Cardiometabolic risk factors in adults with normal weight obesity: A systematic review and meta-analysis.

Normal weight obesity (NWO) is a new emerging phenotype of obesity, defined as a normal body mass index with a high body fat percentage. While several studies have described the impact of NWO on cardiometabolic risk factors, the association between them remains uncertain. This meta-analysis systematically evaluated cardiometabolic risk factors in adults with NWO compared to adults with normal weight lean (NWL). A systematic literature search was performed from the inception until September 21, 2021 in order to comprehensively search for all observational studies that had three important variables, including adults (age ≥18 years old), NWO and cardiometabolic risk factors including metabolic syndrome, hypertension, diabetes mellitus, dyslipidaemia or all laboratory findings related to cardiometabolic risk factors. Twenty-four cross-sectional studies with a total of 75 201 subjects are included in the qualitative and quantitative analysis. Overall, older age and female sex are more likely in NWO population. Compared to NWL, NWO is significantly associated with cardiometabolic risk factors, including metabolic syndrome (OR = 2.24 [1.74, 2.89]; p < .001; I2  = 76%, Pheterogeneity < 0.001), hypertension (OR = 1.60[1.36, 1.89]; p < .001; I2  = 76%, Pheterogeneity < 0.001), diabetes mellitus (OR = 1.72[1.54, 1.92]; p < .001; I2  = 47%, Pheterogeneity < 0.001), dyslipidaemia (OR = 1.50 [1.03, 2.18]; p = .03; I2  = 94%, Pheterogeneity < 0.001) and other laboratory findings, except for C-reactive protein in both sexes group; and adiponectin levels in female group. Our meta-analysis showed that NWO was associated with cardiometabolic risk factors. Thus, the traditional definition of obesity using the BMI criteria should be challenged, as those with NWO might still be exposed to a heightened risk of cardiometabolic disorders. Nonetheless, further prospective cohort studies are needed better to understand this syndrome.

Drug-Coated Balloon Versus Drug-Eluting Stent in Patients With Femoropopliteal Artery Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: In this systematic review and meta-analysis, we aimed to compare drug-coated balloon (DCB) to drug-eluting stent (DES) in patients with femoropopliteal lesions in terms of restenosis, target lesion revascularization (TLR), and mortality. METHODS: A comprehensive literature search was performed through PubMed, Scopus, and Embase databases. The intervention group was patients receiving percutaneous balloon angioplasty using the DCB. The control group was patients receiving percutaneous intervention using the DES. The primary outcome was restenosis, and the secondary outcomes were TLR and mortality. RESULTS: There were 4 studies comprising 812 patients (906 lesions) included in this systematic review and meta-analysis. The rate of restenosis was .19 [.13, .26] in DCB and .24 [.20, .28] in DES. There was a trend toward lower rate of restenosis (OR .73 [.52, 1.03], P = .074; I2: 46.3%) for DCB use compared to DES use. The rate of TLR was .11 [.08, .14] in DCB and .17 [.14, .21] in DES. TLR was lower (OR .61 [.41, .92], P = .017; I2: 1.2%) in the DCB group compared to the DES group. There were no significant differences in mortality (OR 1.38 [.78, 2.44], P = .268; I2: 0%) among the two groups. Meta-regression analysis showed that the rate of restenosis in DCB in this pooled analysis was affected by sex (reference: male, coefficient -.004, P = .009), smoking (coefficient: .003, P = .010), and total occlusion (coefficient: .008, P = .004). CONCLUSION: DCB use in patients with femoropopliteal lesion was associated with similar rate of restenosis, lower TLR, and similar mortality rate compared to DES use.

Endotheliopathy marked by high von Willebrand factor (vWF) antigen in COVID-19 is associated with poor outcome: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to compare the levels of von Willebrand Factor (vWF) antigen in patients with coronavirus disease 2019 (COVID-19) with a poor outcome compared with those with a good outcome, and explored factors that may affect the difference in terms of vWF antigen between the two groups. METHODS: A comprehensive literature search of PubMed, Embase and Scopus databases was undertaken from inception until 7 April 2021. The primary outcome was poor outcome, which is a composite of mortality and severity of COVID-19. RESULTS: Ten studies including a total of 996 patients were included in this systematic review and meta-analysis. vWF antigen was higher in patients with poor outcomes [standardized mean difference (SMD) 0.84 [0.45-1.23], P<0.001; I2=87.3, P<0.001). For subgroup analysis on studies that reported the vWF antigen level as a percentage, the mean difference was 121.6 [(53.7-189.4), P<0.001; I2=92.0, P<0.001]. Meta-regression showed that the SMD between poor outcome and good outcome was affected by the platelet count (coefficient 0.0061, P=0.001), d-dimer level (coefficient 0.0007, P=0.026) and factor VIII level (coefficient 0.0057, P=0.031), but not by age (coefficient -0.0610, P=0.440), gender (coefficient 0.0135, P=0.698), obesity (coefficient 0.0282, P=0.666), hypertension (coefficient 0.0273, P=0.423), diabetes (coefficient 0.0317, P=0.398) or malignancy (coefficient 0.0487, P=0.608). CONCLUSION: This meta-analysis showed that the level of vWF antigen was significantly higher in patients with COVID-19 with a poor outcome, signalling marked endotheliopathy. Meta-regression showed that the differences became larger as the platelet count, d-dimer level and factor VIII level increased.

Statin and mortality in COVID-19: a systematic review and meta-analysis of pooled adjusted effect estimates from propensity-matched cohorts.

PURPOSE: Statin potentially improved outcome in patients with COVID-19. Patients who receive statin generally have a higher proportion of comorbidities than those who did not, which may introduce bias. In this meta-analysis, we aimed to investigate the association between statin use and mortality in patients with COVID-19 by pooling the adjusted effect estimates from propensity-score matching (PSM) matched studies or randomised controlled trials to reduce bias. METHODS: A systematic literature search using the PubMed, Scopus and Embase databases were performed up until 1 March 2021. Studies that were designed the study to assess statin and mortality using PSM with the addition of Inverse Probability Treatment Weighting or multivariable regression analysis on top of PSM-matched cohorts were included. The effect estimate was reported in term of relative risk (RR). RESULTS: 14 446 patients were included in the eight PSM-matched studies. Statin was associated with decreased mortality in patients with COVID-19 (RR 0.72 (0.55, 0.95), p=0.018; I2: 84.3%, p<0.001). Subgroup analysis in patients receiving statin in-hospital showed that it was associated with lower mortality (RR 0.71 (0.54, 0.94), p=0.030; I2: 64.1%, p<0.025). The association of statin and mortality was not significantly affected by age (coefficient: -0.04, p=0.382), male gender (RR 0.96 (0.95, 1.02), p=0.456), diabetes (RR 1.02 (0.99, 1.04), p=0.271) and hypertension (RR 1.01 (0.97, 1.04), p=0.732) in this pooled analysis. CONCLUSION: In this meta-analysis of PSM-matched cohorts with adjusted analysis, statin was shown to decrease the risk of mortality in patients with COVID-19. PROSPERO REGISTRATION NUMBER: CRD42021240137.

Prognostic value of elevated lactate dehydrogenase in patients with COVID-19: a systematic review and meta-analysis.

PURPOSE: This meta-analysis aimed to evaluate the prognostic performance of elevated lactate dehydrogenase (LDH) in patients with COVID-19. METHODS: A systematic literature search was performed using PubMed, Embase and EuropePMC on 19 November 2020. The outcome of interest was composite poor outcome, defined as a combined endpoint of mortality, severity, need for invasive mechanical ventilation and need for intensive care unit care. Severity followed the included studies' criteria. RESULTS: There are 10 399 patients from 21 studies. Elevated LDH was present in 44% (34%-53%) of the patients. Meta-regression analysis showed that diabetes was correlated with elevated LDH (OR 1.01 (95% CI 1.00 to 1.02), p=0.038), but not age (p=0.710), male (p=0.068) and hypertension (p=0.969). Meta-analysis showed that elevated LDH was associated with composite poor outcome (OR 5.33 (95% CI 3.90 to 7.31), p<0.001; I2: 77.5%). Subgroup analysis showed that elevated LDH increased mortality (OR 4.22 (95% CI 2.49 to 7.14), p<0.001; I2: 89%). Elevated LDH has a sensitivity of 0.74 (95% CI 0.60 to 0.85), specificity of 0.69 (95% CI 0.58 to 0.78), positive likelihood ratio of 2.4 (95% CI 1.9 to 2.9), negative likelihood ratio of 0.38 (95% CI 0.26 to 0.55), diagnostic OR of 6 (95% CI 4 to 9) and area under curve of 0.77 (95% CI 0.73 to 0.80). Elevated LDH would indicate a 44% posterior probability and non-elevated LDH would in indicate 11% posterior probability for poor prognosis. Meta-regression analysis showed that age, male, hypertension and diabetes did not contribute to the heterogeneity of the analyses. CONCLUSION: LDH was associated with poor prognosis in patients with COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020221594.

Sofosbuvir with daclatasvir and the outcomes of patients with COVID-19: a systematic review and meta-analysis with GRADE assessment.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the effect of sofosbuvir/daclatasvir (SOF/DCV) on mortality, the need for intensive care unit (ICU) admission or invasive mechanical ventilation (IMV) and clinical recovery in patients with COVID-19. METHODS: We performed a systematic literature search through the PubMed, Scopus and Embase from the inception of databases until 6 April 2021. The intervention group was SOF/DCV, and the control group was standard of care. The primary outcome was mortality, defined as clinically validated death. The secondary outcomes were (1) the need for ICU admission or IMV and (2) clinical recovery. The pooled effect estimates were reported as risk ratios (RRs). RESULTS: There were four studies with a total of 231 patients in this meta-analysis. Three studies were randomised controlled trial, and one study was non-randomised. SOF/DCV was associated with lower mortality (RR: 0.31 (0.12, 0.78); p=0.013; I2: 0%) and reduced need for ICU admission or IMV (RR: 0.35 (0.18, 0.69); p=0.002; I2: 0%). Clinical recovery was achieved more frequently in the SOF/DCV (RR: 1.20 (1.04, 1.37); p=0.011; I2: 21.1%). There was a moderate certainty of evidence for mortality and need for ICU/IMV outcome, and a low certainty of evidence for clinical recovery. The absolute risk reductions were 140 fewer per 1000 for mortality and 186 fewer per 1000 for the need for ICU/IMV. The increase in clinical recovery was 146 more per 1000. CONCLUSION: SOF/DCV may reduce mortality rate and need for ICU/IMV in patients with COVID-19 while increasing the chance for clinical recovery. PROTOCOL REGISTRATION: PROSPERO: CRD42021247510.

Corrigendum: Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fnut.2021.660420.].

The association between triglyceride-glucose index and major adverse cardiovascular events in patients with acute coronary syndrome - dose-response meta-analysis.

BACKGROUND AND AIMS: Triglyceride-Glucose (TyG) index is an accurate biomarker of insulin resistance, which is potentially associated with adverse cardiovascular events. We aimed to assess the dose-response relationship between Triglyceride-Glucose (TyG) Index and Major Adverse Cardiovascular Events (MACE) in patients with Acute Coronary Syndrome (ACS). METHODS AND RESULTS: A systematic literature search was performed using PubMed, Scopus, and Embase for records published from the inception up until 7 February 2021. Studies that fulfilled all of these criteria were included: 1) prospective or retrospective observational studies reporting patients with ACS and 2) assessing the impact of TyG index on MACE with at least three quantitative classifications. The outcome of interest is MACE across the TyG index intervals. MACE was a composite of all-cause mortality, myocardial infarction, unstable angina pectoris, target vessel revascularization, cerebrovascular accidents, and heart failure. The effect estimates were reported as relative risks (RRs). There are 13,684 subjects from 4 studies included in this meta-analysis. This meta-analysis showed that the highest category of TyG index was associated with twofold MACE (RR 2.09 [1.59, 2.76], p < 0.001; I2: 68.4%, p = 0.02) compared to the lowest category in patients with ACS. Dose-response meta-analysis showed that the relationship between TyG index and MACE was non-linear (p < 0.001), with statistical significance reached around TyG index 8.9 and increased non-linearly. The dose-response curve became significantly steeper after TyG index of 9.1-9.2. CONCLUSION: TyG index was associated with MACE in patients with ACS in a non-linear fashion. PROSPERO: CRD42021235765.

Preparation, Properties and Potential of Carrageenan-Based Hard Capsules for Replacing Gelatine: A Review.

Intense efforts to develop alternative materials for gelatine as a drug-delivery system are progressing at a high rate. Some of the materials developed are hard capsules made from alginate, carrageenan, hypromellose and cellulose. However, there are still some disadvantages that must be minimised or eliminated for future use in drug-delivery systems. This review attempts to review the preparation and potential of seaweed-based, specifically carrageenan, hard capsules, summarise their properties and highlight their potential as an optional main component of hard capsules in a drug-delivery system. The characterisation methods reviewed were dimensional analysis, water and ash content, microbial activity, viscosity analysis, mechanical analysis, scanning electron microscopy, swelling degree analysis, gel permeation chromatography, Fourier-transform infrared spectroscopy and thermal analysis. The release kinetics of the capsule is highlighted as well. This review is expected to provide insights for new researchers developing innovative products from carrageenan-based hard capsules, which will support the development goals of the industry.

The Prognostic Value of Hyponatremia for Predicting Poor Outcome in Patients With COVID-19: A Systematic Review and Meta-Analysis.

Background: This meta-analysis aimed to assess the prognostic value of hyponatremia in patients with COVID-19. Methods: We performed a systematic literature search on PubMed, Scopus, ScienceDirect, and Wiley up until January 26, 2021. The key exposure was hyponatremia, defined as sodium level below the reference level. The outcome of interest was poor outcome, which was a composite of mortality, severe COVID-19, and prolonged hospitalization. Severe COVID-19 was defined severe CAP or needing ICU care or IMV. The pooled effect estimate was odds ratio (OR). Sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), diagnostic OR (DOR), and area under curve (AUC) were generated. Results: There were 11,493 patients from eight studies included in this systematic review and meta-analysis. The incidence of hyponatremia was 24%, and incidence of poor outcome was 20%. Hyponatremia was associated with poor outcome in COVID-19 (OR 2.65 [1.89, 3.72], p < 0.001; I2: 67.2%). Meta-regression analysis showed that the association between hyponatremia and poor outcome was reduced by age (OR 0.94 [0.90, 0.98], p = 0.006) and hypertension (OR 0.96 [0.93, 0.94], p < 0.001). Hyponatremia has a sensitivity of 0.37 [0.27, 0.48], specificity of 0.82 [0.72, 0.88], PLR of 2.0 [1.5, 2.7], NLR of 0.77 [0.69, 0.87], DOR of 3 [2, 4], and AUC of 0.62 [0.58, 0.66] for predicting poor outcome. In this pooled analysis, hyponatremia has a 33% posttest probability for poor outcome, and absence of hyponatremia confers to a 16% posttest probability. Conclusion: Hyponatremia was associated with poor outcome in patients with COVID-19. Systematic Review Registration: PROSPERO, CRD42021233592.

Colchicine and mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia: A systematic review, meta-analysis, and meta-regression.

OBJECTIVE: This systematic review, with meta-analysis and meta-regression aims to evaluate the effect of colchicine administration on mortality in patients with coronavirus disease 2019 (COVID-19) and factors affecting the association. METHODS: A systematic literature search using the PubMed, Scopus, and Embase databases were performed from inception of databases up until 3 March 2021. We included studies that fulfill all of the following criteria: 1) observational studies or randomized controlled trials (RCTs) that report COVID-19 patients, 2) reporting colchicine use, and 3) mortality within 30 days. There was no restriction on the age, inpatients or outpatients setting, and severity of diseases. The intervention was colchicine administration during treatment for COVID-19. The control was receiving placebo or standard of care. The outcome was mortality and the pooled effect estimate was reported as odds ratio (OR). Random-effects restricted maximum likelihood meta-regression was performed to evaluate factors affecting the pooled effect estimate. RESULTS: Eight studies comprising of 5530 patients were included in this systematic review and meta-analysis. There were three RCTs and five observational studies. Pooled analysis showed that colchicine was associated with lower mortality in patients with COVID-19 (OR 0.47 [0.31, 0.72], p = 0.001; I2: 30.9, p = 0.181). Meta-regression analysis showed that the association between colchicine and mortality was reduced by increasing age (OR 0.92 [0.85, 1.00], p = 0.05), but not gender (reference: male, p = 0.999), diabetes (p = 0.376), hypertension (p = 0.133), and CAD (p = 0.354). CONCLUSION: This meta-analysis indicates that colchicine may reduce mortality in patients with COVID-19. Meta-regression analysis showed that the benefit was reduced as age increases. PROSPERO: CRD42021240609.

Active prescription of low-dose aspirin during or prior to hospitalization and mortality in COVID-19: A systematic review and meta-analysis of adjusted effect estimates.

BACKGROUND: This study aimed to investigate whether the active prescription of low-dose aspirin during or prior to hospitalization affects mortality in patients with coronavirus disease 2019 (COVID-19). Aspirin is often prescribed for secondary prevention in patients with cardiovascular disease and other comorbidities that might increase mortality, and may therefore falsely demonstrate increased mortality. To reduce bias, only studies that performed an adjusted analysis were included in this review. METHODS: A systematic literature search of PubMed, Scopus, Embase and Clinicaltrials.gov was performed, from inception until 16 April 2021. The exposure was active prescription of low-dose aspirin during or prior to hospitalization. The primary outcome was mortality. The pooled adjusted effect estimate was reported as relative risk (RR). RESULTS: Six eligible studies were included in this meta-analysis, comprising 13,993 patients. The studies had low-to-moderate risk of bias based on the Newcastle-Ottawa Scale. The meta-analysis indicated that the use of low-dose aspirin was independently associated with reduced mortality {RR 0.46 [95% confidence interval (CI) 0.35-0.61], P < 0.001; I2 = 36.2%}. Subgroup analysis on in-hospital low-dose aspirin administration also showed a significant reduction in mortality [RR 0.39 (95% CI 0.16-0.96), P < 0.001; I2 = 47.0%]. CONCLUSION: Use of low-dose aspirin is independently associated with reduced mortality in patients with COVID-19, with low certainty of evidence.

Prognostic value of fasting hyperglycemia in patients with COVID-19 - Diagnostic test accuracy meta-analysis.

AIMS: This meta-analysis aimed to assess the prognostic value of fasting hyperglycemia in patients with COVID-19. METHODS: A systematic literature search on PubMed, Embase, and Scopus were performed up until February 18, 2021. Fasting hyperglycemia was defined as fasting plasma glucose level above the reference value. The outcome of interest was poor outcome, which was a composite of mortality and severe COVID-19. The effect estimate was in odds ratio (OR). RESULTS: There were 9045 patients from 12 studies included in this systematic review and meta-analysis. The prevalence of fasting hyperglycemia was 29%. The incidence of poor outcome was 15%. Fasting hyperglycemia was associated with poor outcome in COVID-19 (OR 4.72 [3.32, 6.72], p < 0.001; I2: 69.8%, p < 0.001). Subgroup analysis in patients without prior history of diabetes showed that fasting hyperglycemia was associated with poor outcome in COVID-19 (OR 3.387 [2.433, 4.714], p < 0.001; I2: 0, p = 0.90). Fasting hyperglycemia has a sensitivity of 0.57 [0.45, 0.68], specificity of 0.78 [0.70, 0.84], PLR of 2.6 [2.0, 3.3], NLR of 0.55 [0.44, 0.69], DOR of 5 [3, 7], and AUC of 0.74 [0.70, 0.78] for predicting poor outcome. In this pooled analysis, fasting hyperglycemia has a 32% post-test probability for poor outcome, and absence of fasting hyperglycemia confers to a 9% post-test probability. Meta-regression and subgroup analysis showed that the sensitivity and specificity varies by chronic kidney disease but not by age, male (gender), hypertension, and chronic kidney disease. CONCLUSION: Fasting hyperglycemia was associated with mortality in COVID-19 patients, with or without diabetes. PROSPERO: CRD42021237997.

Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis.

Background: This systematic review and meta-analysis aimed to assess whether low serum 25-hydroxyvitamin D (25-OHD) level is associated with susceptibility to COVID-19, severity, and mortality related to COVID-19. Methods: Systematic literature searches of PubMed, Scopus, and Embase database up until 9 December 2020. We include published observational prospective and retrospective studies with information on 25-OHD that reported main/secondary outcome. Low serum 25-OHD refers to participants with serum 25-OHD level below a cut-off point ranging from 20 to 30 ng/mL. Other cut-off values were excluded to reduce heterogeneity. The main outcome was mortality defined as non-survivor/death. The secondary outcome was susceptibility and severe COVID-19. Results: There were 14 studies comprising of 999,179 participants. Low serum 25-OHD was associated with higher rate of COVID-19 infection compared to the control group (OR = 2.71 [1.72, 4.29], p < 0.001; I 2: 92.6%). Higher rate of severe COVID-19 was observed in patients with low serum 25-OHD (OR = 1.90 [1.24, 2.93], p = 0.003; I 2: 55.3%), with a sensitivity of 83%, specificity of 39%, PLR of 1.4, NLR of 0.43, and DOR of 3. Low serum 25-OHD was associated with higher mortality (OR = 3.08 [1.35, 7.00], p = 0.011; I 2: 80.3%), with a sensitivity of 85%, specificity of 35%, PLR of 1.3, NLR of 0.44, and DOR of 3. Meta-regression analysis showed that the association between low serum 25-OHD and mortality was affected by male gender (OR = 1.22 [1.08, 1.39], p = 0.002), diabetes (OR = 0.88 [0.79, 0.98], p = 0.019). Conclusion: Low serum 25-OHD level was associated with COVID-19 infection, severe presentation, and mortality.

Dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in coronavirus disease 2019 (COVID-19) - A systematic review, meta-analysis, and meta-regression.

BACKGROUND AND AIMS: This study aims to synthesize evidence on dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in COVID-19 patients and factors affecting it. METHODS: We performed a systematic literature search from PubMed, Scopus, and Embase databases from inception of databases up until 7 March 2021. Studies that met all of the following criteria were included: 1) observational studies or randomized controlled trials that report COVID-19 patients, 2) reporting DPP-4 inhibitor use, 3) mortality, and 4) mortality based on DPP-4 inhibitor use. The exposure was DPP-4 inhibitor, defined as DPP-4 inhibitor use that started prior to COVID-19 hospitalization. The control group was patients with no exposure to DPP-4 inhibitor. The outcome was mortality. The pooled effect estimate was reported as risk ratio (RR). RESULTS: There were 4,477 patients from 9 studies in this systematic review and meta-analysis. 31% of (15%, 46%) the patients use DPP-4 inhibitor. Mortality occurs in 23% (15%, 31%) of the patients. DPP-4 inhibitor was associated with lower mortality in patients with COVID-19 (RR 0.76 [0.60, 0.97], p = 0.030, I2: 44.5%, p = 0.072). Meta-regression analysis showed that the association between DPP-4 inhibitor and mortality was significantly affected by metformin (RR 1.02 [1.00, 1.04], p = 0.048) and angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) use (RR 1.04 [1.01, 1.07], p = 0.006), but not age (p = 0.759), sex (reference: male, p = 0.148), and hypertension (p = 0.218). CONCLUSION: DPP-4 inhibitor use was associated with lower mortality in COVID-19 patients, and the association was weaker in patients who were also taking metformin and/or ACE inhibitors.

Absence of electrocardiographic left ventricular hypertrophy and poor outcome in patients undergoing transcatheter aortic valve replacement-A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate whether the absence of electrocardiographic (ECG) left ventricular hypertrophy (LVH) was associated with poor outcome in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: We performed systematic review search on PubMed, Embase, and Scopus up until January 22, 2021. The key exposure was the absence of ECG LVH, defined as the absence of LVH by electrocardiographic criteria. The outcome of interest was composite poor outcome, which is a composite of mortality and/or rehospitalization after TAVR. The effect estimate was reported as hazard ratio (HR). In addition, we generate sensitivity and specificity, positive and negative likelihood ratio (PLR and NLR), diagnostic odds ratio (DOR), and area under curve (AUC). RESULTS: There are four studies comprising of 827 patients included in this systematic review and meta-analysis. The prevalence of poor outcome in this pooled analysis was 30%. The absence of ECG LVH was associated with increased poor outcome in patients undergoing TAVR (HR: 1.86, [1.34, 2.57], p < .001; I2 : 0%). Absence of ECG LVH was associated with a sensitivity of 0.75 [0.64, 0.83], specificity of 0.42 [0.30, 0.55], PLR of 1.3 [1.1, 1.5], NLR of 0.60 [0.45, 0.80], DOR 2 [1, 5], and AUC of 0.66 [0.62, 0.70]. Fagan's nomogram indicates in a 22% prevalence of poor outcome in the included studies, the absence of ECG LVH and ECG LVH was associated with 27% and 15% posttest probability for poor outcome, respectively. CONCLUSION: Absence of ECG LVH was associated with poor outcome in patients undergoing TAVR.

Prognostic performance of troponin in COVID-19: A diagnostic meta-analysis and meta-regression.

BACKGROUND: Cardiac injury is frequently encountered in patients with coronavirus disease 2019 (COVID-19) and is associated with increased risk of mortality. Elevated troponin may signify myocardial damage and is predictive of mortality. This study aimed to assess the prognostic value of troponin above the 99th percentile upper reference limit (URL) for mortality, and factors affecting the relationship. METHODS: A comprehensive literature search of PubMed (MEDLINE), Scopus and Embase was undertaken, from inception of the databases until 16 December 2020. The key exposure was elevated serum troponin, defined as troponin (of any type) above the 99th percentile URL. The outcome was mortality due to any cause. RESULTS: In total, 12,262 patients from 13 studies were included in this systematic review and meta-analysis. The mortality rate was 23% (20-26%). Elevated troponin was observed in 31% (23-38%) of patients. Elevated troponin was associated with increased mortality [odds ratio (OR) 4.75, 95% confidence interval (CI) 4.07-5.53; P < 0.001; I2 = 19.9%]. Meta-regression showed that the association did not vary with age (P = 0.218), male gender (P = 0.707), hypertension (P = 0.182), diabetes (P = 0.906) or coronary artery disease (P = 0864). The association between elevated troponin and mortality had sensitivity of 0.55 (0.44-0.66), specificity of 0.80 (0.71-0.86), positive likelihood ratio of 2.7 (2.2-3.3), negative likelihood ratio of 0.56 (0.49-0.65), diagnosis odds ratio of 5 (4-5) and area under the curve of 0.73 (0.69-0.77). The probability of mortality was 45% in patients with elevated troponin and 14% in patients with non-elevated troponin. CONCLUSION: Elevated troponin was associated with mortality in patients with COVID-19 with 55% sensitivity and 80% specificity.

The prognostic value of elevated creatine kinase to predict poor outcome in patients with COVID-19 - A systematic review and meta-analysis.

BACKGROUND AND AIMS: Creatine kinase (CK), a marker of muscle damage, is potentially associated with a more severe COVID-19. In this systematic review and meta-analysis, we aim to evaluate the association between the elevated CK and severity and mortality in COVID-19. METHODS: We performed a systematic literature search on PubMed, Scopus, and Embase up until January 26, 2020. The main outcome was poor outcome, a composite of mortality and severe COVID-19. RESULTS: There are 2471 patients from 14 studies included in this systematic review and meta-analysis. The incidence of elevated CK in this pooled analysis was 17% (11%, 22%) and the incidence of poor outcome in this pooled analysis was 27% (19%, 34%). Elevated CK was associated with poor outcome in patients with COVID-19 (OR 3.01 [2.21, 4.10], p < 0.001; I2: 10.2%). The effect estimate did not vary with age (p = 0.610), male (p = 0.449), hypertension (p = 0.490), and diabetes (p = 0.457). Elevated CK has a sensitivity of 0.24 (0.17, 0.32), specificity of 0.91 (0.86, 0.94), PLR of 2.6 (1.9, 3.7), NLR of 0.84 (0.78, 0.90), DOR of 3 (2, 5), and AUC of 0.62 (0.57, 0.66) for predicting poor outcome in patients with COVID-19. In this pooled analysis, elevated CK confers to a 49% probability for poor outcome and a non-elevated CK confers to a 24% probability. Subgroup analysis and univariate meta-regression indicates that the sensitivity and specificity does not vary with age, male, hypertension, and diabetes. CONCLUSION: Elevated CK was associated with increased mortality and severity in patients with COVID-19. PROSPERO: CRD42021233435.

Tricuspid annular plane systolic excursion (TAPSE) measured by echocardiography and mortality in COVID-19: A systematic review and meta-analysis.

BACKGROUND: In this systematic review and meta-analysis, we assessed the association between tricuspid annular plane systolic excursion (TAPSE) measured by echocardiography and mortality in coronavirus disease 2019 (COVID-19). METHODS: We performed a systematic literature search using PubMed, Embase, and Scopus databases with the keywords "COVID-19" OR "SARS-CoV-2" OR "2019-nCoV" AND "Tricuspid annular plane systolic excursion" OR "TAPSE" until January 20, 2021. The main outcome was mortality. The effect estimate was reported as the hazard ratio (HR), which was pooled from the unadjusted and adjusted effect estimates retrieved from the studies included. Mean differences in TAPSE (in mm) between non-survivors and survivors were pooled. RESULTS: In total, 641 patients from seven studies were included in this systematic review and meta-analysis. TAPSE was lower in non-survivors compared with survivors (mean difference = -3.74 [-5.22, -2.26], p < 0.001; I2: 85.5%, p < 0.001). Each 1 mm decrease in TAPSE was associated with increased mortality (HR = 1.24 [1.18, 1.31], p < 0.001; I2: 0.0%, p = 0.491). In the pooled adjusted model, each 1 mm decrease in TAPSE was associated with increased mortality (HR = 1.21 [1.11, 1.33], p < 0.001; I2: 45.1%, p = 0.156). Meta-regression indicated that the difference in TAPSE between non-survivors and survivors was affected by chronic obstructive pulmonary disease (-0.183, p < 0.001) and pulmonary artery systolic pressure (-0.344, p = 0.039), but not by age (p = 0.668), male gender (p = 0.821), hypertension (p = 0.101), diabetes (p = 0.603), coronary artery disease (p = 0.564), smoking (p = 0.140), and left ventricular ejection fraction (p = 0.452). CONCLUSION: Every 1 mm decrease in TAPSE was associated with an increase in mortality of approximately 20%. PROSPERO ID: CRD42021232194.

Left and right ventricular longitudinal strains are associated with poor outcome in COVID-19: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to assess whether ventricular longitudinal strain can be used as a prognostication tool in patients with coronavirus disease 2019 (COVID-19). METHODS: Systematic literature searches of PubMed, Embase, and EuropePMC databases were performed on 16 November 2020. Left ventricular global longitudinal strain (LV-GLS) refers to LV contraction measurement using the speckle tracking-based method refers to the mean of strain values of the RV free wall (three segments) measured using echocardiography. The main outcome was poor outcome, defined as a composite of mortality and severe COVID-19. RESULTS: Seven studies comprising of 612 patients were included in meta-analysis. Six studies have mortality as their outcome, and 1 study has severity as their outcome. Patients with poor outcome have lower LV-GLS (SMD 1.15 (0.57, 1.72), p < 0.001; I2 70.4%). Each 1% decrease in LV-GLS was associated with 1.4x increased risk of poor outcome (OR 1.37 (1.12, 1.67), p = 0.002; I2 48.8%). Patients with poor outcome have lower RV-LS (SMD 1.18 (0.91, 1.45), p < 0.001; I2 0%). Each 1% decrease in RV-LS was associated with 1.3x increased risk of poor outcome (OR 1.25 (1.15, 1.35), p < 0.001; I2 11.8%). Subgroup analysis showed that for every 1% decrease in LV-GLS and RV-LS is increased mortality with OR of 1.30 (1.12, 1.50) and OR of 1.24 (1.14, 1.35), respectively. CONCLUSION: This study shows that lower LV-GLS and RV-LS measurements were associated with poor outcome in patients with COVID-19. TRIAL REGISTRATION: PROSPERO CRD42020221144.