European Journal of Cardiovascular Medicine

Calcified coronaries are a direct consequence of advanced ageing. This has led to percutaneous coronary interventions (PCI) becoming an increasingly complex procedure. The calcified lesions in coronary artery pose multiple procedural challenges during angioplasty like, failure to wire the lesion, failure to track balloon, failure to adequately predilate the lesion, failure to track stent in the stenotic region, failure to deploy stent, extensive dissection, arterial perforation while dilatation, iatrogenic perforation due to rotational ablation, stent mal-apposition, post angioplasty in-stent restenosis, or stent thrombosis. Management of severe calcified coronaries (SCC) includes time proven therapies such as plaque modification with gradually increasing size of non-complaint balloons, using of special balloons during pre-dilatation (scoring ballon, cutting balloon and high pressure ballons), rotational atherectomy (RA), orbital atherectomy (OA), laser excimer, and recently introduced intra-vascular lithotripsy (IVL). There are multiple studies which have proven the efficacy and feasibility of the IVL to manage severe calcified coronaries (SCC) [1]. The calcific coronaries have various patterns of calcium deposition including superficial calcium deposition, deep calcium deposition, and nodular calcium [2]. The data about effectiveness of IVL in dealing with different types of calcific lesions is still lacking. [3]. Data on periprocedural complications are scarce. This study tries to answer these questions and narrow the knowledge gap we have with the usage of IVL.

The study is an outcome of registry maintained at a high flow, single centre, and tertiary care centre. This is a retrospective and observational study, done for a period of 24 months. The basic demographic details along with history of co-morbidities were recorded in detail. Post angioplasty period was noted during regular out-patient department visits and telephonic conversations. As the treatment is universally approved, a routine angioplasty consent was taken from the patient.

All the patients included in this study were diagnosed angiographically with severe calcified lesions. This calcification was confirmed using optical coherence tomography (OCT) during PCI. All the patients underwent OCT imaging of pre-stenting (pre-IVL and post IVL) phase and post-stenting phase. Pre-stenting and post-stenting, lesion dimensions were derived from OCT imaging. The OCT was performed using an Abbot ‘Dragonfly Optis’ catheter. All the angioplasties were performed using ‘Phillips Clarity’ image guided therapy system. The stent used during the angioplasty were Abbot’s ‘Xience Sierra’, ‘Xience Alpine’ and ‘Xience Xpedition’. Conventional standards were followed while performing coronary angiography. Majority of the patients underwent angioplasty immediately following angiogram, especially in single vessel disease or double vessel disease. Patients with severe calcific coronaries and triple vessel disease were discussed in heart team meet for feasibility and then taken for angioplasty in staged manner.

IVL was performed using ‘Shockwave C2’ (Shockwave Medical Inc) balloon based coronary system. The system was prepared as per company instructions. An OCT imaging done in pre-stenting phase was used to measure the exact dimensions like diameter of vessel and the depth of calcium in the calcified vascular plaque. A 1:1 ratio of IVL balloon diameter to vascular dimension was chosen. In one third of the cases the IVL balloon passed easily across the coronary lesion, in the rest of the cases, pre-dilatation is performed with non-complaint balloon before IVL balloon is passed across the lesion. Once IVL balloon is in position, then it is inflated to 4 atmospheres (atm) in first half of the cycle impulses followed by pressure is increased to 6 atm in subsequent impulses. Each cycle delivers 10 impulses. These impulses will create multiplanar and longitudinal fractures which will be confirmed on OCT run.   

Post-angioplasty/ post stenting period was managed by dual antiplatelets and statins (such as aspirin 75mg with ticagrelor 90mg twice daily, high dose statin like atorvastatin of 80mg or rosuvastatin of 40mg). Patients were also started on low molecular weight heparin with normal renal function test, unfractionated heparin in patients with high creatinine, nicorandil infusion for 12–24 hours and other supportive measures. During hospital stay, patients are clinically monitored for major adverse coronary events. A value of troponin I is repeated after 24 hours of post-stenting.

The procedural success is defined as: first is the ability to cross various balloons across the SCC; deploy the intended stent across the SCC; achieving TIMI III flow across the stented lesion; and achieving <20% residual lesion. The therapy outcome is defined by the percentage of the stent expansion achieved at the end of the stent deployment, and it is divided into ‘Sub-par’, ‘Sub-optimal’, and ‘Optimal’ stent expansion. Here, stent expansion is the ratio of reference vessel diameter measured (RVD) at distal to the lesion where the stent will land, to the mean stented area (MSA) in the stent. In CLI-OPCI-II study, the major under-expanded (Sub-par) stent was defined as ratio of RVD to mean MSA in-stent less than 70%. In our study we considered a ratio of less than 80% as ‘Sub-par’ or ‘Major under-expanded’ stent and labelled as un-satisfactory result, requiring further post-dilatation. From 81% to 95% is classified as ‘sub-optimal’ or ‘Minor under-expanded’ stent expansion achieved at the end of stent deployment and post-dilatation; similarly, any result more than 95% is considered ‘Optimal’ stent expansion.

Between January 2022 to December 2023, 52 patients were enrolled from a high flow single, tertiary care centre in Bharat. Baseline demographic variables of the study are provided in Table-1;

Table-1: Baseline Demographic variables of the study.

Similarly baseline clinical, laboratory and special investigation variables are provided in Table-2.

Table-2: Baseline Clinical, Laboratory and Special Investigation variables of the study.

The procedure related variables of the study are mentioned in Table-3.

Table-3: Baseline Intra-procedural variables of the study.

The mean age of the patients operated is 68.21 ± 7.6 years; median age of 67.5 years; maximum age of 87 years and minimum age is 51 years. 28 patients (53.84%) were aged more than or equal to 65 years and 24 patients (46.15%) were aged less than 65 years. Males formed 76.93% (40 out of 52) and females formed 23.07% (12 out of 52) of the total cohort. Among the comorbidities in this cohort, diabetics are 40 out of 52 (76.92%); hypertensives are 41 out of 52 (78.85%); dyslipidaemia are 10 out of 52 (19.23%); chronic kidney disease are 4 out of 52 (7.7%); patients with old cerebrovascular accident are 3 out of 52 (5.77%); hypothyroid are 7 out of 52 (13.46%); peripheral artery disease are 1 out of 52 (1.93%); old coronary artery disease are 10 out of 52 (19.23%); and anaemia are 10 out of 52 (19.23%).

The most common target vessel for PTCA is left anterior descending artery with 38 patients out of 52 patients (73.08%). The mean reference vessel diameter (RVD) is 2.85 ± 0.21 mm. The mean minimum lumen diameter (mean MLD) at lesion on OCT is 1.18 ± 0.67 mm and a mean lesion length of 24.8 ± 8.5 mm. Angiographically, the mean stenosis is 72.3%. Severe calcification is present in 50 out of 52 patients (96.15%). Concentric calcification (270 – 360 degree) is present in 30.77% (16 out of 52) of the patient, whereas calcification arc of 180-269 degree is noted in 69.23% (36 out of 52). 20% of the lesions had side branch involvement. The mean IVL catheters required per lesion is 1.02 ± 0.137. Pre dilatation is performed in all our patients with mean number of balloons used 1.75 ± 0.806. The mean IVL cycles utilized to get good plaque modification is 5.64 ± 1.53. The mean stents used to stent the calcified lesion is 1.27 ± 0.48. Except for one patient, others (98.07%) required post dilatation with a mean number of balloons required is 1.42 ± 0.74.

First 30 day in-hospital mortality is observed in 1 patient (1.93%). The mortality was secondary to non-procedural, non-cardiac cause. The patient was found to have urinary tract infection, severe sepsis, and septic shock with multi-organ failure. Procedural success achieved in 100% of the patients and clinical success rate seen in 98.07% of the cohort. All the patients (100%) had successful plaque modification performed with IVL balloon. The multiplanar cracks with longitudinal cracks were noticed in all the patients, similarly all the patients underwent successful usage of IVL balloon and stent deployment. No slow flow or reflow phenomenon were noted. A total of 10 (19.23%) patients experienced minor and major complications during this procedure. 4 (7.7%) patients were found to have dissection extending further into the normal vascular segment leading to deployment of an additional stent wherever deemed necessary by the primary operator. Other complications include rhythm disturbance like atrial fibrillation noted in 1 case (1.93%), bradycardia noted in 1 case (1.93%), coronary perforation in 1 case (1.93%), side branch myocardial infarction in 1 case (1.93%), balloon burst in 1 case (1.93%) and death of a patient (1.93%) in first 48 hours as shown in Table-4 and Chart-1.

Table-4: Shows various complications observed during Intra-vascular Lithotripsy.

The mean MLD at lesion is 1.18 ± 0.67 mm with a mean lesion length of 24.8 ± 8.5 mm. Post IVL plaque modification, the increase in minimal luminal area is from 1.93 ± 1.28 mm² to 5.7 ± 1.94 mm² (p<0.001) after stent implantation. The OCT revealed cracks/fissures in calcific plaques in all the patients (100%). We did not use rota-ablation as bail out procedure in any of our cases, in case of failure of IVL to modify plaque morphology. The chi square test is used to determine the association between various variables like calcium depth, optimal stent expansion, complication, and number of IVL cycles used. There is significant association between calcium depth and optimal stent expansion (p<0.016); and presence/absence of complication and optimal stent expansion (p<0.0155). There is no association noted between depth of calcium and complication (p: 0.786); Optimum stent expansion and number of IVL cycles given (p: 0.458); and calcium depth and optimum stent expansion (p: 0.696).

Calcified coronaries have been a nightmare for the patients and doctors in terms of revascularization outcomes. The mechanism behind calcification is found to be ‘cellular senescence’ (cells that no longer divide). This cellular senescence is characterized by activation of senescence associated secretory phenotype (SASP) gene. This leads the cells to go into senescence and secrete high levels of inflammatory cytokines, metalloproteases, and various growth factors. This increase in inflammation leads to deposition of calcification in atheroma [4].

Calcification of coronaries possess procedural challenges to the primary operator. This is associated with procedural complications and PCI failure. The calcification may cause failure to deliver stent, malposition of stent [5], stent thrombosis or stent restenosis after PCI [6]. There are five main methods of dealing with calcific arteries. First method is standard balloon angioplasty, second is to use special balloons like scoring balloon and cutting balloons, third is to use rotational/ orbital atherectomy, fourth is laser angioplasty and finally intravascular lithotripsy (IVL). The standard balloon angioplasty involves usage of gradually increasing size of balloons to pre-dilate the calcific coronaries to pave the way for the stent to be deployed. Similarly, some calcific coronaries will have calcium nodules and hard calcific lesions, which might require special balloons like scoring and cutting balloons. These special balloons have either a semi-complaint balloon wrapped with non-slip, nitinol scoring elements at edges or a cutting balloon where 3 to 4 atherotomes (microsurgical blades) fixed on a semi-complaint balloon. These balloons create micro-cuts/ cracks on the plaque initially and further balloon expansion helps to propagate the crack deep inside causing modification of calcific plaque [7]. Rotational/orbital atherectomy uses drilling technique to modify the calcific coronaries [8]. IVL uses a pulsatile sonic shockwave delivered to the calcific coronaries to modify the plaque for proper predilatation / bed preparation for subsequent stent deployment [9].

Each one of these techniques have multiple pros and cons, and selection ofthe techniques depend upon experience and expertise in dealing with the calcific lesions and ability to foresee and deal with the conceivable post procedure complications. Some of these complications associated with the special balloons might cause coronary dissection, perforations, inadequate bed preparation, slow flow, or no flow phenomenon. Similarly, rotational atherectomy again can cause coronary dissection, perforation, side branch injury, periprocedural infarction, slow flow, or no flow phenomenon [10]. Complications specific to laser atherectomy includes thermal injury to coronaries leading to blood thrombosis or embolism and rarely perforation or dissection [11]. Lastly, coronary IVL can rarely cause dissection, perforation, or arrhythmias. IVL has shown its effectiveness in modifying severe calcified plaques for better bed preparation during angioplasty procedure. IVL also scores on safety while performing such complex PCI [12]. Development of calcium fractures, subsequently after IVL usage, forms the mechanism of action of IVL. The denser calcium lesions have higher chance of development of fractures [13]. These calcium fractures are the reason for optimal stent expansion and reduction in rates of restenosis [14]. Therefore, our study provides a real-world data of outcomes of IVL. Also, the study provides a detailed morphological design of calcific lesion and its association to the stent expansion. This will not only confirm the IVL’s utility to improve the compliance of calcified coronaries and the safety aspects of this device

The most common complication is dissection during IVL usage. This is in agreement with other IVL registries as shown in Table-6.

Table-6. Comparison of registry datasets of coronary intravascular lithotripsy.

Some other rare complications observed in our study includes atrial fibrillation, coronary perforation, side branch occlusion, bradycardia, and balloon burst. Each of these rare complications contribute 1.9% each. The in-hospital mortality is observed in 1 patient (1.93%), and the likely causes includes sepsis, multiple co-morbidities, and refractory cardiogenic shock with multi-organ failure, inspite of successful procedure. Therefore, serious complication rates are 2 out of 51 patients (3.8%), which includes side branch MI and coronary perforation. Mild complication rates are 7 out of 51 patients (13.46%), which includes AF, dissection, balloon burst, and bradycardia.

Regarding the detailed morphology of the calcific lesion and its association with peri-procedural outcomes are shown in Table-5.

Table-5: Shows association between various variables.

The calcific lesion with deep/ nodular calcium is significantly associated with suboptimal stent expansion. The chance of stent expansion being suboptimal is high if the lesion has deep/ nodular calcium. Similarly, the suboptimal stent expansion is significantly associated with occurrence of peri-procedural complications. Other statistical tests revealed no association between IVL cycles and stent expansion or calcium depth and stent expansion.  

There are multiple small registries across the world contributing data about the post-procedure outcomes, as in Table-6. Tables 7,8 and 9 mention the variables and the complication rates.

Our study has some robust data as it involves

• Usage of OCT in all the patients for assessment of the lesion pre-IVL and post-IVL to confirm the technical success
• Detailed analysis of the calcific lesion and its statistical correlation with procedure outcomes
• Documentation and detailed analysis of all the common and rare complications in peri-procedural period
• The study is compared with similar studies done recently to compare the outcomes.

When compared to other recent studies, the incidence of major adverse cardiac events (MACE) of 1.9% is comparable to other studies like Buckley et al. [15], El Jattari et al. [16], and Sinclar et al. [17]. Similarly, clinical success in our study was 98.07% which is in agreement with the majority of the studies in recent past. Our study did have 100% procedural/ angiographic/ technical success, with no bailout procedure with rotational atherectomy utilized, which is highest among all the recent studies and registries. In our study we did document and describe in detail some of the rare complications while using IVL like atrial fibrillation, bradycardia, side branch occlusion with subsequent ischaemia, IV, and balloon burst.

VL does play an important role in management of severe calcified coronary lesions. The successful outcome of IVL technique depends on the calcium density of the coronary artery. Superficial calcium deposition has the best outcomes in terms of optimal stent deployment. Similarly, deep calcium has comparatively high rates of suboptimal stent deployment. The commonest reason for complication is coronary dissection. In the majority of cases, it required deploying additional stents.

Conflict Of Interest

We (the authors) have nothing to disclose.

Funding

This research received no grant from any funding agency in the public, commercial, or not-for-profit sectors.

Consent Statement

The patients agreed/ consented to the treating doctors and the hospital to use/ publish patient data, laboratory reports, procedure details, and relevant medical data in the form of research article in any medical research journal.

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