A 62-year old woman was referred from another center for management of recurrent symptomatic in-stent restenosis of the proximal left circumflex artery (pLCx). Her cardiovascular history was significant of non-ST-elevation myocardial infarction and three-vessel coronary artery disease, for which she underwent PCI to the pLCx with 2.75x28 mm Centum drug-eluting stent (June 2024), followed by PCI to the proximal-mid LAD with 3.5x28 mm Centum drug-eluting stent (September 2024).The pLCx stent developed in-stent restenosis within ten months, requiring drug-coated balloon (DCB) angioplasty in April 2025. Repeat angiography in June 2025 confirmed patency, but by December 2025, angiography demonstrated severe recurrent ISR at the same segment, raising concern for a non-neointimal mechanism underlying the repeated failures.Her medical background was notable for moderate aortic stenosis (Vmax 3.9 m/s, AVA 1.17 cm²), hypertension, dyslipidemia, hyperthyroidism, chronic kidney disease stage 2 and prior left renal infarction. Her surgical history includes neck mass excision (2014) and right hip arthroplasty (2023). She had a documented history of long QT syndrome which was complicated with an event of Torsades de pointes, all of which informed the procedural planning and anesthetic approach.

Baseline investigations confirmed preserved renal function (creatinine 1.03 mg/dL) with no acute deterioration. Transthoracic echocardiography (TTE) demonstrated moderate aortic stenosis with preserved left ventricular systolic function (LVEF 63%), relevant both prognostically and in guiding hemodynamic management during the procedure. The rest of her laboratory results were insignificant. The resting ECG was reviewed in the context of the patient’s known long QT history and showed normal sinus rhythm with heart rate of 86 beats per minute and a left bundle branch block. Her medications were carefully reconciled prior to admission and dual antiplatelet therapy was confirmed as ongoing. No contrast allergy was documented.

Coronary angiography confirmed severe focal in-stent restenosis at the proximal LCx stent with TIMI 2 flow. The prior LAD stent was angiographically patent. Given the borderline appearance of a residual mid LAD lesion, fractional flow reserve (FFR) was measured using adenosine infusion, yielding a hyperemic FFR of 0.83 which confirmed a hemodynamically insignificant lesion. The Right coronary artery angiography showed a non-dominant RCA with distal moderate to significant lesion which was left for symptom guided approach in future follow up.The Pivotal finding of this case came from intravascular ultrasound (IVUS), performed after guidewire crossing of the pLCx ISR segment. Rather than the diffuse neointimal hyperplasia expected in a second restenosis after DCB, IVUS revealed heavy circumferential calcification with protruding calcific nodule eroding into the stent lumen, fundamentally redefining the mechanism of ISR and necessitating a complete change in treatment strategy. This finding underscores the indispensable role of intracoronary imaging in recurrent ISR.
4-1 Eman Murad.avi
4-2 Eman Murad.avi

Following diagnostic angiography and IVUS assessment, a sequential calcium modification strategy was adopted, combining rotational atherectomy and intravascular lithotripsy (Rotatripsy), to address the calcific nodule prior to definitive therapy.Access & Anticoagulation: Right femoral artery access was obtained with 7 Fr sheath. Unfractionated heparin was administered to maintain therapeutic ACT. Guiding catheter used was JL 4.0 7 Fr system. Runthrough NS 0.014” guidewire was initially used as a workhorse wire and was parked at distal LCx. Wire was then exchanged to RotaWire 0.009” via Caravel microcatheter.Stepwise debulking was done with Rotablation which was initiated by 3 passes with1.5 mm burr at 172,000 rpm, which then was upsized to 1.75 mm burr with multiple passes at 160,000 rpm, targeting the calcific nodule. Post Rota IVUS confirmed partial calcium disruption with residual nodule and insufficient luminal gain, prompting escalation.Aiming to fracture the deep calcium, Shockwave IVL balloon (3.0 mm) was deployed at 4 atm, aiming to deliver 120 shocks. After 84 shocks the balloon was damaged evident by balloon rupture, hence it was exchanged; lithotripsy was then completed to the full cycle. Post-IVL IVUS demonstrated circumferential calcium fractures, nodule fragmentation, and significant luminal expansion, confirming the additive value of IVL after rotablation.Non-compliant balloon (Selethru NC 3.5x15 mm) was inflated sequentially to 24 atm and 28 atm to optimize stent expansion and achieve full apposition against the now-modified calcium scaffold.Because the mechanism was calcific nodule-related restenosis within an already treated segment, we intentionally avoided further metal implantation and completed treatment with drug coated balloon (SeQuent Please NEO 3.5x20 mm) which was deployed at 6 atm for 60 seconds, delivering Paclitaxel uniformly across the ISR segment, to address both the mechanical and biological contributors to restenosis.Final IVUS confirmed full stent expansion, no residual calcium protrusion, no dissection, and proper luminal gain (Minimum Stent Area- MSA 8.76 m² vs. 3.13 m²). Final angiography demonstrated TIMI 3 flow with no residual stenosis. The patient was hemodynamically stable throughout and was discharged the following day without complications.
5-1 Eman Murad.avi
5-2 Eman Murad.avi
5-3 Eman Murad.avi

This case makes a compelling argument for routine intravascular imaging in all cases of recurrent in-stent restenosis. The eroding calcific nodule identified on IVUS would have been invisible on angiography alone and would almost certainly have led to a third restenosis had the lesion been treated empirically with balloon or DCB without plaque modification. IVUS did not merely guide the procedure, it changed the entire clinical paradigm.The sequential Rotatripsy strategy demonstrates that rotational atherectomy and intravascular lithotripsy are not competing technologies but complementary ones: rotablation disrupts the nodule surface and debulks the calcium scaffold, while IVL propagates deep circumferential fractures that allow full balloon expansion. Together, they created the mechanical substrate necessary for effective DCB drug delivery, the final therapeutic layer addressing the neointimal biology of ISR.Beyond the technical points, this case carries an important message about patient complexity. Successful outcomes in high-risk patients require a deeply individualized approach, precise hemodynamic awareness, and the willingness to adapt strategy in real time based on intracoronary imaging findings.The main key message is that mechanism-directed plaque modification, rather than reflex repeat stenting, may be the key to durable success in complex calcific in-stent restenosis.