Effects of high-intensity interval training on vascular function in patients with cardiovascular disease: a systematic review and meta-analysis

Background: Exercise training improves endothelial function in patients with cardiovascular disease (CVD). However, the influence of training variables remains unclear. The aim of this study was to evaluate the effect of high-intensity interval training (HIIT), compared to moderate intensity training (MIT) and other exercise modalities (i.e., resistance and combined exercise), on endothelial function, assessed by arterial flow-mediated dilation (FMD) or endothelial progenitor cells (EPCs), in patients with CVD. Secondly, we investigated the influence of other training variables (i.e., HIIT protocol).Methods: The PICOS strategy was used to identify randomised and non-randomised studies comparing the effect of HIIT and other exercise modalities (e.g., MIT) on endothelial function in patients with CVD. Electronic searches were carried out in Pubmed, Embase, and Web of Science up to November 2022. The TESTEX scale was used to evaluate the methodological quality of the included studies. Random-effects models of between-group mean difference (MD) were estimated. A positive MD indicated an effect in favour of HIIT. Heterogeneity analyses were performed by the chi-square test and I2 index. Subgroup analyses evaluated the influence of potential moderator variables.Results: Fourteen studies (13; 92.9% randomised) were included. Most of the studies trained 3 days a week for 12 weeks and performed long HIIT. No statistically significant differences were found between HIIT and MIT for improving brachial FMD in patients with coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF) (8 studies; MD+ = 0.91% [95% confidence interval (CI) = −0.06, 1.88]). However, subgroup analyses showed that long HIIT (i.e., > 1 min) is better than MIT for enhancing FMD (5 studies; MD+ = 1.46% [95% CI = 0.35, 2.57]), while no differences were found between short HIIT (i.e., ≤ 1 min) and MIT (3 studies; MD+ = −0.41% [95% CI = −1.64, 0.82]). Insufficient data prevented pooled analysis for EPCs, and individual studies failed to find statistically significant differences (p > .050) between HIIT and other exercise modalities in increasing EPCs.Discussion: Poor methodological quality could limit the precision of the current results and increase the inconsistency. Long HIIT is superior to MIT for improving FMD in patients with CAD or HFrEF. Future studies comparing HIIT to other exercise modalities, as well as the effect on EPCs and in HF with preserved ejection fraction are required.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42022358156

Effects of high-intensity interval training on vascular function in patients with cardiovascular disease: a systematic review and meta-analysis

Background: Exercise training improves endothelial function in patients with cardiovascular disease (CVD). However, the influence of training variables remains unclear. The aim of this study was to evaluate the effect of highintensity interval training (HIIT), compared to moderate intensity training (MIT) and other exercise modalities (i.e., resistance and combined exercise), on endothelial function, assessed by arterial flow-mediated dilation (FMD) or endothelial progenitor cells (EPCs), in patients with CVD. Secondly, we investigated the influence of other training variables (i.e., HIIT protocol). Methods: The PICOS strategy was used to identify randomised and nonrandomised studies comparing the effect of HIIT and other exercise modalities (e.g., MIT) on endothelial function in patients with CVD. Electronic searches were carried out in Pubmed, Embase, and Web of Science up to November 2022. The TESTEX scale was used to evaluate the methodological quality of the included studies. Random-effects models of between-group mean difference (MD) were estimated. A positive MD indicated an effect in favour of HIIT. Heterogeneity analyses were performed by the chi-square test and I2 index. Subgroup analyses evaluated the influence of potential moderator variables. Results: Fourteen studies (13; 92.9% randomised) were included. Most of the studies trained 3 days a week for 12 weeks and performed long HIIT. No statistically significant differences were found between HIIT and MIT for improving brachial FMD in patients with coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF) (8 studies; MD+ = 0.91% [95% confidence interval (CI) = −0.06, 1.88]). However, subgroup analyses showed that long HIIT (i.e., > 1 min) is better than MIT for enhancing FMD (5 studies; MD+ = 1.46% [95% CI = 0.35, 2.57]), while no differences were found between short HIIT (i.e., ≤ 1 min) and MIT (3 studies; MD+ = −0.41% [95% CI = −1.64, 0.82]). Insufficient data prevented pooled analysis for EPCs, and individual studies failed to find statistically significant differences (p > .050) between HIIT and other exercise modalities in increasing EPCs. Discussion: Poor methodological quality could limit the precision of the current results and increase the inconsistency. Long HIIT is superior to MIT for improving FMD in patients with CAD or HFrEF. Future studies comparing HIIT to other exercise modalities, as well as the effect on EPCs and in HF with preserved ejection fraction are required

Effects and Optimal Dose of Exercise on Endothelial Function in Patients with Heart Failure: A Systematic Review and Meta‑Analysis

Background Exercise-based cardiac rehabilitation (CR) is considered an effective treatment for enhancing endothelial function in patients with heart failure (HF). However, recent studies have been published and the optimal “dose” of exercise required to increase the benefits of exercise-based CR programmes on endothelial function is still unknown. Objectives (a) To estimate the effect of exercise-based CR on endothelial function, assessed by flow-mediated dilation (FMD), in patients with HF; (b) to determine whether high-intensity interval training (HIIT) is better than moderate-intensity training (MIT) for improving FMD; and (c) to investigate the influence of exercise modality (i.e. resistance exercise vs. aerobic exercise and combined exercise vs. aerobic exercise) on the improvement of endothelial function. Methods Electronic searches were carried out in PubMed, Embase, and Scopus up to February 2022. Random-effects models of between-group mean differences were estimated. Heterogeneity analyses were performed by means of the chi-square test and I2 index. Subgroup analyses and meta-regressions were used to test the influence of potential moderator variables on the effect of exercise. Results We found a FMD increase of 3.09% (95% confidence interval [CI] = 2.01, 4.17) in favour of aerobic-based CR programmes compared with control groups in patients with HF and reduced ejection fraction (HFrEF). However, the results of included studies were inconsistent (p < .001; I2 = 95.2%). Higher FMD improvement was found in studies which were randomised, reported radial FMD, or performed higher number of training sessions a week. Moreover, HIIT enhanced FMD to a greater extent than MIT (2.35% [95% CI = 0.49, 4.22]) in patients with HFrEF. Insufficient data prevented pooled analyses for the effect of exercise in patients with HF and preserved ejection fraction and the influence of exercise modality on the improvement of endothelial function. Conclusion Aerobic-based CR is a non-pharmacological treatment for enhancing endothelial function in patients with HFrEF. However, higher training frequency and HIIT induce greater adaptation of endothelial function in these patients, which should betaken into consideration when designing exercise-based CR programmes. Trial registration The protocol was prospectively registered on the PROSPERO database (CRD42022304687)

Hypokalemia as a sensitive biomarker of disease severity and the requirement for invasive mechanical ventilation requirement in COVID-19 pneumonia: A case series of 306 Mediterranean patients

Objectives: Serum levels of potassium (K+) appear to be significantly lower in severe cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the clinical significance of this is unknown. The objective was to investigate whether hypokalemia acts as a biomarker of severity in coronavirus disease 2019 (COVID-19) pneumonia and is associated with major clinical outcomes.Methods: A retrospective cohort study of inpatients with COVID-19 pneumonia (March 3 to May 2, 2020) was performed. Patients were categorized according to nadir levels of K+ in the first 72 h of admission: hypokalemia (K+ ≤3.5 mmol/l) and normokalemia (K+ >3.5 mmol/l). The main outcomes were all-cause mortality and the need for invasive mechanical ventilation (IMV); these were analyzed by multiple logistic regression (odds ratio (OR), 95% confidence interval (CI)).Results: Three hundred and six patients were enrolled. Ninety-four patients (30.7%) had hypokalemia and these patients showed significantly higher comorbidity (Charlson comorbidity index ≥3, 30.0% vs 16.3%; p = 0.02) and CURB65 scores (median (interquartile range): 1.5 (0.0-3.0) vs 1.0 (0.0-2.0); p = 0.04), as well as higher levels of some inflammatory parameters at baseline. After adjustment for confounders, hypokalemia was independently associated with requiring IMV during the admission (OR 8.98, 95% CI 2.54-31.74). Mortality was 15.0% (n = 46) and was not influenced by low K+. Hypokalemia was associated with longer hospital and ICU stays.Conclusions: Hypokalemia is prevalent in patients with COVID-19 pneumonia. Hypokalemia is an independent predictor of IMV requirement and seems to be a sensitive biomarker of severe progression of COVID-19

Modelo asistencial ambulatorio de alta resolución COVID-A2R: una solución efectiva en el servicio de urgencias para pacientes con COVID-19 y riesgo de evolución desfavorable

Objetivo. Evaluar la efectividad de un modelo asistencial basado en la derivación desde el servicio de urgencias hospitalarios (SUH) a una consulta presencial precoz de alta resolución (COVID-A2R), para pacientes con infección por SARS-CoV-2 sin insuficiencia respiratoria, pero con factor de riesgo de complicación/deterioro clínico. Método. Cohorte retrospectiva de pacientes remitidos por COVID-19 (RT-PCR) desde el SUH de un hospital terciario a COVID-A2R (7 de enero - 17 de febrero de 2021). Los criterios de inclusión son presencia de alta comorbilidad y elevación de biomarcadores inflamatorios en pacientes sin neumonía, o la presencia de neumonía con elevación de biomarcadores inflamatorios sin insuficiencia respiratoria. La variable de resultado principal fue el no requerimiento de revisita en el SUH con ingreso hospitalario y su distribución temporal. Los objetivos secundarios son la frecuentación en COVID-A2R y el impacto económico potencial. Resultados. Se incluyeron 278 pacientes, edad mediana de 57 años, 57,9% hombres e índice de Charlson de 1. Consultaron en el SUH tras 7 (4-11) días de clínica y un 71,8% de los casos presentaban neumonía. El 64,7% de los pacientes requirió una visita única en COVID-A2R. No se produjo una revisita a urgencias con ingreso en el 87,8% (83,4-91,1) de los pacientes. De los 34 pacientes que ingresaron, el 88,2% lo hizo en menos de 5 días. El ahorro potencial del modelo fue de 1.708 días de ingreso hospitalario. Conclusiones. Un modelo asistencial ambulatorio con una consulta de alta resolución tras el alta de urgencias es efectivo para pacientes con COVID-19 sin insuficiencia respiratoria con marcadores clínicos o analíticos de evolución desfavorable.Objective. To evaluate the effectiveness of a care pathway (Spanish acronym, COVID-A2R) through which patients with SARS-CoV-2 infection were referred by a hospital emergency department (ED) for fast-track in-person outpatient clinic care if they did not have respiratory insufficiency but were at high risk for complications and poor outcome. Methods. Retrospective cohort of patients referred to the COVID-A2R pathway after being diagnosed with COVID-19 by reverse transcription polymerase chain reaction assay in a tertiary care hospital ED between January 7 and February 17, 2021. The inclusion criteria were 1) absence of pneumonia but presence of serious comorbidity and/or elevated biomarkers of inflammation, and 2) pneumonia with or without elevated inflammatory markers but without respiratory insufficiency. The main outcome was need for an emergency department revisit with hospital admission and time from ED evaluation to hospitalization. Secondary outcomes were the number of COVID-A2R visits and the potential economic impact. Results. We included 278 patients with a median age of 57 years (57.9% men) and a median Charlson Comorbidity Index of 1. The median time since onset of symptoms was 7 days (interquartile range, 4–11 days). Pneumonia was diagnosed in 71.8%, and 64.7% required only 1 in-person visit in the COVID-A2R pathway. No revisits to the ED were needed by 87.8% (83.4%–91.1%) of the patients. Of the 34 patients who were hospitalized, 88.2% were admitted within 5 days. The COVID-A2R model potentially saved 1708 days of hospitalization. Conclusion. The fast-track ambulatory care model was effective after emergency department discharge of patients with COVID-19 without respiratory insufficiency but with clinical or laboratory indicators of risk for poor outcome

Is the Verification Phase a Suitable Criterion for the Determination of Maximum Oxygen Uptake in Patients with Heart Failure and Reduced Ejection Fraction? A Validation Study

The verification phase (VP) has been proposed as an alternative to the traditional criteria used for the determination of the maximum oxygen uptake (VO2 max) in several populations. Nonetheless, its validity in patients with heart failure with reduced ejection fraction (HFrEF) remains unclear. Therefore, the aim of this study was to analyse whether the VP is a safe and suitable method to determine the VO2 max in patients with HFrEF. Adult male and female patients with HFrEF performed a ramp-incremental phase (IP), followed by a submaximal constant VP (i.e., 95% of the maximal workload during the IP) on a cycle ergometer. A 5-min active recovery period (i.e., 10 W) was performed between the two exercise phases. Group (i.e., median values) and individual comparisons were performed. VO2 max was confirmed when there was a difference of ≤ 3% in peak oxygen uptake (VO2 peak) values between the two exercise phases. Twenty-one patients (13 males) were finally included. There were no adverse events during the VP. Group comparisons showed no differences in the absolute and relative VO2 peak values between both exercise phases (p = 0.557 and p = 0.400, respectively). The results did not change when only male or female patients were included. In contrast, individual comparisons showed that the VO2 max was confirmed in 11 patients (52.4%) and not confirmed in 10 (47.6%). The submaximal VP is a safe and suitable method for the determination of the VO2 max in patients with HFrEF. In addition, an individual approach should be used because group comparisons could mask individual differences

Is the Verification Phase a Suitable Criterion for the Determination of Maximum Oxygen Uptake in Patients with Heart Failure and Reduced Ejection Fraction? A Validation Study

The verification phase (VP) has been proposed as an alternative to the traditional criteria used for the determination of the maximum oxygen uptake (VO2 max) in several populations. Nonetheless, its validity in patients with heart failure with reduced ejection fraction (HFrEF) remains unclear. Therefore, the aim of this study was to analyse whether the VP is a safe and suitable method to determine the VO2 max in patients with HFrEF. Adult male and female patients with HFrEF performed a ramp-incremental phase (IP), followed by a submaximal constant VP (i.e., 95% of the maximal workload during the IP) on a cycle ergometer. A 5-min active recovery period (i.e., 10 W) was performed between the two exercise phases. Group (i.e., median values) and individual comparisons were performed. VO2 max was confirmed when there was a difference of &le; 3% in peak oxygen uptake (VO2 peak) values between the two exercise phases. Twenty-one patients (13 males) were finally included. There were no adverse events during the VP. Group comparisons showed no differences in the absolute and relative VO2 peak values between both exercise phases (p = 0.557 and p = 0.400, respectively). The results did not change when only male or female patients were included. In contrast, individual comparisons showed that the VO2 max was confirmed in 11 patients (52.4%) and not confirmed in 10 (47.6%). The submaximal VP is a safe and suitable method for the determination of the VO2 max in patients with HFrEF. In addition, an individual approach should be used because group comparisons could mask individual differences