Adenosine Testing Research Articles

Noninvasive identification of ANOCA endotypes by stepwise, multi-stress, multi-marker stress echocardiography

Abstract Background Angina with non-obstructive coronary artery disease (ANOCA) is increasingly recognized in clinical practice, but effective therapy is difficult due to the heterogenity of pathophysiological substrates: organic coronary microvascular dysfunction (CMD), functional (vasospastic) CMD, epicardial artery vasospasm, non-cardiac chest pain. Current guidelines recommend invasive coronary function testing with the inherent cost of catheterization time, radiation exposure, iodinated contrast effects and risks of invasive procedures. Objective To evaluate the feasibility of a step-wise, multi-marker, multi-stress assessment of ANOCA patients by stress echocardiography (SE). Methods In a prospective study design, we enrolled 54 ANOCA patients (age =54±14 years, 14 men, 25 %), without significant coronary artery disease (CAD) on invasive or noninvasive angiography. In all patients hyperventilation (HYPER) test (30 deep breaths/min for 5 min) was performed, followed by semi-supine exercise (EX) if negative. All patients underwent adenosine (ADO) test with coronary flow velocity reserve (CFVR) measurement in the mid-distal left anterior descending artery (LAD). Positivity criteria were a coronary flow velocity (CFV) decrease during HYPER despite the increase in the double product (DP) indicating functional CMD i.e. vasoconstriction); the presence of inducible regional wall motion abnormality (RWMA) with HYPER-EX (microvascular/epicardial spasm), and CFVR ≤2.0 with ADO hyperemia (organic CMD). Results Fifty one pts (94%) had normal increase in CFV at ADO: CFV rest 0.264±0.078 vs ADO 0.608±0.133, p<0.001, while 3pts (5%) showed decrease in CFV at ADO suggesting organic CMD. Double product (DP) increased during HYPER (rest 10061 ±2406 vs. HYPER 13580 ±3356, p<0.001). Twenty-nine pts (53%) showed a paradoxical vasoconstrictor response during HYPER despite the increase in DP (CFV decreased during HYPER: CFV rest 0.261±0.059 vs HYP 0.216±0.057, p<0.001). With HYPER-EX, RWMA was induced in 15 patients (27%), while 7 patients had also RWMA during HYPER. Conclusion In patients with ANOCA, a stepwise multi-marker (CFVR and RWMA) and multi-stress (ADO, HYPER and EX) SE identifies CMD phenotypes and actionable therapeutic targets. According to our results functional vasospastic CMD (paradoxical decrease of CFV with HYPER), is more frequent than organic CMD (reduced CFVR with ADO) in patients with ANOCA. Inducible RWMA with HYPER-EX indicate severe vasoconstrictor response.

Coronary microvascular dysfunction in heart failure: observations from the MICRO registry

Abstract Background Heart failure (HF) is one of the leading causes of hospitalization in the elderly. Coronary microvascular dysfunction (CMD), among other risk factors, is linked to the pathogenesis and clinical manifestations of HF. Purpose This abstract aims to summarize key findings from a comprehensive analysis of CMD in subgroups of HF, shedding light on its association with hemodynamic parameters. Methods Patients experiencing recurrent angina (CCS II-IV) and no relevant epicardial stenosis were enrolled in a prospective registry (MICRO). Epicardial and microvascular responses (pressure, resistance and flow) were assessed at rest and during adenosine and acetylcholine testing. The impact of an elevated left ventricular end-diastolic pressure (LVEDP) in the absence of clinical signs of HF was also investigated. Results Overall, 188 patients (63% (118) women, mean age 65±11 years) with angina and no epicardial stenosis were enrolled. Patients with HF (n=26) displayed lower hyperemic flow in response to endothelium-independent adenosine (5.2±3.1 vs. 7.3±4.4; P=0.004), lower coronary flow reserve (2.9±1.5 vs. 4.4±1.1; P<0.001) and microvascular resistance reserve (3.3±2.1 vs. 5.2±2.7; P<0.001), and increased microvascular resistance during adenosine-induced hyperemia (25±21 vs. 17±11; P=0.045). An increased LVEDP without clinical signs of HF was not associated with a lower coronary flow reserve (4.3±1.9 vs. 2.6±1.2; P=0.006) or microvascular resistance reserve (4.9±2.1 vs. 2.8±1.7; P=0.004). Microvascular resistance during acetylcholine (endothelium-dependent)-induced hyperemia was lower in HF patients (36.2±23.5 vs. 57.4±37.8; P=0.018). Conclusion(s) Patients with heart failure displayed signs of impaired microvascular endothelium-independent responses while endothelium-dependent reactivity appears to be maintained. An elevated LVEDP without clinical HF was not associated with impaired coronary microvascular function.

Evaluation of coronary microvascular dysfunction and vasospasm in patients with angina and non-obstructive coronary artery disease

Abstract Background Angina in the absence of obstructive coronary artery disease (CAD) is a growing cause of morbidity and mortality, exceeding the economic burden of CAD. Roughly 50-70% of patients undergoing invasive angiography for anginal symptoms have non-obstructive CAD. Within this category, there are distinct sub-populations including patients with angina without evidence of ischemia on prior stress testing (ANOCA), evidence of ischemia on stress testing (INOCA), or history of obstructive CAD with prior revascularization (ANOCA-HxCAD). Coronary microvascular dysfunction (CMD) and/or epicardial vasospasm are common causes of angina in the absence of epicardial CAD despite optimal medical therapy. Differences between these groups, in terms of risk factors and diagnoses remain relatively unknown. Purpose To compare clinical characteristics, symptoms, and diagnoses between patients with ANOCA, INOCA, and ANOCA-HxCAD. Methods In a prospective registry-based cohort study of 306 patients without obstructive CAD (<50% stenosis in epicardial artery) undergoing coronary functional angiography (CFA), we assessed differences in clinical characteristics, symptoms, and CFA diagnoses: (1) endothelial-independent CMD (coronary flow reserve [CFR] <2.5) to adenosine testing, (2) endothelial-dependent CMD (coronary blood flow [CBF]<50% or no change in vessel diameter to 54 mcg intracoronary acetylcholine [ACH]), (3) epicardial vasospasm to 108 mcg intracoronary ACH in 3 groups of patients (ANOCA, INOCA, and ANOCA-HxCAD). Results Among the 306 patients undergoing CFA, 89% were female with a median age of 58 years (49, 67). Patients with ANOCA-HxCAD had a significantly higher prevalence of hypertension, diabetes, heart failure with preserved ejection fraction, and experienced worse dyspnea on exertion as measured by University of San Diego Shortness of Breath (UCSD SOB) in comparison to ANOCA or INOCA patients. However, there were no differences between the groups in terms of anginal severity, functional capacity, or quality of life. In terms of CFA diagnoses, vasospasm was more prevalent in ANOCA-HxCAD (p<0.001) and CMD was more prevalent in ANOCA and INOCA patients (p=0.034) (Table 1). Conclusions Despite differences in clinical characteristics, patients without obstructive CAD have similar anginal severity, functional capacity, and quality of life regardless of evidence of ischemia on prior stress imaging or history of revascularization. There are differences in CFA diagnoses with higher prevalence of CMD in ANOCA and INOCA patients and higher prevalence of vasospasm in ANOCA-HxCAD patients. Determining the underlying diagnoses changes clinical management; therefore, CFA should be considered in all patients without obstructive CAD.

Prevalence of Coronary Microvascular Dysfunction and Epicardial Spasm in Patients With Angina and Myocardial Bridge

BackgroundMyocardial bridges (MB) are prevalent but not universally associated with angina. The mechanisms linking MB and angina are poorly defined. The objective of this study was to determine the prevalence of epicardial spasm, microvascular spasm, and/or endothelium-independent coronary microvascular dysfunction (CMD) in patients with MB which might explain symptoms. MethodsPatients with known MB and chest pain at the University of Chicago Medical Center between 2020-2023 were included. All patients underwent dobutamine testing with measurement of resting full-cycle ratio to determine hemodynamic significance (resting full-cycle ratio ≤0.76). Endothelium-independent CMD was defined as coronary flow reserve <2.0 or index of microvascular resistance ≥25 on adenosine testing. Microvascular spasm was defined as chest pain and electrocardiogram changes with nonischemic fractional flow reserve with acetylcholine. Epicardial spasm was defined as dynamic stenosis of >90% of the epicardial vessel or ischemic fractional flow reserve (≤0.8) with acetylcholine. ResultsA total of 30 patients (mean age, 47 ± 10 years; 60% female) with MB were studied. Endothelium-independent CMD, microvascular spasm, and epicardial spasm occurred commonly in 60%, 29%, and 37% of patients respectively, with 77% having at least one abnormality. The MB was hemodynamically significant in 47% of patients, and the prevalence of these coexisting conditions was not affected by hemodynamic significance. ConclusionsEpicardial spasm, microvascular spasm, and endothelium-independent CMD are prevalent in patients presenting with known MB and chest pain irrespective of the hemodynamic significance of the bridge. Invasive coronary function testing may play an important role in uncovering alternative explanations for angina in patients with known MB.

Validation of a prediction model for early reconnection after cryoballoon ablation

BackgroundWe previously developed an early reconnection/dormant conduction (ERC) prediction model for cryoballoon ablation to avoid a 30-min waiting period with adenosine infusion. We now aimed to validate this model based on time to isolation, number of unsuccessful cryo-applications, and nadir balloon temperature.MethodsConsecutive atrial fibrillation patients who underwent their first cryoballoon ablation in 2018–2019 at the Leiden University Medical Center were included. Model performance at the previous and at a new optimal cutoff value was determined.ResultsA total of 201 patients were included (85.57% paroxysmal AF, 139 male, median age 61 years (IQR 53–69)). ERC was found in 35 of 201 included patients (17.41%) and in 41 of 774 veins (5.30%). In the present study population, the previous cutoff value of − 6.7 provided a sensitivity of 37.84% (previously 70%) and a specificity of 89.07% (previously 86%). Shifting the cutoff value to − 7.2 in both study populations resulted in a sensitivity of 72.50% and 72.97% and a specificity of 78.22% and 78.63% in data from the previous and present study respectively. Negative predictive values were 96.55% and 98.11%. Applying the model on the 101 patients of the present study with all necessary data for all veins resulted in 43 out of 101 patients (43%) not requiring a 30-min waiting period with adenosine testing. Two patients (2%) with ERC would have been missed when applying the model.ConclusionsThe previously established ERC prediction model performs well, recommending its use for centers routinely using adenosine testing following PVI.Graphical

Role of the clinical radiopharmacist in patient safety during myocardial perfusion imaging with vasodilator stress agents

AimTo assess the radiopharmacist’s role in a multidisciplinary team focused on the contraindications of regadenoson in order to ensure the safe use of pharmacologic vasodilator stress agents in patients undergoing SPECT-MPI. MethodsWe ambispectively studied its safe use in 1905 patients (54.1% female, mean age: 66.6±11.7 years, range: 20–95 years). Sex, age, medical history, medications, drug allergies, and contraindications for stress testing were registered together with recommendations for the nuclear physician in charge. ResultsDetected contraindications and corresponding recommendations were as follows: risk factors for QTc interval prolongation 7.5% – measurement of QTc interval previously to test and monitor ECG; prior stroke or TIA 4.2% – consider carotid stenosis assessment; salicylates/sulfonamides allergy 3.1% – use 99mTc-sestamibi; epilepsy or risk factors for seizures 2.4% – use of adenosine or reconsider test indication; systemic corticosteroid therapy for severe COPD 1.3% – reassessment of patient’s condition; acute exacerbation of COPD 0.8% – defer test until acute episode is over; severe asthma 0.4% – do not perform test; methylxanthine ingestion 0.3% – avoid consumption previously; other 6.1% – evaluation of other contraindications. No contraindications were detected in 73.6% of patients. The test was canceled due to absolute contraindications in 2.9% of the requests. ConclusionsWorking in a systematic way, the radiopharmacist was able to detect a high number of issues related to regadenoson, with one out of four patients presenting some clinical contraindication. The recommendations given by the radiopharmacist were well accepted by the nuclear physicians who changed their approach contributing to increase the safety of patients referred for MPI.

Papel del radiofarmacéutico clínico en la seguridad del paciente durante los estudios de perfusión miocárdica de esfuerzo con vasodilatadores

AimTo assess the radiopharmacist's role in a multidisciplinary team focused on the contraindications of regadenoson in order to ensure the safe use of pharmacologic vasodilator stress agents in patients undergoing SPECT-MPI. MethodsWe ambispectively studied its safe use in 1905 patients (54.1% female, mean age: 66.6±11.7 years, range: 20-95years). Sex, age, medical history, medications, drug allergies, and contraindications for stress testing were registered together with recommendations for the nuclear physician in charge. ResultsDetected contraindications and corresponding recommendations were as follows: risk factors for QTc interval prolongation 7.5% — measurement of QTc interval previously to test and monitor ECG; prior stroke or TIA 4.2% — consider carotid stenosis assessment; salicylates/sulfonamides allergy 3.1% — use 99mTc-sestamibi; epilepsy or risk factors for seizures 2.4% — use of adenosine or reconsider test indication; systemic corticosteroid therapy for severe COPD 1.3% — reassessment of patient's condition; acute exacerbation of COPD 0.8% — defer test until acute episode is over; severe asthma 0.4% — do not perform test; methylxanthine ingestion 0.3% — avoid consumption previously; other 6.1% — evaluation of other contraindications. No contraindications were detected in 73.6% of patients. The test was cancelled due to absolute contraindications in 2.9% of the requests. ConclusionsWorking in a systematic way, the radiopharmacist was able to detect a high number of issues related to regadenoson, with one out of four patients presenting some clinical contraindication. The recommendations given by the radiopharmacist were well accepted by the nuclear physicians who changed their approach contributing to increase the safety of patients referred for MPI.

Optimization of superior vena cava isolation with aid of ablation index guidance.

To investigate the optimal range of quantitative ablation index (AI) value during superior vena cava (SVC) electrical isolation by radiofrequency catheter ablation (RFCA). First, in a development cohort of patients with atrial fibrillation (AF), the RFCA with 40 W was performed to complete SVC isolation guided by the conduction breakthrough point from the right atrium to SVC. Then, the range of AI value was calculated by offline analysis on different segments of SVC. Lastly, for the validation of AF patients, the safety and effectiveness of SVC isolation with the optimized target range of AI value were evaluated with an additional adenosine test. A total of 101 patients with AF were included in the study (44 patients in the development cohort/57 in the validation cohort). The segmental ablation strategy was applied in 70% of the patients. According to the offline analysis of the AI values in the development cohort, the target AI value range was set as 350-400. The success rate of SVC isolation in the validation cohort was significantly higher than that in the exploration cohort (100% vs. 90.9%, p = .02), and no complications occurred in the exploration cohort. During the adenosine test, the recovery rate of electrical conduction in SVC was significantly lower than that in the pulmonary vein (3.5% vs. 17.5%). The target AI value with a range from 350 to 400 is safe and effective for high-power RFCA to complete SVC isolation.

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.

Syncopal patients without prodromes exhibit a diverse pattern of adenosine release during head-up tilt test

Abstract Background/Introduction In a significant proportion of patients with neurally-mediated syncope (NMS), the mechanism of syncope remains largely undetermined. Adenosine has been proposed as a central humoral factor in various forms of NMS: high Adenosine Plasma Levels (ADP) are encountered in patients with vasovagal syncope (VVS), low ADP in non-prodromes syncope (NPS), while ADP in patients with situational syncope SS are less well determined. Purpose We sought to assess ADP in patients with different clinical forms of syncope, with an emphasis on the presence or absence of prodromal symptoms, as well as the relation between ADP and the outcomes of Head-Up Tilt Table Test (HUTT) and Adenosine test (ADT). Methods Patients with different clinical types of NMS (n=124), i.e., VVS, NPS, or SS, were investigated using a standard protocol including HUTT and ADT. During HUTT, ADP was measured in the supine position, at table tilting, and in syncope. Results Baseline ADP did not differ among groups. ADP at syncope were higher in NPS compared to VVS (1.55±1.29 vs 0.16±0.05 μM, p=0.03) and SS (0.15±0.05 μM, p=0.02). In NPS, ADP increased from the supine position to the time of syncope (0.47±0.25 to 1.55±1.29 μM, p=0.04). In VVS, ADP increased only from the supine to the tilt position (0.23±0.04 to 0.35±0.10 μMu, p=0.02), while in SS ADP did not change in any stage of HUTT. SS was associated with cardioinhibitory HUTT (OR 3.40, 95% CI 1.05 to 9.56, p=0.04) and positive ADT (OR 4.22, 95% CI 1.47 to 11.46, p=0.012). Conclusion(s) A distinct pattern of ADP increase is noted during HUTT in NPS, suggesting that an excessive increase of ADP may play the key role in triggering this type of clinical presentation of syncope independently of the baseline ADP. Cardioinhibition prevails in patients with SS without clear adenosine involvement. Such observations contribute to an enhanced understanding of the pathophysiology of different clinical forms of syncope which may offer the possibility to tailor the management approach appropriately. Funding Acknowledgement Type of funding sources: None.

Thermodilution-derived coronary absolute flow and resistance in patients with different INOCA endotypes

Abstract Background Thermodilution-derived measurement of absolute coronary flow and resistance has been recently validated by using a dedicated microcatheter and a pressure-temperature guidewire. Coronary absolute flow (AbsF) and derived absolute resistance (AbsR) can give precious information about the microcirculation in patients with ischemia and non-obstructive coronary artery disease (INOCA). The correlation with different INOCA endotypes has been so far poorly investigated. Methods 108 INOCA patients underwent a complete evaluation of underwent coronary function testing, including acetylcholine (ACH) provocation testing, adenosine testing (CFR/IMR) and functional assessment of the left anterior descending artery using thermodilution-derived measurement of AbsF and AbsR. Results Among 108 INOCA patients, 64% showed coronary microvascular dysfunction (CMD) with positive ACH reaction (ACH+) and/or abnormal CFR/IMR (CFR/IMR+), of whom 38% presenting with an isolated structural component (CFR/IMR+) and 62% with an isolated vasospastic component (ACH+). Among ACH+ patients, epicardial vasospastic angina was detected in 28.2% of the patients. AbsF was found significantly lower in ACH+ patients than in ACH− patients (0.174±0.09 vs 0.2019±0.09, p=0.03). Similarly, a trend of higher AbsR values was found in ACH+ patients as compared to ACH− (612.5±226.5 vs 524.5±171.2, p=0.07, Fig. 1A). AbsF was found significantly lower in patients with coronary microvascular dysfunction (CMD) than in patients without either vasospastic or structural component of CMD (0.172±0.06 vs 0.202±0.09, p=0.05) and AbsR showed a trend towards higher values in patients with CMD than patients without CMD. (609.3±208.8 vs 557.7±193.1, p=0.08, Fig. 1B) AbsF and AbsR did not differ in patients with and without abnormal adenosine testing only: AbsF (0.176±0.06 vs 0.197±0.09, p=0.31) and AbsR 589.8±183.0 vs 565.2±190.2, p=0.27). A modest correlation was found between AbsQ and IMR (r: −0.2: p: 0.05, Fig. 2). Conclusion Coronary vasomotor dysfunction is highly prevalent in INOCA patients and a complete coronary function evaluation, including provocative test should be performed. Continuous thermodilution is safe and easily implemented in INOCA patients and provide new insights in the assessment of INOCA endotypes with high reproducibility. The exact diagnostic and prognostic value of these measurements, and their optimal cutoff, should be assessed in future studies. Funding Acknowledgement Type of funding sources: None.

Haemodynamic indicators of arteriolar dysregulation during combined hyperventilation and exercise test in patients with ANOCA (SESPASM)

Abstract Introduction In patients with angina and non-obstructed coronary arteries (ANOCA), functional dysregulation such as epicardial coronary spasm and microvascular dysfunction (microvascular spasm and /or impaired microvascular dilatation) frequently coexist. The aim was to analyse haemodynamic indicators of arteriolar dysregulation during combined hyperventilation and exercise stress echo test in patients with ANOCA. Methods In a prospective study we enrolled 38 patients (56±13 years, 31 females) with ANOCA, proven by normal coronary angiogram. Stress echocardiography protocol with Doppler measurements of coronary flow consisted of hyperventilation test for spasm provocation (HYP, respiratory rate of 30 per min for 5') followed by supine bicycle exercise test (HYP+EXE) for assessment of endothelium dependent function. Adenosine test was done (ADO 140 mcg/kg in 1 min) for estimation of endothelium independent vasodilatation. Coronary flow velocity (CFV) was assessed in distal LAD by Transthoracic Doppler echocardiography at the end of the each stage of the test. Abnormal response to HYP was a CFV ratio (stress/rest) &amp;lt;1.0 (vasoconstrictor response). CFV ratio at peak HYP+ EXE was an indicator of endothelial dependent vasodilatation (&amp;lt;2 blunted response). An abnormal response to ADO was a CFV reserve &amp;lt;2.0 (blunted vasodilatory response). Results The double product increased during HYP in comparison to rest (13263 vs 10321, p&amp;lt;0.001), and further increased with EXE (23817 vs HYP, p&amp;lt;0.001). Chest pain was present in 6 pts during HYP, and in additional three pts during HYP+EXE (15.8% vs 23.7%, p=0.25). ST segment depression was present in 6 pts during HYP and 23 during HYP+EXE (15.79% vs 60.52%, p&amp;lt;0.001). Wall motion abnormality was provoked with HYP in three pts (7.89%) and in ten (26.3%) with HYP+EXE (p=0.016). CFV ratio was abnormal for vasoconstriction during HYP in 16 (42.1%) and blunted in 23 (60.52%) pts during HYP+EXE (Fig 1). Vasodilation during ADO was preserved in all patients, but one. There was significant difference between CFV reserve during HYP+EXE vs ADO (1.98±0.49 vs 2.53±0.43 respectively, p&amp;lt;0.001) (Fig. 2). Conclusion Our results indicate that HYP induce microvascular dysfunction with vasospastic component which is reflected in reduced CFV ratio. This prevents the normal hyperemic response during EXE in more than a half of patients. Endothelial independent vasodilatation during ADO hyperemia was perserved in all patients, excluding structural microvasculature remodeling. HYP+EXE provocation with noninvasive measurement of coronary flow is a promising test for assessing mechanism of arteriolar dysregulation in ANOCA patients. Funding Acknowledgement Type of funding sources: None.

ПРОГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ФУНКЦИОНАЛЬНОЙ ПРОБЫ МОЗГОВОГО КРОВОТОКА С АДЕНОЗИНТРИФОСФАТОМ ПО ДАННЫМ ОФЭКТ С 99mTc-ГМПАО У ПАЦИЕНТОВ С АТЕРОСКЛЕРОЗОМ СОННЫХ АРТЕРИЙ

Introduction: Previously, a functional test with intravenous administration of adenosine triphosphate (ATP) was proposed to assess the reactivity of cerebral circulation and the functional significance of internal carotid artery stenoses, with evaluation by brain SPECT (neuroSPECT) with 99mTc-HMPAO. The types of the reaction of the cerebral blood flow during it were identified, with different ratios of internal carotid artery stenoses and the degree of ischemic brain damage assessed according to brain MRI data. However, the prognostic value of the results of the ATP test of cerebral blood flow in relation to disorders of cerebral circulation (NMC) remains unknown. Purpose: In a retrospective study, we tried to study the prognostic value of the ATP test of cerebral blood flow in relation to the risk of subsequent disorders of cerebral circulation. Material and methods: The retrospective study included 37 patients with atherosclerotic stenosis of the carotid arteries, who in 2002–2005 underwent functional studies of cerebral blood flow with a sample with intravenous administration of ATP solution. Brain damage was quantified according to MRI data (Magnetom Open, Siemens) in a T2-weighted mode, according to a previously developed technique. Denoting Iliq – the intensity of the T2 signal from the cerebrospinal fluid in the ventricles of the brain, Iinsult – in the area affected by ischemia, and Inorm – in the area of the unaffected brain, the volume of the damaged tissue (VDT) was calculated as the sum taken from all sections i, where the area of brain damage is visible: VDT=Σid·Si∙[(Iinsult ‒ Inorm)/(Iliq ‒ Inorm)]i, where d is the thickness of the slice, and Si is the area of the ischemia area on the slice i. The quota of damaged tissue in the physical volume of the lesion area is then obviously eqal to : QD={Σid·Si∙[(Iinsult ‒ Inorm)/(Iliq ‒ Inorm)]i}/{Σid·Si}. NeuroSPECT with 99mTc-HMPAO (540 MBq) in each patient was carried out at rest and with intravenous administration of ATP solution (100 μg / kg of weight, intravenously slowly for 1 min under ECG control). The asymmetry of the cerebral blood flow was evaluated at rest and in a sample with ATP as the 99mTc-HMPAO accumulation asymmetry index (AI) – the interhemispheric ratio of the average 99mTc-HMPAO absorption score in the middle cerebral artery basin. Results: In accordance with the previously presented classification, patients were assigned to one of three groups – with different types of brain blood flow reaction to a stress test with ATP. In 14 individuals (type 1), a symmetrical distribution of blood flow at rest was noted (AI=0.98±0.01), while the ATP test caused an asymmetry in the uptake of 99mTc-HMPAO (AI=0.91±0.04), due to a decrease on the side of the stenosis-dependent hemisphere (unilateral stenosis of the common and/or internal carotid arteries, exceeding 55 %), without signs of damage to the cerebral cortex. In 11 patients with previous ischemic brain injuries (type 2), proven by MRI, the carotid arteries were patent, including after carotid endarterectomy (5 patients) or after correction of stenosis with a stent (three). Rest asymmetry of blood flow was present (AI=0.92±0.03). The ATP test increased blood supply on the side of injury if, according to T2-weighted MRI in the ischemic area, QD&lt;0.35. Due to this, in general, there was a significant decrease in the absorption asymmetry of 99mTc-HMPAO (AI=0.96±0.03) during the ATP test. In 12 patients (type 3) with predominantly unilateral 50‒90 % carotid artery stenosis and ischemic stroke on the same side (group III), the hemispheric asymmetry of blood supply to the brain, noted already at rest (AI=0.96±0.03), increased (AI=0.93±0.03) with an adenosine test. When analyzing the results of a two-year follow-up, it turned out that frequent transient ishemic attacs, minor strokes and strokes developed only in patients in whom the adenosine test induced or increased the interhemispheric asymmetry of 99mTc-HMPAO accumulation by more than 5 % – four with type 1 reactivity, and three with type 3 reactivity Conclusions: Thus, perfusion neuroSPECT with 99mTc-HMPAO and ATP stress-test can be employed to identify patients with a reduced reserve of cerebral perfusion, who have an increased risk of ischemic stroke. Quantitative analysis of T2-weighted MRI gives an estimate of the proportion of viable brain tissue in the focus of the past ischemia, in which reactivity is preserved.

Clinical Significance of Adenosine-Induced Atrial Fibrillation after Complete Pulmonary Vein Isolation.

Background: Adenosine can cause dormant electrical conduction between the pulmonary vein and left atrium after pulmonary vein isolation (PVI). Adenosine can also induce atrial fibrillation (AF) during catheter ablation. However, the clinical outcomes and effects of additional ablation for the trigger sites of adenosine-induced AF (AIAF) are unknown. This study therefore aimed to evaluate the clinical significance of AIAF. Methods: Between January 2010 and September 2019, we analyzed 616 consecutive patients with paroxysmal AF (PAF) who underwent radiofrequency catheter ablation (RFCA), including wide-area circumferential pulmonary vein isolation (PVI) and post-PVI adenosine testing. Results: Among 616 patients, 134 (21.7%) and 34 (5.5%) showed dormant conduction and AIAF, respectively. Eight patients (1.3%) had both dormant conduction and AIAF. The AF recurrence rate was not significantly different between patients with and without AIAF (16.7% vs. 18.6%, log-rank p = 0.827) during a mean follow-up period of 17.9 ± 18 months. Additional RFCA for the trigger site was attempted in 10 patients with AIAF; however, the recurrence rate of atrial arrhythmias was also not different between the groups with and without additional ablation (20% vs. 16.7%, log-rank p = 0.704). Conclusions: AIAF after PVI was not clinically associated with recurrence during long-term follow-up. Ablation of the trigger site in AIAF did not improve the clinical outcomes.

Presence of Coronary Endothelial Dysfunction, Coronary Vasospasm, and Adenosine-Mediated Vasodilatory Disorders in Patients With Ischemia and Nonobstructive Coronary Arteries.

Coronary function testing in patients with ischemia and nonobstructive coronary arteries (INOCA) commonly includes assessment of adenosine-mediated vasodilation and acetylcholine spasm provocation. The purpose of this study was to evaluate the diagnostic value of additional endothelial function testing for the diagnosis of vasomotor dysfunction in patients with INOCA. In this retrospective cohort study, we included patients with INOCA who underwent clinically indicated comprehensive coronary function testing. Endothelial dysfunction was defined as a <50% increase in coronary blood flow, determined by Doppler flow, and/or epicardial vasoconstriction compared to baseline, in response to low-dose acetylcholine. Coronary artery spasm (CAS) was defined as vasospastic angina or microvascular angina in response to coronary high-dose acetylcholine. An impaired adenosine-mediated vasodilation was defined as a coronary flow reserve <2.5 and/or hyperemic microvascular resistance ≥2.5. Among all 110 patients, 79% had endothelial dysfunction, 62% had CAS, and 29% had an impaired adenosine-mediated vasodilation. Endothelial dysfunction was present in 80% of patients who tested positively for CAS and/or an impaired adenosine-mediated vasodilation. Endothelial function testing increases the diagnostic yield of coronary function testing that only incorporates adenosine testing and spasm provocation by 17% to 92%. Of patients with normal adenosine-mediated vasodilation and no inducible CAS, 68% had endothelial dysfunction. Concomitant endothelial dysfunction was prevalent in the vast majority of patients with INOCA with inducible CAS and/or an impaired adenosine-mediated vasodilation. In patients with INOCA without inducible CAS and normal adenosine-mediated vasodilation, two-thirds had endothelial dysfunction. These results indicate the relevance to perform endothelial function testing in patients with INOCA in view of its therapeutic implication.

Syncope without prodromes is associated with excessive plasma release of adenosine at the time of syncope during head-up tilt table test

BackgroundIn syncopal patients without underlying structural disease, we sought to investigate the association of Adenosine Plasma Levels (ADP) with the clinical presentation of neurally mediated syncope (NMS) and the outcomes of Head-Up Tilt Table Test (HUTT) and Adenosine test (ADT). MethodsWe studied 124 patients with different clinical types of NMS, i.e., Vasovagal (VVS, n=58), non-prodromes (NPS, n=18), or situational syncope (SS, n=48), using a standard protocol including HUTT and ADT. During HUTT, ADP was measured in the supine position, at table tilting and in syncope. ResultsBaseline ADP did not differ among groups. ADP at syncope were higher in NPS (n=5) compared to VVS (n=20): 0.23 vs. 0.12 μΜ, p=0.03, and SS (n=22): 0.04 μΜ, p=0.02. In NPS, ADP increased from supine to syncope (n=5): 0.15 vs. 0.23 μΜ, p=0.04. In VVS, ADP increased only from supine to tilt position: 0.11 vs. 0.14 μΜ, p=0.02. In SS, ADP did not change during HUTT. In positive vasodepressor HUTT, ADP increased from supine to tilt position (p=0.002) and at syncope (p=0.01). In SS, 20.0% exhibited cardioinhibitory HUTT vs. 6.8% in other forms of syncope (p=0.04). In SS, 22.9% manifested positive ADT vs 6.6% in other types of syncope (p=0.012). ConclusionThe subset of NPS patients with positive HUTT, show excessive ADP release at the time of syncope. This may explain the lack of prodromes in this form of syncope. Such observations contribute to the understanding of distinct profiles of clinical forms of syncope and may differentiate the management approach accordingly.

Adenosine, adenosine- deaminase and implantable recorder outcome in syncopal patients.

Adenosine test was proposed as atool for identification of syncopal patients who benefit from pacemaker implantation. Aim of the study was to assess the relationship between adenosine levels, the outcome of adenosine test and results of implantable loop recorder (ILR) monitoring in patients with syncope. In 29 patients (mean age 59±11 years, 15 men, 14 women) with unexplained syncope ILR was implanted. In addition, adenosine test (intravenous injection of 20mg adenosine bolus) and assays of plasmatic adenosine and adenosine-deaminase were performed. Adenosine test was positive in 15 patients and negative in 14 patients. Patients with positive adenosine test had lower adenosine levels compared to patients with negative test (8.86±2.07ng/ml vs. 15.18±2.14ng/ml, p=.04). No difference was observed in adenosine deaminase levels (16.35±2.20 IU/l vs. 13.20±2.48 IU/l, p=.40). There was a negative correlation between adenosine level and AVB duration during adenosine test (p=.04; R2 =0.22). Patients with positive adenosine test had more frequent asystole during ILR monitoring than patients with negative test (9pts vs. 1pt, p=.005). Adenosine levels were lower in patients with asystolic syncope on ILR compared to vasodepressor syncope 8.20±2.86ng/ml versus 13.27±7.26ng/ml, p=.05). Patients with positive adenosine test have decreased production of endogenous adenosine compared to patients with negative adenosine test. Positivity of adenosine test and low adenosine level in the peripheral blood were associated with more frequent asystolic episodes during ILR monitoring.

PO-710-04 CONTEMPORARY PREVALENCE AND PREDICTORS OF INTACT PULMONARY VEIN ISOLATION IN PATIENTS UNDERGOING REPEAT ATRIAL FIBRILLATION ABLATION

Pulmonary vein isolation (PVI) is the primary goal of atrial fibrillation (AF) ablation. Prior studies have noted a 50-95% prevalence of pulmonary vein (PV) reconnection at the time of repeat ablation. However, the prevalence of PV reconnection with contemporary AF ablation techniques, including high frequency jet ventilation, is unknown. Furthermore, there is an incomplete understanding of predictors of intact PVI at the time of repeat ablation. To assess the prevalence of PV reconnection in a contemporary cohort utilizing jet ventilation, contact force catheters, and adenosine testing for dormant conduction, and identify patient characteristics and ablation techniques that predict PVI at time of repeat ablation. We reviewed 615 consecutive radiofrequency AF ablations from 2013-2019 at an academic medical center performed by a single operator. There were 121 unique patients who underwent a de novo AF ablation followed by a repeat AF ablation. We evaluated clinical and previous procedural characteristics to identify predictors of PVI at the time of repeat ablation, using logistic regression models. Of the 121 patients, 42.1% were female, average age was 64.5 years, and BMI 31. At the time of repeat ablation, 57% (n=69) had intact prior PVI. Baseline characteristics of patients with intact PVI and reconnected PVI were similar, including age (64 years and 65 years; p=0.75), left atrial diameter (4.13 cm and 4.39 cm; p=0.09), left ventricular ejection fraction (54.5 % and 55.4%; p = 0.38), and time to first atrial fibrillation recurrence (237 days v. 344 days, p=0.28). The only significant clinical predictor of intact PVI was the pre-procedure diagnosis of atypical atrial flutter (20.3 % v. 3.8%, p=0.02) (Figure 1). In multivariate analysis, prior mitral line ablation (OR 8.93, 95%CI [3.65, 21.87]: p <0.01) and first pass isolation of right pulmonary vein during the index AF ablation (OR 2.59, 95% CI [1.09, 6.12]: p = 0.03) strongly predicted intact PVI at the time of repeat AF ablation. With contemporary techniques, PVI reconnection is seen in 43% of patients at the time of repeat AF ablation. History of atypical flutter, prior mitral line ablation, and first pass isolation of the right PVs were significant predictors for intact PVI.

Coronary microvascular dysfunction and findings of heart failure with preserved ejection fraction in patients with microvascular angina.

Coronary microvascular dysfunction (CMD) may cause symptoms of myocardial ischemia (microvascular angina [MVA]), but recent studies suggested that it might also contribute to the syndrome of heart failure with preserved ejection fraction (HFpEF). In this study we assessed the relation of CMD with findings of HFpEF in MVA patients. We enrolled 36 consecutive patients with MVA, in whom we assessed: 1) coronary blood flow (CBF) response to adenosine and cold pressor test (CPT) by color-Doppler echocardiography of the left anterior descending coronary artery; 2) complete echocardiographic examination; 3) N-terminal-pro-B-natriuretic peptide (NT-proBNP); 4) grade of dyspnea by the modified Medical Research Scale. Among patients, 15 had definite HFpEF findings (group 1), 12 had equivocal HFpEF findings (group 2) and 9 had no evidence of HFpEF findings (group 3). Group 1 patients were older, had more cardiovascular risk factors and higher NT-proBNP levels (P=0.018), and showed a higher prevalence of diastolic dysfunction. Left ventricle dimensions and systolic function, however, did not differ among groups. Dyspnea was also not significantly different among groups (P=0.19). CBF to adenosine was 1.85±0.47, 1.78±0.40 1.49±0.32 in group 1, 2 and 3, respectively (P=0.13). Similarly, CBF response to CPT was 1.57±0.4, 1.49±0.2 and 1.45±0.3 in the 3 groups, respectively (P=0.74). Both CBF response to adenosine and CPT showed no relation with the severity of dyspnea symptoms. Our data suggest that in patients with MVA there is no relation between the grade of impairment of coronary microvascular dilatation and findings of HFpEF.

Relation Between Coronary Tortuosity and Vasomotor Dysfunction in Patients Without Obstructed Coronaries?

Background: A large proportion of patients with angina and no obstructive coronary artery disease (ANOCA) has underlying coronary vasomotor dysfunction (CVDys), which can be diagnosed by a coronary function test (CFT). Coronary tortuosity is a common angiographic finding during the CFT. Yet, no data exist on the association between vasomotor dysfunction and coronary tortuosity.Aim: To investigate the association between CVDys and coronary tortuosity in patients with ANOCAMethods: All consecutive ANOCA patients who underwent clinically indicated CFT between February 2019 and November 2020 were included. CFT included acetylcholine spasm testing to diagnose epicardial or microvascular spasm, and adenosine testing to diagnose microvascular dysfunction (MVD). MVD was defined as an index of microvascular resistance (IMR) ≥ 25 and/or coronary flow reserve (CFR) <2.0. Coronary tortuosity, was scored (no, mild, moderate or severe) based on the angles of the curvatures in the left anterior descending (LAD) artery on angiography.Results: In total, 228 patients were included (86% female, mean age 56 ± 9 years). We found coronary artery spasm in 81% of patients and MVD in 45% of patients (15%: abnormal CFR, 30%: abnormal IMR). There were 73 patients with no tortuosity, 114 with mild tortuosity, 41 with moderate tortuosity, and no patients with severe tortuosity. No differences were found in cardiovascular risk factors or medical history, and the prevalence of CVDys did not differ between the no tortuosity, mild tortuosity and moderate tortuosity group (82, 82, and 85%, respectively).Conclusion: In this study, CVDys was not associated with coronary tortuosity. Future experimental and clinical studies on the complex interplay between coronary tortuosity, wall shear stress, endothelial dysfunction and coronary flow are warranted.