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Small vessel disease and diffuse coronary artery disease represent particularly challenging subsets for treatment with transcatheter coronary interventional therapies. This pathology is associated with higher risk comorbidities, such as diabetes, and is more frequently associated with female gender and diffuse coronary involvement.1 Small and diffusely diseased vessels are frequently noncompliant, calcified, tortuous, and distal in location, making these targets more technically challenging for intervention. Consequently, a higher incidence of acute complications, including significant vessel dissection, acute vessel closure, myocardial infarction, and emergent coronary bypass grafting, has historically complicated intervention in small and diffusely diseased vessels.2,3 Along with poorer acute outcomes, these subsets are plagued by high restenosis and thrombosis rates, often necessitating repeat intervention or bypass surgery.4,5 Despite the challenges and complexities inherent to small vessel intervention, the problem is common. Between 30% and 67% of all percutaneous coronary interventions involve small vessels, depending on the definition of a small vessel.6-9

This chapter will review the definition and diagnostic approach to small and diffuse coronary artery disease. Acute and long-term outcomes associated with percutaneous interventional therapies, particularly the favorable impact of drug-eluting stents, will be reviewed. Finally, the future role in the treatment of these subsets with drug-eluting balloons and bioabsorbable stents will be examined.


The definition of what constitutes a small vessel in the context of coronary interventional therapy has been quite variable. A number of studies examining small vessel intervention have defined vessels less than 3.0 mm in reference size as being small, and this criterion is in part derived from early stent trials in which patients with vessels less than 3.0 mm were excluded from enrollment.10,11 Other studies have defined small vessels as those less than 2.5 to 2.8 mm in diameter.9,12-14 Certainly, less than 3.0 mm is the most sensitive descriptor, although necessarily less specific. Despite whatever arbitrary cutoff is used, the relationship between vessel size and outcome is not a step function; instead, a continuous inverse relationship exists between outcomes and size.8,15 Consequently, differences in the definition and enrollment criterion frequently help explain apparently conflicting results from various studies of small vessel intervention. Like the small vessel, diffuse disease has had various definitions; however, the most consistent definition is lesion length greater than 20 mm.16

The definition of small vessel has been based on angiography; nevertheless, results of intravascular ultrasound (IVUS) have demonstrated that many angiographically small vessels are in fact “pseudosmall” as a result of angiographically undetected disease in the reference segment and positive remodeling at the lesion site.17 Briguori and colleagues18 compared 344 consecutive patients having 419 lesions in small vessels (angiographic reference vessel ≤2.75 mm) with 953 patients having 1161 lesions in large vessels (>2.75 mm); all underwent concomitant IVUS. The difference in angiographic and IVUS ...

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