An Investigation of Metabolic Risk Factors and Gut Microbiota in Unexplained Syncope.

BACKGROUND: The pathogenesis of many syncopal episodes remains unexplained. Intestinal dysbiosis could be involved in the pathophysiological mechanisms of syncope due to its connection with the central nervous system via the microbiota-gut-brain axis. This pilot study aimed to explore the specific cardiometabolic risk factors and gut microbiota in unexplained syncope (US), compared to other types of syncope, to assess their similarity or verify their different origins. METHODS: We studied 86 participants with syncope, who were divided into four groups: an orthostatic syncope group (OH, n = 24), a neuromediated syncope group (NMS, n = 26), a cardiological syncope group (CS, n = 9), and an unexplained syncope group (US, n = 27). We evaluated the anthropometric, clinical, and metabolic characteristics of the four groups; the α- and ß-diversity; and the differences in the abundance of the microbial taxa. RESULTS: The US group had a lower incidence of systolic hypertension at the first visit and a lower frequency of patients with nocturnal hypertension than the CS group. Compared to the OH and NMS groups, the US group had a higher incidence of carotid plaques and greater carotid intima-media thickness, respectively. The microbiota differed significantly between the US and CS groups, but not between the US group and the OH or NMS group. CONCLUSIONS: We observed significant differences in the gut microbiota between CS and US. Future studies are necessary to evaluate the involvement of the gut microbiota in the complex pathogenesis of syncope and whether its analysis could support the interpretation of the pathophysiological mechasnisms underlying some episodes classifiable as US.

Correlation between Chest Computed Tomography Score and Laboratory Biomarkers in the Risk Stratification of COVID-19 Patients Admitted to the Emergency Department.

BACKGROUND: It has been reported that mid-regional proadrenomedullin (MR-proADM) could be considered a useful tool to stratify the mortality risk in COVID-19 patients upon admission to the emergency department (ED). During the COVID-19 outbreak, computed tomography (CT) scans were widely used for their excellent sensitivity in diagnosing pneumonia associated with SARS-CoV-2 infection. However, the possible role of CT score in the risk stratification of COVID-19 patients upon admission to the ED is still unclear. AIM: The main objective of this study was to assess if the association of the CT findings alone or together with MR-proADM results could ameliorate the prediction of in-hospital mortality of COVID-19 patients at the triage. Moreover, the hypothesis that CT score and MR-proADM levels together could play a key role in predicting the correct clinical setting for these patients was also evaluated. METHODS: Epidemiological, demographic, clinical, laboratory, and outcome data were assessed and analyzed from 265 consecutive patients admitted to the triage of the ED with a SARS-CoV-2 infection. RESULTS AND CONCLUSIONS: The accuracy results by AUROC analysis and statistical analysis demonstrated that CT score is particularly effective, when utilized together with the MR-proADM level, in the risk stratification of COVID-19 patients admitted to the ED, thus helping the decision-making process of emergency physicians and optimizing the hospital resources.

Vasovagal syncope: An overview of pathophysiological mechanisms.

Syncope is a short-term transient loss of consciousness, characterized by rapid onset and complete spontaneous recovery. According to the 2018 European Society of Cardiology guidelines, three different types of syncope have been identified. However, all forms of syncope share a common final pathophysiological event, global cerebral hypoperfusion, which results from the inability of the circulatory system to maintain blood pressure at the level required to efficiently supply blood to the brain. The vasovagal syncope (VVS) is the most common form of syncope. Although, VVS is generally harmless, its frequent occurrence can negatively affect quality of life and increase the risk of adverse events. The pathophysiological mechanisms underlying VVS remain obscure. The multifaceted nature of VVS presents a veritable challenge to understanding this condition and developing preventative strategies. Thus, the aim of this review was to discuss the factors contributing to the pathogenesis of VVS and provide guidance for future research.

Assessment of the Stability of Midregional Proadrenomedullin in Different Biological Matrices.

Midregional proadrenomedullin (MR-proADM) has been shown to play a key role in endothelial dysfunction, with increased levels helping to prevent early stages of organ dysfunction. Recent clinical evidence has demonstrated MR-proADM to be a helpful biomarker to identify disease severity in patients with sepsis as well as pneumonia. This biomarker is helpful at triage in emergency departments to assess risk level of patients. The aim of this study is to evaluate the stability of MR-proADM in different biological matrices. The results, obtained by Bland-Altman and scatter plot analyses, demonstrate that deviation of MR-proADM concentration in serum compared to EDTA plasma unequivocally shows that serum should not be used as a sample matrix. Instead, the excellent correlation of heparin plasma vs EDTA plasma samples shows that heparin plasma can be used without reservation in clinical routine and emergency samples.

Predictive Value of MR-proADM in the Risk Stratification and in the Adequate Care Setting of COVID-19 Patients Assessed at the Triage of the Emergency Department.

In the past two pandemic years, Emergency Departments (ED) have been overrun with COVID-19-suspicious patients. Some data on the role played by laboratory biomarkers in the early risk stratification of COVID-19 patients have been recently published. The aim of this study is to assess the potential role of the new biomarker mid-regional proadrenomedullin (MR-proADM) in stratifying the in-hospital mortality risk of COVID-19 patients at the triage. A further goal of the present study is to evaluate whether MR-proADM together with other biochemical markers could play a key role in assessing the correct care level of these patients. Data from 321 consecutive patients admitted to the triage of the ED with a COVID-19 infection were analyzed. Epidemiological; demographic; clinical; laboratory; and outcome data were assessed. All the biomarkers analyzed showed an important role in predicting mortality. In particular, an increase of MR-proADM level at ED admission was independently associated with a threefold higher risk of IMV. MR-proADM showed greater ROC curves and AUC when compared to other laboratory biomarkers for the primary endpoint such as in-hospital mortality, except for CRP. This study shows that MR-proADM seems to be particularly effective for early predicting mortality and the need of ventilation in COVID-19 patients admitted to the ED.

Identification of COVID-19 patients at risk of hospital admission and mortality: a European multicentre retrospective analysis of mid-regional pro-adrenomedullin.

BACKGROUND: Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. METHODS: An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. RESULTS: Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02 nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2 mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score < 2 if MR-proADM was ≤ 0.83 nmol/L regardless of age. Those at an increased risk of mortality could be identified upon presentation to secondary care with an MR-proADM value of > 0.85 nmol/L, in combination with a SOFA score ≥ 2 and LDH > 720 U/L, or in combination with a CRP > 29.26 mg/L and age ≤ 64, when MR-proADM was > 1.02 nmol/L. CONCLUSIONS: This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient's SOFA score could identify patients at low risk where outpatient treatment may be safe.

Mid-regional pro-adrenomedullin as a supplementary tool to clinical parameters in cases of suspicion of infection in the emergency department.

INTRODUCTION: Mid-regional proadrenomedullin (MR-proADM), a novel biomarker, has recently gained interest particularly with regards to its potential in assisting clinicians' decision making in patients with suspicion of infection in the emergency department (ED). A group of international experts, with research and experience in MR-proADM applications, produced this review based on their own experience and the currently available literature. AREAS COVERED: The review provides evidence related to MR-proADM as a triaging tool in avoiding unnecessary admissions to hospital and/or inadequate discharge, and identifying patients most at risk of deterioration. It also covers the use of MR-proADM in the context of COVID-19. Moreover, the authors provide a proposal on how to incorporate MR-proADM into patients' clinical pathways in an ED setting. EXPERT OPINION: The data we have so far on the application of MR-proADM in the ED is promising. Incorporating it into clinical scoring systems may aid the clinician's decision making and recognizing the 'ill looking well' and the 'well looking ill' sooner. However there are still many gaps in our knowledge especially during the ongoing COVID-19 waves. There is also a need for cost-effectiveness analysis studies especially in the era of increasing cost pressures on health systems globally.

Post-exercise Hypotension in Patients With Coronary Artery Disease.

Background: Blood pressure (BP) and hemodynamic changes occurring in the recovery phase after a single bout of exercise have not been extensively studied in coronary artery patients, despite the potential clinical implications of reducing BP through exercise. This study aimed at investigating the hemodynamic and arterial baroreflex mechanisms possibly involved in post-exercise hypotension (PEH) in patients with coronary artery disease. Methods: In 42 normotensive coronary artery patients undergone a Cardiac Rehabilitation Program, we evaluated before and after their daily exercise training session: blood pressure (BP) and heart rate (HR). In a subgroup (n = 29), daily BP profile was also evaluated by ambulatory BP monitoring. In those patients showing PEH (n = 15), we evaluated: Cardiac Output (CO), Stroke Volume (SV), total peripheral resistances (TPR), forearm (FVR) and calf (CVR) vascular resistances, and spontaneous baroreflex sensitivity (BRS). Results: After exercise TPR was significantly reduced with a similar contribution from CVR and FVR, whereas CO and SV significantly increased. BRS showed a significant reduction mainly due to a BRS decrease in response to hypertensive stimuli. Systolic BP (SBP) was significantly reduced for 12 h after the end of a single exercise session. Conclusion: These findings indicate that in coronary artery patients, the recovery phase after exercise is characterized by PEH which is mediated mainly by a generalized peripheral vasodilation and appears to influence BP behavior throughout the daily life. Finally, the cardiac component of the arterial baroreflex seems to contribute indirectly to BP reduction occurring after exercise.

Complete blood count might help to identify subjects with high probability of testing positive to SARS-CoV-2.

The SARS-CoV-2 pandemic has dramatically increased the workload for health systems and a consequent need to optimise resources has arisen, including the selection of patients for swab tests. We retrospectively reviewed consecutive patients presenting to the emergency department with symptoms suggestive of COVID-19 and undergoing swab tests for SARS-CoV-2. Complete blood counts (CBCs) were analysed looking for predictors of test positivity. Eight significant predictors were identified and used to build a 'complete' CBC score with a discriminatory power for COVID-19 diagnosis of AUC 92% (p<0.0001). When looking at the weight of individual variables, mean corpuscular volume (MCV), age, platelets and eosinophils (MAPE: MCV ≤90 fL, 65 points; age ≥45 years, 100 points; platelets ≤180×103/µL, 73 points; eosinophils <0.01/µL, 94 points) gave the highest contribution and were used to build a 'simplified' MAPE score with a discriminatory power of AUC 88%. By setting the cut-off MAPE score at ≥173 points, sensitivity and specificity for COVID-19 diagnosis were 83% and 82%, respectively, and the actual test positivity rate was 60% as compared to 6% of patients with MAPE score <173 points (odds ratio 23.04, 95% confidence interval [CI] 9.1-58.3, p-value <0.0001). In conclusion, CBC-based scores have potential for optimising the SARS-CoV-2 testing process: if these findings are confirmed in the future, swab tests may be waived for subjects with low score and uncertain symptoms, while they may be considered for asymptomatic or oligosymptomatic patients with high scores.

How biomarkers can improve pneumonia diagnosis and prognosis: procalcitonin and mid-regional-pro-adrenomedullin.

Aim: The diagnostic and prognostic role of procalcitonin (PCT) and mid-regional-pro-adrenomedullin (MR-proADM) were investigated in patients with pneumonia. Material & methods: A total of 168 and 77 patients with pneumonia enrolled in two different hospital settings, an internal medicine unit and an emergency unit were included in the study. PCT and MR-proADM plasma concentrations and pneumonia severity index score were measured. Median values were compared by Mann-Whitney's test. Receiver operating characteristic analysis and rank correlation were used to define the diagnostic and prognostic accuracy. Results: PCT confirmed the diagnostic role at values 0.08-0.10 ng/ml and MR-proADM the prognostic role for severe pneumonia. Significant correlation (p < 0.0001) between MR-proADM and pneumonia severity index score indicated expression of pneumonia severity. Conclusion: This combination of biomarkers presents a high positive predictive value in pneumonia diagnosis and prognosis.

Correction to: The early identification of disease progression in patients with suspected infection presenting to the emergency department: a multi-centre derivation and validation study.

In the publication of this article [1], there are two errors in contributing author affiliations. This has now been included in this correction article.

The early identification of disease progression in patients with suspected infection presenting to the emergency department: a multi-centre derivation and validation study.

BACKGROUND: There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need. METHODS: An observational derivation patient cohort validated by an independent secondary analysis across nine EDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves were used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU admission and hospitalisation > 10 days. RESULTS: One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective 28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest accuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high MR-proADM concentrations (≥ 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0 mmol/L or CRP < 67 mg/L) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised by a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g. SOFA, qSOFA and NEWS HR [95%CI], 45.5 [10.0-207.6], 23.4 [11.1-49.3] and 32.6 [9.4-113.6], respectively) and a greater number of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations (< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities. CONCLUSIONS: In patients presenting to the ED with a suspected infection, the blood biomarker MR-proADM could most accurately identify the likelihood of further disease progression. Incorporation into an early sepsis management protocol may therefore aid rapid decision-making in order to either initiate, escalate or intensify early treatment strategies, or identify patients suitable for safe out-patient treatment.

2-hydroxycaproate predicts cardiovascular mortality in patients with atherosclerotic disease.

BACKGROUND AND AIMS: We aimed to identify novel biomarkers for cardiovascular mortality through a non-targeted metabolomics approach in patients with established atherosclerotic disease from the Tor Vergata Atherosclerosis Registry (TVAR). METHODS: We compared the serum baseline metabolome of 19 patients with atherosclerosis suffering from cardiovascular death during follow-up with the baseline serum metabolome of 20 control patients matched for age, gender, body mass index (BMI) and atherosclerotic disease status, who survived during the observation period. RESULTS: Three metabolites were significantly different in the cardiovascular mortality (CVM) group compared to controls: 2-hydroxycaproate, gluconate and sorbitol. 2-hydroxycaproate (otherwise known as alpha hydroxy caproate) was also significantly correlated with time to death. The metabolites performed better when combined together rather than singularly on the identification of CVM status. CONCLUSIONS: Our analysis led to identify few metabolites potentially amenable of translation into the clinical practice as biomarkers for specific metabolic changes in the cardiovascular system in patients with established atherosclerotic disease.

Cardiovascular and hemodynamic responses to adapted physical exercises in very old adults.

BACKGROUND: Aging is characterized by a physiological reduction in physical activity, which is inversely correlated with survival. AIMS: Aim of the present study is to evaluate the cardiovascular, central hemodynamic and autonomic responses to a single bout of adapted physical exercise in octogenarian subjects. METHODS: We studied cardiovascular, hemodynamic and autonomic responses to adapted physical activity in 33 subjects by a noninvasive methodology (Nexfin®, Edwards Lifesciences Corporation). RESULTS: Our octogenarians presented a significant increase in mean arterial pressure (p < 0.01) and heart rate (p < 0.005) in response to exercise, while both are reduced during the early recovery phase. Central hemodynamic showed a significant increase in stroke volume (p < 0.05), cardiac output (p < 0.01) and left ventricle contractility index (p < 0.01), whereas systemic vascular resistance showed a significant decrease (p < 0.001). We found a reduction in baroreflex control of the sinus node during exercise. DISCUSSION: Our data demonstrate that in very old people adapted physical activity is able to activate cardiovascular system and to induce a postexercise hypotension similarly to adults. The baroreflex control of sinus node seems to contribute in the physiological mechanism of these cardiovascular adaptations. CONCLUSIONS: In very old people, physical activity induces cardiovascular and hemodynamic responses not significantly different from those induced in adult even though some cautions particularly in the early recovery phase after exercise should be exercised.

Frequent Use of Emergency Departments by the Elderly Population When Continuing Care Is Not Well Established.

INTRODUCTION: The elderly, who suffer from multiple chronic diseases, represent a substantial proportion of Emergency Department (ED) frequent users, thus contributing to ED overcrowding, although they could benefit from other health care facilities, if those were available. The aim of this study was to evaluate and characterize hospital visits of older patients (age 65 or greater) to the ED of a university teaching hospital in Rome from the 1st of January to the 31st of December 2014, in order to identify clinical and social characteristics potentially associated with "elderly frequent users". MATERIAL AND METHODS: A retrospective study was performed during the calendar year 2014 (1st January 2014 - 31st December 2014) analyzing all ED admissions to the University Hospital of Rome Tor Vergata. Variables collected included age, triage code, arrival data, discharge diagnosis, and visit outcome. We performed a risk analysis using univariate binary logistic regression models. RESULTS: A total number of 38,016 patients accessed the ED, generating 46,820 accesses during the study period, with an average of 1.23 accesses for patient. The elderly population represented a quarter of the total ED population and had an increased risk of frequent use (OR 1.5: CI 1.4-1.7) and hospitalization (OR 3.8: CI 3.7-4). Moreover, they showed a greater diagnostic complexity, as demonstrated by the higher incidence of yellow and red priority codes compared to other ED populations (OR 3.1: CI 2.9-3.2). DISCUSSION: Older patients presented clinical and social characteristics related to the definition of "elderly frail frequent users". The fact that a larger number of hospitalizations occurred in such patients is indirect evidence of frailty in this specific population, suggesting that hospital admissions may be an inappropriate response to frailty, especially when continued care is not established. CONCLUSION: Enhancement of continuity of care, establishment of a tracking system for those who are at greater risk of visiting the ED and evaluating fragile individuals should be the highest priority in addressing ED frequent usage by the elderly.

Disparities in management of new-onset atrial fibrillation in the emergency department despite adherence to the current guidelines: data from a large metropolitan area.

Atrial Fibrillation management is still a matter for debate. Past research has largely been based on the outpatient setting in which patients are followed during ambulatory visits. Very little data exist on the optimal management of AF in the Emergency Department (ED). This study investigated which factors drive different AF treatments in the ED, describing their use in different hospitals. Finally, the efficacy of different strategies in terms of cardioversion in the ED was analyzed. Charts of patients treated for atrial fibrillation (AF) were collected in 6 EDs in a large metropolitan area over a 24-consecutive month period and were reviewed and analysed. Demographics, comorbidities, treatment strategy and ED outcome were collected. Inclusion criteria were symptom onset <3 weeks and stable hemodynamic conditions at presentation. A propensity score was used to adjust for baseline clinical characteristics and to compare the efficacy of different treatments. 3,085 patients were included in the analysis. Variables associated with a rhythm control strategy were onset of symptoms <48 h, age, dyspnea, palpitations, renal failure and the presence of a mechanical valve. Different EDs applied different strategies in terms of drugs used and the electrocardioversion rate, showing heterogeneity in AF management. Adjusting for the propensity score, electrocardioversion and antidysrhythmic drugs of class Ic were more effective than a wait-and-watch strategy in the ED. Despite international guidelines being respected, AF management is heterogeneous in different ED settings. A rhythm control strategy with electrocardioversion and Class Ic drugs is more effective than a wait-and watch approach during the ED visit. Further research, toward an evidence-based approach to the emergent management of AF in the ED, is still needed.

Investigating feedforward neural regulation of circulation from analysis of spontaneous arterial pressure and heart rate fluctuations in conscious rats.

It has been suggested in anesthetized animals that the occurrence of sequences of consecutive beats characterized by systolic arterial pressure (SAP) and RR or pulse interval (PI) changing in the opposite direction (SAP(+)/RR(-) and SAP(-)/RR(+), nonbaroreflex sequences) might represent the expression of neural cardiovascular regulatory mechanisms operating with feedforward characteristics. The aim of the present study was to study nonbaroreflex sequences in a more physiological experimental model, i.e., in conscious freely moving rats. We studied conscious rats before and after 1) complete autonomic blockade (n = 12), 2) sympathetic blockade (n = 10), 3) alpha (n = 7)- and beta (n = 8)-adrenergic blockade, and 4) parasympathetic blockade (n = 10). Nonbaroreflex sequences were defined as three or more beats in which SAP and PI of the following beat changed in the opposite direction. Complete autonomic blockade reduced the number of nonbaroreflex sequences (95.6 +/- 9.0 vs. 45.2 +/- 4.1, P < 0.001), as did sympathetic blockade (80.9 +/- 12.6 vs. 30.9 +/- 6.1, P < 0.001). The selective alpha-receptor blockade did not induce significant changes (80.9 +/- 12.5 in baseline vs. 79.0 +/- 14.7 after prazosin), whereas beta-receptor blockade significantly reduced nonbaroreflex sequence occurrence (80.9 +/- 12.5 in baseline vs. 48.9 +/- 15.3 after propranolol). Parasympathetic blockade produced a significant increase of nonbaroreflex sequences (95.1 +/- 6.9 vs. 136.0 +/- 12.4, P < 0.01). These results demonstrate the physiological role of the nonbaroreflex sequences as an expression of a feedforward type of short-term cardiovascular regulation able to interact dynamically with the feedback mechanisms of baroreflex origin in the neural control of the sinus node.

Effects of residential exercise training on heart rate recovery in coronary artery patients.

The aims of the present study are twofold: 1) to investigate whether heart rate recovery (HRR) after a cycle ergometry test is affected by exercise training and 2) to test the ability of HRR to replicate the baroreflex sensitivity (BRS) changes that occur in response to an exercise training program in coronary artery patients. We randomized 82 coronary artery patients undergoing a residential cardiac rehabilitation program to an exercise training group (TR; n = 43) and an untrained group (UTR; n = 39). All of the patients underwent an exercise test before and after the rehabilitation program. HRR was recorded at the end of the 1st and 2nd min after exercise. BRS was determined at rest before and after treatment. HRR after the 2nd min was significantly improved in TR patients (-21.4 +/- 0.9 beats/min) compared with UTR patients (-17.8 +/- 1.2 beats/min) at the end of the training program. Improvement in HRR paralleled that in BRS in TR patients (from 3.2 +/- 0.3 to 5.3 +/- 0.8 ms/mmHg; P < 0.001), whereas no significant change was evident in UTR patients (from 3.5 +/- 0 to 4.0 +/- 0.4 ms/mmHg; P = 0.230). Our data show that HRR in the 2nd min after the cessation of a cycle ergometer exercise test increased in coronary artery patients after an exercise training period. This result confirms the positive effect induced by exercise training on HRR and extends the conclusions of previous studies to different modalities of exercise (i.e., cycle ergometer). HRR might provide an additional simple marker of the effectiveness of physical training programs in cardiac patients.

Revisiting the potential of time-domain indexes in short-term HRV analysis.

In the context of HRV analysis, we evaluated the information content of two measures that can easily be derived from the classical RR time-domain indexes. The two measures are: 1) the ratio sd/rmssd, where sd is the RR standard deviation and rmssd is the root mean square of squared differences of consecutive RR beats; and 2) the ratio sd2/sd1, where sd2 and sd1 are extracted from the Poincaré plot and represent the transversal and longitudinal dispersion of the cloud of points (RR(i),RR(i)(+1)). We compared the performance of the two measures with that of the classical LF/HF ratio in a group of healthy subjects who underwent a 70 degrees upright tilt test. The goodness of the results obtained by the two measures, the simplicity of their calculation and their applicability free from a priori assumptions on the characteristics of the data are proposed to the attention of the community involved in the HRV analysis as a possible alternative to the LF/HF ratio.