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.

Prescribing cascades of antigout medications from thiazide diuretics in gout-naïve hypertensive adults receiving first-line pharmacological management.

Prescribing cascade is a significant clinical problem but is often overlooked. We explore the incidence of the prescribing cascades of antigout medications related to thiazide treatment in gout-naïve hypertensive adults newly exposed to the pharmacological treatment. This population-based, retrospective cohort study used the Taiwan National Health Insurance Registry Database. Gout-naïve hypertensive adults who were newly dispensed first-line antihypertensive drugs between January 1, 2000, and December 31, 2016, were enrolled. Patients were divided into the thiazide group (n = 4192) and the non-thiazide group (n = 81,083). The non-thiazide group included patients who received an angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, calcium channel blocker, or beta-blocker. The study utilized propensity score matching and multivariable Cox regression models to investigate the prescribing cascade of antigout agents following antihypertensive treatment, adjusting for factors like age, sex, comorbidities, and concurrent medications. After propensity score matching, each group consisted of 4045 patients, with the thiazide group exhibiting a higher risk of being prescribed antigout medications across different time intervals post-treatment initiation. Specifically, adjusted hazard ratios (aHRs) for the thiazide group were 2.23, 2.07, and 2.41 for < 30 days, 31-180 days, and > 180 days, respectively, indicating a sustained and significant risk over time. Comparative analyses revealed thiazide diuretics were associated with a higher risk of antigout medication prescriptions compared to other antihypertensive classes, particularly evident after 180 days. Subgroup analyses across various demographics and comorbidities consistently showed an increased risk in the thiazide cohort. Gout-naïve hypertensive adults newly dispensed thiazide had a higher risk of subsequently adding antigout agents than those taking other first-line antihypertensive medications. The awareness and interruption of these prescribing cascades are critical to improving patient safety.

Protective Effects of Statins on Limb and Cardiovascular Outcomes in Patients with Peripheral Artery Disease and End-Stage Renal Disease.

Background: Previous studies have reported that statins have inconsistent and marginal cardiovascular (CV) benefits in patients with end-stage renal disease (ESRD). However, whether statins play a secondary preventive role in patients with peripheral artery disease (PAD) and ESRD remains unclear. Objectives: This study aimed to compare the long-term clinical outcomes between statin users and nonusers with PAD and ESRD. Methods: This retrospective cohort study assessed the long-term protective effects of statins using data from the National Health Insurance Research Database in Taiwan. Propensity score matching was performed according to sex, age, index year, related comorbidities, and medications. The main outcomes were limb events and major adverse CV events (MACEs). Results: The statin user group (n = 4,460) was compared with the propensity score-matched statin nonuser group (n = 4,460). The mean age of the matched patients was 64 years, and 40% of the patients were men. The baseline characteristics of the groups were well-balanced. The overall limb event and MACE rates were not different between the two groups. However, the statin user group had lower rates of limb amputation [adjusted hazard ratio (aHR): 0.85, 95% confidence interval (CI): 0.73-0.99], stroke (aHR: 0.71, 95% CI: 0.62-0.83), CV death (aHR: 0.46, 95% CI: 0.32-0.66), and all-cause death (aHR: 0.45, 95% CI: 0.42-0.48) despite having a higher rate of percutaneous transluminal angioplasty for PAD. Conclusions: This population-based retrospective cohort study demonstrated that statin therapy was associated with a lower risk of limb amputation, nonfatal stroke, CV death, and all-cause death in patients with PAD and ESRD.

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.

First-in-human pilot trial of combined intracoronary and intravenous mesenchymal stem cell therapy in acute myocardial infarction.

Background: Acute ST-elevation myocardial infarction (STEMI) elicits a robust cardiomyocyte death and inflammatory responses despite timely revascularization. Objectives: This phase 1, open-label, single-arm, first-in-human study aimed to assess the safety and efficacy of combined intracoronary (IC) and intravenous (IV) transplantation of umbilical cord-derived mesenchymal stem cells (UMSC01) for heart repair in STEMI patients with impaired left ventricular ejection fraction (LVEF 30-49%) following successful reperfusion by percutaneous coronary intervention. Methods: Consenting patients received the first dose of UMSC01 through IC injection 4-5 days after STEMI followed by the second dose of UMSC01 via IV infusion 2 days later. The primary endpoint was occurrence of any treatment-related adverse events and the secondary endpoint was changes of serum biomarkers and heart function by cardiac magnetic resonance imaging during a 12-month follow-up period. Results: Eight patients gave informed consents, of whom six completed the study. None of the subjects experienced treatment-related serious adverse events or major adverse cardiovascular events during IC or IV infusion of UMSC01 and during the follow-up period. The NT-proBNP level decreased (1362 ± 1801 vs. 109 ± 115 pg/mL, p = 0.0313), the LVEF increased (52.67 ± 12.75% vs. 62.47 ± 17.35%, p = 0.0246), and the wall motion score decreased (26.33 ± 5.57 vs. 22.33 ± 5.85, p = 0.0180) at the 12-month follow-up compared to the baseline values. The serial changes of LVEF were 0.67 ± 3.98, 8.09 ± 6.18, 9.04 ± 10.91, and 9.80 ± 7.56 at 1, 3, 6, and 12 months, respectively as compared to the baseline. Conclusion: This pilot study shows that combined IC and IV transplantation of UMSC01 in STEMI patients with impaired LVEF appears to be safe, feasible, and potentially beneficial in improving heart function. Further phase 2 studies are required to explore the effectiveness of dual-route transplantation of UMSC01 in STEMI patients.

Comparison of pharmaco-mechanical thrombolysis and catheter-directed thrombolysis for treating thrombotic or embolic arterial occlusion of the lower limb.

BACKGROUND: Whether pharmaco-mechanical thrombolysis (PMT) results in superior outcomes to catheter-directed thrombolysis (CDT) in treating thrombotic or embolic arterial occlusion of the lower limbs is unclear. METHODS: We enrolled 94 patients with Rutherford class I-IIb due to thrombotic or embolic arterial occlusion in the lower limbs and who received emergency endovascular treatment. Baseline demographics, laboratory data, angiography and clinical outcomes were collected through chart reviews and fluoroscopic imaging. The procedural characteristics (thrombolytic drug dosage, treatment duration, and additional procedures), immediate angiographic outcomes (patency of calf vessels, and complete lysis), complications (major bleeding, and fasciotomy), and primary composite end-points (30-day mortality, amputation, and reocclusion) were compared between patients who received CDT versus PMT. RESULTS: Compared with CDT, PMT was independently associated with lower total UK dosage (standardized coefficient ß=- 0.44; P<0.01) and higher prevalence of complete lysis (odds ratio =1.78, 95% confidence interval: 1.03-3.06; P=0.04) after adjustments of covariates. The PMT group had significantly shorter treatment duration (23.00 [7.25-39.13] vs. 41.00 [27.00-52.50]; P<0.01). No significant intergroup differences were observed for the primary composite end point (10.7% vs. 9.1%; P=0.81), or prevalence of the major bleeding (9.1% vs. 0.0%; P=0.10) despite the PMT group comprising patients with more advanced chronic kidney disease and more diffuse thrombosis. CONCLUSIONS: PMT with a Rotarex is a safe and effective strategy for treating thrombotic or embolic lower limb ischemia. It significantly reduced the thrombolytic drug dosage, and resulted in the complete lysis being more likely.

Sex differences in long-term cardiovascular outcomes among patients with acute myocardial infarction: A population-based retrospective cohort study.

BACKGROUND: Whether a sex difference exists in long-term cardiovascular (CV) outcomes after acute myocardial infarction (AMI) is worth exploration. This study is sought to investigate the relationships among sex, age, and the long-term prognosis after AMI. METHODS: This population-based retrospective cohort study used Taiwan's National Health Insurance Research Database to investigate the sex differences in in-hospital and long-term CV outcomes in patients with AMI. We enrolled patients who were first diagnosed with AMI from January 1, 2000 to December 31, 2013. The outcomes of interest included all-cause mortality, CV death, non-fatal stroke, non-fatal heart failure, and AMI recurrence during hospitalization and 5-year follow up. The CV outcomes were also analyzed by age stratification. RESULTS: Overall, 201 921 patients with AMI were analyzed; 68.72% were men and 31.28% were women, with mean ages of 65.34 ± 14.12 and 73.05 ± 12.22 years, respectively. Major adverse cardiac events during hospitalization and up to 5 years were consistently greater in women than in men. Multivariable regression analysis revealed no sex difference existed in long-term all-cause and CV mortality. Men of all age groups consistently showed higher risk of both short- and long-term recurrence of AMI. Nonetheless, the female sex still independently predicted increased risk of non-fatal stroke and heart failure from hospitalization until 3-year follow up. CONCLUSION: Women with AMI had poorer short-term and long-term outcomes. The sex differences in long-term all-cause and CV death disappear after multivariate analysis. Nonetheless, female AMI patients independently predicted higher risk of stroke and heart failure from hospitalization until a 3-year follow-up. To better understand the pathophysiology of female patients with AMI and develop more effective management, more studies in this field are necessary in the future.

Prognosis Between ST-Elevation and Non-ST-elevation Myocardial Infarction in Older Adult Patients.

Background: Whether there is a difference in prognosis between elderly patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) remains mysterious. Methods: We conducted a retrospective cohort study by analyzing the data in the Longitudinal Health Insurance Database (LHID) in Taiwan to explore differences between STEMI and NSTEMI with respect to in-hospital and long-term (3-year) outcomes among older adult patients (aged ≥65 years). Patients were further stratified based on whether they received coronary revascularization. Results: In total, 5,902 patients aged ≥65 years with acute myocardial infarction (AMI) who underwent revascularization (2,254) or medical therapy alone (3,648) were included. In the revascularized group, no difference was observed in cardiovascular (CV) and all-cause mortality during hospitalization or at 3-year follow-up between the two AMIs. Conversely, in the non-revascularized group, patients with NSTEMI had higher crude odds ratio (cOR) for all-cause death during hospitalization [cOR: 1.33, 95% confidence interval (CI) = 1.07-1.65] and at 3-year follow-up (cOR: 1.47, 95% CI = 1.21-1.91) relative to patients with STEMI. However, after multivariable adjustments, only NSTEMI indicated fewer in-hospital CV death [adjusted odds ratio (aOR): 0.75, 95% CI = 0.58-0.98] than STEMI in non-revascularized group. Moreover, major bleeding was not different between patients with STEMI or NSTEMI aged ≥65 years old. Conclusion: Classification of AMI is not associated with the difference of in-hospital or 3-year CV and all-cause death in older adult patients received revascularization. In a 3-year follow-up period, STEMI was an independent predictor of a higher incidence of revascularization after the index event. Non-ST-elevation myocardial infarction had more incidence of MACE than patients with STEMI did in both treatment groups.

Clinical Outcomes of Patients with Intermediate-to-High-Risk Pulmonary Embolism Undergoing Ultrasound-Assisted Catheter-Based Fibrinolysis Therapy in a Mid-Term Follow-Up Period - A Retrospective Observational Study.

OBJECTIVES: Endovascular therapy with ultrasound-assisted catheter-directed thrombolysis (UACDT) theoretically provides higher efficacy while reducing the bleeding risk compared with conventional systemic thrombolysis. The clinical outcomes of UACDT in treating intermediate-to-high-risk pulmonary embolism (PE) are lacking in an Asian population. METHODS: Forty-two patients who presented with intermediate-to-high-risk PE received UACDT. The patients were divided into two groups based on the incidence of procedure-related bleeding events, and baseline demographics were compared between the two groups. A paired-Student's t test was conducted to evaluate the efficacy of UACDT. Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for significant bleeding events. RESULTS: The average age was 58.93 ± 20.48 years, and 33.33% of the study participants were male. A total of 85.7% of the participants had intermediate-risk PE. Compared with pre-intervention pulmonary artery pressure, the mean pulmonary artery pressure decreased significantly (37.61 ± 9.57 mmHg vs. 25.7 ± 9.84 mmHg, p < 0.01) after UACDT. The cumulative total tissue plasminogen activator dosage and total infusion duration were 44.54 ± 20.55 mg and 39.14 ± 19.06 hours respectively. Overall, 21.43% of the participants had severe bleeding events during the endovascular fibrinolysis treatment period. Forward conditional multivariate logistic regression analysis revealed that the lowest fibrinogen level during thrombolysis was an independent factor associated with moderate-to-severe bleeding (odds ratio: 0.40, 95% confidence interval: 0.19-0.88, p = 0.02). CONCLUSIONS: UACDT exhibited high efficacy, but resulted in a higher-than-expected bleeding rate in this real-world study of an Asian population. The lowest fibrinogen level during thrombolysis was an independent risk factor associated with procedure-related bleeding events.

Severe hypertriglyceridemia secondary to venlafaxine use in an older adult on dialysis -case report.

BACKGROUND: Although the prescribing information for Venlafaxine extended release includes a discussion about possible increases in total cholesterol and triglycerides (TG) seen in healthier adult patients during premarketing clinical trials, no post-marketing studies or case reports, that discuss the effects of venlafaxine on TG in elderly patients with chronic kidney disease. CASE PRESENTATION: We report a 71 year-old male patient with end-stage renal disease on hemodialysis, with a history of coronary artery disease, mild hyperlipidemia, and hypertension. This patient twice demonstrated the severe rises in triglycerides while taking the antidepressant, i.e., venlafaxine, and discontinuing the long-term use of fenofirate. The adverse drug reaction sub-committee at the hospital rated the second event as a "probable reaction" using the Naranjo nomogram, accordingly. CONCLUSIONS: This case demonstrates the risk of changes in lipid profiles while taking venlafaxine and receiving on and off fenofibrate therapy in the older adult patient with chronic kidney disease and under hemodialysis. Regular monitoring for lipid changes after starting venlafaxine is strongly advised for patients with existing risk factors.

Asthma Is Associated With a Subsequent Risk of Peripheral Artery Disease: A Longitudinal Population-Based Study.

Asthma has been associated with the atherosclerosis risk, but not clear of peripheral artery disease (PAD). We attempted to examine the risk of PAD in patients with asthma.From the insurance claims data of Taiwan, we identified 28,158 newly diagnosed asthma patients in 2000 to 2005 and 56,316 persons without asthma randomly selected into the comparison cohort, frequency matched by sex, age, and the date of diagnosis. Both cohorts were followed up until the end of 2011 to estimate the incident PAD. Adjusted hazard ratios (aHRs) of PAD were estimated using the Cox proportional hazards model after controlling for sex, age, and comorbidities.The incidence of PAD was 1.46 times higher in the asthma cohort than in the comparison cohort, with an aHR of 1.34 [95% confidence interval (CI) = 1.24-1.45]. Incidence of PAD was higher in men, the aged, and those with comorbidities in both cohorts. The aHRs of PAD remained significant for the asthma cohort in all subgroups of sex, age, and the presence of comorbidity. The aHRs of PAD were 14.1 (95% CI = 8.18-24.5) in asthma patients with multiple emergency visits and 22.3 (95% CI = 15.6-31.9) for those with multiple hospitalizations.Although smoking is a potential confounding factor, this study suggests patients with asthma have a significantly higher risk of developing PAD than the general population. The results also support the notion that poor control of asthma status is a key factor in subsequent PAD development.

Primary cardiac B-cell lymphoma with atrioventricular block and paroxysmal ventricular tachycardia.

Primary cardiac lymphoma (PCL) is very rare, and is extremely challenging to diagnose due to nonspecific symptoms. When discovered, the right atrium and ventricle are most commonly affected, while diffuse cardiac involvement is uncommon. PCL is fatal unless promptly diagnosed and treated. Herein, we present the case of a 36-year-old immunocompetent male who presented with a 5-year history of non-specific chest symptoms and was diagnosed with primary diffuse cardiac large B-cell lymphoma involving the entire heart.