High-dose Intracoronary Adenosine Research Articles

Feasibility and Improved Diagnostic Yield of Intracoronary Adenosine to Assess Microvascular Dysfunction With Bolus Thermodilution.

Bolus thermodilution and intravenous adenosine are established methods for coronary microcirculatory assessment. Yet, its adoption remains low, partly due to procedural time and patient discomfort associated with intravenous adenosine. We investigated differences between intracoronary and intravenous adenosine using bolus thermodilution in terms of microcirculatory indices, procedural time, and side effects associated with adenosine in patients with myocardial ischemia and nonobstructive coronary arteries. In this prospective, observational study, 102 patients with suspected myocardial ischemia and nonobstructive coronary arteries underwent measurements of mean transit time, coronary flow reserve, index of microcirculatory resistance, procedure time and patient tolerability with low-dose intracoronary adenosine, high-dose intracoronary adenosine (HDIC), and intravenous adenosine. HDIC induced greater hyperemia compared with low-dose intracoronary IC adenosine and intravenous adenosine with a shorter hyperemic mean transit time, P<0.0001. Coronary flow reserve was higher and index of microcirculatory resistance lowest with HDIC, compared with low-dose intracoronary IC adenosine and intravenous adenosine, P<0.05. Low coronary flow reserve was downgraded from 21% with intravenous adenosine to 10% with HDIC adenosine (P=0.031); high index of microcirculatory resistance was downgraded from 23% with intravenous adenosine to 14% with HDIC (P=0.098). Intracoronary adenosine was associated with lower procedural times (P<0.0001). More patients experienced chest pain with intravenous adenosine (P<0.01) and the chest pain intensity was higher compared with intracoronary adenosine (P<0.0001). In patients with suspected myocardial ischemia and nonobstructive coronary arteries undergoing coronary microcirculatory assessment with bolus thermodilution, the use of HDIC compared with intravenous adenosine was associated with enhanced induction of hyperemia. The use of intracoronary adenosine allowed for a shorter procedure time and was better tolerated. URL: clinicaltrials.gov; Unique Identifier: NCT04827498.

Efficacy and Safety of High-Dose Intracoronary Adenosine Injection in Fractional Flow Reserve Assessment.

The recommended dosage of intracoronary adenosine in fractional flow reserve (FFR) assessment is controversial. High-dose adenosine may overcome the biological variability of adenosine response in hyperemia. We aimed to test the efficacy and safety of a high-dose escalation protocol at our institute. Using the adenosine dose escalation protocol, the percentages of FFR ≤ 0.75 and 0.80 after high-dose escalation were compared with those at conventional doses. The chi-squared test was used to evaluate the accuracy of FFR values with the tested doses by comparing them with the results of a non-invasive pretest. A total of 87 patients (130 vessels) were included, and protocol adherence was 93.1%. High-dose intracoronary adenosine was injected in 78.5% of the vessels. The dose escalation strategy was well-tolerated without serious complications. The positive rate increased significantly after conducting the protocol compared to that with a conventional dose (28.2% vs. 23.6% with an FFR threshold of 0.75, and 48.7% vs. 42.5% with a threshold of 0.80, both p < 0.05). In the validation cohort, only FFR ≤ 0.75 was associated with the binary result of the non-invasive pretest (p < 0.01 vs. p = 0.37). The high-dose adenosine escalation strategy did not increase the accuracy of FFR (77.8% vs. 75.6% in conventional dose and high-dose adenosine, respectively). The use of a high-dose escalation strategy increased the positive rate in FFR assessments.

Individual Lesion-Level Meta-Analysis Comparing Various Doses of Intracoronary Bolus Injection of Adenosine With Intravenous Administration of Adenosine for Fractional Flow Reserve Assessment.

Intravenous infusion of adenosine is considered standard practice for fractional flow reserve (FFR) assessment but is associated with adverse side-effects and is time-consuming. Intracoronary bolus injection of adenosine is better tolerated by patients, cheaper, and less time-consuming. However, current literature remains fragmented and modestly sized regarding the equivalence of intracoronary versus intravenous adenosine. We aim to investigate the relationship between intracoronary adenosine and intravenous adenosine to determine FFR. We performed a lesion-level meta-analysis to compare intracoronary adenosine with intravenous adenosine (140 µg/kg per minute) for FFR assessment. The search was conducted in accordance to the Preferred Reporting for Systematic Reviews and Meta-Analysis statement. Lesion-level data were obtained by contacting the respective authors or by digitization of scatterplots using custom-made software. Intracoronary adenosine dose was defined as; low: <40 µg, intermediate: 40 to 99 µg, and high: ≥100 µg. We collected 1972 FFR measurements (1413 lesions) comparing intracoronary with intravenous adenosine from 16 studies. There was a strong correlation (correlation coefficient =0.915; P<0.001) between intracoronary-FFR and intravenous-FFR. Mean FFR was 0.81±0.11 for intracoronary adenosine and 0.81±0.11 for intravenous adenosine (P<0.001). We documented a nonclinically relevant mean difference of 0.006 (limits of agreement: -0.066 to 0.078) between the methods. When stratified by the intracoronary adenosine dose, mean differences between intracoronary and intravenous-FFR amounted to 0.004, 0.011, or 0.000 FFR units for low-dose, intermediate-dose, and high-dose intracoronary adenosine, respectively. The present study documents clinically irrelevant differences in FFR values obtained with intracoronary versus intravenous adenosine. Intracoronary adenosine hence confers a practical and patient-friendly alternative for intravenous adenosine for FFR assessment.

Intracoronary versus intravenous adenosine to assess fractional flow reserve: a systematic review and meta-analysis.

Intravenous infusion of adenosine is the reference method to measure fractional flow reserve (FFR). Intracoronary boluses are often used because of time and convenience, but their effectiveness has yet to be assessed. We conducted a systematic review and meta-analysis of prospective studies directly comparing intravenous and intracoronary adenosine administration for FFR measurement. FFR values and prevalence of functionally critical lesions obtained with the different methods of adenosine administration were compared. Twelve studies evaluating 781 lesions from 731 patients were included (63.7 years, 25.5% women, median FFR 0.82). FFR values were significantly lower with intravenous adenosine than with intracoronary adenosine [mean difference 0.01, 95% confidence interval (CI) 0.00-0.02, P = 0.005], even if no significant differences were observed when only high doses of intracoronary adenosine (≥150 μg) were considered. The prevalence of functionally critical lesions did not significantly differ between intracoronary and intravenous adenosine. Concerning the use of different doses of intracoronary adenosine, low doses (≤60 μg) were associated with higher FFR values (mean difference 0.02, 95% CI 0.01-0.03, P < 0.001) and fewer functionally critical lesions (OR 0.57, 95% CI 0.40-0.81, P = 0.002) compared with high doses. Meta-regression analysis did not show any significant interaction between the way of adenosine administration and main clinical features. Intracoronary adenosine was associated with a higher incidence of atrioventricular blocks, whereas angina and/or systemic symptoms were more frequent with intravenous adenosine. Intracoronary adenosine might be as effective as intravenous adenosine to measure FFR, provided that adequate doses are used. Intracoronary adenosine represents a valuable alternative to intravenous adenosine whenever appropriately administered.

Resting Pd/Pa and haemodynamic relevance of coronary stenosis as evaluated by fractional flow reserve.

Fractional flow reserve (FFR) currently represents the gold standard in the evaluation of the haemodynamic relevance of coronary stenoses. However, both intracoronary and intravenous adenosine may be tolerated poorly by some patients. Therefore, considerable interest had been focused in the last few years on new adenosine-free indexes to define the haemodynamic relevance of coronary stenoses. So far, few data have been reported on resting Pd/Pa and its correlation with FFR as evaluated with high-dose intracoronary adenosine administration, which is the aim of the current study. FFR was assessed in 120 patients with 137 intermediate lesions during cardiac catheterization by a pressure-recording guidewire (PrimeWire). FFR was calculated as the ratio of the distal coronary pressure to the aortic pressure at hyperaemia. Intracoronary doses of adenosine were administered up to 720 μg as intracoronary boli. Exclusion criteria were as follows: (a) allergy to adenosine; (b) baseline bradycardia (heart rate <50 bpm); (c) hypotension (blood pressure <90 mmHg); and (d) refusal to provide signed informed consent. High doses of intracoronary adenosine were well tolerated, with no major side effects. Increasing doses up to 720 μg progressively decreased FFR values and increased the percentage of patients showing an FFR less than 0.80. Resting Pd/Pa showed good accuracy in the identification of patients with significant FFR values (<0.80) [area under the curve=0.9 (0.84-0.96), P<0.0001]. Using receiver-operating characteristic curves, we identified a threshold less than 0.93 as the best accurate cut-off value in the prediction of a positive FFR value. A value up to 0.88 was associated with a 100% positive predictive value, whereas a value of at least 0.95 was associated with a 95% negative predictive value. This study showed that in intermediate lesions, resting Pd/Pa was related linearly to FFR. We identified 0.93 as the best cut-off value in the prediction of haemodynamically significant coronary stenosis as evaluated by FFR. However, cut-off values of 0.88 and 0.95 could provide the maximal predictive positive and negative values, suggesting the additional use of FFR only in patients with resting values within this range.

Diagnostic accuracy of a hybrid approach of instantaneous wave-free ratio and fractional flow reserve using high-dose intracoronary adenosine to characterize intermediate coronary lesions: Results of the PALS (Practical Assessment of Lesion Severity) prospective study.

We sought to investigate the diagnostic accuracy of instantaneous wave-free ratio (iFR) and high-dose intracoronary adenosine fractional flow reserve (IC-FFR) compared with classical intravenous adenosine fractional flow reserve (IV-FFR) to assess coronary stenosis severity. The usefulness of two hybrid strategies combining iFR and high-dose IC-FFR was also evaluated. Physiological assessment of intermediate coronary stenoses to guide revascularization is currently recommended. Consecutive real-world patients with angiographically intermediate coronary stenosis (40-80% diameter stenosis) were prospectively included in the PALS (Practical Assessment of Lesion Severity) study. In every target lesion iFR, high-dose IC-FFR and IV-FFR were systematically measured to assess the accuracy of an hybrid sequential approach combining iFR and IC-FFR. A total of 106 patients with 121 intermediate coronary lesions were analyzed. Both, iFR and IC-FFR showed a significant correlation with IV-FFR (iFR: r = 0.60, 95%CI 0.48-0.70; IC-FFR: r = 0.88; 95%CI: 0.83-0.92). High-dose IC-FFR provided lower FFR values than IV-FFR (0.81 ± 0.08 vs. 0.82 ± 0.09, P = 0.25). Using a receiver-operating-characteristic curve an optimal iFR threshold of 0.91 for the screening test was identified. A sequential test strategy (initial iFR followed by IC-FFR only in lesions with iFR <0.91) yielded an excellent diagnostic accuracy (96.7%, 95%CI 96.7-99.1%) with a sensitivity, specificity, positive and negative predicted values of 100%, 94.7%, 91.8%, and 100%, respectively. A hybrid approach using the previously described iFR gray zone (0.85-0.94) also provided an excellent diagnostic accuracy (95%, 95%CI: 89.5-98.1%). In patients with intermediate coronary lesions a hybrid strategy by using a sequential approach of iFR and high-dose IC-FFR, provided a very good diagnostic performance to identify physiologically significant stenoses. © 2017 Wiley Periodicals, Inc.

TCT-329 Combined use of iFR and FFR With High-Dose Intracoronary Adenosine for the Classification of Intermediate Coronary Lesions

iFR is a new, non-hyperemic, physiologic pressure index proposed for the assessment of intermediate coronary lesions. Recently, it has been suggested the value of a combined approach using iFR and FFR with intravenous adenosine (FFRiv) for the classification of coronary lesions located within the

Effects of high doses of intracoronary adenosine on the assessment of fractional flow reserve

Maximal hyperemia is the critical prerequisite for FFR assessment. Despite IV adenosine currently representing the recommended approach, IC administration of adenosine constitutes a valuable alternative in everyday practice. However, it is surprisingly unclear which IC strategy allows the achievement of FFR values comparable to IV adenosine. This study sought to compare increasing doses of intracoronary (IC) adenosine versus intravenous (IV) adenosine for fractional flow reserve (FFR) assessment. Maximal hyperemia is the critical prerequisite for FFR assessment. Despite IV adenosine currently representing the recommended approach, IC administration of adenosine constitutes a valuable alternative in everyday practice. However, it is surprisingly unclear which IC strategy allows the achievement of FFR values comparable to IV adenosine. Thirty intermediate coronary stenoses undergoing FFR measurement were prospectively and consecutively enrolled. Hyperemia was sequentially induced by bolus of IC adenosine (AND 150 μ g) and by IV adenosine infusion (IVADN) (140 μg/kg/min). FFR values, symptoms, and development of atrioventricular block were recorded. 150 μg dose of IC adenosine were well tolerated and associated with fewer symptoms than IV adenosine. Intracoronary adenosine doses induced a significant decrease of FFR compared with baseline levels ( p 0.00).Among the 6 patients with FFR values > 0.80 with IVADN, 4 were correctly identified also by 150 μ g bolus IC adenosine. Intracoronary adenosine, at doses higher than currently suggested, lows obtaining FFR values similar to IV adenosine. Intravenous adenosine, which remains the gold standard, might thus be reserved for those lesions with equivocal FFR values.

Cardioprotective effect of high‐dose intragraft adenosine infusion on microvascular function and prevention of no‐reflow during saphenous vein grafts intervention

Despite the use of embolic protection devices, no-reflow can still occur during saphenous vein grafts (SVGs) intervention. High-dose intracoronary adenosine infusion preconditions the myocardium, improves coronary flow, and prevents no-reflow. The role of high-dose intragraft adenosine infusion on protection of microvascular function and prevention of no-reflow has not been investigated We investigated the cardioprotective effect of high-dose intragraft adenosine infusion, compared with placebo, on microvascular function and prevention of no-reflow during SVGs intervention. We randomized 22 patients with SVGs stenoses to receive either a 10-min intragraft adenosine infusion (200 μg/min; total dose = 2,000 μg) or normal saline prior to stenting. Average peak velocity (APV), coronary flow velocity reserve (CVR), thrombolysis in myocardial infarction (TIMI) frame count (TFC), TIMI myocardial perfusion grade (TMPG), and the rate of no-reflow were compared between the two groups before adenosine or saline infusions and after stenting After stenting, hyperemic APV, CVR, and TMPG were significantly higher in the adenosine-treated group than in the control group (60 ± 18 vs. 35 ± 10 cm/sec; 2.6 ± 0.54 vs. 1.8 ± 0.47; and 2.8 ± 0.90 vs. 2.1 ± 0.80, respectively; P < 0.05. TFC was significantly lower in the adenosine-treated group than in the control group (14 ± 3.0 vs. 26 ± 13; P < 0.05). In the control group, four patients (36%) developed no-reflow compared to none in the adenosine-treated patient; P < 0.05 CONCLUSIONS: This study provides the first evidence that high-dose intragraft adenosine infusion compared with placebo protects microvascular function and prevents no-reflow during SVGs intervention.

Comparison of low and high dose intracoronary adenosine and acetylcholine in women undergoing coronary reactivity testing: Results from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE)

Women with signs and symptoms of myocardial ischemia who are referred for invasive coronary angiography often have no evidence of obstructive coronary artery disease (CAD) [1]. Forty-five to sixty percent of these patients have abnormal coronary vasomotion due to endothelial or non-endothelial dependent macro- or microvascular coronary dysfunction [1–3]. Abnormal coronary vasomotion is linked with adverse cardiovascular outcomes, suggesting that additional coronary reactivity testing (CRT), beyond standard angiography, is needed in clinical practice to appropriately risk stratify these patients [2–6]. CRT with intra-coronary adenosine and acetylcholine (ACh) is used to identify vascular dysfunction, yet ascending dosing of these agents is time-consuming. We aimed to determine if 1) coronary flow reserve (CFR) was different after low or high dose adenosine, and 2) change in coronary artery cross sectional area (CSA) and coronary blood flow (CBF) was different after low or high dose ACh. Eighty -six women with no obstructive CAD, who were enrolled in the WISE Coronary Vascular Dysfunction Study (WISE-CVD, www.clinicaltrials.gov Identifier {type:clinical-trial,attrs:{text:NCT00832702,term_id:NCT00832702}}NCT00832702), underwent CRT using a Doppler guide wire (Volcano ®FloWire 300cm) in a proximal left coronary. CFR was recorded in response to low dose (18μg) and high dose (36μg) intra-coronary adenosine. Change in CSA and CBF were determined after intra-coronary low dose ACh (10−6 mol/L infusion for total of 0.364μg) and high dose ACh (10−4 mol/L infusion for total of 36.4μg). The protocol was approved by the local institutional review board, and written informed consent was obtained from each participant. On average, the women included in this analysis were 54 (±12.2) years old; 36.7% had hypertension; 13.9% had dyslipidemia; 45.6% had a history of tobacco use; 70.9% were Caucasian; and 10% had diabetes. The average CFR after low dose adenosine was 2.6 ± 0.6, and the average CFR after high dose adenosine was 2.5 ± 0.6. The CFR obtained after low dose adenosine was not significantly different from the CFR obtained after high dose adenosine in the same subject (mean of paired difference 0.06 ± 0.3, p-value = 0.11). The changes in CBF and CSA after low and high dose ACh are shown in the Table. On average CBF increased 15% ± 32% with low dose ACh, but increased 92% ± 102% with high dose ACh. In the same subject the increase in CBF was 77% higher after high dose ACh compared with after low dose ACh (p-value < 0.0001). The CSA of the proximal left anterior descending artery (LAD) and the LAD 5 mm distal to the flow wire remained essentially the same after low dose ACh, but decreased slightly after high dose ACh. On average, in the same subject the change in CSA of the proximal LAD was 4% smaller after high dose ACh compared with after low dose ACh (p-value = 0.05). Table Comparison of cross-sectional area and coronary blood flow change with use of low vs. high dose acetylcholine. Our data indicate that escalating dosing of adenosine to detect non-endothelial dependent microvascular coronary dysfunction may not be needed. These findings are consistent with previous work that suggests that intracoronary doses of adenosine as low as 16 μg achieve maximal hyperemia [7]. For the purpose of our testing, we have used relatively lower doses of adenosine (18 μg and 36 μg) that test its non-endothelial dependent effects on the coronary circulation. At higher doses of adenosine, it becomes an epicardial coronary vasodilator, and would test hyperemic CBF due to both endothelial and non-endothelial dependent effects [8]. Our ACh dosing was selected based on the pioneering work by Ludmer et al. that demonstrated that patients with atherosclerosis and suspected endothelial dysfunction have paradoxical vasoconstriction in response to intra-coronary infusions of ACh at doses of 10−6 mol/L or less [9]. Other studies have demonstrated a very high incidence of abnormal coronary spasm in response to intracoronary ACh in patients with suspected endothelial dysfunction when using even higher doses of intracoronary ACh (100–200 μg) [1,10]. The results of our analysis also suggest that higher dose ACh (36.4μg [10−4 mol/L]) has greater diagnostic utility than lower dose ACh (0.364μg [10−6 mol/L]), as higher dose ACh resulted in a significantly greater increase in CBF compared with low dose ACh, and on average only high dose ACh demonstrated an inappropriate decrease in CSA in this group of women with suspected endothelial dysfunction. Among women with evidence of ischemia but no obstructive CAD, low and high dose adenosine produced similar augmentation in coronary flow velocity, but low and high dose ACh produced different results. For clinically indicated CRT, low dose adenosine but high dose ACh appear to be indicated.

Does high-dose intracoronary adenosine improve regional systolic left ventricular function in patients with acute myocardial infarction?

Background Reperfusion injury limits the beneficial effects of primary percutaneous coronary intervention (PCI) in the setting of acute myocardial infarction (AMI). Adenosine limits reperfusion injury in animal models. Objective Is to study the effects of high-dose intracoronary adenosine administration in the setting of primary PCI on coronary blood flow and regional left ventricular function. Methods Sixty patients with a definite diagnosis of ST elevation AMI within 6 h from the onset of chest pain were randomly allocated to receive adenosine (6 mg) or saline placebo (on a 1:2 ratio) as an adjunct to primary PCI with assessment of TIMI flow, TIMI myocardial blush grade (MBG), and occurrence of no-reflow. Systolic (S) wave velocity was recorded at the mitral annulus in the territory of the infarct related artery using pulsed-wave tissue Doppler within 24 h from admission and one week after PCI. Results Both groups showed no significant difference in terms of age, sex, risk factors, infarct location, and distribution of coronary artery disease. The adenosine group showed a higher incidence of TIMI III flow (95% vs. 65%, p < 0.03), a higher incidence of MBG 2-3 (95% vs. 67.5%, p < 0.007), and a lower incidence of no-reflow (10% vs. 45%, p < 0.006). Only in the adenosine group, there was a significant improvement in the annular pulsed tissue Doppler S wave velocity at the infarct-related territory at day-7 (p < 0.01). Conclusion High-dose adenosine administration in the setting of primary PCI improves myocardial perfusion and regional left ventricular systolic function.

Comparison of Effectiveness of High-Dose Intracoronary Adenosine Versus Intravenous Administration on the Assessment of Fractional Flow Reserve in Patients With Coronary Heart Disease

Intravenous adenosine is considered the drug of choice to obtain maximum hyperemia in the measurement of the fractional flow reserve (FFR). However, comparative studies performed between intravenous and intracoronary administration have not used high doses of intracoronary adenosine. The present study compared the efficacy and safety of high doses of intracoronary adenosine to intravenous administration when calculating the FFR. Intracoronary bolus doses of 60, 180, 300, and 600 μg adenosine were compared to an intravenous administration of 140 μg/kg/min, 200 μg/kg/min, and 140 μg/kg/min plus an intracoronary bolus of 120 μg. All the cases were performed using the radial approach. FFR was assessed in 102 patients with 108 intermediate lesions by an intracoronary pressure wire. The intracoronary dose of 60 μg was associated with a significantly greater FFR compared to the intravenous infusion (0.02 ± 0.03, p = 0.001). The intracoronary doses of 300 (-0.01 ± 0.00; p = 0.006) and 600 μg (-0.02 ± 0.00; p <0.0005) were significantly associated with a smaller FFR compared to the intravenous infusion. An intracoronary dose of 600 μg revealed a significantly greater percentage of lesions with an FFR <0.80 compared to intravenous infusion at 140 μg/kg/min (37.6 vs 31.5%; p <0.05) and 200 μg/kg/min (37.6 vs 32.4%; p <0.05) and compared to intracoronary doses of 60 (26.9%) and 180 μg (31.5%). In conclusion, an intracoronary bolus dose >300 μg can be equal to or more effective than an intravenous infusion of adenosine in achieving maximum hyperemia when calculating the FFR. Its use could simplify these procedures without having an effect on safety.

Letter by Michiels et al Regarding Article, “Diagnostic Accuracy of Combined Intracoronary Pressure and Flow Velocity Information During Baseline Conditions: Adenosine-Free Assessment of Functional Coronary Lesion Severity”

We read with interest the article by van de Hoef and colleagues about the value of the coronary stenosis pressure drop-flow velocity ratio (ΔP/V) in the evaluation of coronary stenosis.1 We congratulate the authors with this meticulous and well-written investigational report; however, we have a number of comments. Again (as with iFR in the recently published ADVISE study),2 the authors claim in their subtitle that they demonstrate the diagnostic performance of an adenosine-free assessment of functional coronary lesion severity. In recent literature, there seems to be an unjustified quest for proving that on one hand (very) high doses of intracoronary adenosine are necessary to …

Effects of Increasing Doses of Intracoronary Adenosine on the Assessment of Fractional Flow Reserve

The purpose of this study was to investigate the effects of increasing dose of intracoronary adenosine on fractional flow reserve (FFR) measurement. FFR is a validated method for the assessment of the severity of coronary artery stenosis. It is based on the change in the pressure gradient across the stenosis after the achievement of maximal hyperemia of the coronary microcirculation that may be obtained by either intracoronary bolus or intravenous infusion of adenosine. No study has explored so far the effects of very high doses of intracoronary adenosine on FFR. FFR was assessed in 46 patients with 50 intermediate lesions during cardiac catheterization by pressure-recording guidewire (PrimeWire, Volcano, San Diego, California). FFR was calculated as the ratio of the distal coronary pressure to the aortic pressure at hyperemia. Increasing doses of adenosine were administrated (60, 120, 180, 360, and 720 μg) as intracoronary boluses. Exclusion criteria were: 1) allergy to adenosine; 2) baseline bradycardia (heart rate <50 beats/min); 3) hypotension (blood pressure <90 mm Hg); and 4) refusal to provide signed informed consent. High doses of intracoronary adenosine were well tolerated, with no major side effects. Increasing doses up to 720 μg progressively decreased FFR values and increased the percentage of patients showing an FFR <0.75. Among angiographic parameters, both percent stenosis and lesion length were independently associated with lower FFR values. This study shows that high doses of intracoronary adenosine (up to 720 μg) increased the sensitivity of FFR in the detection of hemodynamically relevant coronary stenoses. Furthermore, lesion length and stenosis severity were independent angiographic determinants of FFR.

New Set of Intravascular Ultrasound-Derived Anatomic Criteria for Defining Functionally Significant Stenoses in Small Coronary Arteries (Results from Intravascular Ultrasound Diagnostic Evaluation of Atherosclerosis in Singapore [IDEAS] Study)

We sought to determine the intravascular ultrasound-derived anatomic criteria for functionally significant lesions in small coronary arteries with a reference segment diameter <3 mm. A fractional flow reserve (FFR) of <0.75, as determined by pressure wire using high-dose (100 to 150 microg) intracoronary adenosine, was used as the reference standard for functional significance. For the 94 patients/lesions involved in the present study, the average reference vessel diameter was 2.72 mm. The FFR was <0.75 in 38 patients (40.4%) and > or =0.75 in 56 patients (59.6%). Logistic regression analysis identified the minimal lumen area, plaque burden, and lesion length as the 3 most important determinants of the FFR. Using classification and regression tree analysis, the best cutoff values for these determinants to discriminate a FFR of <0.75 versus > or =0.75 were a minimal lumen area of < or =2.0 mm(2) (sensitivity 82.35%, specificity 80.77%), plaque burden of > or =80% (sensitivity 87.9%, specificity 78.9%), and lesion length of > or =20 mm (sensitivity 63.6%, specificity 78.9%). A significant increase was found in the area under the receiver operating characteristic curve of the combined parameters (minimal lumen area plus plaque burden plus lesion length) compared to the plaque burden (p = 0.014) and other individual parameters (p <0.001). In conclusion, we found that intravascular ultrasound-derived anatomic criteria are able to predict the functional significance of intermediate lesions in small coronary arteries. A minimal lumen area of < or =2.0 mm(2), plaque burden of > or =80%, and lesion length of > or =20 mm predicted a FFR of <0.75 with good sensitivity and specificity.

Response to Letter Regarding Article “Effect of High-Dose Intracoronary Adenosine Administration During Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: A Randomized Controlled Trial”

We thank Venetucci et al for their thoughtful comments on our recent article. In 448 patients with ST-elevation myocardial infarction randomized to 2 bolus doses of intracoronary adenosine or placebo, we showed that adenosine does not improve measures of myocardial reperfusion.1 In this study, we infused intracoronary adenosine (2× 120 μg in 20 mL NaCl) or placebo (2× 20 mL NaCl). The first bolus was given directly after thrombus aspiration and the second after stenting of the infarct-related artery. We used bolus doses well in excess of the dose recommended in the …

Letter by Venetucci et al Regarding Article “Effect of High-Dose Intracoronary Adenosine Administration During Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: A Randomized Controlled Trial”

To the Editor: In a recent article published in the August edition of Circulation: Cardiovascular Interventions , Fokkema et al1 demonstrated that the intracoronary adenosine given during primary percutaneous coronary intervention does not reduce infarct size or the incidence of no reflow phenomenon. In this article, the authors argue that the dose of adenosine they used (240 μg given in 2 120-μg boluses) is sufficient to achieve maximal vasodilation, and they cite an article that suggests 16 μg as the dose sufficient to achieve maximal vasodilatation. This is certainly true for normal coronary circulation. However, we do not feel …

Effect of High-Dose Intracoronary Adenosine Administration During Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: A Randomized Controlled Trial

Effect of High-Dose Intracoronary Adenosine Administration During Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: A Randomized Controlled Trial

Effect of High-Dose Intracoronary Adenosine Administration During Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction

Background— Coronary microvascular dysfunction is frequently seen in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention. Previous studies have suggested that the administration of intravenous adenosine resulted in an improvement of myocardial perfusion and a reduction in infarct size. Intracoronary adenosine (bolus of 30 to 60 μg) is a guideline-recommended therapy to improve myocardial reperfusion. The effect of intracoronary adenosine during primary percutaneous coronary intervention has not been investigated in a large randomized trial. Methods and Results— Patients presenting with acute ST-elevation myocardial infarction were randomized to 2 bolus injections of intracoronary adenosine (2�120 μg in 20 mL NaCl) or placebo (2�20 mL NaCl). The first bolus injection was given after thrombus aspiration and the second after stenting of the infarct-related artery. The primary end point was the incidence of residual ST-segment deviation &lt;0.2 mV, 30 to 60 minutes after percutaneous coronary intervention. Secondary end points were ST-segment elevation resolution, myocardial blush grade, Thrombolysis in Myocardial Infarction flow on the angiogram after percutaneous coronary intervention, enzymatic infarct size, and clinical outcome at 30 days. A total of 448 patients were randomized to intracoronary adenosine (N=226) or placebo (N=222). The incidence of residual ST-segment deviation &lt;0.2 mV did not differ between patients randomized to adenosine or placebo (46.2% versus 52.2%, P =NS). In addition, there were no significant differences in secondary outcome measures. Conclusions— In this randomized placebo controlled trial enrolling 448 patients with ST-elevation myocardial infarction, administration of intracoronary adenosine after thrombus aspiration and after stenting of the infarct-related artery did not result in improved myocardial perfusion.

Are high doses of intracoronary adenosine an alternative to standard intravenous adenosine for the assessment of fractional flow reserve?

Background Achievement of maximal hyperemia of the coronary microcirculation is a prerequisite for the measurement of fractional flow reserve (FFR). Intravenous adenosine is considered the standard method, but its use in the catheterization laboratory is time consuming and expensive compared with intracoronary adenosine. Therefore, this study compared different high, intracoronary doses of adenosine for the potential to achieve a maximal hyperemia equivalent to the standard intravenous route. Methods FFR was assessed in 50 patients with 50 intermediate lesions during cardiac catheterization. FFR was calculated as the ratio of the distal coronary pressure to the aortic pressure at hyperemia. Different incremental doses of intracoronary adenosine (60, 90, 120, and 150 μg as boli) and a standard intravenous infusion of 140 μg/kg/min were administered in a randomized fashion. Results Different incremental doses of intracoronary adenosine were well tolerated, with fewer systemic adverse effects than intravenous adenosine. At baseline, there were no significant differences for mean aortic and distal coronary pressure or heart rate in the different adenosine doses and routes. FFR decreased with increasing adenosine doses, with the lowest values observed with the 150-μg intracoronary bolus and 140-μg/kg/min dose of intravenous adenosine. All intracoronary doses, except the 150-μg bolus, resulted in mean FFR values that were significantly ( P <.05) higher than FFR after the administration intravenous adenosine. Furthermore, 5 patients (10%) with a FFR value >0.75 and 3 subjects (6%) with a FFR value >0.80 who received a 60-μg intracoronary bolus reached a value below the cutoff point of 0.75 with the intravenous administration. Conclusions This study suggests a dose-response relationship on hyperemia for intracoronary adenosine doses >60 μg. The administration of very high intracoronary adenosine boli is safe and associated with fewer systemic adverse effects than standard intravenous adenosine. However, intravenous adenosine administration with 140 μg/kg/min produced a more pronounced hyperemia than intracoronary adenosine in most patients and should be the preferred mode of application for the assessment of FFR.