Adenosine Triphosphate Infusion Research Articles

Pd/Pa fluctuation with continuous ATP administration indicates inaccurate FFR measurement caused by insufficient hyperemia.

Continuous intravenous adenosine triphosphate (ATP) administration is the standard method for inducing maximal hyperemia in fractional flow reserve (FFR) measurements. Several cases have demonstrated fluctuations in the ratio of mean distal coronary pressure to mean arterial pressure (Pd/Pa) value during ATP infusion, which raised our suspicions of FFR value inaccuracy. This study aimed to investigate our hypothesis that Pd/Pa fluctuations may indicate inaccurate FFR measurements caused by insufficient hyperemia. We examined 57 consecutive patients with angiographically intermediate coronary lesions who underwent fractional flow reverse (FFR) measurements in our hospital between November 2016 and September 2018. Pd/Pa was measured after continuous ATP administration (150μg/kg/min) via a peripheral forearm vein for 5min (FFRA); and we analyzed the FFR value variation in the final 20s of the 5min, defining 'Fluctuation' as variation range > 0.03. Then, 2mg of nicorandil was administered into the coronary artery during continued ATP infusion, and the Pd/Pa was remeasured (FFRA+N). Fluctuations were observed in 23 of 57 patients. The cases demonstrating discrepancies of > 0.05 between FFRA and FFRA+N were observed more frequently in the fluctuation group than in the non-fluctuation group (12/23 vs. 1/34; p < 0.0001). The discrepancy between FFRA and FFRA+N values was smaller in the non-fluctuation group (mean difference ± SD; -0.00026 ± 0.04636 vs. 0.02608 ± 0.1316). Pd/Pa fluctuation with continuous ATP administration could indicate inaccurate FFR measurements caused by incomplete hyperemia. Additional vasodilator administration may achieve further hyperemia when Pd/Pa fluctuations are observed.

Abstract 12018: Coronary Microvascular Dilatory Dysfunction According to the Types of Coronary Functional Abnormalitiescoronarymicrovascular Dilatory Dysfunction According to the Types of Coronary Functional Abnormalities

Introduction: Recently, there has been an increasing interest in coronary functional abnormalities (CFA), which include epicardial coronary spasm (ECS), microvascular spasm (MVS) and microvascular vasodilatory dysfunction (MVD). However, the frequency of MVD according to the types of CFA remains unclear. Hypothesis: Thus, this study aimed to investigate the frequency of MVD according to the types of CFA in patients with ischemia with non-obstructive coronary arteries (INOCA). Methods: This study included 63 patients with INOCA who underwent coronary angiography (CAG) and coronary function tests (CFT) to evaluate chest pain. In CFT, acetylcholine was first administered intracoronarily in a stepwise manner, followed by chest symptoms, electrocardiographic ST-T changes and CAG. ECS was defined as coronary vasoconstriction of &gt;90% on CAG accompanied by chest symptoms or electrocardiographic ST-T changes. Additionally, a focal spasm was defined as a transient vessel narrowing of &gt;90% within the borders of one isolated coronary segment (as defined by the American Heart Association), and a diffuse spasm was defined as a 90% diffuse vasoconstriction in ≥2 adjacent coronary segments of the coronary artery. Moreover, MVS was defined as the presence of both chest symptoms and ST-T changes with non-significant coronary vasoconstriction (&lt;90%) on CAG. After nitroglycerin administration, coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) were subsequently obtained by transvenous adenosine triphosphate infusion using a pressure wire. MVD was defined as CFR of &lt;2.0 or IMR of ≥25 units. Results: CAG and CFT were performed on 91 coronary arteries in 63 patients with INOCA, the results of which are shown below. Conclusions: These findings suggest that the frequency of MVD differs according to the types of CFA. Properly evaluating the MVD and reflecting this in the therapeutic strategy in patients with INOCA is desirable in clinical settings.

Abstract 12029: The Impact of the Myocardial Bridge on Coronary Functional Test in Patients With Ischemia With Non-Obstructive Coronary Arteries

Introduction: The possibility of myocardial bridge (MB) causing chest pain has been widely reported; however, the effect of MBs on coronary microvessels has not been thoroughly investigated. Hypothesis: Thus, this study evaluated the effects of MB on epicardial coronary artery and coronary microvascular function during coronary angiography (CAG) and coronary function tests (CFT) in patients with ischemia with non-obstructive coronary arteries (INOCA). Methods: This study included 57 patients with INOCA who underwent CAG and CFT to evaluate chest pain. In CFT, acetylcholine was first administered intracoronarily in a stepwise manner, followed by chest symptoms, electrocardiographic changes [Editor1] and CAG. Positive coronary spasm was defined as coronary vasoconstriction of &gt;90% on CAG accompanied by chest symptoms or electrocardiographic ST-T changes. After nitroglycerin administration, CAG was performed to assess MB, which is defined as the systolic narrowing of the coronary artery diameter by &gt;20% compared to that in diastole. Coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were subsequently obtained by transvenous adenosine triphosphate infusion using a pressure wire. Coronary microvascular vasodilatory dysfunction (CMD) was defined as CFR of &lt;2.0 or IMR of ≥25 units. Results: Of the 57 patients, 13 (23%) had MB. The CAG and coronary CFT results in the MB (+) and MB (–) groups are shown below. Conclusions: These findings suggest that MB predisposes to coronary spasms in patients with INOCA. Conversely, MBs may have a limited effect on microvessels, particularly in such patients.

Adenosine triphosphate (ATP): a safe and effective vasodilator for stress perfusion cardiac magnetic resonance imaging

To evaluate the efficiency and safety of adenosine triphosphate (ATP) as a stress agent in a cohort of patients undergoing stress perfusion cardiac magnetic resonance imaging (CMRI). This retrospective study was conducted between December 2019 and October 2021. The study recruited patients who underwent stress perfusion CMRI using ATP as a vasodilator. Adverse events, such as chest pain, flushing, dyspnoea, headache, and splenic switch-off (SSO) phenomenon, were evaluated in the patients who underwent stress perfusion CMRI. The study included 107 patients (age range: 53±11 years; male:female, 62%:38%). The haemodynamic response (heart rate increased by≥10 beats/min) was quick and observed within 2 minutes of ATP infusion. Scanning was stopped in three patients because of atrioventricular block. CMRI images of seven out of 104 patients were excluded from the final analysis because of inferior quality. During ATP infusion, 37/107 patients (35%) experienced mild adverse events, such as chest pain, flushing, dyspnoea, headache, and atrioventricular block. Myocardial infarction and bronchospasms were not observed during ATP infusion. SSO, a marker of adequate stress, was observed in 91% (94/103) of the patients who underwent stress perfusion CMRI. As a coronary vasodilator, ATP was safe for stress perfusion CMRI. In addition, the adverse events during ATP infusion were mild, which were relieved within 2 minutes of ATP injection cessation. SSO could serve as an indicator of stress success in ATP stress perfusion CMRI.

The Impact of Myocardial Bridging on the Coronary Functional Test in Patients with Ischaemia with Non-Obstructive Coronary Artery Disease.

Background: The possibility of myocardial bridging (MB) causing chest pain has been widely reported; however, the effect of MB on coronary microvessels has not been thoroughly investigated. Therefore, this study evaluated the effects of MB on epicardial coronary artery and coronary microvascular function during coronary angiography (CAG) and coronary function test (CFT) in patients with ischaemia with non-obstructive coronary artery disease (INOCA). Methods: This study included 62 patients with INOCA who underwent CAG and CFT for the left anterior descending coronary artery (LAD) to evaluate chest pain. In the CFT, acetylcholine was first administered intracoronarily in a stepwise manner, followed by chest symptoms, electrocardiographic ST-T changes and CAG. Positive coronary spasm was defined as coronary vasoconstriction of >90% on CAG accompanied by chest symptoms or electrocardiographic ST-T changes. After nitroglycerin administration, CAG was performed to assess MB, which was defined as systolic narrowing of the coronary artery diameter by >20% compared with that in diastole. Coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were subsequently obtained via transvenous adenosine triphosphate infusion using a pressure wire. Coronary microvascular vasodilatory dysfunction (CMD) was defined as a CFR of <2.0 or an IMR of ≥25 units. Results: Of the 62 patients, 15 (24%) had MB. The patients’ characteristics did not differ between the two groups. Regarding the CAG and CFT results, the presence of coronary spasm in the LAD was higher in the MB (+) group (87%) than in the MB (−) group (53%, p = 0.02), whereas the values of CFR (MB (+): 2.7 ± 1.4, MB (−): 2.8 ± 1.1) and IMR (MB (+): 26.9 ± 1.0, MB (−): 30.0 ± 17.3) and the presence of CMD (MB (+): 53%, MB (−): 60%) were similar in the two groups. Conclusions: The findings suggest that MB predisposes patients with INOCA to coronary spasms. Conversely, MBs may have a limited effect on microvessels, particularly in such patients.

Prognosis of adenosine triphosphate infusion for anticonvulsants efficacy in patients with intensive cancer pain: a prospective observational study

INTRODUCTION: Pain is a common symptom in cancer patients even when analgesics were given. OBJECTIVE: To assess the prognostic value of intravenous infusion of non-selective purine receptors agonist adenosine triphosphate for effectiveness of anticonvulsant gabapentin in cancer patients with moderate and severe pain who received non-selective inhibitor of cyclooxygenase plus weak opioid tramadol. MATERIALS AND METHODS: Thirty-four cancer patients with intensive pain were scheduled for the study. The intravenous infusion of adenosine triphosphate 35–45 mg∙kg–1∙min–1 was performed within the period from 100 to 160 minutes. Then all patients were taken gabapentin (900 mg in three times daily). Pain was estimated 30 minutes before infusion, 30 minutes after infusion, and after taking 900 mg/day gabapentin for 4 days. Moreover, we studied prognostic significance of adenosine triphosphate infusion for the effectiveness of gabapentin administration. RESULTS: We revealed significant reduction of pain intensity after adenosine triphosphate infusion (Z = 4.0; р &lt; 0.0001 — Wilcoxon signed rank test). The same result was obtained after taking of gabapentin for 4 days (Z = 4.9; р &lt; 0.0001 — Wilcoxon signed rank test). Moreover, we found statistically moderate correlation link (t(N – 2) = 3.94; closeness correlation = 0.57; р &lt; 0.0004 — Spearman’s rank correlation coefficient) between pain intensity value after adenosine triphosphate infusion and taking of gabapentin. Regression analysis demonstrated satisfactory predictive ability of the resulting model (R2 = 0.55 (corrected R2 = 0.53); F = 38.74; р &lt; 0.0001). CONCLUSIONS: 1. Intravenous infusion of adenosine triphosphate may has significance for prognosis of taking anticonvulsant gabapentin effectiveness in cancer patients with moderate and severe pain who received non-selective cyclooxygenase inhibitor plus weak opioid tramadol. 2. Intravenous infusion of adenosine triphosphate or taking anticonvulsant gabapentin may significantly reduce pain intensity in cancer patients who had weak effect of administration of non-selective inhibitor of cyclooxygenase plus weak opioid tramadol.

Evaluation of the Feasibility, Safety and Efficacy of the Use of Intravenous Infusions of Adenosine Triphosphate (ATP) in People Affected by Moderate to Severe Alzheimer's Disease: A Double-Blind Masked Clinical Trial for Dose Finding.

There are currently no drug therapies modifying the natural history of patients suffering Alzheimer's disease (AD). Most recent clinical trials in the field include only subjects in early stage of the disease, while patients with advanced AD are usually not represented. To evaluate the feasibility, safety and efficacy of systemic infusions of adenosine triphosphate (ATP) in patients with moderate to severe AD, and to select the minimum effective dose of infusion. A phase IIb, randomized, double-blind, placebo-controlled clinical trial investigates. A total of 20 subjects with moderate or severe AD were included, 16 in the treatment group and 4 in the placebo group (4:1 randomization) at two dosage regimens, 6-hour or 24-hour infusions. The proof-of-concept study was successfully conducted, with no significant deviations from the study protocol and no serious adverse events reported. Regarding efficacy, only marginal differences were observed between ATP and placebo arms for H-MRS and MMSE variables. Our study demonstrates that the use of ATP infusion as therapy is feasible and safe. Larger studies are however needed to assess the efficacy of ATP in moderate to severe AD.

Detection of symptom-related coronary arteries in patients with coronary artery disease using real-time three-dimensional stress echocardiography with adenosine triphosphate

Aim 1) To develop normative values of global and regional left ventricular longitudinal deformation (LVLD) during real time three-dimensional stress echocardiography with adenosine triphosphate (ATP) and utilization of automated function imaging technology (4D Stress-Echo + LVLD with ATP); 2) to compare the effectiveness of detection of symptom-related coronary arteries during 4D Stress-Echo with ATP using: a) traditional visual assessment of regional myocardial contractility and b) step-by-step analysis of segmental LVLD.Material and Methods 15 healthy subjects and 32 patients with coronary artery disease (CAD) were examined after coronary angiography. All individuals underwent 4D Stress-Echo + LVLD with ATP (Vivid E95, General Electric).Results The normative values of global LVLD at three stages of the pharmacological stress-test (before, during and after ATP infusion) were –19.5 (95% CI: -20.4 – -19.0), –21.6 (95% CI: -22.8 – -20.4) and –19.5 (95% CI: -20.3 – -18.6), respectively; the values of LVLD in each of the 17 segments of left ventricular myocardium in healthy subjects were also determined. In patients with CAD visual control of contractility during stress test revealed dynamic decrease in local thickening of the myocardium, appearance of new zones of contractility disorders and expansion of previously noted in 31.2% of cases, while analysis of deformation detected the appearance of new zones of deformation disturbances and expansion of previously found – in 68.7% (р = 0.0055). Stress-induced worsening of myocardial deformation during ATP infusion in the zones of blood supply of left anterior descending coronary artery, circumflex artery and right coronary artery (with presence of hemodynamically significant stenoses and occlusions detected during coronary angiography) were found in 28.0, 77.7 and 65.2% respectively (р1-3 = 0.0194; р1-2 = 0.0019; р2-3 = 0.2864).Conclusion The normal values of global and segmental LVLD for each stage of 4D Stress-Echo + LVLD with ATP were determined. 4D Stress-Echo + LVLD with ATP can significantly increase the effectiveness of symptom-related coronary arteries identification in patients with CAD in comparison with traditional Stress-Echo with visual assessment of local myocardial contractility.

Coronary microvascular function in patients with angina with no obstructive coronary artery disease-What factors affect it clinically or angiographically?

Abstract Background In the clinical setting, we have often experienced patients with angina with no obstructive coronary artery disease (ANOCA), and it has been proposed that the presence of coronary microvascular dysfunction (CMD) play a pivotal role in the pathogenesis of ANOCA. Thus, it is important to assess coronary microvascular function (CMF). However, it has not been clarified what clinical factors or lesion characteristics on coronary angiography (CAG) affect CMF. Thus, we investigated the relationship between CMF and clinical factors or lesion characteristics on CAG in patients with ANOCA. Methods Thirty-four patients with chest pain, who underwent CAG, spasm provocation test (SPT) and CMF test, were enrolled. We excluded patients who had moderate coronary stenosis (% stenosis &amp;gt;30%). In the SPT with acetylcholine for left coronary artery and right coronary artery (RCA), the coronary spasm was defined as &amp;gt;90% narrowing of coronary artery on CAG accompanied with chest symptoms and/or ST-T changes on ECG during SPT, and coronary microvascular spasm (MVS) was defined as ≤90% narrowing of coronary artery on CAG with accompanied with chest pain and ST-T changes during SPT. In each coronary artery, the presences of atherosclerosis (20%≤%stenosis≤30%), focal spasm (spasm occurred within one segment of AHA classification), diffuse spasm (spasm occurred over two segments of AHA classification) and MVS, were checked. In the CMF test with a pressure-wire during adenosine triphosphate infusion, the index of microvascular resistance (IMR) was measured. IMR values were obtained in 34 of the left anterior descending coronary artery (LAD) and 12 in RCA. In each patient, conventional coronary risk factors, blood chemical parameters, peripheral endothelial function such as flow-mediated dilation (FMD) of brachial artery and left ventricular mass index (LVMI) were checked. Results In 34 patients, clinical factors including blood chemical parameters, FMD and LVMI, except for smoking status did not affect IMR values on LAD. Only the smoking status was associated with IMR values as follows: median IMR values were 44, 22 and 25 in current smokers (n=5), past smokers (n=8) and never smokers (n=21, p=0.03), respectively. In 46 coronary arteries, the presence of atherosclerosis, the type of the coronary spasm, such as focal and diffuse spasm and MVS, did not affect the IMR values, however, it was significantly higher in the RCA (median 38) than that in the LAD (median 26, p=0.02). Conclusion These results suggest that smoking status affected CMF in patients with ANOCA, suggesting the possibility of improvement of CMF by stop smoking in such patients. In addition, in the assessment of CMF, it may be important to take into account which coronary artery being evaluated. Funding Acknowledgement Type of funding sources: None.

Cardiovascular magnetic resonance assessment of coronary flow reserve improves risk stratification in heart failure with preserved ejection fraction

BackgroundCoronary microvascular dysfunction (CMD) has been proposed as a novel mechanism for the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). Recent studies have suggested the potential utility of coronary flow reserve (CFR) as a marker of CMD in patients with HFpEF. Phase contrast (PC) cine cardiovascular magnetic resonance (CMR) of the coronary sinus has emerged as a non-invasive method to quantify CFR. We aimed to investigate the prognostic value of CMR-derived CFR in patients with HFpEF.MethodsData from 163 HFpEF patients (73 ± 9 years; 86 [53%] female) were retrospectively analyzed. Coronary sinus blood flow was measured in all patients, and myocardial blood flow was calculated as coronary sinus blood flow divided by left ventricular mass. CFR was calculated as the myocardial blood flow during adenosine triphosphate infusion divided by that at rest. Adverse events were defined as all-cause death and hospitalization due to HF exacerbation. Event-free survival stratified according to CFR < 2.0 was estimated with Kaplan–Meier survival methods and Log-rank test.ResultsDuring a median follow-up of 4.1 years, 26 patients (16%) experienced adverse events. CMR-derived CFR was significantly lower in HFpEF with adverse events compared with those without (1.93 ± 0.38 vs. 2.67 ± 0.52, p < 0.001). On a Kaplan Meier curve, the rates of adverse events were significantly higher in HFpEF patients with CFR < 2.0 compared with HFpEF with CFR ≥ 2.0 (p < 0.001). The area under the curve of CFR for predicting adverse events was significantly higher than that of LGE (0.881 vs. 0.768, p = 0.037) and GLS (0.881 vs. 0.747, p = 0.036).ConclusionsCFR assessed using coronary sinus PC cine CMR may be useful as a non-invasive prognostic marker for HFpEF patients.

Prognostic value of resting coronary sinus flow determined by phase-contrast cine cardiovascular magnetic resonance in patients with known or suspected coronary artery disease

BackgroundPhase-contrast cine cardiovascular magnetic resonance (CMR) of the coronary sinus has emerged as a non-invasive method to measure coronary sinus blood flow (CSBF) and coronary flow reserve (CFR). We aimed to compare the prognostic value of resting CSBF and CFR for predicting major adverse cardiac events (MACE) in patients with known or suspected coronary artery disease (CAD) who underwent vasodilator stress CMR.MethodsWe studied 693 patients with known CAD and 519 patients with suspected CAD admitted to our hospital between 2009 and 2019. The CFR was calculated as the CSBF during adenosine triphosphate infusion divided by CSBF at rest. MACE was defined as composite of cardiovascular death, acute coronary syndrome, heart failure hospitalization, and sustained ventricular tachyarrhythmia.ResultsDuring a median follow-up of 4.6 years, 92 patients (8%) experienced MACE. The resting CSBF was significantly higher in patients with MACE than in patients without MACE (114.7 ± 44.9 mL/min vs. 84.7 ± 30.9 mL/min, p < 0.001 for known CAD; 122.2 ± 33.3 mL/min vs. 86.6 ± 36.7 mL/min, p < 0.001 for suspected CAD). The resting CSBF remained a significant predictor for MACE after adjusting clinical and CMR variables (hazard ratio [HR] of resting CSBF higher than the median: 3.18, p = 0.0083 for known CAD; HR: 23.3, p < 0.001 for suspected CAD). The area under the curve for predicting MACE was 0.73 for resting CSBF, 0.72 for CFR (p = 0.78) in patients with known CAD, and 0.82 for resting CSBF, 0.83 (p = 0.58) for CFR in patients with suspected CAD.ConclusionsThe resting CSBF may be a useful non-invasive method for the risk stratification of patients with known or suspected CAD without any radiation exposure, contrast media, or pharmacological vasodilator agents.

Impaired coronary flow reserve evaluated by phase-contrast cine magnetic resonance imaging in patients with atrial fibrillations.

Myocardial perfusion and perfusion reserve are diminished in patients with atrial fibrillation (AF). Phase-contrast (PC) cine magnetic resonance imaging (MRI) of the coronary sinus serves as a non-invasive means of quantifying coronary flow reserve (CFR) without any radioactive tracer. The present study aimed to evaluate the utility of PC cine MRI of the coronary sinus for assessing decreased CFR in patients with AF. We studied 362 patients with known or suspected coronary artery disease (CAD) [age 72 ± 9years; 267 (74%) male; 90 (25%) had AF] and 20 age- and gender-matched control subjects [age 72 ± 9years, 14 (70%) male]. Using a 1.5-T MR scanner and cardiac coils, blood flow of the coronary sinus (CBF) was quantified by PC cine MRI. CFR was calculated as CBF during adenosine triphosphate infusion divided by CBF at rest. CFR was significantly lower in patients with AF than in those without AF among all patients (n = 362) (2.45 ± 0.42 vs. 2.71 ± 0.58, p < 0.001), in patients with known CAD (n = 155) (2.40 ± 0.46 vs. 2.72 ± 0.58, p = 0.002), and in those with suspected CAD (n = 207) (2.49 ± 0.40 vs. 2.72 ± 0.59, p = 0.007). Significant differences in CFR were found between controls and patients without AF (3.12 ± 0.52 vs. 2.71 ± 0.58, p < 0.001). AF was independently associated with CFR in both known CAD patients [β = - 0.248, 95% confidence interval (CI): - 0.561 to - 0.119, p = 0.003) and suspected CAD patients (β = - 0.154, 95% CI - 0.353 to - 0.034, p = 0.018). The presence of AF was related to impaired CFR in both known and suspected CAD patients. PC cine MRI of the coronary sinus can be useful for detecting impaired CFR in patients with AF.

Adenosine triphosphate infusion in patients with cancer pain: a pilot study

Introduction. About 50–66 % patients with cancer suffered from intensive pain when are given analgesics. Objectives. We investigated the effectiveness of intravenous infusion of non-selective purine receptors agonist adenosine triphosphate in cancer patients with moderate and severe pain who had being received non-selective inhibitor of cyclooxygenase plus weak opioid tramadol. Materials and methods. Sixty-seven patients in which pain sensations were localized in different regions were scheduled for the study. The intravenous infusion of adenosine triphosphate 35–45 mcg kg(–1) min(–1) was performed within the period from 100 to 160 minutes. Pain severity was estimated by numeric verbal scale where “0” — no pain and “10” — maximal pain. Moreover, we studied prognostic significance of the original scale that was based on patient’s ability to pointed out precisely the pain sensation margins where “1” — patient can specify exactly the margins of pain sensations on the skin; “2” — patient can indicate approximately zone with pain sensation (periarticular tissue or bone or big muscle); and “3” — patient can determine large anatomical region only. Analysis of correlations was performed between scale value and the effectiveness of adenosine triphosphate infusion. Results. We revealed that 79 % (53 out of 67) patients have pointed out to pain relief after infusion with more than 20 % reduction of pain intensity (p = 0.0000001 — Wilcoxon signed rank test). As results, we obtained statistically correlation link (p = 0.02 — gamma-test and p = 0.02 — Kendall tau rank correlation coefficient) between the adenosine triphosphate infusion effectiveness and pain type with high precision of the pain sensation margins. Conclusions. Intravenous infusion of adenosine triphosphate has the high effectiveness for pain relief in cancer patients particularly when pain sensation margins high precisely detected to be.

Effect of Adenosine Triphosphate (ATP) Infusion on Neuropathic Pain in a Patient with Ramsay Hunt Syndrome

Effect of Adenosine Triphosphate (ATP) Infusion on Neuropathic Pain in a Patient with Ramsay Hunt Syndrome

Safety and Effectiveness of Volumetric Computed Tomography of the Heart in Combination with a PharmacologicaTest with Adenosine Triphosphate in the Diagnosis of Coronary Heart Disease

Aim To evaluate safety and efficacy of sodium adenosine triphosphate (ATP) as a vasodilator in assessment of left ventricular (LV) myocardial perfusion and in verification of ischemia by cardiac volumetric computed tomography (CT).Material and methods The study included 58 patients with suspected ischemic heart disease (IHD). For all included patients, cardiac volumetric CT with a pharmacological ATP test was performed. The rate of adverse effects was analyzed during the ATP infusion. Results of the study were compared with data from using other noninvasive methods for IHD diagnosis by calculating Cohen's kappa, the measure of agreement between two variables.Results The test performed during CT showed good tolerability of the ATP infusion, a low rate of moderate adverse reactions (8.6 %), and the absence of severe side effects. Results of diagnosing IHD with cardiac volumetric CT with the ATP pharmacological test were comparable with data from using other methods for noninvasive verification of LV myocardial ischemia (bicycle ergometry, treadmill test, stress echocardiography) in combination with coronarography or CT coronarography.Conclusion ATP appears a safe pharmacological agent for diagnosing transient LV myocardial ischemia. ATP can be recommended as a vasodilator for evaluation of perfusion using cardiac volumetric CT.

New Algorithm of Stress Echocardiography with Adenosine Triphosphate

Objective. Submaximal myocardial hyperemia is known not to be achieved in 16-18% of cases during cardiac stress tests and monotonic intracubital administration of adenosine triphosphate (ATP) at a dose of 140-160 pg/kg/min. The authors set a task to elaborate a new algorithm for stress echocardiography (SEchoCG) with ATP, providing for the possibility of a stepwise increase in the dosage of the drug, as well as to test it in healthy individuals and patients with coronary heart disease (CHD). Material and methods. The authors elaborated a new algorithm for SEchoCG on the basis of an analysis of the main science databases and their first own experience in using ATP during SEchoCG. The key provisions of the new algorithm were: (a) the exercise test consisted of 3 stages (EchoCG data should be recorded before, during, and 5 minutes after ATP infusion); (b) the criterion for achieving submaximal myocardial hyperemia during ATP administration is a systolic blood pressure (SBP) reduction of 5 and more mm Hg; (c) EchoCG was usually recorded at Stage 2 of the test 3 minutes after the start of ATP administration and with a decline in SBP; (d) the initial dose of ATP administration was 140 pg/kg/min; if SBP did not decrease at 3 minutes of the drug administration, the dosage should be first increased up to 175 pg/kg/ min at 1 minute; if there was no effect, the dosage should be increased up to 210 pg/kg/min at another 2-3 minutes. The algorithm was tested in 9 healthy volunteers, and in 26 patients with CHD. Results. Testing the new algorithm showed that all cases achieved submaximal myocardial hyperemia. SBP decreased below 90 mm Hg in 2 patients; 1 patient developed second-degree atrioventricular block; however, a simple decrease in the ATP infusion rate within 30 sec leveled this symptomatology. The SEchoCG data acceptable for the subsequent analysis of myocardial contractility and deformation could be recorded in all the examinees. Conclusion. The new algorithm for SEchoCG with ATP is effective in recording EchoCG findings. To have a final decision on the safety and information value of a new stress test protocol, it may be recommended to further test those in larger groups of patients during SEchoCG and in the use of other imaging procedures to assess myocardial contractility and perfusion.

Abstract 13735: Coronary Endothelial Dysfunction Plays Important Roles on Development of Acute Coronary Syndrome and Fatal Cardiovascular Events During Long-term Follow-up Over 10 Years

Introduction: Although coronary endothelial dysfunction is thought to affect coronary atherothrombogenic processes, there has been little practical evidence for the relationship between clinical evolution of fatal or non-fatal acute coronary syndrome (ACS) and coronary endothelial dysfunction. Hypothesis: We assessed hypothesis that coronary endothelial dysfunction has clinical impacts on development of ACS and fatal cardiovascular events. Methods: Coronary endothelial dysfunction was practically graded by the flow-mediated endothelium-dependent reactive changes in coronary artery diameter (CFMD) to infusion of adenosine triphosphate (ATP ; 50μg) into the normal left coronary artery using quantitative coronary arteriography in 150 patients with stable coronary artery disease. The enrolled patients were categorized into tertile groups according to the values of CFMD, and we prospectively followed-up major adverse clinical cardiac events including ACS and cardiovascular death. Results: For a mean follow-up period of 132 months (range; 120 to 144) with complete follow-up, the patients in the lower third with severe coronary endothelial dysfunction (Group-L) more frequently developed ACS than those in the middle third with mild coronary endothelial dysfunction (Group-M) plus those in the higher third without coronary endothelial dysfunction (Group-H) [Group-L versus Group-M plus Group-H: 15(30%) versus 5(10%) plus 0(0%), p&lt;0.001, by Kaplan-Meier analysis]. Majority of the patients who resulted in cardiovascular death belonged to Group-L, [6(12%) versus 1(2%) plus 0(0%), p=0.014]. Cox hazard proportional model analyses indicated that severe coronary endothelial dysfunction was the strong predictor for future ACS (hazard ratio=7.53, 95%confidential interval; 1.78-12.25, p&lt;0.001) and future cardiovascular death (hazard ratio=13.50, 95%confidential interval; 1.55-25.25, p=0.005). Conclusions: This is the novel and longest follow-up investigation that demonstrates coronary endothelial dysfunction plays important roles on development of ACS and fatal cardiovascular events and therefore the strategies based on status of coronary endothelial dysfunction are required to prevent major adverse ischemic cardiac events.

Influence of caffeine intake on intravenous adenosine-induced fractional flow reserve

Abstract Background This study evaluated whether caffeine abstention is required before fractional flow reserve (FFR) measurement by intravenous adenosine triphosphate (ATP) administration in Japanese patients. Methods and results This study was a subanalysis of a previously published study and a total of 208 intermediate lesions that underwent FFR measurements were enrolled for this analysis. Hyperemia was induced by continuous intravenous ATP infusion at 150μg/kg/min (IVATP150) and 210μg/kg/min (IVATP210), and by intracoronary administration of nicorandil 2mg (ICNIC2mg) as a reference standard. The degree of change in the FFR value both after IVATP150 and after IVATP210, as compared with the FFR value after ICNIC2mg was similar between the caffeine and non-caffeine groups (−0.04±0.05 vs. −0.04±0.07, and 0.00±0.02 vs. 0.01±0.02, respectively). In patients who consumed caffeine before the FFR measurement, the degree of FFR change was independent of the time interval (&amp;lt;12 hours, 12–24 hours, and 24–48 hours) between caffeine intake and catheterization both after IVATP150 and ICNIC2mg and after IVATP210 and ICNIC2mg. Conclusion When compared with the FFR value after ICNIC2mg, the degree of change in the FFR value both after IVATP150 and after IVATP210 remained similar regardless of caffeine intake. Strict caffeine abstention before intravenous ATP-induced FFR measurement may not be required in clinical practice. Funding Acknowledgement Type of funding source: None

Influence of caffeine intake on intravenous adenosine-induced fractional flow reserve

BackgroundThis study evaluated whether caffeine abstention is required before fractional flow reserve (FFR) measurement by intravenous adenosine triphosphate (ATP) administration in Japanese patients. MethodsThis study was a subanalysis of a previously published study and a total of 208 intermediate lesions that underwent FFR measurements were enrolled for this analysis. Hyperemia was induced by continuous intravenous ATP infusion at 150 μg/kg/min (IVATP150) and 210 μg/kg/min (IVATP210), and by intracoronary administration of nicorandil 2 mg (ICNIC2mg) as a reference standard. ResultsThe degree of change in the FFR value after ICNIC2mg and IVATP210 was similar between the caffeine and non-caffeine groups (0.00 ± 0.02 vs. 0.01 ± 0.02). In patients who consumed caffeine before the FFR measurement, the degree of FFR change was independent of the time interval (<12 h, 12–24 h, and 24–48 h) between caffeine intake and catheterization both after IVATP150 and ICNIC2mg and after IVATP210 and ICNIC2mg. ConclusionWhen compared with the FFR value after ICNIC2mg, the degree of change in the FFR value after IVATP210 were similar regardless of caffeine intake. Strict caffeine abstention before intravenous ATP-induced FFR measurement may not be required in clinical practice.

Feasibility of intracoronary nicorandil for inducing hyperemia on fractional flow reserve measurement: Comparison with intracoronary papaverine

BackgroundAdenosine and adenosine triphosphate (ATP) are widely used to induce hyperemia for fractional flow reserve (FFR) measurements. Caffeine attenuates their hyperemic effects, but not those of nicorandil and papaverine. No studies have systematically compared the hyperemic efficacies of nicorandil, papaverine, and ATP with and without caffeine abstention. MethodsFFRs were measured using nicorandil 2 mg (FFRNC2), nicorandil 4 mg (FFRNC4), and papaverine (FFRPAP) in 40 patients (group 1), and using nicorandil 2 mg, ATP (FFRATP), ATP plus nicorandil (FFRATP+NC2), and papaverine in 20 patients with (group 2) and in 20 patients without caffeine abstention (group 3). ResultsIn group 1, FFRNC2 and FFRNC4 did not differ (p = 0.321) and were higher than FFRPAP (p < 0.001 and p = 0.0026). Likewise, FFRNC2 was higher than FFRPAP in groups 2 (p = 0.049) and 3 (p < 0.010). In the whole group, Bland-Altman analysis showed a modest mean difference (0.015, p < 0.001) and narrow 95% limits of agreement (−0.025 and 0.056). FFRNC2 and FFRPAP strongly correlated (r = 0.975, p < 0.001). Compared with FFRPAP, FFRATP and FFRATP+NC2 did not differ in group 2 (p = 1.0 and p = 0.780), but they were higher (p = 0.002 and p = 0.02) in group 3. Adjunctive nicorandil did not decline FFR further in groups 2 (p = 0.942) and 3 (p = 0.294). ConclusionsNicorandil 2 mg is a safe and practical alternative for patients who consume caffeine-containing products before the test or have contraindications for adenosine/ATP. Increasing the nicorandil dose to 4 mg or administering adjunctive nicorandil during ATP infusions does not offer any clinical advantages compared with administering nicorandil 2 mg alone.