Administration Of Adenosine Research Articles

Late Phases of Cardioprotection During Remote Ischemic Preconditioning and Adenosine Preconditioning Involve Activation of Neurogenic Pathway.

The role of the neurogenic pathway in early phases of cardioprotection during remote ischemic preconditioning (RIPC) and adenosine preconditioning is reported. This study was designed to explore the involvement of the neurogenic pathway in late phases of cardioprotection during RIPC and adenosine preconditioning. Fifty-four Wistar rats were used and divided into 9 experimental groups. RIPC was induced by tying the blood pressure cuff around the hind limb and subjecting to 4 cycles of inflation and deflation of 5 minutes each. In early RIPC, the heart was isolated immediately after the last episode of RIPC, whereas in late RIPC, the heart was isolated 24 hours after the last cycle of RIPC. In a similar way, adenosine preconditioning was instituted in early and late phases by either isolating the heart 40 minutes or 24 hours after adenosine (4 mg/kg, intraperitoneally [i.p.]) administration. Isolated hearts were subjected to ischemia-reperfusion (I/R) injury on the Langendorff's system. Both early and late phases of RIPC and adenosine preconditioning significantly abrogated I/R-induced myocardial injury in terms of decrease in the release of lactate dehydrogenase, creatine kinase, and decrease in infarct size. Pretreatment with hexamethonium, a ganglion blocker (20 mg/kg, i.p.), significantly abolished the cardioprotective effects of both early and late phases of RIPC and adenosine preconditioning. Apart from the involvement of the neurogenic pathway in the early phases, there is a critical role of the neurogenic pathway in the late phase of cardioprotection during RIPC and adenosine preconditioning.

A multicentered evaluation of ablation at higher power guided by ablation index: Establishing ablation targets for pulmonary vein isolation.

Pulmonary vein isolation (PVI) using high power delivered by SmartTouch Surround Flow (STSF) catheters guided by ablation index (AI) was evaluated in a multicenter registry. Patients with paroxysmal AF underwent PVI with STSF catheters using 30 W on the posterior wall and 40 W elsewhere. AI targets were 350 posterior walls and 450 elsewhere. Procedures were compared with controls using conventionally irrigated contact force-sensing catheters using conventional powers (25 W posterior wall and 30 W elsewhere) guided by force-time integral (no agreed targets). The waiting period of 30 minutes was observed before adenosine administration to assess acute pulmonary vein (PV) reconnection. One hundred patients from four centers were included: 50 patients in the high power ablation index (HPAI) group and 50 controls. Procedure time was 22% shorter in the HPAI group (156 [133.8-179] vs 199 [178.5-227] minutes; P < 0.001). Duration of the radiofrequency application was 37% shorter in the HPAI group (27.2 [21.5-35.8] vs 43.2 [35.1-52.1] minutes; P < 0.001). Acute PV reconnection was reduced (28 of 200 [14%] vs 48 of 200 [24%] veins; P = 0.015). Reconnection was predicted by a largest interlesion distance greater than 6 mm, a lesion with impedance drop less than 2.5 Ω, contact force less than 6 g, or less than 68% of the regional AI target (all P < 0.001). Freedom from atrial arrhythmia at 1 year off antiarrhythmic drugs after a single procedure was 78% in the HPAI group vs 64% in the control group ( P = 0.186). High-powered ablation guided by AI was safe and led to shorter procedure times with reduced acute PV reconnection compared with conventional ablation.

Supraventricular tachycardia of the sick, a unique entity.

This study explored a unique form of atrioventricular nodal reentrant tachycardia (AVNRT) in which certain acutely ill patients have a first episode of supraventricular tachycardia (SVT) with a short RP interval. A retrospective chart review was conducted of patients at a single institution who developed SVT with short RP and yielded 19 patients. None of the 19 patients had a prior history of AVNRT or any other arrhythmia. The mean age was 58 years, the majority of patients were male (13/19), and there was a presence of hypertension (10/19), diabetes mellitus (5/19), hyperlipidemia (7/19), congestive heart failure (2/19), coronary artery disease (3/19), obstructive sleep apnea (2/19), and active cancer (8/19). The reasons for admission were planned surgery (8/19), sepsis (8/19), drug abuse (2/19), and neurological disorder (2/19). The AVNRT either terminated spontaneously or following the administration of adenosine. The patients were treated with amiodarone (12/19), metoprolol (6/19), or diltiazem (1/19). Follow-up (mean: 370 days) details revealed that patients were on amiodarone (3/19), metoprolol (6/19), were not taking any cardiac medication (5/19), or had passed away (5/19). Only 1 patient had a recurrence of AVNRT, and none of the patients required ablation therapy. 'AVNRT of the sick' has not been previously described in the medical literature, to our knowledge. It can be successfully treated with medications and the chance of recurrence after resolution of the acute illness is small.

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

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

Instantaneous wave-free ratio (iFR®) to determine hemodynamically significant coronary stenosis: A comprehensive review.

Coronary angiography is considered to be the gold standard in the morphological evaluation of coronary artery stenosis. The morphological assessment of the severity of a coronary lesion is very subjective. Thus, the invasive fractional flow reserve (FFR) measurement represents the current standard for estimation of the hemodynamic significance of coronary artery stenosis. The FFR-guided revascularization strategy was initially classified as a Class-IA-recommendation in the 2014 European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines on myocardial revascularization. Both the Deferral vs Performance of Percutaneous Coronary Intervention of Functionally Non-Significant Coronary Stenosis and Flow Reserve vs Angiography for Multivessel Evaluation studies showed no treatment advantage for hemodynamically insignificant stenoses. With the help of FFR (and targeted interventions), clinical results could be improved; however, the use in clinical practice is still limited due to the need of adenosine administration and a significant prolongation of the length of the procedure. Instantaneous wave-free ratio (iFR®) is a new innovative approach for the determination of the hemodynamic significance of coronary stenosis, which can be obtained at rest without the use of vasodilators. Regarding the periprocedural complications as well as prognosis, iFR® showed non-inferiority to FFR in the SWEDEHEART and DEFINE-FLAIR trials. Furthermore, iFR®, enhanced by iFR®-pullback, provides the possibility to display the iFR®-change over the course of the vessel to create a hemodynamic map.

Microsurgical treatment strategy for large and giant aneurysms of the internal carotid artery

ObjectiveWe aimed to summarize our microsurgical treatment results for large (10–25 mm) and giant (≥25 mm) intradural internal carotid artery (ICA) aneurysms over a 7-year period at a single institution and to describe our detailed strategy. Patients and methodsWe reviewed the records of 68 patients with 69 aneurysms, including large and giant intradural ICA aneurysms, treated using microsurgical techniques from January 2008 to December 2014. We used adenosine-induced cardiac standstill or retrograde suction decompression for some aneurysm clipping cases and performed bypass surgery if needed. ResultsFifty-eight large and giant ICA aneurysms (84%) were treated with direct clipping, including 6 aneurysms (9%) clipped using adenosine-induced cardiac standstill and 10 aneurysms (14%) clipped using suction decompression. Eleven unclippable aneurysms (16%) were trapped with extracranial-intracranial bypass. Good or excellent results (modified Rankin Scale scores 0–2) were obtained in 47 patients with unruptured aneurysms (92%) and in 14 patients with ruptured aneurysms (82%) at the 6-month follow-up. Of 17 patients with visual disturbances before treatment, 11 (65%) had improved vision after surgical treatment. A remnant sac was found in 20 cases (29%) on digital subtraction angiography performed immediately postoperatively. At the median follow-up of 22 months, we encountered 3 recurrent aneurysm cases (5%) among the 58 aneurysms that were followed up. ConclusionOur study demonstrated that microsurgical treatment of large and giant intradural ICA aneurysms remains competitive to flow-diverting treatment, if the surgeon is prepared to perform multifarious surgical methods, including adenosine administration, retrograde suction decompression, and bypass vascular anastomosis.

Antagonism of adenosinergic system decrease SWD occurrence via an increment in thalamic NFkB and IL-6 in absence epilepsy

Epilepsy is a major pathological condition, characterized by recurrent seizures and affecting approximately 1% of the population. Many studies have shown a relationship between epilepsy and inflammation. The adenosinergic system contributes to inflammation and epilepsy by regulating the release of neurotransmitters through its various receptors. This study investigates the effect of agonist and antagonist of adenosinergic system on seizure activity and cytokine levels in the WAG/Rij strain, a genetic animal model of absence epilepsy.The WAG/Rij rats used in our study were assigned to saline, Tween 20, adenosine, and caffeine groups. Tripolar electrodes were implanted on the skull, and EEG activities recorded for 3 h. ELISA was used to determine the NFkB, TNF-α, IL-1β, and IL-6 levels in the cortical and thalamic brain regions, as well as the TNF-α, IL-1β, and IL-6 levels in the blood samples.Administration of caffeine to rats resulted in a decreased SWD number at 30 and 60 min as determined by EEG recording after baseline (p < .05), and a significant increase in NFkB and IL-6 levels in the thalamic tissue (p < .05). Administration of adenosine to rats did not change seizures and cytokine levels.Our results show that an increase in thalamic IL-6 and NFkB levels may related with a decrement in absence epilepsy. This study clearly shows the contribution of adenosinergic system in absence seizure in WAG/Rij rats. These results also support the importance of the thalamus on occurrence of SWD in the thalamocortical loop.

Demonstration of pulmonary vein exit block following pulmonary vein isolation: A novel use for adenosine.

Demonstration of exit block after pulmonary vein isolation (PVI) is the cornerstone of ablation for atrial fibrillation (AF). It requires the demonstration of local pulmonary vein (PV) capture and absence of conduction to the atrium but is often challenging due to the inability to see local paced PV-evoked potentials. We retrospectively examined the ability of adenosine to augment this technique during CARTO-based radiofrequency ablation procedures. Retrospective analysis of evoked PV potentials during adenosine administration while testing for PV exit block at a single UK center. One hundred and twenty-nine PVs in 33 patients were isolated using radiofrequency energy to demonstrate entry block. Of those, the pacing of 24 veins under baseline conditions did not clearly demonstrate local PV-evoked potentials sufficient to be sure that the local vein was truly captured and dissociated from the atrium. Adenosine was administered in 19 of these, with 10 of 19 (52.6%) veins then demonstrating clear local PV-evoked potentials transiently during adenosine administration, sufficient to allow assessment of definite exit block. Adenosine administered during PV pacing allows transient visualization of local PV-evoked potentials after PVI facilitating the clearer demonstration of PV exit block in over 50% veins.

Repeat ablation for paroxysmal atrial fibrillation – Does adenosine play a role in predicting pulmonary vein reconnection patterns?

BackgroundPulmonary vein (PV) reconduction after PV isolation (PVI) unmasked by adenosine is associated with a higher risk for paroxysmal atrial fibrillation (PAF) recurrence. It is unknown if the reconnected PVs after adenosine testing and immediate re-ablation can predict reconnection and reconnection patterns of PVs at repeat procedures. We assessed reconnection of PVs with and without dormant-conduction (DC) during the first and the repeat procedure. MethodsWe included 67 patients undergoing PVI for PAF and a second procedure for PAF recurrence. DC during adenosine administration at first procedure was seen in 31 patients (46%). 264 PVs were tested with adenosine; DC was found in 48 PVs (18%) and re-ablated during first procedure. During the second procedure, all PVs where checked for reconnection. ResultsFifty-eight patients (87%) showed PV reconnection during the second procedure. Reconnection was found in 152/264 PVs (58%). Of 216 PVs without reconnection during adenosine testing at the first ablation, 116 PVs (53.7%) showed reconnection at the repeat procedure. Overall, 14.9% of patients showed the same PV reconnection pattern in the first and second procedure, expected statistical probability of encountering the same reconnection pattern was only 6.6%(p = 0.012). ConclusionsIn repeat procedures PVs showed significantly more often the same reconnection pattern as during first procedure than statistically expected. More than 50% of initial isolated PVs without reconnection during adenosine testing showed a reconnection during repeat ablation. Techniques to detect susceptibility for PV re-connection like prolonged waiting-period should be applied. Elimination of DC should be expanded from segmental to circumferential re-isolation or vaster RF application.

Possibilities of using adenosine-induced cardioplegia in microsurgical treatment of cerebral aneurysms

The study objective is to analyze the results of using adenosine-induced cardioplegia during cerebral aneurysms clipping.Materials and methods. The study included 15 patients who underwent microsurgical aneurysm clipping during period from 2016 to 2017. Results. In all cases it was possible to completely isolate the aneurysm from the circulation. No complications associated with the administration of adenosine were observed. It was shown that adenosine-induced cardioplegia can be used when temporary clipping is impossible because of changing in the parent vessel. Also, the using of adenosine is useful for “simple” aneurysms, which leads to a softening of the sack without additional injuries.Conclusion. The combination of adenosine-induced cardioplegia and temporary clipping allows to provide better control over possible intraoperative bleeding and more comfortable positioning of the permanent clip on the aneurysm neck.

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

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

Regulation of human brown adipose tissue by adenosine and A2A receptors \u2013 studies with [15O]H2O and [11C]TMSX PET/CT

PurposeBrown adipose tissue (BAT) has emerged as a potential target to combat obesity and diabetes, but novel strategies to activate BAT are needed. Adenosine and A2A receptor (A2AR) agonism activate BAT in rodents, and endogenous adenosine is released locally in BAT as a by-product of noradrenaline, but physiological data from humans is lacking. The purpose of this pilot study was to investigate the effects of exogenous adenosine on human BAT perfusion, and to determine the density of A2ARs in human BAT in vivo for the first time, using PET/CT imaging.MethodsHealthy, lean men (n = 10) participated in PET/CT imaging with two radioligands. Perfusion of BAT, white adipose tissue (WAT) and muscle was quantified with [15O]H2O at baseline, during cold exposure and during intravenous administration of adenosine. A2AR density of the tissues was quantified with [11C]TMSX at baseline and during cold exposure.ResultsAdenosine increased the perfusion of BAT even more than cold exposure (baseline 8.3 ± 4.5, cold 19.6 ± 9.3, adenosine 28.6 ± 7.9 ml/100 g/min, p < 0.01). Distribution volume of [11C]TMSX in BAT was significantly lower during cold exposure compared to baseline. In cold, low [11C]TMSX binding coincided with high concentrations of noradrenaline.ConclusionsAdenosine administration caused a maximal perfusion effect in human supraclavicular BAT, indicating increased oxidative metabolism. Cold exposure increased noradrenaline concentrations and decreased the density of A2AR available for radioligand binding in BAT, suggesting augmented release of endogenous adenosine. Our results show that adenosine and A2AR are relevant for activation of human BAT, and A2AR provides a future target for enhancing BAT metabolism.

Adenosine Promotes the Recovery of Mice from the Cuprizone-Induced Behavioral and Morphological Changes while Effecting on Microglia and Inflammatory Cytokines in the Brain.

Recent studies have shown that multiple sclerosis (MS) and schizophrenia share similarities in some respects, including white matter damage and neuroinflammation. On the other hand, adenosine was reported to promote oligodendrocyte precursor maturation and remyelinating while influencing microglia activation. The aim of the present study was to examine possible beneficial effects of adenosine on the recovery of cuprizone (CPZ)-exposed mouse which has been used as an animal model of MS and schizophrenia as the CPZ-exposed mouse presents demyelination, oligodendrocyte loss, microglia accumulation, as well as behavioral changes. As reported previously, C57BL/6 mice, after fed CPZ for 5weeks, showed salient demyelination and oligodendrocyte loss in the cerebral cortex (CTX) and hippocampus, in addition to displaying anxiety-like behavior, spatial working memory deficit, and social interaction impairment. Administration of adenosine for 7days during the recovery period after CPZ withdrawal promoted the behavioral recovery of CPZ-exposed mice and accelerated the remyelinating process in the brains of mice after CPZ withdrawal in a dose-dependent manner. In addition, the effective dose (10mg/kg) of adenosine inhibited microglia activation and suppressed abnormal elevation of the pro-inflammatory cytokines IL-1β and TNF-α in CTX and hippocampus, but increased levels of the anti-inflammatory cytokines IL-4 or IL-10 in the same brain regions during the remyelinating process. These results provided an evidence-based rationale for the application of adenosine or its analogues as add-on therapy for schizophrenia.

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

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

Intravenous nicorandil versus adenosine for fractional flow reserve measurement: a crossover, randomized study.

Nicorandil has vasodilatory effects on both the epicardial coronary arteries and the coronary microvasculature, thereby increasing coronary blood flow. The objective of the present study was to investigate the effectiveness of intravenous (IV) nicorandil infusion for fractional flow reserve (FFR) measurement. In this crossover randomized study, 49 patients underwent FFR measurement with a consecutive randomized order of patient-blind infusions of continuous IV adenosine administration and a single bolus IV administration of nicorandil. The primary endpoint was the difference between the FFR by nicorandil and the FFR by adenosine, as assessed by the Bland-Altman method. The mean FFR value measured by nicorandil was not significantly different from that measured by adenosine [0.8125 ± 0.1349 vs. 0.7978 ± 0.124; mean difference, 0.0147 (95% confidence interval - 0.0373, 0.0667); P = 0.58]. There was no clinically significant diagnostic discordance, with the FFR by nicorandil > 0.80 and that by adenosine < 0.75. Hyperemia was achieved earlier using nicorandil than adenosine (34 ± 13 vs. 58 ± 15, P < 0.001). The duration of hyperemia after IV nicorandil was variable (6-570s, mean 89 ± 98s). IV nicorandil decreased systolic blood pressure by 32 ± 16mm Hg (24 ± 10%) from baseline. Linear regression analysis showed that the average FFR value and the difference in systolic blood pressure were significantly associated with the bias in the FFR value between the two drugs. In conclusions, the results of the present study suggest that IV nicorandil can achieve maximal hyperemia easily and rapidly, providing an acceptable diagnostic performance for FFR assessment. However, a wide range of variation in hyperemic plateau and adecrease in blood pressure are the major limitations of this method.

Does a Single Dose of Adenosine in Epidural Space Reduce Cancer-Related Neuropathic Pain? A Randomized Clinical Trial

Background: Systemic and intrathecal adenosine reduce chronic neuropathic and nociceptive pain; however, the effect of adenosine epidural injection in the treatment of neuropathic cancer-related pains remains unclear. Objectives: The objective of this study was to evaluate the efficacy of a single epidural administration of adenosine in alleviating chronic neuropathic pain in patients with primitive neuroectodermal tumors. Methods: In this single-blind randomized clinical trial with the unique ID of IRCT2017031428878N1, 88 patients with chronic neuropathic pain were divided into two equivalent groups. Two groups were treated with a single dose epidural administration of ropivacaine, 0.75 mL/kg from 0.2% solution (both groups), plus adenosine, 50 mcgr/kg (adenosine group), or normal saline (control group). Patients were evaluated on the days 1, 2, 3, 5, 7, 10, and 14 after injection. Results: Both groups showed a reduction in pain severity according to verbal rating scale (VRS) (3 ± 0.09-1 ± 0.05 in adenosine, 4 ± 0.08-1 ± 0.00 in the control group) and visual analogue scale (VAS) (7 ± 0.25-1 ± 0.12 in adenosine, 8 ± 0.22-1 ± 0.06 in the control group); however, this reduction was significantly higher in the control group (P < 0.0005). The intensity of neuropathic pain decreased in both groups according to Douleur Neuropathique 4 questions (DN4) scores (from 5 ± 0.23-1 ± 0.04 in adenosine group, and from 5.5 ± 0.24-1 ± 0.00 in the control group) without a significant difference between the groups (P = 0.19). Adenosine group had less nausea and vomiting (P < 0.0005).There was no significant difference in patient satisfaction levels between adenosine and control groups (P = 0.09). Conclusions: Administration of bolus epidural adenosine is not effective in reducing neuropathic pain in patients with primitive neuroectodermal tumors.

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

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

Coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction.

There are multiple proposed mechanisms for the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). We hypothesized that coronary microvascular dysfunction is common in these patients. In a prospective, observational study, patients undergoing cardiac catheterization with HFpEF [left ventricular (LV) ejection fraction ≥ 50% and with clinical HF] were compared with similar patients without HFpEF. Patients with ≥50% stenosis were excluded, and coronary flow reserve (CFR) and the index of microvascular resistance (IMR) were measured after adenosine administration using a guidewire, with CFR ≤ 2 and IMR ≥ 23 being abnormal. Baseline characteristics and CFR and IMR were compared in 30 HFpEF patients and 14 control subjects. Compared with control subjects, HFpEF patients were older (65.4 ± 9.6 vs. 55.1 ± 3.1 yr, P < 0.01), had higher numbers of comorbidities (4.4 ± 1.5 vs. 2.6 ± 1.9, P = 0.002), had higher median B-type natriuretic peptide [161 (interquartile range: 75-511) pg/dl vs. 37 (interquartile range: 18.5-111) pg/dl, P < 0.01], and had higher LV end-diastolic pressure (17.8 ± 4.2 vs. 8.4 ± 4.2, P < 0.01). HFpEF patients had lower CFR (2.55 ± 1.60 vs. 3.84 ± 1.89, P = 0.024) and higher IMR (26.7 ± 10.3 vs. 19.7 ± 9.7 units, P = 0.037) than control subjects. Most (71.4%) control subjects had normal coronary physiology, whereas 36.7% of HFpEF patients had both abnormal CFR and IMR and another 36.7% had either abnormal CFR or IMR. In conclusion, this is the first study that has reported invasively determined CFR and IMR in HFpEF patients. We demonstrated the presence of four distinct coronary physiology groups in HFpEF patients. Investigation into the potential mechanisms for these findings is needed. NEW & NOTEWORTHY In this prospective observational study of patients with heart failure with preserved ejection fraction (HFpEF), we found that patients with HFpEF had more abnormalities of coronary flow and resistance than asymptomatic control patients, indicating that coronary microvascular dysfunction may play a role in the HFpEF disease process.

Does adenosine testing after second-generation cryoballoon ablation improve clinical success rate for paroxysmal atrial fibrillation?

Adenosine administration after pulmonary vein (PV) isolation using radiofrequency, can unmask PVs dormant conductions and predict atrial fibrillation (AF) recurrence. Our study evaluates whether adenosine-guided pulmonary vein isolation following second-generation cryoballoon (CB-2G) ablation may improve the success rate for paroxysmal AF. One hundred and one consecutive patients scheduled for a first ablation with (CB-2G) were prospectively included between January 2013 and November 2015 in two centers. Intravenous adenosine was administered after PV isolation to unmask dormant conductions (DC) in the first 51 patients and additional applications were performed to ablate DC. The 50 next patients underwent cryoablation without adenosine testing. Symptomatic atrial fibrillation recurrence was evaluated after 3, and 12 months. Acute PV isolation was achieved in all 402 PVs of 101 patients. Moreover, 8/204 VPPV (3,9%) involving 11,7% of patients with adenosine testing showed dormant reconduction, including 1 left superior pulmonary vein, 3 left inferior pulmonary vein, 4 right superior pulmonary vein, and no right inferior pulmonary vein. After a single procedure, success rates for cryoablation were 78,5% in adenosine group and 70% in the group without adenosine ( P = 0.22), with a mean follow-up of 422 days. Mean procedure duration for adenosine and without adenosine group were respectively 151 and 117 minutes ( P = 0.0009), and mean fluroscopy time 36 and 33 minutes ( P = 0.3). Adenosine testing after second-generation cryoballoon ablation can unmask a low rate of DC but does not improve success rate. However, this strategy increases procedural time.

Mechanisms involved in adenosine pharmacological preconditioning-induced cardioprotection.

Adenosine is a naturally occurring breakdown product of adenosine triphosphate and plays an important role in different physiological and pathological conditions. Adenosine also serves as an important trigger in ischemic and remote preconditioning and its release may impart cardioprotection. Exogenous administration of adenosine in the form of adenosine preconditioning may also protect heart from ischemia-reperfusion injury. Endogenous release of adenosine during ischemic/remote preconditioning or exogenous adenosine during pharmacological preconditioning activates adenosine receptors to activate plethora of mechanisms, which either independently or in association with one another may confer cardioprotection during ischemia-reperfusion injury. These mechanisms include activation of KATP channels, an increase in the levels of antioxidant enzymes, functional interaction with opioid receptors; increase in nitric oxide production; decrease in inflammation; activation of transient receptor potential vanilloid (TRPV) channels; activation of kinases such as protein kinase B (Akt), protein kinase C, tyrosine kinase, mitogen activated protein (MAP) kinases such as ERK 1/2, p38 MAP kinases and MAP kinase kinase (MEK 1) MMP. The present review discusses the role and mechanisms involved in adenosine preconditioning-induced cardioprotection.