Intracoronary Administration Of Adenosine Research Articles

Non-hyperaemic coronary flow velocity acceleration indices correlate with hyperaemic microvascular resistance in patients with INOCA

Abstract Background Coronary microvascular dysfunction (CMD) is associated with an overall worse prognosis. While the diagnosis and endo-typing of CMD currently rely on hyperaemic physiological indices, the search for accurate non-hyperaemic techniques continues. Flow velocity acceleration pattern is mechanistically associated with changes in shear stress, endothelial function, arterial stiffness and pressure in pulsatile flow systems (1-3). Purpose We aim to interrogate whether resting flow velocity acceleration indices correlate with hyperaemic microvascular resistance (HMR) in patients with Ischemia and no obstructive coronary artery disease (INOCA). Methods In 21 Patients with INOCA (all of whom had presented with typical angina pectoris, had no significant epicardial stenoses but positive myocardial perfusion scan test for ischemia) invasive physiological assessment was performed by means of intracoronary Doppler. Hyperaemia was induced with intracoronary adenosine administration. Coronary flow reserve (CFR) and HMR were calculated per their definitions. Flow velocity acceleration indices were derived from the first derivative of the averaged resting flow velocity waveforms with respect to time. We have defined 6 wave peaks of interest in all patients (peak diastolic acceleration (initial prominent peak with ventricular relaxation, referred as A), early diastolic deceleration (B), early re-acceleration wave (C), peak presystolic deceleration (seen just before initial systolic acceleration peak, J), initial systolic acceleration peak (X) and pre-diastolic deceleration nadir (Z)) and calculated the ratios between them as well as adjusted them with respect to resting mean flow velocity (Figure 1). Results The mean age was 59 ± 8 years and the majority of the study group was female (%81). Cardiovascular risk factors were common amongst the study group.All patients had CFR < 2.5. Mean CFR and HMR were 2.05 ± 0.32 and 2.20 ± 0.60 mmHg.cm.sec-1 respectively. Raw C peak magnitude was significantly correlated with APVh (rho:-0.457 p:0.037) and HMR (rho:0.612 p:0.004). Adjusting the C magnitudes with APVb at patient level yielded better correlations (APVh rho:-0.496 p:0.022 ; HMR:0.642 p:0.002). The ratio between diastolic reacceleration peak (C) and presystolic peak deceleration (J), C/J , adjusted with the APVb ((C/J)/APVb) showed the most pronounced correlation with HMR (rho: 0.758 p < 0.001) (unadjusted C/J – HMR rho: 0.718 p<0.001)(Figure 2). Conclusion(s) Acceleration characteristics of resting coronary flow velocity correlate with hyperaemic microvascular resistance indicating structurally impaired coronary microcirculation, hence their utilisation may aid developing non-hyperaemic physiological markers for coronary microvascular dysfunction in patients with INOCA.Derived Acceleration WaveformsCorrelations between HMR and C/J Ratio

LINKS BETWEEN CORONARY MICROVASCULAR DYSFUNCTION AND EVIDENCE OF HEART FAILURE WITH PRESERVED EJECTIVE FRACTION

BackgroundIt has been hypothesized that coronary microvascular dysfunction (CMD) may be associated with the development of myocardial abnormalities associated with heart failure with preserved ejective fraction (HFpEF). Making a diagnosis of HFpEF is aided by exercise right heart catheterization (RHC) based on an abnormal pulmonary artery wedge pressure (PAWP) response during exercise. An exercise-associated increase in PAWP adjusted for the change in cardiac output (ΔPAWP/ΔCO) greater than 2 mmHg/L/min is a clinical predictor for HF outcomes and predicts exercise capacity. Although there is speculation that CMD may play a role in the development of early HFpEF, there is limited evidence that directly links CMD as assessed by an invasive coronary physiology study (ICPS) with HFpEF as measured by an exercise RHC.Methods and ResultsThis study was an exploratory, retrospective cohort analysis. The study population included patients experiencing unexplained cardiovascular symptoms including chest pain and dyspnea who were referred to our institution for a RHC with exercise who had also undergone an ICPS. Patients were classified hemodynamically based on a ΔPAWP/ΔCO ≤ or > 2 with exercise. Coronary physiology interventions included Doppler flow assessment after administration of intracoronary adenosine and acetylcholine, where coronary flow reserve (CFR) and the index of microvascular resistance (IMR) were quantified during hyperemia. To date, we identified a cohort of 20 patients who met the study’s inclusion criteria. Of these, 19 completed a RHC exercise study from which 9/19 (47%) had a ΔPAWP/ΔCO > 2. Characteristics of the patients are shown in Table 1. The mean index of microvascular resistance (IMR) for patients with abnormal exercise hemodynamics was 32.6 versus 20.9 (p=0.08).Conclusion BackgroundIt has been hypothesized that coronary microvascular dysfunction (CMD) may be associated with the development of myocardial abnormalities associated with heart failure with preserved ejective fraction (HFpEF). Making a diagnosis of HFpEF is aided by exercise right heart catheterization (RHC) based on an abnormal pulmonary artery wedge pressure (PAWP) response during exercise. An exercise-associated increase in PAWP adjusted for the change in cardiac output (ΔPAWP/ΔCO) greater than 2 mmHg/L/min is a clinical predictor for HF outcomes and predicts exercise capacity. Although there is speculation that CMD may play a role in the development of early HFpEF, there is limited evidence that directly links CMD as assessed by an invasive coronary physiology study (ICPS) with HFpEF as measured by an exercise RHC. It has been hypothesized that coronary microvascular dysfunction (CMD) may be associated with the development of myocardial abnormalities associated with heart failure with preserved ejective fraction (HFpEF). Making a diagnosis of HFpEF is aided by exercise right heart catheterization (RHC) based on an abnormal pulmonary artery wedge pressure (PAWP) response during exercise. An exercise-associated increase in PAWP adjusted for the change in cardiac output (ΔPAWP/ΔCO) greater than 2 mmHg/L/min is a clinical predictor for HF outcomes and predicts exercise capacity. Although there is speculation that CMD may play a role in the development of early HFpEF, there is limited evidence that directly links CMD as assessed by an invasive coronary physiology study (ICPS) with HFpEF as measured by an exercise RHC. Methods and ResultsThis study was an exploratory, retrospective cohort analysis. The study population included patients experiencing unexplained cardiovascular symptoms including chest pain and dyspnea who were referred to our institution for a RHC with exercise who had also undergone an ICPS. Patients were classified hemodynamically based on a ΔPAWP/ΔCO ≤ or > 2 with exercise. Coronary physiology interventions included Doppler flow assessment after administration of intracoronary adenosine and acetylcholine, where coronary flow reserve (CFR) and the index of microvascular resistance (IMR) were quantified during hyperemia. To date, we identified a cohort of 20 patients who met the study’s inclusion criteria. Of these, 19 completed a RHC exercise study from which 9/19 (47%) had a ΔPAWP/ΔCO > 2. Characteristics of the patients are shown in Table 1. The mean index of microvascular resistance (IMR) for patients with abnormal exercise hemodynamics was 32.6 versus 20.9 (p=0.08). This study was an exploratory, retrospective cohort analysis. The study population included patients experiencing unexplained cardiovascular symptoms including chest pain and dyspnea who were referred to our institution for a RHC with exercise who had also undergone an ICPS. Patients were classified hemodynamically based on a ΔPAWP/ΔCO ≤ or > 2 with exercise. Coronary physiology interventions included Doppler flow assessment after administration of intracoronary adenosine and acetylcholine, where coronary flow reserve (CFR) and the index of microvascular resistance (IMR) were quantified during hyperemia. To date, we identified a cohort of 20 patients who met the study’s inclusion criteria. Of these, 19 completed a RHC exercise study from which 9/19 (47%) had a ΔPAWP/ΔCO > 2. Characteristics of the patients are shown in Table 1. The mean index of microvascular resistance (IMR) for patients with abnormal exercise hemodynamics was 32.6 versus 20.9 (p=0.08). Conclusion

Administration of intracoronary adenosine before stenting for the prevention of no-reflow in patients with ST-elevation myocardial infarction

Objectives: No-reflow phenomenon during the primary percutaneous intervention (PCI) for ST-elevation myocardial infarction (STEMI) is accompanied by a poor clinical outcome and mortality. We aimed to determine the effect of intracoronary adenosine in preventing the no-reflow phenomenon, as detected by three different methods, in patients who underwent primary (PCI). Design. In this single-blinded randomized controlled trial, patients with acute STEMI who presented to our center and underwent primary PCI were randomized to the intervention group who received intracoronary adenosine before stenting or the control group who received the standard treatment. No-reflow phenomenon was detected using thrombolysis in myocardial infarction (TIMI) flow grade, TIMI frame count, and myocardial blush grade (MBG). The incidence of the no-reflow phenomenon was then compared between the intervention and control groups. Results. The adenosine group consisted of 110 patients (age = 57 ± 11 years; 92 (84%) male) while 118 patients were in the control group (age = 59 ± 12 years; 89 (75%) male). There was no difference between the study groups in baseline characteristics. The frequency of no-reflow phenomenon was lower in the adenosine group as assessed by TIMI flow grade (15 [14%] vs. 41 [35%]), MBG (23 [21%] vs. 63 [53%]) and TIMI frame count (16 [14%] vs. 50 [42%]) (p < .001 for all). This effect remained significant after adjustment for confounding variables. Conclusion. Intracoronary adenosine could effectively prevent the no-reflow phenomenon in STEMI patients who underwent primary PCI.

546 Antegrade in-stent CTO recanalization

Abstract Methods and results A 64-year-old man with prior PCI and stent of proximal LAD due to an anterior ST-elevation myocardial infarction (STEMI) presented with exertional angina (CCS III), despite optimal medical therapy (OMT). The echocardiogram showed a dilatated left ventricle with anterior and apical akinesia and a severely reduced left ventricle ejection fraction. Coronarography was performed and a chronic total occlusion was found at the proximal edge of the stent previously implanted in the proximal LAD, with a thin tapered entry (J-CTO score 1). Moderate angiographic disease was present in the circumflex (LCX) and in the right coronary artery (RCA). Interventional collaterals were absent. Dobutamine stress echocardiogram was performed to unmask myocardial viability. Indeed, during intravenous Dobutamine administration, we registered an increase in the left ventricle function, whereas only apex remained still akinetic. Accordingly, the patient underwent LAD CTO PCI using a 7 Fr EBU 4.0 guiding catheter, via right femoral artery access. The RCA ostium was engaged with a 6 Fr Judkins right 4.0 guiding catheter, via right radial artery access. Antegrade wire escalation technique was attempted. Due to scarce support, a 7 Fr Guidion guiding catheter extension and a Corsair microcatheter were placed in the proximal LAD. Antegrade crossing was very difficult due to intrastent high plaque burden. The occlusion was crossed with an Asahi Conquest Pro 9 guidewire. Subsequently, an Asahi Gaia third guidewire was advanced through the intrastent segment and then in the distal part of LAD. The advance of microcatheter was challenging but successfully achieved taking advantage of the low profile, high torqueability and trackability of the Asahi Corsair Pro microcatheter. Microcatheter tip injection confirmed the correct position in the vessel’s true lumen. An Asahi Grand Slam guidewire was placed in the distal LAD to provide extra support for delivery of interventional devices. The lesion was pre-dilated with progressively larger balloon, starting from a 1.1 mm diameter semi-compliant over-the-wire balloon (OTW). Two stents were implanted with a minimal overlap at the distal edge of the proximal stent (Resolute Onyx 3.0 × 38 mm and 2.5 × 24 mm). The result was improved with stents high-pressure post-dilatation and with selective intracoronary adenosine and nitroglycerin administration with final Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow. The total amount of contrast media used was 210 ml. The total procedure time was with 125 min with 45 min of fluoroscopy. No complications occurred. Conclusions CTO PCI still represents one of the most challenging subsets of coronary interventions despite the improvement in technology and techniques. Although data regarding percutaneous PCI CTO are still inconsistent, successful CTO recanalization has been associated with relief of angina and ischemia-related dyspnoea (Werner at al., 2018). In stable patients CTO PCI has been associated with a lower risk of death, stroke, and coronary artery bypass grafting and less recurrent angina pectoris in some registry studies (Christakopoulos et al., 2015). Additionally, CTO PCI increased left ventricle function in a subgroup of patients with LAD CTO (Henriques et al., 2016). Conversely, randomized multicentre failed to demonstrate a superiority of CTO PCI medical to OMT in terms of major adverse cardiac events (MACE) and all-cause mortality.

Machine learning aids clinical decision making in patients presenting with angina and non-obstructive coronary artery disease

Abstract Background Coronary microvascular dysfunction (CMD) is associated with an increased risk of cardiovascular morbidity and mortality. The current gold-standard comprehensive assessment of CMD is through a limited-access invasive catheterization lab procedure. Purposes We aimed to develop a point-of-care tool to assist clinical guidance in patients presenting with chest pain and/or an abnormal functional stress test and with non-obstructive coronary artery disease (NOCAD) based on demographic data and resting ECG waveforms. Methods This study included 1,893 NOCAD patients (&amp;lt;50% angiographic stenosis) who underwent CMD evaluation as well as a standard ECG up to 1 year prior. Microvascular endothelial-independent dysfunction was defined by abnormal coronary flow reserve (CFR) &amp;lt;2.5 in response to intracoronary adenosine administration. Microvascular endothelial dysfunction was defined by a maximal percent increase in coronary blood flow (%ΔCBF) ≤50% in response to intracoronary acetylcholine infusion. We trained algorithms to distinguish between the following outcomes: CFR ≤2.5, ΔCBF (%) ≤50, and the combination of both. Two classes of algorithms were trained, one depending on ECG waveforms as input, and another using tabular style clinical data. The optimal classification threshold was determined by maximizing Youden's J. Results Mean age was 51±12 years and 66% were females (n=1,257). AUC values ranged from 0.49 to 0.67 for all the outcomes. The best performance in our analysis was for the outcome CFR ≤2.5 via logistic regression on tabular variables. AUC and accuracy were 0.67 and 60%; while sensitivity and NPV were 70% and 85%. Specificity and PPV were 56% and 0.35%. When decreasing the threshold from the “optimal” one (24%) to 15%, sensitivity and NPV increased to 92% and 90% respectively, while specificity and PPV decreased to 25% and 29% respectively (Figure 2). Conclusion An AI-enabled algorithm may be able to assist clinical guidance by ruling out CMD in patients presenting with chest pain and/or an abnormal functional stress test. This algorithm needs to be prospectively validated in different cohorts. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The James Nutter Family &amp; Maria Long Family Fellowship in Cardiovascular Research and Mayo Clinic Figure 1Figure 2

Impact of Intracoronary Adenosine Administration During Primary PCI

Impact of Intracoronary Adenosine Administration During Primary PCI

COMPARISON OF INTRACORONARY VERAPAMIL VS ADENOSINE FOR RESTORATION OF CORONARY BLOOD FLOW POST PERCUTANEOUS CORONARY INTERVENTION (PCI) IN PATIENTS WITH NO-REFLOW

Objective: To determine the efficacy of intracoronary verapamil vs adenosine in restoration of coronary blood flow, post PCI in patients with No-Reflow.&#x0D; Study Design: Double blind (patient/operator blind) randomized control trial.&#x0D; Place and Duration of Study: Cath lab of AFIC &amp; NIHD Rawalpindi, from Feb 2019 to Aug 2019.&#x0D; Methodology: A total of ninety (n=90) patients of either gender between age 25-80 years of age who underwent angioplasty for STEMI/NSTEMI demonstrating No-Reflow (thrombolysis in myocardial infarction 0,1,2) post PCI were enrolled and were randomized into two groups. Group A received verapamil 500 µg in 10 ml heparinized saline, given slowly over 1 minute and group B received adenosine 60 µg in 10 ml of heparinized saline, given quickly. After the administration of both drugs repeat angiogram was carried out and thrombolysis in Myocardial Infarction flow was assessed. Restoration of blood flow was defined as achievement of thrombolysis in myocardial infarction 3 grade.&#x0D; Results: Efficacy (restoration of thrombolysis in Myocardial Infarction grade 3) was better with intracoronary administration of verapamil when compared with intracoronary administration 2 of adenosine (84.4% vs 80%). The difference was, however, not statistically significant (p=0.581).&#x0D; Conclusion: Efficacy (restoration of thrombolysis in myocardial infarction grade 3) was not statistically significant between intracoronary administration of verapamil and adenosine in no-reflow cases after PCI in patients with STEMI/NSTEMI.

Coronary flow reserve can explain some of FFR and iFR discrepancies. Results from international, multicenter and prospective trial

Abstract Background The trial collected prospective data from physiology measurements of borderline lesions in five Czech, one Japan and one Argentinian cathlabs. The main purposes were to analyze diagnostic agreement between FFR (fractional flow reserve) and iFR (instantaneous wave free ratio) examinations and to find possible explanations for discrepant results. Methods FFR and iFR examinations were analyzed using Philips-Volcano console and coronary flow reserve (CFR) was analyzed by using Combomap machine Philips-Volcano. Hyperemia for FFR and CFR measurements was induced by intracoronary administration of adenosine. We used CFR as a truth for comparison between FFR and iFR, because CFR has higher impact on patients prognosis than pressures indices. Results Data were collected from February 2016 to June 2019 and the database includes 1.789 examinations from 1.492 patients (282 of them, 15.8%, with ACS). CFR were measured in 343 lesions in 293 patients. (ACS 31.2%). Overall correlation between FFR and iFR is high (R=0.86 p&amp;lt;0.0001). The FFR/iFR discrepancy occurred in 84 measurements (24.5%), more frequently it was FFRp (positive) / iFRn (negative) type of discrepancy (65, 18.9%) compare to FFRn/iFRp (19, 5.5%) one. There was no difference in occurrence of FFR/iFR discrepancy in stable patients and ACS ones (25.1%vs. 22.4%, p=0.59). The CFR correlated better with iFR than with FFR (R=0.56, p&amp;lt;0.0001 vs. R= 0.36, p&amp;lt;0.0001) (see table). In lesions with FFRp/iFRn type of discrepancy we found substantially higher CFR value compared to FFR/iFR agreement group (2.4±0.7 vs. 1.5±0.5, p&amp;lt;0.0001). Unlike to FFRn/iFRp discrepancy, where CFR value was similar with agreement group (1.4±0.1 vs. 1.5±0.1, p=0.25) Conclusion The FFR/iFR discrepancy occurred in almost one quarter of examinations. Correlation between CFR and iFR is better than between CFR and FFR. High flow is probably one of the main reason for FFRp/iFRn type of discrepancy. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Czech Health Research Council

An intact animal model for the assessment of coronary blood flow regulation "Coronary blood flow regulation".

Coronary blood flow adapts to metabolic demand ("metabolic regulation") and remains relatively constant over a range of pressure changes ("autoregulation"). Coronary metabolic regulation and autoregulation are usually studied separately. We developed an intact animal experimental model to explore both regulatory mechanisms of coronary blood flow. Coronary pressure and flow‐velocities were measured in four anesthetized and closed‐chest pigs using an intracoronary Doppler wire. Metabolic regulation was assessed by coronary flow reserve defined as the ratio between the maximally vasodilated and the basal flow, with hyperemia achieved using intracoronary administration of adenosine (90 µg) or bradykinin (10–6 M) as endothelium‐independent and ‐dependent vasodilators respectively. For both vasodilators, we found a healthy coronary flow reserve ≥ 3.0 at baseline, which was maintained at 2.9 ± 0.2 after a 6‐hr period. Autoregulation was assessed by the lower breakpoint of coronary pressure‐flow relationships, with gradual decrease in coronary pressure through the inflation of an intracoronary balloon. We found a lower limit of autoregulation between 42 and 55 mmHg, which was stable during a 6‐hr period. We conclude that this intact animal model is adequate for the study of pharmacological interventions on the coronary circulation in health and disease, and as such suitable for preclinical drug studies.

Effect of intracoronary adenosine on ergonovine-induced vasoconstricted coronary arteries.

This study aimed to evaluate the effect of adenosine on epicardial coronary artery diameter during ergonovine provocation testing. A total of 158 patients who underwent an ergonovine provocation test with intracoronary adenosine injection between 2011 and 2014 were selected. Patients were divided into four groups based on the severity of percent diameter stenosis following intracoronary ergonovine administration: Group 1, induced spasm < 50%; Group 2, 50-89%; Group 3, 90-99%; and Group 4, total occlusion. Spasm positivity was observed in 44 (27.8%) cases in the study population (mean age, 57.4 ± ± 10.7 years). Intracoronary adenosine increased the diameter of the ergonovine-induced epicardial artery by 0.51 ± 0.31 mm, 0.73 ± 0.39 mm, 0.44 ± 0.59 mm, and 0.01 ± 0.04 mm in Groups 1, 2, 3, and 4, respectively. Subsequent administration of nitroglycerin further increased vessel diameter by 0.49 ± 0.28 mm, 0.93 ± 0.68 mm, 2.11 ± 1.25 mm, and 2.23 ± 0.69 mm in Groups 1, 2, 3, and 4, respectively. The ratios of adenosine-induced diameter to reference diameter were significantly lower in patients with spasm positive results (0.68 [0.59-0.76] vs. 0.18 [0.00-0.41], p < 0.001 in the study population; 0.60 [0.54-0.67] vs. 0.40 [0.27-0.44], p < 0.001 in Group 2) with the best cut-off value of 0.505 (sensitivity 0.955, specificity 0.921). Intracoronary administration of adenosine dilated the ergonovine-induced vasoconstricted epicardial coronary artery. The ratio of adenosine-induced diameter to reference diameter was significantly lower in patients with spasm positive results.

Comparison of sodium nitroprusside and adenosine for fractional flow reserve assessment: a systematic review and meta-analysis

ABSTRACTBackground: Fractional flow reserve (FFR) has become a useful tool in the assessment of physiological significance of coronary artery stenosis (CAS), and Adenosine (ADE) is associated with a high incidence of transient side effects. Sodium nitroprusside (NPS) has been proposed as an alternative vasodilator agent. A meta-analysis of studies comparing ADE and NPS for FFR assessment in the same coronary lesions was performed.Methods: Authors searched for articles comparing NPS and ADE for FFR assessment in intermediate coronary lesions published through January 2018. The following keywords were used: ‘fractional flow reserve’ AND ‘nitroprusside’. Data were summarized using weighted mean differences for paired data.Results: Seven studies were identified comprising 342 patients and 401 lesions. Four studies evaluated intravenous ADE and 3 studies intracoronary ADE administration. Weighted means FFR values obtained with ADE and NPS were 0.8411 and 0.8445, respectively (weighted mean difference: 0.00, 95% confidence interval (CI) −0.01 to 0.01, p = 0,548). Adverse events were significantly reduced with IC NPS (RR = 0.08, 95%CI 0.02–0.30, P < 0.0001).Conclusions: NPS produces similar FFR measurements compared to ADE with a significant reduction in adverse effects. These results may support its use as a suitable alternative to ADE for FFR assessment.

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

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

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

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

Angiographic and hemodynamic effects of myocardial bridge during supine bicycle exercise

The aim of this study was to evaluate the hemodynamic effect of physiological exercise during coronary angiogram with Pd/Pa, end diastolic Pd/Pa and FFR measurements in symptomatic patients with myocardial bridge (MB). We included all consecutive patients with symptomatic MB without significant coronary artery disease between 2014 and 2015. Coronary angiogram was performed with radial approach and supine bicycle set on the table. A pressure wire was placed downstream the MB. Systolic compression was assessed with quantitative coronary angiography. The exercise protocol started at 50 watts and increased by steps of 15 watts every 2 minutes. After exercise, intracoronary nitrates was used and finally intracoronary adenosine administration for FFR measurement. 9 symptomatic patients with an isolated LAD MB were included. Patients reached 73% ± 10% of maximum heart rate. No complication occurs during this protocol. FFR was significantly lower compared to rest, peak exercise and after nitrates ( P < 0.05 for all) (A). Compression during systole significantly increases in peak exercise compare to rest respectively 78% versus 37% ( P = 0.003) (B). However, Pd/Pa values and end diastolic Pd/Pa did not significantly changed at rest compared to peak exercise respectively 0.90 versus 0.87 ( P = 0.21) for Pd/Pa, and 0.85 versus 0.82 ( P = 0.35) for end diastolic Pd/Pa (C). During the protocol, no significant difference of Pd/Pawas observe between rest, peak exercise and after nitrates ( P > 0.05 for all) ( Fig. 1 ). We reported invasive hemodynamic assessment of MB during physiological exercise conditions with supine bicycle. MB increase systolic compression during exercise with a preserved hemodynamic indices.

21 A comparison of coronary haemodynamics in 40cc versus 50cc intra-aortic balloon pumps

IntroductionRandomised trials have questioned the benefit of intra-aortic balloon pump (IABP) counterpulsation in high-risk PCI and shock. A larger capacity balloon has been introduced into routine clinical practice that has...

Meta-Analysis of Head-to-Head Comparison of Intracoronary Versus Intravenous Adenosine for the Assessment of Fractional Flow Reserve

Intravenous (IV) infusion of adenosine represents the gold standard for measuring fractional flow reserve (FFR). However, IV adenosine is more expensive and time-consuming compared with intracoronary (IC) boluses of adenosine. We conducted a meta-analysis of studies comparing IC with IV adenosine for FFR assessment in the same coronary lesions. We searched for studies comparing IC with IV adenosine and reporting absolute FFR values or rate of abnormal FFR for both routes. Prespecified subgroup analysis was performed to appraise studies using low-dose (<100μg) or high-dose IC adenosine (≥100μg). We retrieved 11 studies amounting to 587 patients and 621 lesions. Six studies evaluated low-dose IC boluses (15 to 80μg) and 5 studies high-dose boluses (120 to 600μg). Absolute FFR values were slightly, yet significantly lower with IV adenosine compared with IC adenosine (mean difference 0.02, 95% confidence interval [CI] 0.00 to 0.03, p= 0.02). This difference, however, did not translate into a significant difference in the rate of abnormal FFR between IC and IV adenosine (hazard ratio 0.93, 95% CI 0.76 to 1.13, p= 0.57); moreover, no statistically significant difference was observed between low-dose and high-dose IC adenosine subgroups. Adverse events were less frequent with IC adenosine compared with IV adenosine (risk ratio 0.17, 95% CI 0.07 to 0.43, p <0.001). In conclusion, IC administration of adenosine, although inducing a slightly lower amount of hyperemia compared with IV infusion of adenosine, yields a similar diagnostic accuracy in identifyinghemodynamically significant coronary stenosis and is better tolerated by the patients.

Temporal dissociation between the minimal distal-to-aortic pressure ratio and peak hyperemia during intravenous adenosine infusion.

The present study sought to compare the temporal relation between maximal coronary flow (peak hyperemia) and minimal coronary-to-aortic pressure ratio (Pd/Pa) for intracoronary (IC) and intravenous (IV) adenosine administration. Peak hyperemia is assumed to coincide with the minimal Pd/Pa value. However, this has not been confirmed for systemic hemodynamic variations during IV adenosine infusion. Hemodynamic responses to IV and IC adenosine administration were obtained in 12 patients (14 lesions) using combined IC pressure and flow velocity measurements. A fluid dynamic model was used to predict the change in Pd/Pa for different stenosis severities and varying Pa Hemodynamic variability during IV adenosine hyperemia was greater than during IC adenosine, as assessed by the coefficient of variation. During IV adenosine, flow velocity peaked 28 ± 4 (SE) s after the onset of hyperemia, while Pd/Pa reached a minimum (0.82 ± 0.01) 22 ± 7 s later (P < 0.05), when Pa had declined by 6.1% and hyperemic velocity by 4.5% (P < 0.01). Model outcomes corroborated the role of variable Pa in this dissociation. In contrast, maximal flow and minimal Pd/Pa coincided for IC adenosine, with IV-equivalent peak velocities and a higher Pd/Pa ratio (0.86 ± 0.01, P < 0.01). Hemodynamic variability during continuous IV adenosine infusion can lead to temporal dissociation of minimal Pd/Pa and peak hyperemia, in contrast to IC adenosine injection, where maximal velocity and minimal Pd/Pa coincide. Despite this variability, stenosis hemodynamics remained stable with both ways of adenosine administration. Our findings suggest advantages of IC over IV adenosine to identify maximal hyperemia from pressure-only measurements.NEW & NOTEWORTHY Systemic hemodynamic variability during intravenous adenosine infusion produces substantial temporal dissociation between peak hyperemia appraised by coronary flow velocity and the minimal distal-to-aortic pressure ratio commonly used to determine functional stenosis severity. This dissociation was absent for intracoronary adenosine administration and tended to be mitigated in patients receiving Ca2+ antagonists.

The REFLO-STEMI (REperfusion Facilitated by LOcal adjunctive therapy in ST-Elevation Myocardial Infarction) trial: a randomised controlled trial comparing intracoronary administration of adenosine or sodium nitroprusside with control for attenuation of microvascular obstruction during primary percutaneous coronary intervention

BackgroundMicrovascular obstruction (MVO) predicts short- and longer-term outcomes following primary percutaneous coronary intervention (PPCI) treatment of ST-elevation myocardial infarction (STEMI). The evidence base supporting the role of adenosine and sodium nitroprusside (SNP), the most evaluated adjunctive therapies aimed at attenuating MVO and infarct size, remains weak as the trials involved have had variable end points and used differing drug doses and modes of delivery.ObjectiveTo determine whether intracoronary administration of adenosine or SNP following thrombus aspiration reduces infarct size and/or MVO measured by cardiac magnetic resonance (CMR) imaging in patients undergoing PPCI within 6 hours of onset of STEMI.DesignMulticentre, prospective, parallel, randomised controlled and open-label trial with blinded end point analysis.SettingFour high-volume UK PPCI centres.ParticipantsPatients with STEMI undergoing PPCI with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0/1 in the infarct-related artery and no significant bystander coronary artery disease on angiography.InterventionsParticipants were anticoagulated with bivalirudin and allocated by an automated 24-hour telephone randomisation service to one of three groups: (1) standard PPCI (control), (2) PPCI with adjunctive adenosine 1–2 mg or (3) PPCI with adjunctive SNP 250 µg. The study drugs were delivered intracoronary immediately following thrombus aspiration and again following successful stenting.Main outcome measuresThe primary outcome was infarct size (% total left ventricular end-diastolic mass; %LVM) measured by CMR imaging undertaken 48–96 hours post PPCI. Secondary outcome measures included MVO (hypoenhancement within the infarct core) on CMR imaging, electrocardiographic and angiographic markers of microvascular perfusion and major adverse cardiac events (MACEs) during a median of 6 months’ follow-up. The study aimed to recruit 240 patients (powered at 80% to detect a 5% absolute reduction in infarct size).ResultsThe trial completed recruitment in April 2014 having randomised 247 patients (standard PPCI group,n = 86; PPCI + adenosine group,n = 82; PPCI + SNP group,n = 79). In total, 79% of participants were male and the mean ± standard deviation age of participants was 59.3 ± 12.3 years. CMR imaging was completed in 197 (80%) patients (standard PPCI,n = 65; PPCI + adenosine,n = 63; PPCI + SNP,n = 69) for the primary outcome. There was no significant difference in infarct size [%LVM, median, interquartile range (IQR)] between the adenosine group (10.1, 4.7–16.2), the SNP group (10.0, 4.2–15.8) and the control group (8.3, 1.9–14.0) (p = 0.062 andp = 0.160 vs. control, respectively). MVO (%LVM, median, IQR) was similar across the groups [1.0, 0.0–3.7 (p = 0.205) and 0.6, 0.0–2.4 (p = 0.244) for adenosine and SNP, respectively, vs. 0.3, 0.0–2.8 for the control]. Using per-protocol analysis, infarct size (%LVM) was increased in adenosine-treated patients compared with control patients (12.0 vs. 8.3;p = 0.031). Increased left ventricular volume and reduced left ventricular ejection fraction were also observed in the adenosine arm. There was a significant increase in MACEs in patients undergoing adenosine-facilitated PPCI compared with control patients, driven by heart failure, at 30 days [hazard ratio (HR) 5.39, 95% confidence interval (CI) 1.18 to 24.60;p = 0.04] and 6 months (HR 6.53, 95% CI 1.46 to 29.2;p = 0.01) post randomisation.ConclusionsHigh-dose intracoronary adenosine and SNP during PPCI did not reduce infarct size or MVO measured by CMR imaging. Furthermore, adenosine may adversely affect mid-term clinical outcome and should not be used during PPCI to prevent reperfusion injury.Trial registrationClinicalTrials.gov NCT01747174 and EudraCT 2010–023211–34.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

Evaluation of Short- and Long-Term Efficacy of Combined Intracoronary Administration of High-Dose Adenosine and Tirofiban during Primary Percutaneous Coronary Intervention.

To assess the influence of combined intracoronary application of high-dose adenosine and tirofiban in primary percutaneous coronary intervention (PCI) on clinical events and cardiac function. Our study evaluated consecutive patients with acute ST-segment elevation myocardial infarction undergoing primary PCI, who were randomly divided into adenosine group (n = 130) and control group (n = 128). Combined with thrombus aspiration and then intracoronary tirofiban, the adenosine group received intracoronary adenosine (2 mg) through the aspiration catheter 2 times. After thrombus aspiration and stenting of the infarct- related artery, the control group received placebo. The primary endpoint of our investigation was major adverse cardiac events (MACE) at the 1-year and 3-year marks. The secondary endpoint comprised left ventricular remodeling (LVR) at 6 months, myocardial blush grade (MBG), thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) after PCI. Our study found that TIMI flow grade post-PCI did not differ significantly between the 2 groups, while CTFC favored the adenosine-treated patients (21.6 ± 6.5 vs. 25.1 ± 7.8, p = 0.001). Although the adenosine group achieved a higher rate of MBG 3 (45.1% vs. 32.0%, p = 0.035) and MBG 2-3 (76.2% vs. 62.3%, p = 0.018) than the control group, the incidences of MACE at 1 year (20.0% vs. 25.0%, p = 0.373) and 3 years (26.9% vs. 32.0%, p = 0.413) were comparable. LVR occurred in 23.1% (27/117) of adenosine-treated patients and in 29.8% (43/114) of the controls (p = 0.296). Intracoronary administration of high-dose adenosine combined with intracoronary tirofiban and thrombus aspiration may further improve myocardial perfusion after primary PCI.

Impact of Intracoronary Adenosine on Myonecrosis in Patients with Unstable Angina Pectoris Undergoing Percutaneous Coronary Intervention.

In this study, we aimed to investigate the impact of prophylactic intracoronary adenosine administered during percutaneous coronary intervention (PCI) due to unstable angina pectoris on myonecrosis by measuring post-procedural levels of cardiac troponin I (cTnI) and creatine kinase-myocardial band (CK-MB). A total of 122 patients with unstable angina undergoing PCI were included in this single-center, double-blind, randomized study. The patients were randomly allocated to adenosine and placebo groups. In the adenosine group, a single-dose of intracoronary adenosine (100μg for the right coronary artery and 150μg for the left coronary artery) was administered. Primary endpoint was post-PCI myonecrosis, which was defined as abnormal levels of periprocedural cTnI. Secondary endpoints were defined as elevated cTnI levels [5 × upper limit of normal (ULN)], abnormal CK-MB levels, angiographic coronary flow measured by Thrombolysis In Myocardial Infarction (TIMI) frame count (TFC), the cumulative incidence of in-hospital death and in-hospital urgent target vessel revascularization (TVR). Clinical and angiographic characteristics of both adenosine (61 patients, 61±9years) and placebo (61 patients, 59±10years) groups were similar (p>0.05 for all). Post-procedural abnormal cTnI levels in the adenosine group were significantly lower than the placebo group (32% vs. 55%, p: 0.011). cTnI >5 × ULN (21% vs. 31%, p: 0.217) and abnormal CK-MB levels (11% vs. 19%, p: 0.263) were similar in both groups. Post-procedural TFCs in the adenosine group were significantly lower than the placebo group (24±4 vs. 27±5, p: 0.004). In-hospital events including death and urgent TVR were not observed in either group. Intracoronary administration of single-dose adenosine in patients with unstable angina undergoing PCI is associated with decreased periprocedural myonecrosis and improved coronary blood flow.