IVUS for Chronic Total Occlusion (CTO) Intervention Guidance
IVUS for CTO interventions can assist in lowering contrast use, and improve the procedure safety. IVUS-guided controlled antegrade and retrograde subintimal tracking (CART or reverse CART) techniques are final CTO revascularisation steps that can be performed safely and effectively with IVUS guidance.43 Alternatively, transvenous IVUS-guided PCI for CTO has been described using the cardiac vein parallel to the target artery.44 The recently acquired Volcano Corporation Pioneer Plus™ Re-Entry Catheter, (Volcano Corporation, Rancho Cordova, CA) is a peripheral reentry device that uses an adjustable access needle coupled to an IVUS for real-time visualisation during CTO vessel re-entry into the distal luminal space.
IVUS Validation for Ischaemia Assessment
Resistance to flow by a stenosis depends on various factors such as entrance effects, friction loss and separation loss. Vessel resistance is inversely related to the stenosis area, and directly proportional to viscosity and stenosis length. Separation loss is magnified by turbulence created by increased flow across a stenosis, and inversely related to the stenosis area and reference area of the vessel downstream to the stenosis. Additionally, the complex interaction between the vascular bed integrity, varying degrees of diffuse disease, vessel remodelling and a branching coronary tree with serial and parallel stenoses leads to complex haemodynamics that confound the use of stenosis area as an optimal single marker for stenosis significance. Fractional flow reserve (FFR) takes many of these factors into account and is the preferred invasive tool to answer what is the physiological significance of coronary stenosis. A caveat with the use of FFR that is most pronounced for left main stenosis assessment is the need to take into account the potential effect of concomitant lesions in either of its branches. A downstream flow limiting lesion will minimise the FFR significance of the left main stenosis as a result of decreased flow crossing the left main. The ultimate clinical decision lies in the conscious operator’s ability to combine various data points to obtain a final answer.
Abizaid et al.45 reported a diagnostic accuracy of 92 % using an IVUS minimal lumen area (MLA) < 4.0 mm2 compared to a Doppler flow wire coronary flow reserve (CFR) of < 2.0. However, this cutoff misclassified 8.3 % of patients as either false negative or false positive (two patients with MLA > 4.0 had CFR < 2.0. and four patients with MLA 4.0 or less had a CFA of 2.0 or above. NPV: 0.95 and PPV: 0.93). Similarly Nishioka et al.46 reported a diagnostic accuracy of 93 % for detecting an abnormal Thallium SPECT perfusion study using the 4.0 MLA cutoff. This study misclassified 7 % of patients (four patients with MLA > 4.0 had an abnormal SPECT study and one had an MLA of 4.0 or less and a negative perfusion study. NPV = 0.83 and PPV = 0.91. Takagi et al.47 found that most MLA values <4.0 mm2 were associated with an FFR <0.75, however, several patients with an MLA <4 mm2 still had FFR values above 0.8. In this study, regression analysis identified MLA <3.0 mm2 and area stenosis > 60 % as optimal IVUS thresholds (sensitivity 83 % and 92 %; specificity 92.3 % and 88.5 % respectively for MLA and area stenosis). In this study the combination of both criteria (MLA <3.0 mm2 and area stenosis >60 %) met an FFR <0.75 without exception. Similarly, Briguori et al.48 reported the combination of percent area stenosis and minimum lumen diameter (MLD) increased the IVUS specificity. IVUS cutoffs of area stenosis >70 %, MLD of 1.8 mm or less, MLA of 4.0 mm2 or less, and lesion length > 10 mm reliably identified lesions with an FFR < 0.75 in this study. As can be observed in these studies, although a MLA <4.0 mm2 in proximal coronary vessels other than the left main or saphenous vein grafts has been frequently associated with the presence of a physiologically significant stenosis, not every MLA <4 mm2 equates to an ischaemia inducing stenosis.
Abizaid et al.49 evaluated 357 non-left main intermediate stenosis in whom intervention was deferred based on IVUS findings. At one year, the event rate of 248 lesions with a MLA of 4.0 mm2 or more was 4.4 % and TLR rate 2.8 %. No events were noted when the MLA was >6.2 mm2. However, the Physiologic and anatomical evaluation prior to and after stent implantation in small coronary vessels (PHANTOM) trial found a lack of correlation between angiography or IVUS, and FFR in patients with moderate stenosis in small coronary arteries (<2.8 mm).50 An MLA of 2.4 mm2 or above correlated with an FFR of 0.8 or higher, however the poor specificity was noted as a significant limitation by Kang et al.51 Similarly, Ahn et al.52 found a lower MLA cutoff of 2.1 mm2 to correlate with myocardial ischaemia by myocardial SPECT. This cutoff was also associated with a poor specificity (50.4 %), and a poor positive predictive value (38.6 %).
Angiographic left main coronary artery stenosis assessment suffers from wide inter-operator variability.53–55 Jasti et al.56 identified an MLD of 2.8 mm and an MLA of 5.9 mm2 as the most accurate cutoffs for determining the significance of a left main stenosis. (Respectively for MLD and MLA, sensitivity 93 % and 93 %; and specificity 98 % and 95 %). Abizaid et al.57 reported an adverse event rate of 14 % in patients who underwent angiographic and IVUS assessment of left main disease and were not referred for intervention. When stratified by IVUS MLD, the event rate was 60 % for an MLD < 2.0 mm, 24 % for an MLD 2.0 to 2.5, 16 % for an MLD 2.5 to 3.0 mm and 3 % for an MLD >3.0 mm. For any given MLD, the event rate was exaggerated in the presence of diabetes mellitus or an untreated lesion in a major vessel with >50 % diameter stenosis. Fassa et al.58 reported the mean 3.3 year follow-up results after deferral of 71 patients with LM stenosis and an MLA >7.5 mm2 and observed no significant difference in target vessel revascularisation, acute MI and death between these patients compared to a group with an MLA <7.5 mm2 who underwent revascularisation (p = 0.28). A multicentre study59 reported comparable (p = 0.3) two year event free survival rates between a group of patients with left main disease and MLA >6 mm2 that deferred intervention (87.3 % ) compared to that of patients with an MLA of 6 mm2 or less who underwent revascularisation (80.6 %). Only 4.4 % of patients in the deferred group required subsequent LMCA revascularisation, none with an infarction. Patients with a LMCA MLA <6 mm2 who did not undergo revascularisation because of operator or patient preferences had an MLA of 5–6 mm2, and 88 % of these had preserved ejection fraction. Frequently these lesions were complex, the estimated surgical risk was high, and patients had issues with dual antiplatelet therapy use or declined surgery. The two year cardiac death-free survival was 86 % (compared to 97.7 % in the deferred group; p = 0.04), and survival free of cardiac death, MI, and revascularisation was 62.5 % (compared to 87.3 % in the deferred group; p = 0.02).