Current IVUS and OCT catheters range from 2.6 to 3.2 French in size and can be introduced through conventional six French guide catheters. Following the administration of nitroglycerine to avoid coronary spasm, the catheters are advanced over standard 0.014 in. guide wires, distal to the region of interest. Image acquisition with both IVUS and OCT is associated with high success rates (92–97 %), even with three-vessel imaging during ST-elevation myocardial infarction [3]. Technical issues are generally related to handling the catheters through diseased and/or tortuous segments, which might be more challenging in women due to smaller vessels. Care should particularly be taken when crossing coronary stents (both metallic and bioresorbable scaffolds) to avoid device displacement and fracture, for the interrogation of thrombosed lesions due to risk of distal embolization, and for assessment of edge dissections after device implantation. Serious complications in terms of coronary artery dissection/perforation or malignant arrhythmias are rare, although slightly more frequent with OCT (~1 %) due to the need for vessel flushing with contrast during image acquisition [3]. Discomfort from ischemia due to catheter obstruction during assessment of tight stenoses may be seen with increasing stenosis and acquisition time with IVUS (standard acquisition rate: 0.5 mm/s, meaning it takes 60 s to scan 30 mm vessel), whereas this is a decreasing issue with new-generation OCT systems with ultrafast acquisition (30 mm vessel in 1.5 s).

Considering the morphometric similarity with pathology, data from intracoronary imaging studies represent an important continuation of the results from autopsy reports. One should, however, keep in mind that findings derived with these techniques need to be interpreted in view of their specific strengths and limitations (Table 2.1).

In general, female cardiac patients are often older and have more risk factors and comorbidities than their male counterparts, frequently resulting in their exclusion from clinical trials. In addition to this selection bias, available studies of atherosclerosis using intracoronary imaging are limited and heterogeneous making comparison and confident conclusion drawing somewhat difficult.

For both genders, VH-IVUS indicates that plaque burden, necrotic core, and calcium content increase significantly with aging [4, 5]. Several studies suggest that women compared to men, at any age, exhibit less extensive coronary artery disease by angiography [6], and smaller plaque burden by IVUS in stable as well as unstable clinical settings [4, 5, 7]. With respect to plaque composition, gender-specific differences have been reported in patients <65 years such that women by VH-IVUS seem to exhibit less necrotic core and dense calcium than men – a difference that is attenuated in patients ≥65 years of age [4, 7].

According to the current paradigm, the thin-cap fibroatheroma (TCFA) is the proposed precursor lesion of ruptured plaques responsible for the majority (60 %) of acute coronary syndromes (ACS) as defined by autopsy [8]. The TCFA is histologically characterized by a large necrotic core, covered by a thin fibrous cap (<65 μm) infiltrated with macrophages. Regions with histology-defined TCFA and VH-IVUS-defined TCFA typically exhibit a large plaque burden with positive remodeling, with a predilection for the proximal coronary arteries [2, 9]. OCT has confirmed that TCFAs are regularly found in culprit lesions of ST-elevation myocardial infarction (STEMI) (51–85 %), are relatively frequent in non-STEMI (22–50 %), and are fairly prevalent in patients with stable angina (SAP) (13–29 %) [2]. Guagliumi et al. recently found in a prospective study of gender differences in culprit plaques in STEMI that the rate of plaque rupture (~50 %) and eroded plaques (~25 %) were similar between genders, as was the composition of aspirated thrombus and inflammatory biomarkers [10].

In the study of the natural history of non-culprit lesions, the PROSPECT trial demonstrated that 51 % of lesions associated with clinical events at 3.4 years exhibited a TCFA by VH-IVUS (”VH-TCFA”) at baseline, while the estimated rate for a VH-TCFA to cause a clinical event was only 4.9 %. Instead, a plaque burden >70 % was found to be the best predictor of events during the follow-up [11]. Among the possible explanations of the absence of a stronger TCFA-signal is the fact that the VH-TCFA definition relies on a composite of criteria, namely the presence of a plaque burden ≥40 % and confluent necrotic core >10 % in direct contact with the lumen [12] – thus representing a surrogate of the histological TCFA. Whether the direct visualization by OCT of the thin fibrous cap of TCFA (Fig. 2.1) may improve the prediction of future coronary events is currently being investigated.

In a gender-specific subanalysis of the PROSPECT trial, vulnerable features such as plaque rupture and total necrotic core volume by VH-IVUS were, as opposed to above, less common in women despite their older age, while the plaque burden and presence of TCFA were similar between genders. At the same time, there were no difference in major adverse cardiac events related to non-culprit lesions up to 3 years. Whereas, the predictors of MACE in men included a minimal lumen area ≤4 mm, plaque burden ≥70 %, and TCFA, only the two latter were predictive in women, and authors suggest that VH-IVUS-defined TCFA may be a stronger marker of vulnerability in women than men [6]. These findings should be interpreted in view of an expected underestimation of VH-IVUS to detect plaque rupture, due to the relatively low resolution.

In the assessment of the influence of different drugs on plaque progression or regression, IVUS has provided inconsistent results in spite of the unequivocal effects of e.g., statins with many possible explanations [2]. In a study of 978 patients (26 % women), there was no difference in the rate of change in plaque burden between genders during treatment with combined statins and ACE-inhibitors, suggestively supporting the use of established medical therapies in women [13]. In a recent report, however, women appeared to have greater plaque regression than men on rosuvastatin, with the benefit appearing in the setting of lower on-treatment LDL-cholesterol levels [14]. Studies using serial evaluation with OCT and/or IVUS/NIRS to assess the medical (IBIS 4: Rosuvastatin) and interventional (PROSPECT 2: bioresorbable vascular scaffolds) effect on plaque burden and vulnerability are currently undergoing and are expected to provide important information that will eventually help us improve cardiovascular outcomes.

Following the introduction of coronary stents, IVUS demonstrated that the majority of these were inadequately expanded despite the appearance of a satisfactory angiographic result, and subsequent data demonstrated that IVUS-guided optimization of stent implantation by high-pressure dilatation is able to reduce the rates of early stent thrombosis, establishing postdilatation as a routine procedure [15]. Accordingly, a threshold of stent expansion of 5.0–5.5 mm² was proposed to predict the occurrence of events. The application of IVUS-guided PCI has subsequently been associated both with reduced rates of stent thrombosis and improved survival in the long term – results that should be interpreted in view of their lack of randomization and prespecified guidelines for performing and acting on IVUS findings [16]. Specific evaluation of gender differences remains to be performed.

With the advent of DES, IVUS confirmed the correlation between reduced restenosis and inhibition of neointimal hyperplasia; and that vascular responses after DES implantation are diverse and may include large numbers of unevenly covered and uncovered segments of IVUS-detected neointimal hyperplasia. These uncovered stent regions have together with varying degrees of late-acquired stent malapposition been frequently observed in cases of late stent thrombosis [2]. Limited by the resolution, IVUS has gradually been replaced by OCT which is diligently used in the preclinical testing and clinical evaluation of the healing responses following coronary device implantation, notably, to evaluate stent tissue coverage, apposition, the natural history of dissections and other acute effects of stent implantation, and extent and composition of neoatherosclerosis but also with the purpose of revealing the underlying mechanisms in patients with stent failure. With respect to edge dissections, these were in a study found to be more common in women only for proximal dissections (31 vs. 16 %), where they exhibited more complex features (longer and thicker) than in men [17]. Predictors included a combination of clinical (diabetes, hypertension) and procedural characteristics (stent oversizing) and gender, where it would have been interesting to know whether this was related to vessel size. Short- and long-term clinical and healing outcomes were not evaluated.