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Frontiers in Nutrition 2024Coaches and athletes are increasingly interested in understanding athletes' serum vitamin D levels, their impact on strength, physical performance, and athletic...
Effects of vitamin D3 supplementation on strength of lower and upper extremities in athletes: an updated systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Coaches and athletes are increasingly interested in understanding athletes' serum vitamin D levels, their impact on strength, physical performance, and athletic outcomes. Previous meta-analyses were reported with limited sample size and no significant overall effect was found. Hence, it is crucial to conduct a thorough and up-to-date systematic examination and meta-analysis to elucidate the potential advantages of supplementing with vitamin D3 in enhancing muscle strength for athletes.
METHODS
We performed a thorough investigation, spanning three databases (PubMed, EBSCO, and Cochrane Library), seeking randomized controlled trials (RCTs) in all languages. These trials delved into the influence of vitamin D3 supplementation on the changes of pre- and post-intervention muscle strength in healthy athletes. Our systematic examination and meta-analysis took into account serum 25(OH)D levels exceeding 30 ng/mL as a marker of adequacy.
RESULTS
Ten RCTs, comprising 354 athletes (185 in the vitamin D3 group and 169 in the placebo group), fulfilled the inclusion criteria. During the study, 36 athletes were lost to follow-up, leaving 318 athletes (166 in the vitamin D3 group and 152 in the placebo group) with documented complete results. In comparison with the placebo group, there is a significant increase between the changes of pre- and post-intervention serum 25(OH)D levels among athletes following a period of vitamin D3 supplementation (MD 14.76, 95% CI: 8.74 to 20.77, < 0.0001). Overall effect of four strength measurements including handgrip, one repetition maximum Bench Press (1-RM BP), vertical jump, and quadriceps contraction was not significantly improved (SMD 0.18, 95% CI: -0.02 to 0.37, = 0.08), but there was a significant increase in quadriceps contraction (SMD 0.57, 95% CI: 0.04 to 1.11, = 0.04).
CONCLUSION
This updated meta-analysis indicates the potential benefits of vitamin D supplementation for enhancing muscle strength in athletes when analyzing its quantitatively synthesized effects. With limited available studies for the quantitative synthesis, it cannot warrant significant overall enhancements in muscle strength when athletes attain adequate serum 25(OH)D levels through supplementation.
PubMed: 38860160
DOI: 10.3389/fnut.2024.1381301 -
Korean Circulation Journal Apr 2024The efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) may depend on renal function, and this raises theoretical concern over its effects on cardiovascular...
Cardiovascular Outcomes of Sodium-Glucose Cotransporter-2 Inhibitors Therapy in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Systematic Review and Updated Meta-Analysis.
BACKGROUND AND OBJECTIVES
The efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) may depend on renal function, and this raises theoretical concern over its effects on cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).
METHODS
This systematic review and updated meta-analysis of randomized controlled trials (RCTs) compared cardiovascular outcomes of patients with T2DM and CKD treated with SGLT2i to placebo. PubMed, Embase, and Cochrane were systematically searched. Prespecified subgroup analyses were performed in strata of estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m² and 45 to 59 mL/min/1.73 m².
RESULTS
Nine RCTs comprising 29,146 patients were selected. Average follow-up ranged from 0.75 to 4.2 years. SGLT2i were shown to reduce the risk of all-cause mortality (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.97; p=0.01), the composite of cardiovascular mortality or hospitalizations for heart failure (HHF: HR, 0.71; 95% CI, 0.65-0.78; p<0.001), cardiovascular mortality (HR, 0.86; 95% CI, 0.76-0.98; p=0.02), HHF (HR, 0.62; 95% CI, 0.55-0.71; p<0.001), major adverse cardiovascular events (HR, 0.85; 95% CI, 0.77-0.94; p=0.002), stroke (HR, 0.76; 95% CI, 0.59-0.97; p=0.03), and myocardial infarction (HR, 0.78; 95% CI, 0.67-0.91; p=0.001). These findings were consistent over strata of eGFR, albeit with a lower incidence of stroke in patients treated with SGLT2i with eGFR <45 mL/min/1.73 m² (p-value for interaction=0.04).
CONCLUSIONS
Compared with a placebo, patients with T2DM and CKD treated with SGLT2i experience a reduction in all-cause mortality, cardiovascular mortality, and HHF.
TRIAL REGISTRATION
PROSPERO Identifier: CRD42023401081.
PubMed: 38859642
DOI: 10.4070/kcj.2023.0241 -
Translational Psychiatry Jun 2024The treatment of suicidal ideation in patients with depression has been a major problem faced by psychiatric and emergency departments, and reasonable drug selection is... (Meta-Analysis)
Meta-Analysis
The treatment of suicidal ideation in patients with depression has been a major problem faced by psychiatric and emergency departments, and reasonable drug selection is particularly important. Ketamine has been shown to reduce suicidal ideation rapidly, but the strength of the effect is unclear and there is little evidence-based medical evidence to support this. We systematically searched all articles published on PubMed, Cochrane Library, Web of Science, CNKI and EMBASE. Stata 15 and R 4.1.3 were used for meta-analysis, and odds ratios were calculated in fixed effects or random effects models based on the heterogeneity test results. Our search resulted in 505 articles; we analyzed 14 studies, which included 1,380 participants. The 14 studies included 10 randomized controlled trial (RCT) studies and 4 single-arm studies. Our study suggests that, ketamine has a significant therapeutic effect on suicidal ideation throughout the treatment cycle. We performed network meta-analyses(NMA) and pairwise meta-analyses to compare the efficacy of ketamine in the reduction of suicidal ideation. There was a significant reduction in suicidal ideation within the first day after treatment (NMA ketamine day1 RR = 10.02, 95%CI = 4.24 to 23.68). In repeated treatment, the degree of recovery of suicidal ideation after the last dose was significantly greater than that after the first dose (RR = 0.56, 95%CI = 0.51 to 0.62). Recovery of suicidal ideation was also significantly better in the treatment end point than in the placebo group at the same time point (NMA ketamine day26 RR = 4.29, 95%CI = 1.41 to 13.08). This is the first network meta-analysis to demonstrate the role of ketamine in the alleviation of suicidal ideation. Our network meta-analysis also compared the effects of different drugs at different time points, which was not done in previous studies. This is of great reference significance for future drug research andrational drug use.
Topics: Ketamine; Humans; Suicidal Ideation; Antidepressive Agents; Depressive Disorder; Network Meta-Analysis; Treatment Outcome; Depression
PubMed: 38858391
DOI: 10.1038/s41398-024-02973-1 -
SAGE Open Medicine 2024Functional electrical stimulation is important for the rehabilitation of patients with chronic heart failure. This meta-analysis of randomized controlled trials compared... (Review)
Review
The effect of functional electrical stimulation of the legs on cardiopulmonary function and quality of life in patients with chronic heart failure: A systematic review and meta-analysis.
INTRODUCTION
Functional electrical stimulation is important for the rehabilitation of patients with chronic heart failure. This meta-analysis of randomized controlled trials compared the efficacy of functional electrical stimulation versus conventional exercise training or placebo in patients with chronic heart failure.
METHODS
Studies were searched through PubMed, Embase, and the Cochrane Library databases up to 1 November 2023. The outcomes were cardiopulmonary function index (6-minute walking distance), peak oxygen consumption, and Minnesota Heart Failure Life Questionnaire quality of life scores. A subgroup analysis was conducted according to the ejection fraction. The 95% confidence interval and mean difference represented the outcome of the effect size.
RESULTS
Seventeen studies involving 732 participants were included. Compared with the control, functional electrical stimulation significantly improved peak oxygen consumption (MD = 2.84 ml/kg/min, 95% Cl: 1.99-3.68 ml/kg/min), increased 6-minute walking distance (MD = 49.52 m, 95% Cl: 22.61-76.43 m), and improved the life quality scores (MD = -12.86, 95% Cl: -17.48 to -7.88). Compared with functional electrical stimulation, exercise training also improved peak oxygen consumption (MD = -0.94 ml/kg/min, 95% Cl: -1.36 to -0.52 ml/kg/min), and the quality of life (QoL, MD = 0.66, 95% Cl: 0.34-0.98, < 0.05, = 38%), but the result of 6-minute walking distance (MD = -6.97 m, 95% Cl: -18.32 to -4.38 m) did not show a difference. Further subgroup analysis showed that outcomes including the above, significantly improved under the functional electrical stimulationfor both HF patients with reduced ejection fraction and HF patients with preserved ejection fraction patients, but difference is insignificant of the results between groups of aerobic exercise and functional electrical stimulationacted on patients with HF patients with reduced ejection fraction.
CONCLUSIONS
Our study demonstrates that compared with placebo, functional electrical stimulation benefits the patients with chronic heart failure on cardiopulmonary function and quality of life. Furthermore, HF patients with reduced ejection fraction patients benefit more from functional electrical stimulation than HF patients with reduced ejection fraction patients. Therefore, functional electrical stimulation is a promising complementary therapy for patients with chronic heart failure.
PubMed: 38855004
DOI: 10.1177/20503121241245003 -
Annals of Saudi Medicine 2024Acute respiratory distress syndrome (ARDS), which results in lung injury as a consequence of sepsis and septic shock, is associated with severe systemic inflammation and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute respiratory distress syndrome (ARDS), which results in lung injury as a consequence of sepsis and septic shock, is associated with severe systemic inflammation and is responsible for a high worldwide mortality rate.
OBJECTIVE
Investigate whether corticosteroids could benefit clinical outcomes in adult with ARDS.
METHODS
A comprehensive search of electronic databases Ovid MEDLINE, Ovid EMbase, and Cochrane Library from their inception to 7 May 2023 was conducted to identify studies that met the eligibility criteria, including only randomized controlled trials. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the methods of trial sequential analysis.
MAIN OUTCOME MEASURES
Mortality rates, including including the 14-, 28-, 45-, and 60-day mortality, hospital mortality, and intensive care unit (ICU) mortality.
SAMPLE SIZE
17 studies with 2508 patients.
RESULTS
Data relating to mortality at 14, 28, 45, and 60 days were not significantly different when treatments with corticosteroids and placebo were compared. In terms of hospital and ICU mortality, the mortality of those who had received corticosteroids was significantly lower than that of those who had not. ARDS patients who received assisted ventilation benefited from corticosteroid therapy, as revealed by the significant difference in outcome days between those who received assisted ventilation and those who did not. Corticosteroid had significantly more days free from mechanical ventilation, ICU-free days, and MODS-free days during the first 28 days, but not more organ support-free days up to day 28.
CONCLUSION
Although corticosteroid therapy did not reduce mortality rates at different observation periods, it significantly reduced hospital and ICU mortality. Administering corticosteroids to ARDS patients significantly decreased the days of assisted ventilation and time cost consumption. This study confirmed that long-term use of low-dose glucocorticoids may have a positive effect on early ARDS.
LIMITATION
Risk of bias due to the differences in patient characteristics.
Topics: Adult; Humans; Adrenal Cortex Hormones; Hospital Mortality; Intensive Care Units; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Distress Syndrome; Treatment Outcome
PubMed: 38853475
DOI: 10.5144/0256-4947.2024.167 -
International Journal of Cardiology Sep 2024Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are anti-hyperglycemic drugs and have been proven to have cardiovascular protective effects for patients with heart... (Meta-Analysis)
Meta-Analysis
Effect of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and structural changes following myocardial infarction: A systematic review and meta-analysis.
BACKGROUND
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are anti-hyperglycemic drugs and have been proven to have cardiovascular protective effects for patients with heart failure regardless of their diabetes status. However, the benefit of SGLT2i following myocardial infarction (MI) remains incompletely established. This review aimed to investigate the impact of SGLT2i on NT-proBNP levels and structural changes post-MI.
METHOD
Medline, ClinicalTrial.gov, Scopus, and Directory of open-access journals were searched to retrieve the relevant articles. Eligible studies were randomized clinical trials that assessed NT-proBNP and cardiac structural changes in patients who received SGLT2i compared to placebo following MI. Two reviewers independently screened articles, extracted data, and assessed study quality.
RESULT
Four studies were included in this review, including patients with and without diabetes. While two studies showed no marked decrease from the baseline in NT-proBNP levels between the SGLT2i group and the control group, two studies reported a substantial reduction. The meta-analysis included three of these studies, with a total of 238 participants. The meta-analysis did not find a statistically significant drop in NT-proBNP levels post-MI in the SGLT2 inhibitors group compared to placebo (pooled SMD = 0.16, 95% CI 0.57-0.26, P 0.45). Furthermore, different echocardiographic parameters were reported in the included trials, yet no meta-analysis could be conducted to assess the influence of SGLT2i on cardiac remodeling post-MI.
CONCLUSION
SGLT2i did not result in a statistically significant reduction of NT-proBNP level subsequent to myocardial infarction. A knowledge gap exists regarding the impact of these agents on cardiac remodeling post-MI. Future high-quality clinical trials are needed to provide more robust evidence.
Topics: Humans; Natriuretic Peptide, Brain; Sodium-Glucose Transporter 2 Inhibitors; Peptide Fragments; Myocardial Infarction; Randomized Controlled Trials as Topic; Biomarkers; Diabetes Mellitus, Type 2; Treatment Outcome
PubMed: 38852858
DOI: 10.1016/j.ijcard.2024.132239 -
Journal of Pharmaceutical Health Care... Jun 2024Based on several case reports and observational studies, there is a growing concern regarding the potential association between roxadustat, a hypoxia-inducible factor...
BACKGROUND
Based on several case reports and observational studies, there is a growing concern regarding the potential association between roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor, and suppression of thyroid function. In this systematic review and meta-analysis (PROSPERO: CRD42023471516), we aimed to evaluate the relationship between roxadustat use and suppression of thyroid function.
METHODS
We conducted a comprehensive search of MEDLINE via PubMed, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials databases using the search term "roxadustat" to identify all relevant studies. The study population comprised adults with renal anemia who participated in a randomized controlled trial or observational study, with roxadustat as the intervention and a placebo or erythropoiesis-stimulating agent (ESA) as the comparator. The primary outcome was suppression of thyroid function and the secondary outcome was hypothyroidism. A meta-analysis was conducted using the DerSimonian-Laird random effects model based on the size of the intention-to-treat population, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. Two reviewers independently screened the articles, extracted data, and assessed studies using the ROBINS-I tool.
RESULTS
Of the six studies eligible for inclusion, a meta-analysis was performed using data from two observational studies comparing roxadustat and ESA. The meta-analysis showed that the incidence of suppression of thyroid function was significantly higher with roxadustat use than with ESA use (OR: 6.45; 95% CI: 3.39-12.27; I = 12%). Compared with ESA, roxadustat seemed to potentially increase the risk for suppression of thyroid function in patients with renal anemia.
CONCLUSIONS
Our findings highlighted the importance of monitoring thyroid function in patients treated with roxadustat. The results of this review may enhance the safety of using roxadustat to treat renal anemia through advance recognition of the risk for suppression of thyroid function.
PubMed: 38851711
DOI: 10.1186/s40780-024-00351-z -
The Lancet. Psychiatry Jul 2024Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms has not been quantified. An estimate of antidepressant discontinuation symptoms incidence could inform patients and clinicians in the discontinuation of treatment, and provide useful information to researchers in antidepressant treatments. We aimed to assess the incidence of antidepressant discontinuation symptoms in patients discontinuing both antidepressants and placebo in the published literature.
METHODS
We systematically searched Medline, EMBASE, and CENTRAL from database inception until Oct 13, 2022 for randomised controlled trials (RCTs), other controlled trials, and observational studies assessing the incidence of antidepressant discontinuation symptoms. To be included, studies must have investigated cessation or tapering of an established antidepressant drug (excluding antipsychotics, lithium, or thyroxine) or placebo in participants with any mental, behavioural, or neurodevelopmental disorder. We excluded studies in neonates, and those using antidepressants for physical conditions such as pain syndromes due to organic disease. After study selection, summary data extraction, and risk of bias evaluation, data were pooled in random-effects meta-analyses. The main outcome was the incidence of antidepressant discontinuation symptoms after discontinuation of antidepressants or placebo. We also analysed the incidence of severe discontinuation symptoms. Sensitivity and meta-regression analyses tested a selection of methodological variables.
FINDINGS
From 6095 articles screened, 79 studies (44 RCTs and 35 observational studies) covering 21 002 patients were selected (72% female, 28% male, mean age 45 years [range 19·6-64·5]). Data on ethnicity were not consistently reported. 16 532 patients discontinued from an antidepressant, and 4470 patients discontinued from placebo. Incidence of at least one antidepressant discontinuation symptom was 0·31 (95% CI 0·27-0·35) in 62 study groups after discontinuation of antidepressants, and 0·17 (0·14-0·21) in 22 study groups after discontinuation of placebo. Between antidepressant and placebo groups of included RCTs, the summary difference in incidence was 0·08 [0·04-0·12]. The incidence of severe antidepressant discontinuation symptoms after discontinuation of an antidepressant was 0·028 (0·014-0·057) compared with 0·006 (0·002-0·013) after discontinuation of placebo. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms. Heterogeneity of results was substantial.
INTERPRETATION
Considering non-specific effects, as evidenced in placebo groups, the incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication. Subgroup analyses and heterogeneity figures point to factors not accounted for by diagnosis, medication, or trial-related characteristics, and might indicate subjective factors on the part of investigators, patients, or both. Residual or re-emerging psychopathology needs to be considered when interpreting the results, but our findings can inform clinicians and patients about the probable extent of antidepressant discontinuation symptoms without causing undue alarm.
FUNDING
None.
Topics: Humans; Antidepressive Agents; Incidence; Substance Withdrawal Syndrome; Randomized Controlled Trials as Topic
PubMed: 38851198
DOI: 10.1016/S2215-0366(24)00133-0 -
Medicine Jun 2024Traditionally, herbal medicines have been used to alleviate nausea and vomiting; however, a comprehensive clinical evaluation for postoperative nausea and vomiting... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Traditionally, herbal medicines have been used to alleviate nausea and vomiting; however, a comprehensive clinical evaluation for postoperative nausea and vomiting (PONV), especially after laparoscopic surgery, remains limited. This review aimed to evaluate the efficacy and safety of herbal medicine as an alternative therapy to prevent and manage nausea and vomiting after laparoscopic surgery compared with untreated, placebo, and Western medicine groups.
METHODS
We searched 11 databases, including EMBASE, PubMed, and the Cochrane Library, to collect randomized controlled trials (RCTs) of herbal medicines on PONV after laparoscopic surgery on July 7, 2022. Two independent reviewers screened and selected eligible studies, extracted clinical data, and evaluated the quality of evidence using the Cochrane risk-of-bias tool. The primary outcome was the incidence of PONV, whereas the secondary outcomes included the frequency and intensity of PONV, symptom improvement time, antiemetic requirement frequency, and incidence of adverse events. Review Manager Version 5.3. was used for the meta-analysis.
RESULTS
We identified 19 RCTs with 2726 participants comparing herbal medicine with no treatment, placebo, and Western medicine. The findings showed that compared with no treatment, herbal medicine demonstrated significant effects on vomiting incidence (risk ratio [RR] = 0.43, 95% confidence interval [CI] 0.32-0.57, P < .00001). Compared with placebo, herbal medicine revealed a significant effect on the severity of nausea 12 hours after laparoscopic surgery (standardized mean difference = -2.04, 95% CI -3.67 to -0.41, P = .01). Herbal medicines showed similar effects with Western medicine on the incidence of postoperative nausea (RR = 0.94, 95% CI 0.63-1.42, P = .77) and vomiting (RR = 0.68, 95% CI 0.25-1.84, P = .45). Furthermore, comparing the experimental group containing herbal medicine and control group excluding herbal medicine, adverse events were considerably lower in the group with herbal medicine (RR = 0.45, 95% CI 0.27-0.72, P = .001).
CONCLUSION
Herbal medicine is an effective and safe treatment for nausea and vomiting secondary to laparoscopic surgery. However, the number of studies was small and their quality was not high; thus, more well-designed RCTs are warranted in the future.
Topics: Humans; Postoperative Nausea and Vomiting; Laparoscopy; Randomized Controlled Trials as Topic; Antiemetics; Phytotherapy; Drugs, Chinese Herbal; Herbal Medicine
PubMed: 38847692
DOI: 10.1097/MD.0000000000038334 -
Frontiers in Cardiovascular Medicine 2024This systematic review and meta-analysis aimed to explore the effects of different sodium-glucose cotransporter-2 inhibitors (SGLT2i) on prognosis and cardiac structural...
BACKGROUND
This systematic review and meta-analysis aimed to explore the effects of different sodium-glucose cotransporter-2 inhibitors (SGLT2i) on prognosis and cardiac structural remodeling in patients with heart failure (HF).
METHODS
Relevant studies published up to 20 March 2024 were retrieved from PubMed, EMBASE, Web of Science, and Cochrane Library CNKI, China Biomedical Literature Service, VIP, and WanFang databases. We included randomized controlled trials of different SGLT2i and pooled the prognosis data of patients with HF. We compared the efficacy of different SGLT2i in patients with HF and conducted a sub-analysis based on left ventricular ejection fraction (LVEF).
RESULTS
We identified 77 randomized controlled trials involving 43,561 patients. The results showed that SGLT2i significantly enhanced outcomes in HF, including a composite of hospitalizations for HF and cardiovascular death, individual hospitalizations for HF, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, left atrial volume index (LAVi), and LVEF among all HF patients (< 0.05) compared to a placebo. Sotagliflozin was superior to empagliflozin [RR = 0.88, CI (0.79-0.97)] and dapagliflozin [RR = 0.86, CI (0.77-0.96)] in reducing hospitalizations for HF and CV death. Dapagliflozin significantly reduced hospitalizations [RR = 0.51, CI (0.33-0.80)], CV death [RR = 0.73, CI (0.54-0.97)], and all-cause mortality [RR = 0.69, CI (0.48-0.99)] in patients with HF with reduced ejection fraction (HFrEF). SGLT2i also plays a significant role in improving cardiac remodeling and quality of life (LVMi, LVEDV, KCQQ) (< 0.05). Among patients with HF with preserved ejection fraction (HFpEF), SGLT2i significantly improved cardiac function in HFpEF patients (< 0.05). In addition, canagliflozin [RR = 0.09, CI (0.01-0.86)] demonstrated greater safety compared to sotagliflozin in a composite of urinary and reproductive infections of HFpEF patients.
CONCLUSION
Our systematic review showed that SGLT2i generally enhances the prognosis of patients with HF. Sotagliflozin demonstrated superiority over empagliflozin and dapagliflozin in a composite of hospitalization for HF and CV death in the overall HF patients. Canagliflozin exhibited greater safety compared to sotagliflozin in a composite of urinary and reproductive infections of HFpEF. Overall, the efficacy of SGLT2i was greater in HFrEF patients than in HFpEF patients.
PubMed: 38845687
DOI: 10.3389/fcvm.2024.1379765