Safety and efficacy of early varenicline prescription in hospitalized patients with acute myocardial infarction: East Asian population.

BACKGROUND: Smoking is a strong risk factor for patients with acute myocardial infarction (AMI). Varenicline is commonly used as a smoking cessation medication, but little is known about its usage in patients with AMI, particularly in hospitalized patients. METHODS: This is a prospective observational, single-center study collected from May 2018 to July 2021. Study patients underwent percutaneous coronary intervention for AMI. The primary end point was set as safety of varenicline, focusing on any serious adverse cardiac events within 24 weeks after treatment. Efficacy of smoking abstinence was also assessed through self-reports of complete abstinence over a week before the 24- week clinic visit. RESULTS: A total of 162 patients hospitalized with AMI were enrolled in our study. Mean age was 56.7 ± 9.95 years and 97% of the patients were male. Most patients (93.2%) received their first dose of varenicline during hospitalization. Time from admission to first dose of study medication was 2.31 ± 2.73 days and duration of drug intake was 7.41 ± 5.18 weeks. At week 24, only one patient had recurrent myocardial infarction, five patients had undergone revascularization for target lesion failure, and no additional patients developed stroke or died. In terms of efficacy, the rate of smoking abstinence was 79%. Light smokers found it easier to quit smoking than heavy smokers. CONCLUSION: This study may represent the first report on the safety and efficacy of early initiation of varenicline treatment in East Asian population hospitalized due to AMI who recently underwent percutaneous coronary intervention.

MicroRNA Let-7a, -7e and -133a Attenuate Hypoxia-Induced Atrial Fibrosis via Targeting Collagen Expression and the JNK Pathway in HL1 Cardiomyocytes.

Fibrosis is a hallmark of atrial structural remodeling. The main aim of this study was to investigate the role of micro-ribonucleic acids (miRNAs) in the modulation of fibrotic molecular mechanisms in response to hypoxic conditions, which may mediate atrial fibrosis. Under a condition of hypoxia induced by a hypoxia chamber, miRNA arrays were used to identify the specific miRNAs associated with the modulation of fibrotic genes. Luciferase assay, real-time polymerase chain reaction, immunofluorescence and Western blotting were used to investigate the effects of miRNAs on the expressions of the fibrotic markers collagen I and III (COL1A, COL3A) and phosphorylation levels of the stress kinase c-Jun N-terminal kinase (JNK) pathway in a cultured HL-1 atrial cardiomyocytes cell line. COL1A and COL3A were found to be the direct regulatory targets of miR-let-7a, miR-let-7e and miR-133a in hypoxic atrial cardiac cells in vitro. The expressions of COL1A and COL3A were influenced by treatment with miRNA mimic and antagomir while hypoxia-induced collagen expression was inhibited by the delivery of miR-133a, miR-let-7a or miR-let-7e. The JNK pathway was critical in the pathogenesis of atrial fibrosis. The JNK inhibitor SP600125 increased miRNA expressions and repressed the fibrotic markers COL1A and COL3A. In conclusion, MiRNA let-7a, miR-let-7e and miR-133a play important roles in hypoxia-related atrial fibrosis by inhibiting collagen expression and post-transcriptional repression by the JNK pathway. These novel findings may lead to the development of new therapeutic strategies.

CHA2DS2-VASc score as an independent outcome predictor in patients hospitalized with acute ischemic stroke.

PURPOSE: Atrial fibrillation (AF) is a significant independent risk factor for 1-year mortality in patients with first acute ischemic stroke (AIS). The CHA2DS2-VASc score was initially developed to assess the risk of stroke in patients with AF. Recently, this scoring system has been demonstrated to have clinical value for predicting long-term clinical outcomes in AIS but the evidence is insufficient. This large-scale prospective cohort study investigated the independent predictive value of the score in such patients. METHODS: We included patients with AIS from the Taiwan Stroke Registry (TSR) during 2006-2016 as the present study population. Patients were divided into those with high (≥2) and low (<2) CHA2DS2-VASc scores. We further analyzed and classified patients according to the presence of AF. The clinical endpoint was major adverse cardiac and cerebrovascular events (MACCEs) at 1 year after the index AIS. RESULTS: A total of 62,227 patients with AIS were enrolled. The median age was 70.3 years, and 59% of the patients were women. After confounding factors were controlled, patients with high CHA2DS2-VASc scores had significantly higher incidence of 1-year MACCEs (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI] = 1.52, 1.76), re-stroke (adjusted HR = 1.28; 95% CI = 1.16, 1.42), and all-cause mortality (adjusted HR = 2.03; 95% CI = 1.83, 2.24) than those with low CHA2DS2-VASc scores did. In the comparison between AF and non-AF groups, the AF group had increased MACCEs (adjusted HR = 1.74; 95% CI = 1.60, 1.89), myocardial infarction (adjusted HR = 4.86; 95% CI = 2.07, 11.4), re-stroke (adjusted HR = 1.47; 95% CI = 1.26, 1.71), and all-cause mortality (adjusted HR = 1.90; 95% CI = 1.72, 2.10). The Kaplan-Meier curve revealed that both CHA2DS2-VASc scores and AF were independent risk predictors for 1-year MACCEs and mortality. CONCLUSIONS: The CHA2DS2-VASc score and AF appeared to consistently predict 1-year MACCEs of AIS patients and provide more accurate risk stratification. Therefore, increased use of the CHA2DS2-VASc score may help improve the holistic clinical assessment of AIS patients with or without AF.

The Impact of Oxygen Pulse and Its Curve Patterns on Male Patients with Heart Failure, Chronic Obstructive Pulmonary Disease, and Healthy Controls-Ejection Fractions, Related Factors and Outcomes.

Oxygen pulse (O2P) is a function of stroke volume and cellular oxygen extraction and O2P curve pattern (O2PCP) can provide continuous measurements of O2P. However, measurements of these two components are difficult during incremental maximum exercise. As cardiac function is evaluated using ejection fraction (EF) according to the guidelines and EF can be obtained using first-pass radionuclide ventriculography, the aim of this study was to investigate associations of O2P%predicted and O2PCP with EF in patients with heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) and chronic obstructive pulmonary disease (COPD), and also in normal controls. This was a prospective observational cross-sectional study. Correlations of resting left ventricular EF, dynamic right and left ventricular EFs and outcomes with O2P% and O2PCP across the three participant groups were analyzed. A total of 237 male subjects were screened and 90 were enrolled (27 with HFrEF/HFmrEF, 30 with COPD and 33 normal controls). O2P% and the proportions of the three types of O2PCP were similar across the three groups. O2P% reflected dynamic right and left ventricular EFs in the control and HFrEF/HFmrEF groups, but did not reflect resting left ventricular EF in all participants. O2PCP did not reflect resting or dynamic ventricular EFs in any of the subjects. A decrease in O2PCP was significantly related to nonfatal cardiac events in the HFrEF/HFmrEF group (log rank test, p = 0.01), whereas O2P% and O2PCP did not predict severe acute exacerbations of COPD. The findings of this study may clarify the utility of O2P and O2PCP, and may contribute to the currently used interpretation algorithm and the strategy for managing patients, especially those with HFrEF/HFmrEF. (Trial registration number NCT05189301.).

Association of hydroxychloroquine and cardiac arrhythmia in patients with systemic lupus erythematosus: A population-based case control study.

OBJECTIVES: Hydroxychloroquine is widely used to treat certain viral and rheumatic diseases including systemic lupus erythematosus. Cardiac arrhythmia is an important safety issue with hydroxychloroquine. The aim of this study was to investigate whether hydroxychloroquine increases new-onset arrhythmia among patients with systemic lupus erythematosus. METHODS: This was a nested case-control study using data from the Longitudinal Health Insurance Database of Taiwan. A conditional logistic regression model was used to analyse differences in the risk of arrhythmia between systemic lupus erythematosus patients with and without hydroxychloroquine treatment after controlling for related variables. RESULTS: A total of 2499 patients with newly diagnosed systemic lupus erythematosus were identified (81% females), of whom 251 were enrolled in the new-onset arrhythmia group (mean age 50.4 years) and 251 in the non-arrhythmia group (mean age 49.1 years). There was no significantly increased risk of cardiac arrhythmia (adjusted odds ratio = 1.49, 95% confidence interval: 0.98-2.25) or ventricular arrhythmia (adjusted odds ratio = 1.02, 95% confidence interval: 0.19-5.41) between the patients with and without hydroxychloroquine treatment. In addition, there were no significant differences in the risk of arrhythmia between those receiving hydroxychloroquine treatment for <180 days or ≥180 days, with a drug adherence rate of <50% or ≥50%, and receiving a daily dose of <400 mg or ≥400 mg. CONCLUSION: In patients with systemic lupus erythematosus, hydroxychloroquine treatment did not significantly increase the risk of cardiac arrhythmia or life-threatening ventricular arrhythmia regardless of the different hydroxychloroquine treatment duration, drug adherence rate, or daily dose.

Role of the ROS-JNK Signaling Pathway in Hypoxia-Induced Atrial Fibrotic Responses in HL-1 Cardiomyocytes.

By promoting atrial structural remodeling, atrial hypoxia contributes to the development of the atrial fibrillation substrate. Our study aimed to investigate the modulatory effect of hypoxia on profibrotic activity in cultured HL-1 cardiomyocytes and explore the possible signaling transduction mechanisms of profibrotic activity in vitro. Hypoxia (1% O2) significantly and time-dependently increased the expression of hypoxia-inducible factor (HIF)-1α and fibrotic marker proteins collagen I and III (COL1A and COL3A), transforming growth factor (TGF)-ß1 and α-smooth muscle actin (SMA). Western blot or immunohistochemistry analysis showed that hypoxia-induced increase in COL1A and COL3A was significantly attenuated by the addition of SP600125 (a specific c-Jun N-terminal kinase [JNK] inhibitor) or expression of dominant-negative JNK before hypoxia treatment. The inhibition of hypoxia-activated phosphorylation of JNK signal components (JNK, MKK4, nuclear c-Jun and ATF-2) by pre-treatment with SP600125 could suppress hypoxia-stimulated HIF-1α upregulation and fibrotic marker proteins expression. Hypoxia significantly increased reactive oxygen species (ROS) production in cultured HL-1 atrial cells. Pre-treatment with N-acetylcysteine significantly abrogated the expression of nuclear HIF-1α, JNK transduction components and fibrotic marker proteins. Taken together, these findings indicated that the hypoxia-induced atrial profibrotic response occurs mainly via the ROS/JNK pathway, its downstream upregulation of HIF-1α and c-Jun/ATF2 phosphorylation and nuclear translocation to up-regulate the expression of fibrosis-related proteins (COL1A, COL3A, TGF-ß1 and α-SMA). Our result suggests that suppression of ROS/JNK signaling pathway is a critical mechanism for developing a novel therapeutic strategy against atrial fibrillation.

Hydroxychloroquine Does Not Increase the Risk of Cardiac Arrhythmia in Common Rheumatic Diseases: A Nationwide Population-Based Cohort Study.

Objectives: Hydroxychloroquine (HCQ) is widely used to treat rheumatic diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). Cardiac arrhythmia has been concerned as important safety issue for HCQ. The aim of this study was to investigate whether hydroxychloroquine increases new-onset arrhythmia among patients with RA, SLE or SS. Methods: This was a retrospective cohort study that conducted from the longitudinal health insurance database of Taiwan. Patients with newly diagnosed RA, SLE or SS with age ≥20 years old were selected from 2000 to 2012. Patients who received HCQ and without HCQ treatment groups were matched by propensity score to minimize the effect of selection bias and confounders. The Cox proportional hazard model was used to analyze the risk of arrhythmia between the two groups after controlling for related variables. Results: A total of 15892 patients were selected to participate and finally 3575 patients were enrolled in each group after matching. There was no different risk of all arrhythmia in patients using HCQ than without HCQ (adjusted hazards ratio 0.81, 95% CI 0.61-1.07) and ventricular arrhythmia as well. The incidence of arrhythmia did not increase when HCQ co-administrated with macrolides. The arrhythmia risk was also not different regardless of daily HCQ dose <400mg or ≥400mg or follow-up duration of ≦4 months or >4 months. Conclusion: The administration of HCQ did not increase the risk of all cardiac arrhythmia and ventricular arrhythmia regardless of different duration of treatment (≦4 months or >4 months) or cumulative dose (<400mg or ≥400mg) in patients with common autoimmune diseases such as RA, SLE and SS.

Immediate Results and Long-Term Outcomes Following Percutaneous Radiofrequency Ablation of Unilateral Aldosterone-Producing Adenoma.

BACKGROUND: The aim of this study was to evaluate early and long-term clinical and laboratory findings in patients with resistant hypertension secondary to aldosterone-producing adenoma (APA) treated with radiofrequency ablation (RFA). METHODS: From July 2009 to September 2017, eight adult patients underwent percutaneous computed tomography (CT)-guided RFA for APA. The safety, efficacy and complications of the procedure were determined. Blood pressure (BP), number of antihypertensive agents, serum potassium, plasma aldosterone and aldosterone-to-renin ratio (ARR) were analyzed before RFA and immediately, short-term and long-term after RFA. RESULTS: The technical success rate was 100%. Two patients developed minor complications but there were no major complications. Clinical improvement was achieved immediately and short-term after RFA. In the long-term (mean follow-up duration of 6.7 ± 2.1 years) there were significant improvements in systolic (from 162.3 mmHg ± 18.6 to 125 mmHg ± 16.1, p = 0.02) and diastolic (from 96.3 mmHg ± 12.7 to 68.5 mmHg ± 6.3, p = 0.02) BP, with a significant reduction in the number of antihypertensive agents (from 3.33 ± 0.82 to 1.33 ± 1.21, p = 0.02). Hypokalemia improved significantly (serum potassium from 2.16 meq/L ± 0.22 to 4.34 meq/L ± 0.54, p = 0.04). Although the plasma aldosterone level decreased significantly, ARR did not (from 100.7 ± 124.4 to 28.7 ± 30.7 ng/dL-per-ng/mL/h, p = 0.13). Hypertension was cured in 33.3% of the patients, and the BP of all patients was more easily controlled regardless of the plasma aldosterone and renin status. CONCLUSIONS: CT-guided percutaneous RFA appears to be effective and safe to treat patients with APA, with clinical improvements in BP, reduced number of antihypertensive agents, and normalization of serum potassium level. These favorable outcomes persisted in short-term and long-term follow-up.

Using the Pulse Contour Method to Measure the Changes in Stroke Volume during a Passive Leg Raising Test.

The pulse contour method is often used with the Windkessel model to measure stroke volume. We used a digital pressure and flow sensors to detect the parameters of the Windkessel model from the pulse waveform. The objective of this study was to assess the stability and accuracy of this method by making use of the passive leg raising test. We studied 24 healthy subjects (40 ± 9.3 years), and used the Medis® CS 1000, an impedance cardiography, as the comparing reference. The pulse contour method measured the waveform of the brachial artery by using a cuff. The compliance and resistance of the peripheral artery was detected from the cuff characteristics and the blood pressure waveform. Then, according to the method proposed by Romano et al., the stroke volume could be measured. This method was implemented in our designed blood pressure monitor. A passive leg raising test, which could immediately change the preloading of the heart, was done to certify the performance of our method. The pulse contour method and impedance cardiography simultaneously measured the stroke volume. The measurement of the changes in stroke volume using the pulse contour method had a very high correlation with the Medis® CS 1000 measurement, the correlation coefficient of the changed ratio and changed differences in stroke volume were r² = 0.712 and r² = 0.709, respectively. It was shown that the stroke volume measured by using the pulse contour method was not accurate enough. But, the changes in the stroke volume could be accurately measured with this pulse contour method. Changes in stroke volume are often used to understand the conditions of cardiac preloading in the clinical field. Moreover, the operation of the pulse contour method is easier than using impedance cardiography and echocardiography. Thus, this method is suitable to use in different healthcare fields.