Heart Failure (HF) poses a significant clinical and economic burden globally. Due to its progressive and chronic nature, HF requires both continuous medical management and acute care related to hospitalization. This study aimed to estimate the economic burden of HF in the Philippines, covering both outpatient care and inpatient management.

The study utilized a bottom-up micro-costing approach to determine the economic burden of heart failure with mildly reduced ejection fraction (HFmrEF)/heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) across all NYHA classifications using a societal perspective. Price data were gathered from clinical experts, public and private hospitals, while quantity and probability assumptions were derived from published literature, subsequently validated through clinical expert consensus.

In 2022, an estimated 914,892 individuals were diagnosed with HF in the Philippines, based on a prevalence rate of 0.82%. This equates to a total economic burden of PHP 80.9B (USD 1.5B). Direct costs accounted for 90% of the total burden at PHP 72.8B (USD 1.3B). Hospital and medication expenses represented 61% of the total cost-of-illness, amounting to PHP 49.2B (USD 887.6 M).

HF management poses a significant burden-of-disease for Filipinos. The annual societal costs of HF management potentially expose Filipinos to catastrophic health spending and impoverishment, especially in a system where a substantial portion of healthcare expenses are paid out-of-pocket. These findings highlight the urgent need to prioritize preventive public health interventions and enhance financial risk protection for HF patients.

This cross-sectional analysis from the CZecking Heart Failure in patients with advanced Chronic Kidney Disease trial (ISRCTN18275480) examined pulmonary hypertension and right ventricular-pulmonary arterial coupling in patients on chronic hemodialysis. The aims of this analysis were: 1. To analyze relations between pulmonary hypertension and right ventricular-pulmonary arterial coupling with dialysis access flow and current hydration; 2. To analyze structural heart changes associated with right ventricular-pulmonary arterial uncoupling; 3. To reveal the prevalence, etiology and severity of pulmonary hypertension in the Czech hemodialysis population.

We performed expert echocardiography, vascular access flow measurements, bioimpedance analysis, and laboratory testing in 336 hemodialysis patients.

Pulmonary hypertension was present in 34% (114/336) patients and right ventricular-pulmonary arterial uncoupling was present in 25% of patients with pulmonary hypertension. Only weak associations between the flow of the dialysis arteriovenous access and estimated pulmonary arterial systolic pressure and right ventricular-pulmonary arterial coupling was proved. There was a strong association between hydration status assessed by estimated central venous pressure with pulmonary arterial systolic pressure (Rho 0.6, p < 0.0001) and right ventricular-pulmonary arterial coupling (Rho -0.52, p < 0.0001) and association between overhydration to extracellular water ratio with pulmonary arterial systolic pressure (Rho 0.31, p = 0.0001) and right ventricular-pulmonary arterial coupling (Rho -0.29, p = 0.002). The prevalence of heart failure was significantly higher in patients with right ventricular-pulmonary arterial uncoupling (88% vs. 52%, p = 0.0003).

These findings suggest that optimizing volume status and treating heart failure should be prioritized in hemodialysis patients to prevent pulmonary hypertension progression and right ventricular-pulmonary arterial uncoupling.

Aging is a primary driver of the escalating prevalence of heart failure (HF). Age-associated gut microbiota dysbiosis has been implicated in various age-related diseases, yet its role in age-related HF remains largely unexplored. In this study, we sought to explore the potential link between age-related gut microbiota alterations and HF in the elderly. We analyzed a publicly available single-cell sequencing dataset, which revealed markedly increased ferroptosis activity in cardiac myocytes of elderly individuals compared to their younger counterparts. Notably, treatment with the ferroptosis inhibitor, ferrostatin-1, mitigated cardiac ferroptosis and prevented cardiac dysfunction in aging rats. Furthermore, fecal microbiota transplantation from elderly HF patients significantly increased cardiac ferroptosis activity and induced cardiac dysfunction in healthy recipient rats. Integrated 16S rRNA sequencing and PCR quantification revealed a marked depletion of Faecalibacterium prausnitzii (F. prausnitzii) in elderly individuals, with a more pronounced decline in elderly patients with HF. Oral administration of F. prausnitzii or its metabolite butyrate effectively attenuated age-related HF through inhibiting ferroptosis. Additionally, gene-editing techniques were employed to generate F. prausnitzii BCoAT mutant deficient in butyrate production. Intriguingly, the protective effect was lost in the butyrate-deficient F. prausnitzii strain. Mechanistically, butyrate reduced intracellular iron accumulation and suppressed ferroptosis by downregulating LCN2 expression in senescent cardiomyocytes. Our findings highlight the critical role of aged microbiota-induced ferroptosis in HF and propose F. prausnitzii or butyrate may serve as potential targets for the prevention and treatment of age-related HF.

Objectives. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used to provide cardiorespiratory support in cardiogenic shock (CS), but selection of patients and timing of ECMO-start remain a challenge. This study aims to describe the 1 year outcome of VA-ECMO for CS with focus on etiology and severity of shock. Methods. VA-ECMO was used on 371 occasions between 2004 and 2019 at our center. Of these, 177 patients received VA-ECMO for CS and were included in this retrospective single-center study. Univariable and multivariable logistic regression models were used to determine predictors of all-cause mortality at 1 year. Results. Patients were grouped according to underlying etiology: non-ischemic heart failure (NIHF, N = 49), ischemic heart disease (IHD, N = 83) and miscellaneous diagnoses (Misc, N = 45). Markers of disease severity were lower for patients with NIHF. One year survival was 40% for all patients, 57%, 36% and 27% for the NIHF-, IHD and Misc-groups, respectively (p < .01). Univariable logistic regression analysis identified several variables associated with 1-year mortality, such as underlying etiology, pH and lactate, while biventricular failure was associated with a better prognosis. However, in the multivariable analysis, only ECPR remained significantly associated with increased mortality (OR 3.67, (CI 1.66-8.31), p < .01) Conclusions. In this retrospective study of VA-ECMO for CS, we found an acceptable one-year survival rate of 40%, with a more favorable outcome for NIHF-patients. The negative association of ECPR with a higher 1 year mortality suggests the importance of patient selection as well as timing of the VA-ECMO before deterioration to cardiac arrest.

Patients with atrial fibrillation (AF) are often treated with antiarrhythmic drugs (AADs) to maintain sinus rhythm and with heart rate-lowering drugs to achieve the optimal rate control. In this study, we investigated trends in the use of AADs and rate control drugs in Finnish patients with AF.

The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study is a nationwide study including all patients with AF in Finland from 2007 to 2018. The number of AAD purchases and the proportions of all prevalent AF patients in a certain year of interest were calculated. In total, 391030 AF patients were identified between 2007 and 2018, and 39,816 (10.2%) of them had purchased either class I or III AADs. The proportion of patients using classes I and III AADs decreased from 8.6% to 6.3%. Flecainide and amiodarone were the most often used AADs. The use of flecainide and amiodarone decreased from 4.9% to 3.9% and 1.9% to 1.5%, respectively. The proportion of patients on beta-blockers remained stable at 75%. Dronedarone became available in 2011 when it also was the most used (0.8% of patients), but the use decreased thereafter. The use of sotalol and digoxin decreased from 1.5% to 0.6% and 24.6% to 11.0% over the study period.

The number of AAD purchases increased alongside with the increasing prevalence of AF, whereas the proportion of AF patients on classes I and III AADs and digoxin decreased between 2007 and 2018. Flecainide remained the most used AAD followed by amiodarone.

Hyperkalemia (HK) is prevalent in patients with chronic kidney disease (CKD) and heart failure, particularly those on renin-angiotensin-aldosterone system inhibitors (RAASi). However, HK treatment often necessitates RAASi discontinuation. Sodium zirconium cyclosilicate (SZC), reimbursed in Italy since 2021, offers a new treatment option for HK. This study aimed to assess real-world SZC use and resulting economic rebounds in Italy.

Using administrative databases of healthcare entities covering about 6 million residents, patients with at least one prescription of SZC from Jan-2022 to Jun-2023 were identified. Patients receiving other potassium binders after SZC initiation were excluded. A logistic regression model estimated odds ratios (OR) with 95% confidence interval (95%CI) for predictors of long-term SZC use (>90 days), including age, sex, CKD status, and comorbidities. Univariate regression identified the potential association between each individual predictor and the likelihood of long-term treatment, followed by multivariate analysis adjusted for confounders. A backward stepwise logistic regression method retained only significant predictors, enhancing model accuracy.

The study identified 355 SZC-treated patients (mean age 70.4 years, 64.2% male). CKD was found in 69.3% (47.6% on dialysis), with common comorbidities including hypertension (57.5%), diabetes (43.4%), and heart failure (23.4%). RAASi use was observed in 68.7% before SZC initiation, and RAASi discontinuation was lower in long-term SZC users compared to short-term SZC users (41.2 vs. 56.6%, p = 0.048). Short-term SZC treatment (≤90 days) was more frequent (83.1%) and predicted by dialysis (OR = 0.22). Healthcare costs over 6 months averaged €7,943 for short-term users (dialysis: €3,452) and €6,647 for long-term users (dialysis: €1,130).

This real-world study showed that nearly 17% of patients continued SZC therapy for ≥90 days. Long-term therapy was associated with lower RAASi discontinuation and reduced healthcare costs due to hospitalizations and outpatient specialist services, suggesting that SZC can potentially provide clinical and economic benefits for HK management.

Alpha-ketoglutarate (AKG), is a major intermediate metabolite of the tricarboxylic acid cycle, and is closely associated with cardiometabolic disease prognosis. Previous studies indicated that AKG is related to myocardial energy expenditure levels and reflects adverse short-term outcomes in heart failure (HF) patients. In this prospective cohort study, we examined the long-term prognostic value of AKG levels in acute HF (AHF) patients.

Plasma AKG levels were assessed in patients hospitalized with AHF. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were calculated via multiple Cox regression. All-cause mortality was compared between patients with NT-proBNP < 1000 pg/ml and those with NT-proBNP ≥ 1000 pg/ml via subgroup analysis.

Patients with AKG ≥ 9.83 μg/ml had higher heart rates and NT-proBNP and lower left ventricular ejection fraction (LVEF) and systolic blood pressure (SBP). After multiple adjustment, higher AKG was associated with an increased all-cause mortality risk (HR = 1.078, p < 0.001). Compared with AKG < 9.83 μg/ml, AKG ≥ 9.83 μg/ml nearly doubled (HR = 1.929, p < 0.001) and quadrupled (HR = 4.160, p < 0.001) the all-cause mortality risk in patients with NT-proBNP ≥ 1000 pg/ml and those with NT-proBNP < 1000 pg/ml, respectively.

Plasma AKG was independently associated with greater all-cause mortality risk in patients with AHF. Higher AKG levels retained prognostic value for patients with relatively low NT-proBNP.

Empagliflozin confers cardioprotective benefits among patients with heart failure, across the range of ejection fraction (EF), regardless of type 2 diabetes status. The long-term cost-effectiveness of empagliflozin for the treatment of heart failure (HF) in the Philippines remains unclear. This study aims to determine the economic benefit of adding empagliflozin to the standard of care (SoC) vs the SoC alone for HF in the Philippines.

Using a Markov model, we predicted lifetime costs and clinical outcomes associated with treating HF in the Philippine setting. We used estimates of treatment efficacy, event probabilities, and derivations of utilities from the EMPEROR trials. Costs were derived from hospital tariffs and expert consensus. Separate analyses were performed for patients with left ventricular EF > 40%, categorized under mid-range ejection fraction or preserved ejection fraction (HFmrEF/HFpEF), and patients with left EF ≤ 40%, categorized under HF with reduced ejection fraction (HFrEF).

Our model predicted an average of 0.09 quality-adjusted life year (QALY) gains among HFmrEF/HFpEF patients and HFrEF patients when empagliflozin was compared to SoC. The addition of empagliflozin in the treatment results in a discounted incremental lifetime cost of PHP 62,692 (USD 1,129.99) and PHP 17,215 (USD 308.67) for HFmrEF/HFpEF and HFrEF, respectively. The incremental cost-effectiveness ratio (ICER) of empagliflozin is PHP 198,270 (USD 3,570.72)/QALY and PHP 742,604 (USD 13,385.08)/QALY for HFrEF and HFmrEF/HFpEF, respectively.

This study employed parameters derived from short-term clinical trial data, alongside metrics representative of Asian populations, which are not specific to the Philippine cohort.

Adding empagliflozin to the SoC in comparison to the SoC is associated with improved clinical outcomes and quality-of-life, at additional costs for both HFrEF and HFmrEF/HFpEF.

Heart failure (HF) is a leading cause of mortality among patients with cardiovascular disease and is often associated with myocardial apoptosis and endoplasmic reticulum stress (ERS). While hydrogen has demonstrated potential in reducing oxidative stress and ERS, recent evidence suggests that magnesium may aid in hydrogen release within the body, further enhancing these protective effects. This study aimed to investigate the cardioprotective effects of magnesium in reducing apoptosis and ERS through hydrogen release in a rat model of isoproterenol (ISO)-induced HF. Magnesium was administered orally to ISO-induced HF rats, which improved cardiac function, reduced myocardial fibrosis and cardiac hypertrophy, and lowered the plasma levels of creatine kinase-MB, cardiac troponin-I, and N-terminal B-type natriuretic peptide precursor in ISO-induced HF rats. It also inhibited cardiomyocyte apoptosis by upregulating B-cell lymphoma-2, downregulating Bcl-2-associated X protein, and suppressing ERS markers (glucose-related protein 78, activating transcription factor 4, and C/EBP-homologous protein). Magnesium also elevated hydrogen levels in blood, plasma, and cardiac tissue, as well as in artificial gastric juice and pure water, where hydrogen release lasted for at least four hours. Additionally, complementary in vitro experiments were conducted using H9C2 cardiomyocyte injury models, with hydrogen-rich culture medium as the intervention. Hydrogen-rich culture medium improved the survival and proliferation of ISO-treated H9C2 cells, reduced the cell surface area, inhibited apoptosis, and downregulated ERS pathway proteins. However, the protective effects of hydrogen were negated by tunicamycin (an inducer of ERS) in H9C2 cells. In conclusion, magnesium exerts significant cardioprotection by mitigating ERS and apoptosis through hydrogen release effects in ISO-induced HF.

There are limited data addressing the scoring systems for clinical outcome prediction in patients admitted to a contemporary cardiac intensive care unit (CICU). We aimed to compare the Acute Physiology and Chronic Health Evaluation (APACHE), Sequential Organ Failure Assessment (SOFA), Mayo CICU Admission Risk Score (MCARS), and Clinical Frailty Scale (CFS) scores, in predicting 90-day mortality in an unselected CICU population.

This is a single-center prospective, cohort study that included all patients admitted to the CICU of a tertiary care center during two consecutive years. The performances of the risk scores in predicting mortality were compared with respect to discriminative ability, calibration, accuracy and net reclassification improvement (NRI). Multivariate Cox regression analysis was also performed.

A total of 1449 consecutive patients were included. The median (IQR) age was 73 (62-82) years, 970 (67 %) were males. The CICU, hospital and 90-day mortality rates were 11 %, 14 % and 17 %, respectively. Compared to APACHE II and SOFA scores, MCARS demonstrated superior calibration (Hosmer-Lemeshow test P = 0.661), accuracy (Brier score = 0.069) and overall performance (area under curve [AUC] = 0.905), as well as the NRI (0.76). It was also independently associated with 90-day mortality after adjustment for several factors (HR = 1.578, 95 % CI: 1.478-1.683, P < 0.001). CFS was also independently associated with 90-day mortality (HR = 1.153, 95 % CI: 1.123-1.185, P < 0.001). However, its goodness-of-fit, overall performance and reclassification improvement were inferior to MCARS. Additionally, MCARS was a reliable predictor for CICU mortality (AUC = 0.935).

MCARS outperforms standard risk scores for prediction of 90-day mortality in patients admitted to a contemporary CICU.

Pulmonary arterial hypertension (PAH) patients require risk stratification for targeted drug therapy strategies. The risk stratification tool includes cardiac function classifications, hemodynamic, and echocardiographic indicators but lack measures of PAH impact on left ventricular diastolic function.

In this single-center observational study, left ventricular-pulmonary arterial (LV-PA) coupling was assessed using the ratios of hemodynamically measured LV transmural pressure/mean pulmonary artery pressure (LVTMP/mPAP) or echocardiographically measured LV end-diastolic diameter/PASPe (LVEDD/PASPe). The associations of the LV-PA coupling indicators with prognosis were evaluated by Cox regression and Kaplan-Meier analyses. Correlations with hemodynamic parameters were assessed using Spearman analyses.

A total of 179 patients met the study criteria, with 74 patients (41.3 %) experienced clinical worsening events, including 19 deaths (10.6 %). Cox regression analyses identified four predictors of clinical worsening events, LVTMP (P = 0.005), LVEDD (P = 0.010), LVTMP/mPAP (P = 0.003), and LVEDD/PASPe (P = 0. 001). Kaplan-Meier curves revealed significantly higher clinical worsening events rate when LVTMP/mPAP <0.04 at baseline or LVEDD/PASPe <0.51 mm/mmHg at baseline. Spearman correlation analyses revealed that LVTMP/mPAP (R = -0.38, P < 0.001), LVEDD/PASPe (R = -0.60, P < 0.001) were significantly correlated with pulmonary vascular resistance (PVR).

The LV-PA coupling indicators, LVTMP/mPAP and LVEDD/PASPe, are significant and independent predictors of prognosis in PAH patients and exhibit a direct correlation with the severity of PAH.

[ClinicalTrials.gov], identifier [NCT05417373], data[06/09/2022], retrospectively registered.

Education is essential for disease management in patients with Heart Failure (HF). Video education, based on adult learning and self-efficacy theories, may enhance outcomes by combining visual and auditory information. No study has comprehensively reviewed the impact of video education on mortality, HF) hospitalization, and Quality of Life (QOL) in patients with HF.

To evaluate the effectiveness of video education in improving the clinical outcomes of patients with HF.

This systematic review followed the 2020 PRISMA guidelines. We included randomized controlled trials that assessed the effectiveness of video education combined with usual care for patients with HF compared with those receiving usual care only. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, PEDro, and CINAHL until December 2023. We pooled data on mortality, HF hospitalization, and QOL as the primary outcomes.

The certainty of evidence was evaluated by the GRADE approach. We included 22 studies with a total of 6614 patients with HF. The evidence is very uncertain about the effect of video education, compared with usual care, on mortality (risk ratio 0.90, 95 % CI 0.70 to 1.15; I2 = 10 %; very low certainty evidence), HF hospitalization (risk ratio 1.10, 95 % CI 0.85 to 1.44; I2 = 14 %; very low certainty evidence), and QOL (standardized mean difference -0.35, 95 % CI -1.07 to 0.37; I2 = 89 %; very low certainty evidence).

Currently, video education may not take precedence over established interventions in the management of HF.

Intravascular lithotripsy (IVL) is increasingly utilized for the treatment of heavily calcified coronary lesions. However its use in conjunction with temporary mechanical circulatory support (tMCS) remains underexplored.

This study aims to evaluate the current use of tMCS and IVL for the treatment of heavily calcified coronary lesions.

From the BENELUX-IVL prospective registry, patients who underwent IVL during PCI and required tMCS during the procedure were selected. The primary technical endpoint was procedural success <30%, defined as a composite of device success (the ability to deliver the IVL catheter across the target lesion, and delivery of IVL pulses without angiographic complications) with residual stenosis <30%, final Thrombolysis In Myocardial Infarction grade 3 flow, and no in-hospital major adverse cardiovascular events (MACE). The primary clinical outcome was in-hospital MACE, including cardiac death, non-fatal myocardial infarction, or target lesion revascularization.

Between May 2019 and March 2024, a total of 454 patients were included, of whom 12 (2.6%) necessitated tMCS (for a total of 13 tMCS devices). Upon admission, the mean LV-EF was 39.5 ± 11.9%. The median Syntax score was 37 (25-49). A bail-out indication was the most common reason for tMCS initiation (58.3%), even if none was directly started due to IVL-related complications. Microaxial Flow Pump was the main utilized device (75%), followed by VA-ECMO (25%) and IABP (8.3%). One case required both VA-ECMO and Impella due to a coronary perforation complicated by cardiac tamponade. Procedural success < 30% was achieved in 91.6% of the cases. MACE occurred in one patient (8.3%).

In a large cohort of patients with complex heavily calcified coronary lesions requiring IVL, the need for tMCS was low (2.6%), with the main indication being bail-out.

Blood pool signals on T2 map can reflect intracardiac blood oxygenation. This study aimed to evaluate the T2 RV/LV blood pool ratio (T2 ratio) as a potential parameter for risk stratification in heart failure (HF) patients.

217 HF patients undergoing cardiac MRI were categorized into major adverse cardiovascular events (MACE) and No MACE groups. Regions of interest were delineated in the bi-ventricular blood pools on T2 maps to calculate T2 ratios. Clinical and imaging parameters were compared between groups, and independent predictors of MACE were identified using Cox regression analysis. Associations between T2 ratios and other parameters were explored. Survival analyses were conducted across low, moderate, and high-risk groups. Finally, predictive performance for MACE was compared among different models.

The T2 ratio was lower in MACE group (0.65 ± 0.12 vs 0.75 ± 0.12, P < 0.001) and was identified as an independent prognostic predictor of adverse outcomes in HF (HR: 0.966, P = 0.044). The association between T2 ratio and left ventricular ejection fraction (LVEF) followed distinct patterns in different ranges, with a transition around LVEF ≈ 50 %. Survival analysis demonstrated a stepwise decline in event-free survival from low- to high-risk groups (P < 0.05). Finally, the predictive model G incorporating myocardial T1 and T2 ratio demonstrated superior predictive efficacy (C-statistic: 0.806, IBS: 0.087).

A lower T2 ratio was associated with a higher risk of MACE in HF patients. This parameter may serve as a valuable tool for risk stratification in clinical practice.

MicroRNAs (miRNAs) play a pivotal role in various physiological and pathological processes. In particular, miRNA-21 holds significant potential as a novel biomarker for the diagnosis of heart failure. The development of miRNA detection methods is rapidly advancing, with point-of-care testing (POCT) platforms garnering considerable attention. However, traditional methods are often hampered by their reliance on expensive instruments and complex procedures, limiting clinical applicability. Therefore, there is an urgent need to develop a simple, portable, sensitive, and rapid POCT platform for miRNA-21 detection.

In this work, we proposed a portable POCT platform using a colorimetric biosensor specifically sensitive for miRNA-21. The platform utilized 3,3',5,5'-tetramethylbenzidine as the signaling molecule, and a Linear G-quadruplex loaded with Blocker Nanostructures (LGBN) generated by the RCA reaction as the probe. Furthermore, changes in primary color channels (R/G/B) of TMB for miRNA-21 detection were analyzed via smartphone-based digital image recognition. Under optimal conditions, the platform showed a linear detection range between 0.01 nM and 1 nM, with limits of detection of 8.3 pM (colorimetric methods) and 9.5 pM (digital image colorimetry). Moreover, the colorimetric biosensor exhibited excellent specificity and resistance to interference, successfully detecting miRNA-21 in serum samples from heart failure patients.

This detection method has an accuracy consistent with RT-qPCR results, providing a novel and practical approach with POCT for miRNA-21 detection.

N-terminal pro B-type natriuretic peptide (NT-proBNP) is a key biomarker for assessing cardiac function and hemodynamic stress. However, clinical guidelines lack clear recommendations on its utility in populations at risk of heart failure (HF), including those with hypertension, diabetes, or dyslipidemia. This study aimed to characterize the distribution of NT-proBNP levels in HF-prone individuals and establish population-specific screening thresholds.

A cross-sectional analysis was conducted across three cohorts: 2421 patients with HF risk factors (hypertension, diabetes, or dyslipidemia), 625 patients with congestive HF, and 833 healthy controls. NT-proBNP levels were stratified by cardiovascular risk categories based on established guidelines. Receiver operating characteristic (ROC) curves were used to determine optimal screening thresholds. Key findings included.

NT-proBNP levels effectively mirror cardiovascular risk stratification in HF-susceptible populations. Adopting risk-stratified reference values (106.0-116.7 pg/mL vs. 124.6 pg/mL in healthy adults) may enhance early HF detection and personalized risk management.

Heart failure (HF) is a major complication in patients with end-stage renal disease (ESRD) and is the leading cause of death in this high-risk population. Sacubitril/Valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) that has been shown to improve treatment outcomes in patients with ESRD accompanied by HF. Unfortunately, in clinical practice, some patients who received sacubitril/valsartan treatment not only did not show a good therapeutic effect, but also got worse with the passage of time. To explore potential biomarkers for predicting the clinical efficacy of sacubitril/valsartan, serum samples were prospectively collected upon admission and again collected after sacubitril/valsartan treatment was completed. Patients were divided into good response group (GR) and poor response group (PR). At the same time, samples before treatment were divided into GR group and PR group by sample tracing and matching, and metabolomics analysis was conducted. In the end, a total of 9 different metabolites were identified between patients in the early GR and PR groups. In order to find more effective biomarkers, two algorithms, random forest (RF) and support vector machine (SVM), were used for metabolite selection and performance evaluation, and three kinds of Lysophosphatidylcholine (LysoPC) metabolites showed good predictive effect, and the expression of the enzyme phospholipase A2 group IVA (PLA2G4A), associated with this metabolite was significantly elevated in the PR group. The disordered metabolism may reduce the sensitivity of patients to sacubitril/valsartan treatment, and PLA2G4A targeted inhibitors may be a promising therapeutic strategy to improve the sensitivity of patients with ESRD and HF to sacubitril/valsartan treatment.

Iron deficiency (ID) is frequent in chronic heart failure (HF). Among HF-ID patients those with impaired iron transport (IIT) (Transferrin saturation (TSAT) < 20 %) have the worst prognosis. In HF survival is strictly related to exercise limitation but the link between IIT, exercise limitation and survival is at present undefined.

We evaluated in 999 consecutive patients hospitalized for worsening HF whether IIT affects prognosis through cardiopulmonary exercise test (CPET), i.e. peak oxygen uptake (VO2) and ventilation vs. carbon dioxide (VE/VCO2) slope. In all patients at stabilization iron metabolism and maximal CPET were performed. Survival was assessed as all cause death, urgent LVAD and heart transplant were considered death equivalents. The causal relationship between survival and IIT, peakVO2 and VE/VCO2slope was assessed applying path analysis.

PeakVO2, VE/VCO2slope and TSAT were 68 ± 44 %pred, 35 ± 9 and 24.4 ± 12.9, respectively. PeakVO2 and, VE/VCO2slope were 61 ± 18 vs. 72 ± 53 %pred and 38 ± 10 vs. 33 ± 8, in IIT vs. non IIT patients (p < 0.0001 in both). At univariable and multivariable analysis a correlation between survival and VO2, VE/VCO2slope and TSAT was observed; at Kaplan-Myer lower peakVO2, higher VE/VCO2slope and lower TSAT showed worst survival; at path analysis IIT showed both an important effect on survival independent from peakVO2 and VE/VCO2slope (48 %) and an effect on survival independently mediated by VE/VCO2slope and peakVO2 (52 %), contributing to the IIT negative effect on survival.

The adverse impacts of low TSAT on prognosis are in part direct and in part mediated by mechanisms related to reduced peakVO2 and increased @VE/VCO2slope.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Despite extensive studies into the causes and therapies for CVDs, their incidence and prevalence continue to increase. Periodontitis is a multifactorial, chronic inflammatory disease related to systemic health. Current research suggests that periodontitis may be an unconventional risk factor for CVDs and it may increase the risk of CVDs such as atherosclerosis, coronary heart disease, myocardial infarction, hypertension, heart failure as well as cardiomyopathy. For all these reasons, it is quite plausible that prevention of periodontitis has an impact on the onset or progression of CVDs. Therefore, in this review, we investigated the association between periodontitis caused by oral microorganisms and different CVDs. In addition, we discuss the various mechanisms by which periodontitis contributes to the onset and progression of CVDs. Our review aims to raise global awareness of periodontitis, particularly its role in CVDs, provide a basis for the prevention and treatment of CVDs and offer potential therapeutic targets.

The high-sensitivity detection of low-concentration multicomponent biomarkers in the blood of heart failure (HF) patients using surface-enhanced Raman spectroscopy (SERS) remains a significant challenge. In this study, an ultrasensitive biosensor for the detection of multicomponent HF biomarkers was designed. This biosensor utilizes Au@Ag nanoparticles (Au@Ag NPs) functionalized with Raman reporter molecules (RaRs) as SERS probes, and Ag-coated Fe3O4 nanoparticles (Fe3O4-Ag NPs) modified with internal standard (IS) molecules as the capture substrate, offering the dual advantages of magnetic enrichment and SERS enhancement. Additionally, specific aptamers or antibodies were conjugated to the surfaces of Au@Ag NPs and Fe3O4-Ag NPs to specifically recognize target proteins to construct a three-layer composite structure (Fe3O4-Ag/HF biomarkers/Au@Ag). The limit of detection (LOD) of HF markers for cTnI, NT-proBNP, and sST2 is 0.1 pg/mL, 1.0 fg/mL, and 1.0 fg/mL, respectively, surpassing most reported methods. Additionally, the analysis of 45 clinical serum samples revealed no statistically significant differences between the SERS-based results and those obtained by conventional clinical methods, as confirmed by the Shapiro-Wilk test (p > 0.05). In conclusion, this SERS biosensor successfully developed an easy-to-operate accurate diagnosis method capable of simultaneous, quantitative detection of multiple HF biomarkers and provided a new technique for accurate diagnosis of other diseases in clinical testing.

Heart failure (HF) is associated with multi-organ dysfunction and significant morbidity and mortality. Despite advances in treatment, prognosis remains poor, highlighting the need to explore adjunctive therapies such as integrative medicine. This umbrella review synthesises top-tier evidence from systematic reviews and meta-analyses of randomised controlled trials (RCTs) assessing the safety and effectiveness of integrative medicine in patients with HF, in order to inform clinical decision-making.

We searched MEDLINE, Cochrane, PsycINFO and EMBASE until April 2024. Primary outcomes included mortality, hospitalisation rates, and severity or prognostic indicators, including brain natriuretic peptide (BNP) and exercise capacity. A hierarchical evidence synthesis method was used whereby we included the most recent, highly ranked and comprehensive reviews for our research question. We assessed review quality using 'A MeaSurement Tool to Assess systematic Reviews' and, where possible, evidence certainty for our primary outcomes using the Grading of Recommendations Assessment, Development and Evaluation approach.

Twenty-two reviews were included. Co-enzyme Q10 or Tai Chi may reduce mortality and hospitalisation rates (moderate certainty evidence), and acupuncture or intravenous Chinese herbal medicines may improve BNP (low to very low certainty evidence). The benefits of yoga and other nutrient supplements including L-carnitine remain unclear. Vitamin E may increase hospitalisation rates and should be avoided.

The evidence for most integrative medicine modalities for adjunctive management of HF remains limited. Well-designed and rigorous RCTs are needed, particularly with long-term follow up and evaluation of clinically meaningful outcomes.

This study investigates the therapeutic mechanisms of Qiliqiangxin (QLQX) capsules in treating Heart Failure with Preserved Ejection Fraction (HFpEF). The study aims to understand how QLQX impacts cardiac function and underlying molecular pathways.

HFpEF was induced in a rat model through unilateral nephrectomy, DOCA pellet implantation, and a high-salt diet. Cardiac function was assessed via M-mode imaging and Doppler flow measurements, focusing on key parameters like ejection fraction and diastolic function. A network pharmacology approach identified active QLQX components and potential targets, followed by comprehensive multi-omics analyses-including transcriptomics, proteomics, and metabolomics-to uncover the molecular mechanisms modulated by QLQX. Quantitative RT-PCR was employed to measure mRNA levels of key cardiac markers, providing further insights into QLQX's impact on cardiac remodeling.

QLQX treatment significantly improved cardiac function, with notable enhancements in ejection fraction and left ventricular diastolic function. Network pharmacology revealed 530 potential targets of QLQX, with 38 overlapping HFpEF targets. Key pathways identified include cGMP-PKG, adrenergic signaling, and calcium signaling. Transcriptomic analysis showed significant gene expression changes related to inflammation, energy metabolism, and myocardial remodeling, which were reversed by QLQX. Proteomic analysis identified 401 differentially expressed proteins, enriched in pathways such as cGMP-PKG and NF-κB signaling. Metabolomic profiling highlighted the role of lipid metabolism and adrenergic signaling in HFpEF, which were normalized by QLQX. In vivo validation confirmed the involvement of the cGMP-PKG pathway, with increased serum NO and cGMP levels, improved endothelial function, and reduced pro-fibrotic markers following QLQX treatment.

QLQX exerts multifaceted therapeutic effects on HFpEF by modulating gene expression, protein function, and metabolic pathways, particularly through the cGMP-PKG signaling pathway. These findings support QLQX as a promising therapeutic intervention for HFpEF, offering improvements in cardiac function and reversing pathological changes at multiple molecular levels.

Right ventricular dysfunction (RVD) predicts poor survival in chronic heart failure (HF). Sex differences in RVD have been suggested but are still unraveled. We studied the influence of sex in the prognostic impact of RVD in chronic HF. We retrospectively analyzed adult ambulatory chronic HF patients with left ventricular systolic dysfunction (LVSD) followed from January 2012 to December 2020. Patients with no data on right ventricular function were excluded. Primary outcome: all-cause mortality; follow-up: January 2023. A Cox-regression analysis was used to determine the prognostic impact of RVD, adjustment for confounders was performed. Interaction between sex and RVD was tested. The analysis was stratified according to sex. We studied 1,152 patients, 65% male, mean age 71 years. RVD coexisted in 192 (17%). Patients with RVD were younger, more often presented atrial fibrillation and nonischemic HF, they had more severe LVSD, were more symptomatic, and presented higher BNP levels. During a median 44-month follow-up, 618 (54%) patients died. Patients with RVD presented higher all-cause mortality: multivariate-adjusted HR = 1.86 (1.26 to 2.76). When the analysis was stratified according to sex this negative prognostic impact was only present in females: multivariate-adjusted HR = 1.56 (1.02 to 2.39). The present of RVD was not prognostic associated in men. There was interaction between sex and RVD, p = 0.03. In conclusion, RVD appears to be associated with ominous outcome only in female patients: women with systolic HF with RVD presented a 56% higher risk of dying. In male HF patients, RVD showed no prognostic implications. Sex seems to influence the prognostic impact of RDV in chronic HF.

The early identification of conditions that lead to increased myocardial wall thickness, such as transthyretin amyloid cardiomyopathy (ATTR-CM), severe aortic stenosis (AS), hypertrophic cardiomyopathy (HCM), and hypertensive heart disease (HHD), is challenging due to overlapping features. Delayed diagnosis can postpone appropriate treatment and worsen prognosis. This study aimed to evaluate the frequency of key electrocardiographic patterns in these conditions, with a specific emphasis on differentiating ATTR-CM from other causes of wall thickening.

Electrocardiograms (ECGs) from the medical records of 400 patients over 60 years old were analyzed, divided into four groups (ATTR-CM, HCM, HHD, and AS) with confirmed diagnoses and septal thickening (≥12 mm). Specific electrocardiographic patterns, including left ventricular hypertrophy, left atrial enlargement, low voltage, pseudoinfarction, and left ventricular pressure overload, were assessed. Multiple chi-square tests with Bonferroni adjustment were used to detect significant differences between groups.

The Sokolow-Lyon criteria was absent in all ATTR-CM cases, compared to 13 % in other conditions (p = 0.001). Additionally, ATTR-CM showed a higher prevalence of low voltage (45 % vs. 18.3 %, p = 0.001) and pseudoinfarction pattern (32 % vs. 22 %, p = 0.007), but a lower prevalence of left atrial enlargement (8 % vs. 30 %, p = 0.005). Absence of the Sokolow criteria was the best predictor of ATTR-CM (sensitivity 100 %, NPV 100 %, PPV 27 %), followed by the presence of low voltage and pseudoinfarction.

Significant differences were observed in the prevalence of electrocardiographic patterns between ATTR-CM and other wall thickening phenotypes. These findings may aid in the early detection and diagnosis of ATTR-CM, allowing for more timely intervention.

This study co-designed and feasibility tested a novel psychoeducational intervention delivered online to carers of patients with heart failure (HF) and examined the potential impact on carer-related outcomes.

The HEart faiLure carer support Programme (HELP) was co-designed with carers and healthcare professionals at a large University hospital. This intervention comprises an information booklet and six psychoeducational support group sessions delivered online by a multidisciplinary team. A convergent mixed-method design examined the feasibility, acceptability, and potential impact of HELP. Carers of patients with HF were recruited in the United Kingdom (UK) via clinical teams along with printed and online advertisements. Quantitative measurements included carer-related outcomes (carer burden, carer preparedness, quality of life, anxiety, depression, stress, and social support) and feasibility assessments (recruitment rates, attrition, and intervention usefulness). Focus groups conducted post-intervention qualitatively investigated the acceptability of HELP. Data was collected at baseline, 6 weeks post-intervention, and 3 months post-intervention. Quantitative and qualitative data were analyzed with descriptive and thematic analysis, respectively. The results were integrated to generate a holistic understanding of the findings.

51 carers were eligible and 22 (43 %) provided consent. Of those 22, 18 (89 %) participated and 12 (67 %) completed all intervention sessions. Participants highly rated the usefulness of the intervention via a feedback questionnaire (4.7 ± 0.59 out of 5, overall) and positive changes were found across the following carer-related outcomes: anxiety, depression, caregiver burden, stress, preparedness, and social support. Data integration generated three key findings: (1) Improved carer preparedness and knowledge, (2) Support from group environment, and (3) Emotional support and personal wellbeing.

HELP delivery to carers of patients with HF is feasible and potentially provides emotional support and empowerment in their caring role.

HELP will advance to implementation testing across the UK to inform large-scale adoption in routine clinical practice.

The competency-based Internal Medicine Milestones (IMM) assesses physician training outcomes through six key competencies. This pilot study introduced IMM concepts through an echocardiography report interpretation course for postgraduate students (PGYs) and residents (Rs). We aimed to help young physicians understand and track competency development as they receive cardiovascular training, with a view to expanding IMM usage for all junior physicians.

A single-center prospective study was conducted from August 2022 through December 2023. Pre- and post-course test scores and baseline IMM scores from 15 selected milestones were obtained. Follow-up IMM changes were tracked at the 3rd and 6th months after the course.

We analyzed scores of 193 junior physicians (mean age 26 ± 2 years; 68% male; 136 PGYs and 57 Rs) who attended the echocardiography report interpretation course. Of 193 participants, 77 completed the 3rd and 6th month IMM questionnaires. Compared with average pre-course scores, average post-course scores improved significantly (n = 193; 2.9 ± 1.3 vs 4.3 ± 1.3; P < 0.001) without differences between sexes or ranks (P ≥ 0.21). Post-course scores were not associated with baseline, 3rd-month, or 6th-month IMM scores (n = 77, P ≥ 0.42). IMM scores improved from baseline to 3rd month (5.8 ± 1.2 vs. 7.2 ± 1.3, P < 0.001), but plateaued from 3rd to 6th months (7.2 ± 1.3 vs. 7.2 ± 1.0, P = 0.78).

The significant post-course scores improvements indicate that the course was taught effectively and the test questions were well-formulated. Course participants showed improvements in IMM scores as they continued clinical training. Our results offer a reference for future curriculum design and competency development for junior physicians in internal medicine.

This is the phase 3 study in Japan designed to verify the superiority of patiromer over placebo using the change in serum potassium level (sK-level).

This study was a multicenter, randomized withdrawal study targeting Japanese hyperkalemic patients. It consisted of the run-in period and the double-blind period. The run-in period was an active single-arm, open-label period (4 or 5 weeks). The double-blind period was a randomized, placebo-controlled, parallel-group, double-blind period (4 weeks). Patients whose sK-level was within the normal range at week 4 or 5 of the run-in period entered the double-blind period. Patients who entered the double-blind period were randomly assigned to the patiromer group or the placebo group.

As a result of the primary analysis, the change of the sK-level (95% CI) from baseline to week 4 in the double-blind-period, was - 0.02 (- 0.19, 0.15) mmol/L in the patiromer group, and 0.78 (0.60, 0.96) mmol/L in the placebo group, with a statistically significant difference between the two treatment groups (p < 0.001). Similarly, statistically significant differences were also observed between the two groups at weeks 1, 2, and 3. Furthermore, the proportion of patients whose sK-level was maintained within the normal range were statistically significantly higher in the patiromer group than in the placebo group at all time points. No adverse events requiring particular attention were observed.

Patiromer can improve hyperkalemia by lowering sK-level and can suppress the recurrence of hyperkalemia with continued administration, and is safe and easy-to-use for a wide range of patients.

Patients with cancer undergoing chemotherapy with an anthracycline-based regimen are at increased risk of cardiotoxicity, predisposing to heart failure, arrhythmias and death. Whether carvedilol may confer benefit to prevent anthracycline-induced cardiotoxicity remains to be determined.

CARDIOTOX is a double-blind, placebo controlled randomized clinical trial that plan to enroll 1,018 patients across 25 study sites in Brazil. Patients with active cancer scheduled to undergo an anthracycline-based chemotherapy regimen are eligible. Patients with prior HF or cardiomyopathy are excluded. Patients are randomized in 1:1 ratio to carvedilol (starting dose 6.25mg BID up titrated to 25mg BID or maximum tolerated dose) or placebo, stratified by site and use of renin-angiotensin blockers at baseline. Study drug is administered through the duration of chemotherapy and up to 30 days after the last dose of anthracycline. Patients are scheduled to undergo echocardiographic evaluations at baseline and at 3, 6, and 12 months. The study primary endpoint is the composite of new left ventricle ejection fraction (LVEF) reduction by at least 10% leading to an LVEF <50%, cardiovascular death, myocardial infarction, urgent care visit or hospitalization for heart failure, or clinically significant arrhythmias at 12 months. Echocardiographic images will be analyzed by a central core lab, clinical outcomes will be adjudicated, and safety endpoints include serious adverse events and adverse events of special interest (symptomatic bradycardia, hypotension, syncope and bronchospasm).

The CARDIOTOX trial is the largest trial to date analyzing the potential role of beta-blockers as prophylactic therapy to prevent cardiotoxicity induced by anthracyclines.

Effects of Carvedilol on Cardiotoxicity in Cancer Patients Submitted to Anthracycline Therapy (CardioTox).

gov ID NCT04939883. https://clinicaltrials.gov/study/NCT04939883.

This study investigates the prognosis of acute decompensated heart failure (ADHF) on admission (i.e., primary ADHF) as compared to ADHF onset during course of hospitalization (i.e., secondary ADHF) in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF). Limited data regarding the prognostic impact of the timing of onset of ADHF is available. Consecutive patients with HFmrEF and ADHF were retrospectively included at one institution from 2016 to 2022. Patients with primary ADHF were compared to patients with secondary ADHF with regard to the primary endpoint all-cause mortality at 30 months. Kaplan-Meier, uni- and multivariable Cox proportional regression analyses were applied for statistics. From a total of 484 patients hospitalized with HFmrEF and ADHF, 67.98% (n = 329) were admitted with primary ADHF. Patients with secondary ADHF had higher rates of concomitant acute myocardial infarction, alongside with a higher extend of coronary artery disease. The risk of all-cause mortality at 30 months was not affected by the timing of ADHF (hazard ratio (HR) = 0.853; 95% confidence interval (CI) 0.653-1.115; p = 0.246). However, patients with primary ADHF were associated with a higher risk of HF-related rehospitalization at 30 months (HR = 2.513; 95% CI 1.555-4.065; p = 0.001), which was still evident after multivariable adjustment (HR = 2.347; 95% CI 1.418-3.883; p = 0.001). The timing of onset of ADHF was not associated with long-term mortality in HFmrEF, however primary ADHF was associated with a higher risk of HF-related rehospitalization.

We aimed to investigate the cardiovascular profile, including risk factors and cardiovascular abnormalities, in patients with idiopathic inflammatory myopathies (IIMs).

In this cross-sectional study, 109 IIM patients and 20 age- and gender-matched healthy controls were enrolled and underwent electrocardiographic and transthoracic echocardiographic examinations. We analysed blood levels of cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP), assessed IIM disease-specific features, and evaluated the medical history of cardiovascular risk factors. IIM patients were stratified into two groups: those with previous cardiac involvement and those without.

IIM patients had a higher body mass index (BMI) and a greater prevalence of diabetes mellitus and dyslipidaemia than healthy controls (p = 0.023, p = 0.024, and p = 0.042, respectively). They also showed significantly higher rates of arrhythmia, cardiac axis deviation, negative T-waves, and suspected pulmonary hypertension, along with elevated NT-proBNP levels (p = 0.041, p = 0.004, p = 0.041, p = 0.012, and p = 0.034, respectively). A significantly higher proportion (p = 0.037) of immune-mediated necrotizing myopathy (IMNM) subtype (50%) was found among IIM with previous cardiac involvement compared to those without (20%). cTnI levels were significantly higher in IIM with cardiac involvement than in IIM without cardiac involvement (p = 0.009).

Cardiovascular complications in patients with IIM may result from an increased prevalence of traditional cardiovascular risk factors, such as higher BMI, diabetes mellitus, and dyslipidaemia, and/or from direct cardiac involvement, such as previous myocarditis. Cardiac involvement in IIM is notably associated with the IMNM subtype.

Heart failure (HF) management lacks clarity regarding fluid balance strategies, with some studies suggesting potential benefits of liberal fluid intake. This review aims to evaluate both unrestricted and restricted fluid intake, including sodium restriction, in adult HF.

A thorough search of electronic databases, including PubMed, MEDLINE, and Cochrane Library, identified relevant studies examining fluid intake effects on adult heart failure patients, categorized by liberal or restricted intake, with subgroup analysis on sodium restriction. Pooled odds ratios (OR) and weighted mean differences (WMD) were calculated, employing trial sequential analysis (TSA) for reliability. Nine studies involving 961 patients were included, with follow-up durations ranging from 2 days to 6 months.

Daily fluid intake ranged from 0.8 to 1.5 L for the intervention group, and sodium intake varied from 2.0 to 5.0 g per day across five studies. No significant differences were observed in re-hospitalization rate, mortality rate, thirst, quality of life, doses of diuretics, or serum sodium levels between liberal and restricted intake groups. However, fluid-restricted patients exhibited increased serum creatinine levels, decreased serum B-type natriuretic peptide (BNP) levels and reduced body weight.

In summary, the existing studies on this topic are hindered by heterogeneity and relatively small sample sizes. However, when the available data is combined, it suggests that HF patients managed with either liberal or restrictive fluid intake exhibit similar clinical outcomes. It's worth noting that fluid restriction in HF patients might lead to increased serum creatinine levels, decreased BNP and body weight.

Early initiation of empagliflozin, a sodium-glucose cotransporter 2 inhibitor, in acute heart failure (AHF) patients increases urine output, reduces hospital stays, and enhances quality of life post-hospital discharge.

This trial aims to investigate the effectiveness and safety of early canagliflozin initiation compared to empagliflozin in hospitalized AHF patients with volume overload.

This was a multicenter, prospective, open-labeled, randomized equivalence trial. AHF diabetic and non-diabetic patients were randomized within 24 h from hospital admission to either receive 100 mg canagliflozin or 10 mg empagliflozin in addition to the standardized protocol for an intravenous loop diuretic. The primary outcome was the median of daily diuresis during the hospitalization period.

Hospitalized AHF patients were enrolled (71 patients per group). The median daily diuresis during the hospitalization period was 4200 ml in the canagliflozin group, which was statistically equivalent to empagliflozin (4117 ml) with a difference of 83 ml, which falls within the predefined equivalence margin (±10) % of the median of daily diuresis of empagliflozin; Δ = ±411.7 mL), confirming equivalence via bootstrap TSOT p < 0.001. No difference was observed in diuretic response, dyspnea score, orthodema congestion score or length of hospital stay. The NT-proBNP level at day 30 post-discharge and the change in KCCQ-TSS from baseline to day 90 were statistically comparable between both groups, without differences in safety event incidence.

Canagliflozin could be a part of usual care for hospitalized AHF patients and an alternative to empagliflozin without safety concerns.