In patients with heart failure with reduced ejection fraction (HFrEF), the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan has consistently demonstrated a beneficial therapeutic effect, vastly in non-Chagas trials. Less is known about the efficacy and safety of sacubitril-valsartan compared with standard of care in patients with Chagas cardiomyopathy, a common but often neglected etiology of nonischemic HFrEF. We aimed to perform a systematic review and meta-analysis to investigate whether sacubitril-valsartan is superior to enalapril in patients with heart failure (HF) due to Chagas cardiomyopathy. PubMed, Embase and Cochrane database were searched for randomized controlled trials (RCTs) that compared sacubitril-valsartan with enalapril in patients with HF due to Chagas cardiomyopathy. Efficacy outcomes were (1) cardiovascular (CV) death; (2) HF hospitalization; (3) relative change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline; and safety outcomes were (4) serious adverse events (SAEs); and (5) drug discontinuation due to adverse events (AEs). Cochrane's Review Manager Version 7.2.0 (RevMan, 2024) was used for all statistical analyses. Heterogeneity was examined with I² statistics. Hazard ratios (HR), risk ratios (RR), and mean differences (MD) with 95% confidence intervals (CIs) were pooled using an inverse-variance random-effects model. Three RCTs comprising 1,112 patients were included, of whom 463 (38%) were females. A total of 615 (50.02%) patients received sacubitril–valsartan, while 610 (49.8%) were treated with enalapril. The mean age was 63.67±10.6 years, and the mean left ventricular ejection fraction (LVEF) was 29.8%±7.2%. There was no statistically significant difference in CV death (HR 0.92; 95% CI 0.72 to 1.18; p=0.51; I²=0; Figure 1A) and HF hospitalization (HR 0.93; 95% CI 0.72 to 1.20; p=0.59; I²=0; Figure 1B) between sacubitril-valsartan and enalapril groups. However, there was a statistically significant reduction in NT-proBNP favoring enalapril over sacubitril-valsartan (MD 0.68; 95% CI 0.63 to 0.73; p<0.00001; I²=0; Figure 1C). No statistically significant difference in SAEs was found between the two treatment arms (RR 0.90; 95% CI 0.79 to 1.03; p=0.12; I²=0; Figure 2A), but there was a trend towards fewer drug discontinuations due to AEs with sacubitril–valsartan compared with enalapril (RR 0.51; 95% CI 0.26 to 1.01; p=0.05; I²=32% Figure 2B). In this meta-analysis of 1,112 patients with HF due to Chagas cardiomyopathy, sacubitril-valsartan did not statistically significantly reduce CV death or HF hospitalization, relative to enalapril. There was a significant difference between groups in terms of NT-proBNP reduction favoring enalapril. Moreover, sacubitril-valsartan was not superior to enalapril with respect to safety outcomes.Figure 1.Efficacy outcomes.For image description, please refer to the figure legend and surrounding text.Figure 2.Safety outcomes.For image description, please refer to the figure legend and surrounding text.

In the realm of preventive medicine, reinforcement of a zero-tolerance stance on cigarette smoking is imperative. The use of heat-not-burn (HnB) technology by individuals who are unable to quit smoking has prompted strong discussions in both the public health and clinical domains. This raises the question of whether exposure to cigarettes or HnB products has a different effect on blood pressure (BP) values and whether this effect depends on the concentration of heavy metals. A total of 33 participants were divided into four exposure groups: passive HnB exposure (n=7), active HnB users (n=4), passive cigarette smokers (n=11), and active cigarette smokers (n=9). Blood concentrations of cadmium (Cd) and lead (Pb) were determined by atomic absorption spectroscopy (AAS) using a Graphite Furnace Atomic Absorption Spectrometer, Agilent 240Z AA (Agilent Technologies, Santa Clara, CA, USA). Samples were prepared by wet digestion with nitric acid solution. After centrifugation, the supernatant was transferred into vials for AAS analysis. Concentrations of Cd and Pb were measured before and after exposure, and changes were analyzed using generalized linear models (GLM) adjusted for sex, age, and body mass index (BMI). All participants were smokers who had stopped smoking five days prior to the experiment. None of the participants had any chronic diseases. After a five-day abstinence (washout period), they were exposed to active and passive consumption of HnB or traditional cigarettes. BP was measured before and after exposure to tobacco smoke. Average Cd levels were similar across all groups (p = 0.55): passive HnB 1.59 µg/L, active HnB 1.29 µg/L, passive cigarette smokers 1.65 µg/L, and active cigarette smokers 1.64 µg/L. Pb levels varied significantly by exposure type (p = 0.006), as follows: 35.95 µg/L with passive HnB exposure, 26.98 µg/L with active HnB exposure, 52.45 µg/L and 36.50 µg/L in passive and active cigarette smokers, respectively. Upon monitoring, an elevation in Cd levels was significantly associated with a rise in systolic pressure (p = 0.026) and a decrease in diastolic pressure (p = 0.006), indicating an increase in pulse pressure and potential arterial stiffness. Pb concentration showed no direct effect on hemodynamic parameters. These findings suggest that Cd and Pb levels vary based on type of exposure. There was a significant difference between traditional cigarettes and HNB products, with the latter exhibiting lower concentrations, as well as between active and passive exposure. Changes in BP tend to be more closely linked to Cd, as higher levels correlate with increased systolic and decreased diastolic pressures, indicating its role in arterial stiffness and early vascular dysfunction.

Inclisiran effectively reduces low-density lipoprotein cholesterol (LDL-C) by suppressing proprotein convertase subtilisin/kexin type 9 (PSCK9) in patients on maximally tolerated statins with atherosclerotic cardiovascular disease (ASCVD) or risk equivalent. However, less is known about the efficacy of inclisiran as a monotherapy strategy for LDL-C reduction in patients with elevated levels but who are not on statins, ezetimibe, or any other lipid-lowering therapy (LLT). To investigate whether the lipid-lowering efficacy of inclisiran in LDL-C reduction indicates a significant pharmacodynamic effect regardless of baseline cardiovascular risk in patients with hypercholesterolemia without any LLT. We conducted a comprehensive search of PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing inclisiran sodium at dose of 300 mg (equivalent to 284 mg inclisiran) with placebo in adults with hypercholesterolemia who were not on statin, ezetimibe, nor any other LLT at baseline for evaluating the lipid-lowering efficacy of inclisiran as monotherapy. Outcomes of interest were (1) primary efficacy endpoint as percentage change in LDL-C from baseline, in patients without any background LLT and in those without statin use, and (2) percentage change in PCSK9 levels from baseline. R software version 4.3.1 was used for statistical analysis to estimate pooled effects of mean difference (MD) and 95% confidence intervals (CI) under e random-effects model. Heterogeneity was examined with I² statistics. We included five RCTs comprising 540 patients, of whom 311 (58%) were treated with inclisiran monotherapy, and the remaining 229 (42%) received placebo. Median follow-up ranged from 6 to 18 months (or 183 to 540 days). When compared with placebo, patients treated with inclisiran monotherapy who were not on any LLT had a significant decrease in percentage change in LDL-C from baseline (MD −46.24%; 95% CI −51.35 to −41.12; p<0.01; Figure 1A), with no significant difference when stratified by low risk versus high-risk population (test for subgroup difference p=0.33; Figure 1A). Similarly, inclisiran monotherapy lowered the LDL-C from baseline in patients without statin at baseline by about 53% more compared with placebo (MD −52.57%; 95% CI −62.34 to −42.80; p<0.01; Figure 1B). Moreover, the inclisiran group showed a significant 77% reduction in PCSK9 levels compared with the placebo group (MD −77.29%; 95% CI −84.31 to −70.27; p<0.01; Figure 2A). In this meta-analysis of RCTs evaluating patients with hypercholesterolemia without any background LLTs, inclisiran monotherapy significantly reduced percentage change in LDL-C from baseline, regardless of ASCVD risk. These findings were consistent in a sensitivity analysis only in patients without statin use at baseline, as well as in reduction of PSCK9 levels.Inclisiran Figure 1For image description, please refer to the figure legend and surrounding text.  Inclisiran Figure 2For image description, please refer to the figure legend and surrounding text.

Oral anticoagulation (OAC) and antiplatelet therapy (APT) represent a well-established preventative strategy against stroke, stent-related, and coronary ischemic events in patients with atrial fibrillation (AF) and coronary artery disease (CAD) following percutaneous coronary intervention (PCI). Less is known about the efficacy and safety of OAC as monotherapy compared with combined antithrombotic therapy in the subgroup of patients with drug-eluting stent (DES) implantation. To investigate whether deescalating from combination therapy of OAC with single APT to OAC monotherapy provides similar protection from major ischemic and bleeding endpoints in patients with AF and stable CAD following DES implantation. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) that compared OAC monotherapy (vitamin K antagonist or direct oral anticoagulant) with combination antithrombotic therapy of OAC plus single APT in patients with AF and CAD who underwent PCI with DES and reported the efficacy and safety composite outcomes of mortality, ischemia (myocardial infarction, stroke, or systemic embolism), and major bleeding or clinically relevant bleeding (CRNB). Cochrane's Review Manager Version 7.12.0 (RevMan, 2024) was used for statistical analysis to estimate pooled effects of hazard ratio (HR) with 95% confidence intervals (CI) under a random-effects model. Heterogeneity was examined with I² statistics. We included four RCTs comprising a total of 2570 patients, of whom 1302 (51%) were treated with OAC monotherapy, and the remaining 1268 (49%) were treated with combination therapy of OAC+APT. Median follow-up ranged from 12 to 30 months. There was no statistically significant difference in the efficacy endpoints of major ischemic composite (HR 0.94; 95% CI 0.65 to 1.36; p=0.75; Figure 1A) and the net clinical composite (HR 0.77; 95% CI 0.37 to 1.60; p=0.49; Figure 1B) between OAC monotherapy and OAC+APT combination therapy. However, there was a statistically significant reduction in the safety endpoint composite of major bleeding or CRNB with OAC monotherapy (HR 0.47; 95% CI 0.30 to 0.75; p=0.001; Figure 2A) compared with OAC+APT combination therapy, which was consistent in a sensitivity analysis of patients treated with predominantly new-generation DES (HR 0.38; 95% CI 0.25 to 0.59; p<0.0001; Figure 2B). Among patients with AF and prior PCI with DES implantation, OAC monotherapy statistically significantly reduced major bleeding or CRNB endpoint by 52% compared with combined antithrombotic therapy, but there was no significant difference between groups in terms of major ischemia or net clinical benefit.OAC Figure 1For image description, please refer to the figure legend and surrounding text.  OAC Figure 2For image description, please refer to the figure legend and surrounding text.

ObjectiveTo evaluate the predictive value of LA strain parameters and LASI for AF recurrence following electrical CV, and to compare them to conventional echocardiographic, biochemical, and clinical markers.MethodsIn this prospective, observational pilot study, 31 patients with persistent AF underwent electrical CV and were followed for six months. Echocardiographic evaluation included LA reservoir, conduit, and contractile strain, left atrial stiffness index, left atrial volume index (LAVI), left atrial appendage (LAA) morphology, left ventricular ejection fraction (LVEF), right atrial (RA) area, and right ventricular systolic pressure (RVSP). AF recurrence was assessed at three and six months.ResultsAt three months post-CV, LA reservoir, conduit, and contractile strain values were significantly negatively associated with AF recurrence (p < 0.001), while LASI and E/E' ratios were positively associated (p < 0.001). At six months, only contractile strain retained prognostic significance (p = 0.008). LVEF showed a positive correlation with recurrence at six months (p = 0.003), potentially reflecting the role of diastolic dysfunction.ConclusionLA strain parameters and LASI are valuable tools for predicting AF recurrence after CV, particularly in the early post-procedural period. Contractile strain may serve as a more reliable long-term predictor, emphasizing the importance of longitudinal atrial function assessment in rhythm outcome prediction. However, given the small sample size and single-center design, these results should be considered hypothesis-generating, requiring validation in larger studies.

INTRODUCTION AI-based ECG has shown good accuracy in diagnosing heart failure. However, due to the heterogeneity of studies regarding cutoff points, its precision for specifically detecting heart failure with left ventricle reduced ejection fraction (LVEF <40%) is not yet well established. What is the sensitivity and specificity of artificial-based electrocardiogram to diagnose heart failure with low ejection fraction (cut-off of 40%. AIMS We conducted a meta-analysis and systematic review to evaluate the accuracy of artificial intelligence electrocardiograms in estimating an ejection fraction below 40%. METHODS We searched PubMed, Embase, and Cochrane Library for studies evaluating the performance of AI ECGs in diagnosing heart failure with reduced ejection fraction. We computed true positives, true negatives, false positives, and false negatives events to estimate pooled sensitivity, specificity, and area under the curve, using R software version 4.3.1, under a random-effects model. RESULTS We identified 9 studies, including patients with a paired artificial intelligence-enabled electrocardiogram with an echocardiography. patients had an ejection fraction below 40% according to the echocardiogram. The AI-ECG data yielded areas under the receiver operator of, the sensitivity of), specificity of, and area under the curve of. The mean/median age ranged from 60±9 to 68.05± 11.9 years. CONCLUSIONS In this systematic review and meta-analysis, the use of electrocardiogram-based artificial intelligence models demonstrated high sensitivity and specificity to estimate a left ventricular ejection fraction below 40%.

Lung ultrasound (LUS) is a valuable, non-invasive tool for detecting pulmonary congestion in patients with acute heart failure (AHF), with a higher sensitivity relative to physical examination. However, the association between LUS-detected pulmonary congestion and cardiovascular outcomes in patients with ST-segment elevation (STEMI) is not well established. This systematic review and meta-analysis evaluated cardiovascular outcomes in patients with STEMI and congested (wet) or non-congested (dry) lungs by LUS. We searched PubMed, Embase, and Cochrane databases, and conference abstracts for clinical trials evaluating LUS-congestion (LUS+) versus non-LUS-congestion (LUS-) in patients with STEMI. Risk ratios (RRs) and hazard ratios (HR) with 95%CIs were pooled using R software under random-effects models. We also calculated LUS sensitivity, specificity, and area under the curves (AUCs) for the prediction of in-hospital mortality and cardiogenic shock. We included five studies with 1,454 patients. The mean age was 60 to 65 years; 1,066 (73.3%) were male, and 451 (31%) had congested lungs (LUS+). Patients with congestion on LUS had a significantly higher risk of the composite endpoint of death, heart failure, acute coronary syndrome, and cardiogenic shock (HR 4.00; 95%CI 2.12-7.54; p<0.01; Figure 1A). There was also a higher risk of in-hospital mortality (RR 5.09; 95%CI 2.25-11.49; p<0.001; Figure 1B) and cardiogenic shock (RR 5.01; 95%CI 2.47-10.17; p<0.001; Figure 1C) compared to patients with non-congested lungs. Reinfarction was similar between groups (p=0.08; Figure 1D). LUS had high diagnostic accuracy for in-hospital mortality (SROC-AUC: 0.82) and cardiogenic shock (SROC-AUC: 0.77); a high sensitivity (0.84; 95%CI 0.49-0.97; Figure 2A), and moderate specificity (0.78; 95%CI 0.67-0.87; Figure 2A) for in-hospital mortality; and moderate sensitivity (0.75; 95%CI 0.42-0.93; Figure 2B) and specificity (0.76; 95% CI 0.61-0.87; Figure 2B) for cardiogenic shock. Congested lungs on LUS are significantly associated with a higher risk of in-hospital mortality and cardiogenic shock in patients with STEMI. Moreover, LUS has a high AUC for identifying in-hospital mortality and cardiogenic shock in this patient population. Figure 1 Figure 2

Introduction: The efficacy and safety of use and impact of pulmonary artery catheter (PAC) in patients with cardiogenic shock (CS) treated with Impella remains unclear. The use of PAC in conjunction with Impella for patients with CS might be associated with improved clinical outcomes and increased safety compared to the use of Impella alone. We aimed to perform a systematic review and meta-analysis comparing Impella with versus without PAC for patients with CS. Methods: We systematically searched PubMed, Embase, and Cochrane databases for studies comparing PAC use in patients with CS treated with Impella. We pooled odds ratios (OR) with 95% confidence intervals (CI) applying random-effects model. We used R version 4.3.2 for statistical analyses. Results: We included two observational studies comprising 11,463 patients, of whom 6,058 (53%) had PAC. Compared with no PAC, the use of PAC was associated with a significantly lower in short-term mortality rates (37% vs. 42%; OR 0.83; 95% CI 0.77-0.90; p<0.01; Figure 1A). There was no significant difference in the incidence of arrhythmias 59% vs. 63%; OR 1.14; 95% CI 0.92-1.41 p=0.44; Figure 1B) or renal complications between groups (47% vs. 50%; OR 1.08; 95% CI 1.00-1.17; p=0.06; Figure 1C). Conclusions: In patients with CS, adjunctive PAC to Impella is associated with lower mortality rates, but no significant difference in arrhythmias and renal complications. Randomized controlled trials are warranted to further validate this results.

Background: Cyclophosphamide is an alkylating agent of the nitrogen mustard class that has become standard of care for graft-versus-host disease prophylaxis after hematopoietic stem cell transplantation. Although its cardiac toxicity in conditioning regimens is well-documented, data on cardiac events after administration of post-transplant cyclophosphamide (PT-Cy) administration remains limited. Research Question: Is PT-Cy associated with a higher incidence of cardiac adverse events compared with no PT-Cy? Aims: We aimed to perform a systematic review and meta-analysis of cardiac events from studies comparing PT-Cy versus no PT-Cy in patients with hematological disorders who received hematopoietic stem cell transplantation. Methods: We searched PubMed, Embase, and Cochrane Library for studies comparing PT-Cy versus no PT-Cy in patients with hematological conditions who received hematopoietic stem cell transplantation. We pooled risk ratios (RR) with 95% confidence intervals (CI). Statistical analyses were performed using Review Manager 5.4.1, under a random-effects model. Heterogeneity was assessed using I2 statistics. Results: We included four studies, all of which were retrospective, with 1,546 patients, of whom 826 (53%) received PT-Cy. Age ranged from 18 to 77 years, and 840 (54%) were male. A total of 1549 allogeneic transplants were performed, primarily for malignant hematological conditions. The conditioning regimens used were myeloablative (52%), reduced intensity (33%), non-myeloablative (8%), and sequential (7%). The most common cardiac events in patients receiving PT-Cy were heart failure (28%) and cardiomyopathy (27%), followed by arrhythmias (25%), pericarditis/pericardial effusion (14%) and acute coronary syndrome (5%). The incidence of adverse cardiac events was significantly higher in patients who received PT-Cy compared with those who did not receive PT-Cy (RR 2.05; 95% CI 1.36, 3.10; p<0.001; I 2 =44%). Conclusion: These findings suggest that PT-Cy is associated with a higher incidence of adverse cardiac events, the most common of which is heart failure/cardiomyopathy.