Lipoprotein(a) as a cardiovascular risk factor among patients with and without diabetes Mellitus: the Mass General Brigham Lp(a) Registry.

BACKGROUND: Diabetes mellitus (DM) and Lp(a) are well-established predictors of coronary artery disease (CAD) outcomes. However, their combined association remains poorly understood. OBJECTIVE: To investigate the relationship between elevated Lp(a) and DM with CAD outcomes. METHODS: Retrospective analysis of the MGB Lp(a) Registry involving patients ≥ 18 years who underwent Lp(a) measurements between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasms, and prior atherosclerotic cardiovascular disease (ASCVD). The primary outcome was a combination of cardiovascular death or myocardial infarction (MI). Elevated Lp(a) was defined as > 90th percentile (≥ 216 nmol/L). RESULTS: Among 6,238 patients who met the eligibility criteria, the median age was 54, 45% were women, and 12% had DM. Patients with DM were older, more frequently male, and had a higher prevalence of additional cardiovascular risk factors. Over a median follow-up of 12.9 years, patients with either DM or elevated Lp(a) experienced higher rates of the primary outcome. Notably, those with elevated Lp(a) had a higher incidence of the primary outcome regardless of their DM status. The annual event rates were as follows: No-DM and Lp(a) < 90th% - 0.6%; No-DM and Lp(a) > 90th% - 1.3%; DM and Lp(a) < 90th% - 1.9%; DM and Lp(a) > 90th% - 4.7% (p < 0.001). After adjusting for confounders, elevated Lp(a) remained independently associated with the primary outcome among both patients with DM (HR = 2.66 [95%CI: 1.55-4.58], p < 0.001) and those without DM (HR = 2.01 [95%CI: 1.48-2.74], p < 0.001). CONCLUSIONS: Elevated Lp(a) constitutes an independent and incremental risk factor for CAD outcomes in patients with and without DM.

Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials.

OBJECTIVES: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes. We performed a meta-analysis to assess tirzepatide's weight reduction efficacy and safety. METHODS: We searched PubMed, Embase, and Cochrane for randomized controlled trials published from inception to July 2022, comparing tirzepatide with placebo for the co-primary endpoints of absolute and percent change in weight. Mean difference (MD) and odds ratio (OR) were calculated for continuous and binary outcomes, respectively. Review Manager 5.4.1 and RStudio were used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. RESULTS: Of 397 search results, 6 studies (4036 participants) ranging from 12 to 72 weeks were included. Pooled analysis showed that tirzepatide 5 mg, 10 mg, and 15 mg were more effective than placebo, with MD in body weight of -7.7 kg (95% CI -11.0, -4.4; p < 0.001), -11.6 kg (95% CI -18.8, -4.3; p = 0.002), and -11.8 kg (95% CI -17.4, -6.2; p < 0.001), respectively, and MD in percent change in weight of -8.1% (95% CI -11.0, -5.2; p < 0.001), -11.9% (95% CI -18.1, -5.6; p < 0.001), and -12.4% (95% CI -17.2, -7.5; p < 0.001), respectively. Tirzepatide also reduced BMI and waist circumference. Adverse events were more common with tirzepatide with respect to nausea (OR 4.2; 95% CI 2.4, 7.5; p < 0.001), vomiting (OR 7.0; 95% CI 4.3, 11.4; p < 0.001), and diarrhea (OR 2.8; 95% CI 1.6, 4.9; p < 0.001) (15 mg dose), when compared with placebo. CONCLUSIONS: The results support that tirzepatide leads to substantial weight reduction and constitutes a valuable therapeutic option for weight management, despite an increase in gastrointestinal symptoms. PROTOCOL REGISTRATION: CRD42022348576.

Pretreatment with P2Y12 inhibitors in ST-elevation myocardial infarction: A systematic review and meta-analysis.

BACKGROUND: Pretreatment with oral P2Y12 inhibitors is a standard practice for ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). However, the efficacy and safety of P2Y12 inhibitors pretreatment remain unclear. OBJECTIVES: We conducted a meta-analysis to investigate the impact of P2Y12 inhibitor pretreatment on thrombotic and hemorrhagic endpoints in STEMI patients. METHODS: We searched multiple databases for studies that compared P2Y12 inhibitor pretreatment with no pretreatment in STEMI patients and reported endpoints of interest. Random effects model was used for the meta-analysis. RESULTS: Our meta-analysis included 3 randomized controlled trials and 14 observational studies, comprising 70,465 patients assigned to either P2Y12 inhibitor pretreatment (50,328 patients) or no pretreatment (20,137 patients). Compared to no pretreatment, P2Y12 inhibitor pretreatment did not result in significant reductions in all-cause mortality (risk ratio [RR] 0.73; 95% confidence interval [CI]: 0.52-1.03; p = 0.07), myocardial infarction (RR 0.75; 95% CI: 0.53-1.07; p = 0.11), or major bleeding (RR 0.80; 95% CI: 0.56-1.16; p = 0.22) at 30 days. However, our subgroup analysis revealed that P2Y12 inhibitor pretreatment administered in the pre-hospital setting was associated with a significant reduction in the incidence of myocardial infarction compared to no pretreatment (RR 0.73; 95% CI: 0.56-0.91; p < 0.01). CONCLUSION: Our analysis suggests that pretreatment with oral P2Y12 inhibitors before PCI in patients with STEMI was not associated with reduced all-cause mortality, myocardial infarction, or major bleeding. However, pretreatment with P2Y12 inhibitors in the pre-hospital setting appears to be beneficial in reducing reinfarction.

Extra-coronary Calcification and Cardiovascular Events: What Do We Know and Where Are We Heading?

PURPOSE OF REVIEW: The coronary artery calcium score is a guideline-endorsed aid for further risk stratification in the primary prevention of atherosclerotic cardiovascular disease. The non-contrast scan performed for detection of coronary artery calcium also gives an opportunity to visualize calcifications in the thoracic aorta and in the heart valves, at no additional cost or radiation exposure. The purpose of this review was to discuss the potential clinical value of measuring thoracic aortic calcification, aortic valve calcification, and mitral annulus calcification. RECENT FINDINGS: After two decades of active research, all three calcifications have been extensively evaluated, across various cohorts. We discuss classic and recent studies, current knowledge gaps, and future directions in this space. The added value of these measurements has traditionally been considered modest at best, and they are not currently discussed in relevant primary prevention guidelines in North America and Europe. However, recent studies evaluating high thoracic calcification thresholds and younger populations have further enriched this space. Specifically, some studies suggest that detection of severe thoracic aortic calcification may be helpful in further risk assessment and that detection of aortic valve calcifications may have important prognostic implications in younger individuals. Although more research is needed, particularly in larger young-to-middle-aged cohorts, future guidelines might consider including these features as risk-enhancing factors.

Long-term outcomes of percutaneous versus surgical revascularization in patients with diabetes and left main coronary artery disease: A meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy and safety of percutaneous coronary interventions (PCI) relative to coronary artery bypass grafting (CABG) in patients with diabetes and unprotected left main coronary artery disease (LMCAD) are not well established. OBJECTIVES: To perform a meta-analysis evaluating the long-term outcomes after PCI with drug-eluting stents (DES), as compared with CABG, in patients with diabetes and unprotected LMCAD. METHODS: MEDLINE, Cochrane, and Embase were searched for randomized controlled trials (RCTs) that reported outcomes after PCI with DES versus CABG in unprotected LMCAD among patients with diabetes. To evaluate the long-term effects of these interventions, we restricted this analysis to studies with a minimum follow-up period of 3 years. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. Quality assessment and risk of bias were performed according to Cochrane recommendations. RESULTS: Four RCTs with a total of 1080 patients were included, 553 (51.2%) of whom underwent PCI. There was no difference for individual outcomes of all-cause mortality (RR: 1.21; 95% CI: 0.86-1.71; p = .27; I2 = 28%), cardiovascular death (RR 1.29; 95% CI: 0.76-2.18; p = .34; I2 = 0%), or myocardial infarction (MI) (RR: 0.94; 95% CI: 0.61-1.45; p = .79; I2 = 0%). However, the risk of stroke was reduced with PCI relative to CABG (RR: 0.41; 95% CI: 0.18-0.94; p = .04; I2 = 0%), whereas the risk of any repeat revascularization was higher in the PCI group (RR: 1.99; 95% CI: 1.44-2.75; p < .001; I2 = 0%). The risk of the composite outcome of all-cause mortality, MI, stroke, or repeat revascularization was higher after PCI compared with CABG (RR: 1.30; 95% CI: 1.09-1.56; p = .004; I2 = 0%). CONCLUSION: In this meta-analysis with more than 1000 patients with diabetes and unprotected LMCAD followed for a minimum of 3 years, the incidence of repeat revascularization was higher among those treated with PCI, whereas the risk of stroke was higher in patients treated with CABG.

Prevention of Stroke in Atrial Fibrillation After Coronary Stenting.

Background and Purpose- The optimal antithrombotic strategy to balance thromboembolic and bleeding events, especially acute stroke, for patients with atrial fibrillation following coronary stenting remains a matter of debate. We conducted a network meta-analysis to identify the antithrombotic regimen associated with the lowest rate of bleeding and thromboembolic events in atrial fibrillation after coronary stenting. Methods- PubMed, Scopus, and Cochrane Central were searched for randomized controlled trials and observational studies of patients with atrial fibrillation after coronary stenting. The outcomes of interest were stroke, myocardial infarction, major adverse cardiac events, mortality, and major bleeding. A network meta-analysis was performed comparing the available antithrombotic regimens in the literature. Results- Three randomized and 15 observational studies were included, with a total of 23 478 participants. Median follow-up was 2 years. Network meta-analysis demonstrated that vitamin K antagonist plus single antiplatelet therapy or direct-acting oral anticoagulant plus single antiplatelet therapy were the most effective regimens in preventing stroke. Direct-acting oral anticoagulant regimens were associated with lower major bleeding rates than vitamin K antagonist regimens. Regimens with dual antiplatelet therapy were associated with lower rates of myocardial infarction. Vitamin K antagonist plus dual antiplatelet therapy was associated with a lower mortality and low-dose direct-acting oral anticoagulants with decreased major cardiovascular adverse events. Conclusions- Direct-acting oral anticoagulant regimens were associated with less major bleeding and major cardiovascular adverse events, but vitamin K antagonists were associated with decreased mortality and stroke. These results suggest that the decision of antithrombotic therapy in patients with atrial fibrillation after percutaneous coronary intervention needs to be individualized.

Endo-epicardial vs endocardial-only catheter ablation of ventricular tachycardia: A meta-analysis.

INTRODUCTION: The efficacy of endocardial catheter ablation for ventricular tachycardia (VT) can be limited by intramural or epicardial substrates. Adding epicardial mapping and ablation may improve arrhythmia outcomes compared with an endocardial-only approach. METHODS: We performed a systematic review and meta-analysis of studies comparing a strategy of endo-epicardial catheter ablation to an endocardial-only approach for VT. Subanalyses were performed for ischemic and nonischemic cardiomyopathies. RESULTS: A total of 22 studies including 1138 patients were included in the meta-analysis. Of those, 44% underwent an endo-epicardial approach. During intermediate to long-term follow-up (average 7 to 70 months), recurrent VT or appropriate implantable cardioverter defibrillator (ICD) therapies were significantly lower with the endo-epicardial strategy (OR, 0.52; P < .01). All-cause mortality was also lower in this group (OR, 0.50; P = .03). No difference between endo-epicardial and endocardial-only ablation was noted in nonischemic cardiomyopathies. Among 323 patients with ischemic cardiomyopathy, recurrent VT or appropriate ICD therapies was less frequent in the endo-epicardial group (OR, 0.39; P = .01), as was all-cause mortality (OR, 0.38; P = .05). In patients with arrhythmogenic right ventricular cardiomyopathy, recurrent VT or appropriate ICD therapy was also lower in the endo-epicardial group (OR, 0.42; P = .04). CONCLUSION: These results suggest that a strategy of combined endo- and epicardial access for mapping and ablation of VT may provide superior efficacy to an endocardial-only approach in selected patients. Randomized trials are warranted to further investigate this question.

Cryoballoon versus Radiofrequency Catheter Ablation in Atrial Fibrillation: A Meta-Analysis.

INTRODUCTION: Radiofrequency (RF) and cryoballoon (CB) catheter ablation are effective for pulmonary vein isolation (PVI) in atrial fibrillation (AF). This report presents an updated meta-analysis comparing the efficacy and safety of CB versus RF ablations in AF. METHODS: Databases and conference abstracts were systematically searched for studies that directly compared CB and RF PVI, and reported safety or efficacy outcomes in follow-up ≥12 months. Recurrent atrial tachyarrhythmias (AT) were defined as AF, atrial flutter, or atrial tachycardia. RESULTS: Twenty-two studies and 8,668 patients were included. Freedom from AT was not significantly different between CB and RF ablations in the pooled population (OR 1.12; 95%CI 0.97-1.29; P = 0.13) and in randomized trials (OR 1.0; 95%CI 0.65-1.56; P = 0.99). Second-generation CB (CB2; 78.1%) and contact-force (CF) sensing RF (78.2%) have improved procedure success rate as compared to first-generation technology (57.9% CB, 58.1% RF). As compared to CF-RF, CB2 demonstrated similar freedom from recurrent AT (OR 1.04; 95%CI 0.71-1.51; P = 0.84). The incidence of pericardial effusions (OR 0.44; 95%CI 0.28-0.69; P < 0.01), tamponade (OR 0.31; 95%CI 0.15-0.64; P < 0.01), and non-AF AT (OR 0.46; 95%CI 0.26-0.83; P < 0.01) were significantly lower with CB ablation, whereas transient phrenic nerve palsy was more incident after CB (OR 7.40; 95%CI 2.56-21.34; P < 0.01). CONCLUSION: There was comparable freedom from AT between CB and RF in patients with AF undergoing PVI. Additionally, freedom from AT was similar between CB2 and CF-RF. However, CB was associated with a lower incidence of pericardial effusions or tamponade, albeit with a higher rate of transient phrenic nerve palsies.

The Prevalence of Atrial Fibrillation and Conduction Abnormalities in Chagas' Disease: A Meta-Analysis.

BACKGROUND/OBJECTIVES: Chagas' disease (CD) has been associated with atrial fibrillation (AF) and electrocardiographic (ECG) conduction defects. However, prior studies have shown conflicting results. We performed a meta-analysis comparing the prevalence of AF and conduction abnormalities between CD and non-CD patients. METHODS: PubMed, EMBASE, Cochrane Central, and Latin American databases were searched for studies that directly compared the prevalence of AF and conduction defects in CD and non-CD patients. Odds ratios (OR) were computed using random-effects model due to anticipated heterogeneity. We further performed subanalyses limited to studies that included only patients with cardiomyopathy. RESULTS: A total of 17,238 patients from 30 studies were included, of whom 6,840 (40%) had a positive serology for CD. In the pooled data, AF was significantly more prevalent in the CD group (OR 1.62; 95%CI 1.21-2.15; P = 0.001). However, no significant difference was observed between groups when the analysis included only patients with cardiomyopathy (OR 1.21; 95%CI 0.97-1.50; P = 0.08) or heart failure (OR 1.09; 95%CI 0.81-1.47; P = 0.55). The combination of right bundle branch block (RBBB) and left anterior fascicular block (LAFB) had the highest OR for increased prevalence in patients with Chagas' cardiomyopathy compared to non-CD etiologies (OR 5.31; 95%CI 1.23-22.86; P = 0.03). CONCLUSIONS: Our meta-analysis suggests that the prevalence of AF in patients with Chagas' cardiomyopathy is not significantly different from non-CD cardiomyopathies. The pattern of RBBB and LAFB in patients with cardiomyopathy of unknown etiology and epidemiologic risk factors should raise the possibility of CD and prompt specific diagnostic testing.

Prestenting for prevention of melody valve stent fractures: A systematic review and meta-analysis.

INTRODUCTION: The role of right ventricular outflow tract (RVOT) prestenting in the prevention of Melody valve stent fractures (SFs) is not well defined. We aimed to perform a systematic review and meta-analysis comparing the incidence of SF in Melody valve transcatheter pulmonary implants with and without prestenting. METHODS: PubMed, EMBASE, and Cochrane Central were searched for studies that reported the incidence of SF in Melody valve transcatheter pulmonary implants stratified by the presence or absence of RVOT prestenting. Subgroup analyses were performed for (1) SF associated with a loss of stent integrity and (2) SF requiring reintervention. RESULTS: Five studies and 360 patients were included, of whom 207 (57.5%) received prestenting. Follow-up ranged from 15 to 30 months. SF were significantly reduced in the prestenting group (16.7%) when compared to no prestenting (33.5%) (odds-ratio [OR] 0.39; 95%CI 0.22-0.69). Patients who received prestenting also had a lower incidence of (1) SF associated with loss of stent integrity (OR 0.16; 95%CI 0.05-0.48) and (2) SF requiring reintervention (OR 0.15; 95%CI 0.02-0.91). CONCLUSION: Our findings suggest that stenting of the RVOT prior to Melody valve implantation is associated with a reduction in the incidence of SF and fracture-related reinterventions.

Vascular brachytherapy versus drug-eluting stents in the treatment of in-stent restenosis: A meta-analysis of long-term outcomes.

INTRODUCTION: Clinical trials have shown a short-term benefit of drug-eluting stents (DES) compared to vascular brachytherapy (VBT) for treatment of in-stent restenosis (ISR). The long-term benefits of DES vs. VBT are conflicting in the literature. This study aimed to do a meta-analysis of long-term outcomes of DES compared to VBT for treatment of ISR. METHODS: PubMed, EMBASE, Cochrane Central and unpublished data were searched for cohort studies and randomized controlled trials (RCTs) that directly compared VBT to DES for the treatment of ISR. We evaluated the following outcomes at 2-5 years of follow-up: target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), stent thrombosis, cardiovascular (CV) mortality, and overall mortality. Heterogeneity was defined as I(2) values > 25%. Review Manager 5.1 was used for statistical analysis. RESULTS: We included 1,375 patients from five studies, of which three were RCTs. VBT was used to treat ISR in 685 (49.8%) patients. After a 2-5 year follow-up, no significant differences were found between treatment groups regarding MI (P = 0.49), stent thrombosis (P = 0.86), CV mortality (P = 0.35), and overall mortality (P = 0.71). TLR (OR 2.37; CI 1.55-3.63; P < 0.001) and TVR (OR 2.23; CI 1.01-4.94; P = 0.05) were significantly increased in patients who received VBT. CONCLUSION: This study suggests that DES are associated with decreased long-term revascularization procedures when compared to VBT for the treatment of ISR. This benefit does not appear to be associated with a significant reduction in mortality or myocardial infarction.

Complications and Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement With Edwards SAPIEN & SAPIEN XT Valves: A Meta-Analysis of World-Wide Studies and Registries Comparing the Transapical and Transfemoral Accesses.

INTRODUCTION: Both transfemoral (TF) and transapical (TA) routes are utilized for Transcatheter Aortic Valve Replacement (TAVR) using Edwards SAPIEN & SAPIEN XT valves. We intended to perform a meta-analysis comparing the complication rates between these two approaches in studies published before and after the standardized Valve Academic Research Consortium (VARC) definitions. METHODS: We performed a comprehensive electronic database search for studies published until January 2014 comparing TF and TA approaches using the Edwards SAPIEN/SAPIEN XT aortic valve. Studies were analyzed based on the following endpoints: 1-year mortality, 30-day mortality, stroke, new pacemaker implantation, bleeding, and acute kidney injury. RESULTS: Seventeen studies were included in the meta-analysis. Patients undergoing TA TAVR had a significantly higher logistic EuroSCORE (24.6 ± 12.9 vs. 21.3 ± 12.0; P < 0.001). The cumulative risks for 30-day mortality (RR 0.61; 95%CI 0.46-0.81; P = 0.001), 1-year mortality (RR 0.68; 95%CI 0.55-0.84; P < 0.001), and acute kidney injury (RR 0.53; 95%CI 0.38-0.73; P < 0.001) were significantly lower for patients undergoing TF as compared to TA approach. Both approaches had a similar incidence of 30-day stroke, pacemaker implantation, and major or life-threatening bleeding. Studies utilizing the VARC definitions and those pre-dating VARC yielded similar results. CONCLUSION: This meta-analysis demonstrates a decreased 30-day and 1-year mortality in TF TAVR as compared to TA TAVR. Post-procedure acute kidney injury and the need for renal replacement therapy are also significantly lower in the TF group. These differences hold true even after utilizing the standardized Valve Academic Research Consortium criteria.

ICD discrimination of SVT versus VT with 1:1 V-A conduction: A review of the literature.

Inappropriate ICD shocks are associated with increased mortality. They also impair patients' quality of life, increase hospitalizations, and raise health-care costs. Nearly 80% of inappropriate ICD shocks are caused by supraventricular tachycardia. Here we report the case of a patient who received a single-lead dual-chamber sensing ICD for primary prevention of sudden cardiac death and experienced inappropriate ICD shocks. V-A time, electrogram morphology, and response to antitachycardia pacing suggested atrioventricular nodal reentry tachycardia, which was confirmed in an electrophysiology study. Inspired by this case, we performed a literature review to discuss mechanisms for discrimination of supraventricular tachycardia with 1:1 A:V relationship from ventricular tachycardia with 1:1 retrograde conduction.

Chagas cardiomyopathy is associated with higher incidence of stroke: a meta-analysis of observational studies.

BACKGROUND: Chagas disease (CD) has been associated with an elevated risk of stroke, but current data are conflicting and prospective controlled studies are lacking. We performed a systematic review and meta-analysis examining the association between stroke and CD. METHODS: Pubmed, Embase, Cochrane Central, Latin American database, and unpublished data were searched with the use of the following terms: ("Chagas" OR "American trypanosomiasis") AND ("dilated" OR "ischemic" OR "idiopathic" OR "nonChagasic" OR "stroke" OR "cerebrovascular"). We included studies that reported prevalence or incidence of stroke in a CD group compared with a non-CD control group. Odds ratios (ORs) and their 95% confidence intervals (CIs) were computed with the use of a random-effects model. RESULTS: A total of 8 studies and 4,158 patients were included, of whom 1,528 (36.7%) had CD. Risk of stroke was elevated in the group of patients with CD (OR 2.10, 95% CI 1.17-3.78). Similar results were observed in a subanalysis of cardiomyopathy patients (OR 1.74, 95% CI 1.02-3.00) and in sensitivity analysis with removal of each individual study. Furthermore, exclusion of studies at higher risk for bias also yielded consistent results (OR 1.70, 95% CI 1.06-2.71). Subanalysis restricted to studies that included patients with the indeterminate form found no significant difference in the stroke prevalence between CD and non-CD patients (OR 3.10, 95% CI 0.89-10.77). CONCLUSIONS: CD is significantly associated with cerebrovascular events, particularly among patients with cardiomyopathy. These findings underline the need for prospective controlled studies in patients with Chagas cardiomyopathy to ascertain the prognostic significance of cerebrovascular events and to evaluate the role of therapeutic anticoagulation in primary prevention.

The relation between FoxP3⁺ regulatory T cells and fungal density in oral paracoccidioidomycosis: a preliminary study.

Regulatory T (Treg) cells may play an important role in the pathogenesis of paracoccidioidomycosis (PCM), but data on the role of Treg cells in the context of oral PCM are still scarce. The objectives of this study were to investigate the density of FoxP3(+) T regulatory cells in oral PCM and to correlate the results with the density of Paracoccidioides brasiliensis in the lesions. Cases of chronic oral PCM seen between 2000 and 2008 were included in this study. The diagnosis of all lesions was confirmed with histopathological examination and Grocott-Gomori staining. The quantitative analysis of the viable fungi was conducted in all cases with Grocott-stained slides. Treg cells were identified using antibodies against FoxP3. Pearson correlation coefficient was used to test the correlation between the density of fungi and Treg cells. Results were considered significant when P < 0.05. A total of 11 cases of oral PCM were obtained. There was a positive correlation between fungal density and FoxP3(+) Treg cells density in oral lesions, however, without statistical significance. A positive relation between Treg cells and fungal density was seen in oral PCM. Further studies are required to further elucidate the role of these cells in the pathogenesis of oral PCM, as well the clinical significance of these findings.

Chronic Anticoagulation in Patients with Atrial Fibrillation and COVID-19: A Systematic Review and Meta-Analysis. / Anticoagulação Crônica em Pacientes com Fibrilação Atrial e COVID-19: Uma Revisão Sistemática e Metanálise.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with hypercoagulability. It remains uncertain whether ongoing anticoagulation for atrial fibrillation (AF) in patients who later contract COVID-19 improves clinical outcomes. OBJECTIVES: To compare chronic oral anticoagulation with no previous anticoagulation in patients with AF who contracted a COVID-19 infection concerning the outcomes of all-cause mortality, COVID-19 mortality, intensive care unit (ICU) admission, and hospitalization. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for eligible studies from inception to December 2022. We included studies comparing COVID-19 outcomes in patients with versus without prior chronic anticoagulation for AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random-effects model. The level of significance was set at p < 0.05. Quality assessment and risk of bias were performed according to Cochrane recommendations. RESULTS: Ten studies comprising 1,177,858 patients with COVID-19 and AF were identified, of whom 893,772 (75.9%) were on prior chronic anticoagulation for AF. In patients with COVID-19, being on chronic anticoagulation for AF significantly reduced all-cause mortality (RR 0.75; 95% CI 0.57 to 0.99; p = 0.048; I2 = 89%) and COVID-19-related mortality (RR 0.76; 95% CI 0.72 to 0.79; p < 0.001; I2 = 0%) when compared with no prior anticoagulation. In contrast, there was no difference between groups regarding hospitalization (RR 1.08; 95% CI 0.82 to 1.41; p = 0.587; I2 = 95%) or ICU admission (RR 0.86; 95% CI 0.68 to 1.09; p = 0.216; I2 = 69%). CONCLUSIONS: In this meta-analysis, chronic anticoagulation for patients with AF who contracted COVID-19 was associated with significantly lower rates of all-cause mortality and COVID-19-related mortality as compared with no previous anticoagulation.

FUNDAMENTO: A doença por coronavírus 2019 (COVID-19) está associada à hipercoagulabilidade. Permanece incerto se a anticoagulação contínua para fibrilação atrial (FA) em pacientes que posteriormente contraem COVID-19 melhora os desfechos clínicos. OBJETIVOS: Comparar a anticoagulação oral crônica com ausência de anticoagulação prévia em pacientes com FA que contraíram uma infecção por COVID-19 em relação aos desfechos de mortalidade por todas as causas, mortalidade por COVID-19, admissão em unidade de terapia intensiva (UTI) e hospitalização. MÉTODOS: Buscamos sistematicamente no PubMed, Embase e Cochrane Library estudos elegíveis desde o início até dezembro de 2022. Incluímos estudos que compararam desfechos de COVID-19 em pacientes com e sem anticoagulação crônica prévia para FA. Foram agrupadas razões de risco (RR) com intervalos de confiança (IC) de 95% por meio de um modelo de efeitos aleatórios. O nível de significância foi estabelecido em p < 0,05. As avaliações da qualidade e do risco de viés foram realizadas de acordo com as recomendações da Cochrane. RESULTADOS: Foram identificados 10 estudos abrangendo 1.177.858 pacientes com COVID-19 e FA, dos quais 893.772 (75,9%) estavam em anticoagulação crônica prévia para FA. Em pacientes com COVID-19, a anticoagulação crônica para FA reduziu significativamente a mortalidade por todas as causas (RR 0,75; IC 95% 0,57 a 0,99; p = 0,048; I2 = 89%) e a mortalidade relacionada à COVID-19 (RR 0,76; IC 95% 0,72 a 0,79; p < 0,001; I2 = 0%) quando comparada com a ausência de anticoagulação prévia. Em contrapartida, não houve diferença entre os grupos em relação à hospitalização (RR 1,08; IC 95% 0,82 a 1,41; p = 0,587; I2 = 95%) ou internação em UTI (RR 0,86; IC 95% 0,68 a 1,09; p = 0,216; I2 = 69%). CONCLUSÕES: Nesta metanálise, a anticoagulação crônica para pacientes com FA que contraíram COVID-19 foi associada a taxas significativamente mais baixas de mortalidade por todas as causas e mortalidade relacionada à COVID-19 em comparação com a ausência de anticoagulação anterior.

Changes in use of preventive medications after assessment of chest pain by coronary computed tomography angiography: A meta-analysis.

BACKGROUND: Coronary computed tomography angiogram (CCTA) is a crucial tool for diagnosing CAD, but its impact on altering preventive medications is not well-documented. This systematic review aimed to compare changes in aspirin and statin therapy following CCTA and functional stress testing in patients with suspected CAD, and in those underwent CCTA when stratified by the presence/absence of plaque. RESULTS: Eight studies involving 42,812 CCTA patients and 64,118 cardiac stress testing patients were analyzed. Compared to functional testing, CCTA led to 66 â€‹% more changes in statin therapy (pooled RR, 95 â€‹% CI [1.28-2.15]) and a 74 â€‹% increase in aspirin prescriptions (pooled RR, 95 â€‹% CI [1.34-2.26]). For medication modifications based on CCTA results, 13 studies (47,112 patients with statin data) and 11 studies (12,089 patients with aspirin data) were included. Patients with any plaque on CCTA were five times more likely to use or intensify statins compared to those without CAD (pooled RR, 5.40, 95 â€‹% CI [4.16-7.00]). Significant heterogeneity remained, which decreased when stratified by diabetes rates. Aspirin use increased eightfold after plaque detection (pooled RR, 8.94 [95 â€‹% CI, 4.21-19.01]), especially with obstructive plaque findings (pooled RR, 9.41, 95 â€‹% CI [2.80-39.02]). CONCLUSION: In conclusion, CCTA resulted in higher changes in statin and aspirin therapy compared to cardiac stress testing. Detection of plaque by CCTA significantly increased statin and aspirin therapy.

Early Initiation of PCSK9 Inhibitor Therapy Versus Placebo in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

In patients with stable atherosclerotic cardiovascular disease, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) have shown a 50% to 60% reduction in low-density lipoprotein cholesterol (LDL-C) from baseline when added to high-intensity statin therapy. However, less is known about the impact of PCSK9is in the setting of an acute coronary syndrome (ACS). Therefore, we performed a systematic review and meta-analysis comparing PCSK9is with placebo in the setting of ACS added to guideline-directed high-intensity or maximally tolerated statin therapy. We included randomized controlled trials with initiation of a PCSK9i or placebo within 1 week of presentation or percutaneous coronary intervention for ACS. PubMed, EMBASE, and Cochrane Central were searched. This study followed the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations. A total of 6 randomized controlled trials were included, with a total of 996 patients, of whom 503 (50.5%) received PCSK9is. The mean follow-up ranged from 4 to 52 weeks. The LDL-C (mean difference [MD] -44.0 mg/100 ml, CI -54.3 to -33.8, p <0.001) and lipoprotein (a) levels (MD -24.0 nmol/L, confidence interval [CI] -43.0 to -4.9, p = 0.01) were significantly lower at follow-up with PCSK9is. Similarly, the total cholesterol (MD -49.2 mg/100 ml, CI -59.0 to -39.3), triglycerides (MD -19.0 mg/100 ml, CI -29.9 to -8.2), and apolipoprotein B (MD -33.3 mg/100 ml, CI -44.4 to -22.1) were significantly reduced with PCSK9is. In conclusion, in patients with ACS, early initiation of PCSK9i added to statin significantly reduces LDL-C and lipoprotein (a) levels compared with placebo. Whether the differences in these atherogenic lipoproteins translate into a reduction in clinical end points is yet to be determined.

Artificial Intelligence in Coronary Artery Calcium Scoring Detection and Quantification.

Coronary artery calcium (CAC) is a marker of coronary atherosclerosis, and the presence and severity of CAC have been shown to be powerful predictors of future cardiovascular events. Due to its value in risk discrimination and reclassification beyond traditional risk factors, CAC has been supported by recent guidelines, particularly for the purposes of informing shared decision-making regarding the use of preventive therapies. In addition to dedicated ECG-gated CAC scans, the presence and severity of CAC can also be accurately estimated on non-contrast chest computed tomography scans performed for other clinical indications. However, the presence of such "incidental" CAC is rarely reported. Advances in artificial intelligence have now enabled automatic CAC scoring for both cardiac and non-cardiac CT scans. Various AI approaches, from rule-based models to machine learning algorithms and deep learning, have been applied to automate CAC scoring. Convolutional neural networks, a deep learning technique, have had the most successful approach, with high agreement with manual scoring demonstrated in multiple studies. Such automated CAC measurements may enable wider and more accurate detection of CAC from non-gated CT studies, thus improving the efficiency of healthcare systems to identify and treat previously undiagnosed coronary artery disease.