Cardiovascular and haematological events post COVID-19 vaccination: A systematic review.

Since COVID-19 took a strong hold around the globe causing considerable morbidity and mortality, a lot of effort was dedicated to manufacturing effective vaccines against SARS-CoV-2. Many questions have since been raised surrounding the safety of the vaccines, and a lot of media attention to certain side effects. This caused a state of vaccine hesitancy that may prove problematic in the global effort to control the virus. This review was undertaken with the aim of putting together all the reported cardiovascular and haematological events post COVID-19 vaccination in published literature and to suggest possible mechanisms to explain these rare phenomena.

LDL-C-lowering therapies reduce major vascular events in patients aged ≥75 y.

SOURCE CITATION: Gencer B, Marston NA, Im K, et al. Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2020;396:1637-43. 33186535.

Systemic inflammation in COVID-19 patients may induce various types of venous and arterial thrombosis: A systematic review.

COVID-19 is a global pandemic with a daily increasing number of affected individuals. Thrombosis is a severe complication of COVID-19 that leads to a worse clinical course with higher rates of mortality. Multiple lines of evidence suggest that hyperinflammation plays a crucial role in disease progression. This review compiles clinical data of COVID-19 patients who developed thrombotic complications to investigate the possible role of hyperinflammation in inducing hypercoagulation. A systematic literature search was performed using PubMed, Embase, Medline and Scopus to identify relevant clinical studies that investigated thrombotic manifestations and reported inflammatory and coagulation biomarkers in COVID-19 patients. Only 54 studies met our inclusion criteria, the majority of which demonstrated significantly elevated inflammatory markers. In the cohort studies with control, D-dimer was significantly higher in COVID-19 patients with thrombosis as compared to the control. Pulmonary embolism, deep vein thrombosis and strokes were frequently reported which could be attributed to the hyperinflammatory response associated with COVID-19 and/or to the direct viral activation of platelets and endothelial cells, two mechanisms that are discussed in this review. It is recommended that all admitted COVID-19 patients should be assessed for hypercoagulation. Furthermore, several studies have suggested that anticoagulation may be beneficial, especially in hospitalized non-ICU patients. Although vaccines against SARS-CoV-2 have been approved and distributed in several countries, research should continue in the field of prevention and treatment of COVID-19 and its severe complications including thrombosis due to the emergence of new variants against which the efficacy of the vaccines is not yet clear.

Attenuated heart rate recovery is associated with higher arrhythmia recurrence and mortality following atrial fibrillation ablation.

AIMS: Heart rate recovery (HRR), the decrease in heart rate occurring immediately after exercise, is caused by the increase in vagal activity and sympathetic withdrawal occurring after exercise and is a powerful predictor of cardiovascular events and mortality. The extent to which it impacts outcomes of atrial fibrillation (AF) ablation has not previously been studied. The aim of this study is to investigate the association between attenuated HRR and outcomes following AF ablation. METHODS AND RESULTS: We studied 475 patients who underwent EST within 12 months of AF ablation. Patients were categorized into normal (>12 b.p.m.) and attenuated (≤12 b.p.m.) HRR groups. Our main outcomes of interest included arrhythmia recurrence and all-cause mortality. During a mean follow-up of 33 months, 43% of our study population experienced arrhythmia recurrence, 74% of those with an attenuated HRR, and 30% of those with a normal HRR (P < 0.0001). Death occurred in 9% of patients in the attenuated HRR group compared to 4% in the normal HRR cohort (P = 0.001). On multivariable models adjusting for cardiorespiratory fitness (CRF), medication use, left atrial size, ejection fraction, and renal function, attenuated HRR was predictive of increased arrhythmia recurrence (hazard ratio 2.54, 95% confidence interval 1.86-3.47, P < 0.0001). CONCLUSION: Heart rate recovery provides additional valuable prognostic information beyond CRF. An impaired HRR is associated with significantly higher rates of arrhythmia recurrence and death following AF ablation.

Atrial fibrillation ablation in patients with transthyretin cardiac amyloidosis.

AIMS: Atrial fibrillation (AF) occurs in as many as 70% of patients with transthyretin cardiac amyloidosis (ATTR CA). The aim of our study was to investigate the impact of AF ablation on freedom from recurrent arrhythmia, hospitalization for AF or heart failure (HF), and mortality. METHODS AND RESULTS: This was a retrospective observational cohort study of 72 patients with ATTR CA and AF, of whom 24 underwent AF ablation and were matched in a 2:1 manner based on age, gender, ATTR CA stage, New York Heart Association functional class, ejection fraction, and date of AF diagnosis with 48 patients with ATTR CA and AF undergoing medical management. During a mean follow-up of 39 ± 26 months, 10 (42%) patients remained free of recurrent arrhythmia following ablation. Ablation was significantly more effective in those with Stage I or II ATTR CA, with 9/14 (64%) patients with Stage I or II ATTR CA remaining free of recurrent arrhythmia compared to only 1/10 (10%) patients with Stage III disease (P = 0.005). Death occurred in 7 (29%) patients in the ablation group compared to 36 (75%) in the non-ablation arm (P = 0.01). Rates of ischaemic stroke were similar in both groups. Ablation was associated with a significant reduction in the frequency of hospitalization for HF/arrhythmia (1.7 ± 2.4 hospitalizations vs. 4 ± 3.5, P = 0.005). On Cox proportional hazards analyses, ablation was associated with improved survival (hazard ratio 0.38, 95% confidence intervals 0.17-0.86; P = 0.02). CONCLUSION: Atrial fibrillation ablation is associated with reduced mortality in ATTR CA and is most effective when performed earlier during the disease process.

Impact of Novel Low-Density Lipoprotein-Cholesterol Assessment on the Utility of Secondary Non-High-Density Lipoprotein-C and Apolipoprotein B Targets in Selected Worldwide Dyslipidemia Guidelines.

BACKGROUND: Selected dyslipidemia guidelines recommend non-high-density lipoprotein-cholesterol (non-HDL-C) and apolipoprotein B (apoB) as secondary targets to the primary target of low-density lipoprotein-cholesterol (LDL-C). After considering 2 LDL-C estimates that differ in accuracy, we examined: (1) how frequently non-HDL-C guideline targets could change management; and (2) the utility of apoB targets after meeting LDL-C and non-HDL-C targets. METHODS: We analyzed 2518 adults representative of the US population from the 2011 to 2012 National Health and Nutrition Examination Survey and 126 092 patients from the Very Large Database of Lipids study with apoB. We identified all individuals as well as those with high-risk clinical features, including coronary artery disease, diabetes mellitus, and metabolic syndrome who met very high- and high-risk guideline targets of LDL-C <70 and <100 mg/dL using Friedewald estimation (LDL-CF) and a novel, more accurate method (LDL-CN). Next, we examined those not meeting non-HDL-C (<100, <130 mg/dL) and apoB (<80, <100 mg/dL) guideline targets. In those meeting dual LDL-C and non-HDL-C targets (<70 and <100 mg/dL, respectively, or <100 and <130 mg/dL, respectively), we determined the proportion of individuals who did not meet guideline apoB targets (<80 or <100 mg/dL). RESULTS: A total of 7% to 9% and 31% to 36% of individuals had LDL-C <70 and <100 mg/dL, respectively. Among those with LDL-CF<70 mg/dL, 14% to 15% had non-HDL-C ≥100 mg/dL, and 7% to 8% had apoB ≥80 mg/dL. Among those with LDL-CF<100 mg/dL, 8% to 10% had non-HDL-C ≥130 mg/dL and 2% to 3% had apoB ≥100 mg/dL. In comparison, among those with LDL-CN<70 or 100 mg/dL, only ≈2% and ≈1% of individuals, respectively, had non-HDL-C and apoB values above guideline targets. Similar trends were upheld among those with high-risk clinical features: ≈0% to 3% of individuals with LDL-CN<70 mg/dL had non-HDL-C ≥100 mg/dL or apoB ≥80 mg/dL compared with 13% to 38% and 9% to 25%, respectively, in those with LDL-CF<70 mg/dL. With LDL-CF or LDL-CN<70 mg/dL and non-HDL-C <100 mg/dL, 0% to 1% had apoB ≥80 mg/dL. Among all dual LDL-CF or LDL-CN<100 mg/dL and non-HDL-C <130 mg/dL individuals, 0% to 0.4% had apoB ≥100 mg/dL. These findings were robust to sex, fasting status, and lipid-lowering therapy status. CONCLUSIONS: After more accurately estimating LDL-C, guideline-suggested non-HDL-C targets could alter management in only a small fraction of individuals, including those with coronary artery disease and other high-risk clinical features. Furthermore, current guideline-suggested apoB targets provide modest utility after meeting cholesterol targets. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01698489.

Association between pre-ablation bariatric surgery and atrial fibrillation recurrence in morbidly obese patients undergoing atrial fibrillation ablation.

AIMS: Obesity decreases arrhythmia-free survival after atrial fibrillation (AF) ablation by mechanisms that are not fully understood. We investigated the impact of pre-ablation bariatric surgery (BS) on AF recurrence after ablation. METHODS AND RESULTS: In this retrospective observational cohort study, 239 consecutive morbidly obese patients (body mass index ≥40 kg/m2 or ≥35 kg/m2 with obesity-related complications) were followed for a mean of 22 months prior to ablation. Of these patients, 51 had BS prior to ablation, and our primary outcome was whether BS was associated with a lower rate of AF recurrence during follow-up. Adjustment for confounding was performed with multivariable Cox proportional hazard models and propensity-score based analyses. During a mean follow-up of 36 months after ablation, 10/51 patients (20%) in the BS group had recurrent AF compared with 114/188 (61%) in the non-BS group (P < 0.0001). In the BS group, 6 patients (12%) underwent repeat ablation compared with 77 patients (41%) in the non-BS group, (P < 0.0001). On multivariable analysis, the association between BS and lower AF recurrence remained significant. Similarly, after weighting and adjusting for the inverse probability of the propensity score, BS was still associated with a lower hazard of AF recurrence (hazard ratio 0.14, 95% confidence interval 0.05-0.39; P = 0.002). CONCLUSION: Bariatric surgery is associated with a lower AF recurrence after ablation. Morbidly obese patients should be considered for BS prior to AF ablation, though prospective multicentre studies should be performed to confirm our novel finding.

Visit-to-visit cholesterol variability correlates with coronary atheroma progression and clinical outcomes.

Aims: Utilizing serial intravascular ultrasonography (IVUS), we aimed to exam the association of intra-individual lipid variability, coronary atheroma progression, and clinical outcomes. Methods and results: We performed a post hoc patient-level analysis of nine clinical trials involving 4976 patients with coronary artery disease who underwent serial coronary IVUS in the setting of a range of medical therapies. We assessed the associations between progression in percent atheroma volume (ΔPAV), clinical outcomes, and visit-to-visit lipid variability including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC)/HDL-C, and apolipoprotein B (ApoB). Variability of lipid parameters was measured using intra-individual standard deviation over 3, 6, 12, 18, and 24 months. Atherogenic lipoprotein variability significantly associated with ΔPAV [odds ratio (95% confidence interval; P-value), LDL-C: 1.09 (1.02, 1.17, P = 0.01); non-HDL-C: 1.10 (1.02, 1.18, P = 0.01); TC/HDL-C: 1.14 (1.06, 1.24, P = 0.001); ApoB: 1.13 (1.03, 1.24, P = 0.01)]. Survival curves revealed significant stepwise relationships between cumulative major adverse cardiovascular events and increasing quartiles of atherogenic lipoprotein variability at 24-months follow-up (log-rank P < 0.01 for all lipoproteins except HDL-C). Stronger associations were noted between achieved lipoprotein levels and ΔPAV [LDL-C: 1.27 (1.17, 1.39; P < 0.001); non-HDL-C: 1.32 (1.21, 1.45; P < 0.001); TC/HDL-C: 1.31 (1.19, 1.45; P < 0.001); ApoB: 1.20 (1.07, 1.35; P = 0.003)]. Conclusion: Greater visit-to-visit variability in atherogenic lipoprotein levels significantly associates with coronary atheroma progression and clinical outcomes, although the association between achieved atherogenic lipoproteins and atheroma progression appears stronger. These data highlight the importance of achieving low and consistent atherogenic lipoprotein levels to promote plaque regression and improve clinical outcomes.

Accuracy of low-density lipoprotein cholesterol estimation at very low levels.

BACKGROUND: As the approach to low-density lipoprotein cholesterol (LDL-C) lowering becomes increasingly intensive, accurate assessment of LDL-C at very low levels warrants closer attention in individualized clinical efficacy and safety evaluation. We aimed to assess the accuracy of LDL-C estimation at very low levels by the Friedewald equation, the de facto clinical standard, and compare its accuracy with a novel, big data-derived LDL-C estimate. METHODS: In 191,333 individuals with Friedewald LDL-C < 70 mg/dL, we compared the accuracy of Friedewald and novel LDL-C values in relation to direct measurements by Vertical Auto Profile ultracentrifugation. We examined differences (estimate minus ultracentrifugation) and classification according to levels initiating additional safety precautions per clinical practice guidelines. RESULTS: Friedewald values were less than ultracentrifugation measurement, with a median difference (25th to 75th percentile) of -2.4 (-7.4 to 0.6) at 50-69 mg/dL, -7.0 (-16.2 to -1.2) at 25-39 mg/dL, and -29.0 (-37.4 to -19.6) at < 15 mg/dL. The respective values by novel estimation were -0.1 (-1.5 to 1.3), -1.1 (-2.5 to 0.3), and -2.7 (-4.9 to 0.0) mg/dL. Among those with Friedewald LDL-C < 15, 15 to < 25, and 25 to < 40 mg/dL, the classification was discordantly low in 94.9%, 82.6%, and 59.9% of individuals as compared with 48.3%, 42.4%, and 22.4% by novel estimation. CONCLUSIONS: Estimation of even lower LDL-C values (by Friedewald and novel methods) is even more inaccurate. More often than not, a Friedewald value < 40 mg/dL is underestimated, which translates into unnecessary safety alarms that could be reduced in half by estimation using our novel method.

Non-HDL Cholesterol and Triglycerides: Implications for Coronary Atheroma Progression and Clinical Events.

OBJECTIVES: Non-high-density lipoprotein cholesterol (non-HDLC) levels reflect the full burden of cholesterol transported in atherogenic lipoproteins. Genetic studies suggest a causal association between elevated triglycerides (TGs)-rich lipoproteins and atherosclerosis. We evaluated associations between achieved non-HDLC and TG levels on changes in coronary atheroma volume. APPROACH AND RESULTS: Data were analyzed from 9 clinical trials involving 4957 patients with coronary disease undergoing serial intravascular ultrasonography to assess changes in percent atheroma volume (ΔPAV) and were evaluated against on-treatment non-HDLC and TG levels. The effects of lower (<100 mg/dL) versus higher (≥100 mg/dL) achieved non-HDLC levels and lower (<200 mg/dL) versus higher (≥200 mg/dL) achieved TG levels were evaluated in populations with variable on-treatment low-density lipoprotein cholesterol (LDLC) 0) was associated with achieved TG levels >200 mg/dL, respectively. Lower on-treatment non-HDLC and TG levels associated with significant PAV regression compared with higher non-HDLC and TG levels across all levels of LDLC and C-reactive protein and irrespective of diabetic status (P<0.001 across all comparisons). ΔPAV were more strongly influenced by changes in non-HDLC (ß=0.62; P<0.001) compared with changes in LDLC (ß=0.51; P<0.001). Kaplan-Meier sensitivity analyses demonstrated significantly greater major adverse cardiovascular event rates in those with higher versus lower non-HDLC and TG levels, with an earlier separation of the non-HDLC compared with the LDLC curve. CONCLUSIONS: Achieved non-HDLC levels seem more closely associated with coronary atheroma progression than LDLC. Plaque progression associates with achieved TGs, but only above levels of 200 mg/dL. These observations support a more prominent role for non-HDLC (and possibly TG) lowering in combating residual cardiovascular risk.

Patient-Level Discordance in Population Percentiles of the Total Cholesterol to High-Density Lipoprotein Cholesterol Ratio in Comparison With Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol: The Very Large Database of Lipids Study (VLDL-2B).

BACKGROUND: The total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio, estimated low-density lipoprotein cholesterol (LDL-C), and non-HDL-C are routinely available from the standard lipid profile. We aimed to assess the extent of patient-level discordance of TC/HDL-C with LDL-C and non-HDL-C, because discordance suggests the possibility of additional information. METHODS AND RESULTS: We compared population percentiles of TC/HDL-C, Friedewald-estimated LDL-C, and non-HDL-C in 1 310 432 US adults from the Very Large Database of Lipids. Lipid testing was performed by ultracentrifugation (Vertical Auto Profile, Atherotech, AL). One in 3 patients had ≥25 percentile units discordance between TC/HDL-C and LDL-C, whereas 1 in 4 had ≥25 percentile units discordance between TC/HDL-C and non-HDL-C. The proportion of patients with TC/HDL-C > LDL-C by ≥25 percentile units increased from 3% at triglycerides <100 mg/dL to 51% at triglycerides 200 to 399 mg/dL. On a smaller scale, TC/HDL-C > non-HDL-C discordance by ≥25 percentile units increased from 6% to 21%. In those with <15th percentile levels of LDL-C (<70 mg/dL) or non-HDL-C (<93 mg/dL), a respective 58% and 46% were above the percentile-equivalent TC/HDL-C of 2.6. Age, sex, and directly measured components of the standard lipid profile explained >86% of the variance in percentile discordance between TC/HDL-C versus LDL-C and non-HDL-C. CONCLUSIONS: In this contemporary, cross-sectional, big data analysis of US adults who underwent advanced lipid testing, the extent of patient-level discordance suggests that TC/HDL-C may offer potential additional information to LDL-C and non-HDL-C. Future studies are required to determine the clinical implications of this observation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01698489.

A novel automated peak frequency annotation algorithm for identifying deceleration zones and ventricular tachycardia ablation sites.

BACKGROUND: Current annotation of local fractionated signals during ventricular electroanatomic mapping (EAM) requires manual input subject to variability and error. OBJECTIVES: The purpose of this study was to evaluate a novel peak frequency (PF) annotation software for its ability to automatically detect late potentials (LPs) and local abnormal ventricular activity (LAVA), determine an optimal range for display, and assess its impact on isochronal late activation mapping (ILAM). METHODS: EAM data from 25 patients who underwent ventricular tachycardia (VT) ablation were retrospectively analyzed. Samplings of electrogram PFs from areas of normal bipolar voltage, areas of low voltage, and areas of low voltage with fractioned signals were performed. An optimal range of frequency display was identified from these patients and applied to a validation cohort of 10 prospective patients to assess high PF within scar as a predictor of VT ablation target sites, in particular deceleration zones (DZs) identified by ILAM, LP, and LAVA. RESULTS: Voltage and PF ranges of normal endocardial tissue varied widely. Using 220 Hz as a frequency cutoff value in areas of low bipolar voltage, areas of high fractionation were identified with sensitivity of 91% and specificity of 85% There was no significant reduction in targeted DZ surface areas, and colocalization with DZs was observed in all cases. Applied to the prospective cohort, PF predicted fractionated areas and DZ in 9 of 10 patients. CONCLUSION: A PF annotation algorithm with a cutoff of 220 Hz accurately identifies areas of fractioned signals and accurately predicts DZs during ILAM.

Accuracy and consistency of online large language model-based artificial intelligence chat platforms in answering patients' questions about heart failure.

BACKGROUND: Heart failure (HF) is a prevalent condition associated with significant morbidity. Patients may have questions that they feel embarrassed to ask or will face delays awaiting responses from their healthcare providers which may impact their health behavior. We aimed to investigate the potential of large language model (LLM) based artificial intelligence (AI) chat platforms in complementing the delivery of patient-centered care. METHODS: Using online patient forums and physician experience, we created 30 questions related to diagnosis, management and prognosis of HF. The questions were posed to two LLM-based AI chat platforms (OpenAI's ChatGPT-3.5 and Google's Bard). Each set of answers was evaluated by two HF experts, independently and blinded to each other, for accuracy (adequacy of content) and consistency of content. RESULTS: ChatGPT provided mostly appropriate answers (27/30, 90%) and showed a high degree of consistency (93%). Bard provided a similar content in its answers and thus was evaluated only for adequacy (23/30, 77%). The two HF experts' grades were concordant in 83% and 67% of the questions for ChatGPT and Bard, respectively. CONCLUSION: LLM-based AI chat platforms demonstrate potential in improving HF education and empowering patients, however, these platforms currently suffer from issues related to factual errors and difficulty with more contemporary recommendations. This inaccurate information may pose serious and life-threatening implications for patients that should be considered and addressed in future research.

Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile.

IMPORTANCE: In clinical and research settings worldwide, low-density lipoprotein cholesterol (LDL-C) is typically estimated using the Friedewald equation. This equation assumes a fixed factor of 5 for the ratio of triglycerides to very low-density lipoprotein cholesterol (TG:VLDL-C); however, the actual TG:VLDL-C ratio varies significantly across the range of triglyceride and cholesterol levels. OBJECTIVE: To derive and validate a more accurate method for LDL-C estimation from the standard lipid profile using an adjustable factor for the TG:VLDL-C ratio. DESIGN, SETTING, AND PARTICIPANTS: We used a convenience sample of consecutive clinical lipid profiles obtained from 2009 through 2011 from 1,350,908 children, adolescents, and adults in the United States. Cholesterol concentrations were directly measured after vertical spin density-gradient ultracentrifugation, and triglycerides were directly measured. Lipid distributions closely matched the population-based National Health and Nutrition Examination Survey (NHANES). Samples were randomly assigned to derivation (n = 900,605) and validation (n = 450,303) data sets. MAIN OUTCOMES AND MEASURES: Individual patient-level concordance in clinical practice guideline LDL-C risk classification using estimated vs directly measured LDL-C (LDL-CD). RESULTS: In the derivation data set, the median TG:VLDL-C was 5.2 (IQR, 4.5-6.0). The triglyceride and non-high-density lipoprotein cholesterol (HDL-C) levels explained 65% of the variance in the TG:VLDL-C ratio. Based on strata of triglyceride and non-HDL-C values, a 180-cell table of median TG:VLDL-C values was derived and applied in the validation data set to estimate the novel LDL-C (LDL-CN). For patients with triglycerides lower than 400 mg/dL, overall concordance in guideline risk classification with LDL-CD was 91.7% (95% CI, 91.6%-91.8%) for LDL-CN vs 85.4% (95% CI, 85.3%-85.5%) for Friedewald LDL-C (LDL-CF) (P < .001). The greatest improvement in concordance occurred in classifying LDL-C lower than 70 mg/dL, especially in patients with high triglyceride levels. In patients with an estimated LDL-C lower than 70 mg/dL, LDL-CD was also lower than 70 mg/dL in 94.3% (95% CI, 93.9%-94.7%) for LDL-CN vs 79.9% (95% CI, 79.3%-80.4%) for LDL-CF in samples with triglyceride levels of 100 to 149 mg/dL; 92.4% (95% CI, 91.7%-93.1%) for LDL-CN vs 61.3% (95% CI, 60.3%-62.3%) for LDL-CF in samples with triglyceride levels of 150 to 199 mg/dL; and 84.0% (95% CI, 82.9%-85.1%) for LDL-CN vs 40.3% (95% CI, 39.4%-41.3%) for LDL-CF in samples with triglyceride levels of 200 to 399 mg/dL (P < .001 for each comparison). CONCLUSIONS AND RELEVANCE: A novel method to estimate LDL-C using an adjustable factor for the TG:VLDL-C ratio provided more accurate guideline risk classification than the Friedewald equation. These findings require external validation, as well as assessment of their clinical importance. The implementation of these findings into clinical practice would be straightforward and at virtually no cost. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01698489.

Associations of Adipokine Levels with Levels of Remnant Cholesterol: the Multi-Ethnic Study of Atherosclerosis (MESA).

Background: The metabolic syndrome phenotype of individuals with obesity is characterized by elevated levels of triglyceride (TG)-rich lipoproteins and remnant particles, which have been shown to be significantly atherogenic. Understanding the association between adipokines, endogenous hormones produced by adipose tissue, and remnant cholesterol (RC) would give insight into the link between obesity and atherosclerotic cardiovascular disease. Methods: We studied 1,791 MESA participants of an ancillary study on body composition who had adipokine levels measured (leptin, adiponectin, resistin) at either visit 2 or 3. RC was calculated as non-high density lipoprotein cholesterol minus low-density lipoprotein cholesterol (LDL-C), measured at the same visit as the adipokines, as well as subsequent visits 4 through 6. Multivariable-adjusted linear mixed effects models were used to assess the cross-sectional and longitudinal associations between adipokines and levels of RC. Results: Mean (SD) age was 64.5±9.6 years and for body mass index (BMI) was 29.9±5.0 kg/m2; 52.0% were women. In fully adjusted models that included BMI, LDL-C and lipid-lowering therapy, for each 1-unit increment in adiponectin, there was 14.4% (12.0, 16.8) lower RC. With each 1-unit increment in leptin and resistin, there was 4.5% (2.3, 6.6) and 5.1% (1.2, 9.2) higher RC, respectively. Lower adiponectin and higher leptin were also associated with longitudinal increases in RC levels over median follow-up of 5(4-8) years. Conclusions: Lower adiponectin and higher leptin levels were independently associated with higher levels of RC at baseline and longitudinal RC increase, even after accounting for BMI and LDL-C. CLINICAL PERSPECTIVE: What is new?: - Among individuals without history of cardiovascular disease, adiponectin is inversely associated with cross-sectional levels of remnant cholesterol, whereas leptin and resistin are directly associated.- Adiponectin had an inverse association with progression of remnant cholesterol levels over time.What are the clinical implications?: - Adiponectin levels were not associated with LDL-C levels but with levels of triglyceride-rich lipoproteins, particularly remnant cholesterol.-Incrementing adiponectin via lifestyle modification and/or pharmacological therapies (i.e. GLP-1 agonists) could be a mechanism to reduce remnant cholesterol levels and ultimately cardiovascular risk.

Understanding Cardiology Practitioners' Interpretations of Electrocardiograms: An Eye-Tracking Study.

BACKGROUND: Visual expertise refers to advanced visual skills demonstrated when performing domain-specific visual tasks. Prior research has emphasized the fact that medical experts rely on such perceptual pattern-recognition skills when interpreting medical images, particularly in the field of electrocardiogram (ECG) interpretation. Analyzing and modeling cardiology practitioners' visual behavior across different levels of expertise in the health care sector is crucial. Namely, understanding such acquirable visual skills may help train less experienced clinicians to interpret ECGs accurately. OBJECTIVE: This study aims to quantify and analyze through the use of eye-tracking technology differences in the visual behavior and methodological practices for different expertise levels of cardiology practitioners such as medical students, cardiology nurses, technicians, fellows, and consultants when interpreting several types of ECGs. METHODS: A total of 63 participants with different levels of clinical expertise took part in an eye-tracking study that consisted of interpreting 10 ECGs with different cardiac abnormalities. A counterbalanced within-subjects design was used with one independent variable consisting of the expertise level of the cardiology practitioners and two dependent variables of eye-tracking metrics (fixations count and fixation revisitations). The eye movements data revealed by specific visual behaviors were analyzed according to the accuracy of interpretation and the frequency with which interpreters visited different parts/leads on a standard 12-lead ECG. In addition, the median and SD in the IQR for the fixations count and the mean and SD for the ECG lead revisitations were calculated. RESULTS: Accuracy of interpretation ranged between 98% among consultants, 87% among fellows, 70% among technicians, 63% among nurses, and finally 52% among medical students. The results of the eye fixations count, and eye fixation revisitations indicate that the less experienced cardiology practitioners need to interpret several ECG leads more carefully before making any decision. However, more experienced cardiology practitioners rely on their skills to recognize the visual signal patterns of different cardiac abnormalities, providing an accurate ECG interpretation. CONCLUSIONS: The results show that visual expertise for ECG interpretation is linked to the practitioner's role within the health care system and the number of years of practical experience interpreting ECGs. Cardiology practitioners focus on different ECG leads and different waveform abnormalities according to their role in the health care sector and their expertise levels.

Systemic Inflammation May Induce Cardiac Injury in COVID-19 Patients Including Children and Adolescents Without Underlying Cardiovascular Diseases: A Systematic Review.

Coronavirus disease 2019(COVID-19) is an ongoing global pandemic with a daily increasing number of affected individuals and a relatively high mortality rate. COVID-19 patients that develop cardiac injury are at increased risk of a worse clinical course with higher rates of mortality. Increasing amounts of evidence suggest that a system-wide inflammatory response and a cytokine storm mediated type syndrome plays a crucial role in disease progression. This systematic review investigates the possible role of hyperinflammation in inducing cardiac injury as one of the severe complications of COVID-19. A systematic literature search was performed using PubMed, Embase and Scopus databases to identify relevant clinical studies that investigated cardiovascular injury manifestations and reported inflammatory and cardiac biomarkers in COVID-19 patients. Only 29 studies met our inclusion criteria and the majority of these studies demonstrated significantly elevated inflammatory and cardiac blood markers. It was evident that underlying cardiovascular diseases may increase the risk of developing cardiac injury. However, many COVID-19 patients included in this review, developed different types of cardiac injury without having any underlying cardiovascular diseases. Furthermore, many of these patients were either children or adolescents. Therefore, age and comorbidities may not always be the two main risk factors that dictate the severity and outcome of COVID-19. Further investigations are required to understand the underlying mechanisms of pathogenicity as an urgent requirement to develop the appropriate treatment and prevention strategies. These strategies may specifically target hyperinflammation as a suspected driving factor for some of the severe complications of COVID-19.

New Antidiabetes Medications and Their Cardiovascular and Renal Benefits.

After 12 years of rigorous cardiovascular outcome trials (CVOTs), sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) emerged as new therapeutic options for patients with type 2 diabetes mellitus to reduce the risk of heart disease. SGLT2i additionally cause a reduction in heart failure and renal events in patients both with and without diabetes. This article reviews the major CVOTs that support the use of these agents, describes the mechanisms of action that lead to their broad cardiorenal benefits, explains current guidelines, and offers practical clinical advice to initiate and monitor treatment with these agents.