BACKGROUND: Dynamic arterial elastance (Eadyn) has been investigated for its ability to predict hypotension during the weaning of vasopressors. Our study focused on assessing Eadyn\'s performance in the context of critically ill adult patients admitted to the intensive care unit, regardless of diagnosis.
METHODS: Our study was conducted in accordance with the Preferred Reported Items for Systematic Reviews and Meta-Analysis checklist. The protocol was registered in PROSPERO (CRD42023421462) on May 26, 2023. We included prospective observational studies from the MEDLINE and Embase databases through May 2023. Five studies involving 183 patients were included in the quantitative analysis. We extracted data related to patient clinical characteristics, and information about Eadyn measurement methods, results, and norepinephrine dose. Most patients (76%) were diagnosed with septic shock, while the remaining patients required norepinephrine for other reasons. The average pressure responsiveness rate was 36.20%. The synthesized results yielded an area under the curve of 0.85, with a sensitivity of 0.87 (95% CI 0.74-0.93), specificity of 0.76 (95% CI 0.68-0.83), and diagnostic odds ratio of 19.07 (95% CI 8.47-42.92). Subgroup analyses indicated no variations in the Eadyn based on norepinephrine dosage, the Eadyn measurement device, or the Eadyn diagnostic cutoff to predict cessation of vasopressor support.
CONCLUSIONS: Eadyn, evaluated through subgroup analyses, demonstrated good predictive ability for the discontinuation of vasopressor support in critically ill patients.

Heart failure with preserved ejection fraction (HFpEF) is associated with high morbidity and mortality. Important risk factors for the development of HFpEF are similar to risk factors for the progression of tricuspid regurgitation (TR), and both conditions frequently coexist and thus is a distinct phenotype or a marker for advanced HF. Many patients with severe, symptomatic atrial secondary TR have been enrolled in current transcatheter device trials, and may represent patients at an advanced stage of HFpEF. Management of HFpEF thus may affect the pathophysiology of TR, and the physiologic changes that occur following transcatheter treatment of TR, may also impact symptoms and outcomes in patients with HFpEF. This review discusses these issues and suggests possible management strategies for these patients.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) commonly experience exercise intolerance, resulting in reduced cardiorespiratory fitness. This is characterised by a decreased maximal oxygen uptake (V̇O2peak), which is determined by the product of cardiac output (CO) and arteriovenous oxygen difference (a-vDO2). While exercise training has been shown to improve V̇O2peak in HFpEF patients, the effects on CO remain unclear. The aim of this study is to systematically review and analyse the current evidence on the effects of supervised exercise training on CO in patients with HFpEF.
METHODS: We will systematically search for literature describing the effects of supervised exercise training on CO in patients with HFpEF. All eligible studies published before 30 June 2023 in the following electronic databases will be included: MEDLINE (Ovid), Embase (Ovid), SPORTDiscus (EBSCOhost), and CENTRAL (Cochrane Library). Effect sizes will be extracted for CO before and after a supervised exercise training intervention at rest and maximal exercise. Mass of heterogeneity (I2) will be calculated, and either fixed-effect models or random-effect models will be used for meta-analysis. To detect a potential publication bias, funnel plot analyses will be performed.
CONCLUSIONS: While several studies have reported a positive effect of supervised exercise training on cardiorespiratory fitness, attempts to assess the underlying determinants of V̇O2peak, CO, and a-vDO2 are much scarcer, especially in patients with HFpEF. From a physiological perspective, measuring CO before and after supervised exercise training seems to be a reasonable way to accurately operationalise a potential improvement in cardiac function.
BACKGROUND: PROSPERO CRD42022361485.

BACKGROUND: Mesenchymal stem cells (MSCs) have emerged as living biodrugs for myocardial repair and regeneration. Recent randomized controlled trials (RCTs) have reported that MSC-based therapy is safe and effective in heart failure patients; however, its dose-response relationship has yet to be established. We aimed to determine the optimal MSC dose for treating HF patients with reduced ejection fraction (EF) (HFrEF).
METHODS: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Cochrane Handbook guidelines were followed. Four databases and registries, i.e., PubMed, EBSCO, clinicaltrials.gov, ICTRP, and other websites, were searched for RCTs. Eleven RCTs with 1098 participants (treatment group, n = 606; control group, n = 492) were selected based on our inclusion/exclusion criteria. Two independent assessors extracted the data and performed quality assessments. The data from all eligible studies were plotted for death, major adverse cardiac events (MACE), left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and 6-minute walk distance (6-MWD) as safety, efficacy, and performance parameters. For dose-escalation assessment, studies were categorized as low-dose (< 100 million cells) or high-dose (≥ 100 million cells).
RESULTS: MSC-based treatment is safe across low and high doses, with nonsignificant effects. However, low-dose treatment had a more significant protective effect than high-dose treatment. Subgroup analysis revealed the superiority of low-dose treatment in improving LVEF by 3.01% (95% CI; 0.65-5.38%) compared with high-dose treatment (-0.48%; 95% CI; -2.14-1.18). MSC treatment significantly improved the 6-MWD by 26.74 m (95% CI; 3.74-49.74 m) in the low-dose treatment group and by 36.73 m (95% CI; 6.74-66.72 m) in the high-dose treatment group. The exclusion of studies using ADRCs resulted in better safety and a significant improvement in LVEF from low- and high-dose MSC treatment.
CONCLUSIONS: Low-dose MSC treatment was safe and superior to high-dose treatment in restoring efficacy and functional outcomes in heart failure patients, and further analysis in a larger patient group is warranted.

BACKGROUND: The treatment of choice for Extra-osseous Ewing\'s sarcoma/primitive neuroectodermal tumor (ES/PNET), a rare neoplasm, is the VAC/IE regimen. This regimen includes Doxorubicin, Vincristine, Cyclophosphamide, Ifosfamide, and Etoposide, all of which have cardiotoxic effects. Myocarditis, a potentially threatening side effect following cancer therapy, can be accurately managed and diagnosed.
METHODS: In the current study, we report the case of a 19-year-old female with a mass on the abdominal wall, diagnosed with ES/PNET. She was treated with the VAC/IE regimen. A month after the last session of chemotherapy, she experienced dyspnea. Upon evaluation, a high level of troponin and a low left ventricular ejection fraction (LVEF) were detected via transthoracic echocardiography. She was treated with anti-heart failure drugs, but the response was unsatisfactory. The possibility of Cancer therapy-related myocarditis was suspected, and cardiac magnetic resonance imaging (CMR) confirmed acute myocarditis. This patient exhibited a significant response to intravenous immunoglobulin (IVIG), with her LVEF improving from 30-35% to 50% within three months.
CONCLUSIONS: In this case, based on negative tests and the absence of viral signs and symptoms, Cancer therapy-related myocarditis is highly suspected as the cause of myocarditis. This case underscores the importance of accurately utilizing CMR as a non-invasive method for diagnosing myocarditis. It effectively highlights the identification of reversible myocarditis with appropriate treatment and the notable response to IVIG, suggesting its potential as a favorable treatment for myocarditis in younger patients.

BACKGROUND: Chronic disease self-management (CDSM) is a vital component of congestive heart failure (CHF) programmes. Recent CHF guidelines have downgraded CDSM programmes citing a lack of gold-standard evidence. This protocol describes the aims and methods of a systematic review to collate and synthesise the published research evidence to determine the effectiveness of CDSM programmes and interventions for patients treated for CHF.
METHODS: Medline, PubMed, Embase, CENTRAL, CINAHL, Cochrane Central Register of Controlled Trials, PsycINFO, SCOPUS, Web of Science, the Science Citation Index and registers of clinical trials will be searched from 1966 to 2024. In addition, the reference lists of shortlisted articles will be reviewed. Randomised controlled trials, with case management interventions of CDSM and CHF with reported major adverse cardiovascular events (MACEs), will be extracted and analysed. There is no restriction on language. Study protocol template developed from Cochrane Collaboration and Reporting adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines for systematic review and meta-analyses 2020. Two independent authors will apply inclusions and exclusion criteria to limit article search and assess bias and certainty of evidence rating. Data extraction and study description of included studies will include quality appraisal of studies and quantitative synthesis of data will then be undertaken to ascertain evidence for the study aims. Subgroup analyses will be conducted for different CDSM programmes. The primary outcome will be a significant change in MACE parameters between intervention and control arms. Meta-analysis will be conducted using statistical software, if feasible.
BACKGROUND: Ethics approval is not sought as the study is not collecting primary patient data. The results of this study will be disseminated through peer-reviewed scientific journals and also presented to audiences through meetings and scientific conferences.
UNASSIGNED: CRD42023431539.

Heart failure (HF) is a prevalent clinical syndrome characterized by significant morbidity and is often precipitated by impaired left ventricular myocardial function. The condition can be categorized into two primary forms based on the ejection fraction (EF): Heart failure with preserved ejection fraction (HFpEF) and Heart failure with reduced ejection fraction (HFrEF). Evidence-based treatments for HF have been instrumental in reducing morbidity and mortality, particularly in patients with HFrEF. Mineralocorticoid receptor antagonists (MRAs) represent a cornerstone in the pharmacological management of HF, with a strong indication for use in HFrEF. Notably, pharmacological nuances exist among MRAs, which may influence therapeutic decision-making for individual patients. Moreover, MRAs have been shown to enhance heart rate variability and improve cardiac sympathetic nervous system function in HF patients. Spironolactone, an MRA, has been a pivotal agent in the clinical management of HFrEF since its introduction. However, its use has been tempered by certain side effects, including gynecomastia and hyperkalemia, leading to considerable discontinuation rates among patients. To address these challenges, numerous randomized clinical trials (RCTs) have been conducted to assess the efficacy and safety profiles of alternative steroidal and non-steroidal MRAs. Eplerenone, a steroidal MRA introduced subsequent to spironolactone, has demonstrated efficacy with a more favorable side effect profile.

BACKGROUND: Hypertension (HTN) is a co-morbidity that is commonly associated with heart failure with preserved ejection fraction (HFpEF). However, it remains unclear whether treatment of hypertension in HFpEF patients is associated with improved cardiovascular outcomes.
OBJECTIVE: The purpose of this meta-analysis is to evaluate the association of anti-hypertensive medical therapy with cardiovascular outcomes in patients with HFpEF.
METHODS: We performed a database search for studies reporting on the association of anti-hypertensive medications with cardiovascular outcomes and safety endpoints in patients with HFpEF. The databases searched include OVID Medline, Web of Science, and Embase. The primary endpoint was all-cause mortality. Secondary endpoints include cardiovascular (CV) mortality, worsening heart failure (HF), CV hospitalization, composite major adverse cardiovascular events (MACE), hyperkalemia, worsening renal function, and hypotension.
RESULTS: A total of 12 studies with 14062 HFpEF participants (7010 treated with medical therapy versus 7052 treated with placebo) met inclusion criteria. Use of anti-hypertensive medications was not associated with lower all-cause mortality, CV mortality or CV hospitalization compared to treatment with placebo (OR 1.02, 95% CI 0.77-1.35; p = 0.9, OR 0.88, 95% CI 0.73-1.06; p = 0.19, OR 0.99, 95% CI 0.87-1.12; p = 0.83, OR 0.90, 95% CI 0.79-1.03; p = 0.11). Anti-hypertensive medications were not associated with lower risk of subsequent acute myocardial infarction (AMI) (OR 0.53, 95% CI 0.07-3.73; p = 0.5). Use of anti-hypertensive medications was associated with a statistically significant lower risk of MACE (OR 0.90, 95% CI 0.83-0.98; p = 0.02).
CONCLUSIONS: While treatment with anti-hypertensive medications was not associated with lower risk of all-cause mortality, their use may be associated with reduce risk of adverse cardiovascular outcomes in patients with HFpEF regardless of whether they have HTN. Additional high quality studies are required to clarify this association and determine the effect based on specific classes of medications.

BACKGROUND: Despite maximal treatment, heart failure (HF) remains a major clinical challenge. Besides neurohormonal overactivation, myocardial energy homoeostasis is also impaired in HF. Trimetazidine has the potential to restore myocardial energy status by inhibiting fatty acid oxidation, concomitantly enhancing glucose oxidation. Trimetazidine is an interesting adjunct treatment, for it is safe, easy to use and comes at a low cost.
OBJECTIVE: We conducted a systematic review to evaluate all available clinical evidence on trimetazidine in HF. We searched Medline/PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov to identify relevant studies.
METHODS: Out of 213 records, we included 28 studies in the meta-analysis (containing 2552 unique patients), which almost exclusively randomised patients with HF with reduced ejection fraction (HFrEF). The studies were relatively small (median study size: N=58) and of short duration (mean follow-up: 6 months), with the majority (68%) being open label.
RESULTS: Trimetazidine in HFrEF was found to significantly reduce cardiovascular mortality (OR 0.33, 95% CI 0.21 to 0.53) and HF hospitalisations (OR 0.42, 95% CI 0.29 to 0.60). In addition, trimetazidine improved (New York Heart Association) functional class (mean difference: -0.44 (95% CI -0.49 to -0.39), 6 min walk distance (mean difference: +109 m (95% CI 105 to 114 m) and quality of life (standardised mean difference: +0.52 (95% CI 0.32 to 0.71). A similar pattern of effects was observed for both ischaemic and non-ischaemic cardiomyopathy.
CONCLUSIONS: Current evidence supports the potential role of trimetazidine in HFrEF, but this is based on multiple smaller trials of varying quality in study design. We recommend a large pragmatic randomised clinical trial to establish the definitive role of trimetazidine in the management of HFrEF.

BACKGROUND: Ultramarathon running poses physiological challenges, impacting cardiac function. This systematic review and meta-analysis explore the acute effects of single-stage ultramarathon running on cardiac function.
METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations were followed. Searches covered Medline, Embase, CINAHL, SPORTDiscus, Web of Science, Central Cochrane, and Scopus. Random effects meta-analyses assessed left ventricular (LV) and right ventricular (RV) variables, expressed as mean differences (MD) with 95% confidence intervals (CI).
RESULTS: Among 6972 studies, 17 were included. Post-ultramarathon reductions were found in LV end-diastolic diameter (LVEDD) (-1.24; 95% CI = -1.77, -0.71 mm), LV end-diastolic volume (LVEDV) (-9.92; 95% CI = -15.25, -4.60 ml), LV stroke volume (LVSV) (-8.96 ml, 95% CI -13.20, -4.72 ml), LV ejection fraction (LVEF) (-3.71; 95% CI = -5.21, -2.22%), LV global longitudinal strain (LVGLS) (-1.48; 95% CI = -2.21, -0.76%), E/A (-0.30; 95% CI = -0.38, -0.22 cm/s), .E\' (-1.35 cm/s, 95% CI -1.91, -0.79 cm/s), RV fractional area change (RVFAC) (-3.34, 95% CI = -5.84, -0.84%), tricuspid annular plane systolic excursion (TAPSE) (-0.12, 95% CI = -0.22, -0.02 cm), RV global longitudinal strain (RVGLS) (-1.73, 95% CI = -2.87, -0.59%), with increases in RV end-diastolic area (RVEDA) (1.89, 95% CI = 0.63, 3.14 cm2), RV Peak A\' (1.32 cm/s, 95% CI 0.20, 2.44), and heart rate (18.24, 95% CI = 15.16, 21.32). No significant differences were observed in LV end-systolic diameter (LVESD), LV end-systolic volume (LVESV), RV end-diastolic diameter (RVEDD), RV Peak E\', and RV Peak S\'.
CONCLUSIONS: Evidence suggests immediate impairment of systolic and diastolic cardiac function post-ultramarathon running.