Heparin-induced thrombocytopenia (HIT) is infrequent and often goes unrecognized. It occurs in ~1% to 5% of the patients given unfractionated heparin,¹ about 25–50% of whom will develop HIT with thrombotic syndrome (HITTS).² Morbidity and mortality are high, and more than 50% of patients suffering thrombotic complications will die.³ Patients with recognized HIT may require anticoagulation for acute coronary syndromes (ACS) or percutaneous coronary intervention (PCI), thus presenting a clinical challenge given the limited alternatives for anticoagulation treatment.

Percutaneous coronary intervention is a common procedure, with over 750,000 interventions performed in the United States per year. Balloon inflation and stent deployment cause endothelial injury and plaque disruption, leading to platelet activation, thrombin generation and an inflammatory response. Aspirin, clopidogrel, platelet glycoprotein (GP) IIb/IIIa receptor inhibitors and unfractionated or low-molecular weight heparin are routinely used to counteract the effects of thrombin and the stimulated platelet population. The GP IIb/IIIa inhibitors block the final common pathway of platelet activation and the heparins in conjunction with antithrombin III attenuate the action of thrombin. Both the GP IIb/IIIa inhibitors and the heparins can lead to thrombocytopenia. Heparin-induced thrombocytopenia (HIT) has been associated with clinical thrombosis.

Heparin-induced thrombocytopenia (HIT) is a rather rare complication of heparin therapy, but may occasionally lead to devastating or even life-threatening complications. HIT is more frequent after therapy with unfractionated than low molecular weight heparin. The inherent problem of prothrombosis in HIT can be a major obstacle in patients who need therapy with percutaneous coronary interventions (PCI), especially with stent implantation. This is due to the iatrogenic plaque disruption and promotion of an endovascular thrombosis process during PCI, and the added risk of stent thrombosis. Therefore, it is evident that if the interventional cardiologist does not pay appropriate attention to this syndrome, a major, life-threatening complication may occur in the catheterization laboratory or shortly after the PCI procedure.

Cutting balloon (CB) technology combines the features of microsurgical incision with balloon dilation to treat atherosclerotic lesions. The CB has a non-compliant dilation balloon with microsurgical blades (atherotomes) attached to the outer surface. The cutting blades serve to radially incise the atherosclerotic lesion prior to balloon expansion. Linear incisions made by the blades facilitate expansion of the atherosclerotic lesion at lower inflation pressures, resulting in less barotrauma-related injury to the vessel wall.1 In addition, the symmetric and orderly disruption of the plaque lesion with the CB is believed to result in less injury to the vessel during expansion compared to conventional balloon angioplasty. Clinical studies using the CB have shown promising results.

Stents were introduced as a bail-out therapy for threatened abrupt closure1–5 following plain balloon coronary angioplasty. They were subsequently demonstrated to lower the restenosis rates in selected patient populations.6–8 The smooth appearance of the vessel after stenting has seduced the interventionist. The stenting rates are reported to be approximately 70%9 and move toward 100%. Stenting, albeit an essential and effective tool, has downsides such as stent thrombosis (still a concern in spite of newer antiplatelet drugs) and intricate in-stent restenosis. The long and diffuse variety of in-stent restenosis has been the bane of stenting, with only partial reprieve provided with the use of costly intracoronary radiation.10 Even the promising drug-eluting stents will not eliminate this problem. Increased stent use has resulted in higher coronary angioplasty costs.11 This will be further compounded with the ever-growing use of stents.

Neointimal hyperplasic response following angioplasty (PTCA), and especially stent implantation, is linked to overstretch injury, causing modulation of the vascular cytoskeleton and subsequent production of mediators.1 These result in smooth muscle cell migration and replication, and production of extra cellular matrix.2–7 These processes associated with vascular remodeling or lack of adequate vascular compliance result in restenosis. Stents have been demonstrated to affect a larger post-angioplasty lumen.8,9 This results in reduced restenosis, in spite of an increased neointimal response when compared with balloon alone.10 New stent designs have emerged in an attempt to improve on the deficiencies of the first-generation stents such as excessive rigidity, articulation gaps and non-uniform expansion.11 The ability to adequately deploy a stent with fewer traumas to the vessel wall due to improved radial compliance may therefore result in reduced neointimal formation.

On September 16th, 1977, Andreas Gruentzig performed the first coronary angioplasty on a 38-year-old man with a discrete proximal left anterior descending artery lesion. The procedure was a success, and the field of interventional cardiology was born.1,2 Percutaneous coronary intervention (PCI) grew over the next 25 years to become the dominant mode of coronary revascularization with over 1 million annual procedures performed in the United States alone. Even with its success, PCI remains in a constant state of technological evolution. The challenge for the interventionalist is to decide when is the right time to adopt a new technology, in which patients, and at what cost.

For more than a decade, quantitative coronary angiography (QCA) has been the gold standard for the assessment of coronary stenosis because of its accuracy and objectivity as compared to visual and hand-held caliper measurements.1–3 After the introduction of intracoronary brachytherapy, the QCA methodology for the assessment of irradiated coronaries had to be adjusted to this new mode of therapy because of the existence of new regions of interest: the target segment, injured segment, irradiated segment and vessel segment.4 In a recent report, lumen enlargement (negative late loss) was demonstrated in a subset of vessels receiving 18 Gy of catheter-based ß-radiation after balloon angioplasty alone.5 Previously, we reported vessel enlargement accommodating plaque increase in a volumetric 3-dimensional (3-D) intravascular ultrasound (IVUS) investigation.6 In that report, the lumen remained unchanged at follow-up as an average.

While stents have reduced the risk of restenosis,1–3 they induce neointimal hyperplasia,4 and rates of in-stent restenosis following intervention may be as high as 60%,5 particularly in long lesions.6 Studies of gamma-radiation therapy following treatment for in-stent restenosis have demonstrated considerable reduction in the incidence of clinical and angiographic restenosis as compared with placebo.7–11 Late thrombosis has been a problem, and while its origin is poorly understood, it appears to be linked to the short duration of ticlopidine therapy, placement of new stents or the use of multiple coronary stents.12–15

“It’s not enough if I succeed, everyone else should fail.”
- Atila the Hun

Since the introduction of stents almost a decade ago, they have become the mainstream for the treatment of patients with coronary artery disease. Nevertheless, restenosis following stent implantation has been the major limitation of stents. Serial intravascular ultrasound studies have shown that restenosis after conventional balloon angioplasty represents a complex interaction between elastic recoil, smooth muscle proliferation and vascular remodeling, whereas restenosis after stent deployment is due almost entirely to smooth muscle hyperplasia and matrix proliferation.1 Despite intensive investigation and preliminary optimistic results in animal models, most pharmacological agents were found to be ineffective in preventing restenosis after balloon angioplasty or stenting when subjected to rigorous, properly conducted clinical trials.