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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.)

Introduction Atrial fibrillation (AF) was a significant independent risk factor for 1-year mortality of first acute ischemic stroke. The CHA2DS2-VASc scores were initially developed to assess the risk of stroke or systemic embolism in patients with AF. Recently, this scoring system have been demonstrated to have clinical value for predicting the severity of infarction and long-term clinical outcomes in acute ischemic stroke but the evidence is not strong enough due to limited numbers and single center data. Purpose This large-scale prospective cohort study aimed to investigate the independent predictive value of CHA2DS2-VASc scores and AF in such patients. Materials and methods We included patients from Taiwan Stroke Registry (TSR) with ischemic stroke within 2006 to 2016 as the present study population. Patients were mainly divided in atrial fibrillation (AF) group and non-AF group. We future classified patient by CHA2DS2-VASc (congestive heart failure, hypertension, age≥75 years, diabetes, previous stroke, vascular disease, age 65–74 years, sex category) score 0–1 and ≥2. The primary outcome was major adverse cardiovascular events (MACE), which include re-stroke, myocardial infarction and cardiovascular death, occurred within 1 year after the onset of stroke. The secondary outcome was the all-cause mortality. Results We defined 2972 patients with MACE and 61,937 patients without MACE. With adjusting with the confounding of CHA2DS2-VASc scores, The AF group was associated with increased MACE (OR=1.15; 95% CI=1.00, 1.33), myocardial infarction (adjusted OR=3.89; 95% CI=1.81, 8.34), CV death (OR=5.73; 95% CI=3.77, 8.69) and all-cause mortality (OR=1.50; 95% CI=1.37, 1.65) but not in re-stroke (adjusted OR=1.02; 95% CI=0.88, 1.18). After controlling for AF, patients with CHA2DS2-VASc scores ≥2 had significantly higher odds of MACE (OR=1.28; 95% CI=1.16, 1.41), re-stroke (OR=1.27; 95% CI=1.16, 1.40) and all-cause mortality (OR=2.26; 95% CI=2.06, 2.48) than that of patients with CHA2DS2-VASc scores 0–1. The survival curve revealed both AF and CHA2DS2-VASc scores are independent risk factors of 1 year MACE and mortality. By investigating the individual risk factor of CHA2DS2-VASc score, diabetes, hypertension and age over 65 years old increase the risk of MACE significantly. Conclusions CHA2DS2-VASc scores appear to have potent independent value as AF for predicting 1 year MACE and all-cause mortality in patients of acute ischemic stroke. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

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)-β1 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-β1 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.

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.

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 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.

We read with interest the study by Graef et al ,1 who mentioned about the treatment and safety of hydroxychloroquine (HCQ) for the current COVID-19 pandemic. They described that decades of research strongly support the well control of disease activity and survival benefit of HCQ use in rheumatic diseases, such as systemic lupus erythematosus and rheumatoid arthritis (RA). They also highlight that HCQ should be used with caution in patients with COVID-19, including the safety concern, especially when combined with administration of azithromycin because both of them are known corrected QT interval (QTc) prolongation agents. During early outbreak, HCQ, combined with azithromycin, has been used as a treatment option for COVID-19.2 3 Recently, an observational study with 1446 patients with COVID-19 reported that HCQ administration was not associated with a lower risk of intubation or death.4 However, the reasons for mortality were not illustrated. Multiple confounding factors like histories of ischaemic heart disease, heart failure and cardiac arrhythmia were not well adjusted. The main functional site of HCQ in COVID-19 is the entry via ACE2 preceptor.5 6 We believe that patient selection in early phases of COVID-19 infection would be more appropriate than well-established pneumonia or cytokines storm cases. The risk of cardiac arrhythmias is an important safety issue. HCQ …

Systemic lupus erythematosus (SLE) can affect all heart structures including the conduction system, with either reversible or permanent derangement. However, only a few cases of adult SLE and complete atrioventricular (AV) block have been reported. We describe a young pregnant woman who initially presented with complete AV block on electrocardiography before the diagnosis of SLE. Syncope subsequently developed during the postpartum period due to frequent nonsustained polymorphic ventricular tachycardia, suggesting lupus myocarditis. The ventricular arrhythmia was successfully treated by intravenous corticosteroids, lidocaine and implantation of a permanent pacemaker. This may represent the first report of complete AV block with polymorphic ventricular tachycardia, which was identified before the other clinical features of SLE fully manifested. SLE should be considered if a patient presents with complete AV block without other clinical features. It may warn for early diagnosis and appropriate treatment of SLE including lupus-related heart disease.

Patient Initials or Identifier Number Mr. W ### Relevant Clinical History and Physical Exam A 67-year-old man has a past history of hypertensive cardiovascular disease, Diabetes mellitus and dyslipidemia with medications control. He presented with intermittent chest tightness for 2 years

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 &plusmn, 9.3 years), and used the Medis&reg, 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&reg, 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.