Intracoronary Bolus Injection Research Articles

Clinical Outcome of Revascularization Deferral With Instantaneous Wave-Free Ratio and Fractional Flow Reserve: A 5-Year Follow-Up Substudy From the iFR-SWEDEHEART Trial.

Background Although physiology-based assessment of coronary artery stenosis using instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) are established methods of guiding coronary revascularization, its clinical outcome in long-term deferral needs further evaluation, especially with acute coronary syndrome as a clinical presentation. The aim was to evaluate the long-term clinical outcome of deferral of revascularization based on iFR or FFR. Methods and Results This is a substudy of the iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trial, where patients deferred from revascularization from each study arm were selected. Nine hundred eight patients deferred from coronary revascularization with iFR (n=473) and FFR (n=435) were followed for 5 years. The national quality registry, SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies), was used for patient data collection and clinical follow-up. The end point was major adverse cardiac events and their individual components all-cause death, cardiovascular death, noncardiovascular death, nonfatal myocardial infarction, and unplanned revascularization. No significant difference was found in major adverse cardiac events (iFR 18.6% versus FFR 16.8%; adjusted hazard ratio, 1.08 [95% CI, 0.79-1.48]; P=0.63) or their individual components. Conclusions No differences in clinical outcomes after 5-year follow-up were noted when comparing iFR versus FFR as methods for deferral of coronary revascularization in patients presenting with stable angina pectoris and acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02166736.

Comparative study of fractional flow reserve and diastolic pressure ratio using a guidewire with a sensor for measuring intravascular pressure

This study aimed to evaluate the correlation and diagnostic agreement between diastolic pressure ratio (dPR) and fractional flow reserve (FFR) in a Japanese real-world setting. Prospective multicenter observational study. This study included 100 patients with intermediate coronary artery stenosis at 4 Japanese hospitals. For these lesions, FFR and dPR were measured using a guidewire with a sensor and a monitor to measure intravascular pressure. The correlation and diagnostic agreement between FFR and dPR were assessed. When both FFR and dPR were negative or positive, the results were considered to be concordant. When one was positive and the other was negative, the result was regarded as discordant (positive discordance, FFR > 0.80 and dPR ≤ 0.89; negative discordance, FFR ≤ 0.80 and dPR > 0.89). Overall, the FFR and dPR were well-correlated (R = 0.841). FFR and dPR were concordant in 89% of cases (concordant normal, 43%; concordant abnormal, 46%) and discordant in 11% (positive discordance, 7%; negative discordance, 4%). No significant difference was observed in the rate of concordant results between patients with and without diabetes mellitus. The diagnostic concordance rate was significantly different among the 3 coronary arteries (right coronary artery, 93.3%; left anterior descending artery, 93.2%; and left circumflex artery, 58.3%; P = .001). Additionally, the rate of concordant results tended to be higher when using intravenous administration of adenosine than when using intracoronary bolus injection of nicorandil (adenosine, 95.1%; nicorandil, 84.7%; P = .103). We found that dPR was highly correlated with FFR, and diagnostic discordance was observed in 11% of the lesions. Several factors, including lesion location and medication for hyperemia, may cause the diagnostic discordance between dPR and FFR.

Comparison between intracoronary versus intravenous bolus injection of tirofiban on infarct size during primary PCI in patients with acute anterior ST segment elevation myocardial infarction

Abstract Background The latest guidelines considered glycoprotein IIb/IIIa inhibitors (GPI) as a bailout strategy in selected situations in patients presented with acute ST segment elevation myocardial infarction (STEMI) however, did not recommend route of administration over another and did not correlate it to infarct size. Infarct size correlates generally with prognosis following acute myocardial infarction and Reduction in infarct size can boost clinical outcomes and decrease rate of heart failure hospitalization. Purpose To evaluate intracoronary vs intravenous use of tirofiban on reduction of infarct size in STEMI treated with primary PCI. Methods Between February, 2018, and October, 2019, one hundred patients presented within 6 hours of anterior STEMI undergoing primary PCI after exclusion of (rescue PCI, TIMI flow less than II post PCI, Previous MI, Stent thrombosis, Previous CABG, Significant left main occlusion, Pulmonary edema and Cardiogenic shock). Group (A): 50 patients who were treated by intracoronary bolus infusion of tirofiban followed by IV maintenance dose infusion of tirofiban. Group (B): 50 patients who were treated by intravenous bolus infusion of tirofiban followed by IV maintenance dose infusion of tirofiban. Primary endpoint: Infarct size was assessed 1 month after randomization by SPECT. Secondary endpoint: Major adverse cardiovascular events (MACE) during hospital stay (cardiac death, MI, stroke or target vessel revascularization), heart failure and bleeding. Results Patients randomized to intracoronary tirofiban compared with intravenous tirofiban had a significant decrease in the primary end point of infarct size (mean [SD], 14.46% [7.79%] vs 18.06% [7.83%]; P=0.02). Also associated with lower incidence of heart failure (number [%], 8 [16%] vs 17 [34%]; P=0.037). There were no significant differences in any of the MACE or bleeding between the randomized groups at 30 days. Conclusions In patients with anterior STEMI presenting early after symptom onset, intracoronary tirofiban administration when compared to intravenous route during primary PCI resulted in infarction size reduction and lower heart failure incidence mainly driven by enhanced left ventricular systolic function however no distinction between two strategies on MACE or bleeding risk. Results Funding Acknowledgement Type of funding source: None

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.

CRT-100.21 Comparison Between Intracoronary and Intravenous Eptifibatide Bolus Injection Regimens During Primary PCI in Patients Presenting With Anterior STEMI

Eptifibatide achieves high local concentration via direct intracoronary injection as it promotes clot disaggregation, but it remains unclear if it is of superior benefit than the routine intravenous administration. The current study aimed to examine the safety and efficacy of intracoronary versus

Safety and efficacy of intracoronary nicorandil as hyperaemic agent for invasive physiological assessment: a patient-level pooled analysis.

Our aim was to evaluate the safety and efficacy of intracoronary (IC) nicorandil as an alternative choice of hyperaemic agent for invasive physiologic studies. A total of 480 intermediate coronary lesions from 429 patients enrolled from six Japanese and Korean centres were analysed. IC nicorandil showed earlier achievement of hyperaemia (time to the lowest FFR: 18.0 s [1st and 3rd quartile value 15.6-21.5] vs. 44.0 s [36.0-60.0], p<0.001) with similar hyperaemic efficacy, compared with intravenous (IV) adenosine/ATP (FFR 0.82 [0.75-0.87] vs. 0.82 [0.74-0.88], p=0.207). FFR measurements with both agents showed excellent correlation and classification agreement (CA) for FFR ≤0.80 (r=0.941, ICC 0.980, CA 90.8%, kappa=0.814, AUC of nicorandil 0.980, all p<0.001). Only three patients (0.7%) showed changes in classification across the grey zone (0.75-0.80). IC nicorandil produced fewer changes in blood pressure (BP) and heart rate (HR) and showed less chest pain than IV adenosine/ATP (all p<0.001). When comparing ΔFFR according to ΔBP or ΔHR between IV adenosine/ATP and IC nicorandil, there were no correlations, either between ΔFFR and ΔBP (r=-0.114, p=0.091), or between ΔFFR and ΔHR (r=1.000, p=0.151). Nicorandil IC bolus injection is a simple, safe and effective hyperaemic method for FFR measurement and can be used as a substitute for adenosine.

Sex-Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction.

BackgroundEndothelial dysfunction is an early stage of atherosclerosis. Single‐nucleotide polymorphisms (SNPs) have been associated with vascular dysfunction, cardiac events, and coronary artery remodeling. We aimed to detect SNPs associated with endothelial dysfunction and determine whether these associations are sex specific.Methods and ResultsSix hundred forty‐three subjects without significant obstructive coronary artery disease underwent invasive coronary endothelial function assessment. We collected data from 1536 SNPs that had previously been associated with vasoreactivity, angiogenesis, inflammation, artery calcification, atherosclerotic risk factors, insulin resistance, hormone levels, blood coagulability, or with coronary heart disease. Coronary vascular reactivity was assessed by the percent change in coronary artery diameter ≤ −20% after an intracoronary bolus injection of acetylcholine on invasive coronary physiology study. SNPs significantly associated with coronary epicardial endothelial dysfunction were ADORA1,KCNQ1, and DNAJC4 in the whole cohort, LPA, MYBPH, ADORA3, and PON1 in women and KIF6 and NFKB1 in men (P<0.01).ConclusionsWe have identified several significant SNPs that are associated with an increased risk of coronary endothelial dysfunction. These associations appear to be sex specific and may explain gender‐related differences in development of atherosclerosis.

Fractional Flow Reserve Assessment of a Significant Coronary Stenosis Masked by a Downstream Serial Lesion.

Fractional flow reserve (FFR) has been recognized as an effective tool to determine functional significance in intermediate coronary lesions and FFR-guided percutaneous coronary intervention (PCI) improves clinical outcomes. However, hemodynamic interaction between serial stenoses within one coronary artery complicates the assessment of functional severity of each individual lesion. We present a case in which FFR measurement by intracoronary bolus injection of adenosine helps to make appropriate revascularization decision in serial stenoses when the procedures are performed systemically and properly.

TCT-297 Safety and Efficacy of Intracoronary Nicorandil as Hyperemic Agent for Invasive Physiological Assessment: Patient-Level Pooled Analysis of Current Evidence

Fractional flow reserve (FFR) has become standard invasive assessment for determining the functional significance of coronary artery stenosis. Intravenous (IV) infusion of adenosine is the gold standard method for the induction of hyperemia. Intracoronary (IC) bolus injection of nicorandil, a

Abstract 18397: Left Ventricular End Diastolic Pressure as a Tool to Detect Intracoronary Ergonovine-Induced Myocardial Ischemia During Provocation Test

A drug-induced coronary spasm provocation test is regarded as the gold standard for detection of variant angina. However, a suitable method to detect myocardial ischemia during provocation test is still lacking. We evaluated the feasibility of left ventricular end diastolic pressure (LVEDP) as a tool to detect myocardial ischemia caused by intracoronary (IC) bolus injection of ergonovine. Twenty-nine patients having chest pain without any significant (&gt; 80%) coronary stenosis underwent IC ergonovine provocation test. Epicardial artery spasm of more than 90% was considered as positive. LVEDP was monitored during the entire procedure using a pig-tail catheter. Of the overall 29 patients, ischemic symptom occurred in 16 (55%) and provocation positive was confirmed in 6 (21%). The amount of LVEDP change (ΔLVEDP) was significantly larger in symptomatic group (5.6±4.2 vs. 1.2±2.0 mmHg, p=0.002). The optimal cut-off value of ΔLVEDP for symptom was 4.4 (area under the curve 0.803, sensitivity 69%, specificity 92%) (Figure 1). Of the 6 patients of positive test, five occurred in RCA, one in LAD. Two patients with big patent LCX were not associated with LVEDP elevation more than 4.4 despite significant RCA spasm (Figure 2). Except for the 2, LVEDP elevated significantly in positive test group (7.9±2.9 mmHg, p &lt;0.001, n=4). Elevation of blood pressure and heart rate by IC ergonovine did not correlate with ΔLVEDP (p=0.142 and 0.154, respectively). In conclusion, ΔLVEDP is a specific marker for myocardial ischemia independent of hemodynamic parameters. LVEDP may aid detection of myocardial ischemia which is not associated with significant epicardial spasm during provocation test.

Utility of nicorandil for the measurement of coronary fractional flow reserve

Nicorandil, an adenosine triphosphate (ATP)-sensitive potassium channel opener, has been used as an anti-angina drug that causes coronary vasodilation of both epicardial and resistance vessels. We assessed the hyperaemic efficacy of nicorandil for the measurement of coronary fractional flow reserve (FFR). In this prospective, single-centre study, we enrolled 20 consecutive patients (20 lesions) with intermediate coronary artery stenosis. Hyperaemic efficacy of intracoronary bolus injection of nicorandil (2mg) was compared with that of continuous intravenous infusion of adenosine triphosphate (ATP, 150μg/kg/min). The intra-patient difference of FFR value between the two hyperaemic stimuli was evaluated using a non-inferiority design with the margin of 0.03. Among study patients, no serious event occurred with administration of either stimulus. A strong and linear correlation of FFR with ATP and nicorandil was observed (r (2)=0.98, P<0.0001). The intra-patient difference of the FFR between nicorandil and ATP was 0.003 (95% confidence interval -0.004 to 0.011), and the probability for the non-inferiority margin of 0.03 was <0.0001. In conclusion, bolus intracoronary injection of nicorandil was non-inferior to continuous intravenous injection of ATP in achieving maximal hyperaemia. Nicorandil could be considered as an alternative option for achieving maximal coronary and myocardial hyperaemia for the assessment of FFR.

Safety and efficacy of a novel hyperaemic agent, intracoronary nicorandil, for invasive physiological assessments in the cardiac catheterization laboratory

Maximal hyperaemia is a key element of invasive physiological studies and adenosine is the most commonly used agent. However, infusion of adenosine requires additional venous access and can cause chest discomfort, bronchial hyper-reactivity, and atrioventricular conduction block. The aim of this study was to evaluate the feasibility and efficacy of intracoronary (IC) nicorandil as a novel hyperaemic agent for invasive physiological studies. We enrolled 210 patients who underwent fractional flow reserve (FFR) measurement. Hyperaemic efficacy of the following methods was compared: IC bolus injection of adenosine; intravenous (i.v.) infusion of adenosine (140 μg/kg/min); and IC bolus of nicorandil (1 and 2 mg). In 70 patients, the index of microcirculatory resistance was also measured. Hyperaemic efficacy of IC nicorandil 2 mg was non-inferior to that of i.v. adenosine infusion (FFR: 0.82 ± 0.10 vs. 0.82 ± 0.10; P for non-inferiority < 0.001). There was a strong correlation between FFRs measured by i.v. adenosine and IC nicorandil (R² = 0.934). Nicorandil produced fewer changes in blood pressure, heart rate and PR interval, and less chest pain than adenosine (all P-values < 0.05). Atrioventricular block occurred in 12 patients with IC adenosine, 4 patients with i.v. adenosine and none with IC nicorandil. The index of microcirculatory resistance was 18.3 ± 8.7 with i.v. adenosine and 17.2 ± 7.6 with IC nicorandil (P = 0.126). This study suggests that IC bolus injection of nicorandil is a simple, safe, and effective way to induce steady-state hyperaemia for invasive physiological evaluations. Clinicaltrials.gov number: NCT01331902.

MYOCARDIAL PROTECTIVE EFFECTS OF ANISODAMINE IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION UNDERGOING EARLY PERCUTANEOUS CORONARY INTERVENTION FOLLOWING THROMBOLYSIS

ObjectivesTo evaluate the additional benefit of preventive administration of anisodamine to tirofiban during primary PCI on myocardial reperfusion.MethodsThis study was prospectively observed the hemodynamic effects of anisodemine in STEMI patients...

Comparison of Hyperemic Efficacy Between Central and Peripheral Venous Adenosine Infusion for Fractional Flow Reserve Measurement

Maximal hyperemia is a prerequisite for the accurate measurement of fractional flow reserve (FFR). Although continuous infusion of adenosine via the femoral vein is considered to be the gold standard, this requires an additional invasive procedure for femoral vein access and is difficult to use during transradial coronary catheterization. We performed this prospective study to evaluate the feasibility and efficacy of peripheral intravenous infusion of adenosine for FFR measurement. Seventy-one patients were prospectively enrolled, and FFR was measured using a 0.014-inch coronary pressure wire. Hyperemic efficacy of adenosine was compared among intracoronary bolus injection and continuous IV infusion (140 μg/min/kg) via the femoral and via the forearm vein. In 20 patients, hyperemic mean transit time and index of microcirculatory resistance were also measured. Mean FFR after bolus administration of adenosine was 0.81±0.10. As compared with femoral vein infusion (FFR: 0.80±0.10), hyperemic efficacy of forearm vein infusion of adenosine (FFR: 0.80±0.11) was not inferior (P for noninferiority=0.01). The number of functionally significant stenoses (FFR <0.75) was also not different between the 2 methods (femoral vein versus forearm vein; 17 (25.0%) versus 17 (25.0%), P=1.0). Both hyperemic mean transit time and index of microcirculatory resistance were not different between the 2 routes of adenosine infusion. Additional bolus injection of adenosine during IV infusion did not improve the hyperemic efficacy but increased the risk of atrioventricular block. This study suggests that continuous intravenous infusion of adenosine via the forearm vein is a convenient and effective way to induce steady-state hyperemia for invasive physiological measurements. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01070420.

Platelet inhibition and GP IIb/IIIa receptor occupancy by intracoronary versus intravenous bolus administration of abciximab in patients with ST-elevation myocardial infarction

In patients with ST-elevation myocardial infarction (STEMI), direct intracoronary bolus administration of the glycoprotein (GP) IIb/IIIa receptor antagonist abciximab is associated with a reduction in infarct size, better myocardial salvage, less microvascular obstruction and improved myocardial blush grade as compared to intravenous bolus injection, presumably caused by higher local drug concentrations leading to a more pronounced inhibition of platelet aggregation. We investigated whether there are differences in the degree of GP IIb/IIIa receptor occupancy and platelet inhibition in blood drawn from the coronary sinus (CS) shortly after intracoronary versus intravenous abciximab bolus administration. A total of 16 patients with acute STEMI undergoing primary percutaneous coronary intervention within 12h of symptom onset underwent blood sampling from the CS before, immediately after and 30min after abciximab bolus administration (intracoronary bolus: n=8 patients; intravenous bolus: n=8 patients). Immediately after bolus application, GP IIb/IIIa receptor occupancy in CS blood was significantly higher in patients who received direct intracoronary bolus injection compared to administration via a peripheral vein (intracoronary bolus: 93.5% [IQR 92.7-95.4]; intravenous bolus: 74.0% [IQR 17.6-94.0], p=0.04). The degree of platelet inhibition was also markedly higher with intracoronary compared to intravenous dosing. At late sampling after 30min no significant differences were found between groups for both platelet reactivity and GP IIb/IIIa receptor occupancy. Acutely, direct intracoronary bolus injection resulted in a more pronounced local inhibition of platelet function and a higher degree of GP IIb/IIIa receptor occupancy as compared to standard intravenous bolus injection.

Protective effects of salvianolate on microvascular flow in a porcine model of myocardial ischaemia and reperfusion

Microvascular reflow is crucial for myocyte survival during ischaemia/reperfusion injury. We aimed to assess if salvianolate, a highly purified aqueous extract from Radix salviae miltiorrhizae, could improve impaired microvascular reflow induced by ischaemia/reperfusion injury, using a porcine closed-chest model. Left anterior descending coronary artery ligation was created by balloon occlusion for 2 h followed by reperfusion for 14 days. Salvianolate was administrated intravenously for 7 days at low dose (5 mg/kg/day), high dose (10 mg/kg/day) or high dose combined with one 20 mg intracoronary bolus injection just at the beginning of reperfusion. Control-group animals were only given the same volume of saline. After 14 days of reperfusion, animals treated with high-dose salvianolate showed improved myocardial perfusion assessed by real-time myocardial contrast echocardiography and coloured microspheres. The beneficial effect was further supported by increased capillary density and decreased infarct size. All these effects eventually resulted in well-preserved cardiac function detected by echocardiography. Moreover, we also demonstrated that salvianolate administration was associated with elevated superoxide dismutase activity, thioredoxin activity and glutathione concentration, and reduced malondialdehyde concentration, which, in turn, resulted in a significant decrease in terminal deoxynucleotide transferase-mediated dUTP nick end labelling-positive cells and an increased ratio of Bcl-2 to Bax expression. Intravenous salvianolate at a dose of 10 mg/kg/day for 7 days had significant beneficial effects on myocardial microvascular reflow, which were associated with decreased oxidative stress and apoptosis.

Intermedin (IMD/AM2) dilates the pig coronary vascular bed through release of nitric oxide

Background: This study investigated the effects of intermedin/ adrenomedullin-2 (IMD/AM2), an endogenous agonist for calcitonin-like calcitonin receptors, on coronary and systemic hemodynamics. Methods: Ultrasonic transit time flow probes were placed around the left anterior descending (LAD) artery in the anesthetized, open-chest pig (n=6). A catheter was placed into the proximal LAD. Intracoronary arterial bolus injections of IMD, adrenomedullin (hADM13-52) and calcitonin gene related peptide (CGRP) (1, 3, 10 &#956;g) were performed and the changes in the velocity of coronary blood flows were continuously recorded. Results: Intracoronary artery bolus injections of IMD, hADM13-52 and CGRP increased coronary blood flow in a dose-dependent manner. At the studied doses, IMD was more potent than CGRP and hADM13-52 and did not alter systemic arterial pressure, cardiac output and cardiac index. Intracoronary artery injection of NG-Nitro-Larginine- methyl ester (L-NAME) significantly decreased the coronary vasodilator response (CVR) to IMD. Conclusion: The present data suggest that IMD possesses marked vasodilator activity in the pig coronary vascular bed. The present data further suggest that IMD acts on a receptor in the coronary vascular bed that is coupled to endothelial nitric oxide release. The degree of the CVR to IMD may serve as functional marker for the integrity of endothelial cells in resistance segments of the coronary circulation

Utilidad de la terapia intracoronaria con células progenitoras en pacientes con miocardiopatía dilatada: ¿puente o alternativa al trasplante cardiaco?

Introduction and objectivesSome paediatric publications have recently raised the value of intracoronary therapy with autologous bone marrow-derived progenitor cells (APCs) in children with dilated cardiomyopathy (DCM) and heart failure. We describe the usefulness of this treatment in two infants with severe DCM and heart failure, who had been transferred to our hospital for cardiac transplant evaluation. Patients and methodsThe first patient was a 3 months old male weighing 4kg. The second was a 4 months old male weighing 5kg. At the time of admission, both were in poor clinical condition (NYHA IV), with severe dilation and systolic dysfunction (ejection fraction [EF]<30%) of the left ventricle and marked elevation of NT-proBNP, requiring treatment with mechanical ventilation and inotropic iv infusion. After mobilization with G-CSF for 4days, APCs were obtained from peripheral blood by leukocytapheresis, administering them by a slow intracoronary bolus injection using a stop-flow technique (6.15x106 CD34-positive cells/Kg in the first patient, and 10.55x106 CD34-positive cells/Kg in the second). ResultsSince the first week after the procedure, clinical status of patients improved and echocardiography showed a decrease in left ventricular dilation. A month later, there was a significant improvement in EF (> 40%) and NT-proBNP levels, subsequently maintained throughout the follow-up. However, four months later in the first patient, the left ventricle dilated again and its function slightly worsened, but without any significant impact in his clinical status. ConclusionsIntracoronary therapy with APCs can be an alternative in children, especially infants, with DCM and heart failure. It can reduce the waiting list mortality, improve clinical status and provide more time on the waiting list to receive a suitable organ, or even to make transplantation unnecessary.

Intermedin (IMD/AM2) dilates the pig coronary vascular bed through release of nitric oxide

The present study was designed to investigate the effects of IMD/AM2 (IMD), an endogenous agonist for calcitonin-like calcitonin receptors (CLCR), on coronary and systemic hemodynamics. Ultrasonic transit time flow probes were placed around the left anterior descending artery in the anesthetized, open-chest pig. Intracoronary arterial bolus injections (IAB) of IMD, hADM13–52 and CGRP increased coronary blood flow in a dose-dependent manner. IMD at the doses studied was more potent than CGRP and hADM13–52 and did not alter systemic arterial pressure, cardiac output and cardiac index. IAB of L-NAME significantly decreased the coronary vasodilatory response (CVR) to IMD. The present data suggest that IMD possesses marked vasodilator activity in the pig coronary vascular bed. The present data further suggest the CVR to IMD in the pig is mediated by release of nitric oxide from endothelial CLCR. The degree of the CVR to IMD may serve as functional marker for the integrity of endothelial cells in resistance segments of the coronary circulation. This study was supported by Gulhane Military School of Medicine (# AR-2006-20).

Optimal Dosage and Method of Administration of Adenosine for Measuring the Coronary Flow Reserve and the Fractional Flow Reserve in Koreans

Background and Objectives:The achievement of maximal vasodilatation is mandatory for obtaining valid measurements of the coronary flow reserve (CFR) and the fractional flow reserve (FFR). Recent studies have indicated that an incremental dose or a high dose of adenosine is necessary to achieve maximal hyperemia. We performed this study to examine the response of the physiologic parameters to different doses and to different methods of administration of adenosine in Koreans. Subjects and Methods:CFR: The CFR was measured in 25 consecutive patients with angiographically normal coronary arteries by using a Doppler wire. Three different doses (9, 18 and 36 μg in the left coronary artery (LCA), and 6, 12 and 24 μg in the right coronary artery (RCA)) of adenosine were used. FFR: In a phase I study, 102 consecutive patients with 188 intermediate lesions (160 LCA and 28 RCA lesions) underwent FFR measurements with using a pressure wire. Three different bolus doses (20, 40 and 80 μg) were administered in an incremental fashion. In a phase II study, the hyperemic efficacy of 3 different doses of intracoronary (IC) infusion (180, 240 and 300 μg/min) and of 3 methods of administration (IC infusion, intravenous infusion and IC bolus) were compared. Results:CFR: The higher 2 dose of adenosine had a tendency to achieve a higher CFR than the lower 1st dose. But when we increased the adenosine to more than 20 μg (LCA 36 and RCA 24 μg), there was a tendency towards obtaining a lower CFR than that obtained after the 2 dose of adenosine (LCA: 2.78±0.71 vs. 2.66±0.60, p=0.055, RCA: 3.19 ±0.88 vs. 3.04±0.80, p=0.86). FFR: Phase I: The dose of adenosine that achieved maximal hyperemia was 51 ±16 μg in the LCA and 35±20 μg in the RCA. In 73 (46%) of the LCA lesions and 12 (42%) of the RCA lesions, a further reduction of the FFR occurred when a higher dose of adenosine was used (LCA>40 ug, RCA>20 μg). Phase II: The FFR obtained after an IC bolus injection (0.83±0.06) was significantly higher than obtained with an IV infusion (0.79±0.07) and an IC (0.78±0.09) infusion (p<0.01). However, no difference in the FFR was observed for the IC and IV infusions. Conclusion:This study suggests that more than 20 μg adenosine does not have an additive effect on measuring the CFR. Adenosine 40 μg for the LAD and 20 μg for the RCA seems to be optimal as a intracoronary bolus injection for measuring the FFR in most cases. However, for the patients with borderline FFR, a higher bolus adenosine dose or an adenosine continuous infusion may be necessary. (Korean Circulation J 2006;36:300-307)