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As our therapeutic armamentarium for HFpEF is insufficient, research has been focusing on the potential beneficial effect of existing pharmaceutical regimens on this specific patient population. A series of RCTs have recently examined the impact of various pharmaceutical treatments with proven benefit in HFrEF, on the improvement of symptoms of HFpEF patients. This systematic review and meta-analysis comprised studies of adult patients with HFpEF and evaluated the impact of different cardiovascular acting medication on cardiorespiratory fitness, reflected by peak VO

Hypertrophic cardiomyopathy (HCM) is a common cause of sudden cardiac death in athletes. Cardiac Magnetic Resonance (CMR) imaging is considered an excellent tool to differentiate between HCM and athlete's heart. The aim of this systematic review was to highlight the novel CMR-derived parameters with significant discriminative capacity between the two conditions. A systematic search in the MEDLINE, EMBASE and Cochrane Reviews databases was performed. Eligible studies were considered the ones comparing novel CMR-derived parameters on athletes and HCM patients. Therefore, studies that only examined Cine-derived volumetric parameters were excluded. Particular attention was given to binary classification results from multi-variate regression models and ROC curve analyses. Bias assessment was performed with the Quality Assessment on Diagnostic Accuracy Studies. Five (5) studies were included in the systematic review, with a total of 284 athletes and 373 HCM patients. Several novel indices displayed discriminatory potential, such as native T1 mapping and T2 values, LV global longitudinal strain, late gadolinium enhancement and whole-LV fractal dimension. Diffusion tensor imaging enabled quantification of the secondary eigenvalue angle and fractional anisotropy in one study, which also proved capable of reliably detecting HCM in a mixed athlete/patient sample. Several novel CMR-derived parameters, most of which are currently under development, show promising results in discerning between athlete's heart and HCM. Prospective studies examining the discriminatory capacity of all promising modalities side-by-side will yield definitive answers on their relative importance; diagnostic models can incorporate the best performing variables for optimal results.

BACKGROUND Dipeptidyl peptidase-4 (DPP-4) inhibitors are a generally safe and well tolerated antidiabetic drug class with proven efficacy in type 2 diabetes mellitus (T2DM). Recently, a series of large, randomized controlled trials (RCTs) addressing cardiovascular outcomes with DPP-4 inhibitors have been published. AIM To pool data from the aforementioned trials concerning the impact of DPP-4 inhibitors on surrogate cardiovascular efficacy outcomes and on major cardiac arrhythmias. METHODS We searched PubMed and grey literature sources for all published RCTs assessing cardiovascular outcomes with DPP-4 inhibitors compared to placebo until October 2020. We extracted data concerning the following “hard” efficacy outcomes: fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization and cardiovascular death. We also extracted data regarding the risk for major cardiac arrhythmias, such as atrial fibrillation, atrial flutter, ventricular fibrillation and ventricular tachycardia. RESULTS We pooled data from 6 trials in a total of 52520 patients with T2DM assigned either to DPP-4 inhibitor or placebo. DPP-4 inhibitors compared to placebo led to a non-significant increase in the risk for fatal and non-fatal myocardial infarction [risk ratio (RR) = 1.02, 95%CI: 0.94-1.11, I2 = 0%], hospitalization for heart failure (RR = 1.09, 95%CI: 0.92-1.29, I2 = 65%) and cardiovascular death (RR = 1.02, 95%CI: 0.93-1.11, I2 = 0%). DPP-4 inhibitors resulted in a non-significant decrease in the risk for fatal and non-fatal stroke (RR = 0.96, 95%CI: 0.85-1.08, I2 = 0%) and coronary revascularization (RR = 0.99, 95%CI: 0.90-1.09, I2 = 0%), Finally, DPP-4 inhibitors demonstrated a neutral effect on the risk for hospitalization due to unstable angina (RR = 1.00, 95%CI: 0.85-1.18, I2 = 0%). As far as cardiac arrhythmias are concerned, DPP-4 inhibitors did not significantly affect the risk for atrial fibrillation (RR = 0.95, 95%CI: 0.78-1.17, I2 = 0%), while they were associated with a significant increase in the risk for atrial flutter, equal to 52% (RR = 1.52, 95%CI: 1.03-2.24, I2 = 0%). DPP-4 inhibitors did not have a significant impact on the risk for any of the rest assessed cardiac arrhythmias. CONCLUSION DPP-4 inhibitors do not seem to confer any significant cardiovascular benefit for patients with T2DM, while they do not seem to be associated with a significant risk for any major cardiac arrhythmias, except for atrial flutter. Therefore, this drug class should not be the treatment of choice for patients with established cardiovascular disease or multiple risk factors, except for those cases when newer antidiabetics (glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) are not tolerated, contraindicated or not affordable for the patient.

BACKGROUND Echocardiography (ECHO) is a type of ultrasonographic procedure for examining the cardiac function and morphology, with functional parameters of the left ventricle (LV), such as the ejection fraction (EF) and global longitudinal strain (GLS), being important indicators. Estimation of LV-EF and LV-GLS is performed either manually or semiautomatically by cardiologists and requires a nonnegligible amount of time, while estimation accuracy depends on scan quality and the clinician’s experience in ECHO, leading to considerable measurement variability. OBJECTIVE The aim of this study is to externally validate the clinical performance of a trained artificial intelligence (AI)–based tool that automatically estimates LV-EF and LV-GLS from transthoracic ECHO scans and to produce preliminary evidence regarding its utility. METHODS This is a prospective cohort study conducted in 2 phases. ECHO scans will be collected from 120 participants referred for ECHO examination based on routine clinical practice in the Hippokration General Hospital, Thessaloniki, Greece. During the first phase, 60 scans will be processed by 15 cardiologists of different experience levels and the AI-based tool to determine whether the latter is noninferior in LV-EF and LV-GLS estimation accuracy (primary outcomes) compared to cardiologists. Secondary outcomes include the time required for estimation and Bland-Altman plots and intraclass correlation coefficients to assess measurement reliability for both the AI and cardiologists. In the second phase, the rest of the scans will be examined by the same cardiologists with and without the AI-based tool to primarily evaluate whether the combination of the cardiologist and the tool is superior in terms of correctness of LV function diagnosis (normal or abnormal) to the cardiologist’s routine examination practice, accounting for the cardiologist’s level of ECHO experience. Secondary outcomes include time to diagnosis and the system usability scale score. Reference LV-EF and LV-GLS measurements and LV function diagnoses will be provided by a panel of 3 expert cardiologists. RESULTS Recruitment started in September 2022, and data collection is ongoing. The results of the first phase are expected to be available by summer 2023, while the study will conclude in May 2024, with the end of the second phase. CONCLUSIONS This study will provide external evidence regarding the clinical performance and utility of the AI-based tool based on prospectively collected ECHO scans in the routine clinical setting, thus reflecting real-world clinical scenarios. The study protocol may be useful to investigators conducting similar research. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/44650

Cardiopulmonary exercise testing (CPET) is a significant tool for evaluating exercise capacity in healthy individuals and in various pulmonary and cardiovascular conditions, quantifying symptoms and predicting outcomes. Atrial fibrillation (AF) poses a significant burden on patients and health systems; a research marathon is ongoing for discovering the pathophysiologic substrate, natural history, prognostic tools and optimal treatment strategies for AF. Among the plethora of variables measured during CPET, there is a series of parameters of interest concerning AF.We conducted a scoping review aiming to identify significant CPET-related parameters linked to AF, as well as indicate the impact of other cardiac disease-related variables. We searched PubMed from its inception to 12 January 2022 for reports underlining the contribution of CPET in the assessment of patients with AF. Only clinical trials, observational studies and systematic reviews were included, while narrative reviews, expert opinions and other forms of manuscripts were excluded.In our scoping review, we report a group of heterogeneous, thus noteworthy parameters relevant to the potential contribution of CPET in AF. CPET helps phenotype AF populations, evaluates exercise capacity after cardioversion or catheter ablation, and assesses heart rate response to exercise; peak VOCPET seems to hold a clinically important predictive value for future cardiovascular events both in patients with pre-existing cardiac conditions and in healthy individuals. CPET variables may play a fundamental role in the prediction of future AF-related events.

Aims Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a clinical entity with several causes and pathophysiologic mechanisms. Secondary prevention with medical therapy used in patients with obstructive coronary artery disease has unclear benefits in MINOCA patients. Methods and results A literature search was conducted until 8 March 2022. Random-effect frequentist and hierarchical Bayesian meta-analyses were performed to assess the clinical impact of medical therapy [renin–angiotensin–aldosterone system (RAAS) inhibitors, statins, dual antiplatelet therapy (DAPT), β-blockers] in MINOCA patients. Outcomes of interest were all-cause mortality and major adverse cardiovascular events (MACE). A total of 12 663 MINOCA patients among five observational studies were analysed. The mean follow-up ranged from 12 to 90 months across studies. In frequentist meta-analysis, statins and β-blockers were associated with a lower risk of all-cause mortality [pooled adjusted hazard ratios (aHRs) 0.53 and 0.81, with 95% confidence intervals (CIs) (0.37–0.76) and (0.67–0.97), respectively]. Only RAAS inhibitors were associated with a lower risk of MACE [pooled aHR: 0.69, with 95% CI (0.53–0.90)]. Bayesian meta-analysis based on informative prior assumptions offered strong evidence only for the benefit of statins on decreasing the risk of all-cause death [Bayes factor (BF): 33.2] and moderate evidence for the benefit of RAAS inhibitors on decreasing the risk of MACE (BF: 9); assigning less informative prior distributions did not affect the results, yet it downgraded the level of evidence to anecdotal. Conclusion In this meta-analysis, statins and RAAS inhibitors were consistently associated with a lower risk of all-cause mortality and MACE, respectively, in patients with MINOCA. Neutral prognostic evidence was demonstrated for β-blockers and DAPT.

Background The contribution of atrial and ventricular function in neurocardiogenic syncope (NCS) pathophysiology is elusive. Hypothesis We assessed the influence of echocardiographic properties to the age of presentation and NCS recurrences. Methods We assigned 124 patients with symptoms suggesting NCS, to those with syncope initiation at age 35 years (group B, n = 68). Echocardiographic indices were measured before head‐up tilt test (HUTT). Results A total of 55 had positive HUTT (44%) with a trend favoring group A (p = .08). Group A exhibited lower left atrial (LA) volume index (17 ± 6 vs. 22 ± 11 ml/m2, p = .015), higher LA ejection fraction (69 ± 10 vs. 63 ± 11%, p = .008), LA peak strain (reservoir phase 41 ± 13 vs. 31 ± 14%, p = .001, contraction phase 27 ± 11 vs. 15 ± 10%, p 3 recurrences (82.0% vs. 50.1%, p

Background: Arterial stiffness represents an established cardiovascular risk marker. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have significant cardio-protective effects. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV). Methods: We searched PubMed, Cochrane Library, and grey literature from inception to 7th February 2022 for randomized controlled trials (RCTs) enrolling adult subjects with or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus control and addressing their effect on PWV. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. Results: We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. Overall, SGLT-2 inhibitor treatment compared to control resulted in a nonsignificant decrease in PWV. Exclusion of a trial utilizing cardiac magnetic resonance imaging for the assessment of PWV demonstrated that SGLT-2 inhibitors induce a significant reduction in PWV by 0.21 m/s. When we restricted our analysis to RCTs enrolling subjects with T2DM, we observed that SGLT-2 inhibitor compared to control resulted in a significant decrease in PWV by 0.17 m/s. Conclusion: SGLT-2 inhibitors do not decrease PWV in patients with established cardiovascular disease or cardiovascular risk factors. However, we have shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with T2DM. The latter finding is of great value, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), a group of novel antidiabetic agents, demonstrated beneficial cardiovascular effects in recent large, placebo-controlled randomised clinical trials (RCTs); their clear antiarrhythmic benefit has not been yet underlined. The purpose of the present meta-analysis is to clarify the impact of GLP-1RAs on different types of cardiac arrhythmias.We searched PubMed from its inception up to 8 October 2020 for all available cardiovascular and renal outcome, placebo-controlled RCTs utilising GLP-1RAs versus placebo. The present meta-analysis is reported according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) statement.We included data from 7 RCTs with GLP-1RAs in a total of 55,943 participants. Treatment with GLP-1RAs did not provide significant benefit in the risk for atrial fibrillation (RR = 0.81, 95%CI; 0.78-1.15,In patients with type 2 diabetes mellitus, treatment with GLP-1RAs does not significantly affect the risk for major cardiac arrhythmias.

Hypertrophic cardiomyopathy (HCM) represents one of the primary cardiomyopathies and may lead to heart failure and sudden cardiac death. Among various histologic features of the disease examined, assessment of myocardial fibrosis may offer valuable information, since it may be considered the common nominator for all HCM connected complications. Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) has emerged as the reference noninvasive method for visualizing and quantifying myocardial fibrosis in patients with HCM. T1 mapping, a promising new CMR technique, may provide an advantage over conventional LGE-CMR, by permitting a more valid quantification of diffuse fibrosis. On the other hand, echocardiography offers a significantly more portable, affordable, and easily accessible solution for the study of fibrosis. Various echocardiographic techniques ranging from integrated backscatter and contrast-enhanced ultrasound to two- (2D) or three-dimensional (3D) deformation and shear wave imaging may offer new insights into substrate characterization in HCM. The aim of this review is to describe thoroughly all different modalities that may be used in everyday clinical practice for HCM fibrosis evaluation (with special focus on echocardiographic techniques), to concisely present available evidence and to argue in favor of multi-modality imaging application. It is essential to understand that the role of various imaging modalities is not competitive but complementary, since the information provided by each one is necessary to illuminate the complex pathophysiologic pathways of HCM, offering a personalized approach and treatment in every patient.

Neurally mediated syncope (NMS) is the most common type of syncope, and head up tilt test (HUTT) is, so far, the most appropriate tool to identify NMS. In this work, an effort to predict the NMS before performing the HUTT is attempted. To achieve this, the heart rate variability (HRV) at rest and during the first minutes of tilting position during HUTT was analyzed using both time and frequency domains. Various features from HRV regularity and complexity, along with wavelet higher-order spectrum (WHOS) analysis in low-frequency (LF) and high-frequency (HF) bands were examined. The experimental results from 26 patients with history of NMS have shown that at rest, a time domain entropy measure and WHOS-based features in LF band exhibit significant differences between positive and negative HUTT as well as among 10 healthy subjects and NMS patients. The best performance of multilayer perceptron neural network (MPNN) was achieved by using an input vector consisted of WHOS-based HRV features in the LF zone and systolic blood pressure from the resting period, yielding an accuracy of 89.7%, assessed by 5-fold cross-validation. The promising results presented here pave the way for an early prediction of the HUTT outcome from resting state, contributing to the identification of patients at higher risk NMS. The HRV analysis along with systolic blood pressure at rest predict NMS using a multilayer perceptron neural network.

5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent that can cause cardiotoxicity manifesting, among others, as chest pain. Capecitabine is an oral prodrug of 5-FU, with reported preferential activation in malignant cells that may also cause cardiotoxic reactions. Standard treatment of 5-FU and capecitabine induced chest pain with vasodilators is mostly effective, but there are several cases of patients unresponsive to these agents.We performed a PubMed search on 31st May 2020. We used a three keyword search strategy using Boolean search operators. More specifically, we included fluorouracil or 5-FU or capecitabine and chest pain or angina and mechanism or treatment or management. We included primary reports of clinical and non-clinical data, as well as systematic reviews. Narrative reviews, expert opinions, letters to the editor and other forms of non-primary literature were excluded.Our search yielded a total of 1595 reports. Of these, 1460 were narrative reviews or irrelevant to the topic and were excluded. A total of 135 reports were used for our review. We used 81 reports for data extraction, which included 13 clinical trials, 4 retrospective reports, 61 case reports, and 3 systematic reviews.We report the incidence and predisposing factors, the value of available diagnostic procedures, and standard medical and invasive treatments. We also speculate on the potential benefit of arginine as a promising option both in prevention as well as treatment of 5-FU-induced chest pain. Finally, gaps of evidence are identified and proposals are made in terms of future research.

IntroductionMining of electronic health record (EHRs) data is increasingly being implemented all over the world but mainly focuses on structured data. The capabilities of artificial intelligence (AI) could reverse the underusage of unstructured EHR data and enhance the quality of medical research and clinical care. This study aims to develop an AI-based model to transform unstructured EHR data into an organised, interpretable dataset and form a national dataset of cardiac patients.Methods and analysisCardioMining is a retrospective, multicentre study based on large, longitudinal data obtained from unstructured EHRs of the largest tertiary hospitals in Greece. Demographics, hospital administrative data, medical history, medications, laboratory examinations, imaging reports, therapeutic interventions, in-hospital management and postdischarge instructions will be collected, coupled with structured prognostic data from the National Institute of Health. The target number of included patients is 100 000. Natural language processing techniques will facilitate data mining from the unstructured EHRs. The accuracy of the automated model will be compared with the manual data extraction by study investigators. Machine learning tools will provide data analytics. CardioMining aims to cultivate the digital transformation of the national cardiovascular system and fill the gap in medical recording and big data analysis using validated AI techniques.Ethics and disseminationThis study will be conducted in keeping with the International Conference on Harmonisation Good Clinical Practice guidelines, the Declaration of Helsinki, the Data Protection Code of the European Data Protection Authority and the European General Data Protection Regulation. The Research Ethics Committee of the Aristotle University of Thessaloniki and Scientific and Ethics Council of the AHEPA University Hospital have approved this study. Study findings will be disseminated through peer-reviewed medical journals and international conferences. International collaborations with other cardiovascular registries will be attempted.Trial registration numberNCT05176769.

Objective In 2008, the radiofrequency ablation (RFA) procedures registry of the Hellenic Society of Cardiology was created. This online database allowed electrophysiologists around the country to input data for all performed ablation procedures. The aim of this study is to provide a thorough report and interpretation of the data submitted to the registry between 2008 and 2018. Methods In 2008, a total of 27 centers/medical teams in 24 hospitals were licensed to perform RFA in Greece. By 2018, the number had risen to 31. Each center was tasked with inserting their own data into the registry, which included patient demographics (anonymized), type of procedure and technique, complications, and outcomes. Results A total of 18587 procedures in 17900 patients were recorded in the period of 2008-2018. By 2018, slightly more than 70% of procedures were performed in 7 high-volume centers (>100 cases/year). The most common procedure since 2014 was atrial fibrillation ablation, followed by atrioventricular nodal reentry tachycardia ablation. Complication rates were low, and success rates remained high, whereas the 6-month relapse rates declined steadily. Conclusion This online RFA registry has proved that ablation procedures in Greece have reached a very high standard, with results and complication rates comparable to European and American standards. Ablation procedures for atrial fibrillation are increasing constantly, with it being the most common intervention over the last 6-year period, although the absolute number of procedures still remains low, compared to other European countries.

In 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).We 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.Baseline 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).The 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.

The Hellenic Heart Failure Association has undertaken the initiative to develop a national network of heart failure clinics (HFCs) and cardio‐oncology clinics (COCs). We conducted two questionnaire surveys among these clinics within 17 months and another during the coronavirus disease 2019 outbreak to assess adjustments of the developing network to the pandemic. Out of 68 HFCs comprising the network, 52 participated in the first survey and 55 in the second survey. The median number of patients assessed per week is 10. Changes in engaged personnel were encountered between the two surveys, along with increasing use of advanced echocardiographic techniques (23.1% in 2018 vs. 34.5% in 2020). Drawbacks were encountered, concerning magnetic resonance imaging and ergospirometry use (being available in 14.6% and 29% of HFCs, respectively), exercise rehabilitation programmes (applied only in 5.5%), and telemedicine applications (used in 16.4%). There are 13 COCs in the country with nine of them in the capital region; the median number of patients being assessed per week is 10. Platforms for virtual consultations and video calls are used in 38.5%. Coronavirus disease 2019 outbreak affected provision of HFC services dramatically as only 18.5% continued to function regularly, imposing hurdles that need to be addressed, at least temporarily, possibly by alternative methods of follow‐up such as remote consultation. The function of COCs, in contrast, seemed to be much less affected during the pandemic (77% of them continued to follow up their patients). This staged, survey‐based procedure may serve as a blueprint to help building national HFC/COC networks and provides the means to address changes during healthcare crises.

Background: Left bundle branch block (LBBB) in heart failure (HF) patients is a negative predictor of survival. This pattern is occasionally recorded in individuals without structural heart disease. The LBBB morphology has not been previously analyzed in a time-frequency domain using wavelet analysis), and thus the factors distinguish LBBB patients from individuals without structural heart disease remain unexplored. The purpose of this analysis was to investigate the variations and the differences in LBBB morphology between healthy individuals with LBBB and patients with HF and LBBB. Methods: HF patients with LBBB and individuals with LBBB were included in this study. Signal-averaged 90-second Holter monitor recordings were extracted from each subject in orthogonal leads. QRS decomposition in 9 time-frequency bands (TFB) was performed using Complex Morlet wavelets transformation, while the mean and maximum energies of the QRS complexes were calculated for each of the 9 TFBs. The wavelet parameters of HF patients were compared with those of healthy controls. Results: Wavelet analysis was performed on ECG recordings of 69 HF patients and 17 individuals without cardiac disease. The mean and max wavelet energies of the QRS complex in all TFBs were higher for heart failure patients with LBBB, as compared to healthy individuals with LBBB. Differences were statistically significant in TFB4 and TFB7 (max energy, axis X), TFB4 and TFB7 (max energy, axis Y) and TFB4 and TFB7 (mean energy, axis Y). A multivariate logistic regression model, comprising of the aforementioned wavelet parameters, proved reasonably capable of distinguishing between HF patients and healthy controls with LBBB (AUC=0.854, 80.2% sensitivity and 80.3% specificity). Conclusion: QRS wavelet analysis revealed differences in the template of the QRS complex between healthy individuals with LBBB and heart failure patients with LBBB. This feature could be used as part of the diagnostic algorithm, a possibility that should be investigated further.

Adenosine is a purine ribonucleoside with important roles in various physiological processes. A number of studies have indicated the importance of adenosine in cardiovascular diseases including syncope, however, the accurate determination of adenosine in human blood is challenging due to the molecule’s instability. In the present study, we report a simple method for the pre-treatment of blood samples and the development of a fast and efficient hydrophilic interaction chromatographic tandem mass spectrometry method for the analysis of adenosine in patient blood. During collection, samples were mixed directly with a solvent mixture containing 95% acetonitrile and 10 mM ammonium formate in a Vacutainer tube, resulting in successful prevention of adenosine metabolic processes and direct blood sample deproteinization. The method was validated according to bioanalytical industry guidelines and found to be accurate, repeatable, specific and sensitive with LLOQ 0.005 μg/mL, thus allowing its application in the analysis of real clinical samples.