Fractional flow reserve in below the knee arteries with critical limb ischemia and validation against gold-standard morphologic, functional measures and long term clinical outcomes.

INTRODUCTION: The aim of this study was to assess the applicability of fractional flow reserve measurement (FFR) in below-the-knee (BTK) arteries and to evaluate its correlation with non-invasive functional parameters before and after angioplasty. METHODS: We enrolled 39 patients with severe BTK arterial lesions. Inclusion criteria were critical limb ischemia (Rutherford 4-6) and angiographically proven arterial stenosis of the distal lower limb (percent diameter stenosis >/=70%). Exclusion criteria were chronic total occlusion, diabetic foot syndrome and non-viable distal lower limb. The transstenotic distal/proximal pressure ratio was measured under resting (Pd/Pa) and hyperemic (FFR) conditions induced by 40mg intra-arterial Papaverin and was compared with quantitative angiography-, laser Doppler- and duplex ultrasound-derived measurements before and after percutaneous angioplasty (PTA). RESULTS: Comparing measurements before and after PTA, we found significant improvements in the resting Pd/Pa values (0.79 [0.67-0.90] vs 0.90 [0.85-0.97]; p<0.001) and FFR values (0.60+/-0.19 vs 0.76+/-0.15; p<0.001), respectively. At baseline, Pd/Pa ratio and FFR were significantly albeit weakly correlated with % area stenosis (r:-0.31, p=0.05 and r:-0.31, p=0.05, respectively). After PTA, neither Pd/Pa nor FFR remained correlated with % area stenosis. Similarly, prior PTA, Pd/Pa ratio and FFR were significantly correlated with TcO2% and perfusion unit change (r:0.48, p<0.01 and r:0.34, p<0.05, respectively), but after intervention, these significant correlations vanished. Pd/Pa and FFR values did not show correlation with duplex ultrasound-derived measurements. At 1year, major adverse events (MAEs) and major adverse cardiovascular and cerebrovascular (MACCEs) were observed in 7 (17.9%) and in 9 (23.1%) patients, respectively. CONCLUSION: CLI due to severe BTK arterial disease was associated with several impediments of baseline pressure measurements which were significantly improved after successful PTA and stenting. Significant relationships between pressure data and functional and imaging parameters existed prior intervention but vanished after. Further studies are required to determine the clinical value of pre- and post-PTA pressure measurements in BTK arterial disease

Influence of contrast media dose and osmolality on the diagnostic performance of contrast fractional flow reserve

Background—Contrast fractional flow reserve (cFFR) is a method for assessing functional significance of coronary stenoses, which is more accurate than resting indices and does not require adenosine. However, contrast media volume and osmolality may affect the degree of hyperemia and therefore diagnostic performance. Methods and Results—cFFR, instantaneous wave–free ratio, distal pressure/aortic pressure at rest, and FFR were measured in 763 patients from 12 centers. We compared the diagnostic performance of cFFR between patients receiving low or iso-osmolality contrast (n=574 versus 189) and low or high contrast volume (n=341 versus 422) using FFR≤0.80 as a reference standard. The sensitivity, specificity, and overall accuracy of cFFR for the low versus iso-osmolality groups were 73%, 93%, and 85% versus 87%, 90%, and 89%, and for the low versus high contrast volume groups were 69%, 99%, and 83% versus 82%, 93%, and 88%. By receiver operating characteristics (ROC) analysis, cFFR provided better diagnostic performance than resting indices regardless of contrast osmolality and volume (P&lt;0.001 for all groups). There was no significant difference between the area under the curve of cFFR in the low- and iso-osmolality groups (0.938 versus 0.957; P=0.40) and in the low- and high-volume groups (0.939 versus 0.949; P=0.61). Multivariable logistic regression analysis showed that neither contrast osmolality nor volume affected the overall accuracy of cFFR; however, both affected the sensitivity and specificity. Conclusions—The overall accuracy of cFFR is greater than instantaneous wave–free ratio and distal pressure/aortic pressure and not significantly affected by contrast volume and osmolality. However, contrast volume and osmolality do affect the sensitivity and specificity of cFFR

Physiological predictors of acute coronary syndromes: emerging insights from the plaque to the vulnerable patient

In this review, the authors explore the evolving evidence linking physiological assessment of coronary artery disease with plaque progression and vulnerability. Reducing adverse clinical events remains the ultimate goal for diagnostic tests, and this review highlights evidence supporting the prognostic value of physiological metrics in predicting outcomes. Historical and contemporary studies support synergy among lesion severity, ischemia, plaque vulnerability, and patient prognosis. Ischemia contributes to clinical events through association with plaque burden, but this review addresses the emerging concept that it associates with atherothrombosis via disturbed lesion hemodynamics. Biomechanical pathophysiological forces including endothelial shear stress-the frictional force generated by blood flow on the vessel wall-are increasingly linked with atherogenesis, vulnerable plaque morphology, and platelet and leukocyte activation. The authors conclude by transitioning from the model of the vulnerable plaque to the concept of the "vulnerable patient," looking more broadly at physiological contributors to Virchow's triad underpinning acute coronary syndrome

Intracoronary EnalaPrilat to Reduce MICROvascular Damage During Percutaneous Coronary Intervention (ProMicro) study.

Intracoronary angiotensin-converting enzyme inhibitors have been shown to relieve myocardial ischemia in stable patients and to improve epicardial flow in patients with ST-segment elevation myocardial infarction. Yet, it is still unclear whether these effects are mediated by a modulation of the coronary microcirculation. Methods We randomly assigned 40 patients to receive either an intracoronary bolus of enalaprilat (50 g) or placebo before elective PCI. The index of microvascular resistance was measured at baseline, 10 minutes after study drug administration, and after PCI. High-sensitivity cardiac troponin T was measured as a marker of myocardial injury. Results Infusion of enalaprilat resulted in a significant reduction in index of microvascular resistance (27 11 at baseline vs. 19 9 after drug vs. 15 8 after PCI), whereas a significant post-procedural increase in index of microvascular resistance levels was observed in the placebo group (24 15 at baseline vs. 24 15 after drug vs. 33 19 after PCI). Index of microvascular resistance levels after PCI were significantly lower in the enalaprilat group (p 0.001). Patients pre-treated with enalaprilat also showed lower peak values (mean: 21.7 ng/ml, range: 8.2 to 34.8 ng/ml vs. mean: 32.3 ng/ml, range: 12.6 to 65.2 ng/ml, p 0.048) and peri-procedural increases of high-sensitivity cardiac troponin T (mean: 9.9 ng/ml, range: 2.7 to 19.0 ng/ml vs. mean: 26.6 ng/ml, range: 6.3 to 60.5 ng/ml, p 0.025). Conclusions Intracoronary enalaprilat improves coronary microvascular function and protects myocardium from procedurerelated injury in patients with coronary artery disease undergoing PCI. Larger studies are warranted to investigate whether these effects of enalaprilat could result into a significant clinical benefit. (J Am Coll Cardiol 2013;61:615–21) © 2013 by the American College of Cardiology Foundatio

Mismatch between morphological and functional assessment of the length of coronary artery disease

Background: Morphological evaluation of coronary lesion length is a paramount step during invasive assessment of coronary artery disease. Likewise, the extent of epicardial pressure losses can be measured using longitudinal vessel interrogation with fractional flow reserve (FFR) pullbacks. We aimed to quantify the mismatch in lesion length between morphological (based on quantitative coronary angiography, QCA, and optical coherence tomography, OCT) and functional evaluations. Methods: This is a prospective and multicenter study of patients evaluated by QCA, OCT and motorized fractional flow reserve pullbacks (mFFR). The difference in lesion length between the functional and anatomical evaluations was referred to as FAM. Results: 117 patients (131 vessels) were included. Median lesion length derived from angiography was 16.05 mm [11.40–22.05], from OCT was 28.00 mm [16.63–38.00] and from mFFR 67.12 mm [25.38–91.37]. There was no correlation between QCA and mFFR lesion length (r = 0.124, 95% CI -0.168-0.396, p = 0.390). OCT lesion length did correlate with mFFR (r = 0.469, 95% CI 0.156–0.696, p = 0.004). FAM was strongly associated with the improvement in vessel conductance with percutaneous coronary intervention (PCI), higher mismatch was associated with lower post-PCI FFR. Conclusions: Lesion length assessment differs between morphological and functional evaluations. The morphological-functional mismatch in lesion length is frequent, and influences the results of PCI in terms of post-PCI FFR. Integration of the extent of pressure losses provides clinically relevant information that may be useful for clinical decision-making concerning revascularization strategy

Functional SYNTAX Score for Risk Assessment in Multivessel Coronary Artery Disease

ObjectivesThis study was aimed at investigating whether a fractional flow reserve (FFR)-guided SYNTAX score (SS), termed “functional SYNTAX score” (FSS), would predict clinical outcome better than the classic SS in patients with multivessel coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).BackgroundThe SS is a purely anatomic score based on the coronary angiogram and predicts outcome after PCI in patients with multivessel CAD. FFR-guided PCI improves outcomes by adding functional information to the anatomic information obtained from the angiogram.MethodsThe SS was prospectively collected in 497 patients enrolled in the FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) study. FSS was determined by only counting ischemia-producing lesions (FFR ≤0.80). The ability of each score to predict major adverse cardiac events (MACE) at 1 year was compared.ResultsThe 497 patients were divided into tertiles of risk based on the SS. After determining the FSS for each patient, 32% moved to a lower-risk group as follows. MACE occurred in 9.0%, 11.3%, and 26.7% of patients in the low-, medium-, and high-FSS groups, respectively (p < 0.001). Only FSS and procedure time were independent predictors of 1-year MACE. FSS demonstrated a better predictive accuracy for MACE compared with SS (Harrell's C of FSS, 0.677 vs. SS, 0.630, p = 0.02; integrated discrimination improvement of 1.94%, p < 0.001).ConclusionsRecalculating SS by only incorporating ischemia-producing lesions as determined by FFR decreases the number of higher-risk patients and better discriminates risk for adverse events in patients with multivessel CAD undergoing PCI. (Fractional Flow Reserve versus Angiography for Multivessel Evaluation [FAME]; NCT00267774