Administration Of Adenosine Research Articles

504 Topical adenosine treatment inhibits inflammation and mucus production in viral acute rhinosinusitis

OBJECTIVES/GOALS: Viral acute rhinosinusitis (ARS), a.k.a, the common cold, affects millions every year. The symptoms caused by viral ARS dramatically affect the general well-being and functional levels of patients, causing work and school absence, and antibiotic abuse. In this study, we examined the therapeutic potential of topical adenosine in viral ARS METHODS/STUDY POPULATION: Rhinosinusitis was induced in WT and adenosine receptor (AR) knockout mice by respiratory syncytial virus (RSV) infection in the upper airways. Mice were subjected to adenosine or vehicle control within the sinuses. Adenosine receptor expression, inflammatory cytokine expression, and histologic mucus and inflammation score was assessed. The effect of endogenous adenosine accumulation within the sino-nasal tract was assessed in adenosine deaminase knockout (ADA-/-) mice. RESULTS/ANTICIPATED RESULTS: Topical administration of adenosine significantly inhibited the expression of pro-inflammatory cytokines, mucus production, and cell damage in the nose of mice with viral ARS, without prolonging virus clearance. This inhibitory effect was primarily mediated by the A2A adenosine receptor (AR). We also examined and compared the expression of ARs in the nasal tissue, trachea, and lungs. The nasal tissue exhibited the lowest baseline expression of ARs as compared to the lung and trachea which was further downregulated following adenosine treatment. Additionally, accumulation of endogenous adenosine in ADA-/- mice showed no signs of inflammation within the nasal tissue. Together, we demonstrated that topical adenosine effectively decreased inflammation and mucus production in a mouse model of viral ARS. DISCUSSION/SIGNIFICANCE: Previously, we found that topical adenosine dramatically enhances mucociliary clearance in the nose and sinuses. In this study, we found that nasal topical adenosine effectively decreased inflammation and mucus production in viral ARS. Our data suggest that nasal topical adenosine is an effective topical therapeutic option for viral ARS.

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

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

Safety of Adenosine for the Treatment of Supraventricular Tachycardia in Hospitalized Patients with COVID-19 Pneumonia.

Coronavirus disease 2019 (COVID-19) is associated with pulmonary involvement and cardiac arrhythmias, including supraventricular tachycardia (SVT). Adenosine is commonly used to treat SVT and is generally safe, but is rarely associated with bronchospasm. There are no data regarding the safety of adenosine use in patients with COVID-19 pneumonia and physicians may hesitate to use it in such patients. We surveyed resident physicians and cardiology attendings regarding their level of comfort in administering adenosine to hospitalized COVID-19 patients. We compared a study group of 42 COVID-19 hospitalized patients who received adenosine for SVT to a matched (for age, sex, and co-morbidities) control group of 42 non-COVID-19 hospitalized patients during the same period, all of whom received IV adenosine for SVT. Escalation of care following intravenous adenosine administration was defined as increased/new pressor requirement, need for higher O2 flow rates, need for endotracheal intubation, new nebulizer therapy, or transfer to intensive care unit within 2 h of adenosine administration. Survey results showed that 82% (59/72) of residents and 62% (16/26) of cardiologists expressed hesitation/significant concerns regarding administering adenosine in hospitalized COVID-19 patients. Adenosine use was associated with escalation of care in 47.6% (20/42) COVID-19 as compared to 50% (21/42) non-COVID-19 patients (odds ratio 0.95, 95% CI 0.45-2.01, p = NS). Escalation of care was more likely in patients who were on higher FiO2, on prior nebulizer therapy, required supplemental oxygen, or were already on a ventilator. In conclusion, we identified significant hesitation among physicians regarding the use of adenosine for SVT in hospitalized COVID-19 patients. In this study, there was no evidence of increased harm from administering adenosine to patients with SVT and COVID-19. This finding needs to be confirmed in larger studies. Based on the current evidence, adenosine for treatment of SVT in this setting should not be avoided. Key Points: Question: Given the known bronchospastic effects of adenosine, is the use of adenosine safe for treatment of supraventricular tachycardia in hospitalized patients with COVID-19? Findings: A survey of residents and cardiology attending identified that a majority expressed some level of apprehension in using adenosine for SVT in COVID-19 patients. In our matched cohort study, we found adenosine use to be comparably safe in COVID-19 and non-COVID-19 hospitalized patients. Meaning: Based on current evidence, adenosine for treatment of SVT in this setting should not be avoided.

The single-syringe versus the double-syringe techniques of adenosine administration for supraventricular tachycardia: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Intravenous double-syringe technique (DST) of adenosine administration consists of an intravenous bolus of adenosine via three-way stopcock followed by an immediate 10-20ml sodium chloride 0.9% flush and is the recommended first-line treatment for stable supraventricular tachycardia (SVT). However, an alternative single-syringe technique (SST) method for adenosine administration has been described. This consists of diluting adenosine with sodium chloride 0.9% to a total volume of 15-20ml and was recently found to be potentially beneficial in several studies. Purpose We aimed to perform a meta-analysis of the SST versus the DST of adenosine administration as treatments for SVT. Methods We systematically searched EMBASE, PubMed, Cochrane, and ClinicalTrials.gov databases for randomised controlled trials (RCTs) and non-randomised studies of intervention (NRSIs) comparing the DST to SST adenosine administration in patients with SVT. The risk of bias was assessed by RoB-2 for RCTs and ROBINS-I for NRSIs. Outcomes included termination rate, termination rate at first dose, total administered dose, adverse effects, and discharge rate. Results We included four studies (three RCTs and one NRSI) with a total of 180 (60.55% female) patients, of whom 100 (55.55%) underwent the SST of adenosine administration. The three RCTs were considered of some concerns due to no pre-specified analysis in all studies and deviation from the intended intervention in one study. The NRSI was considered to carry a serious risk of bias by no analysis method that controlled for confounding, the possible influence of the outcome measure by knowledge of the intervention received, and no pre-specified analysis. No significant difference was found between treatment groups regarding termination rate (p = 0.22, Fig 1a), termination rate restricted to RCTs (p = 0.49, Fig 1b), total administered dose (p = 0.29, Fig 2a) and discharge rate (p = 0.1, Fig 2b). Termination rate at first dose (OR 2.87; CI 1.11-7.41; p = 0.03; I² = 0%, Fig 1c) was significantly increased in patients who received the SST. Major adverse effects were observed in only one study, with one patient suffering extravasation and phlebitis in the DST group. Conclusion To our knowledge, this is the first meta-analysis studying SST versus conventional DST for the management of SVT. This study suggests that the SST may be as safe as DST, equally effective for SVT termination, or even potentially more effective with the first dose. The SST would represent a simpler and more rapid approach, obviating the need for syringe switching or three-way stopcock, and reducing the margin of error in adenosine administration. To our knowledge, this is the highest quality evidence to date. Our results demonstrate that the current evidence is sufficient to support both SST and DST. However, favouring one technique over the other is not feasible given the limited sample size.

Early dose of Adenosine, postRadiofrequency abLation of accessory pathwaYin determining acute procedural success (EARLY study).

Post ablation of the accessory pathway (AP), the patient is observed in the catheterization laboratory for a variable period for resumption of pathway conduction. Aim of the study was to determine whether the administration of intravenous adenosine at 10 min after ablation of APwould have the same diagnostic accuracy as waiting for 30 min in predicting the resumption of AP conduction. This was a prospective interventional study conducted in two centers. Post ablation of the AP, intravenous adenosine was administered at 10 min to look for dormant pathway conduction. The response was recorded as positive (presence of pathway conduction), negative (absence), or indeterminate (not able to demonstrate AV and VA block and inability to ascertain AP conduction). The study included 110 procedures performed in 109 patients. Adenosine administration at 10 min showed positive result in 3 cases (2.7%), negative result in 99 cases (90%) and indeterminate result in 8 cases (7.3%). Reconnection of accessory pathway at 30 min postablation was seen in 8 cases (7.3%). Of these 8 cases, 10 minadenosine administration showed positive test in 3 patients and negative test in 5 patients. Adenosine test at 10 min has a sensitivity, specificity, positive predictive value, and negative predictive value of 37.5%, 100%, 100%, and 94.9% in identifying the recurrence of accessory pathway conduction at 30 min, respectively. Absence of pathway conduction on administration of adenosine 10 min postablation does not help predict the absence of resumption of conduction thereafter.

A Clinical Score for Predicting the Paroxysmal Supraventricular Tachycardia's Recurrence Risk; a Retrospective Cross-sectional Study.

Identifying prognostic variables associated with the probability of recurrent paroxysmal supraventricular tachycardia (PSVT) would aid decision-making regarding disposition of the patients. This study aims to develop a clinical scoring system to predict PSVT recurrence after adenosine administration in the emergency department (ED). This retrospective cross-sectional study was conducted on patients who were referred to the emergency department of Ramathibodi Hospital, a university-affiliated super-tertiary care hospital in Bangkok, Thailand, with diagnosis of PSVT during a 10-year period from 01 January 2010 until 31 December 2020. The cases were divided into recurrent and non-recurrent PSVT based on the response to standard treatment and the independent predictors of recurrence were studied using multivariable logistic regression analysis. 264 patients were diagnosed with PSVT and successfully converted by adenosine. 24 (9.1%) had recurrent PSVT, and 240 (90.9%) had no recurrent PSVT in the same ED visit. The risk of PSVT recurrence in ED corresponded with the history of hypertension (p = 0.059), valvular heart disease (p = 0.052), heart rate ≥ 100 (p = 0.012), and systolic blood pressure < 100 after electrocardiogram (ECG) converted to sinus rhythm (p = 0.022) and total dose of adenosine (p = 0.002). We developed a clinical prediction score of PSVT recurrence with an accuracy of 79.5%. A score of 0 (low risk), 1-2 (moderate risk), and > 2 (high risk) had a positive likelihood ratio (LR+) of 0.31, 0.56 and 2.33, respectively. It seems that, using the PSVT recurrence score we could screen the high-risk patients for PSVT recurrence (score>2) who need to be observed for at least 6-12 hours and receive cardiologist consultation in ED. In addition, the moderate and low-risk group (score 0-2) need to be observed for 1 hour and can be discharged from ED.

The effect of iron deficiency and goiter on the adaptation process of iatrogenic cerebral vasodilation and cardiac parameters

Aim: Adenosine is a pharmacological stress agent used in many nuclear medicine clinics. It causes different and widespread effects in different tissues. It causes widespread inhibition and cerebral vasodilation through A1 and A2a receptors in the central nervous system. We evaluated the duration of side effects in patients with iron deficiency and euthyroid goiter. Materials and Methods: Our study included 183 patients with atypical chest pain who underwent myocardial perfusion scintigraphy to investigate the presence of coronary artery disease. Adenosine infusion was administered intravenously at a rate of 140 µg/kg/min for 6 minutes. Complaints that occurred during intravenous administration of adenosine were questioned. The presence of at least three of the most common complaints of flushing, headache, nausea, and feeling of ill feeling was considered to have prominent complaints. If these complaints continued for at least 30 minutes, the presence of prolonged prominent complaints was accepted. Patients who developed prolonged complaints were categorized as group 1 and patients without prolonged complaints as group 2. Results: The number of patients diagnosed with euthyroid goiter was significantly higher in Group 1 (p&lt;0.005). Additionally, thyroid size was significantly larger in patients in Group 1 compared to those in Group 2, with respective medians (minimum-maximum) of 20 (11-18 ml) and 15 (11-28 ml) (p&lt;0.005). In group 1, 44 (86.3%) patients had iron deficiency, while in group 2 37 (28%) patients had iron deficiency (p&lt;0.005). The free variables determining the development of prolonged prominent complaints in patients who received adenosine infusion were found to be goiter size (Odds: 1.437, confidence interval: 1.264-1.633; p&lt;0.005) and presence of iron deficiency (Odds: 135.744, confidence interval: 27.055-681.074; p&lt;0.005). Conclusion: Iron deficiency and euthyroid goiter are common subclinical conditions in the Turkish population. In the presence of subclinical diseases followed without treatment, the duration of drug effects may be prolonged. Prospective and more comprehensive studies are needed on this subject.

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

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

Topical Adenosine Inhibits Inflammation and Mucus Production in Viral Acute Rhinosinusitis.

Viral acute rhinosinusitis (ARS) is the leading cause of work and school absence and antibiotic over-prescription. There are limited treatment options available to ameliorate the symptoms caused by viral ARS. We have previously demonstrated that topical adenosine treatment enhances mucociliary clearance in the sino-nasal tract. Here, we assessed the therapeutic potential of topical adenosine in a mouse model of viral ARS. The effect of topical adenosine on inflammatory response and mucin gene expression was examined in a mouse model of viral ARS induced by respiratory syncytial virus (RSV) nasal-only infection. We also investigated the inflammatory effect of both endogenous and exogenous adenosine in the sino-nasal tract. Topical adenosine significantly inhibited the expression of pro-inflammatory cytokines, goblet hyperplasia, mucin expression, and cell damage in the nose of mice with viral ARS. This treatment did not prolong virus clearance. This inhibitory effect was primarily mediated by the A2A adenosine receptor (AR). Although previous studies have shown that adenosine induces a robust inflammatory response in the lungs, neither endogenous nor exogenous adenosine produced inflammation in the sino-nasal tract. Instead, exogenous adenosine inhibited the baseline expression of TNF and IL-1β in the nose. Additionally, baseline expression of ARs was lower in the nose than that in the trachea and lungs. We demonstrated that intranasal adenosine administration effectively decreased inflammation and mucus production in a mouse model of viral ARS. N/A Laryngoscope, 133:2095-2103, 2023.

Adenosine as adjunctive therapy in acute coronary syndrome: a meta-analysis of randomized controlled trials.

Adenosine has been tested in several randomized controlled trials (RCTs) to minimize the incidence of coronary microvascular obstruction (CMVO). The aim of this study was to pool all the RCTs comparing intracoronary or intravenous adenosine versus placebo in patients with acute coronary syndrome (ACS) undergoing myocardial revascularization. PubMed and Scopus electronic databases were scanned for eligible studies up to 5th June 2022. A total of 26 RCTs with 5843 patients were included. Efficacy endpoints were major adverse cardiac events (MACE), all-cause death, non-fatal myocardial infarction, and heart failure. Atrioventricular blocks and ventricular fibrillation/sustained ventricular tachycardia (VF/SVT) were the safety endpoints. Myocardial blush grade, thrombolysis in myocardial infarction (TIMI) flow grade, left ventricular ejection fraction (LVEF), infarct size, and ST-segment resolution were also assessed. Adenosine administration was not associated with any clinical benefit in terms of MACE, all-cause death, non-fatal myocardial infarction, and heart failure. However, adenosine was associated with an increased rate of advanced atrioventricular blocks and of VF/SVT in studies with total mean ischaemic time>3h, compared to placebo. Remarkably, among patients undergoing percutaneous coronary intervention, adenosine was associated with reduced myocardial blush grade 0-1 and TIMI flow grade 0-2, compared to placebo. Furthermore, adenosine did not show favourable effects on LVEF and infarct size. Adenosine infusion, as adjunctive therapy in ACS, was associated with an increased risk of advanced atrioventricular blocks and increased rates of adenosine-triggered ventricular arrhythmias in patients with long ischaemic time, without providing any clinical benefit compared to placebo.

Comparison of sinus conversion rates and body weights after 6 mg adenosine administration in supraventricular tachycardia

BackgroundTo evaluate the relationship between body weight and the success rate of supraventricular tachycardia (SVT) termination after an initial 6-mg adenosine administration. MethodsThis retrospective observational study was conducted with medical records of patients who visited a single tertiary emergency department and underwent an electrophysiologic study with an SVT diagnosis. Patients under 18 years of age or those with SVT aberrancy, recurring SVT after radiofrequency catheter ablation, premedication of non-dihydropyridine calcium channel blocker, and signs of shock were excluded. ResultsData from 124 patients were collected. There were 69 women (55.6%); mean age, 49.7 years. The mean weight and height were 66.8 kg and 164.8 cm, respectively. Adenosine dose was 0.09 mg/kg. For the first sinus conversion (SC) success group (83 patients, 67%), the mean weight, height, and adenosine dose were 61.0 ± 11.5 kg, 161.9 ± 8.1 cm, and 0.10 ± 0.02 mg/kg. For the first SC failure group, these values were 78.4 ± 17.0 kg, 170.7 ± 8.9 cm, and 0.079 ± 0.02 mg/kg, respectively. To evaluate factors associated with the first SC, we performed bivariate logistic regression with weight (odds ratio [OR]: 1.093; 95% confidence interval [CI]: 1.045–1.144; P < 0.001) and height (OR: 1.071; 95% CI: 1.008–1.138; P = 0.027). Receiver operating characteristics curves and the cut-off values for adenosine dose and weight were 0.90 mg/kg and 66.5 kg with 71.1% sensitivity and 73.2% specificity (area under the curve: 0.814; 95% CI: 0.73–0.90; P < 0.001). ConclusionWeight and height were significant predictors of the first SC success rate among SVT patients. Consequentially, it is necessary to consider other adenosine administration methods, including increasing the initial drug dose or changing the flushing strategy after adenosine injection.

Myocardial mass affects diagnostic performance of non-hyperemic pressure-derived indexes in the assessment of coronary stenosis

Background Several non-hyperemic pressure-derived Indexes (NHPI) have been introduced for the assessment of coronary stenosis, showing a good correlation with fractional flow reserve (FFR). Notably, either the assessment of NHPI during adenosine administration (NHPIADO) or the Hybrid Approach (NHPIHA), combining NHPI with FFR, have been showed to increase the accuracy of such indexes. It remains unclear whether diagnostic performance might be affected by the extent of the subtended myocardial mass. Methods. We enrolled consecutive patients with an intermediate coronary stenosis assessed with NHPI and FFR. NHPI were also measured during adenosine (ADO) administration (NHPIADO). The amount of jeopardized myocardium was assessed using the Duke Jeopardy Score (DJS). With FFR as reference, we assessed the accuracy of NHPI, NHPIADO and NHPIHA according to the extent of the subtended myocardium. Results. One-hundred-seventy stenoses from 151 patients were grouped according to the DJS as follows: A) Small Extent (SE, n = 82); B) Moderate Extent (ME, n = 53); C) Large Extent (LE, n = 35). As compared with FFR, NHPI showed a significantly different accuracy, as assessed by the Youden's index, according to the extent of the jeopardized myocardium (SE: 0.39 ± 0.05, ME: 0.68 ± 0.06, LE: 0.28 ± 0.06, p < 0.001). Conversely, both the NHPIADO (SE: 0.76 ± 0.02, ME: 0.88 ± 0.02, LE: 0.82 ± 0.02, p = 0.72) and NHPIHA (SE: 0.82 ± 0.07, ME: 0.84 ± 0.02, LE: 0.88 ± 0.02, p = 0.70) allowed for a better diagnostic accuracy regardless of the amount of myocardium subtended. Conclusions. Diagnostic performance of NHPI might be affected by the extent of myocardial territory subtended by the coronary stenosis. A hybrid approach might be useful to overcome this limitation.

Side effects and major adverse cardiac events caused by fractional flow reserve measurement: a systematic review and meta-analysis of 12,215 patients

Abstract Background Current guidelines recommend revascularization based on fractional flow reserve (FFR) in angiographically intermediate coronary stenoses. Side effects of FFR caused by adenosine administration are usually transient with little relevance. However, major adverse cardiac events (MACE), such as coronary artery occlusion, may infrequently occur as a consequence of intracoronary wire manipulation and little is known about their incidence. This systematic review aims to analyze the rate of side effects including MACE caused by FFR measurement as reported in large multicenter studies. Methods A PubMed database query for “fractional flow reserve” of the type “multicenter study” identified 348 records. Subsequently, one retracted record was excluded, another record was excluded as it contained no digital object identifier, 52 records were excluded since access could not be obtained, and one was a duplicate. Of the 293 records screened, only 15 contained relevant information on adverse effects or events due to FFR measurement and had included at least 100 patients. To systematically report the frequency of adverse events, the micro average for each event type was calculated across all studies where it was described. Results This systematic review includes data from 15 studies with a total of 12,215 patients. Measurement of FFR was successful in 99.1% (5,163 of 5,210). Hyperemia for FFR measurement was usually induced by adenosine, in most cases administered intravenously. Adverse effects are summarized in Figure 1. With 34.5% (778 of 2,257) of patients reporting chest pain or discomfort, this was the most common side effect of adenosine administration. Dyspnea was noted by 20.0% (250 of 1,250) of patients. Heart-rhythm disturbances occurred in 3.3% (185 of 5,646) of patients. More specifically, a transient atrioventricular block was reported in 2.6% (115 of 4,396) of patients, whereas ventricular arrhythmia was considerably less frequent with 0.2% (11 of 5,864). Hypotension was described by 0.9% (14 of 1,574) of patients, vomiting or nausea by 0.9% (11 of 1,250), and bronchospasm by 0.2% (11 of 4,836). MACE were infrequent, but not negligible: the pressure wire used for FFR measurement was reported to cause coronary artery dissection in 0.2% (8 of 4,158) of patients, coronary artery occlusion in 0.2% (4 of 2,381) of patients, and coronary artery perforation in 0.1% (2 of 3,228) of patients. Conclusions Chest pain, dyspnea, and transient arrhythmias are commonly experienced by patients in the context of adenosine but bear limited clinical relevance. The analysis of a large patient cohort revealed that MACE caused by vessel injury, while infrequent, occur at a rate of approximately 0.5% and should hence be considered relevant. Funding Acknowledgement Type of funding sources: None.

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

Supraventricular tachycardia with double trouble.

A 23-year-old healthy woman who was 10 weeks pregnant presented to the hospital with palpitations. Her presenting rhythm is shown in Figure 1A. The tachycardia terminated with administration of adenosine. Her baseline sinus rhythm electrocardiogram (ECG) is shown in Figure 1B. Metoprolol was initiated, but she had a recurrence of tachycardia. What is your interpretation of the ECGs? What are treatment options?

Dual Atrioventricular Nodal Non-Reentrant Tachycardia Misdiagnosed as Rapid Atrial Fibrillation - The Role of Adenosine.

We report a case of a 56-year-old man diagnosed with non-ischemic cardiomyopathy in 2017 with progressive decline in left ventricular systolic function and frequent hospitalisations for heart failure in the context of a presumed atrial fibrillation with high ventricular rate. Electrocardiographic changes after adenosine administration raised the suspicion of dual atrioventricular nodal non-reentrant tachycardia, a diagnosis that was confirmed by electrophysiological study, making adenosine a potential diagnostic aid in such cases. The ablation of the slow pathway terminated the tachycardia and led to a marked improvement in symptomatology and echocardiographic parameters.

Effectiveness and Safety of High-Power Radiofrequency Ablation Guided by Ablation Index for the Treatment of Atrial Fibrillation.

Background To investigate the efficacy and safety of ablation index- (AI-) guided high-power radiofrequency ablation in the treatment of atrial fibrillation (AF). Methods Outcomes of radiofrequency (RF) applications were compared in a swine ventricular endocardial model (n = 10 each for 50 W, 40 W, and 30 W; AI = 500). And a total of 100 consecutive patients with paroxysmal AF undergoing pulmonary vein isolation (PVI) were included. The patients were divided into two groups (n = 50 for each) as follows: control group, treated with conventional power (30 W) ablation mode; and study group, treated with high power (40 W) radiofrequency ablation mode. All groups were treated with the same AI value guided the ablation (target AI = 400/500 on posterior/anterior wall, respectively). Acute pulmonary vein (PV) reconnection was assessed post adenosine administration 20 minutes after ablation. Subsequently, pathological observation of porcine heart lesions and necrotic tissue was performed. Additionally, statistical analyses were carried out on patients' baseline clinical characteristics, surgical data, and total RF energy. Results In swine ventricular endocardial RF applications, compared with 40 W and 30 W, the use of 50 W was associated with shallower tissue lesion depth (p < 0.001) and greater lesion maximum diameter (p < 0.001). Compared with 40 W and 30 W, tissue necrosis caused by 50 W was the deepest and largest (p < 0.001). In pulmonary vein isolation (PVI), there was no significant difference in baseline data between the study group and control group (p > 0.05). In patients with paroxysmal atrial fibrillation, the procedure time in the high-power group was significantly shortened (p < 0.001). The ablation time was significantly shorter (p < 0.001). Compared with control group, RF energy per point and acute pulmonary vein (PV) reconnection were lower (p < 0.001), and first-pass PVI was higher (p < 0.01) in study group. There were no significant differences in complications and sinus rhythm maintenance at 12 months between the two groups (p > 0.05). Conclusions Compared with conventional (30 W) PVI, AI-guided high-power (40 W) was safe and associated with shorter procedure time and reduced acute PV reconnection.

Adenosine Alleviates Necrotizing Enterocolitis by Enhancing the Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Newborns.

Necrotizing enterocolitis (NEC) is a common disorder in premature infants that is characterized by hyperinflammation and severe necrosis in the intestine. The pathogenesis of NEC remains to be elucidated. In this study, we demonstrate that adenosine, a metabolite more abundant in infants than in adults, plays an important role in the prevention of NEC. Administration of adenosine or its analog, adenosine-5'-N-ethyluronamide (NECA), dramatically relieved the severity of NEC in neonatal mice. Meanwhile, adenosine treatment significantly enhanced the immunosuppressive function, antibacterial activity, and migration of myeloid-derived suppressor cells (MDSCs). However, depletion of MDSCs or inhibition of their migration using the CXCR2 inhibitor SB225002 almost completely abrogated the protective effect of adenosine on NEC. Mechanistic studies showed that MDSCs in newborns expressed abundant adenosine receptor A2B (A2BR) that elicits intracellular cAMP signaling and its downstream target NF-κB. Importantly, intestinal tissues from patients with NEC showed significantly lower infiltration of A2BR-positive MDSCs than those from healthy donors. These observations revealed that adenosine-induced MDSCs represent an essential immune axis for intestinal homeostasis in newborns.

Persistent Coronary Vasomotor Tone During Myocardial Ischemia Occurs at the Capillary Level and May Involve Pericytes.

BackgroundThere is persistent coronary vasomotor tone during myocardial ischemia, despite ongoing coronary arteriolar dilatation. The mechanism underlying this vasodilatory tone, which can be unmasked by coronary vasodilators, is unclear. We hypothesized that persistent microvascular resistance during myocardial ischemia occurs at the level of capillaries and may be caused by pericytes.MethodsWe studied nine instrumented dogs where coronary blood flow and coronary driving pressure were reduced to half by placement of stenoses. Myocardial blood flow and myocardial blood volume were measured with myocardial contrast echocardiography before and during adenosine administration. In three animals, the heart was perfusion-fixed under these conditions for electron microscopic assessment of capillary and pericyte size.ResultsDuring ischemia, myocardial blood volume decreased and myocardial vascular resistance remained unchanged. Adenosine administration reversed the decline in myocardial blood volume and decreased myocardial vascular resistance. Electron microscopy showed larger capillaries in ischemic beds receiving adenosine than ischemic beds not receiving adenosine. Pericytes in beds receiving adenosine also tended to be larger.ConclusionCapillaries are the site of persistent vasomotor tone during myocardial ischemia; any other site of vascular regulation (arterioles or venules) cannot explain these myocardial contrast echocardiography findings, which are confirmed on post-mortem electron microscopic examination. The decrease in capillary size is likely caused by pericyte contraction in an attempt to maintain a constant capillary hydrostatic pressure. Adenosine relaxes pericytes, restores myocardial blood volume, reduces myocardial vascular resistance, and improves regional function during ischemia. These findings could have important therapeutic implications.

An Evaluation of Prehospital Adenosine Use

Background Adenosine has been safely used by paramedics for the treatment of stable supraventricular tachycardia since the mid-1990s. However, there continues to be variability in paramedics’ ability to identify appropriate indications for adenosine administration. As the first of a planned series of studies aimed at improving the accuracy of SVT diagnosis and successful administration of adenosine by paramedics, this study details the current usage patterns of adenosine by paramedics. Methods This cross-sectional retrospective study investigated adenosine use within a large northeast EMS region from January 1, 2019, through September 30, 2021. Excluding pediatric and duplicate case reports, we created a dataset containing patient age, sex, and vital signs before, during, and after adenosine administration; intravenous line location; and coded medical history from paramedic narrative documentation, including a history of atrial fibrillation, suspected arrhythmia diagnosis, and effect of adenosine. In cases with available prehospital electrocardiograms (EKGs) for review, two physicians independently coded the arrhythmia diagnosis and outcome of adenosine administration. Statistical analysis included interrater reliability with Cohen’s kappa statistic. Results One hundred eighty-three cases were included for final analysis, 84 did not have a documented EKG for review. Categorization of presenting rhythms in these cases occurred by a physician reviewing EMS narrative and documentation. Forty of these 84 cases (48%) were adjudicated as SVT likely, 32 (38%) as SVT unlikely and 12 (14%) as uncategorized due to lack of supporting documentation. Of the 99 cases with EKGs available to review, there was substantial agreement of arrhythmia diagnosis interpretation between physician reviewers (Cohen’s kappa 0.77–1.0); 54 cases were adjudicated as SVT by two physician reviewers. Other identified cardiac rhythms included atrial fibrillation (16), sinus tachycardia (11), and ventricular tachycardia (2). Adenosine cardioversion occurred in 47 of the 99 cases with EKGs available for physician review (47.5%). Adenosine cardioversion was also deemed to occur in 87% (47/54) of cases when the EKG rhythm was physician adjudicated SVT. Conclusions This study supports the use of adenosine as a prehospital treatment for SVT while highlighting the need for continued efforts to improve paramedics’ identification and management of tachyarrhythmias.