Recurrence After Atrial Fibrillation Ablation and Investigational Biomarkers of Cardiac Remodeling.

BACKGROUND: Recurrence after atrial fibrillation (AF) ablation remains common. We evaluated the association between recurrence and levels of biomarkers of cardiac remodeling, and their ability to improve recurrence prediction when added to a clinical prediction model. METHODS AND RESULTS: Blood samples collected before de novo catheter ablation were analyzed. Levels of bone morphogenetic protein-10, angiopoietin-2, fibroblast growth factor-23, insulin-like growth factor-binding protein-7, myosin-binding protein C3, growth differentiation factor-15, interleukin-6, N-terminal pro-brain natriuretic peptide, and high-sensitivity troponin T were measured. Recurrence was defined as ≥30 seconds of an atrial arrhythmia 3 to 12 months postablation. Multivariable logistic regression was performed using biomarker levels along with clinical covariates: APPLE score (Age >65 years, Persistent AF, imPaired eGFR [<60 ml/min/1.73m2], LA diameter ≥43 mm, EF <50%; which includes age, left atrial diameter, left ventricular ejection fraction, persistent atrial fibrillation, and estimated glomerular filtration rate), preablation rhythm, sex, height, body mass index, presence of an implanted continuous monitor, year of ablation, and additional linear ablation. A total of 1873 participants were included. A multivariable logistic regression showed an association between recurrence and levels of angiopoietin-2 (odds ratio, 1.08 [95% CI, 1.02-1.15], P=0.007) and interleukin-6 (odds ratio, 1.02 [95% CI, 1.003-1.03]; P=0.02). The area under the receiver operating characteristic curve of a model that only contained clinical predictors was 0.711. The addition of any of the 9 studied biomarkers to the predictive model did not result in a statistically significant improvement in the area under the receiver operating characteristic curve. CONCLUSIONS: Higher angiopoietin-2 and interleukin-6 levels were associated with recurrence after atrial fibrillation ablation in multivariable modeling. However, the addition of biomarkers to a clinical prediction model did not significantly improve recurrence prediction.

Right ventricular longitudinal strain on CMR predicts ventricular arrhythmias and mortality in cardiac sarcoidosis.

Background: Right ventricular (RV) dysfunction and late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) are associated with ventricular arrhythmias (VA) and mortality in cardiac sarcoidosis (CS). However, image resolution limits the detection of RV LGE. Global longitudinal RV strain (RVS) correlates to RV scar on electroanatomical mapping and RV function. Objective: We evaluated the association between RVS on CMR and VA/death (combined-primary-endpoint (CPE)) in patients with CS. Methods: RVS and RV LGE on MRI were retrospectively compared to variables known to predict outcomes in 66 patients with CS. Outcomes were obtained from electronic medical records and implantable cardioverter defibrillator (ICD) interrogations over median [IQR] 3.7[1.7, 6.3] years. Cox proportional hazard models were used to evaluate survival. Harrell's C-statistic was used to compare variables in risk prediction models. Results: 62.1 % of patients were male, with a mean age [SD] of 52.3 [9.6] years and left ventricular ejection fraction (LVEF) of 51.1[17.5]%. 9 patients with the primary endpoint were more likely to be Caucasian (p = 0.01) with prior VAs (p = 0.002), be on anti-arrhythmic drugs (p = 0.001) with an ICD (p = 0.002). In multivariable analyses adjusted for age, race, and history of VA, RVS (1.18 [1.05-1.31], p = 0.004), RV EDVI (1.08[1.01, 1.14], p = 0.02), and LV LGE (1.07[1.00, 1.13], p = 0.04) predicted the CPE. Risk prediction models including RVS (Cstatistic 0.94), outperformed those including RV and LV LGE (0.89-0.92). Conclusion: RVS on CMR was the best predictor of VA and mortality in CS.

Application of the very high risk criterion and evaluation of cholesterol guideline adherence in acute myocardial infarction patients at an urban academic medical center.

Objective: The 2018 AHA/ACC cholesterol guidelines recommend considering non-statin agents among very high-risk (VHR) patients with LDL-C ≥ 70 mg/dL after maximizing statin therapy. We aimed to evaluate the prevalence of VHR status in acute myocardial infarction (AMI) patients at hospital discharge and the adherence to guideline-directed cholesterol therapy (GDCT) within one-year follow-up post-AMI. Methods: We performed a retrospective analysis of patients who suffered a type 1 AMI between October 2015 and March 2019, and then were followed at our institution for 1 year after hospital discharge. We calculated the percentage of patients at VHR and among those with follow up lipid panels, we determined the proportion able to achieve GDCT. Results: The mean age of the 331 AMI patients was 61.0 (SD 11.9) years and 33.6% were women. Overall, 268 (81.0%) patients were categorized as having VHR at discharge. Among patients at VHR, a lipid panel was rechecked in 153 individuals (57.1%) within 1 year of discharge, with the median time to lipid recheck being 22.4 weeks (interquartile range: 10.9-40.7 weeks). Among those with a lipid panel re-check, 100 (65.4%) of patients achieved GDCT. Conclusions: Approximately 4 out of 5 AMI patients were considered VHR per the 2018 AHA/ACC guidelines, only about half had follow up lipid panels in the year following AMI, and about two-thirds of those with follow up lipid panels achieved GDCT.

Comparison of Methods to Estimate Low-Density Lipoprotein Cholesterol in Patients With High Triglyceride Levels.

Importance: Low-density lipoprotein cholesterol (LDL-C) is typically estimated with the Friedewald or Martin/Hopkins equation; however, if triglyceride levels are 400 mg/dL or greater, laboratories reflexively perform direct LDL-C (dLDL-C) measurement. The use of direct chemical LDL-C assays and estimation of LDL-C via the National Institutes of Health Sampson equation are not well validated, and data on the accuracy of LDL-C estimation at higher triglyceride levels are limited. Objective: To compare an extended Martin/Hopkins equation for triglyceride values of 400 to 799 mg/dL with the Friedewald and Sampson equations. Design, Setting, and Participants: This cross-sectional study evaluated consecutive patients at clinical sites across the US with patient lipid distributions representative of the US population in the Very Large Database of Lipids from January 1, 2006, to December 31, 2015, with triglyceride levels of 400 to 799 mg/dL. Data analysis was performed from November 9, 2020, to March 23, 2021. Main Outcomes and Measures: Accuracy in LDL-C classification according to guideline-based categories and absolute errors between estimated LDL-C and dLDL-C levels. Patients were randomly assigned 2:1 to derivation and validation data sets. Levels of dLDL-C were measured by vertical spin-density gradient ultracentrifugation. The LDL-C levels were estimated using the Friedewald method, with a fixed ratio of triglycerides to very low-density lipoprotein cholesterol (VLDL-C ratio of 5:1), extended Martin/Hopkins equation with a flexible ratio, and Sampson equation with VLDL-C estimation by multiple least-squares regression. Results: A total of 111 939 patients (mean [SD] age, 52 [13] years; 65.0% male) with triglyceride levels of 400 to 799 mg/dL were included, representing 2.2% of 5 081 680 patients in the database. Across all individual guideline LDL-C classes (<40, 40-69, 70-99, 100-129, 130-159, 160-189, and ≥190), estimation of LDL-C by the extended Martin/Hopkins equation was most accurate (62.1%) compared with the Friedewald (19.3%) and Sampson (40.4%) equations. In classifying LDL-C levels less than 70 mg/dL across all triglyceride strata, the extended Martin/Hopkins equation was most accurate (67.3%) compared with Friedewald (5.1%) and Sampson (26.4%) equations. In addition, for classifying LDL-C levels less than 40 mg/dL across all triglyceride strata, the extended Martin/Hopkins equation was most accurate (57.2%) compared with the Friedewald (4.3%) and Sampson (14.4%) equations. However, considerable underclassification of LDL-C occurred. The magnitude of error between the Martin/Hopkins equation estimation and dLDL-C was also smaller: at LDL-C levels less than 40 mg/dL, 2.7% of patients had 30 mg/dL or greater differences between dLDL-C and estimated LDL-C using the Martin/Hopkins equation compared with the Friedewald (92.5%) and Sampson (38.7%) equations. Conclusions and Relevance: In this cross-sectional study, the extended Martin/Hopkins equation offered greater LDL-C accuracy compared with the Friedewald and Sampson equations in patients with triglyceride levels of 400 to 799 mg/dL. However, regardless of method used, caution is advised with LDL-C estimation in this triglyceride range.

Inflammation, atrial fibrillation, and the potential role for colchicine therapy.

Increasing evidence suggests that the "NACHT-LRR and PYD domain-containing protein 3" (NLRP3) inflammasome plays an important role in atherosclerotic cardiovascular disease (ASCVD). Recent preclinical evidence has suggested that the NLRP3 inflammasome may play a prominent role in the pathogenesis of atrial fibrillation (AF). As such, the therapies that have shown efficacy in reducing ASCVD events may also prove beneficial in AF. In this article, we review the findings that implicate the NLRP3 inflammasome in the pathogenesis of AF, discuss existing evidence behind the use of anti-inflammatory agents for AF, and discuss the future role that colchicine and other anti-inflammatory agents may play in the prevention and treatment of AF.

Importance of the triglyceride level in identifying patients with a Type III Hyperlipoproteinemia phenotype using the ApoB algorithm.

BACKGROUND: Hyperlipoproteinemia Type III (HLP3), also known as dysbetalipoproteinemia, is defined by cholesterol and triglyceride (TG) enriched remnant lipoprotein particles (RLP). The gold standard for diagnosis requires demonstration of high remnant lipoprotein particle cholesterol (RLP-C) by serum ultracentrifugation (UC), which is not readily available in daily practice. The apoB algorithm can identify HLP3 using total cholesterol (TC), plasma triglyceride (TG), and apoB. However, the optimal TG cutoff is unknown. OBJECTIVE: We analyzed apoB algorithm defined HLP3 at different TG levels to optimize the TG cutoff for the algorithm. METHODS: 128,485 UC lipid profiles in the Very Large Database of Lipids (VLDbL) were analyzed. RLP-C was assessed at TG ≥ 133 mg/dL, ≥175 mg/dL, ≥200 mg/dL, and ≥ 250 mg/dL. Sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and prevalence adjusted and bias-adjusted kappa (PABAK) were calculated against UC Criterion (VLDL-C/TG ≥ 0.25) for HLP3. RESULTS: The median age (IQR) was 57 years (46-68). 45% were men, 20.1% had diabetes, and 25.5% had hypertension. The median RLP-C level for the TG cutoffs (mg/dL) of ≥ 133, ≥ 175, ≥ 200, and ≥ 250 were 34, 43, 50, and 62 mg/dL, respectively, compared to 67 mg/dL in UC defined HLP3. TG ≥ 133 mg/dL yielded optimal results (Sn 29.5%, Sp 98.5%, PABAK 0.96, PPV 13.6%, NPV 99.4%). CONCLUSION: TG ≥ 133 mg/dL allows for high sensitivity in screening for HLP3. Higher TG cutoffs may identify more severe HLP3 phenotypes, but with a large loss in sensitivity for HLP3.

Inflammatory hypothesis of atherogenesis: Will colchicine be added to the armamentarium in the prevention of coronary artery disease?

Chronic inflammation promotes the development and progression of atherosclerosis. Despite aggressive risk reduction, patients with coronary artery disease have a significant residual risk of myocardial infarction and cardiovascular death related in part to ongoing inflammation within coronary vasculature. In this review, we summarize the clinical trials that provide evidence for the inflammatory hypothesis of atherogenesis. Additionally, we describe studies suggesting colchicine may be able to reduce residual inflammatory risk via the NLRP3 pathway. Given its tolerable side effect profile, safety, and low cost, colchicine holds promise as an anti-inflammatory agent in primary and secondary prevention of coronary disease.

Coronary Artery Dose-Volume Parameters Predict Risk of Calcification After Radiation Therapy.

BACKGROUND: Radiation exposure increases the risk of coronary artery disease (CAD). We explored the association of CAD with coronary artery dose-volume parameters in patients treated with 3D-planned radiation therapy (RT). METHODS: Patients who received thoracic RT and were evaluated by cardiac computed tomography ≥ 1 year later were included. Demographic data and cardiac risk factors were retrospectively collected. Dosimetric data (mean heart dose, dmax, dmean, V50 - V5) were collected for the whole heart and for each coronary artery. A coronary artery calcium (CAC) Agatston score was calculated on a per-coronary basis and as a total score. Multivariable generalized linear mixed models were generated. The predicted probabilities were used for receiver operating characteristic analyses. RESULTS: Twenty patients with a median age of 53 years at the time of RT were included. Nine patients (45%) had ≥ 3/6 conventional cardiac risk factors. Patients received RT for breast cancer (10, 50%), lung cancer (6, 30%), or lymphoma/myeloma (4, 20%) with a median dose of 60 Gy. CAC scans were performed a median of 32 months after RT. CAC score was significantly associated with radiation dose and presence of diabetes. In a multivariable model adjusted for diabetes, segmental coronary artery dosimetric parameters (dmax, dmean, V50, V40 V30, V20, V10, and V5) were significantly associated with CAC score > 0. V50 had the highest area under the ROC curve (0.89, 95% confidence interval, 0.80-0.97). CONCLUSIONS: Coronary artery radiation exposure is strongly correlated with subsequent segmental CAC score. Coronary calcification may occur soon after RT and in individuals with conventional cardiac risk factors.

Aspergillus endocarditis of the mitral valve with ventricular myocardial invasion, cerebral vasculitis, and intracranial mycotic aneurysm formation in a patient with hemophagocytic lymphohistiocytosis.

Aspergillus endocarditis is a rare infection and reported mainly in immunocompromised hosts. We report a case of mitral valve aspergillus endocarditis with ventricular myocardial invasion, cerebral vasculitis and intracranial fungal aneurysm formation in a patient with hemophagocytic lymphohistiocytosis (HLH). This case illustrates the importance of prompt investigation and treatment of masses seen on an echocardiogram for rare infections such as Aspergillus endocarditis in immunocompromised patients.

Erythrocytosis Following Testosterone Therapy.

INTRODUCTION: A rapid increase in awareness of androgen deficiency has led to substantial increases in prescribing of testosterone therapy (TTh), with benefits of improvements in mood, libido, bone density, muscle mass, body composition, energy, and cognition. However, TTh can be limited by its side effects, particularly erythrocytosis. This review examines the literature on testosterone-induced erythrocytosis and polycythemia. AIM: To review the available literature on testosterone-induced erythrocytosis, discuss possible mechanisms for pathophysiology, determine the significance of formulation, and elucidate potential thromboembolic risk. METHODS: A literature review was performed using PubMed for articles addressing TTh, erythrocytosis, and polycythemia. MAIN OUTCOME MEASURES: Mechanism, pharmacologic contribution, and risk of testosterone-induced erythrocytosis. RESULTS: For men undergoing TTh, the risk of developing erythrocytosis compared with controls is well established, with short-acting injectable formulations having the highest associated incidence. Potential mechanisms explaining the relation between TTh and erythrocytosis include the role of hepcidin, iron sequestration and turnover, erythropoietin production, bone marrow stimulation, and genetic factors. High blood viscosity increases the risk for potential vascular complications involving the coronary, cerebrovascular, and peripheral vascular circulations, although there is limited evidence supporting a relation between TTh and vascular complications. CONCLUSION: Short-acting injectable testosterone is associated with greater risk of erythrocytosis compared with other formulations. The mechanism of the pathophysiology and its role on thromboembolic events remain unclear, although some data support an increased risk of cardiovascular events resulting from testosterone-induced erythrocytosis. Ohlander SJ, Varghese B, Pastuszak AW. Erythrocytosis Following Testosterone Therapy. Sex Med Rev 2018;6:77-85.

Dynamic interrogator for elastic wave sensing using Fabry Perot filters based on fiber Bragg gratings.

Use of in-fiber Fabry-Perot (FP) filters based on fiber Bragg gratings as both sensor as well as an interrogator for enhancing the detection limit of elastic wave sensing is investigated in this paper. The sensitivity of such a demodulation scheme depends on the spectral discrimination of the sensor and interrogator gratings. Simulations have shown that the use of in-fiber FP filters with high finesse provide better performance in terms of sensitivity compared to the demodulation using fiber Bragg gratings. Based on these results, a dynamic interrogator capable of sensing acoustic waves with amplitude of less than 1 micro-strain over frequencies of 10 kHz to several 100 kHz has been implemented. Frequency response of the fiber Bragg gratings in the given experimental setup has been compared to that of the conventional piezo sensors demonstrating that fiber Bragg gratings can be used over a relatively broad frequency range. Dynamic interrogator has been packaged in a compact box without any degradation in its performance.

Molecular catch bonds and the anti-Hammond effect in polymer mechanochemistry.

While the field of polymer mechanochemistry has traditionally focused on the use of mechanical forces to accelerate chemical processes, theoretical considerations predict an underexplored alternative: the suppression of reactivity through mechanical perturbation. Here, we use electronic structure calculations to analyze the mechanical reactivity of six mechanophores, or chemical functionalities that respond to mechanical stress in a controlled manner. Our computational results indicate that appropriately directed tensile forces could attenuate (as opposed to facilitate) mechanochemical phenomena. Accompanying experimental studies supported the theoretical predictions and demonstrated that relatively simple computational models may be used to design new classes of mechanically responsive materials. In addition, our computational studies and theoretical considerations revealed the prevalence of the anti-Hammond (as opposed to Hammond) effect (i.e., the increased structural dissimilarity between the reactant and transition state upon lowering of the reaction barrier) in the mechanical activation of polyatomic molecules.