ADVERTISEMENT
Intravascular Lithotripsy for Optimal Angioplasty of Infrapopliteal Calcified Lesions
Abstract
Background. Infrapopliteal arterial disease results from 2 major etiologies: medial calcification and intimal atheromatous plaque. Lesion calcification constitutes one of the most widely encountered risk factors for percutaneous transluminal angioplasty failure. Intravascular lithotripsy (IVL) creates selective fracturing of calcium deposits in the arterial wall, increasing the compliance of the target artery and facilitating angioplasty. Results regarding IVL utilization at femoropopliteal and infrapopliteal lesions have been very promising in terms of safety and efficacy. This review presents currently available data on IVL outcomes for infrapopliteal lesions and provides technical information for optimal use of IVL in these challenging lesions.
J INVASIVE CARDIOL 2022;34(2):E132-E141.
Key words: critical limb ischemia, infrapopliteal disease, intravascular lithotripsy, IVL, PAD
Introduction
Infrapopliteal disease affects below-the-knee (BTK) arteries and is the leading cause of critical limb ischemia (CLI), the most severe form of peripheral artery disease (PAD).1-3 Endovascular revascularization has been increasingly utilized for the treatment of PAD, offering fewer periprocedural adverse events and similar amputation rates compared with open bypass surgery.4-8 As such, percutaneous transluminal angioplasty (PTA) comprises the treatment of choice for most BTK endovascular interventions.9 However, BTK disease is technically more challenging to treat than above-the-knee (ATK) lesions, mainly limited by elastic recoil, post-PTA dissections, and late-term restenosis.10-14 These limitations are attributed to the unique anatomical characteristics of BTK disease, including longer lesion length, smaller target-vessel diameter, poor run-off, and extensive calcification.15
Experience from coronary and femoropopliteal arteries has shown that calcification constitutes one of the most widely encountered risk factors for technical failure of PTA and late restenosis.16-21 The introduction of alternative distal access sites and advanced crossing techniques has optimized the current endovascular treatment approaches for BTK.22 However, moderate/severe calcification of target lesions remains a challenge of PTA and has been associated with all-cause mortality and limb-related risk for adverse vascular events.23 Nonetheless, innovative devices have been developed to overcome the calcification burden of infrapopliteal disease, including the technology of intravascular lithotripsy (IVL).9,24
IVL creates selective fracturing of intimal and medial calcium deposits in the arterial wall of affected arteries,25-30 without harming surrounding normal soft tissues.25-32 The effect of IVL is based on mechanical pulse waves created from acoustic energy that disrupts the calcium plaques,25-32 eventually increasing the compliance of the target artery.26,29 Increased vessel compliance facilitates acute luminal gain after PTA, while also lowering the risk of postangioplasty dissections.26,29,33 Previous reports studying cases of coronary, iliac, or ATK lesions have provided significant evidence regarding the safety and efficacy of IVL.26,34-38 This manuscript reviews contemporary data on IVL of infrapopliteal lesions in patients with PAD and focuses on how IVL could optimize currently available treatment approaches for BTK disease. Additionally, 4 cases of calcified infrapopliteal disease, treated with IVL + PTA, are presented, highlighting important technical aspects of the IVL technique.
Methods
Review of literature. The PubMed/Medline, Scopus, and Cochrane Central databases and presentations at conferences were searched for English-language prospective or retrospective analyses reporting on IVL use adjuvant to PTA for the endovascular treatment of ATK and BTK lesions. Cases reports were not included. The search was conducted up to February 2021. Data were extracted for the following variables: population demographics, treatment arms and main comparisons, lesion location, follow-up duration, primary outcomes (ie, rates of target-lesion revascularization, primary patency, freedom from major amputation), and major conclusions from each individual study. Due to between-study differences in design, comparisons made and reporting methods, the findings were summarized from each study, but the results were not pooled.
Case series. The electronic medical records of 4 patients (median age, 73 years; interquartile range [IQR], 11; 3 men), who underwent IVL followed by PTA for the treatment of calcified infrapopliteal lesions at the Rocky Mountain Regional VA Medical Center were reviewed. The target lesion was located in the first patient (case 1) at the popliteal artery, in the second patient (case 2) at the peroneal and anterior tibial (AT) arteries, in the third patient (case 3) at the peroneal and posterior tibial (PT) arteries, and in the fourth patient (case 4) in a below-the-ankle lesion. All lesions were de novo lesions, with median degree of stenosis of 90% and median lesion length of 100 mm. In all cases, IVL was deemed necessary in order to facilitate PTA results and the patients gave informed consent for IVL use and other adjunctive technologies prior to the index procedure.
Results
Calcification in infrapopliteal vessels. The presence of vascular calcification is often associated with atherosclerosis, a chronic systemic inflammatory disease.39 Thus, BTK lesions are attributed to both intimal atherosclerotic plaque formation and arterial calcification.40 In general, calcification develops within the intima and/or media of the arterial vessel wall.23,40,41 However, pathology studies have shown that the composition of atherosclerotic arterial lesions differs significantly based on the anatomic location of PAD,42-44 likely attributed to the unique biomechanical stress conditions of each vascular bed45-47 and differences in cellular biological pathways.48,49
Medial calcification constitutes the most prevalent form of calcification in the infrapopliteal segment, with approximately half of tibial chronic occlusions attributed to thrombosis and half to medial calcification.23,40,41 In contrast to intimal calcification, medial calcification is most commonly asymptomatic early in the disease course.50 However, at a later stage, the infrapopliteal arteries become inelastic due to medial calcification, leading to rheological changes of laminal blood flow, which eventually leads to atherosclerotic plaque development and luminal stenosis.40,50 Nonetheless, the exact role of medial calcification and other cellular elements (eg, antiplatelets, coagulation factors, etc) in plaque formation remains uncertain.51,52
Additionally, it has been suggested that comorbidities such as diabetes and chronic kidney disease increase the likelihood of vascular calcification,53,54 and are independent predictors of technical failure and limb loss due to poor initial run-off.16,55,56 Furthermore, among patients with infrapopliteal lesions, about two-thirds have multilevel diffuse disease with concomitant ATK lesions, while one-third of patients have isolated BTK disease.57-59 Isolated BTK disease is usually observed among older, diabetic patients and patients with end-stage renal disease (ESRD), which place the patients at higher cardiovascular risk.55,60 Thus, exposure to several cardiovascular risk factors contributes to the unique characteristics of BTK disease, including medial calcification.61-64
Nonetheless, calcium at the infrapopliteal arteries is commonly unequally distributed,13,40 resistant to stretching forces of PTA, in a non-uniform fashion.40,65 This inevitably leads to segments of the artery that expand more than others, and as such, dissection occurs (intima and/or media dehiscence from deeper arterial wall layers).40,65,66 Additionally, calcification alters the accuracy of quantitative angiography and makes appropriate sizing and device selection challenging, further increasing the risk for post-PTA dissections and/or residual stenosis.67,68 It is estimated that post-PTA dissection for BTK disease occurs in 6.4%-30.7% of cases,68,69 which has been associated with both short- and long-term poor outcomes.70-72 Moreover, calcium could affect the effectiveness of drug-eluting technology (eg, drug-coated balloons [DCBs], drug-eluting stents, etc), which is commonly used for the endovascular treatment of PAD, as calcium may hinder the delivery/transfer of the antiproliferative agent to the arterial wall.16,73,74 Therefore, calcification constitutes a significant burden of BTK endovascular interventions,68,69 warranting additional therapies to optimize PTA results (eg, atherectomy, specialty balloons, IVL, etc.).75-80
IVL with the Shockwave peripheral system (Shockwave Medical) constitutes an emerging treatment option that may facilitate balloon dilation in the setting of severe infrapopliteal calcification, by modifying the calcified atherosclerotic plaque and increasing the vessel compliance. Additionally, this technique enables inflation of the angioplasty balloon at lower pressures, thereby minimizing vessel trauma and decreasing the risk for post-PTA flow-limiting dissections. A summary of all current studies reporting on the outcomes of IVL adjuvant to PTA for ATK and BTK lesions is presented in Table 1 and Table 2, Part 1 and Part 2.
Relevant data regarding IVL safety and efficacy for ATK lesions. The DISRUPT PAD I (Safety and Performance Study of the Shockwave Lithoplasty System; ClinicalTrials.gov identifier NCT02071108) study was a prospective, premarket, single-arm, multicenter trial that included 35 patients from several sites in Europe and New Zealand.26 DISRUPT PAD I was the first study to evaluate the performance of IVL for the treatment of calcified, de novo femoropopliteal lesions.26 Main inclusion criteria were the presence of moderate or severe calcification of the target lesions, a reference vessel diameter ranging from 3.5 to 7.0 mm, and target-lesion stenosis ≥70% with lesion length ≤150 mm.26 Patients were also required to have at least 1 patent run off vessel to the foot in order to be included.26
Cases with significant inflow disease, Rutherford classification 5 or 6, or significant renal disease at baseline were excluded from the study.26 Almost two-thirds of the patients presented with severely calcified lesions26 The average pretreatment target lesion stenosis was 76.3% and the average calcified length was 80.3 mm.26 IVL was technically successful in all patients, although 14.3% of the lesions required postdilation.26 Lesion patency rates of 100% and 82.1% were found at 1-month and 6-month follow-up, respectively, with no major adverse events.26 Thus, this study suggested that IVL for calcified femoropopliteal lesions is safe and effective.26
The DISRUPT PAD II (Shockwave Lithoplasty DISRUPT Trial for PAD; ClinicalTrials.gov identifier NCT02369848) study was a core-lab adjudicated trial that investigated the use of stand-alone IVL exclusively for heavily calcified femoropopliteal lesions (73.3% superficial femoral artery [SFA]; 26.7% popliteal artery).28 This was a multicenter study (8 sites in Europe and New Zealand) as well that recruited 60 subjects with intermittent claudication. Severe calcification of the target lesion (according to Peripheral Academic Research Consortium [PARC] criteria) was found in 85% of cases, with an average calcification length of 98.1 mm, while 16.7% of the lesions were chronic total occlusions (CTOs).28
The procedural success rate was 100%; only 3.3% and 1.7% of the cases required postdilation and stent placement, respectively.28 Within 30 days from the index procedure, all lesions were patent, and no target-lesion revascularization (TLR) was required.28 During a 12-month follow-up period, the primary patency rate was 54.5% and the freedom from clinically driven TLR was 79.3%.28 However, in patients who were treated with optimal IVL technique (ie, correct device sizing and avoidance of therapeutic miss), the clinically driven TLR rate was lower than 9%, indicating that IVL could be safely utilized in this high-risk population, promising low revascularization rates with minimal vessel injury.28
The Disrupt PAD III (Shockwave Medical Peripheral Lithoplasty System Study for PAD; ClinicalTrials.gov identifier NCT02923193) observational study is a prospective, single-arm study that will include up to 1500 subjects.81 An interim analysis included 200 patients from 18 international sites who were treated with IVL for 220 calcified femoropopliteal lesions.81 The DISRUPT PAD III observational study comprised more challenging cases compared with previous DISRUPT PAD trials.81 For example, 77.9% of the lesions were severely calcified as per the PARC criteria, while 32.9% were CTOs.81 The mean target-lesion length was 103.4 mm and the mean target-lesion stenosis was 80.7%.81
Overall, additional or adjunctive therapy was required in about 92% of the lesions, with IVL more commonly combined with balloon angioplasty rather than atherectomy or stenting.81 The mean acute luminal gain was 3.4 mm, corresponding to a mean residual stenosis of 23.6%.81 Periprocedural angiographic complications were very rare, with only 2 dissections (grade D) observed that were deemed to be unrelated to IVL.81 Additionally, no distal embolization or thrombotic events were observed. Thus, this study utilizing real-world data provided significant evidence that peripheral IVL for heavily calcified lesions can facilitate endovascular interventions, leading to low residual stenosis and improved acute luminal gain without significant injury to the vessel.81
The DISRUPT PAD III (Shockwave Medical Peripheral Lithoplasty System Study for PAD; ClinicalTrials.gov identifier NCT02923193) trial was a randomized (1:1), core-lab adjudicated, multicenter study that investigated the outcomes of IVL followed by DCB angioplasty vs PTA followed by DCB only for the treatment of moderately and severely calcified de novo femoropopliteal disease.82 Key inclusion criteria included Rutherford classification 2-4 at baseline, reference vessel diameter ranging from 4 to 7 mm, target lesion length ≤180 mm, and stenosis ≥70%.82 Moderate/severe calcification was defined as the presence of fluoroscopic evidence suggestive of calcium on parallel sides of the vessels and extending for more than 50% of the lesion length with a minimum calcification of 20 mm.82 Patients with significant renal disease, planned target-limb major amputation, and non-successfully treated inflow disease were excluded.82
While the study is still ongoing, the early (30-day) outcomes of the study were presented at the Vascular Interventional Advances (VIVA) conference in 2020.82 Overall, 306 subjects from 45 sites in Europe, the United States, and New Zealand (February 2017 to May 2020) were assigned to IVL + DCB (153 patients) or PTA + DCB only (153 patients).82 Based on angiographic core lab data, procedural success rate, defined as residual stenosis ≤30% without flow-limiting dissection (grade D-F) prior to DCB angioplasty, was 65.8% and 50.4% in the IVL and PTA groups, respectively, with a statistically significant difference observed (P<.01).82 Hereby, IVL reduced by 75% and 69% the need for bail-out stenting and need for postdilation compared with PTA.82 Additionally, the 30-day major adverse event rate was 0.0% in the IVL group and 1.3% in the PTA group, without being statistically different.82 Thus, the DISRUPT PAD III randomized study—similar to the DISRUPT PAD III observational study—confirmed the benefits of IVL treatment in complex lesions and constituted the first level 1 evidence for the treatment of heavily calcified PAD.82
Current clinical data for IVL use In BTK disease. The DISRUPT BTK (Safety and Feasibility of the Shockwave Lithoplasty System for the Treatment of Peripheral Vascular Stenosis; ClinicalTrials.gov identifier NCT02911623) study was a prospective, single-arm, postmarket study that was designed to assess the safety and performance of IVL use for the treatment of heavily calcified BTK lesions.27 IVL was utilized as stand-alone therapeutic modality.27 Overall, 20 patients from 3 European sites were included and followed up for 30 days.27 The majority of the patients were men, had a history of hypertension, diabetes, and/or dyslipidemia and presented primarily with CLI (Rutherford classification 4 [1 patient]; Rutherford classification 5 [15 patients]).27
Moderate or severe calcification, as defined by a core laboratory, was observed in 11 and 9 patients, respectively, with a mean calcification length of 72.1 mm.27 The mean lumen diameter was 0.9 mm, corresponding to an average target-lesion stenosis of 72.6%.27 Delivery of the IVL catheter was not feasible in 1 patient, while IVL was successful in the remaining 19 patients, with residual diameter stenosis ≤50.0%.27 The average acute luminal gain was 1.5 mm, corresponding to a lumen stenosis of 26.2%.27 As such, IVL reduced the percent diameter stenosis by 46.5%.27 Overall, no IVL-related adverse events were observed and 30-day freedom from clinically driven TLR was 100%.27 Thus, the authors suggested that IVL at the infrapopliteal segment is feasible and can be safely performed for BTK disease.27 Nonetheless, additional studies with longer follow-up and standardized treatment protocols are needed to better understand the durability of IVL treatment in calcified BTK lesions.
An interim analysis of the DISRUPT PAD III observational study including only the cases with calcified infrapopliteal lesions was presented at the Leipzig Interventional Course (LINC) conference in 2021.83 Overall, 101 patients with 114 BTK lesions were treated with IVL at the discretion of the operator.83 Seventy percent of the patients underwent revascularization for CLI, and most patients were men and had a history of diabetes, hypertension, and/or hyperlipidemia.83 Additionally, almost one-half of the patients had significant chronic kidney disease at baseline, with 23.8% of the cohort requiring hemodialysis.83
Most lesions were located at the anterior tibial artery (34%), followed by the tibioperoneal trunk (33%). Less frequently, lesions were located at the peroneal (17%) and posterior tibial artery (16%).83 Based on core-lab adjudicated data, 69.3% of the lesions exhibited moderate/severe classification.83 In most cases the calcification was concentric (86%) vs eccentric (14%).83 The average lesion length was 65 mm, while the average calcification length was 53 mm.83 The mean minimal lumen diameter was 0.5 mm, corresponding to a mean percent diameter stenosis of 85%, while the mean reference lumen diameter was 3.1 mm.83 In 77% of the patients treated, IVL was a stand-alone calcium modification technique.83 Postdilation was required in 50.5% of the cases.83 DCB or stents were utilized in addition to IVL in 15% and 11% of the cases, respectively.83
The average post-IVL percent diameter stenosis was 28%, while the final percent diameter stenosis was 23%.83 Three severe dissections (grade D-F), which occurred in CTOs, and 1 distal embolization were observed after IVL.83 Nonetheless, after final interventions, no severe angiographic complications were present.83 Additionally, no perforation, slow/no reflow, or abrupt closure occurred.83 Thus, this interim analysis of data from the DISRUPT PAD III observational study showed significant reduction of diameter stenosis with IVL, with no significant angiographic adverse events at the end of the procedure.83
Optimal intravascular lithotripsy technique for Infrapopliteal intervention. Angioplasty remains the cornerstone of infrapopliteal intervention. Due to the lack of dedicated implants or approved bail-out therapies for infrapopliteal vessels, it is crucial to optimize the results of angioplasty while minimizing the likelihood of severe dissection or other vessel-related complications. We recently proposed an algorithm for optimal angioplasty of infrapopliteal vessels based on the concepts of optimal vessel sizing, selection of plaque modification technologies, prolonged balloon inflation, and careful assessment of postangioplasty dissection.80 Similar concepts apply to optimal application of IVL for infrapopliteal vessels (Figure 1).
Optimal sizing is crucial to maximizing the efficacy of IVL. Ideally, the IVL balloon should be sized 1.1:1 relative to the reference vessel diameter of the target lesion. Adequate apposition of the balloon to the vessel wall is important for both angioplasty and efficient transfer of the lithotripsy pulses to the surrounding calcium. Intravascular ultrasound may be helpful in these cases to ensure adequate balloon sizing, as prior studies have suggested that the use of intravascular ultrasound results in the use of balloon diameters on average 0.5-1 mm larger.84
Currently, IVL balloons are available in 2 configurations known as the M5 and S4 catheters. The M5 balloons are 60 mm in length, available in diameters of 3.5-7.0 mm, and deliver up to 300 pulses. The S4 balloons are 40 mm in length, available in diameters of 2.5-4.0 mm, and deliver up to 160 pulses. For infrapopliteal applications, the S4 catheters are generally preferred due to their longer shaft length and availability in smaller diameters. However, the M5 catheter may be used for larger reference vessel sizes, especially in the below-the-knee popliteal segment (Figure 2).
When utilizing IVL for infrapopliteal angioplasty, we recommend inflating the IVL balloon to 4 atm and delivering at least 40 pulses per segment treated. In cases of longer lesions, multiple IVL inflations may be necessary. In these cases, we recommend approximately 10 mm balloon overlap to minimize geographic miss and ensure optimal angioplasty throughout the target lesion. Based on the 40 mm length of the S4 catheters, it is therefore possible to treat lesion lengths of 130 mm with a single balloon. For longer lesions, an additional IVL balloon can be used, or a technique of long angioplasty balloon inflation followed by “spot” IVL at areas of residual stenosis can be employed. With this technique, the likelihood of severe dissection or recoil is minimized. If there is continued stenosis or dissection after IVL, postdilation can be performed with an additional balloon, and scaffolds can be considered for cases of continued dissection. Figure 3, Figure 4, and Figure 5 demonstrate additional cases of IVL application for infrapopliteal lesions, with an emphasis on the sizing and techniques used for each case.
Conclusion
Vessel calcification constitutes one of the most widely encountered risk factors for acute PTA technical failure due to higher risk for residual stenosis and severe dissections, while also limiting the efficacy of drug-eluting technology, associated as such with long-term sequelae. However, patients with moderate/severe calcification of infrapopliteal arteries are often excluded from clinical trials investigating the outcomes of endovascular revascularization for PAD. As a result, few data are available in order to guide clinical decision-making regarding endovascular treatment of this challenging patient population. The IVL results from the DISRUPT trials are encouraging, showing that IVL can improve acute luminal gain and facilitate endovascular therapy. Therefore, these studies strongly indicate that IVL could have a crucial role in the management of BTK disease, as infrapopliteal lesions are often complicated with moderate/severe calcification. Nonetheless, both cost-effective analyses and additional studies with standardized treatment protocols and long-term follow-up data are necessary before recommending PTA with adjunctive IVL as the first-line treatment for all calcified infrapopliteal lesions.
Affiliations and Disclosures
From the 1Division of Cardiology, Rocky Mountain Regional VA Medical Center, University of Colorado, Denver, Colorado; and 2Adventist Health St. Helena Hospital, St. Helena, California.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Armstrong is a consultant to Abbott Vascular, Boston Scientific, Cardiovascular Systems, Inc, Medtronic, Philips, PQ Bypass, and Shockwave Medical. Dr Giannopoulos reports no conflicts of interest regarding the content herein.
Manuscript accepted April 12, 2021.
Address for correspondence: Ehrin J. Armstrong, MD, MSc, Adventist Health St. Helena, 6 Woodland Rd #304, St. Helena, CA 94574. Email: Ehrin.armstrong@gmail.com
Related Articles
- ELCA-Tripsy: Combination of Laser and Lithotripsy for Severely Calcified Lesions
- Real-World Experience of Coronary Intravascular Lithotripsy in an Asian Population: A Retrospective, Observational, Single-Center, All-Comers Registry
- Shockwave Intravascular Lithotripsy for Calcified Coronary Lesions: First Real-World Experience
- The Utility of Peripheral Intravascular Lithotripsy in Calcific Coronary Artery Disease: A Case Series
- Treatment of Heavily Calcified Unprotected Left Main Disease With Lithotripsy: The First Case Series
References
1. Singh S, Armstrong EJ, Sherif W, et al. Association of elevated fasting glucose with lower patency and increased major adverse limb events among patients with diabetes undergoing infrapopliteal balloon angioplasty. Vasc Med. 2014;19(4):307-314.
2. Westin GG, Armstrong EJ, Bang H, et al. Association between statin medications and mortality, major adverse cardiovascular event, and amputation-free survival in patients with critical limb ischemia. J Am Coll Cardiol. 2014;63(7):682-690.
3. Shammas AN, Jeon-Slaughter H, Tsai S, et al. Major limb outcomes following lower extremity endovascular revascularization in patients with and without diabetes mellitus. J Endovasc Ther. 2017;24(3):376-382.
4. Antoniou GA, Georgiadis GS, Antoniou SA, Makar RR, Smout JD, Torella F. Bypass surgery for chronic lower limb ischaemia. Cochrane Database Syst Rev. 2017;4(4):CD002000.
5. Goksel OS, Karpuzoglu E, Issever H, Cinar B. Midterm results with drug-coated balloons for SFA lesions in patients with CLI: comparison with conventional bypass surgery. Int Angiol. 2018;37(5):365-369.
6. Reijnen M, van Wijck I, Zeller T, et al. Outcomes after drug-coated balloon treatment of femoropopliteal lesions in patients with critical limb ischemia: a post hoc analysis from the IN.PACT Global Study. J Endovasc Ther. 2019;26(3):305-315.
7. Armstrong EJ, Ryan MP, Baker ER, Martinsen BJ, Kotlarz H, Gunnarsson C. Risk of major amputation or death among patients with critical limb ischemia initially treated with endovascular intervention, surgical bypass, minor amputation, or conservative management. J Med Econ. 2017;20(11):1148-1154.
8. Bradbury AW, Adam DJ, Bell J, et al. Multicentre randomised controlled trial of the clinical and cost-effectiveness of a bypass-surgery-first versus a balloon-angioplasty-first revascularisation strategy for severe limb ischaemia due to infrainguinal disease. The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial. Health Technol Assess. 2010;14(14):1-210, iii-iv.
9. Katsanos K, Kitrou P, Spiliopoulos S, Diamantopoulos A, Karnabatidis D. Comparative effectiveness of plain balloon angioplasty, bare metal stents, drug-coated balloons, and drug-eluting stents for the treatment of infrapopliteal artery disease: systematic review and bayesian network meta-analysis of randomized controlled trials. J Endovasc Ther. 2016;23(6):851-863.
10. Laird JR, Jain A, Zeller T, et al. Nitinol stent implantation in the superficial femoral artery and proximal popliteal artery: twelve-month results from the complete SE multicenter trial. J Endovasc Ther. 2014;21(2):202-212.
11. Schillinger M, Sabeti S, Dick P, et al. Sustained benefit at 2 years of primary femoropopliteal stenting compared with balloon angioplasty with optional stenting. Circulation. 2007;115(21):2745-2749.
12. Singh GD, Brinza EK, Hildebrand J, et al. Midterm outcomes after infrapopliteal interventions in patients with critical limb ischemia based on the TASC II classification of below-the-knee arteries. J Endovasc Ther. 2017;24(3):321-330.
13. Armstrong EJ, Bishu K, Waldo SW. Endovascular treatment of infrapopliteal peripheral artery disease. Curr Cardiol Rep. 2016;18(4):34.
14. Bosiers M, Hart JP, Deloose K, Verbist J, Peeters P. Endovascular therapy as the primary approach for limb salvage in patients with critical limb ischemia: experience with 443 infrapopliteal procedures. Vascular. 2006;14(2):63-69.
15. Schamp KB, Meerwaldt R, Reijnen MM, Geelkerken RH, Zeebregts CJ. The ongoing battle between infrapopliteal angioplasty and bypass surgery for critical limb ischemia. Ann Vasc Surg. 2012;26(8):1145-1153.
16. Fanelli F, Cannavale A, Gazzetti M, et al. Calcium burden assessment and impact on drug-eluting balloons in peripheral arterial disease. Cardiovasc Intervent Radiol. 2014;37(4):898-907.
17. Halwani DO, Anderson PG, Brott BC, Anayiotos AS, Lemons JE. The role of vascular calcification in inducing fatigue and fracture of coronary stents. J Biomed Mater Res B Appl Biomater. 2012;100(1):292-304.
18. Schillinger M, Minar E. Percutaneous treatment of peripheral artery disease: novel techniques. Circulation. 2012;126(20):2433-2440.
19. Adlakha S, Sheikh M, Wu J, et al. Stent fracture in the coronary and peripheral arteries. J Interv Cardiol. 2010;23(4):411-419.
20. Shammas NW, Lam R, Mustapha J, et al. Comparison of orbital atherectomy plus balloon angioplasty vs. balloon angioplasty alone in patients with critical limb ischemia: results of the CALCIUM 360 randomized pilot trial. J Endovasc Ther. 2012;19(4):480-488.
21. Mattesini A, Di Mario C. Calcium: a predictor of interventional treatment failure across all fields of cardiovascular medicine. Int J Cardiol. 2017;231:97-98. Epub 2017 Jan 10.
22. Kondapalli A, Jeon-Slaughter H, Lu H, et al. Comparative assessment of patient outcomes with intraluminal or subintimal crossing of infrainguinal peripheral artery chronic total occlusions. Vasc Med. 2018;23(1):39-45.
23. Rocha-Singh KJ, Zeller T, Jaff MR. Peripheral arterial calcification: prevalence, mechanism, detection, and clinical implications. Catheter Cardiovasc Interv. 2014;83(6):E212-220.
24. DeRubertis BG, Faries PL, McKinsey JF, et al. Shifting paradigms in the treatment of lower extremity vascular disease: a report of 1000 percutaneous interventions. Ann Surg. 2007;246(3):415-422; discussion 422-414.
25. Ali ZA, Brinton TJ, Hill JM, et al. Optical coherence tomography characterization of coronary lithoplasty for treatment of calcified lesions: first description. JACC Cardiovasc Imaging. 2017;10(8):897-906.
26. Brodmann M, Werner M, Brinton TJ, et al. Safety and performance of lithoplasty for treatment of calcified peripheral artery lesions. J Am Coll Cardiol. 2017;70(7):908-910.
27. Brodmann M, Holden A, Zeller T. Safety and feasibility of intravascular lithotripsy for treatment of below-the-knee arterial stenoses. J Endovasc Ther. 2018;25(4):499-503.
28. Brodmann M, Werner M, Holden A, et al. Primary outcomes and mechanism of action of intravascular lithotripsy in calcified, femoropopliteal lesions: results of Disrupt PAD II. Catheter Cardiovasc Interv. 2019;93(2):335-342.
29. Patel MR, Conte MS, Cutlip DE, et al. Evaluation and treatment of patients with lower extremity peripheral artery disease: consensus definitions from Peripheral Academic Research Consortium (PARC). J Am Coll Cardiol. 2015;65(9):931-941.
30. Adams G, Shammas N, Mangalmurti S, et al. Intravascular lithotripsy for treatment of calcified Llower extremity arterial stenosis: initial analysis of the Disrupt PAD III Study. J Endovasc Ther. 2020;27(3):473-480.
31. U.S. Food and Drug Administration. Shockwave Medical, Inc; Shockwave Medical Intravascular Lithotripsy (IVL) System. June 27, 2018. Accessed January 11, 2022. https://www.accessdata.fda.gov/cdrh_docs/pdf18/K180454.pdf
32. Holden A. The use of intravascular lithotripsy for the treatment of severely calcified lower limb arterial CTOs. J Cardiovasc Ther. 2019;60(1):3-7.
33. Giannopoulos S, Armstrong EJ. Newly approved devices for endovascular treatment of femoropopliteal disease: a review of clinical evidence. Expert Rev Cardiovasc Ther. 2019;17(10):729-740.
34. Armstrong EJ, Soukas PA, Shammas N, et al. Intravascular lithotripsy for treatment of calcified, stenotic iliac arteries: a cohort analysis from the Disrupt PAD III study. Cardiovasc Revasc Med. 2020;21(10):1262-1268.
35. Adams G, Shammas N, Mangalmurti S, et al. Intravascular lithotripsy for treatment of calcified lower extremity arterial stenosis: initial analysis of the Disrupt PAD III study. J Endovasc Ther. 2020;27(3):473-480.
36. Armstrong EJ, Soukas PA, Shammas N, et al. Intravascular lithotripsy for treatment of calcified, stenotic iliac arteries: a cohort analysis from the Disrupt PAD III study. Cardiovasc Revasc Med. 2020;21(10):1262-1268.
37. Madhavan MV, Shahim B, Mena-Hurtado C, Garcia L, Crowley A, Parikh SA. Efficacy and safety of intravascular lithotripsy for the treatment of peripheral arterial disease: an individual patient-level pooled data analysis. Catheter Cardiovasc Interv. 2020;95(5):959-968.
38. Giannopoulos S, Speziale F, Vadalà G, et al. Intravascular lithotripsy for treatment of calcified lesions during carotid artery stenting. J Endovasc Ther. 2021;28(1):93-99.
39. Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study. Circulation. 1995;92(8):2157-2162.
40. Mustapha JA, Diaz-Sandoval LJ, Saab F. Infrapopliteal calcification patterns in critical limb ischemia: diagnostic, pathologic and therapeutic implications in the search for the endovascular holy grail. J Cardiovasc Surg. 2017;58(3):383-401.
41. Shanahan CM, Cary NR, Salisbury JR, Proudfoot D, Weissberg PL, Edmonds ME. Medial localization of mineralization-regulating proteins in association with Monckeberg's sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation. 1999;100(21):2168-2176.
42. Steenman M, Espitia O, Maurel B, et al. Identification of genomic differences among peripheral arterial beds in atherosclerotic and healthy arteries. Sci Rep. 2018;8(1):3940.
43. Herisson F, Heymann MF, Chetiveaux M, et al. Carotid and femoral atherosclerotic plaques show different morphology. Atherosclerosis. 2011;216(2):348-354.
44. Heymann MF, Herisson F, Davaine JM, et al. Role of the OPG/RANK/RANKL triad in calcifications of the atheromatous plaques: comparison between carotid and femoral beds. Cytokine. 2012;58(2):300-306.
45. Huang H, Virmani R, Younis H, Burke AP, Kamm RD, Lee RT. The impact of calcification on the biomechanical stability of atherosclerotic plaques. Circulation. 2001;103(8):1051-1056.
46. Dalager S, Paaske WP, Kristensen IB, Laurberg JM, Falk E. Artery-related differences in atherosclerosis expression: implications for atherogenesis and dynamics in intima-media thickness. Stroke. 2007;38(10):2698-2705.
47. Waxman S, Dixon SR, L'Allier P, et al. In vivo validation of a catheter-based near-infrared spectroscopy system for detection of lipid core coronary plaques: initial results of the SPECTACL study. JACC Cardiovasc Imaging. 2009;2(7):858-868.
48. Majesky MW. Developmental basis of vascular smooth muscle diversity. Arterioscler Thromb Vasc Biol. 2007;27(6):1248-1258.
49. Leroux-Berger M, Queguiner I, Maciel TT, Ho A, Relaix F, Kempf H. Pathologic calcification of adult vascular smooth muscle cells differs on their crest or mesodermal embryonic origin. J Bone Miner Res. 2011;26(7):1543-1553.
50. London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 2003;18(9):1731-1740.
51. Tripodi A. Thrombin generation assay and its application in the clinical laboratory. Clin Chem. 2016;62(5):699-707.
52. Kuijpers MJE, van der Meijden PEJ, Feijge MAH, et al. Factor XII regulates the pathological process of thrombus formation on ruptured plaques. Arterioscler Thromb Vasc Biol. 2014;34(8):1674-1680.
53. Fuchs U, Caffier P, Schulz HG, Wieniecki P. Arterial calcification in diabetics. Virchows Arch A Pathol Anat Histopathol. 1985;407(4):431-439.
54. Johnson RC, Leopold JA, Loscalzo J. Vascular calcification: pathobiological mechanisms and clinical implications. Circ Res. 2006;99(10):1044-1059.
55. Fernandez N, McEnaney R, Marone LK, et al. Multilevel versus isolated endovascular tibial interventions for critical limb ischemia. J Vasc Surg. 2011;54(3):722-729.
56. Fitzgerald PJ, Ports TA, Yock PG. Contribution of localized calcium deposits to dissection after angioplasty. An observational study using intravascular ultrasound. Circulation. 1992;86(1):64-70.
57. Gray BH, Grant AA, Kalbaugh CA, et al. The impact of isolated tibial disease on outcomes in the critical limb ischemic population. Ann Vasc Surg. 2010;24(3):349-359.
58. Sadek M, Ellozy SH, Turnbull IC, Lookstein RA, Marin ML, Faries PL. Improved outcomes are associated with multilevel endovascular intervention involving the tibial vessels compared with isolated tibial intervention. J Vasc Surg. 2009;49(3):638-643; discussion 643-634.
59. Graziani L, Silvestro A, Bertone V, et al. Vascular involvement in diabetic subjects with ischemic foot ulcer: a new morphologic categorization of disease severity. Eur J Vasc Endovasc Surg. 2007;33(4):453-460.
60. Lehto S, Niskanen L, Suhonen M, Rönnemaa T, Laakso M. Medial artery calcification. A neglected harbinger of cardiovascular complications in non-insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol. 1996;16(8):978-983.
61. Diehm N, Shang A, Silvestro A, et al. Association of cardiovascular risk factors with pattern of lower limb atherosclerosis in 2659 patients undergoing angioplasty. Eur J Vasc Endovasc Surg. 2006;31(1):59-63.
62. Burns DM. Epidemiology of smoking-induced cardiovascular disease. Prog Cardiovasc Dis. 2003;46(1):11-29.
63. Aboyans V, Lacroix P, Criqui MH. Large and small vessels atherosclerosis: similarities and differences. Prog Cardiovasc Dis. 2007;50(2):112-125.
64. Laclaustra M, Casasnovas JA, Fernandez-Ortiz A, et al. Femoral and carotid subclinical atherosclerosis association with risk factors and coronary calcium: the AWHS study. J Am Coll Cardiol. 2016;67(11):1263-1274.
65. de Athayde Soares R, Matielo MF, Brochado Neto FC, et al. Impact of calcification and infrapopliteal outflow on the outcome of endovascular treatment of femoropopliteal occlusive disease. JRSM Cardiovasc Dis. 2019;8:2048004019828941.
66. Castaneda-Zuniga WR, Formanek A, Tadavarthy M, et al. The mechanism of balloon angioplasty. Radiology. 1980;135(3):565-571.
67. Kashyap VS, Pavkov ML, Bishop PD, et al. Angiography underestimates peripheral atherosclerosis: lumenography revisited. J Endovasc Ther. 2008;15(1):117-125.
68. Armstrong EJ, Brodmann M, Deaton DH, et al. Dissections after infrainguinal percutaneous transluminal angioplasty: a systematic review and current state of clinical evidence. J Endovasc Ther. 2019;26(4):479-489.
69. Razavi MK, Mustapha JA, Miller LE. Contemporary systematic review and meta-analysis of early outcomes with percutaneous treatment for infrapopliteal atherosclerotic disease. J Vasc Interv Radiol. 2014;25(10):1489-1496, 1496.e1481-e.1483.
70. Tepe G, Zeller T, Schnorr B, et al. High-grade, non-flow-limiting dissections do not negatively impact long-term outcome after paclitaxel-coated balloon angioplasty: an additional analysis from the THUNDER study. J Endovasc Ther. 2013;20(6):792-800.
71. Tepe G, Zeller T, Albrecht T, et al. Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med. 2008;358(7):689-699.
72. Kobayashi N, Hirano K, Yamawaki M, et al. Simple classification and clinical outcomes of angiographic dissection after balloon angioplasty for femoropopliteal disease. J Vasc Surg. 2018;67(4):1151-1158.
73. Kaladji A, Vent PA, Danvin A, et al. Impact of vascular calcifications on long femoropopliteal stenting outcomes. Ann Vasc Surg. 2018;47:170-178. Epub 2017 Sep 8.
74. Tepe G, Beschorner U, Ruether C, et al. Drug-eluting balloon therapy for femoropopliteal occlusive disease: predictors of outcome with a special emphasis on Calcium. J Endovasc Ther. 2015;22(5):727-733.
75. Shammas NW, Torey JT, Shammas WJ. Dissections in peripheral vascular interventions: a proposed classification using intravascular ultrasound. J Invasive Cardiol. 2018;30(4):145-146.
76. Armstrong EJ, Alam S, Henao S, et al. Multidisciplinary care for critical limb ischemia: current gaps and opportunities for improvement. J Endovasc Ther. 2019;26(2):199-212.
77. Armstrong EJ, Shishehbor MH. Commentary: contemporary outcomes of endovascular interventions for peripheral artery disease: the LIBERTY to determine optimal treatment strategies. J Endovasc Ther. 2019;26(2):155-157.
78. Topfer LA, Spry C. New technologies for the treatment of peripheral artery disease. In: CADTH Issues in Emerging Health Technologies. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; April 1, 2018.1-19. Accessed January 14, 2022. https://www.ncbi.nlm.nih.gov/books/NBK519606/.
79. Kokkinidis DG, Giannopoulos S, Jawaid O, Cantu D, Singh GD, Armstrong EJ. Laser atherectomy for infrapopliteal lesions in patients with critical limb ischemia. Cardiovasc Revasc Med. 2021;23:79-83. Epub 2020 Sep 11.
80. Giannopoulos S, Varcoe RL, Lichtenberg M, et al. Balloon angioplasty of infrapopliteal arteries: a systematic review and proposed algorithm for optimal endovascular therapy. J Endovasc Ther. 2020;27(4):547-564.
81. Holden A. Intravascular lithotripsy (IVL): study status (DISRUPT PAD II and III) and lessons from real world registry. Accessed January 14, 2022. https://shockwavemedical.com/wp-content/uploads/2019/04/Disrupt-PAD-III-OS_Holden_Cx-2019.pdf.
82. Rastan A, Tepe G, Krankenberg H, et al. Sirolimus-eluting stents vs. bare-metal stents for treatment of focal lesions in infrapopliteal arteries: a double-blind, multi-centre, randomized clinical trial. Eur Heart J. 2011;32(18):2274-2281.
83. Bosiers M, Scheinert D, Peeters P, et al. Randomized comparison of everolimus-eluting versus bare-metal stents in patients with critical limb ischemia and infrapopliteal arterial occlusive disease. J Vasc Surg. 2012;55(2):390-398.
84. Soga Y, Takahara M, Ito N, et al. Clinical impact of intravascular ultrasound-guided balloon angioplasty in patients with chronic limb threatening ischemia for isolated infrapopliteal lesion. Catheter Cardiovasc Interv. 2021;97(3):E376-E384.
