Intravenous Adenosine Infusion Research Articles

Radionuclide Imaging Findings in Iatrogenic Stress in Cases with Reduced Left Ventricular Ejection Fraction

Objective: This study aims to contribute to the existing literature by assisting in the selection of stress protocols for patients with reduced left ventricular ejection fraction (LVEF). We also aim to provide insights into patient follow-up based on changes in post-stress LVEF determined by echocardiography. Methods: Our retrospective study encompassed 487 patients initially diagnosed with coronary artery disease. Left ventricular function was assessed using echocardiography and myocardial perfusion scintigraphy. Among them, 250 patients with LVEF values within normal limits constituted Group-1, while 237 patients with LVEF values below 50% formed Group-2. Exercise stress testing was performed using a treadmill according to the Bruce protocol. For vasodilator stress testing, intravenous adenosine infusion at a rate of 140 μg/kg/min was administered for 6 minutes. Tc-99m-sestamibi was intravenously administered (8-12 mCi) for stress imaging and (24-36 mCi) for rest imaging. Results: The median age of all patients in the study was 64 (52-79) years, with 283 (58.1%) being male. Myocardial perfusion, assessed by myocardial perfusion scintigraphy, revealed a fixed perfusion defect in all patients. Reversible perfusion defects were observed in 172 (35.3%) patients. Among patients with reduced echo-LVEF values, those who underwent exercise stress testing showed significantly lower post-stress EF values compared to those who underwent vasodilator stress testing (35 (25-42) vs. 36 (30-47), p: 0.0005). Post-stress LVEF was notably lower in patients with reversible perfusion defects, indicating a higher rate of LVEF decrease due to stress (p: 0.0005). Conclusion: Left ventricular ejection fraction (LVEF) serves as a valuable metric for assessing left ventricular function. The findings from this study support its utility in guiding the selection of a suitable stress protocol and monitoring patients during iatrogenic cardiac stress applications.

Myocardial microvascular dysfunction in asymptomatic patients with hereditary dyslipidemia

Abstract Introduction Microvascular dysfunction underlies the pathophysiology of many cardiovascular disease (CVD) conditions and is strongly associated with future cardiovascular events. Hereditary forms of dyslipidaemia such as familial hypercholesterolemia (FH) and high levels of lipoprotein(a) [Lp(a)] are associated with premature atherosclerotic CVD but the degree of microvascular dysfunction in asymptomatic individuals is not fully explored. Purpose To evaluate the presence of microvascular dysfunction in asymptomatic individuals with the hereditary dyslipidaemias FH and high Lp(a). Methods Asymptomatic individuals without manifest CVD were recruited to four groups with 30 subjects in each; 1) controls with Lp(a)<30 nmol/L, 2) FH+Lp(a)<30 nmol/L, 3) FH+Lp(a)>125 nmol/L, and 4) isolated Lp(a)>125 nmol/L without FH. FH diagnoses were confirmed by genetic analysis. Transthoracic doppler echocardiography was used to record coronary flow in the distal part of the left anterior descending artery at rest and during hyperaemia induced by intravenous infusion of adenosine. Coronary flow reserve (CFR) was calculated by dividing hyperaemic to basal flow. Peripheral microvascular endothelial function was determined by recording reactive hyperaemia index (RHI) by peripheral arterial tonometry in the index fingers of both hands. CFR and RHI were considered impaired if values were <2.5 and <1.67, respectively. Results The four groups were balanced in age (mean 42.6±8.4 years), sex (50% females), BMI (mean 25.0±4.7 kg/m2), and smoking status (5.0% current smokers). Low-density lipoprotein cholesterol was also similar across the four groups (mean 2.8±1.1 mmol/L) with the two FH groups being on cholesterol lowering treatment while the other two were pharmacologically naïve. The three groups with hereditary dyslipidaemia had a higher proportion of subjects with impaired CFR, 30.0% in each group compared to 6.6% in controls (p=0.014) (Figure 1A). The FH+Lp(a)<30 nmol/L and FH+Lp(a)>125 nmol/L groups had received cholesterol lowering treatment for a median (inter quartile range, IQR) of 4.0 (8.0) and 11.0 (11.0) years respectively (p<0.001). In the FH+Lp(a)>125 nmol/L group individuals with normal CFR had received significantly longer treatment (p=0.006) but not in the FH+Lp(a)<30 nmol/L group (p=0.568) (Figure 1B). There were no major differences in median CFR (p=0.550) (Figure 2A) or median RHI (p=0.341) (Figure 2B) levels between the four groups. Conclusion Asymptomatic individuals with the hereditary dyslipidaemias FH and/or high Lp(a) have a higher degree of coronary microvascular dysfunction compared to healthy controls. For individuals with combined traits FH and high Lp(a), the total treatment years of cholesterol lowering is associated with preserved coronary microvascular function suggesting CFR as a potential useful non-invasive tool for cardiovascular risk-stratification in patients with hereditary dyslipidaemias.Figure 1Figure 2

Ticagrelor Treatment is Associated With Increased Coronary Flow Reserve in Survivors of Myocardial Infarction.

The pleiotropic action of ticagrelor, with effects in addition to platelet inhibition, has been shown to improve endothelial function in patients with coronary artery disease. These positive effects are possibly adenosine mediated. This study investigated the association of ticagrelor therapy and coronary artery flow reserve in survivors of myocardial infarction (MI). This was an exploratory, cross-sectional, open substudy of PROFLOW. High-risk individuals with a history of MI were identified. Coronary flow reserve (CFR) was measured non-invasively in the left anterior descending artery using transthoracic Doppler echocardiography. Coronary flow velocity was measured at rest and at maximal flow after induction of hyperaemia by intravenous infusion of adenosine at 140 μg/kg/min. Patients receiving ticagrelor (n=75) were compared with those not receiving ticagrelor (n=506), using simple and multiple linear regression models. Most patients in both groups were treated with aspirin (97% in the ticagrelor and 94% in the non-ticagrelor group). Adjustment for traditional risk factors was conducted. The mean age at study inclusion was 68.5±6.8 years, and most patients were male (81.8%). The simple linear regression analysis showed ticagrelor treatment to be significantly associated with increased CFR: ticagrelor 2.95±0.76 (mean±SD), non-ticagrelor 2.70±0.77, (coefficient 0.25; 95% CI 0.063-0.438; p=0.009). This association was significant in two of the three multiple linear regression models with increasing numbers of variables: Model 1 (0.28; 0.06-0.50; p=0.014), Model 2 (0.26; 0.03-0.48; p=0.025), and borderline significant in Model 3 (0.21; -0.01 to 0.43; p=0.058). Ticagrelor treatment was associated with increased CFR in this high-risk population. Increased CFR may be a clinically important therapeutic effect of ticagrelor in addition to platelet inhibition.

Factors Associated With Discrepancy of FFR-Based Lesion Classification Between Intracoronary Bolus and Intravenous Infusion of Adenosine

Factors Associated With Discrepancy of FFR-Based Lesion Classification Between Intracoronary Bolus and Intravenous Infusion of Adenosine

ST-Elevation Myocardial Infarction Patients with Hyperglycemia: Effects of Intravenous Adenosine

BackgroundAdmission hyperglycemia is common in subjects with acute myocardial infarction (AMI). Reperfusion therapy with primary percutaneous coronary intervention (PPCI) represents the leading therapeutic choice, in particular in ST-segment elevation myocardial infarction (STEMI). Despite this, mortality, re-hospitalizations and complications remain a relevant problem. Adenosine, a purine nucleoside, may reduce no-reflow. Therefore, whe studied the effects of intravenous infusion of adenosine in addition to primary percutaneous coronary intervention (PPCI) in hyperglycemic patients with STEMI. MethodsWe evaluated 836 patients with STEMI and admission hyperglycemia (glycemia >140 mg/dL). At the end, 399 patients were entered into the database. Patients were grouped on the basis of whether they received adenosine or not. ResultsA total of 199 patients received intravenous adenosine infusion and PPCI and 200 patients did not. Kaplan–Meier analysis demonstrated significant differences in all death, cardiac death, re-hospitalization for heart failure and for acute coronary syndrome in the adenosine treated group. ConclusionsThe effects of intravenous infusion of adenosine and PPCI on clinical outcomes are significant but we need future larger studies with larger follow-up and statistical analysis to confirm our results.

Cardiorespiratory Effects of Three Infusion Doses of Adenosine in Conscious Goats: A Preliminary Study

Adenosine (AD) has been implicated in human healthcare as an endogenous signaling nucleotide in both physiologic and pathologic states. The effects of AD on cardiorespiratory parameters in ruminants has not yet been studied. The objective of this study was to evaluate the cardiac and respiratory changes that resulted from an intravenous AD infusion in goats. Six clinically healthy adult goats weighing 28 ± 2 kg were randomly assigned to one of four treatments in a crossover design with a seven day washout period. The goats received a 0.9 % saline solution (SAL treatment) and three AD treatments (AD 50, 100 and 200) intravenously at a dose rate of 50, 100 and 200 μg/kg/min. Cardiorespiratory and key cardiac parameters were measured before the treatment (baseline), during the infusion (dInf) and at 1, 3, 5 and 10 min after each infusion was discontinued. The AD 100 produced a significant increase in HR (p = 0.001) and the AD 200 resulted in significant rises in HR (p = 0.006) and RR (p = 0.001) compared with the baseline. This study concluded that the AD infusion could trigger an increase in HR and RR in a dose-dependent manner in healthy goats.

Simplified Assessment of the Index of Microvascular Resistance.

Background To validate a simplified invasive method for the calculation of the index of microvascular resistance (IMR). Methods This is a prospective, single-center study of patients with chronic coronary syndromes presenting with nonobstructive coronary artery disease. IMR was obtained using both intravenous (IV) adenosine and intracoronary (IC) papaverine. Each IMR measurement was obtained in duplicate. The primary objective was the agreement between IMR acquired using adenosine and papaverine. Secondary objectives include reproducibility of IMR and time required for the IMR measurement. Results One hundred and sixteen IMR measurements were performed in 29 patients. The mean age was 68.8 ± 7.24 years, and 27.6% was diabetics. IMR values were similar between papaverine and adenosine (17.7 ± 7.26 and 20.1 ± 8.6, p=0.25; Passing-Bablok coefficient A 0.58, 95% CI −2.42 to 3.53; coefficient B 0.90, 95% CI −0.74 to 1.07). The reproducibility of IMR was excellent with both adenosine and papaverine (ICC 0.78, 95% CI 0.63 to 0.88 and ICC 0.93, 95% CI 0.87 to 0.97). The time needed for microvascular assessment was significantly shortened by the use of IC papaverine (3.23 (2.84, 3.78) mins vs. 5.48 (4.94, 7.09) mins, p < 0.0001). Conclusion IMR can be reliably measured using IC papaverine with similar results compared to intravenous infusion of adenosine with increased reproducibility and reduced procedural time. This approach simplifies the invasive assessment of the coronary microcirculation in the catheterization laboratory.

The non-invasive coronary flow reserve predicts exercise capacity in patients undergoing cardiac rehabilitation

The benefit of exercise on peripheral muscles is established but the exact role of the coronary microcirculation in exercise capacity after cardiac rehabilitation (CR) is unclear. Our aim was to test the relationship between non-invasive coronary flow reserve (CFR) and exercise capacity in patients undergoing CR after acute myocardial infarction (AMI). CFR was performed by transthoracic Doppler echocardiography in the left anterior descending artery 24 h after angioplasty (CFR1) and after 20 sessions of CR program (at 4 ± 1 months)(CFR2) in 60 consecutive patients (57 ± 11 years, 30% women) with an anterior AMI successfully treated by primary coronary angioplasty. CFR was performed in a modified parasternale view using intravenous adenosine infusion (0.14 mg/kg/min within 2 minutes). CR program consisted of a half hour of fractioned exercise added of a half hour session of general gymnastics and bodybuilding. To test the exercise capacity, symptom limited exercise echocardiography was performed just after the CFR2, in a semi-supine position, starting at 25 watts, with 20-25 watts increments of workload every two minutes. CFR was measured successfully in all patients, and CFR2 was significantly higher than CFR1 (2.9 ± 0.65 vs. 1.9 ± 0.4, P < 0.001). Though CFR1 was correlated to left ventricular systolic function and its improvement at follow-up (all, P < 0.01), CFR2 was independently related to exercise capacity (mean workload 100 ± 30 watts, percent maximal heart rate 83 ± 12%, no ischemia, no new wall motion abnormalities in all tests) after adjusting for age, sex, and body mass index ( r = 0.6, P < 0.01). CFR predicts exercise capacity in patients undergoing a CR program after AMI. The improvement of CFR contributes to cardiac performance.

Safety and efficacy of a hyperaemic agent, intracoronary nicorandil 4mg, for invasive physiological assessments during fractional flow reserve measurement

Abstract Background Fractional flow reserve (FFR) is one of most reliable index for the determining the functional severity coronary artery stenosis. Adenosine is the most commonly used agent for maximal hyperaemia. However, adenosine can cause chest discomfort, bronchial hyper-reactivity, and atrioventricular block. The aim of this study is to evaluate the safety and efficacy of intracoronary nicorandil as an alternative hyperaemic agent for FFR. Methods and results We enrolled consecutive 82 patients (87 lesions) who underwent FFR measurement in our center from Nov. 2018. We compared three groups; intravenous infusion of adenosine (150 μg/kg/min); and adenosine added intracoronary nicorandil 2mg; and intracoronary nicorandil 4mg. Mean FFR value was 0.83±0.09, 0.82±0.09, 0.82±0.08, There was a strong correlation among three groups (R2&amp;gt;0.9). Mean cyclic change in FFR was 0.026±0.023, 0.019±0.010, 0.016±0.014, respectively, cyclic change was smallest in intracoronary nicorandil 4mg group (vs ATP; p&amp;lt;0.001, vs ATP + nicorandil 2mg; p&amp;lt;0.001). By Wilcoxon test, mean FFR value of nicorandil 4mg was significant lower than ATP (p=0.0021), and equal to ATP + nicorandil 2mg (p=0.98). Conclusions Intracoronary nicorandil 4mg is a simple, safe, and effective way to induce steady-state hyperaemia for FFR. Figure 1 Funding Acknowledgement Type of funding source: None

Clinical implications of coronary artery morphology of patients with ischemia and non-obstructive coronary artery disease (INOCA) -An intracoronary OCT study-

Abstract Introduction Ischemia and non-obstructive coronary artery disease (INOCA), including microvascular spasm (MVS) and epicardial spasm, has recently attracted much attention, for which in vivo imaging evaluation for coronary artery morphology is warranted for better understanding of this disorder. Besides the improved diagnostic accuracy of optical coherence tomography (OCT) for coronary plaques, we have recently demonstrated its capability for in vivo visualization of coronary adventitial vasa vasorum (VV) and the enhanced VV formation in patients with epicardial spasm. Purpose We aimed to examine OCT-delineated morphological characteristics in patients with INOCA in vivo. Methods A total of 335 consecutive INOCA patients, who underwent pharmacological spasm provocation tests, lactate sampling, and OCT imaging over the entire length of the left anterior descending (LAD) coronary arteries, were enrolled at our institute over 68 months from April 2013. They were classified into 4 groups; control with non-cardiac chest pain, MVS, diffuse spasm (DS), or focal spasm (FS) (Fig. 1A). MVS was diagnosed when negative lactate extraction ratio (coronary orifice &amp;lt; coronary sinus) was detected despite the absence of epicardial spasm during the spasm provocation test. DS was defined as epicardial spasm induced in more than 2 coronary segments in LAD, and FS as epicardial spasm in one segment. Quantitative analyses for adventitial inflammation and atherosclerotic changes were performed by calculating VV density and %area stenosis (AS) on OCT (Fig. 1B, E). Furthermore, index of microcirculatory resistance (IMR), a marker of microvascular disorder with a cut-off value of ≥25, was measured during intravenous infusion of adenosine, which was then correlated with VV densities in the MVS and DS groups. Coronary plaque with a necrotic core was classified as fibroatheroma (FA), and the number of OCT frames with internal VV (IVV) in the atheroma was counted. Results VV density was significantly higher in MVS as compared with the controls (Fig. 1B). DS was most prevalent in INOCA (Fig. 1A) with highest VV density (Fig. 1B). Patients with IMR≥25 were predominantly distributed with a gradual increase in the MVS, DS, and FS groups, but none in the controls (Fig. 1C). Importantly, there was a significant positive correlation between VV densities and IMR in the MVS and DS groups (Fig. 1D). In addition, FS had the largest plaque size and showed the highest prevalence of FA and IVV (Fig. 1E–G). Conclusions These results indicate that MVS and DS are characterized by vasomotion abnormalities associated with adventitial inflammation and microvascular disorder, while FS by vulnerable atherosclerotic phenotype, suggesting that OCT may be useful for screening high-risk populations in INOCA. Figure 1 Funding Acknowledgement Type of funding source: None

Age alters peripheral vascular endothelial function without affecting coronary flow reserve in healthy volunteers

Abstract Background Age is a key risk factor contributing to vascular endothelial dysfunction. Whether the impact of ageing is uniform on various vascular beds is unknown. Endothelial function is classically evaluated by the brachial flow mediated dilatation (FMD) after a brief occlusion which mainly involves nitric oxide (NO) production. However, FMD measurement, requiring highly trained technicians, has been shown to be associated with a high degree of variability. Endothelial function could be also assessed by cutaneous iontophoresis combined with Laser Doppler. By contrast to FMD, this method is easily done by nurses and shows less variability. In parallel, myocardial imaging allows measurement of coronary flow reserve (CFR) coupled with an adenosine challenge leading to both a NO release and a modulation of potassium channels. Purpose The aim of this study was to determine the impact of ageing on vasodilation of peripheral (cutaneous) and coronary blood vessels in healthy volunteers. Methods This prospective single German center study enrolled 75 healthy non-smoking normotensive volunteers, taking no medication. They were divided into three age-subgroups (n=25/group): 18–30, 50–59, and 60–70 years (women: 54, 27 and 23%, respectively). All subjects underwent clinical and laboratory evaluation. Peripheral endothelial function, expressed in cutaneous blood flow (delta CBF), was assessed through cutaneous microcirculation dilation by the non-invasive method using Laser Doppler Speckle Contrast Imaging (LSCI, Perimed) coupled with iontophoresis to locally deliver 125 nmoles of acetylcholine (Ach). The CFR was determined by cardiac magnetic resonance (CMR) coupling with an intravenous infusion of adenosine at 140 μg/kg/min for at least 3 minutes. Results Age was associated with a 23% reduction of peripheral endothelial function (delta CBF, p=0.005) in the elderly group (60–70y) vs. the younger one (18–30y) (median: 56.4 vs. 73.6). By contrast, calculated CFR was unchanged (median: 4.1 vs. 4.2, p=0.38). No relationship was observed between peripheral endothelial function (delta CBF) and CFR (r=0.01, p&amp;gt;0.97) in healthy volunteers. Conclusion In healthy volunteers, ageing is associated with a progressive peripheral but not with a coronary vascular dysfunction. This suggests that the impact of age on endothelial dysfunction depends on different vascular beds. Peripheral endothelial function assessment does not predict coronary vascular function in healthy volunteers. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Servier

Continuous intracoronary versus standard intravenous infusion of adenosine for fractional flow reserve assessment: the HYPEREMIC trial.

The aim of this study was to evaluate the accuracy of a continuous intracoronary (IC) adenosine infusion, administered through the novel HYPEREM™IC over-the-wire microcatheter, to measure fractional flow reserve (FFR). The HYPEREMIC trial was a randomised, non-inferiority, crossover study in which patients with intermediate coronary lesions were enrolled for sequential pressure wire studies. FFR was measured using intravenous (IV) (140-180 mcg/kg/min) versus continuous non-weight-adjusted IC (360 mcg/min) adenosine. Patients were randomised and blinded to the order in which they received the adenosine, separated by a washout period. The primary endpoint was the mean hyperaemic FFR. Forty-one patients were enrolled at three UK sites between June and November 2016. The mean (standard deviation) FFR was 0.82 (±0.09) after IC versus 0.84 (±0.09) after IV adenosine. The difference of -0.02 (95% confidence interval [CI]: -0.03 to -0.01) confirmed the non-inferiority (margin <0.05) of IC to IV adenosine. Intracoronary adenosine was associated with a shorter mean time to maximal hyperaemia (difference -44 [95% CI: -59 to -29] seconds; p<0.0001). Chest discomfort was reported in 32/41 (78.0%) patients during IV adenosine versus 12/41 (29.3%) patients during IC adenosine. Continuous IC adenosine was a reliable, faster and better tolerated method of achieving maximal hyperaemia compared to IV adenosine.

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.

P5620Clinical and hemodynamic determinants of coronary flow reserve in non-obstructed coronary arteries - A patient level pooled analysis of the DEBATE and ILIAS studies

Abstract Aim Coronary Flow Reserve (CFR) is a valuable physiological index for the assessment of myocardial flow impairment due to focal or microcirculatory coronary artery disease (CAD). Coronary flow capacity (CFC) is another flow-based concept in diagnosing ischemic heart disease (IHD), based on hyperemic average peak velocity (hAPV) and CFR. We evaluated clinical and hemodynamic factors which potentially influence CFR and CFC in non-obstructed coronary arteries. Methods We analysed CFR and CFC of 396 non-obstructed vessels of patients from two large multi-center trials (DEBATE and ILIAS) with stable CAD who were scheduled for percutaneous coronary intervention (PCI). Doppler flow measurements were performed after inducing hyperemia with either intracoronary or intravenous infusion of adenosine. Results Akaike's Information Criterion (AIC) revealed the parameters age, female gender, a history of myocardial infarction, hypercholesterolemia, current or previous smoking and rate pressure product (RPP) as independent predictors in the best model of fit for CFR in an angiographically non-obstructed vessel. After multivariate regression analysis age, female gender and RPP remained as determinants of CFR in angiographically non-obstructed vessels. Subsequently, ordered logistic regression analysis revealed that age is associated with a worse CFC. Conclusion Clinical and hemodynamic parameters are associated with CFR and to a lesser extent CFC in an angiographically non-obstructed coronary artery. CFC is less sensitive to variations in clinical and hemodynamic parameters than CFR and therefore a promising tool in contemporary clinical decision making in the cardiac catheterization laboratory. Acknowledgement/Funding DEBATE: Cardiometrics INC. ILIAS: Dutch Health Insurance Board; RADI Medical Systems, Uppsala, Sweden; and Endosonics, Rancho Cordova, CA.

P6220The non-invasive coronary flow reserve predicts exercise capacity in patients undergoing cardiac rehabilitation

Abstract Background The benefit of exercise on peripheral muscles is established but the exact role of the coronary microcirculation in exercise capacity after cardiac rehabilitation (CR) is unclear. Objective: Our aim was to test the relationship between non-invasive coronary flow reserve (CFR) and exercise capacity in patients undergoing CR after acute myocardial infarction (AMI). Methods CFR was performed by transthoracic Doppler echocardiography in the left anterior descending artery 24 h after angioplasty (CFR1) and after 20 sessions of CR program (at 4±1 months) (CFR2) in 60 consecutive patients (57±11 years, 30% women) with an anterior AMI successfully treated by primary coronary angioplasty. CFR was performed in a modified parasternal view using intravenous adenosine infusion (0.14 mg/kg/min within 2 minutes). CR program consisted of a half hour of fractioned exercise added of a half hour session of general gymnastics and body building. To test the exercise capacity, symptom limited exercise echocardiography was performed just after the CFR2, in a semi-supine position, starting at 25 watts, with 20–25 watts increments of workload every two minutes. Results CFR was measured successfully in all patients, and CFR2 was significantly higher than CFR1 (2.9±0.65 vs 1.9±0.4, p&lt;0.001). Though CFR1 was correlated to left ventricular systolic function and its improvement at follow-up (all, p&lt;0.01), CFR2 was independently related to exercise capacity (mean workload 100±30 watts, percent maximal heart rate 83±12%, no ischemia, no new wall motion abnormalities in all tests) after adjusting for age, sex, and body mass index (r=0.6, p&lt;0.01). Conclusion CFR predicts exercise capacity in patients undergoing a CR program after AMI. The improvement of CFR contributes to cardiac performance.

PROspective evaluation of coronary FLOW reserve and molecular biomarkers in patients with established coronary artery disease the PROFLOW-trial: cross-sectional evaluation of coronary flow reserve.

BackgroundSurvivors of myocardial infarction (MI) are at high risk of new major adverse cardiovascular events (MACE). Coronary flow reserve (CFR) is a strong and independent predictor of MACE. Understanding the prevalence of impaired CFR in this patient group and identifying risk markers for impaired CFR are important steps in the development of personalized and targeted treatment for high-risk individuals with prior MI.MethodsPROFLOW is a prospective, exploratory, cross-sectional open study. We used information from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) to identify high-risk patients with a history of type-1 MI. We measured CFR non-invasively in a left anterior descending artery (LAD) using transthoracic Doppler echocardiography. Coronary flow velocity was measured at rest and at maximal flow after induction of hyperemia by intravenous infusion of adenosine (140 μg/kg/min). Independent predictors of CFR were assessed with multiple linear regression.ResultsWe included 619 patients. The median age was 69 (IQR 65–73), and 114 (18.4%) were women. Almost one-half of the patients, 285 (46.0%) had the multi-vessel disease, and 147 (23.7%) were incompletely revascularized. The majority were on optimal standard treatment eg ASA (93.1%), statins (90.0%), ACEI/ARB (82.6%) and beta-blockers (80.8%). The majority, 547 (88.4%) had no angina pectoris, and 572 (92.2%) were in NYHA class I. Evaluation of CFR was possible in 611 (98.7%) patients. Mean CFR was 2.74 (±0.79 (mean ± SD)). A substantial number of patients (39.7%) had CFR ≤2.5. In a multiple linear regression model age, dyslipidemia, smoking, hypertension, body mass index, incomplete revascularization, and treatment with angiotensin receptor blockers were independent predictors of CFR.ConclusionIn this high-risk group of patients with prior MI, the prevalence of impaired CFR was high. Further risk stratification with CFR in addition to traditional cardiovascular risk factors may improve predictive accuracy for future MACE in this patient population.

Comparison of hyperemic efficacy between femoral and antecubital fossa vein adenosine infusion for fractional flow reserve assessment

IntroductionIntravenous infusion of adenosine via the femoral vein is commonly used to achieve maximum hyperemia for fractional flow reserve (FFR) assessment in the catheterization laboratory. In the era of transradial access for coronary interventions, obtaining additional venous access with sheath insertion in the groin is unpractical and may be associated with a higher risk of bleeding complications. In a vast majority of cases, patients scheduled for the catheterization laboratory are already equipped with peripheral vein access in antecubital fossa vein. However, only limited data exist to support non-central vein infusion of adenosine instead of the femoral vein for FFR assessment.AimTo compare infusion of adenosine via a central versus a peripheral vein for the assessment of peak FFR.Material and methodsWe enrolled 50 consecutive patients with 125 borderline coronary lesions that were assessed by FFR using adenosine femoral and antecubital vein infusion of 140 µg/kg/min.ResultsPhysiological severity assessed with femoral vein adenosine infusion at 140 µg/kg/min was mean 0.82 ±0.09, and with antecubital vein adenosine infusion at 140 µg/kg/min was 0.82 ±0.09. The mean time from initiation of adenosine infusion to maximal stable hyperemia was significantly shorter for 140 µg/kg/min femoral vein infusion as compared to antecubital vein infusion (49 ±19 s vs. 68 ±23 s; p < 0.001). There was a strong correlation between FFR values obtained from 140 µg/kg/min femoral and antecubital vein infusion (r = 0.99; p < 0.001).ConclusionsAntecubital vein adenosine infusion achieved FFR values are very similar to those obtained using femoral vein adenosine administration. However, time to maximal hyperemia is longer with infusion via the antecubital vein.

Resting Coronary Flow Varies With Normal Cardiac Catheter Laboratory Stimuli.

Growing evidence supports physiology-guided revascularization, with Fractional Flow Reserve (FFR) the most commonly used invasive measure of coronary blood flow impairment at the time of diagnostic angiography. Recently, there has been growing interest in stenosis severity indices measured at rest, such as Instantaneous Wave Free Ratio (iFR) and the ratio of distal coronary to aortic pressure at rest (resting Pd/Pa). Their reliability may, theoretically, be more susceptible to changes in microvascular tone and coronary flow. This study aimed to assess variability of resting coronary flow with normal catheter laboratory stimuli. Simultaneous intracoronary pressure (Pd) and Doppler Average Peak Flow Velocity (APV) recordings were made at rest and following the verbal warning preceding an intravenous adenosine infusion. 72 patients undergoing elective angiography were recruited (mean age 62 years, 52.7% male) with a wide range of coronary artery disease severity (FFR 0.86 ± 0.09). Average peak flow velocity varied significantly between measurements at rest and just prior to commencement of adenosine, with a mean variation of 10.2% (17.82 ± 9.41 cm/s vs. 19.63 ± 10.44 cm/s, p < 0.001) with an accompanying significant drop in microvascular resistance (6.27 ± 2.73 mm Hg·cm-1·s-1 vs. 5.8 ± 2.92 mm Hg·cm-1·s-1, p < 0.001). These changes occurred without significant change in systemic hemodynamic measures. Whilst there was a trend for an associated change in the resting indices, Pd/Pa and iFR, this was statistically and clinically not significant (0.92 ± 0.08 vs. 0.92 ± 0.08, p = 0.110; and 0.90 ± 0.11 vs. 0.89 ± 0.12, p = 0.073). Resting coronary flow and microvascular resistance vary significantly with normal catheter laboratory stimuli, such as simple warnings. The clinical impact of these observed changes on indices of stenosis severity, particularly those measured at rest, needs further assessment within larger cohorts.

Saline-induced Pd/Pa ratio predicts functional significance of coronary stenosis assessed using fractional flow reserve.

Fractional flow reserve (FFR), assessed using distal coronary pressure/aortic pressure (Pd)/(Pa) ratio, functionally evaluates coronary stenosis. An assessment method without vasodilators would be helpful. A single intracoronary bolus of saline decreases Pd because of the speculated low-viscosity effect. We hypothesised that saline-induced Pd/Pa ratio (SPR) could functionally evaluate coronary stenosis. This study aimed to test the accuracy and utility of SPR for predicting FFR ≤0.80. In 137 coronary lesions with over 50% angiographic diameter stenosis, SPR was assessed using an intracoronary bolus of saline (2 mL/s) for five heartbeats (SPR-5) and three heartbeats (SPR-3). FFR was obtained after intravenous adenosine infusion (140 µg/kg/min). There was a strong correlation between FFR and SPR-5 or SPR-3 (R=0.941 and R=0.933, respectively). Receiver operating characteristic (ROC) curve analysis demonstrated good accuracy (86.3%) for SPR-5, with a cut-off of ≤0.84 for predicting FFR ≤0.80 (area under ROC curve 0.96, specificity 94.3, sensitivity 79.9). Thirty-three lesions (24%) were located in the "grey zone" (SPR 0.83-0.88). No complications were observed in 673 SPR measurements. SPR may accurately predict FFR and can limit adenosine use to one in four lesions. Further studies are needed to confirm the validity of SPR.

The impact of Objective Mathematical Analysis during Fractional Flow Reserve measurement: results from the OMA-FFR study

Fractional flow reserve (FFR), the reference standard for guiding coronary revascularisation, is most commonly acquired during intravenous adenosine infusion. Results may be sensitive to system- and operator-dependent variability in how pressure data are analysed and interpreted. To quantify FFR objectively, we developed a computational protocol to process the recorded pressure signals in a consistent manner. We studied the impact on lesion (re)classification and compared this with the operator-selected FFR obtained during cardiac catheterisation. The algorithm used a moving average and Fourier transformation to identify the Pd/Pa ratio at its nadir (FFRmin) and during the stable hyperaemic period (FFRstable) in <2 s with 100% repeatability, in 163 coronary stenoses (93 patients). The mean operator-selected FFR (FFRCL) was higher than FFRmin and lower than FFRstable (0.779 vs. 0.762 vs. 0.806, p=<0.01). Compared with FFRmin, FFRstable resulted in 16.5% of all lesions being reclassified, all from significant to non-significant (p<0.01). FFRCL classified lesion significance differently from both FFRstable and FFRmin (11.7% and 6.1% lesions reclassified, respectively, p<0.01). Subtle differences in how pressure data are analysed and interpreted by the operator during adenosine infusion result in significant differences in the classification of physiological lesion significance. An algorithmic analysis may be helpful in standardising FFR analysis, providing an objective and repeatable result.