Myocardial bridging (MB) is a common incidental finding noted on coronary angiography and has been considered a benign condition. However, there are a number of reports that have related MB with myocardial ischemia, acute coronary syndrome, arrhythmia, and sudden cardiac death [8, 9]. So the functional assessment of MB is important, and, recently, diastolic FFR was reported to be useful in evaluation of functional significance of MB.

Diefenbach et al. were the first to demonstrate that inotropic stimulation (a beta-agonist) unmasked angiographically silent MB [10], and Escaned et al. reported that the diagnostic value of dobutamine challenges for physiologic assessment of MB in 12 symptomatic patients with positive stress test. Although both FFR and diastolic FFR decreased significantly after dobutamine infusion, diastolic FFR identified hemodynamic significance of MB in five patients (diastolic FFR < 0.76), whereas FFR was <0.75 in only one patient [11].

In contrast to patients with fixed coronary stenosis, FFR measurement after adenosine infusion underestimates the significance of stenosis in patient with MB , but FFR measurement after high-dose dobutamine infusion (40 μg/kg/min) is a promising strategy to unmask the significance of MB [12]. (Fig. 29.2).

Multivessel (MV) coronary artery disease (CAD) exists in approximately half of acute myocardial infarction (AMI) patients [13, 14]. In these patients, the proper management for non-culprit lesions remains still controversial.

In AMI patients with angiographically significant MV CAD, the incidence of heart failure [15] and recurrent acute coronary syndrome [16] and need for further revascularization [17] have been reported to be significantly higher, and survival has been reported to be significantly lower [18] than single-vessel disease CAD.

Even though the measuring FFR at the time of primary PCI has disadvantages such as higher amount of contrast medium and radiation, the need for additional instruments, and prolonged procedure time, current studies have confirmed the reliability and safety of FFR measurements in setting of MI.

Ntalianis et al. reported the reliability of FFR measurements of non-culprit lesions during the acute phase of MI and a very good reproducibility of FFR. In this study, FFR measurements of 112 non-culprit lesions were done immediately after PCI of the culprit vessel and were repeated within 35 days. The FFR value of the non-culprit lesion did not change between the acute and follow-up. In only two patients, the FFR value changed from >0.8 during primary PCI to <0.75 at follow-up [19].

Functional assessment with FFR of non-culprit lesions in AMI patients could be a valuable guide of decision about the additional revascularization and might contribute to a better risk stratification. (Fig. 29.3).

FFR has been validated as a useful index to determine the functional significance of coronary stenosis and the performance of percutaneous coronary intervention [20]. In-stent restenosis (ISR ) after stent implantation cannot be easily measured with conventional angiography because metallic component of stent makes it difficult to estimate the severity of stenosis [21].

In patients with restenosis after bare-metal stent, a poor correlation between angiographic quantification and FFR of moderate ISR was found. Conservative management of moderate 40–70% in-stent restenotic lesions with FFR value ≥0.75 is safe avoiding unnecessary revascularizations based solely on the angiography (Fig. 29.4) [22]. In patients with restenosis after drug-eluting stent (DES), a discrepancy was found between functional ischemia measured by the FFR and the angiographic % diameter stenosis, in moderate- or diffuse-type restenotic lesions after DES implantation. The incidence of adverse events during the 12 months of follow-up after FFR-guided treatment was 18.0% (23.3% in the FFR < 0.80 group and 10.0% in FFR > 0.80 group). The outcome of FFR-guided deferral in patients with DES in-stent restenosis seems favorable [23]. Another study in patients with moderate angiographic restenosis after paclitaxel-eluting stent (PES) implantation revealed that FFR was also preserved, and the functional severity of restenosis is often limited. Although percent diameter stenosis was not significantly different between the two groups (PES group, 40.6 ± 11.2%; de novo group, 40.6 ± 9.0%, P=0.981), the functional severity of stenosis was significantly less in the PES group than in the de novo group (FFR: PES group, 0.86 ± 0.07; de novo group, 0.79 ± 0.10, P=0.002). Revascularization should be performed with caution for patients with moderate angiographic restenosis after drug-eluting stent deployment [24]. In summary, a favorable prognosis was found in patients who had angiographic restenosis and preserved FFR regardless of stent types (both BMS and DES).

Left ventricular hypertrophy (LVH ) has been well known as a marker of hypertension-related target organ damage and an important independent predictor of adverse cardiovascular (CV) events [25]. The precise mechanisms underlying the adverse CV events in patients with LVH have not been identified. Coronary microvascular dysfunction (CMD) with structural abnormalities has been accepted as a potential pathophysiology of adverse events in patients with hypertrophic cardiomyopathy (HCM) and essential hypertension [26]. However, there are no definite diagnostic tools to visualize directly the coronary microcirculation in humans. Functional assessments, such as myocardial blood flow and coronary flow reserve which is an integrated measure of flow through both the large epicardial coronary arteries and the microcirculation, have been studied in patients with LVH [26]. Structural abnormalities have been presumed pathologically responsible for CMD in patients with LVH. Morphologic changes are characterized by an adverse remodeling of intramural coronary arterioles consisting of vessel wall thickening, mainly due to hypertrophy of smooth muscle cells and increased collagen deposition in the tunica media, with variable degrees of intimal thickening [26]. In the absence of epicardial obstruction, therefore, the abnormal coronary circulation appeared to be mainly based on CMD in patients with pathologic LVH (Fig. 29.5) [27]. Previous studies showed the growth of vascular structure in patients with left ventricular hypertrophy is not proportional to increase of muscular mass [28]. Therefore, it was believed that the coronary flow reserve in the myocardial vascular bed would be reduced as left ventricular hypertrophy develops and the cutoff value of 0.75 would probably not to be valid anymore. It seemed to become higher with more severely hypertrophied. But recent study revealed that FFR of coronary lesions in patients with high LVMI is no different than FFR of angiographically matched lesions in patients with normal LVMI, suggesting that high LV mass should not limit the utility of FFR as an index of coronary lesion severity [29]. Since there is controversy in this issue, it is recommended to be careful in the interpretation of FFR in patients with left ventricular hypertrophy.

Cardiac allograft vasculopathy (CAV) after organ transplantation remains a major cause of morbidity and mortality in cardiac transplant recipients [30]. It is limited to detect CAV with noninvasive imaging or coronary angiography [31]. Intravascular ultrasound (IVUS) could easily identify the anatomic evidence of transplant arteriopathy involving the epicardial arterial system and the progression of CAV over time [32]. The functional evaluation of the coronary vasculature with fractional flow reserve (FFR) and with the index of microcirculatory resistance (IMR) for epicardial and microvascular structure predicts clinical outcomes in patients with ischemic heart diseases [33]. In cardiac transplant recipients, changes in FFR have been shown to correlate with IVUS parameters, whereas IMR is a predictor of development of CAV and poor cardiac function in this population [34]. Invasive measures of coronary physiology (fractional flow reserve and IMR) determined early after heart transplantation are significant predictors of late death or retransplantation (Fig. 29.6). Moreover, patients with an improvement in microvascular function as assessed by a decrease in IMR from baseline to 1 year had better survival compared with those with worsening microvascular function [35].