The Diagnostic Accuracy of Procalcitonin and Its Combination with Other Biomarkers for Candidemia in Critically Ill Patients.

Background: The aim of this study was to investigate the usefulness of serum procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte count ratio (NLR), and their combination, in distinguishing candidemia from bacteremia in intensive care unit (ICU) patients. Methods: This is a retrospective study in ICU patients with documented bloodstream infections (BSIs) and with both serum PCT and CRP measurements on the day of the positive blood sample. Illness severity was assessed by sequential organ failure assessment (SOFA) score on both admission and BSI day. Demographic, clinical, and laboratory data, including PCT and CRP levels and NLR on the day of the BSI, were recorded. Results: A total of 63 patients were included in the analysis, of whom 32 had bacteremia and 31 had candidemia. PCT, CRP, and NLR values were all significantly lower in candidemia compared with bacteremia (0.29 (0.14-0.69) vs. 1.73 (0.5-6.9) ng/mL, p < 0.001, 6.3 (2.4-11.8) vs. 19 (10.7-24.8) mg/dl, p < 0.001 and 6 (3.7-8.6) vs. 9.8 (5.3-16.3), p = 0.001, respectively). PCT was an independent risk factor for candidemia diagnosis (OR 0.153, 95%CI: 0.04-0.58, p = 0.006). A multivariable model consisting of the above three variables had better predictive ability (AUC-ROC = 0.88, p < 0.001), for candidemia diagnosis, as compared to that of PCT, CRP, and NLR, whose AUC-ROCs were all lower (0.81, p < 0.001, 0.78, p < 0.001, and 0.68, p = 0.015, respectively). Conclusions: A combination of routinely available laboratory tests, such as PCT, CRP, and NLR, could prove useful for the early identification of ICU patients with candidemia.

Low-Medium and High-Intensity Inspiratory Muscle Training in Critically Ill Patients: A Systematic Review and Meta-Analysis.

Background and objectives: Mechanical ventilation is often used in intensive care units to assist patients' breathing. This often leads to respiratory muscle weakness and diaphragmatic dysfunction, causing weaning difficulties. Inspiratory muscle training (IMT) has been found to be beneficial in increasing inspiratory muscle strength and facilitating weaning. Over the years, different protocols and devices have been used. Materials and Methods: The aim of this systematic review and meta-analysis was to investigate the effectiveness of low-medium (LM-IMT) and high-intensity (H-IMT) threshold inspiratory muscle training in critically ill patients. A systematic literature search was performed for randomized controlled trials (RCTs) in the electronic databases Google Scholar, PubMed, Scopus, and Science Direct. The search involved screening for studies examining the effectiveness of two different intensities of threshold IMT in critically ill patients published the last 10 years. The Physiotherapy Evidence Database (PEDro) scale was chosen as the tool to assess the quality of studies. A meta-analysis was performed where possible. Results: Fourteen studies were included in the systematic review, with five of them having high methodological quality. Conclusions: When examining LM-IMT and H-IMT though, neither was able to reach statistically significant improvement in their maximal inspiratory pressure (MIP), while LM-IMT reached it in terms of weaning duration. Additionally, no statistical difference was noticed in the duration of mechanical ventilation. The application of IMT is recommended to ICU patients in order to prevent diaphragmatic dysfunction and facilitate weaning from mechanical ventilation. Therefore, further research as well as additional RCTs regarding different protocols are needed to enhance its effectiveness.

Strong ion gap and anion gap corrected for albumin and lactate in patients with sepsis in the intensive care unit.

INTRODUCTION: Metabolic acidosis is very common amongst critically ill sepsis patients partly due to the presence of unmeasured ions in serum. These ions can be detected by anion gap (AG) or strong ion gap (SIG) concentration values. The purpose of this study is to assess the correlation and potential agreement of the two methods in critically ill patients with sepsis. MATERIALS AND METHODS: The present is a retrospective study including septic patients admitted to the Intensive Care Unit from December 2014 to July 2016. The [SIG] and the [AG] corrected for albumin and lactate ([AGcl]) were calculated on admission and on sepsis remission or deterioration. The correlation of the two parameters was assessed in all patient groups using the Pearson correlation coefficient and linear regression analysis and the agreement with Bland-Altman plots. ROC survival curves were also generated for the patients in relation to the values of [AGcl], [SIG] and inorganic [SIG] ([SIGi]) on admission. RESULTS: There was a strong correlation linking [AGcl] and [SIG] values (r>0.9, P<0.05) in all patient groups. The results from all three linear regression equations were statistically significant as the models predicted the [AGcl] value from the [SIG] value with high accuracy. The mean difference of the two methods (i.e. [AGcl] - [SIG] in every patient separately) in septic patients on admission was 11.75 mEq/l with 95% limits of agreement [9.7-13.8]; in patients with sepsis deterioration, it was 11.8 mEq/l with 95% limits of agreement [9.8-13.7] and in patients with sepsis remission, it was 11.5 mEq/l with 95% limits of agreement [10.4-12.7]. ROC survival curves demonstrated a small area under the curve (AUC): [SIG] AUC: 0.479, 95% CI [0.351, 0.606], [SIGi] AUC: 0.581, 95% CI [0.457, 0.705], [AGcl] AUC: 0.529, 95% CI [0.401, 0.656]. CONCLUSION: [AGcl] and [SIG] demonstrate excellent correlation in septic patients, with a mean difference of about 12 mEq/l. Both parameters failed to demonstrate any predictive ability regarding patient mortality.

Circulating microvesicles across a population with various degree of cardiovascular burden are associated with systolic blood pressure.

Circulating microvesicles (MVs) have been studied in heterogeneous, divergent, and rather small patient populations with cardiovascular risk . Therefore, we measured endothelial (EMVs), platelet (PMVs) and erythrocyte (RMVs) MVs in patients with divergent cardiovascular risk. We then compared them to coronary artery disease (CAD) and healthy subjects and identified independent MVs' predictors. We enrolled consecutive patients from our Cardiology, Hypertension, Diabetic, Rheumatic, and Nephrology Outpatient Units with MVs measurements. Central blood pressure (BP) was measured by either applanation tonometry or Mobil-O-graph device, while MVs by a standardized flow cytometry protocol. We studied 369 participants with increased cardiovascular risk: 63 with high cardiovascular risk (47 diabetes mellitus type II/DM and 16 end-stage renal disease/ESRD), 92 with chronic inflammatory disorders and 73 with untreated essential hypertension/UEH. We further included 53 subjects with CAD and 87 otherwise healthy individuals. All MVs were lower in patients with increased cardiovascular risk compared to CAD, showing predictive value with high sensitivity and specificity. Furthermore, PMVs and EMVs were increased in patients with cardiovascular risk compared to healthy individuals. DM and ESRD patients had increased EMVs versus UEH and chronic inflammatory disorders. In the whole study population, RMVs were associated only with history of essential hypertension. In multivariate analysis, systolic BP predicted PMVs. Aage, systolic BP, and DM predicted EMVs. In a large population of patients with divergent cardiovascular risk, MVs are independently associated with systolic blood pressure.

Incidence and peri-operative risk factors for development of acute kidney injury in patients after cardiac surgery: A prospective observational study.

BACKGROUND: Patients admitted to intensive care unit (ICU) after cardiac surgery develop acute kidney injury (AKI) immediately post-operation. We hypothesized that AKI occurs mainly due to perioperative risk factors and may affect outcome. AIM: To assess peri-operative risk factors for AKI post cardiac surgery and its relationship with clinical outcome. METHODS: This was an observational single center, tertiary care setting study, which enrolled 206 consecutive patients, admitted to ICU after cardiac surgery. Patients were followed-up until ICU discharge or death, in order to determine the incidence of AKI, perioperative risk factors for AKI and its association with outcome. Univariate and multivariate logistic regression analysis was performed to assess predictor variables for AKI development. RESULTS: After ICU admission, 55 patients (26.7%) developed AKI within 48 h. From the logistic regression analysis performed, high EuroScore II (OR: 1.18; 95%CI: 1.06-1.31, P = 0.003), white blood cells (WBC) pre-operatively (OR: 1.0; 95%CI: 1.0-1.0, P = 0.002) and history of chronic kidney disease (OR: 2.82; 95%CI: 1.195-6.65, P = 0.018) emerged as independent predictors of AKI among univariate predictors. AKI that developed AKI had longer duration of mechanical ventilation [1113 (777-2195) vs 714 (511-1020) min, P = 0.0001] and ICU length of stay [70 (28-129) vs 26 (21-51) h, P = 0.0001], higher rate of ICU-acquired weakness (16.4% vs 5.3%, P = 0.015), reintubation (10.9% vs 1.3%, P = 0.005), dialysis (7% vs 0%, P = 0.005), delirium (36.4% vs 23.8%, P = 0.001) and mortality (3.6% vs 0.7%, P = 0.046). CONCLUSION: Patients present frequently with AKI after cardiac surgery. EuroScore II, WBC count and chronic kidney disease are independent predictors of AKI development. The occurrence of AKI is associated with poor outcome.

Common Pathogenetic Pathways of Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are two cardinal manifestations of the metabolic syndrome, which is becoming a growing global pandemic and a health care burden. They constitute a pathogenetic duo, with complex interplay through interrelated, but still partly understood, pathophysiological pathways, which mainly involve lipid toxicity (expressed through increased hepatic de novo lipogenesis, hepatic and peripheral insulin resistance, upregulated lipolysis, lipoprotein abnormalities, hyperinsulinemia), impaired autophagy, mitochondrial dysfunction, endoplasmic reticulum stress, adipose tissue dysfunction with a consequent latent inflammatory state, inflammasome activation, genetic and epigenetic factors, altered gut microbiota and finally dietary factors. In this review, based on data from recent studies and focusing mainly on common molecular mechanisms, we will highlight the common pathophysiological grounds and the interplay between NAFLD and T2DM.

Serum inflammatory and brain injury biomarkers in COVID-19 patients admitted to intensive care unit: A pilot study.

Background: The aim of this study was to measure serum brain injury biomarkers in patients with COVID-19 admitted to intensive care unit (ICU), without evidence of brain impairment, and to determine potential correlations with systemic inflammatory markers, illness severity, and outcome. Methods: In patients admitted to the ICU with COVID-19, without clinical evidence of brain injury, blood S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE) and interleukin-6 (IL-6) were measured on admission. Clinical, routine laboratory data and illness severity were recorded. Comparisons between 28-day survivors and non-survivors and correlations of neurological biomarkers to other laboratory data and illness severity, were analyzed. Results: We included 50 patients, median age 64 [IQR 58-78] years, 39 (78%) males, 39 (78%) mechanically ventilated and 11 (22%) under high flow nasal oxygen treatment. S100B and NSE were increased in 19 (38%) and 45 (90%) patients, respectively. S100B was significantly elevated in non-survivors compared to survivors: 0.15 [0.10-0.29] versus 0.11 [0.07-0.17] µg/L, respectively, (p = 0.03), and significantly correlated with age, IL-6, arterial lactate, noradrenaline dose, illness severity and lymphocyte count. IL-6 was significantly correlated with C-reactive protein, noradrenaline dose and organ failure severity. NSE was correlated only with lactate dehydrogenase. Conclusion: Brain injury biomarkers were frequently elevated in COVID-19 ICU patients, in the absence of clinical evidence of brain injury. S100B was significantly correlated with IL-6, low lymphocyte count, hypoperfusion indices, illness severity, and short-term outcome. These findings indicate a possible brain astrocytes and neurons involvement, also suggesting a broader role of S100B in systemic inflammatory response.

Thromboinflammation in Sepsis and Heparin: A Review of Literature and Pathophysiology.

BACKGROUND/AIM: Thromboinflammation is the pathophysiologic mechanism in which coagulation and inflammation interact and complement each other. It is observed in a number of degenerative diseases, one of them being sepsis. Quiescent endothelial cells exert antithrombotic and anti-inflammatory actions that are reduced during sepsis. The concomitant effect of the subsequent dysregulation of coagulation and complement actuation is platelet activation and aggregation, and leukocyte recruitment, with detrimental effects on the vascular endothelium. Tissue factor and α-thrombin are major sentinels in the pathogenesis of this process. This literature review aimed to cover the basic principles of the mechanisms implicated in thromboinflammation occurring during sepsis and also investigates the role of heparin as a possible therapeutic agent, since it exhibits both anticoagulant and anti-inflammatory functions. MATERIALS AND METHODS: PubMed, SCOPUS and ScienceDirect databases were used for search of literature from inception to April 2022. To be included in our review, studies had to refer to the pathophysiologic mechanisms leading to coincident coagulation and inflammation, or to the administration of heparin either for treatment or prophylaxis, both in the context of sepsis. RESULTS: A total of 276 articles were drawn from the initial literature search. 124 were duplicated and out of the remaining 152 articles, 29 met our inclusion criteria and were reviewed. CONCLUSION: Clinical trials among sepsis patients have indicated that the thromboinflammatory process is more complex than believed, as adverse bleeding events continue to occur despite the use of anticoagulants with different pharmacodynamics. However, heparin has a pleiotropic effect that might provide protection against sepsis and related complications and merits further research.

A Novel Non-invasive Index of Cardiopulmonary Reserve for the Prediction of Failure of Weaning From Mechanical Ventilation.

PURPOSE: To develop an easy-to-implement prediction index of weaning failure for ICU patients. Materials and methods: We developed a prediction index modifying respiratory exchange ratio (RER), Mod-RER, a parameter measured during the cardiopulmonary exercise test (CPET) based on respiratory quotient. The Mod-RER index is the ratio of partial pressure of CO2 in central venous blood over the difference of partial pressure of O2 in arterial and central venous blood (Mod-RER=PcvCO2/PaO2-PcvO2, where PcvCO2 = partial pressure of CO2 in central venous blood, PaO2 = partial pressure of O2 in arterial blood, and PcvO2 = partial pressure of O2 in central venous blood). We prospectively tested its predictive value, compared to other indices of weaning outcome, in an observational study of difficult-to-wean ICU patients. RESULTS: Mod-RER index increased significantly only in failed trials and receiver operating characteristic (ROC) analysis for prediction of outcome based on Mod-RER index change had an area under the curve (AUC) 0.80 (p<0.001). Mod-RER change exhibited the highest sensitivity (84.6%) and specificity (78.1%) among the tested indices, with the optimal cut-off of 19.3%. Comparison of AUCs did not reach statistical significance (p=0.106). CONCLUSIONS: We conclude that Mod-RER index is an accurate, easy-to-use prediction tool of weaning failure, useful in decision making of timely extubation of ICU patients, especially in the demanding era of the coronavirus disease 2019 (COVID-19) pandemic.

Epidemiology of Candidemia and Fluconazole Resistance in an ICU before and during the COVID-19 Pandemic Era.

The objectives of this study were to investigate the incidence of candidemia, as well as the factors associated with Candida species distribution and fluconazole resistance, among patients admitted to the intensive care unit (ICU) during the COVID-19 pandemic, as compared to two pre-pandemic periods. All patients admitted to the ICU due to COVID-19 from March 2020 to October 2021, as well as during two pre-pandemic periods (2005-2008 and 2012-2015), who developed candidemia, were included. During the COVID-19 study period, the incidence of candidemia was 10.2%, significantly higher compared with 3.2% and 4.2% in the two pre-pandemic periods, respectively. The proportion of non-albicans Candida species increased (from 60.6% to 62.3% and 75.8%, respectively), with a predominance of C. parapsilosis. A marked increase in fluconazole resistance (from 31% to 37.7% and 48.4%, respectively) was also observed. Regarding the total patient population with candidemia (n = 205), fluconazole resistance was independently associated with ICU length of stay (LOS) before candidemia (OR 1.03; CI: 1.01-1.06, p = 0.003), whereas the presence of shock at candidemia onset was associated with C. albicans (OR 6.89; CI: 2.2-25, p = 0.001), and with fluconazole-susceptible species (OR 0.23; CI: 0.07-0.64, p = 0.006). In conclusion, substantial increases in the incidence of candidemia, in non-albicansCandida species, and in fluconazole resistance were found in patients admitted to the ICU due to COVID-19, compared to pre-pandemic periods. At candidemia onset, prolonged ICU LOS was associated with fluconazole-resistant and the presence of shock with fluconazole-susceptible species.

Older adults with severe coronavirus disease 2019 admitted to intensive care unit: prevalence, characteristics and risk factors for mortality.

BACKGROUND: Although older adults are at high risk for severe coronavirus disease 2019 (COVID-19) requiring intensive care unit (ICU) admission, age is often used as a selection criterion in case of ICU beds scarcity. We sought to compare the proportion, clinical features and mortality between patients ≥70 years old and younger ICU patients with COVID-19. METHODS: All patients, consecutively admitted to our COVID ICU, where age was not used as an admission criterion, from March 2020 through April 2021, were included. Demographics, clinical and laboratory characteristics were recorded. Illness severity and Charlson comorbidity Index (CCI) were calculated. Patients≥70 years old were compared to youngers. RESULTS: Of 458 patients (68 [59-76] years, 70% males), 206 (45%) were ≥70 years old. Compared to younger, older patients had higher illness severity scores (APACHE II 18 [14-23] versus 12 [9-16], P<0.001, SOFA 8 [6-10] versus 6 [2-8], P<0.001, CCI 5 [4-6] versus 2 [1-3], P<0.001), increased need for mechanical ventilation (92% vs. 72%, P<0.001) and ICU mortality (74% versus. 29%, P<0.001). Age (HR: 1.045, CI: 1.02-1.07, P=0.001), CCI (HR: 1.135, CI: 1.037-1.243, P=0.006) and APACHE II (HR: 1.070, CI: 1.013-1.130, P=0.015) were independently associated with mortality. Among comorbidities, obesity, chronic pulmonary disease and chronic kidney disease were independent risk factors for death. CONCLUSIONS: When age is not used as criterion for admission to COVID ICU, patients ≥70 years old represent a considerable proportion and, compared to younger ones, they have higher mortality. Age, severity of illness and CCI, and certain comorbidities are independent risk factors for mortality.

Immunostimulation and Coagulopathy in COVID-19 Compared to Patients With H1N1 Pneumonia or Bacterial Sepsis.

BACKGROUND/AIM: Multiple reports from all over the world link COVID-19 with endothelial/coagulation disorders as well as a dysregulated immune response. This study tested the hypothesis that immunostimulation will be greater in COVID-19 patients than in patients with H1N1 infection or bacterial sepsis. Also, whether an increase in immune stimulation will be accompanied by a more severely affected endothelium/coagulation system was examined. PATIENTS AND METHODS: Twenty-three septic patients, admitted in the Intensive Care Unit (ICU), were enrolled (9 with SARS-CoV-2, 5 with H1N1 pneumonia, 9 with bacterial sepsis). Myeloperoxidase (MPO) activity along with certain endothelial/coagulation factors were assessed on admission (time point 1) and at either improvement or deterioration (time point 2). RESULTS: MPO levels were significantly higher in COVID-19 patients compared to both other groups. Furthermore, in patients with COVID-19, vWF levels did not differ significantly, fVIII levels were lower while ADAMTS-13 activity was higher compared to patients with H1N1 pneumonia and bacterial sepsis (a trend in the latter). CONCLUSION: Increased immunostimulation was noted in COVID-19 patients compared to other septic patients; however, this was not accompanied by greater disturbance of the clotting system and/or more severe endothelial injury.

Dantrolene Induces Mitigation of Myocardial Ischemia-Reperfusion Injury by Ryanodine Receptor Inhibition.

The impairment of intracellular calcium homeostasis plays an essential role during ischemia-reperfusion injury. Calcium release from sarcoplasmic reticulum which is triggered by myocardial ischemia is mainly mediated by ryanodine receptors. Dantrolene sodium is a ryanodine receptor antagonist. The objective of the present study was to evaluate the in-vivo impact of dantrolene sodium on myocardial ischemia-reperfusion injury in swine models. An in vivo, experimental trial comparing 10 experimental animals which received dantrolene sodium with 9 control swine models was conducted. Their left anterior descending coronary artery was temporarily occluded for 75 minutes via a vessel tourniquet, which was then released. Myocardial reperfusion was allowed for 24 hours. Dantrolene was administered at the onset of the reperfusion period and levels of troponin, creatine phosphokinase and creatine kinase myocardial band between the two groups were compared. Additionally, various other hemodynamic parameters and left ventricular morphology and function were examined. There were significantly lower values of troponin, creatine phosphokinase and creatine kinase myocardial band in the dantrolene group indicating less ischemia-reperfusion injury. Moreover, the postischemic cardiac index was also greater in the dantrolene group, whereas viable myocardium was also better preserved. In conclusion, the in vivo cardioprotective role of dantrolene sodium against ischemia-reperfusion injury in swine models was indicated in this study. Therefore, dantrolene sodium administration could be a promising treatment against ischemia-reperfusion injury in humans. However, large randomized clinical studies should be firstly carried out to prove this hypothesis.

Dexamethasone in the Treatment of COVID-19: Primus Inter Pares?

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread globally, becoming a huge public health challenge. Even though the vast majority of patients are asymptomatic, some patients present with pneumonia, acute respiratory distress syndrome (ARDS), septic shock, and death. It has been shown in several studies that the severity and clinical outcomes are related to dysregulated antiviral immunity and enhanced and persistent systemic inflammation. Corticosteroids have been used for the treatment of COVID-19 patients, as they are reported to elicit benefits by reducing lung inflammation and inflammation-induced lung injury. Dexamethasone has gained a major role in the therapeutic algorithm of patients with COVID-19 pneumonia requiring supplemental oxygen or on mechanical ventilation. Its wide anti-inflammatory action seems to form the basis for its beneficial action, taming the overwhelming "cytokine storm". Amid a plethora of scientific research on therapeutic options for COVID-19, there are still unanswered questions about the right timing, right dosing, and right duration of the corticosteroid treatment. The aim of this review article was to summarize the data on the dexamethasone treatment in COVID-19 and outline the clinical considerations of corticosteroid therapy in these patients.

Unfractionated heparin reduces hepcidin levels in critically ill patients.

A strong anti-hepcidin activity has been observed in heparins. Mean hepcidin levels were significantly reduced compared to baseline, following the first day of unfractionated heparin administration in critically patients. Heparin displayed a strong independent negative association with hepcidin. These results may lead to future treatment methods of forms of anaemia characterised by hepcidin excess, common among the critically ill.

Cardiovascular Responses During Sepsis.

Sepsis is the life-threatening organ dysfunction arising from a dysregulated host response to infection. Although the specific mechanisms leading to organ dysfunction are still debated, impaired tissue oxygenation appears to play a major role, and concomitant hemodynamic alterations are invariably present. The hemodynamic phenotype of affected individuals is highly variable for reasons that have been partially elucidated. Indeed, each patient's circulatory condition is shaped by the complex interplay between the medical history, the volemic status, the interval from disease onset, the pathogen, the site of infection, and the attempted resuscitation. Moreover, the same hemodynamic pattern can be generated by different combinations of various pathophysiological processes, so the presence of a given hemodynamic pattern cannot be directly related to a unique cluster of alterations. Research based on endotoxin administration to healthy volunteers and animal models compensate, to an extent, for the scarcity of clinical studies on the evolution of sepsis hemodynamics. Their results, however, cannot be directly extrapolated to the clinical setting, due to fundamental differences between the septic patient, the healthy volunteer, and the experimental model. Numerous microcirculatory derangements might exist in the septic host, even in the presence of a preserved macrocirculation. This dissociation between the macro- and the microcirculation might account for the limited success of therapeutic interventions targeting typical hemodynamic parameters, such as arterial and cardiac filling pressures, and cardiac output. Finally, physiological studies point to an early contribution of cardiac dysfunction to the septic phenotype, however, our defective diagnostic tools preclude its clinical recognition. © 2021 American Physiological Society. Compr Physiol 11:1605-1652, 2021.

The acute and long-term effects of a cardiac rehabilitation program on endothelial progenitor cells in chronic heart failure patients: Comparing two different exercise training protocols.

BACKGROUND: Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Endothelial progenitor cells (EPCs) are also impaired. The purpose of the study was to assess the effect of a cardiac rehabilitation (CR) program on the increase of EPCs at rest and on the acute response after maximal exercise in patients with CHF and investigate whether there were differences between two exercise training protocols and patients of NYHA II and III classes. METHODS: Forty-four patients with stable CHF enrolled in a 36-session CR program and were randomized in one training protocol; either high-intensity interval training (HIIT) or HIIT combined with muscle strength (COM). All patients underwent maximum cardiopulmonary exercise testing (CPET) before and after the CR program and venous blood was drawn before and after each CPET. Five endothelial cellular populations, expressed as cells/106 enucleated cells, were quantified by flow cytometry. RESULTS: An increase in all endothelial cellular populations at rest was observed after the CR program (p < 0.01). The acute response after maximum exercise increased in 4 out of 5 endothelial cellular populations after rehabilitation. Although there was increase in EPCs at rest and the acute response after rehabilitation in each exercise training group and each NYHA class, there were no differences between HIIT and COM groups or NYHA II and NYHA III classes (p > 0.05). CONCLUSIONS: A 36-session CR program increases the acute response after maximum CPET and stimulates the long-term mobilization of EPCs at rest in patients with CHF. These benefits seem to be similar between HIIT and COM exercise training protocols and between patients of different functional classes.