Routine pressure-derived fractional flow reserve guidance: from diagnostic to everyday practice

The pressure-derived fractional flow reserve (FFR) is a valuable and well validated index for assessing the ischemic significance of coronary lesions. The 0.75 cutoff value of FFR discriminates between lesions with and without ischemic potential, helps decision making as to whether to revascularize a coronary stenosis and assists in evaluating the results of catheter-based treatment. Recent data show that the FFR index is also useful in managing patients with complex coronary disease. The aim of this paper is to provide an overview of the theoretical background of this index and its clinical applicability in the catheterization laboratory.     

Correlation between myocardial uptake of technetium-99m-sestamibi and pressure-derived myocardial fractional flow reserve

OBJECTIVES: Development of the coronary pressure wire has facilitated the measurement of fractional flow reserve (FFR) to assess the functional severity of coronary artery stenoses. METHODS: This study evaluated the correlations between FFR and myocardial direct counts of technetium-99m(99mTc)-sestamibi in 20 patients (16 men, 4 women, mean age 66 +/- 8 years) who underwent 99mTc-sestamibi single-photon emission computed tomography (SPECT) with the 2-day protocol using 740 MBq of 99mTc-sestamibi each day. Visual assessment of myocardial imaging and quantitative analysis with the measurement of percent uptake and direct count of 99mTc-sestamibi were performed. RESULTS: Visual assessment of myocardial imaging revealed that reversibility of 99mTc-sestamibi perfusion defects was correlated with FFR of < 0.75, which is regarded as functionally important stenosis (17/20 vs 3/20, kappa = 0.71, p < 0.002). Regional reversibility score did not correlate with FFR (r = -0.40, p = NS). Quantitative analysis revealed that the change in 99mTc-sestamibi percent uptake with pharmacologic stress using adenosine triphosphate disodium (ATP) also did not correlate with FFR (r = 0.35, p = NS). In contrast, percent increase in 99mTc direct counts with ATP was lower in patients with FFR of < 0.75 than in those with FFR of > = 0.75 (-4 +/- 16% vs 24 +/- 30%, p < 0.01). In addition, a significant correlation (r = 0.70, p < 0.001) was observed between percent increase in 99mTc direct counts with ATP and FFR. CONCLUSIONS: These results suggest that quantitative analysis of 99mTc-sestamibi scintigraphy enables the assessment of the magnitude of functional significance of coronary stenosis.     

Coronary balloon angioplasty through diagnostic 6 French catheters

We investigated the use of ultralow profile balloon catheters (Scimed ACE, USCI Probe, Cordis, Orion) for coronary angioplasty through 6 French diagnostic catheters (Schneider, Cordis). Contrast injection was assisted with a Hercules pump (Cordis) in all cases. During 21 procedures, angioplasty of 27 lesions in 20 selected patients was attempted (1.3 lesion/procedure). Twelve lesions were in the right, 10 in the left anterior descending, and 5 in the left circumflex coronary artery. Balloon size varied between 2.5 and 3.5 mm. Twenty lesions could be successfully dilated (74%) through the 6 French catheter and 7 lesions required an exchange to a 7 French angioplasty guiding catheter. For 5 cases, another balloon was also necessary to complete the procedure. The final overall success rate was 100% per patient and per lesion and there were no major complications. Despite the small internal catheter lumen (1.22 mm) coronary visualization was adequate, and mechanical support was good. Failures of 6 French catheters were attributed to insufficient torque control and excessive friction when the balloon crossed the tapered end of the diagnostic catheter. Coronary angioplasty through a diagnostic 6 French catheter is feasible and may represent a reasonable alternative for simple cases that are done during the same session as the diagnostic angiography. Once available, 6 French high flow angioplasty guiding catheters without a tapered tip should improve success while retaining the advantage of a small femoral puncture site.     

Myocardial fractional flow reserve

Revascularization of coronary artery lesions should be based on objective evidence of ischemia, as recommended by the guidelines of the European Society of Cardiology. However, even in the case of stable coronary artery disease and elective percutaneous coronary intervention (PCI), pre-procedural noninvasive stress test results are available in a minority of patients only. It is common practice for physicians to make decisions on revascularization in the catheterization laboratory after a cursory review of the angiogram, despite the well-recognized inaccuracy of such an approach. Myocardial fractional flow reserve (FFR) measured by a coronary pressure wire is a specific index of the functional significance of a coronary lesion, with superior diagnostic accuracy for the detection of ischemia than any noninvasive stress test. FFR trials on patients with single and multivessel disease, such as the DEFER and FAME studies, have demonstrated that the clinical benefit of PCI with respect to patient outcome is greatest when revascularization is limited to lesions inducing ischemia, whereas lesions not inducing ischemia should be treated medically.     

Reliability of pressure-derived myocardial fractional flow reserve in assessing coronary artery stenosis in patients with previous myocardial infarction

In 167 patients with suspected coronary artery disease, 74 of whom had myocardial infarction (MI), measurement of myocardial fractional flow reserve (FFR) in previous infarction territories, using a cut-off point of 0.75, showed a sensitivity of 79% and a specificity of 79% for myocardial ischemia as demonstrated by thallium-201 myocardial imaging. This sensitivity and specificity were similar to a sensitivity of 79% and a specificity of 72% observed in territories not related to MI. In addition, a receiver-operating characteristic curve analysis revealed that the best predictability of FFR for myocardial ischemia was between 0.74 and 0.76, regardless of the presence or absence of MI.     

Long-term clinical outcomes after deferral of percutaneous coronary intervention of intermediate coronary stenoses based on coronary pressure-derived fractional flow reserve

Coronary pressure-derived fractional flow reserve (FFR) has been used to evaluate functional severity of coronary artery stenoses. The cut-off point of 0.75 was considered to be the indication for percutaneous coronary intervention (PCI). In this study, we examined the prognosis of patients in whom PCI was deferred because the lesion was not significant by FFR (≥0.75). We measured FFR of 44 patients (50 lesions with angiographically intermediate stenoses by pressure wire between 2002 and 2009. Out of 44 patients (50 lesions), functionally non-significant stenoses with FFR≥0.75 were 29 patients (33 lesions) and PCI was deferred. In the remaining 15 patients (17 lesions), FFR was <0.75 and PCI was performed. Patients were followed up for an average period of 53 months with endpoints of major adverse cardiac events (MACE; cardiac death, acute coronary syndrome, PCI, and coronary artery bypass grafting). The rate of MACE was 2/29 (6.9%) in patients with FFR≥0.75 and 2/15 (13.3%) in those with FFR<0.75, and it was not statistically different between the two groups. Since long-term clinical outcomes after deferral of PCI of intermediate coronary stenoses based on FFR were excellent (annual event rate 1.6%/year), FFR is a useful index to judge the indication of PCI and risk-stratify patients for MACE.     

Myocardial perfusion during transient slow-flow in the patient with old vein graft intervention: assessment by serial measurement of pressure-derived fractional flow reserve and thermodilution-derived coronary flow reserve.

A patient with distal slow-flow after stenting in the old vein graft intervention was reported. This case is a first in whom guidewire-based serial measurement of pressure-derived fractional flow reserve (FFR(myo)) and thermodilution-based coronary flow reserve (CFR(thermo)) clearly demonstrated the serial change of microvascular circulation. During slow-flow, CFR(thermo) remained in low value despite significant improvement of FFR(myo) from 0.61 to 0.90. After thrombus aspiration and nicorandil injection, coronary flow reestablished immediately. CFR(thermo) improved significantly from 1.3 during slow-flow to 3.6 after restoration of flow.     

Application of pressure-derived myocardial fractional flow reserve in assessing the functional severity of coronary artery stenosis in patients with diabetes mellitus.

BACKGROUND: Although the development of a coronary guidewire mounted with a pressure sensor has facilitated the measurement of pressure-derived fractional flow reserve (FFR) to assess the functional severity of coronary artery stenoses, the theoretical limitations include diabetes mellitus because of the associated microvascular abnormalities. METHODS AND RESULTS: In the present study 304 vessels and their coronary territories in 96 diabetic and 149 nondiabetic patients were evaluated by pressure-derived FFR and thallium-201 single photon emission computed tomography (SPECT) to determine the applicability of measuring FFR in diabetic subjects. The best cut-off value for FFR to detect myocardial ischemia, as demonstrated by (201)Tl SPECT, was 0.725 in the diabetic and 0.745 in the nondiabetic patients. Sensitivity and specificity were similar for the 2 groups (83% and 75% (diabetic) vs 79% and 83%). However, diabetic patients with homoglobin (Hb) A(1c) >or=7.0% showed lower specificity in comparison with those having HbA(1c) <7.0% (64 vs 88%; p=0.045); however, sensitivities were similar (83 vs 83%; p=NS). CONCLUSIONS: The cut-off value of 0.75 for FFR can detect myocardial ischemia in diabetic patients, although the adequacy of glycemic control should be taken into consideration when assessing the FFR measurements.     

Four French catheters for diagnostic coronary angiography.

A randomized study was conducted to assess the feasibility of 4 Fr catheters for diagnostic coronary angiograms. A total of 1,114 consecutive patients were randomized to 4 or 5 Fr catheters. Ease of use of catheters was subjectively assessed by the primary operator and the picture quality was assessed by two independent observers with a good interobserver variability (r = 0.94; P < 0.001). Predischarge local complications were recorded by the attending physician. No statistically significant difference was observed in the picture quality for the left coronary artery, right coronary artery, aorta, left ventricle, venous grafts, or renal arteries between the two groups. Fluoroscopy time (7.1 +/- 5.6 for 4 Fr vs. 6.7 +/- 5.7 min for 5 Fr) and contrast quantity (140 +/- 58 vs. 144 +/- 57 ml) were comparable between the two groups. There was a statistically significant difference in favor of the 5 Fr group as regards maneuverability of catheters (93% vs. 79%; P < 0.001), and 5 Fr pigtail catheters crossed the aortic valve easier than the 4 Fr pigtail catheters (91% vs. 81%; P < 0.001). Crossover to the other catheter size or a larger sheath was more frequent with 4 Fr catheters (33/522 vs. 3/592; P < 0.001). Median time to hemostasis was 9 min for 4 Fr and 14 min for 5 Fr (P < 0.001). Of the 4 Fr patients, 84% could be mobilized at 1 hr and 86% of 5 Fr patients at 2 hr. Significant hematomas were observed in 2% with 4 Fr or 5 Fr and small hematomas in 10% and 16%, respectively (P = NS). Time to discharge was comparable in both groups (4.0 +/- 3.2 with 4 Fr vs. 4.3 +/- 3.7 hr with 5 Fr). The 4 Fr catheters are a good alternative for diagnostic coronary angiograms. The increased difficulty in maneuverability and a need for catheter changes in 70% are compensated for in part by easier hemostasis. With increasing use and finesse of these catheters, the difficulty in maneuverability are likely to be overcome.