflations used (4-6 atm) and the absence of distal embolization of calcific remnants. 14 Our findings were consistent with this hypothesis and demonstrated low rates of procedural complications or inpatient adverse events.
Rates of no-reflow were low (4%, compared to reported rates of 20-30% 17,22 ) with no cases of perforation reported in keeping with safety rates previously published for IVL. 23 The low incidence of no-reflow may reflect a lower need for repeated high pressure balloon inflation to achieve lesion expansion.
Given the strong association of CAC with age and diabetes it is not surprising that the patients described within this cohort were older (73, compared to the average age of STEMI in the United Kingdom (UK)-63 for men, 72 for women within the UK registry 2 ) and had a high incidence of diabetes (22%, compared to 20.5% of men and 22.4% of women presenting with STEMI within the UK registry. 2 ) In total, 57% of patients in this cohort had significant bystander disease, slightly higher than previously published rates of between 28 and 53% of multivessel disease in patients presenting with STEMI. 15,18,24 IVL was used within the culprit lesion in all these patients, and included in this were culprit lesions occurring in previously placed stents (15%), and in cases in which the newly deployed stent remained underexpanded despite high pressure postdilatation (6%). Overall, IVL was used for under-expanded stents (whether newly placed or pre-existing) in 21% of cases, an indication which has previously been described. 9 The threshold of appropriate use for IVL remains poorly defined, within our series high pressure NC balloons were used unsuccessfully in 76% of cases prior to IVL.
Coronary angiography is insensitive for the diagnosis of CAC which may explain the high incidence of intravascular imaging within our cohort (55%, compared to 2.7% in a large US registry of all acute myocardial infarctions, and compared to 9% in all PCI in the UK. (20,21) Our findings were consistent and demonstrated low rates of procedural complications or inpatient adverse events related to the PCI.
Rates of no-reflow were low (4%, compared to reported rates of 20%-30% 17,22 ) with no cases of perforation reported in keeping with safety rates previously published for IVL. 23 The low incidence of noreflow may reflect a lower need for repeated high pressure balloon inflation to achieve lesion expansion.
The 30 day mortality rate of this cohort was 17%, significantly higher than 30 day mortality rates for STEMI of 9% from both UK and Swedish national registries. 2,25 Of the 12 deaths, eight were cardiac F I G U R E 5 Intravascular ultrasound (IVUS) demonstrating satisfactory stent expansion within the heavily calcified segment of left anterior descending (LAD) deaths, and all due to cardiogenic shock or ventricular arrhythmia in patients with severe LV impairment, most of whom were older than 80 years. The non-cardiac deaths included one due to hypoxic brain injury complicating out of hospital arrest, two were due to malignancy and one perforated cholecystitis.
Although this study is limited by the lack of control group and modest sample size, it provides a "real-world" demonstration of the utility and safety of IVL use in STEMI and adds to the growing body of evidence of the important role of IVL in coronary calcium modification.

| CONCLUSION
In the setting of primary PCI for STEMI, IVL appears to be a safe and effective tool for modification of calcified coronary lesions prior to stent implantation.
T A B L E 2 d l h i i