Novel prognostic impact and cell specific role of endocan in patients with coronary artery disease.

BACKGROUND: Both the clinical and mechanistic impacts of endocan were not well elucidated especially in coronary artery disease (CAD). OBJECTIVE: This study aimed to investigate the prognostic and potential pathological role of endocan for cardiovascular (CV) events in stable CAD patients. METHODS: A total of 1,071 stable CAD patients with previous percutaneous coronary intervention (PCI) were enrolled prospectively in a nationwide Biosignature study. Another cohort of 76 CAD patients with or without PCI were enrolled for validation. Baseline biomarkers including endocan level was measured and total CV events especially hard CV events (including CV mortality, non-fatal myocardial infection and stroke) during follow-up were identified. Circulating endothelial progenitor cells (EPCs) as an in vivo biological contributor to vascular repairment from CAD patients were used for the in vitro functional study. RESULTS: After 24 months, there were 42 patients (3.92%) with hard CV events and 207 (19.3%) with total CV events in the study group. The incidence of both events was increased with the tertiles of baseline endocan level (hard events: 1.7%,3.4%, and 6.7% in 1st,2nd, and 3rd tertile respectively, p = 0.002; total events: 13.8%vs.16.2%vs.28.0%, p < 0.0001). Multivariate regression analysis revealed the independent association of endocan level with total and hard CV events. These findings were validated in another cohort with a 5-year follow-up. Furthermore, in vitro inhibition of endocan improved cell migration and tube formation capacities, and reduced cell adhesiveness of EPCs from CAD patients. CONCLUSIONS: Endocan might be a novel prognostic indicator, mechanistic mediator, and potential therapeutic target for clinical CAD.

Extracorporeal cardiopulmonary resuscitation for patients with refractory out-of-hospital cardiac arrest: a propensity score matching, observational study.

Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly performed as an adjunct to conventional cardiopulmonary resuscitation (CCPR) for refractory out-of-hospital cardiac arrest (OHCA). However, the specific benefits of ECPR concerning survival with favorable neurological outcomes remain uncertain. This study aimed to investigate the potential advantages of ECPR in the management of refractory OHCA. We conducted a retrospective cohort study involved OHCA patients between January 2016 and May 2021. Patients were categorized into ECPR or CCPR groups. The primary endpoint assessed was survival with favorable neurological outcomes, and the secondary outcome was survival rate. Multivariate logistic regression analyses, with and without 1:2 propensity score matching, were employed to assess ECPR's effect. In total, 1193 patients were included: 85underwent ECPR, and 1108 received CCPR. Compared to the CCPR group, the ECPR group exhibited notably higher survival rate (29.4% vs. 2.4%; p < 0.001). The ECPR group also exhibited a higher proportion of survival with favorable neurological outcome than CCPR group (17.6% vs. 0.7%; p < 0.001). Multivariate logistic regression analysis demonstrated that ECPR correlated with increased odds of survival with favorable neurological outcome (adjusted odds ratio: 13.57; 95% confidence interval (CI) 4.60-40.06). Following propensity score matching, the ECPR group showed significantly elevated odds of survival with favorable neurological outcomes (adjusted odds ratio: 13.31; 95% CI 1.61-109.9). This study demonstrated that in comparison to CCPR, ECPR may provide survival benefit and increase the odds of favorable neurological outcomes in selected OHCA patients.

Role of low-density lipoprotein electronegativity and sexual dimorphism in contributing early ventricular tachyarrhythmias following ST-elevation myocardial infarction.

Background: Early ventricular tachycardia/fibrillation (VT/VF) in patients with ST-elevation myocardial infarction (STEMI) has higher morbidity and mortality. This study examines gender-differentiated risk factors and underlying mechanisms for early onset VT/VF in STEMI. Methods: We analyzed data from 2,964 consecutive STEMI patients between January 1, 2008 and December 31, 2021. Early VT/VF was defined as occurrence of spontaneous VT/VF of ≥30 s or requirement of immediate cardioversion/defibrillation within the first 48 h after symptoms. An ex vivo ischemic-reperfusion experiments were conducted in 8-week-old ApoE-/- mice fed a high-fat diet to explore the underlying mechanisms of early VT/VF. Results: In 255 of out 2,964 STEMI patients who experienced early VT/VF, the age was younger (58.6 ± 13.8 vs. 61.0 ± 13.0 years old, P = 0.008) with a male predominance. The plasma levels of L5, the most electronegative subclass of low-density lipoprotein, was higher in early VT/VF patients compared to those without early VT/VF (n = 21, L5: 14.1 ± 22.6% vs. n = 46, L5: 4.3 ± 9.9%, P = 0.016). In the experimental setup, all male mice (n = 4) developed VT/VF post sham operation, whereas no such incidence was observed in the female mice (n = 3). Significantly, male mice exhibited considerably slower cardiac conduction velocity as compared to their female counterparts in whole heart preparations (25.01 ± 0.93 cm/s vs.42.32 ± 5.70 cm/s, P < 0.001), despite analogous action potential durations. Furthermore, isolated ventricular myocytes from male mice showed a distinctly lower sodium current density (-29.20 ± 3.04 pA/pF, n = 6) in comparison to female mice (-114.05 ± 6.41 pA/pF, n = 6, P < 0.001). This decreased sodium current density was paralleled by a reduced membrane expression of Nav1.5 protein (0.38 ± 0.06 vs. 0.89 ± 0.09 A.U., P < 0.001) and increased cytosolic Nav1.5 levels (0.59 ± 0.06 vs. 0.29 ± 0.04 A.U., P = 0.001) in male mice. Furthermore, it was observed that the overall expressions of sorting nexin 27 (SNX27) and vacuolar protein sorting 26 (VPS26) were significantly diminished in male mice as compared to female littermates (0.91 ± 0.15 vs. 1.70 ± 0.28, P = 0.02 and 0.74 ± 0.09 vs. 1.57 ± 0.13, P < 0.01, respectively). Conclusions: Our findings reveal that male STEMI patients with early VT/VF are associated with elevated L5 levels. The gender-based discrepancy in early VT/VF predisposition might be due to compromised sodium channel trafficking, possibly linked with increased LDL electronegativity.

Fatty acid-binding protein-3 and renal function decline in patients with chronic coronary syndrome.

BACKGROUND: Renal dysfunction is common in patients with coronary artery disease. Due to the shared vascular pathogenesis between the two conditions, novel biomarkers such as the fatty acid-binding protein-3 (FABP-3) have been proposed for diagnosis and prognosis prediction. This multicentre prospective cohort study investigates the association between FABP-3 and renal dysfunction. HYPOTHESIS: We hypothesized that higher FABP-3 levels are correlated to worse renal outcome. METHODS: Patients with chronic coronary syndrome were classified into three groups based on the initial serum FABP-3 levels. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to estimate the patient's renal function. Renal events were defined as >25% and >50% decline in estimated glomerular filtration rate (eGFR). Cox multivariable regression was employed to delineate the correlation between FABP-3 and renal dysfunction. RESULTS: A total of 1606 subjects were included. During a mean follow-up of 35.9 months, there were 239 patients with eGFR >25% reduction and 60 patients with >50% reduction. In the Kaplan-Meier survival curve and log-rank test, increased levels of FABP-3 were significantly correlated with eGFR >25% reduction (p < .001) and >50% reduction (p < .001). Multivariate Cox regression model revealed that subjects with higher FABP-3 exhibited a greater risk of eGFR >25% reduction (Group 2: hazard ratio [HR] = 2.328, 95% confidence interval [CI] = 1.521-3.562, p < .001; Group 3: HR = 3.054, 95% CI = 1.952-4.776, p < .001) and >50% reduction (Group 3: HR = 4.838, 95% CI = 1.722-13.591, p = .003). CONCLUSIONS: Serum FABP-3 may serve as a novel biomarker to predict eGFR decline in patients with chronic coronary syndrome.

Inflammation and renal function decline in chronic coronary syndrome: a prospective multicenter cohort study.

BACKGROUND: Renal function decline is a frequently encountered complication in patients with chronic coronary syndrome. Aside from traditional cardiovascular risk factors, the inflammatory burden emerged as the novel phenotype that compromised renal prognosis in such population. METHODS: A cohort with chronic coronary syndrome was enrolled to investigate the association between inflammatory status and renal dysfunction. Levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), tumour necrosis factor-α (TNF-α), adiponectin, matrix metalloproteinase-9, interleukin-6, lipoprotein-associated phospholipase A2, were assessed. Renal event was defined as > 25% decline in estimated glomerular filtration rate (eGFR). Inflammatory scores were calculated based on the aggregate of hs-CRP, TNF-α, and adiponectin levels. RESULTS: Among the 850 enrolled subjects, 145 patients sustained a renal event during an averaged 3.5 years follow-up. Multivariate analysis with Cox regression suggested elevations in hs-CRP, TNF-α, and adiponectin levels were independent risk factors for the occurrence of a renal event. Whereas, Kaplan-Meier curve illustrated significant correlation between high TNF-α (P = 0.005), adiponectin (P < 0.001), but not hs-CRP (P = 0.092), and eGFR decline. The aggregative effect of these biomarkers was also distinctly correlated with renal events (score 2: P = 0.042; score 3: P < 0.001). CONCLUSIONS: Inflammatory burden was associated with eGFR decline in patients with chronic coronary syndrome.

Gut butyrate-producers confer post-infarction cardiac protection.

The gut microbiome and its metabolites are increasingly implicated in several cardiovascular diseases, but their role in human myocardial infarction (MI) injury responses have yet to be established. To address this, we examined stool samples from 77 ST-elevation MI (STEMI) patients using 16 S V3-V4 next-generation sequencing, metagenomics and machine learning. Our analysis identified an enriched population of butyrate-producing bacteria. These findings were then validated using a controlled ischemia/reperfusion model using eight nonhuman primates. To elucidate mechanisms, we inoculated gnotobiotic mice with these bacteria and found that they can produce beta-hydroxybutyrate, supporting cardiac function post-MI. This was further confirmed using HMGCS2-deficient mice which lack endogenous ketogenesis and have poor outcomes after MI. Inoculation increased plasma ketone levels and provided significant improvements in cardiac function post-MI. Together, this demonstrates a previously unknown role of gut butyrate-producers in the post-MI response.

2023 Expert Consensus of the Taiwan Society of Cardiology on the Diagnosis and Treatment of Cardiac Amyloidosis.

Cardiac amyloidosis is one form of systemic amyloidosis caused by abnormal amyloid fibrils deposited in the extracellular space of the myocardium causing heart failure because of restrictive cardiomyopathy and conduction disturbances. The incidence and prevalence of cardiac amyloidosis are higher than previously noted, particularly among special populations. The most common forms of cardiac amyloidosis are light chain and transthyretin amyloid cardiomyopathy. Even though more than 70% of patients with systemic amyloidosis have cardiac amyloidosis, the diagnosis is often delayed, suggesting significant gaps in the knowledge of cardiac amyloidosis and a lack of multidisciplinary teamwork in our daily practice. The Taiwan Society of Cardiology Heart Failure Committee organized experts to draft the "Expert Consensus on the diagnosis and treatment of cardiac amyloidosis." This statement aims to help clinicians and healthcare professionals improve early diagnosis and management of cardiac amyloidosis in Taiwan. The expert panel met virtually to review the data and discuss the consensus statements. Our review provided practical information about diagnostic methods and algorithms, clinical clues and red-flag signs, cardiac amyloidosis per se and its comorbidities treatment modalities, and follow-up plans for asymptomatic transthyretin gene carriers. We especially innovate two acronyms, "HFpEF MUTED CALL" and "HFmrEF MUST COUNT", to help in the early diagnosis and screening of transthyretin amyloid cardiomyopathy as shown in the Central Illustration.

Low-density lipoprotein electronegativity and risk of death after acute coronary syndromes: A case-cohort analysis.

BACKGROUND AND AIMS: Low-density lipoprotein (LDL)-cholesterol (LDL-C) promotes atherosclerotic cardiovascular disease (ASCVD), with changes in LDL electronegativity modulating its pro-atherogenic/pro-thrombotic effects. Whether such alterations associate with adverse outcomes in patients with acute coronary syndromes (ACS), a patient population at particularly high cardiovascular risk, remains unknown. METHODS: This is a case-cohort study using data from a subset of 2619 ACS patients prospectively recruited at four university hospitals in Switzerland. Isolated LDL was chromatographically separated into LDL particles with increasing electronegativity (L1-L5), with the L1-L5 ratio serving as a proxy of overall LDL electronegativity. Untargeted lipidomics revealed lipid species enriched in L1 (least) vs. L5 (most electronegative subfraction). Patients were followed at 30 days and 1 year. The mortality endpoint was reviewed by an independent clinical endpoint adjudication committee. Multivariable-adjusted hazard ratios (aHR) were calculated using weighted Cox regression models. RESULTS: Changes in LDL electronegativity were associated with all-cause mortality at 30 days (aHR, 2.13, 95% CI, 1.07-4.23 per 1 SD increment in L1/L5; p=.03) and 1 year (1.84, 1.03-3.29; p=.04), with a notable association with cardiovascular mortality (2.29; 1.21-4.35; p=.01; and 1.88; 1.08-3.28; p=.03). LDL electronegativity superseded several risk factors for the prediction of 1-year death, including LDL-C, and conferred improved discrimination when added to the updated GRACE score (area under the receiver operating characteristic curve 0.74 vs. 0.79, p=.03). Top 10 lipid species enriched in L1 vs. L5 were: cholesterol ester (CE) (18:2), CE (20:4), free fatty acid (FA) (20:4), phosphatidyl-choline (PC) (36:3), PC (34:2), PC (38:5), PC (36:4), PC (34:1), triacylglycerol (TG) (54:3), and PC (38:6) (all p < .001), with CE (18:2), CE (20:4), PC (36:3), PC (34:2), PC (38:5), PC (36:4), TG (54:3), and PC (38:6) independently associating with fatal events during 1-year of follow-up (all p < .05). CONCLUSIONS: Reductions in LDL electronegativity are linked to alterations of the LDL lipidome, associate with all-cause and cardiovascular mortality beyond established risk factors, and represent a novel risk factor for adverse outcomes in patients with ACS. These associations warrant further validation in independent cohorts.

Early Experience of Patients with left Bundle Branch Block Corrected through Left Bundle Branch Area Pacing Compared with Conventional Right Ventricular Pacing: A Single-Center Retrospective Study.

Background: Left bundle branch area pacing (LBBAP) has the advantages of narrow QRS duration, rapid peak left ventricular (LV) activation, and LV dyssynchrony correction with a low, stable pacing output. Here we report our experience with patients undergoing LBBAP with a left bundle branch block (LBBB) for clinically indicated pacemaker or cardiac resynchronization therapy implantation. We compared the initial follow-up data of these patients and patients undergoing conventional right ventricular pacing (RVP). Methods: This retrospective study was performed between January 2017 and December 2020 and recruited 19 consecutive patients (mean age: 63 years; 8 women, 11 men) who underwent LBBAP (13 LBBAP only and 6 LBBAP + LV pacing), and 14 consecutive patients (mean age: 75 years; 8 women, 6 men) who underwent RVP. Demographic data, QRS durations, and echocardiographic parameters were compared before and after the procedures. Results: LBBAP substantially shortened the QRS duration and improved LV dyssynchrony echocardiographic parameters. However, RVP was not significantly associated with prolonged QRS duration and worse LV dyssynchronization. LBBAP improved cardiac contractility in selected patients. We did not find adverse effects of LBBAP on patients with preserved systolic function, possibly due to the limited number of patients and follow-up time. However, two of the 11 patients with preserved systolic function at baseline who underwent conventional RVP developed heart failure after implantation. Conclusions: In our experience, LBBAP improves LBBB-related ventricular dyssynchrony. However, LBBAP requires greater skill, and doubts remain about lead extraction. LBBAP may be an option for patients with LBBB when performed by an experienced operator, however further studies are needed to verify our findings.

Sympathetic Modulation in Cardiac Arrhythmias: Where We Stand and Where We Go.

The nuance of autonomic cardiac control has been studied for more than 400 years, yet little is understood. This review aimed to provide a comprehensive overview of the current understanding, clinical implications, and ongoing studies of cardiac sympathetic modulation and its anti-ventricular arrhythmias' therapeutic potential. Molecular-level studies and clinical studies were reviewed to elucidate the gaps in knowledge and the possible future directions for these strategies to be translated into the clinical setting. Imbalanced sympathoexcitation and parasympathetic withdrawal destabilize cardiac electrophysiology and confer the development of ventricular arrhythmias. Therefore, the current strategy for rebalancing the autonomic system includes attenuating sympathoexcitation and increasing vagal tone. Multilevel targets of the cardiac neuraxis exist, and some have emerged as promising antiarrhythmic strategies. These interventions include pharmacological blockade, permanent cardiac sympathetic denervation, temporal cardiac sympathetic denervation, etc. The gold standard approach, however, has not been known. Although neuromodulatory strategies have been shown to be highly effective in several acute animal studies with very promising results, the individual and interspecies variation between human autonomic systems limits the progress in this young field. There is, however, still much room to refine the current neuromodulation therapy to meet the unmet need for life-threatening ventricular arrhythmias.

Association of Major Adverse Cardiac Events and Beta-Blockers in Patients with and without Atherosclerotic Cardiovascular Disease: Long-Term Follow-Up Results of the T-SPARCLE and T-PPARCLE Registry in Taiwan.

Beta-blockers are widely used, but the benefit is now challenged in patients at risk of atherosclerotic cardiovascular disease (ASCVD) in the present coronary reperfusion era. We aimed to identify the risk factors of a major adverse cardiac event (MACE) and the long-term effect of beta-blockers in two large cohorts in Taiwan. Two prospective observational cohorts, including patients with known atherosclerosis cardiovascular disease (T-SPARCLE) and patients with at least one risk factor of ASCVD but without clinically evident ASCVD (T-PPARCLE), were conducted in Taiwan. The primary endpoint is the time of first occurrence of a MACE (cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, and cardiac arrest with resuscitation). Between December 2009 and November 2014, with a median 2.4 years follow-up, 11,747 eligible patients (6921 and 4826 in T-SPARCLE and T-PPARCLE, respectively) were enrolled. Among them, 273 patients (2.3%) met the primary endpoint. With multivariate Cox PH model analysis, usage of beta-blocker was lower in patients with MACE (42.9% vs. 52.4%, p < 0.01). In patients with ASCVD, beta-blocker usage was associated with lower MACEs (hazard ratio 0.72; p < 0.001), but not in patients without ASCVD. The event-free survival of beta-blocker users remained higher during the follow-up period (p < 0.005) of ASCVD patients. In conclusion, in ASCVD patients, reduced MACE was associated with beta-blocker usage, and the effect was maintained during a six-year follow-up. Prescribing beta-blockers as secondary prevention is reasonable in the Taiwanese population.

Risk of Acute Myocardial Infarction in Pneumoconiosis: Results from a Retrospective Cohort Study.

BACKGROUND: Pneumoconiosis (PCN) has several comorbidities, most notably pulmonary and cardiovascular diseases. However, much is still unknown about the relationship between PCN and acute myocardial infarction (AMI). The present study aimed to clarify the association between PCN and subsequent AMI risk using a retrospective cohort study design. METHODS: This was a population-based, retrospective cohort study that used data from Taiwan's National Health Insurance Database. A total of 7556 newly diagnosed patients with PCN and 7556 individuals without PCN were included in the PCN and comparison cohort (PC and CC), respectively, between 2008 and 2018, with propensity score matching for age, gender, comorbidity, medication, and date of PCN diagnosis. The occurrence of AMI was monitored until the end of 2019, and AMI risk was assessed using Cox proportional hazard regression models. RESULTS: The overall incidence of AMI was 1.34-fold higher in the PC than in the CC (4.33 vs. 3.23 per 1000 person-years, respectively, p < 0.05), with an adjusted hazard ratio (aHR) of 1.36 (95% confidence interval (CI): 1.08-1.72) after controlling for age, gender, comorbidity, and medication. Further analyses showed a higher risk of AMI with increased annual number of emergency department visits among patients with PCN (aHR: 1.30, 95% CI: 1.01-1.66 (<1) and aHR: 1.68, 95% CI: 1.13-2.50 (≥1)). CONCLUSION: Patients with PCN had a significantly higher risk of developing AMI than those without PCN. Clinicians should pay more attention to prevent AMI episodes in patients with PCN.

Worldwide survey on implantation of and outcomes for conduction system pacing with His bundle and left bundle branch area pacing leads.

BACKGROUND: Adoption and outcomes for conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), in real-world settings are incompletely understood. We sought to describe real-world adoption of CSP lead implantation and subsequent outcomes. METHODS: We performed an online cross-sectional survey on the implantation and outcomes associated with CSP, between November 15, 2020, and February 15, 2021. We described survey responses and reported HBP and LBBAP outcomes for bradycardia pacing and cardiac resynchronization CRT indications, separately. RESULTS: The analysis cohort included 140 institutions, located on 5 continents, who contributed data to the worldwide survey on CSP. Of these, 127 institutions (90.7%) reported experience implanting CSP leads. CSP and overall device implantation volumes were reported by 84 institutions. In 2019, the median proportion of device implants with CSP, HBP, and/or LBBAP leads attempted were 4.4% (interquartile range [IQR], 1.9-12.5%; range, 0.4-100%), 3.3% (IQR, 1.3-7.1%; range, 0.2-87.0%), and 2.5% (IQR, 0.5-24.0%; range, 0.1-55.6%), respectively. For bradycardia pacing indications, HBP leads, as compared to LBBAP leads, had higher reported implant threshold (median [IQR]: 1.5 V [1.3-2.0 V] vs 0.8 V [0.6-1.0 V], p = 0.0008) and lower ventricular sensing (median [IQR]: 4.0 mV [3.0-5.0 mV] vs. 10.0 mV [7.0-12.0 mV], p < 0.0001). CONCLUSION: In conclusion, CSP lead implantation has been broadly adopted but has yet to become the default approach at most surveyed institutions. As the indications and data for CSP continue to evolve, strategies to educate and promote CSP lead implantation at institutions without CSP lead implantation experience would be necessary.

The clinical significance of osteopontin on the cardiovascular outcomes in patients with stable coronary artery disease.

BACKGROUND: Osteopontin (OPN) is a noncollagenous matricellular protein which is mainly present in bone matrix. A high OPN level has been associated with heart failure and acute coronary syndrome, however data on patients with chronic coronary syndrome (CCS) are lacking. The present study aimed to evaluate the association between OPN and the prognosis of Taiwanese patients with CCS. METHODS: We enrolled participants from the Biosignature Registry, a nationwide prospective cohort study conducted at nine different medical centers throughout Taiwan. The inclusion criteria were participants who had received successful percutaneous coronary intervention at least once previously, and stable under medical therapy for at least 1 month before enrollment. They were followed for at least 72 months. Logistic regression and Cox proportional hazard model were used to investigate the association between OPN and clinical outcomes. The outcomes of this study were the first occurrence of hard cardiovascular events and composite cardiovascular outcomes including cardiovascular mortality, revascularization, hospitalization for acute myocardial infarction (AMI) or heart failure. RESULTS: A total of 666 patients with both hs-CRP and osteopontin measurements were enrolled and followed for 72 months. OPN was correlated positively with AMI-related hospitalization, where the highest tertile (Tertile 3) of baseline OPN had the highest risk of AMI-related hospitalization, which remained significant after multivariate adjustments (HR 3.20, p = 0.017). In contrast, combining OPN and hs-CRP did not improve the prediction of CV outcomes. CONCLUSION: OPN may be a potentially valuable biomarker in predicting CV outcomes. During 6 years of follow-up period, an OPN level >4810 pg/ml was associated with a significantly higher incidence of AMI-related hospitalization in CCS patients who received successful PCI before the enrollment.

Correlations between myocardial injury current and lead performance in His bundle pacing compared with left bundle branch area pacing and right ventricular septum pacing.

BACKGROUND: Conduction system pacing by implanting the lead in the His bundle (HBP) region or in the left bundle branch area (LBBAP) has gained popularity. Myocardial injury current (IC) is useful for predicting adequate lead fixation in right ventricular septal pacing (RVSP). OBJECTIVES AND METHODS: We compared the correlations between IC and lead performance among patients receiving HBP (n = 41), LBBAP (n = 53), and historical RVSP (n = 88). LBBAP was an alternative if optimal HBP was not achieved. A positive IC (STpost-screw-in - STpre-screw-in) was defined as > 0.2 mV or a > 25% ST elevation and prolongation of the ventricular electrograms > 10 ms from baseline. RESULTS: HBP patients with a positive IC (48%, 0.84 ± 0.4 V/0.4 ms) exhibited a similar pacing threshold to their LBBAP counterparts (76%, 0.75 ± 0.3 V/0.4 ms, p = 0.329), but a higher pacing threshold than their RVSP counterparts (67%, 0.50 ± 0.1 V/0.4 ms, p < 0.001) at implantation. The R-wave (5.70 ± 3.4 mV) and impedance (660.91 ± 140.8 Ω) were both lower than those of LBBAP (10.35 ± 6.0 mV, p = 0.002; 822.36 ± 235.8 Ω, p = 0.005) and RVSP (11.24 ± 4.9 mV, p < 0.001; 754.27 ± 126.4 Ω, p = 0.006) patients respectively at implantation. The trend of electrical parameter comparisons remained unchanged during follow-up (3.56 ± 1.4 months). Notably, HBP patients without ICs had a higher pacing threshold (1.24 ± 0.6 V/0.4 ms) compared to their LBBAP (0.73 ± 0.3 V/0.4 ms, p = 0.009) and RVSP (0.53 ± 0.1 V/0.4 ms, p < 0.001) counterparts at implantation and during follow-up. CONCLUSIONS: The detection of positive changes of myocardial ICs during HBP was associated with a better capture threshold equivalent to the LBBAP counterpart both at implantation and during short-term follow-up. Further large-scale studies with longer follow-up are necessary to confirm these findings.

PD-L1 and AKT Overexpressing Adipose-Derived Mesenchymal Stem Cells Enhance Myocardial Protection by Upregulating CD25+ T Cells in Acute Myocardial Infarction Rat Model.

This study explores the synergistic impact of Programmed Death Ligand 1 (PD-L1) and Protein Kinase B (Akt) overexpression in adipose-derived mesenchymal stem cells (AdMSCs) for ameliorating cardiac dysfunction after myocardial infarction (MI). Post-MI adult Wistar rats were allocated into four groups: sham, MI, ADMSC treatment, and ADMSCs overexpressed with PD-L1 and Akt (AdMSC-PDL1-Akt) treatment. MI was induced via left anterior descending coronary artery ligation, followed by intramyocardial AdMSC injections. Over four weeks, cardiac functionality and structural integrity were assessed using pressure-volume analysis, infarct size measurement, and immunohistochemistry. AdMSC-PDL1-Akt exhibited enhanced resistance to reactive oxygen species (ROS) in vitro and ameliorated MI-induced contractile dysfunction in vivo by improving the end-systolic pressure-volume relationship and preload-recruitable stroke work, together with attenuating infarct size. Molecular analyses revealed substantial mitigation in caspase3 and nuclear factor-κB upregulation in MI hearts within the AdMSC-PDL1-Akt group. Mechanistically, AdMSC-PDL1-Akt fostered the differentiation of normal T cells into CD25+ regulatory T cells in vitro, aligning with in vivo upregulation of CD25 in AdMSC-PDL1-Akt-treated rats. Collectively, PD-L1 and Akt overexpression in AdMSCs bolsters resistance to ROS-mediated apoptosis in vitro and enhances myocardial protective efficacy against MI-induced dysfunction, potentially via T-cell modulation, underscoring a promising therapeutic strategy for myocardial ischemic injuries.

Corrigendum: Artificial intelligence-assisted remote detection of ST-elevation myocardial infarction using a mini-12-lead electrocardiogram device in prehospital ambulance care.

[This corrects the article DOI: 10.3389/fcvm.2022.1001982.].

Implementation of an All-Day Artificial Intelligence-Based Triage System to Accelerate Door-to-Balloon Times.

OBJECTIVE: To implement an all-day artificial intelligence (AI)-based system to facilitate chest pain triage in the emergency department. METHODS: The AI-based triage system encompasses an AI model combining a convolutional neural network and long short-term memory to detect ST-elevation myocardial infarction (STEMI) on electrocardiography (ECG) and a clinical risk score (ASAP) to prioritize patients for ECG examination. The AI model was developed on 2907 twelve-lead ECGs: 882 STEMI and 2025 non-STEMI ECGs. RESULTS: Between November 1, 2019, and October 31, 2020, we enrolled 154 consecutive patients with STEMI: 68 during the AI-based triage period and 86 during the conventional triage period. The mean ± SD door-to-balloon (D2B) time was significantly shortened from 64.5±35.3 minutes to 53.2±12.7 minutes (P=.007), with 98.5% vs 87.2% (P=.009) of D2B times being less than 90 minutes in the AI group vs the conventional group. Among patients with an ASAP score of 3 or higher, the median door-to-ECG time decreased from 30 minutes (interquartile range [IQR], 7-59 minutes) to 6 minutes (IQR, 4-30 minutes) (P<.001). The overall performances of the AI model in identifying STEMI from 21,035 ECGs assessed by accuracy, precision, recall, area under the receiver operating characteristic curve, F1 score, and specificity were 0.997, 0.802, 0.977, 0.999, 0.881, and 0.998, respectively. CONCLUSION: Implementation of an all-day AI-based triage system significantly reduced the D2B time, with a corresponding increase in the percentage of D2B times less than 90 minutes in the emergency department. This system may help minimize preventable delays in D2B times for patients with STEMI undergoing primary percutaneous coronary intervention.

Mesenchymal stem cell therapy on top of triple therapy with remdesivir, dexamethasone, and tocilizumab improves PaO2/FiO2 in severe COVID-19 pneumonia.

Background: Despite patients with severe coronavirus disease (COVID-19) receiving standard triple therapy, including steroids, antiviral agents, and anticytokine therapy, health condition of certain patients continue to deteriorate. In Taiwan, the COVID-19 mortality has been high since the emergence of previous variants of this disease (such as alpha, beta, or delta). We aimed to evaluate whether adjunctive infusion of human umbilical cord mesenchymal stem cells (MSCs) (hUC-MSCs) on top of dexamethasone, remdesivir, and tocilizumab improves pulmonary oxygenation and suppresses inflammatory cytokines in patients with severe COVID-19. Methods: Hospitalized patients with severe or critical COVID-19 pneumonia under standard triple therapy were separated into adjuvant hUC-MSC and non-hUC-MSC groups to compare the changes in the arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio and biological variables. Results: Four out of eight patients with severe or critical COVID-19 received either one (n = 2) or two (n = 2) doses of intravenous infusions of hUC-MSCs using a uniform cell dose of 1.0 × 108. Both high-sensitivity C-reactive protein (hs-CRP) level and monocyte distribution width (MDW) were significantly reduced, with a reduction in the levels of interleukin (IL)-6, IL-13, IL-12p70 and vascular endothelial growth factor following hUC-MSC transplantation. The PaO2/FiO2 ratio increased from 83.68 (64.34-126.75) to 227.50 (185.25-237.50) and then 349.56 (293.03-367.92) within 7 days after hUC-MSC infusion (P < 0.001), while the change of PaO2/FiO2 ratio was insignificant in non-hUC-MSC patients (admission day: 165.00 [102.50-237.61]; day 3: 100.00 [72.00-232.68]; day 7: 250.00 [71.00-251.43], P = 0.923). Conclusion: Transplantation of hUC-MSCs as adjunctive therapy improves pulmonary oxygenation in patients with severe or critical COVID-19. The beneficial effects of hUC-MSCs were presumably mediated by the mitigation of inflammatory cytokines, characterized by the reduction in both hs-CRP and MDW.

Artificial intelligence-assisted remote detection of ST-elevation myocardial infarction using a mini-12-lead electrocardiogram device in prehospital ambulance care.

Objective: To implement an all-day online artificial intelligence (AI)-assisted detection of ST-elevation myocardial infarction (STEMI) by prehospital 12-lead electrocardiograms (ECGs) to facilitate patient triage for timely reperfusion therapy. Methods: The proposed AI model combines a convolutional neural network and long short-term memory (CNN-LSTM) to predict STEMI on prehospital 12-lead ECGs obtained from mini-12-lead ECG devices equipped in ambulance vehicles in Central Taiwan. Emergency medical technicians (EMTs) from the 14 AI-implemented fire stations performed the on-site 12-lead ECG examinations using the mini portable device. The 12-lead ECG signals were transmitted to the AI center of China Medical University Hospital to classify the recordings as "STEMI" or "Not STEMI". In 11 non-AI fire stations, the ECG data were transmitted to a secure network and read by available on-line emergency physicians. The response time was defined as the time interval between the ECG transmission and ECG interpretation feedback. Results: Between July 17, 2021, and March 26, 2022, the AI model classified 362 prehospital 12-lead ECGs obtained from 275 consecutive patients who had called the 119 dispatch centers of fire stations in Central Taiwan for symptoms of chest pain or shortness of breath. The AI's response time to the EMTs in ambulance vehicles was 37.2 ± 11.3 s, which was shorter than the online physicians' response time from 11 other fire stations with no AI implementation (113.2 ± 369.4 s, P < 0.001) after analyzing another set of 335 prehospital 12-lead ECGs. The evaluation metrics including accuracy, precision, specificity, recall, area under the receiver operating characteristic curve, and F1 score to assess the overall AI performance in the remote detection of STEMI were 0.992, 0.889, 0.994, 0.941, 0.997, and 0.914, respectively. During the study period, the AI model promptly identified 10 STEMI patients who underwent primary percutaneous coronary intervention (PPCI) with a median contact-to-door time of 18.5 (IQR: 16-20.8) minutes. Conclusion: Implementation of an all-day real-time AI-assisted remote detection of STEMI on prehospital 12-lead ECGs in the field is feasible with a high diagnostic accuracy rate. This approach may help minimize preventable delays in contact-to-treatment times for STEMI patients who require PPCI.