BackgroundAlthough intravascular lithotripsy (IVL) has been an emerging novel option to treat vascular calcification, the specific effects on histology have not been systematically examined. ObjectivesThe authors examined the histologic effects of IVL on coronary calcified lesions from human autopsy hearts and evaluated the diagnostic ability of optical coherence tomography (OCT) and micro-computed tomography (CT) to detect calcium fracture as identified by the gold standard histology. MethodsEight coronary lesions were treated with IVL, and 7 lesions were treated with 10 atm inflation using an IVL catheter balloon without lithotripsy pulses (plain old balloon angioplasty [POBA]). OCT and micro-CT imaging were performed before and after treatment, and the presence of calcium fracture was assessed. The frequency and size of fractures were measured and compared with the corresponding histology. ResultsAll 15 treated lesions were diagnosed as sheet calcium by histology. Histological evidence of calcium fracture was significantly greater in the IVL group compared with the POBA group (62.5% vs 0.0%; P = 0.01). Calcified lesions with fracture had a larger maximum arc degree of calcification (median 145.6 [IQR: 134.4-300.4] degrees vs 107.0 [IQR: 88.9-129.1] degrees; P = 0.01). Micro-CT and histology showed an excellent correlation for fracture depth (R2 = 0.83; P < 0.0001), whereas OCT showed less correlation (R2 = 0.37; P = 0.11). The depth of fractures measured by OCT were significantly shorter than with those measured by histology (0.49 [IQR: 0.29-0.77] mm vs 0.88 [IQR: 0.64-1.07] mm; P = 0.008). ConclusionsIVL demonstrated a histologically superior fracturing effect on coronary calcified lesions compared with POBA. OCT failed to identify the presence of some calcium fractures and underestimated the depth of fracture when compared with micro-CT.

Thrombo-occlusive disease is one of the leading causes of death worldwide. There has been active research on safe and effective thrombolysis in preclinical and clinical studies. Recently, the dual-frequency transcutaneous sonothrombolysis with contrast agents [microbubbles (MBs)] has been reported to be more efficient in trigging the acoustic cavitation, which leads to a higher lysis rate. Therefore, there is increasing interest in applying dual-frequency technique for more significant efficacy improvement in intravascular sonothrombolysis since a miniaturized intravascular ultrasound transducer typically has a limited power output to fully harness cavitation effects. In this work, we demonstrated this efficacy enhancement by developing a new broadband intravascular transducer and testing dual-frequency sonothromblysis in vitro. A broadband intravascular transducer with a center frequency of 750 kHz and a footprint size of 1.4 mm was designed, fabricated, and characterized. The measured -6-dB fractional bandwidth is 68.1%, and the peak negative pressure is 1.5 MPa under the driving voltage of 80 Vpp. By keeping one frequency component at 750 kHz, the second frequency component was selected from 450 to 650 kHz with an interval of 50 kHz. The in vitro sonothrombolysis tests were conducted with a flow model and the results indicated that the MB-mediated, dual-frequency (750+500 kHz) sonothrombolysis yields an 85% higher lysis rate compared with the single-frequency treatment, and the lysis rate of dual-frequency sonothrombolysis increases with the difference between the two frequency components. These findings suggest a dual-frequency excitation technique for more efficient intravascular sonothrombolysis than conventional single-frequency excitation.

The Society for Cardiovascular Angiography and Interventions (SCAI) Think Tank is a collaborative venture that brings together interventional cardiologists, administrative partners, and select members of the cardiovascular industry community annually for high-level field-wide discussions. The 2021 Think Tank was organized into four parallel sessions reflective of the field of interventional cardiology: (a) coronary intervention, (b) endovascular medicine, (c) structural heart disease, and (d) congenital heart disease. Each session was moderated by a senior content expert and co-moderated by a member of SCAI's Emerging Leader Mentorship program. This document presents the proceedings to the wider cardiovascular community in order to enhance participation in this discussion, create additional dialog from a broader base, and thereby aid SCAI, the industry community and external stakeholders in developing specific action items to move these areas forward.

A significant proportion of lesions treated with transcatheter interventions in the coronary and peripheral vascular beds exhibit moderate to severe calcific plaques known to portend lower procedural success rates, increased peri-procedural adverse events, and unfavorable clinical outcomes compared with noncalcific plaques. Adapted from lithotripsy technology used for treatment of ureterorenal calculi, intravascular lithotripsy (IVL) is a novel technique for the treatment of severely calcific plaque lesions that uses acoustic shockwaves in a balloon-based delivery system. Shockwaves induce calcium fractures, which facilitate stent expansion and luminal gain. In this review, the authors summarize the physics, preclinical and clinical data on IVL use in the coronary and peripheral vasculature, and future directions of IVL in transcatheter cardiovascular therapies.

Coronary calcification limits optimal stent expansion and apposition and worsens safety and effectiveness outcomes of percutaneous coronary intervention (PCI). Current ablative technologies that modify calcium to optimize stent deployment are limited by guidewire bias and periprocedural complications related to atheroembolization, coronary dissection, and perforation. Intravascular lithotripsy (IVL) delivers pulsatile ultrasonic pressure waves through a fluid-filled balloon into the vessel wall to modify calcium and enhance vessel compliance, reduce fibroelastic recoil, and decrease the need for high-pressure balloon (barotrauma) inflations. IVL has been used in peripheral arteries as stand-alone revascularization or as an adjunct to optimize stent deployment. STUDY DESIGN AND OBJECTIVES: Disrupt CAD III (clinicaltrials.gov identifier: NCT03595176) is a prospective, multicenter, single-arm study designed to assess safety and efficacy of the Shockwave coronary IVL catheter to optimize coronary stent deployment in patients with de novo calcified coronary stenoses. The primary safety end point is freedom from major adverse cardiovascular events (composite of cardiac death, myocardial infarction, and target vessel revascularization) at 30 days compared to a prespecified performance goal. The primary effectiveness end point is procedural success without in-hospital major adverse cardiovascular events. Enrollment will complete early in 2020 with clinical follow-up ongoing for 2 years. CONCLUSION: Disrupt CAD III will evaluate the safety and effectiveness of the Shockwave coronary IVL catheter to optimize coronary stent deployment in patients with calcified coronary stenoses.

The goal of our research was demonstrated that multiple molecules in microenvironments of the early osteoarthritis (OA) joint tissue may be actively responded to extracorporeal shockwave therapy (ESWT) treatment, which potentially regulated biological function of chondrocytes and synovial cells in early OA knee. We demonstrated that shockwave treatment induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which was a significant mediator of the 1α,25-Dihydroxyvitamin D 3 (1α,25(OH)2D3) rapid signaling pathway, using two-dimensional electrophoresis, histological analysis and quantitative polymerase chain reaction (qPCR). We observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of other group at 4, 8, and 12 weeks post-shockwave treatment in early OA rat knee model. The other factors of the rapid membrane signaling pathway, including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were examined and were found to be significantly increased at 2 weeks post-shockwave treatment by qPCR in early OA of the knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of OA joint tissue that could be actively responded to ESWT, which may potentially regulate the biological functions of chondrocytes and osteoblasts in the treatment of the early OA of the knee.