An Updated Meta-Analysis on the Clinical Outcomes of Percutaneous Left Atrial Appendage Closure Versus Direct Oral Anticoagulation in Patients With Atrial Fibrillation.

The availability of direct oral anticoagulants (DOACs) with known lower bleeding risk compared with warfarin have raised questions about the role of left atrial appendage closure (LAAC). We aimed to perform a meta-analysis to compare the clinical outcomes for LAAC versus DOACs. All studies directly comparing LAAC with DOACs up to January 2023 were included. The outcomes studied included the combined major adverse cardiovascular (CV) events outcomes, ischemic stroke and thromboembolic events, major bleeding, CV mortality, and all-cause mortality. Hazard ratios (HRs) and their 95% confidence interval were extracted or estimated from the data and pooled together with a random-effects model. A total of 7 studies (1 randomized controlled trial, 6 propensity-matched observational studies) were finally included, with a pooled population of 4,383 patients who underwent LAAC and 4,554 patients on DOACs. There were no significant differences between patients who underwent LAAC and patients on DOACs in terms of baseline age (75.0 vs 74.7, p = 0.27), CHA2DS2-VASc score (5.1 vs 5.1, p = 0.33), or HAS-BLED score (3.3 vs 3.3, p = 0.36). After a mean weighted follow-up of 22.0 months, LAAC was associated with significantly lower rates of combined major adverse CV event outcomes (HR 0.73 [0.56 to 0.95], p = 0.02), all-cause mortality (HR 0.68 [0.54 to 0.86], p = 0.02), and CV mortality (HR 0.55 [0.41 to 0.72], p<0.01). There were no significant differences in the rates of ischemic stroke or systemic embolism (HR 1.12 [0.92 to 1.35], p = 0.25), major bleeding (HR 0.94 [0.67 to 1.32], p = 0.71), or hemorrhagic stroke (HR 1.07 [0.74 to 1.54], p = 0.74) between LAAC and DOAC. In conclusion, percutaneous LAAC was found to be as efficacious as DOACs for stroke prevention, with lower all-cause and CV mortality. The rates of major bleeding and hemorrhagic stroke were similar. LAAC has a potential role to play in stroke prevention in patients with atrial fibrillation in the era of DOACs, but further randomized data are needed.

Severe mitral regurgitation from Libman-Sacks endocarditis treated with MitraClip: a case report.

BACKGROUND: Systemic lupus erythematosus (SLE) valvulopathy can manifest as a spectrum of pathologies and treatment of severe valvular dysfunction thus far has been surgical. However, surgery in patients with SLE is frequently associated with high morbidity and mortality due to the presence of significant co-morbidities. CASE SUMMARY: We report the case of a 41-year-old woman with SLE and anti-phospholipid syndrome with extensive co-morbidities including lupus nephritis, pancytopaenia, cerebrovascular accident, and severe airway obstruction from ipsilateral lung collapse and bronchiectasis. She had severe mitral regurgitation (MR) from Libman-Sacks endocarditis and in recent months developed heart failure with progressive exertional dyspnoea from New York Heart Association (NYHA) functional Class from New York Heart Association (NYHA) functional class II to III. In addition, there was progressive left ventricular dilatation and reduction in left ventricular ejection fraction. In view of the high surgical risk, she underwent transcatheter edge-to-edge repair (TEER) of the mitral valve with the MitraClip system. At 1-month follow-up, she was back to NYHA functional Class II with mild MR. DISCUSSION: Our case demonstrates that in select patient with suitable anatomy, TEER is a potential treatment option for severe MR from SLE valvulopathy.

Diagnosis of anomalous origin and course of coronary arteries using non-contrast cardiac CT scan and detection features.

BACKGROUND: Anomalous origin and course of coronary arteries (AOCA) is a potential cause of sudden cardiac death. Coronary CT angiography (coronary CTA) enables detailed 3-dimensional visualization of AOCA. Data are limited about the diagnostic performance of noncontrast cardiac CT obtained during coronary calcium scan for detecting AOCA. OBJECTIVE: We assessed the feasibility of using noncontrast cardiac CT for detecting AOCA. METHODS: Participants had noncontrast cardiac CT and coronary CTA performed (2005-2010). Cases had AOCA as diagnosed with coronary CTA. Controls were without AOCA. Noncontrast cardiac CT images were independently evaluated for AOCA by a cardiologist and a radiologist blinded to prior AOCA diagnosis. Detection features to assist AOCA diagnosis on noncontrast cardiac CT were evaluated. RESULTS: The study enrolled 54 cases and 155 controls. Sensitivity and specificity for detecting AOCA were 82% (95% CI, 69%-90%) and 90% (95% CI, 85%-94%) for observer 1, respectively, and 82% (95% CI, 69%-90%) and 85% (95% CI, 79%-90%) for observer 2, respectively. Average sensitivity and specificity were 82% and 88%, respectively. Interobserver agreement (Cohen κ) was κ = 0.65 (95% CI, 0.53-0.76). Inability to visualize the right coronary artery (RCA) origin at the right sinus significantly predicted RCA anomaly. Inability to visualize the left main coronary artery branching point into the left anterior descending coronary artery and the left circumflex coronary artery significantly predicted left coronary artery anomaly. CONCLUSION: Noncontrast cardiac CT in conjunction with detection features has the potential for use in the diagnosis of AOCA. A prospective study is needed for validation and to determine the modality's accuracy for detecting AOCA.

Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice.

Mycolic acids are attractive diagnostic markers for tuberculosis (TB) infection because they are bacteria-derived, contain information about bacterial species, modulate host-pathogen interactions and are chemically inert. Here, we present a novel approach based on mass spectrometry. Quantification of specific precursor → fragment transitions of approximately 2000 individual mycolic acids (MAs) resulted in high analytical sensitivity and specificity. We next used this tool in a retrospective case-control study of patients with pulmonary TB with varying disease burdens from South Korea, Vietnam, Uganda and South Africa. MAs were extracted from small volume sputum (200 µl) and analysed without the requirement for derivatization. Infected patients (70, 19 of whom were HIV+) could be separated from controls (40, 20 of whom were HIV+) with a sensitivity and specificity of 94 and 93%, respectively. Furthermore, we quantified MA species in lung tissue of TB-infected mice and demonstrated effective clearance of MA levels following curative rifampicin treatment. Thus, our results demonstrate for the first time the feasibility and clinical relevance of direct detection of mycobacterial lipids as biomarkers of TB infection.

Derivatization-independent cholesterol analysis in crude lipid extracts by liquid chromatography/mass spectrometry: applications to a rabbit model for atherosclerosis.

Direct measurement of various sterols in crude lipid extracts in a single experiment from limited biological samples is challenging. Current mass spectrometry (MS) based approaches usually require chemical derivatization before subjecting to MS analysis. Here, we present a derivatization-independent method for analyzing various sterols, including cholesterol and its congeners, using liquid chromatography and atmospheric pressure chemical ionization mass spectrometry. Based on the specific tandem mass spectrometry pattern of cholesterol, multiple reaction monitoring (MRM) transitions were used to quantify free cholesterol and its fatty acyl esters. Several cholesterol oxidation products could also be measured using the upfront liquid chromatography separation and specific MRM transitions. The method was validated alongside established enzymatic assays in measuring total cholesterol. As a proof of concept, we analyzed plasma sterols in rabbits administrated with a high cholesterol diet (HCD) which is a classical atherosclerotic model. Free cholesterol, cholesterol esters, 7-hydroxycholesterol, and 7-ketocholesterol were elevated in plasma of rabbits on HCD. This method could also serve as an excellent tool for quantitative analysis of other sterols such as ergosterol and sitosterol in other organisms beside mammalian. In Saccharomyces cerevisiae, our results indicated dramatic increases of the ratio of ergosterol esters to free ergosterol in both yeh2Δ and tgl1Δ cells, which are consistent with the function of the respective enzymes.