CORRIGENDUM: Diagnostic Performance and Pressure Stability of a Novel Myocardial Ischemic Diagnostic Index　- The Intracoronary-Electrocardiogram-Triggered Distal Pressure/Aortic Pressure Ratio.

[This corrects the article DOI: 10.1253/circrep.CR-20-0099.].

Effect of QTU prolongation on hyperemic instantaneous wave-free ratio value: a prospective single-center study.

We hypothesized that in patients with QT prolongation, resistance might not decrease in the wave-free period, because QTU prolongation cannot be detected by instantaneous wave-free ratio (iFR) analysis software. We investigated whether corrected QTU (QTUc) prolongation affects the hyperemic iFR value. Forty-two consecutive patients with intermediate stenosis (≥ 50%) in the left anterior descending coronary artery (LAD) were analyzed. Fractional flow reserve (FFR) and hyperemic iFR were simultaneously and continuously recorded with intravenous adenosine triphosphate (ATP) and papaverine infusions. In 17 patients with stenosis in the proximal LAD, coronary flow was measured. Patients were divided into two groups according to the median absolute deviation of the QTUc by ATP administration/QTUc by papaverine administration. FFR, hyperemic iFR, and flow data were compared between each stimulus and group. Moreover, influences of pressure and electrocardiogram parameters on differences in iFR values under ATP and papaverine administration were compared between the following two groups (group 1: the absolute difference of hyperemic iFR values between ATP and papaverine administration is ≤ 0.05; group 2: that is > 0.05). The paired t test and t test were used in analysis. Hyperemic iFR values of patients under the use of papaverine were lower than those of patients under the use of ATP when QTUc was more prolonged by papaverine administration than by ATP administration (ATP 0.74 ± 0.14, papaverine 0.71 ± 0.15, P = 0.025). No significant differences were observed in the FFR value and flow data between the groups. Regarding QTU, QTUc, and QTUc by ATP/QTUc by papaverine, significant differences were observed between group 1 and group 2. Pressure parameters did not induce significant differences. QTUc prolongation induced by papaverine was associated with lower hyperemic iFR values. An iFR-based assessment might lead to inappropriate treatment of patients with QTUc prolongation.

Diagnostic Performance and Pressure Stability of a Novel Myocardial Ischemic Diagnostic Index　- The Intracoronary-Electrocardiogram-Triggered Distal Pressure/Aortic Pressure Ratio.

Background: We hypothesized that the intracoronary-electrocardiogram (IC-ECG)-based pressure index would be more stable and precise than the instantaneous flow reserve (iFR). We investigated the usefulness of the IC-ECG-based pressure index for diagnosing myocardial ischemia. Methods and Results: Thirty-seven consecutive patients with coronary stenosis requiring physiological assessment were enrolled in the study. iFR was measured at rest and under hyperemia in 51 and 40 lesions, respectively. The IC-ECG-triggered distal pressure (Pd)/aortic pressure (Pa) ratio (ICE-T) was defined as the mean Pd/Pa ratio in the period corresponding to the isoelectric line. The ICE-T was significantly lower than the iFR both at rest and during hyperemia (P<0.00001 for both). Fluctuations in the ICE-T pressure parameters (Pd/Pa, Pa, and Pd) were significantly smaller than those of iFR both at rest and during hyperemia. The diagnostic accuracy of predicting a fractional flow reserve (FFR) ≤0.80 of the ICE-T at rest was significantly higher than that of iFR (P=0.008). Receiver operating characteristic curve analyses showed that the ICE-T predicts FFR ≤0.80 more accurately than the iFR (area under curve 0.897 vs. 0.810 for ICE-T and iFR, respectively). Conclusions: We identified the period in the IC-ECG in which resting Pd/Pa was low and constant. The IC-ECG-based algorithm may improve the accuracy of diagnosing myocardial ischemia, without increasing invasiveness, compared with pressure-dependent indices.

Effects of caffeine on fractional flow reserve values measured using intravenous adenosine triphosphate.

We investigated the effects of caffeine intake on fractional flow reserve (FFR) values measured using intravenous adenosine triphosphate (ATP) before cardiac catheterization. Caffeine is a competitive antagonist for adenosine receptors; however, it is unclear whether this antagonism affects FFR values. Patients were evenly randomized into 2 groups preceding the FFR study. In the caffeine group (n = 15), participants were given coffee containing 222 mg of caffeine 2 h before the catheterization. In the non-caffeine group (n = 15), participants were instructed not to take any caffeine-containing drinks or foods for at least 12 h before the catheterization. FFR was performed in patients with more than intermediate coronary stenosis using the intravenous infusion of ATP at 140 µg/kg/min (normal dose) and 170 µg/kg/min (high dose), and the intracoronary infusion of papaverine. FFR was followed for 30 s after maximal hyperemia. In the non-caffeine group, the FFR values measured with ATP infusion were not significantly different from those measured with papaverine infusion. However, in the caffeine group, the FFR values were significantly higher after ATP infusion than after papaverine infusion (P = 0.002 and P = 0.007, at normal and high dose ATP vs. papaverine, respectively). FFR values with ATP infusion were significantly increased 30 s after maximal hyperemia (P = 0.001 and P < 0.001 for normal and high dose ATP, respectively). The stability of the FFR values using papaverine showed no significant difference between the 2 groups. Caffeine intake before the FFR study affected FFR values and their stability. These effects could not be reversed by an increased ATP dose.

Efficacy of biolimus A9-eluting stent for treatment of right coronary ostial lesion with intravascular ultrasound guidance: a multi-center registry.

The aim of this study was to assess the efficacy of a biolimus A9-eluting stent in patients with a right coronary artery (RCA) ostial lesion. Ostial lesions of the RCA have been a limitation of percutaneous coronary intervention even in the drug-eluting stent (DES) era. However, clinical outcomes after the deployment of a second generation DES to an RCA ostial lesion with intravascular ultrasound (IVUS) guidance have not been fully elucidated. From September 2011 to March 2013, 74 patients were enrolled in 17 centers from Japan. RCA ostial lesion was defined as de novo significant stenotic lesion located within 15 mm from ostium. IVUS was used for all cases to confirm the location of ostium and evaluate stent coverage of ostium. Patients with hemodialysis were excluded. The primary endpoint is a major adverse cardiac event (MACE) at 1 year. Forty two percent of patients had multi-vessel disease. Angiographically severe calcification was observed in 26% of the lesions. The mean stent diameter was 3.3 ± 0.3 mm (3.5 mm, 72%, 3.0 mm, 25%, and 2.75 and 2.5 mm, 3%), stent length was 17.5 ± 5.8 mm, and dilatation pressure of stenting was 15.6 ± 4.1 atm. RCA ostium was covered by stent in all lesions in IVUS findings. Post dilatation was performed for 64% of lesions (balloon size 3.7 ± 0.6 mm). MACE rate at 1 year was 5.4% (target lesion revascularization 5.4%, myocardial infarction 1.2%, and no cardiac death). The biolimus A9-eluting stent for RCA ostial lesions with IVUS guidance showed favorable results at 1-year follow-up.

Papaverine-induced polymorphic ventricular tachycardia during coronary flow reserve study of patients with moderate coronary artery disease.

BACKGROUND: Papaverine is useful for evaluating the functional status of a coronary artery, but it may provoke malignant ventricular arrhythmia (VA). The aim of this study was to investigate the incidence, and clinical and ECG characteristics of patients with papaverine-induced VAs. METHODS AND RESULTS: The 182 consecutive patients underwent fractional flow reserve (FFR) measurement of 277 lesions. FFR was determined after intracoronary papaverine administration by standard procedures. The clinical and ECG characteristics were compared between patients with and without ventricular tachycardia (VT: ≥3 successive premature ventricular beats (PVBs), or ventricular fibrillation (VF)). After papaverine administration, the QTc interval, QTUc interval, and T-peak to U-end interval were prolonged significantly. Single PVBs on the T-wave or U-wave type developed in 29 patients (15.9%). Polymorphic VT (torsade de pointes) occurred in 5 patients (2.8%), and of those, VF developed in 3 patients (1.7%). No clinical and baseline ECG parameters were predictors for VT or VF except for sex and administration of papaverine into the left coronary artery. Excessive prolongation of QT (or QTU), T-peak to U-end intervals and giant T-U waves were found immediately prior to the ventricular tachyarrhythmias (VTAs), which were unpredictable from the baseline data. CONCLUSIONS: Intracoronary administration of papaverine induced fatal VTAs, although the incidence is rare. Excessive prolongation of the QT (and QTU) interval appeared prior to VTAs; however, they were unpredictable.

[Intracoronary temperature in patients with coronary artery disease].

OBJECTIVES: Measurements of changes in plaque temperature may predict plaque rupture. The present study investigated variations in temperature within the atherosclerotic coronary artery using a pressure guide wire with thermal sensor (dual sensor guide wire). METHODS AND RESULTS: Seventy-seven patients (78 lesions), who had no significant lesion at the orifice of the culprit coronary artery, were studied. The patients had acute myocardial infarction (22 patients), unstable angina pectoris (20 patients), and stable angina pectoris (35 patients). The thermal sensor was calibrated at the orifice of the coronary artery, and then inserted into the culprit coronary artery. deltaT was defined as the difference between the intracoronary temperature at the position of the pressure gradient and at the orifice. deltaT was higher in patients with acute myocardial infarction and unstable angina pectoris than in patients with stable angina pectoris (0.09 +/- 0.07 and 0.07 +/- 0.07 vs 0.03 +/- 0.04 degrees C, p < 0.001, p = 0.02, respectively). There was no significant difference in deltaT between patients with acute myocardial infarction and unstable angina pectoris (p = 0.48). Patients with acute myocardial infarction and unstable angina pectoris showed a significant relationship between deltaT and C-reactive protein (r = 0.59, p = 0.0004). CONCLUSIONS: The variations in intracoronary temperature of the culprit coronary arteries in patients with acute coronary syndrome were higher than those in patients with stable angina pectoris. These variations may be related to inflammation of vulnerable plaque.

Usefulness of fractional flow reserve in determining the indication of target lesion revascularization.

The objective of this study was to examine the usefulness of fractional flow reserve (FFR) in determining the indication of target lesion revascularization (TLR) at follow-up angiography after percutaneous coronary intervention (PCI). One hundred forty-seven patients with 155 lesions that had intermediate restenosis took part in this study. FFR was measured in all patients for the evaluation of stenosis severity. Then TLR was performed when FFR was < 0.75, and TLR was deferred when FFR was > or = 0.75. Patients in whom TLR was deferred were followed up clinically (25 +/- 11 months). In 98 patients (67%) who underwent stress myocardial scintigraphy before angiography, the results of the scintigraphy were compared with FFR results. TLR was performed in 34 lesions (22%). After TLR, the Canadian Cardiovascular Society class decreased significantly (from 1.5 +/- 0.7 to 1.1 +/- 0.5; P < 0.05). In 113 patients who did not undergo TLR, only 4 patients (3.5%) had cardiac events (re-PCI in 1 patient and a positive SPECT in 3 patients). Discordance between the results of scintigraphy and FFR was observed in 30 patients (30%), but the patients who had good values of FFR > or = 0.75 showed a nil event rate (0%). FFR might be useful for the determination of the indication of TLR.

[Influence of serum homocysteine level on coronary atherosclerosis in Japanese].

OBJECTIVES: This study investigated the relationship between serum homocysteine level and coronary artery disease in Japanese. METHODS: Serum homocysteine level was measured in 200 consecutive patients who underwent coronary angiography for the assessment of ischemic heart disease. Patients with acute myocardial infarction were excluded, so 197 patients were included in this study. The patients were classified into four groups based on number of diseased vessels identified by coronary angiography: no significant stenosis group (non-vessel group), one-vessel group, two-vessel group, and three-vessel group. More than 50% stenosis was defined as diseased vessels. RESULTS: Serum homocysteine level in the three-vessel group (13.5 +/- 8.0 microM) was significantly higher than that in the non-vessel group (9.9 +/- 2.7 microM), one-vessel group (9.1 +/- 2.3 microM), and two-vessel group (10.4 +/- 3.3 microM). Patients were classified into quartile groups according to the serum homocysteine level. The number of diseased vessels and frequency of three-vessel disease tended to be higher with increasing serum homocysteine level. There was no significant relationship between serum homocysteine level and coronary risk factors (diabetes mellitus, hyperlipidemia, smoking habit) except hypertension. Multivariate analysis for the predictor of number of diseased vessels showed diabetes mellitus, hypertension, and serum homocysteine level were independent predictors. CONCLUSIONS: Elevation of plasma homocysteine level is related to the severity of coronary artery disease in Japanese.

Coronary flow--pressure relationship distal to epicardial stenosis.

To assess the coronary flow velocity - pressure relationship distal to a stenosis, and to evaluate the influence of microvascular abnormalities on this relationship, coronary flow velocity and coronary pressure were measured simultaneously in 38 patients (42 vessels). The instantaneous peak coronary flow velocity was plotted against the simultaneous measured distal coronary pressure, and the slope of the relation in the phase of diastolic flow decrease was calculated as the flow - pressure slope index (FPSI) and the X-intercept of the slope was calculated as zero-flow pressure (Pzf). The slope of the curve increased from 2.0+/-2.6 to 4.5+/-4.1 (p<0.001) and the X-intercept decreased from 42+/-16 to 27+/-13 mmHg (p<0.001) after papaverine injection. After successful coronary intervention, Pzf increased from 23+/-10 to 35+/-11 (p<0.01) and FPSI decreased from 6.8+/-5.1 to 3.5+/-1.8 (p<0.05). Pzf was higher in patients with an old myocardial infarction. It is feasible to assess the relationship between coronary flow and pressure distal to a stenosis in the clinical setting, and the relationship may provide additional information regarding coronary microcirculation. Microvascular abnormalities may play an important role in the coronary flow - pressure relationship distal to stenosis.

[Measurement of fractional and coronary flow reserve using dual sensor guide wire].

OBJECTIVES: Fractional flow reserve and coronary flow reserve (CFR) are indices of the severity of coronary artery stenosis influenced by both epicardial and microcirculatory dysfunction. The CFR was measured using the new pressure guide wire with thermal sensor (dual sensor guide wire) on the basis of the thermodilution principle (CFR-thermo), and compared to the CFR as measured by the Doppler method (CFR-Doppler), and the relationships were evaluated between CFR-thermo, fractional flow reserve and stress myocardial scintigraphy. METHODS AND RESULTS: CFR-thermo and CFR-Doppler were measured in 14 patients (20 vessels) by the dual sensor guide wire and Doppler guide wire, respectively. A significant positive correlation was found between CFR-Doppler and CFR-thermo (y = 0.80 x + 0.10, r = 0.70, p < 0.0001). Stress myocardial perfusion single photon emission computed tomography (SPECT) was performed before coronary angiography in 56 patients (70 vessels), and then fractional flow reserve and CFR-thermo were measured using the dual sensor guide wire. CFR-thermo and fractional flow reserve were significantly lower in coronary segments with positive SPECT image (n = 32) than in coronary segments with negative SPECT image (n = 38) (1.29 +/- 0.24 vs 1.96 +/- 0.69, p < 0.0001; 0.61 +/- 0.13 vs 0.85 +/- 0.09, p < 0.0001). The cut-off values of CFR-thermo and fractional flow reserve for detection of ischemic segments demonstrated by SPECT image were 1.47 and 0.76, respectively. The sensitivity and specificity for detecting ischemia were 78% and 84% for CFR-thermo, 88% and 92% for fractional flow reserve, respectively. CONCLUSIONS: A significant correlation was found between CFR-thermo measured by the thermodilution principle using the dual sensor guide wire and CFR measured by the Doppler method. CFR-thermo measured by the dual sensor guide wire may be useful to detect myocardial ischemia.