Intravenous Adenosine Research Articles

Feasibility and Improved Diagnostic Yield of Intracoronary Adenosine to Assess Microvascular Dysfunction With Bolus Thermodilution.

Bolus thermodilution and intravenous adenosine are established methods for coronary microcirculatory assessment. Yet, its adoption remains low, partly due to procedural time and patient discomfort associated with intravenous adenosine. We investigated differences between intracoronary and intravenous adenosine using bolus thermodilution in terms of microcirculatory indices, procedural time, and side effects associated with adenosine in patients with myocardial ischemia and nonobstructive coronary arteries. In this prospective, observational study, 102 patients with suspected myocardial ischemia and nonobstructive coronary arteries underwent measurements of mean transit time, coronary flow reserve, index of microcirculatory resistance, procedure time and patient tolerability with low-dose intracoronary adenosine, high-dose intracoronary adenosine (HDIC), and intravenous adenosine. HDIC induced greater hyperemia compared with low-dose intracoronary IC adenosine and intravenous adenosine with a shorter hyperemic mean transit time, P<0.0001. Coronary flow reserve was higher and index of microcirculatory resistance lowest with HDIC, compared with low-dose intracoronary IC adenosine and intravenous adenosine, P<0.05. Low coronary flow reserve was downgraded from 21% with intravenous adenosine to 10% with HDIC adenosine (P=0.031); high index of microcirculatory resistance was downgraded from 23% with intravenous adenosine to 14% with HDIC (P=0.098). Intracoronary adenosine was associated with lower procedural times (P<0.0001). More patients experienced chest pain with intravenous adenosine (P<0.01) and the chest pain intensity was higher compared with intracoronary adenosine (P<0.0001). In patients with suspected myocardial ischemia and nonobstructive coronary arteries undergoing coronary microcirculatory assessment with bolus thermodilution, the use of HDIC compared with intravenous adenosine was associated with enhanced induction of hyperemia. The use of intracoronary adenosine allowed for a shorter procedure time and was better tolerated. URL: clinicaltrials.gov; Unique Identifier: NCT04827498.

Comparison of adenosine, dobutamine and bicycle exercise on intracoronary physiological indices in patients with myocardial bridges

Abstract Background We have recently demonstrated that patients with angina and nonobstructive coronary arteries (ANOCA) with myocardial bridges (MBs) exhibit maladaptive exercise physiology, due to abnormal wave energies arising at the tunnelled segment (1). Intracoronary pressure-derived indices in response to dobutamine and adenosine are used to identify an ischaemic substrate in these patients in clinical practice (2). However, it remains unknown if the changes induced by dobutamine and adenosine are comparable with physical exercise. Methods Patients with ANOCA and a MB in the left anterior descending artery underwent simultaneous acquisition of intracoronary pressure and flow sequentially during rest, supine bicycle exercise and intravenous adenosine and dobutamine infusion. We compared coronary perfusion efficiency (accelerating energy/total energy flux) and changes in specific wave energies in response to these three stressors. Results Twenty-five patients were enrolled (36% females, 59±9 years old). Patients had a high symptom burden (88% CCS II-IV) and myocardial bridge muscle index (79±30). Fractional flow reserve and coronary flow reserve were 0.86±0.05 and 2.5±0.5. Microvascular resistances during adenosine, dobutamine and exercise were 2.0±0.7, 3.4±1.4 and 4.3±1.3 mmHg.cm-1.s-1 respectively (p&amp;lt;0.001). There was a reduction in coronary perfusion efficiency in response to adenosine (64±8% to 51±12%), dobutamine (65±9% to 53±13%) and exercise (66±10% to 56±9%) (all p&amp;lt;0.001), with no between stressor differences in delta perfusion efficiency (ANOVA p=0.641). However, the impact of each stressor on the wave energy arising from the tunnelled segment was different whereas no such difference (between stressors) was observed in the wave energies arising from the microcirculation. There was no difference in tunnelled-segment derived delta wave energies between dobutamine and exercise (Figure 1). Conclusions Adenosine, dobutamine and exercise have different effects on coronary microvascular resistance and cardiac coronary coupling in patients with myocardial bridges. Our findings provide novel mechanistic insights into the pathophysiology of ANOCA in combination with MB, and suggest that dobutamine (but not adenosine) could be used as a surrogate for physical exercise during intracoronary physiological assessment.Figure 1.

Evaluation of Intravenous Versus Intracoronary Adenosine in Coronary Reactivity Testing

Coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) obtained through coronary bolus thermodilution are used to assess and treat patients with angina and no obstructive coronary artery disease. Previous studies demonstrate comparable results assessing epicardial ischemia by fractional flow reserve using intravenous (IV) or intracoronary (IC) adenosine. It is unknown if there is a similarity between IC and IV hyperemia with adenosine when performing coronary reactivity testing (CRT). We reviewed CRT data and baseline demographics in a cohort of patients who underwent CRT for ischemia and no obstructive coronary artery disease. We evaluated CFR and IMR in patients whereby maximal hyperemia was obtained by both IC and IV means using linear regression, one-way analysis of variance, Wilcoxon, and Bland-Altman analysis. We assessed 62 patients with a median age of 60.5 years (50 to 67), and 72% were females. The average CFR with IC adenosine was 3.12 (2.31 to 4.06) and 2.71 (2.0 to 3.88) with IV adenosine, with an R2 value of 0.50 (p <0.0001). The average IMR with IC adenosine was 28.23 (16.24 to 50.72) and 22.27 (14.79 to 37.0) with IV adenosine, with an R2 value of 0.33 (p <0.0001). Average intra-method variability between IC and IV adenosine was nonsignificant (p = 0.31 for CFR and p = 0.55 for IMR). Bland-Altman analysis showed reasonable agreement between IV and IC adenosine for CFR and IMR with slightly higher values using IC adenosine. Therefore, in CRT with bolus thermodilution, CFR and IMR values obtained with IC adenosine correlate well with those obtained with IV adenosine. This presents a potential alternative to IV adenosine for bolus thermodilution CRT.

Factors Contributing to Coronary Microvascular Dysfunction in Patients with Angina and Non-Obstructive Coronary Artery Disease.

Coronary microvascular dysfunction (CMD), characterised by a reduced coronary flow reserve (CFR) or an increased index of microcirculatory resistance (IMR), has received considerable attention as a cause of chest pain in recent years. However, the risks and causes of CMD remain unclear; therefore, effective treatment strategies have not yet been established. Heart failure or coronary artery disease (CAD) is a risk factor for CMD, with a higher prevalence among women. However, the other contributing factors remain unclear. In this study, we assessed the risk in patients with angina and non-obstructive coronary artery disease (ANOCA), excluding those with heart failure or organic stenosis of the coronary arteries. Furthermore, we analysed whether the risk of CMD differed according to component factors and sex. This study included 84 patients with ANOCA (36 men and 48 women; mean age, 63 years) who underwent coronary angiography and functional testing (CFT). The CFT included a spasm provocation test (SPT), followed by a coronary microvascular function test (CMVF). In the SPT, patients were mainly provoked by acetylcholine (ACh), and coronary spasm was defined as >90% transient coronary artery constriction on coronary angiography, accompanied by chest pain or ischaemic changes on electrocardiography. In 15 patients (18%) with negative ACh provocation, ergonovine maleate (EM) was administered as an additional provocative drug. In the CMVF, a pressure wire was inserted into the left anterior descending coronary artery using intravenous adenosine triphosphate, and the CFR and IMR were measured using previously described methods. A CFR < 2.0 or IMR ≥ 25 was indicative of CMD. The correlations between various laboratory indices and CMD and its components were investigated, and logistic regression analysis was performed, focusing on factors where p < 0.05. Of the 84 patients, a CFR < 2.0 was found in 22 (26%) and an IMR ≥ 25 in 40 (48%) patients, with CMD identified in 46 (55%) patients. CMD was correlated with smoking (p = 0.020) and the use of EM (p = 0.020). The factors that correlated with a CFR < 2.0 included the echocardiograph index E/e' (p = 0.013), which showed a weak but positive correlation with the CFR (r = 0.268, p = 0.013). Conversely, the factors correlated with an IMR ≥ 25 included RAS inhibitor usage (p = 0.018) and smoking (p = 0.042). Assessment of the risk of CMD according to sex revealed that smoking (p = 0.036) was the only factor associated with CMD in men, whereas the left ventricular mass index (p = 0.010) and low glycated haemoglobin levels (p = 0.012) were associated with CMD in women. Our results indicated that smoking status and EM use were associated with CMD. The risk of CMD differed between the two CMD components and sex. Although these factors should be considered when treating CMD, smoking cessation remains important. In addition, CMD assessment should be performed carefully when EM is used after ACh provocation. Further validation of our findings using prospective studies and large registries is warranted.

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

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

Use of coronary physiology to guide revascularization in clinical practice: results of the F(FR)2 registry

BackgroundDespite the recommendation of coronary physiology to guide revascularization in angiographically intermediate stenoses without established correlation to ischemia, its uptake in clinical practice is slow.AimsThis study aimed to analyze the use of coronary physiology in clinical practice.MethodsBased on a multicenter registry (Fractional Flow Reserve Fax Registry, F(FR)2, ClinicalTrials.gov identifier NCT03055910), clinical use, consequences, and complications of coronary physiology were systematically analyzed.ResultsF(FR)2 enrolled 2,000 patients with 3,378 intracoronary pressure measurements. Most measurements (96.8%) were performed in angiographically intermediate stenoses. Out of 3,238 lesions in which coronary physiology was used to guide revascularization, revascularization was deferred in 2,643 (78.2%) cases.Fractional flow reserve (FFR) was the most common pressure index used (87.6%), with hyperemia induced by an intracoronary bolus of adenosine in 2,556 lesions (86.4%) and intravenous adenosine used for 384 measurements (13.0%). The route of adenosine administration did not influence FFR results (change-in-estimate -3.1% for regression model predicting FFR from diameter stenosis). Agreement with the subsequent revascularization decision was 93.4% for intravenous and 95.0% for intracoronary adenosine (p = 0.261).Coronary artery occlusion caused by the pressure wire was reported in two cases (0.1%) and dissection in three cases (0.2%), which was fatal once (0.1%).ConclusionsIn clinical practice, intracoronary pressure measurements are mostly used to guide revascularization decisions in angiographically intermediate stenoses. Intracoronary and intravenous administration of adenosine seem equally suited. While the rate of serious complications of wire-based intracoronary pressure measurements in clinical practice seems to be low, it is not negligible.Graphical abstract

OR8-2 | Intravenous vs Intracoronary Adenosine for the Determination of Coronary Flow Reserve and Index of Microcirculatory Resistance

OR8-2 | Intravenous vs Intracoronary Adenosine for the Determination of Coronary Flow Reserve and Index of Microcirculatory Resistance

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.

Combined modified Valsalva maneuver with adenosine supraventricular tachycardia: A comparative study

Background and importanceParoxysmal supraventricular tachycardia (PSVT) is an arrhythmia commonly seen in the emergency department. Both modified Valsalva maneuver (MVM) and intravenous adenosine are the first line treatment, of which the former has e lower success rate while the latter has a higher success rate but some risks and adverse effects. Given both of these reverse rhythms quickly, combining them may achieve a better effect. ObjectiveThe objective of this study is to evaluate the success rate and potential risk of combining the use of intravenous adenosine while patients were doing MVM as a treatment for paroxysmal supraventricular tachycardia(pSVT). Design, settings and participantsWe recruited patients with pSVT from 2017 to 2022, and randomly assigned them into 3 groups, MVM group, intravenous adenosine group, and combination therapy group, in which MVM was allowed to be performed twice, while intravenous adenosine was given in a titration manner to repeat three times, recorded the success rate and side effects in each group. Main resultsThe success rate of the MVM group, adenosine group, and combination group are 42.11%, 75.00 and 86.11%, respectively. The success rate of the adenosine group and combination group is significantly higher than the n MVSM group (p < 0.01, p < 0.001), while the success rate of the combination group is higher than the adenosine group, it has no significant difference (p = 0.340). In terms of safety, the longest RR durations (asystole period) are 1.61 s, 1.60s, and 2.27 s, there is a statistical difference among the three groups (p < 0.01) and between the adenosine and combination group (0.018). ConclusionTherefore, we can conclude that combination therapy has a relatively high success rate and good safety profile, but the current study failed to show its superiority to adenosine.

Rationale and design of the NODE-303 study: evaluating the safety of symptom-prompted, self-administered etripamil for paroxysmal supraventricular tachycardia episodes in real-world settings

Paroxysmal supraventricular tachycardia (PSVT) is a common episodic arrhythmia characterized by unpredictable onset and burdensome symptoms including palpitations, dizziness, chest pain, distress, and shortness of breath. Treatment of acute episodes of PSVT in the clinical setting consists of intravenous adenosine, beta-blockers, and calcium channel blockers (CCBs). Etripamil is an intranasally self-administered L-type CCB in development for acute treatment of AV-nodal dependent PSVT in a non-medical supervised setting. This paper summarizes the rationale and study design of NODE-303 that will assess the efficacy and safety of etripamil. In the randomized, double-blinded, placebo-controlled, Phase 3 RAPID trial, etripamil was superior to placebo in the conversion of single PSVT episodes by 30 minutes post initial dose when administered in the non-healthcare setting; this study required a mandatory and observed test dosing prior to randomization. The primary objective of NODE-303 is to evaluate the safety of symptom-prompted, self-administered etripamil for multiple PSVT episodes in real-world settings, without the need for test dosing prior to first use during PSVT. Secondary endpoints include efficacy and disease burden. Upon perceiving a PSVT episode, the patient applies an electrocardiographic monitor, performs a vagal maneuver, and, if the vagal maneuver is unsuccessful, self-administers etripamil 70 mg, with an optional repeat dose if symptoms do not resolve within 10 minutes after the first dose. A patient may treat up to four PSVT episodes during the study. Adverse events are recorded as treatment-emergent if they occur within 24 hours after the administration of etripamil. Efficacy endpoints include time to conversion to sinus rhythm within 30 and 60 mins after etripamil administration, and the proportion of patients who convert at 3, 5, 10, 20, 30, and 60 min. Patient-reported outcomes are captured by the Brief Illness Perception Questionnaire, the Cardiac Anxiety Questionnaire, the Short Form Health Survey 36, the Treatment Satisfaction Questionnaire for Medication and a PSVT survey. Overall, these data will support the development of a potentially paradigm-changing long-term management strategy for recurrent PSVT.

Rethinking the false positive exercise stress test in the context of coronary microvascular dysfunction

Abstract Background Exercise stress testing (EST) was the traditional tool to detect myocardial ischaemia, but its use has declined due to its perceived high false positive rate. However, EST was historically validated against the reference standard of obstructive coronary artery disease (CAD). It is now well recognised that myocardial ischaemia can occur in the absence of CAD and this cohort, termed angina with non-obstructive coronary arteries (ANOCA), comprises nearly 50% of all patients presenting with stable angina. Purpose Our study assesses the accuracy of EST in detecting a substrate for myocardial ischaemia, with the reference standard being comprehensive coronary physiology assessment in patients with ANOCA. Methods Patients with typical angina and non-obstructive coronary arteries underwent physiological characterisation of the coronary circulation using a dual sensor-tipped intracoronary guidewire in the left anterior descending artery. The epicardial vessel was assessed by Fractional Flow Reserve (FFR) and the microcirculation by both endothelium-independent function (coronary flow reserve, CFR, using intravenous adenosine) and endothelium-dependent function (acetylcholine flow reserve, AChFR, using intracoronary acetylcholine infusion). Those with FFR≤0.80 were excluded per protocol. Coronary microvascular dysfunction was defined a priori as impaired CFR (&amp;lt;2.5) or impaired AChFR (≤1.5). All patients underwent a treadmill EST, using a standard Bruce protocol, with ischaemic electrocardiographic (ECG) changes defined as the appearance of 0.1mV ST-segment depression 80 milliseconds from the J-point. Patients, physiologists, and researchers were all blinded to the coronary physiology data. All data are presented as mean±SD or median (IQR). Results Ninety-one patients [67% female, 62±9 years, CCS 3 (2 to 3)] were recruited into this study. EST was performed 27 (15 to 139) days after angiography. Twenty-seven patients (30%) developed ischaemic ECG changes during their EST (Ischaemic group), whereas 64 patients (70%) did not (Control group). Both groups were phenotypically similar for demographics, risk factors, exercise time and FFR (Figure 1). 100% of the Ischaemic group and 69% of the control group had CMD. Conversely, 38% of patients with CMD developed ischaemic ECG changes on exercise but none (0%) of those with normal microvascular function did (p=0.001) (Figure 2A). The false positive rates with progressively granular reference standards are depicted in Figure 2B; there were no false positive ESTs using a comprehensive physiological reference standard. Angina reported during EST was less specific for CMD than induced ECG changes (70% vs 100%, p&amp;lt;0.001). Conclusions In patients with ANOCA a positive EST is always indicative of CMD. The potential utility of EST as a rule-in test for CMD makes it an attractive non-invasive widely available test that could be re-integrated into clinical pathways for assessing new onset angina.Patient characteristicsEST versus coronary physiology

Evaluation of the residual myocardial ischemia after PCI to long diffuse left anterior descending artery lesions: comparison of IVUS vs FFR

Abstract Background Up to 30% of coronary artery lesions continue to induce myocardial ischemia (FFR ≤ 0.8) despite angiographically successful PCI. This proportion is even larger after PCI to the left anterior descending (LAD) artery as it supplies blood to the largest myocardial territory and often has diffuse disease. Post PCI FFR is an important tool to risk stratify patients, as lower values are associated with a worse prognosis. Therefore, achieving a good functional PCI result after LAD treatment is crucial. PCI optimization tools such as intravascular ultrasound (IVUS) and FFR were both proven to be superior to angiography-guided PCI, however, there is a lack of studies comparing these two modalities head-to-head, especially in the long LAD lesions. Purpose To compare functional PCI result assessed with FFR measured immediately post PCI and at 9-12 months follow-up between IVUS optimization and FFR optimization strategies after percutaneous treatment of long LAD lesions. Methods This was a single center observational study, which enrolled 127 patients. 61 patients underwent PCI optimized with FFR (historical FFR optimization group) and for 66 patients PCI was optimized with IVUS. FFR measurement was performed using intravenous adenosine with a pullback before and after PCI for all patients. Post PCI FFR was recorded in both groups when the PCI result was considered to be final and no more optimization was performed afterwards. Patients also underwent invasive follow-up at 9-12 months post PCI with FFR measurement at the same location (Figure 1). A case example of IVUS optimization strategy is demonstrated in Figure 2. Results The average patients age (66.5 ± 9.5) and baseline clinical characteristics (males 70.1%, diabetes 20.5%, hypertension 92.1%, dyslipidemia 91.3%, smoking 23.0%, chronic kidney disease 21.3%) did not differ between IVUS and FFR optimization groups. IVUS strategy resulted in the longer stented segment compared to FFR group (62 [48-75] mm vs 52 [36-63] mm, p=0.03). The proportion of patients with optimal functional PCI result (FFR &amp;gt; 0.9) did not differ significantly between two groups (16.7% in IVUS group vs 15% in FFR group), however, there was a lower incidence of residual myocardial ischemia in the IVUS optimization group: 0% of patients with post-PCI FFR ≤ 0.8 in the IVUS group vs 13.3% in the FFR group (p=0.002). The trend for smaller ischemia prevalence in IVUS optimization strategy continued during follow-up: there were 4.5% of patients with target vessel related myocardial ischemia in IVUS group and 18.0% in FFR group (p=0.015). Conclusion(s) In the treatment of long LAD lesions IVUS PCI optimization strategy was associated with lower incidence of poor functional PCI result and smaller ischemia burden at follow-up compared to FFR optimization strategy. The implementation of intravascular imaging should be mandatory in the treatment of long diffuse coronary disease.Figure 1Figure 2

Changes in cardiac electrical biomarker with hyperaemic stress: an experimental perspective

Abstract Background "Cardiac electrical biomarker" (CEB) is a numerical index measured by the Vectraplex ECG (vECG) System with Vectraplex AMI software that measures changes in the cardiac electrical field vectors from dipolar to multipolar during myocardial ischemia. CEB performs well in detecting NSTEMI and STEMI against physician adjudicated diagnosis. Purpose To assess changes in CEB during adenosine stress induced ischaemia. Method Thirty-three patients, in the VECTRA-PCI trial, with normal surface ECG (sECG) had CEB measured before (CEB0), at maximal hyperaemia (CEBh)) and 1-(CEB1), 2-(CEB2) and 3-(CEB3) hours after standard fractional flow reserve (FFR) assessment using intravenous adenosine. vECGs were adjudicated for quality by 2 blinded observers. vECGs with artefacts and arrhythmias were discarded and CEBs from best traces were analysed. Forty-nine individuals with non-cardiac chest pain, without past medical history or risk factors for CAD, on no medications, normal ECGs, normal blood profile acted as controls. CEBs (median, IQR) were compared using appropriate tests. Results FFR was normal (&amp;gt;/=0.80) (nFFR) in 25 and ischaemic (&amp;lt;0.80) (iFFR) in 8 patients. CEB0 in nFFR and iFFR groups were similar to each other (p=0.785) (Fig 1) and to controls (30.0; IQR 17.0-44.0, vs nFFR: p=0.057, vs iFFR: p=0.241). Compared to CEB0, CEBh was higher in nFFR (p=0.014) (Fig 1A) and iFFR (p=0.016) groups (Fig 1B). CEBh in iFFR (126.0; 109.5-216.0) higher than nFFR (44.0; 27.8-104.8), (p=0.039). In nFFR group, CEB1, 2 and 3, though numerically lower, were statistically similar to CEBh and CEB0 (Fig 1A) suggesting quick recovery. In iFFR group CEB1 was similar to and CEB2 and 3 were lower than CEBh (Fig 1B) suggesting a slower recovery of CEB. Both CEBh and change from CEB0 to CEBh (δCEB0-h), but not CEB0, predicted ischaemic FFR with similar accuracy (p=0.570) (Fig 2). CEBh &amp;gt;96 and δCEB0-h &amp;gt;28 had similar sensitivity of 87.5% with specificity of 68% and 80% respectively. Conclusion Obstructive coronary atheroma is associated with higher CEB than non-obstructive atheroma under hyperaemic stress. Both CEBh and δCEB0-h accurately predict ischaemic FFR with higher specificity of δCEB0-h. This is the first study to measure CEB changes with hyperaemic stress in patients with coronary artery disease and could have potential for wider clinical application. Figure 1. Changes in the CEB during and after hyperaemic stress in patients with normal (A) and ischaemic (B) FFR. Figure 2. Area under the ROC curve to determine the diagnostic accuracy of pre-procedural CEB, hyperaemic CEB and change in CEB from baseline to hyperaemia in determining ischaemic FFR.Fig 1. Changes in CEB with stress.Fig 2. CEB for ischaemic FFR

Coronary flow reserve predicts response to anti-ischaemic therapy in patients with angina with non-obstructive coronary arteries

Abstract Background Half of all patients with angina have non-obstructive coronary arteries (ANOCA) and therapy is often empirical. The CorMicA trial showed improved symptom scores with a physiology-guided approach but the mechanistic relationship between physiological classification and outcome remains unclear. Purpose To assess if invasively assessed coronary flow reserve (CFR) can predict change in exercise time (ET) and angina-specific quality of life (QOL) in response to anti-ischaemic therapy in patients with ANOCA. Methods Prospective, randomised, crossover trial of consecutively evaluated patients with ANOCA. Inclusion criteria: (i) typical and limiting angina; (ii) non-obstructive coronary arteries (fractional flow reserve &amp;gt;0.80); (iii) normal left ventricular systolic function. Coronary physiological assessment was performed using a pressure and Doppler dual sensor-tipped wire in the left anterior descending artery and microvascular dysfunction defined a priori as CFR&amp;lt;2.5 in response to intravenous Adenosine. Patients, clinicians, and researchers were blinded to coronary physiology data. All patients were then sequentially treated with Amlodipine and Ranolazine (in a randomised order), in 4 week blocks with 1 week washout (Figure 1). The outcome measures are 1) Primary (objective): change in ET on exercise stress testing and 2) Secondary (subjective): change in angina-specific QOL on Seattle Angina Questionnaire (SAQ). Data are presented as mean±SD or median (IQR). Results Sixty-six patients with ANOCA were enrolled into the study [62±8 years, 64% females, CCS 3 (2, 3)]; eight patients were excluded. Forty patients had an impaired CFR (2.0±0.3), whilst 18 patients had normal CFR (3.1±0.6), with similar baseline ET (324±133 vs 321±136 seconds, respectively; p=0.94). Patients with an impaired CFR improved their exercise capacity with Ranolazine (ΔET 70±108 seconds; p&amp;lt;0.01) and Amlodipine (ΔET 70±82 seconds; p&amp;lt;0.01). However, there was no such improvement in patients with normal CFR, with either Ranolazine (ΔET 16±88 seconds; p=0.49) or Amlodipine (ΔET 21±59 seconds; p=0.18) (Figure 2). There was no evidence of a training effect (ΔET between visit 1 and visit 4 was 15±112 seconds; p=0.57). Angina-specific QOL improved in patients with impaired CFR [Ranolazine ΔSAQ 12±18 (p&amp;lt;0.01) and Amlodipine ΔSAQ 8±13 (p&amp;lt;0.01)]; the change in SAQ was less marked in patients with normal CFR [Ranolazine ΔSAQ 7±14 (p=0.07) and Amlodipine ΔSAQ 6±10 (p=0.03)]. Conclusion Patients with impaired CFR demonstrated an improved exercise capacity, whereas patients with normal CFR did not. CFR-guided management of ANOCA is likely to be superior to an empirical strategy. This type of physiology-blinded study design could act as a template for future therapy trials in patients with stable angina.Study design for therapeutic trialResponse to anti-ischaemic therapy

The importance of baseline fractional flow reserve to detect significant coronary artery stenosis in different patient populations.

Fractional flow reserve (FFR) assessment compares the blood flow on either side of a blockage in the coronary artery and indicates how severe the stenosis is in the artery. Intravenous adenosine is widely used to achieve conditions of stable hyperaemia for the measurement of FR. However, intravenous adenosine affects both systemic and coronary vascular beds differentially. Therefore, FFR has some limitations, such as the side effects of adenosine and the long procedure time. In addition, there are not enough studies on the evaluation of the baseline ratio of distal coronary pressure to aortic pressure (Pd/Pa) according to standard cut-off values in coronary stenosis under special clinical conditions. This study aimed to assess the diagnostic power of the baseline FFR value for critical coronary stenosis and to determine its predictive value in special patient groups. This retrospective study included 158 patients, who were stratified as Q1 (< 0.89), Q2 (0.89-0.92), Q3 (0.93-0.95) and Q4 (> 0.95) based on baseline FFR values. The baseline Pd/Pa value, the change in adenosine FFR and the raw FFR change were recorded. Its predictive value was also calculated for specific patient groups. The threshold value of baseline FFR level for predicting critical stenosis was ≤ 0.92 with a sensitivity of 92.8% and a specificity of 82% (upper limit of Q2 cartilage). Patients with a baseline FFR value ≤ 0.92 had a 58.4-fold greater likelihood of a critical outcome compared with patients with a baseline FFR value > 0.92 (OR: 58.4; 95% CI: 20.3-124.6). In patients with a baseline FFR ≤ 0.92, the Q1 group had a 10.23-fold higher odds of critical stenosis compared with the Q2 group (OR: 10.23; 95% CI: 2.14-48.84). The same values had similar diagnostic power for all specific patient groups. The baseline FFR value could be used to predict critical coronary stenosis in our patients and had similar value for predicting lesion severity in all the subgroups.

Abstract 13713: Coronary Endothelial Dysfunction and Microvascular Vasospasm in Patients With Postural Orthostatic Tachycardia Syndrome

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by autonomic dysfunction-related symptoms such as orthostatic intolerance, palpitations, dizziness, and chest pain. The mechanisms driving chest pain in POTS are unclear. Hypothesis: We hypothesized that coronary endothelial dysfunction (ED) and abnormal microvascular reactivity may be a contributor to chest pain in POTS. Methods: Patients (n=6) were diagnosed with POTS or had significant tachycardia despite medical therapy out of 67 patients in our cohort. All patients reported persistent chest pain and were referred for coronary function testing (CFT) to test macro- and micro-vascular function. CFT was performed to test endothelium-dependent and non-endothelium dependent function using graded doses of intracoronary acetylcholine (ACH), and intravenous adenosine (ADO). Coronary Flow Reserve&lt;2.0 and Index of Microvascular Resistance&gt;25 diagnosed coronary microvascular dysfunction. Coronary artery diameter narrowing to ACH (100 mcg) was used to diagnose ED. Epicardial coronary spasm was defined as &gt;90% constriction to ACH. Microvascular spasm was diagnosed by ACH provoked-chest pain and EKG changes in the absence of epicardial spasm. Results: Mean age was 44.1 ± 15.2 years, 67% were female, and all tolerated CFT without complications. POTS symptoms, baseline medications, and CFT results are shown ( Table ). All had an abnormal response to ACH, indicating ED and microvascular spasm. Non-endothelium function was normal in all patients. Anti-anginal medications were changed based on CFT information, with improvement in chest pain with calcium channel blocker use. Conclusion: In all 6 pts, CP was associated with ED and microvascular spasm. Mechanistic links between ED and POTS need further investigation. Given that ED is a prognostic marker associated with recurrent angina hospitalization and events, investigation of therapies that target ED in POTS may be warranted.

Abstract 13210: A Hidden Right Atrial Lipoma in a Patient With Recurrent Sustained Supraventricular Tachycardias

Introduction: Cardiac lipomas, known for their benign nature, compose 8 percent of primary cardiac tumors. Advanced imaging modalities allow improved diagnosis, yet little of their potential complications involving the heart's conduction system is known. Case: A 65-year-old male presented to the Emergency Department with palpitations. History was significant for recurrent sustained orthodromic atrioventricular reentrant tachycardia using a concealed left posterior accessory pathway from a prior EP study. He was treated with ablation twice in the past. The patient was hemodynamically stable on evaluation. ECG showed supraventricular tachycardia (SVT) involving orthodromic re-entry with a ventricular rate of 227 bpm. Computer tomography (CT) of the chest revealed a large, low-attenuated lesion with -102 Hounsfield unit (HU) attached to the right atrial roof, extending to both SVC and IVC. No sparing of foramen ovale was seen. Findings suggest right atrial lipoma. A transthoracic echocardiogram (TTE) visualized the same echo-dense structure without increased vascularity. The patient responded to intravenous Adenosine. We discussed the case with the Cardiothoracic surgery team. Outpatient cardiac MRI and elective surgery were planned. Discussion: The case presented clinically significant atrial arrhythmia in a patient with a massive right atrial lipoma. Although most cardiac lipomas remain asymptomatic, arrhythmias coinciding with the location of involved chambers have been reported. In addition, the recurrence of orthodromic tachycardia despite previous ablation suggests the potential benefit of surgical intervention.

Abstract 14776: Myopericarditis Mimicking Myocardial Infarction With Non-Obstructive Coronary Arteries

This is a case of a 76-year-old female with a past medical history of recurrent paroxysmal symptomatic supraventricular tachycardia (SVT), atherosclerotic heart disease, mild aortic and mitral valve regurgitation, mild-moderate tricuspid regurgitation, right bundle branch block, hypothyroidism and bronchiectasis who presented to her dermatology appointment with palpitations and dizziness. She visited the cardiologist's office and was found to have SVT on electrocardiogram which did not terminate with Valsalva maneuvers. She arrived at the emergency department with chest pain and converted to sinus rhythm after 6 mg of intravenous adenosine was administered. Her troponin peaked to 0.21 and she was admitted with concerns for non-ST segment elevation myocardial infarction. Transthoracic echocardiogram showed left ventricular ejection fractions of 61 percent with no wall motion abnormalities and left atrial and inferior vena cava dilation. She underwent left heart catheterization which only showed mild calcification and minimal luminal irregularities of the left anterior descending artery. Cardiac MRI showed myopericarditis and she was discharged with 0.6 mg of colchicine twice daily with plans for outpatient follow up. Discussion Patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) are discovered to have myocarditis on cardiac MRI 25-30% of time. However, this case uniquely demonstrates myopericarditis as the cause for MINOCA which may not have been previously specified. In addition, it is important to emphasize the utility of Cardiac MRI as a non-invasive modality to diagnose MINOCA “mimics”, especially in the female population.

Tolerability and efficacy of a reduced dose adenosine stress cardiac magnetic resonance protocol under general anesthesia in infants and children.

Intravenous adenosine induces pharmacological stress by causing vasodilatation and thus carries the risk of severe hypotension when combined with vasodilatory effects of anesthetic agents. This study describes our experience with a reduced dose adenosine cardiac magnetic resonance imaging (MRI) protocol in young children under general anesthesia (GA). This is a retrospective report of all patients from birth to 18years who underwent adenosine stress cardiac MRI under GA between August 2018 and November 2022. Based on our anecdotal experience of severe adverse effects in patients receiving adenosine infusion under GA and in discussion with the pediatric anesthesia team, we developed a modified protocol starting at a dose of 110 mcg/kg/min with incremental escalation to a full dose of 140 mcg/kg/min to achieve desired hemodynamic effect. Twenty-two children (mean age 6.5years, mean weight 28kg) satisfied the inclusion criteria. The diagnoses included Kawasaki disease (7), anomalous aortic origin of left coronary artery (3), anomalous aortic origin of right coronary artery (2), coronary fistula (3), repaired d-transposition of great arteries (2), repaired anomalous left coronary artery from pulmonary artery (2), repaired truncus arteriosus with left coronary artery occlusion (1), extracardiac-Fontan with left coronary artery myocardial bridge (1), and post heart transplantation (1). Nine patients needed dose escalation beyond 110 mcg/kg/min. Two patients had transient hypotension during testing (systemic blood pressure drop > 25mmHg). No patient developed significant heart block or bronchospasm. Six patients (repeat study in one) demonstrated inducible perfusion defects (27%) on stress perfusion sequences-5 of whom had confirmed significant coronary abnormalities on angiography or direct surgical inspection. A reduced/incremental dose adenosine stress cardiac MRI protocol under GA in children is safe and feasible. This avoids severe hypotension which is both unsafe and may result in inaccurate data.

PO-02-122 TRACKING AND ABLATING THE MUSCLE SLEEVE/FASCICLE FOR PULMONARY VEIN ISOLATION

Pulmonary vein isolation (PVI) remains the cornerstone for atrial fibrillation (AF) ablation. However, it yields unsatisfactory outcomes requiring repeat procedures especially in persistent AF. Additional linear ablation, or of complex fractionated atrial electrograms, atrial rotors or ganglionated plexi prolongs procedure time and increases complications with small additional benefits. We evaluated the efficacy of a new method of tracking and ablating pulmonary vein (PV) muscle sleeve/fascicle followed by wide area circumferential ablation (WACA) as a method of treatment of AF. To track a muscle sleeve/fascicle, a Lasso catheter was placed into one PV and based on the electrograms pattern on the catheter, sites of exit of muscle sleeves/fascicles were determined along the wide area circumferential ablation (WACA) line. (Panel A of figure shows the electrogram pattern, which suggests two muscle fascicles [red and blue arrows]). Focal ablation at sites on the planned WACA line was then performed to interrupt the muscle sleeve/fascicle connection with atrium (Panel B and C of figure shows point ablation resulting in partial and complete isolation; black arrow marks the location of ablation catheter). The same method was repeated to the ipsilateral PV before full WACA of both PVs was commenced. The strategy was repeated on the contralateral PVs. Ablation of these fascicle-atrium connections resulted in PVI isolation before WACA was completed in all 18 patients. Intravenous adenosine was used at the end to elicit dormant PV connections. We schematically labeled the areas around the PVs into zones and summarized the location of these muscle fascicles in each patient. (Panel D; each dot represents a fascicle and color matches with the PV with which it is associated). Eighteen patients (61±11 years old, 56% male) with AF (12 persistent {67%}) were analyzed in this study. Fascicles were identified in all patients and focal ablation of fascicles resulted in isolation of the PVs. In addition to PVI, 8 had Cavotricuspid isthmus ablation, 1 for right focal atrial tachycardia (AT), one left focal AT, and 1 for biatrial reentrant AT. With a follow-up of 155 ±120 days, 83% of paroxysmal and 75% of persistent AF remained in sinus rhythm. Left atrial dwell time for PVI alone was less than 2 hrs and no complications were seen. The tracking and ablating muscle sleeve/fascicle before performing WACA is a strategy with outcomes superior to previously reported in literature.