Prognostic value of left atrial strain in aortic stenosis: A systematic review.

PURPOSE: Aortic stenosis (AS) is a common valvular heart disease with high morbidity and mortality. Recently, the association between peak atrial longitudinal strain (PALS) and AS clinical outcomes has been identified. This systematic review evaluates the prognostic value of PALS for adverse events in AS. METHODS: We performed a systematic literature review to identify clinical studies that evaluated Speckle-Tracking Echocardiography (STE)-derived PALS to predict adverse outcomes in patients with AS. We excluded studies that compared echocardiography to computed tomography and studies that focused on diseases other than AS. RESULTS: We included 18 studies reporting on 2660 patients. Patients with symptomatic AS had decreased PALS when compared to patients with asymptomatic AS. Patients with AS who had adverse events had decreased PALS when compared to patients with AS with no events. Each unit increase of PALS was independently associated with decreased risk for the primary endpoint. PALS cut-off values were associated with increased risk for the primary endpoint. CONCLUSION: This systematic review suggests PALS as an independent predictor for cardiovascular events in patients with AS and highlights the importance of evaluating LA mechanics for AS prognosis.

Perioperative myocardial injury and infarction after noncardiac surgery: a review of pathophysiology, diagnosis, and management.

Perioperative myocardial injury is a relatively common complication after noncardiac surgery associated with significant morbidity and mortality. It is frequently driven by physiologic factors such as hypotension, tachycardia, and anemia. Diagnosis of perioperative myocardial injury after noncardiac surgery is based on elevated cardiac troponin levels, greater than the 99th percentile of the assay's upper reference limit within 30 days of surgery. Perioperative myocardial injury is further classified into non-ischemic and ischemic based on the underlying pathophysiology. Ischemic injury, also called myocardial injury after non-cardiac surgery (MINS), is further classified into perioperative myocardial infarction or myocardial injury without infarction. Classifying perioperative myocardial injury further is particularly important for clinical management and prognosis. MINS-with or without infarction-is independently and strongly associated with short- and long-term mortality. Compared to nonoperative myocardial infarction, perioperative myocardial infarction carries an increased risk of adverse outcomes including all-cause mortality. Preventative measures include a thorough preoperative risk assessment, risk factor optimization, and avoidance of intraoperative mismatch of myocardial oxygen supply and demand. Surveillance of patients at higher risk of cardiovascular complications is warranted and can lead to early recognition, closer monitoring, and appropriate management. This review will provide a framework for understanding perioperative myocardial injury and highlight the contemporary literature addressing its diagnosis and management.

Low Contrast and Low kV CTA Before Transcatheter Aortic Valve Replacement: A Systematic Review.

BACKGROUND: Minimizing contrast dose and radiation exposure while maintaining image quality during computed tomography angiography (CTA) for transcatheter aortic valve replacement (TAVR) is desirable, but not well established. This systematic review compares image quality for low contrast and low kV CTA versus conventional CTA in patients with aortic stenosis undergoing TAVR planning. METHODS: We performed a systematic literature review to identify clinical studies comparing imaging strategies for patients with aortic stenosis undergoing TAVR planning. The primary outcomes of image quality as assessed by the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were reported as random effects mean difference with 95% confidence interval (CI). RESULTS: We included 6 studies reporting on 353 patients. There was no difference in cardiac SNR (mean difference, -1.42; 95% CI, -5.71 to 2.88; p = 0.52), cardiac CNR (mean difference, -3.83; 95% CI, -9.98 to 2.32; p = 0.22), aortic SNR (mean difference, -0.23; 95% CI, -7.83 to 7.37; p = 0.95), aortic CNR (mean difference, -3.95; 95% CI, -12.03 to 4.13; p = 0.34), and ileofemoral SNR (mean difference, -6.09; 95% CI, -13.80 to 1.62; p = 0.12) between the low dose and conventional protocols. There was a difference in ileofemoral CNR between the low dose and conventional protocols with a mean difference of -9.26 (95% CI, -15.06 to -3.46; p = 0.002). Overall, subjective image quality was similar between the 2 protocols. CONCLUSIONS: This systematic review suggests that low contrast and low kV CTA for TAVR planning provides similar image quality to conventional CTA.

Interrelationship Between Inflammatory Biomarkers and Collagen Remodeling Proteins in Atrial Fibrillation.

INTRODUCTION: Atrial Fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide. Inflammation and structural remodeling of the left atrium are thought to be involved in the pathogenesis of AF. This study explores collagen remodeling and inflammatory biomarkers in AF patients compared to healthy controls to discern their role in AF. MATERIALS AND METHODS: Plasma samples were collected from AF patients undergoing first AF ablation (n = 72) and compared with commercially available human plasma samples from healthy subjects (n = 62). The collagen remodeling biomarkers and inflammatory biomarkers in the AF patients and control population were quantified using sandwich ELISA kits. GraphPad prism was used to perform statistical analyses. RESULTS: There was a statistically significant elevation in all the collagen remodeling biomarkers and inflammatory biomarkers in the AF patients compared to healthy controls. Spearman correlation analysis demonstrated significant correlations between inflammatory and collagen remodeling biomarkers, and among the collagen biomarkers. Of note, CRP was found to be correlated with TIMP-1, ICTP and PIIINP. IL6 and TIMP-1 were also found to be intercorrelated. Furthermore, correlations were noted among the different collagen remodeling peptides, and between TNFα and IL6, two of the inflammatory markers explored in this study. CONCLUSIONS: The elevation of the inflammatory biomarkers and collagen remodeling proteins in AF patients is suggestive of inflammation and increased collagen turnover. The association between inflammatory biomarkers and collagen remodeling proteins may contribute to their regulation and role in the remodeling process.

Association of left atrial size and function by cardiac magnetic resonance imaging with long term outcomes in patients with hypertrophic cardiomyopathy.

Left atrial (LA) function and strain are being investigated as markers of disease progression in hypertrophic cardiomyopathy (HCM). To assess LA function and strain by cardiac magnetic resonance imaging (MRI) in patients with HCM and evaluate the association of these parameters with long-term clinical outcomes. We retrospectively evaluated 50 HCM patients and 50 patients with no significant cardiovascular disease (control) who underwent clinically indicated cardiac MRI. We calculated LA volumes using the Simpson area-length method to derive LA ejection fraction and expansion index. MRI-derived left atrial reservoir (ƐR), conduit (ƐCD), and contractile strain (ƐCT) were measured using dedicated software. A multivariate regression analysis with endpoints of ventricular tachyarrhythmias (VTA) and heart failure hospitalization (HFH) was performed. HCM patients had significantly higher LV mass, higher LA volumes and lower LA strain compared to controls. During the median follow up of 15.6 months (interquartile range 8.4-35.4 months), 11 patients (22%) experienced a HFH, while 10 patients (20%) had VTA. Multivariate analysis demonstrated that ƐCT (odds ratio (OR) 0.96, confidence interval (CI) 0.83-1.00) and LA ejection fraction (OR 0.89, CI 0.79-1.00) were significantly associated with VTA and HFH respectively.

Association of Left Atrial Hemodynamics by Magnetic Resonance Imaging With Long-Term Outcomes in Patients With Cardiac Amyloidosis.

BACKGROUND: Left atrial (LA) function and strain patterns by magnetic resonance imaging (MRI) have been investigated as markers of several cardiovascular pathologies, including cardiac amyloidosis (CA). However, associations with clinical outcomes have not been investigated. PURPOSE: To compare LA function and strain by MRI in CA patients to a matched cohort of patients without cardiovascular disease (CVD) and evaluate the association with long-term clinical outcomes in CA patients. STUDY TYPE: Retrospective case control. POPULATION: A total of 51 patients with CA and 51 age-, gender-, and race-matched controls without CVD who underwent MRI in sinus rhythm. FIELD STRENGTH/SEQUENCE: ECG-gated balanced steady-state free precession sequence at 1.5 T. ASSESSMENT: All measurements were completed by one investigator (M.M.B.). LA function and strain parameters were measured including LA indexed minimum and maximum volumes, LA reservoir (R), contractile (CT), and conduit (CD) strain. We compared groups after adjusting for age, hypertension, New York Heart Association class, modified staging system (troponin-I, BNP, estimated GFR) and left ventricular ejection fraction (LVEF) for an endpoint of all-cause mortality and a composite endpoint of heart failure hospitalization (HFH) or death. STATISTICAL TESTS: Differences between groups were evaluated with t tests for continuous variables or χ2 tests for categorical variables. A multivariable regression model was used to assess the associations of the P values-two-sided tests-<0.05 were considered statistically significant. RESULTS: CA patients with median follow up of 4.9 (8.5) months had significantly lower LA strain and higher LA volumes in comparison to the matched cohort. In the multivariable analysis, only LVEF was significantly associated with death while ƐCT (OR 0.6, CI: 0.41-0.89), indexed minimum LA volume (OR 1.06, CI: 1.02-1.13) and indexed maximum LA volume (OR 1.08, CI: 1.01-1.15) were significantly associated with the composite outcome of death or HFH. CONCLUSION: In this retrospective study of CA patients, ƐCT and indexed minimum and maximum LA volumes were significantly associated with the composite outcome of death or HFH. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Comparison of LGE quantitation methods in cardiac sarcoidosis to predict clinical outcomes.

We sought to investigate the optimal method of quantifying late gadolinium enhancement (LGE) in cardiac sarcoidosis (CS) using cardiac magnetic resonance imaging (MRI). We retrospectively studied 53 patients with CS. LGE quantitation was performed using (a) semi-automated segmentation using Signal Threshold versus Reference Mean (STRM) cutoffs of > 2, > 3 and > 5 standard deviations (SD); (b) full-width-half-max (FWHM) method and (c) manual segmentation (MS) of affected myocardial segments. Primary outcome was a composite of cardiovascular death and ventricular tachyarrhythmia (VTA). A multivariate regression analysis was performed comparing the techniques adjusting for age, gender, NYHA class and LVEF. Mean age was 56.3 ± 12 years, 71.6% males, 66% white. Mean LVEF was 45.1% ± 14.7%. Over median follow-up of 28.1 months, 2 patients had cardiac death (3.7%) and 8 (15.1%) had VTA. On multivariate analysis, MS, > 2SD, > 3SD, > 5SD and FWHM had OR of 1.39 [CI 1.04-1.79], 1.09 [CI 0.99-1.21], 1.15 [CI 1.03-1.29], 1.16 [CI 1.04-1.27] and 1.08 [CI 0.96-1.21], respectively, for predicting the composite outcome. ROC curve analysis showed MS to have the highest AUC 0.89 followed by 0.81 for > 3SD and > 5SD, 0.75 for > 2SD and lowest 0.69 for FWHM method. Reproducibility was lower for manual method (ICC 0.7) than for > 3SD (ICC 0.991) and > 5SD (ICC 0.997). CS quantitation of LGE with MS or semi-automated quantitation with STRM > 3SD or > 5SD was significantly associated with the composite outcome of cardiac death and VTA. Semi-automated quantitation with STRM > 3SD provided the best combination of accuracy and reproducibility.

Collagen Remodeling and Fatty Acid Regulation Biomarkers in Understanding the Molecular Pathogenesis of Atrial Fibrillation.

INTRODUCTION: Atrial Fibrillation (AF) is the most common cardiac arrythmia in the world. Structural remodeling and fatty acid metabolism dysregulation are believed to play a role in the development of AF. This study explored different biomarkers in the blood of AF patients and a control population to determine if there was a significant difference between the two groups. MATERIAL AND METHODS: Plasma samples were collected from 73 patients with confirmed diagnosis of AF from Loyola University Clinic. Control group represented commercially available plasma (n = 50). Sandwich ELISA kits were used to quantify the collagen remodeling proteins and liver type fatty acid binding protein (L-FABP) in the AF population and the control population. Non-esterified fatty acids (NEFAs) were measured using an enzymatic colorimetric kit from Wako Diagnostics. Statistical analyses were performed using GraphPad Prism. RESULTS: All the collagen remodeling biomarkers were significantly higher in AF patients compared to the control group. The fatty acid dysregulation biomarkers were elevated in the AF patients. Spearman correlation analyses yielded significant correlations between L-FABP and TIMP-1 (r = 0.47, P < 0.001), NEFA and TIMP-2 (r = 0.41, P = 0.002), NEFA and ICTP (r = 0.41, P =0 .002), and NEFA and PIIINP (r = 0.61, P < 0.0001). SUMMARY AND CONCLUSIONS: The elevation of collagen remodeling biomarkers suggests an upregulation of these biomarkers and their potential role in AF, which may contribute to atrial fibrosis. L-FABP and NEFAs were elevated in AF patients. The correlations between the collagen remodeling and fatty acid dysregulation biomarkers may be due to their involvement in structural remodeling of the atria.

Impact of late gadolinium enhancement extent, location, and pattern on ventricular tachycardia and major adverse cardiac events in patients with ischemic vs. non-ischemic cardiomyopathy.

Background: Left ventricular late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) has been associated with increased risk for life-threatening ventricular tachyarrhythmias. The differences in association between LGE characteristics and prognosis in patients with ischemic (ICM) vs. non-ischemic (NICM) cardiomyopathy is incompletely understood. Methods: A total of 168 consecutive patients who underwent CMR imaging with either ICM or NICM were included in our study. LGE extent, location and pattern were examined for association to the primary endpoint of ventricular tachycardia (VT) and secondary endpoint of major adverse cardiac events (MACE). Results: Of 68 (41%) patients with ICM and 97 (59%) patients with NICM, median LGE mass was 15% (IQR 9-28) for the ICM group and 10% (IQR 6-15) for the NICM group. On multivariate analysis for both groups, LGE characteristics were prognostic while LVEF was not. In patients with ICM, septal and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median) and inferior wall LGE independently predicted the primary endpoint. In patients with NICM, anterior, inferior and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median, number of LGE segments, LGE stratified per 5% increase) and midwall LGE were independent predictors of the primary endpoint. Conclusions: Although LGE was an independent predictor of prognosis in both groups, LGE extent, location, and pattern characteristics were more powerful correlates to worse outcomes in patients with NICM than ICM.

Association of left atrial strain by cardiovascular magnetic resonance with recurrence of atrial fibrillation following catheter ablation.

BACKGROUND: Atrial fibrillation (AF) is a progressive condition, which is characterized by inflammation/fibrosis of left atrial (LA) wall, an increase in the LA size/volumes, and decrease in LA function. We sought to investigate the relationship of anatomical and functional parameters obtained by cardiovascular magnetic resonance (CMR), with AF recurrence in paroxysmal AF (pAF) patients after catheter ablation. METHODS: We studied 80 consecutive pAF patients referred for ablation, between January 2014 and December 2019, who underwent pre- and post-ablation CMR while in sinus rhythm. LA volumes were measured using the area-length method and included maximum, minimum, and pre-atrial-contraction volumes. CMR-derived LA reservoir strain (ℇR), conduit strain (ℇCD), and contractile strain (ℇCT) were measured by computer assisted manual planimetry. We used a multivariate logistical regression to estimate the independent predictors of AF recurrence after ablation. RESULTS: Mean age was 58.6 ± 9.4 years, 75% men, mean CHA2DS2-VASc score was 1.7, 36% had prior cardioversion and 51% were taking antiarrhythmic drugs. Patients were followed for a median of 4 years (Q1-Q3 = 2.5-6.2 years). Of the 80 patients, 21 (26.3%) patients had AF recurrence after ablation. There were no significant differences between AF recurrence vs. no recurrence groups in age, gender, CHA2DS2-VASc score, or baseline comorbidities. At baseline, patients with AF recurrence compared to without recurrence had lower LV end systolic volume index (32 ± 7 vs 37 ± 11 mL/m2; p = 0.045) and lower ℇCT (7.1 ± 4.6 vs 9.1 ± 3.7; p = 0.05). Post-ablation, patients with AF recurrence had higher LA minimum volume (68 ± 32 vs 55 ± 23; p = 0.05), right atrial volume index (62 ± 20 vs 52 ± 19 mL/m2; p = 0.04) and lower LA active ejection fraction (24 ± 8 vs 29 ± 11; p = 0.05), LA total ejection fraction (39 ± 14 vs 46 ± 12; p = 0.02), LA expansion index (73.6 ± 37.5 vs 94.7 ± 37.1; p = 0.03) and ℇCT (6.2 ± 2.9 vs 7.3 ± 1.7; p = 0.04). Adjusting for clinical variables in the multivariate logistic regression model, post-ablation minimum LA volume (OR 1.09; CI 1.02-1.16), LA expansion index (OR 0.98; CI 0.96-0.99), and baseline ℇR (OR 0.92; CI 0.85-0.99) were independently associated with AF recurrence. CONCLUSION: Significant changes in LA volumes and strain parameters occur after AF ablation. CMR derived baseline ℇR, post-ablation minimum LAV, and expansion index are independently associated with AF recurrence.

Comparison of left atrial strain by feature-tracking cardiac magnetic resonance with speckle-tracking transthoracic echocardiography.

Left atrial (LA) strain is a novel non-invasive parameter for assessing LA hemodynamics and function. We sought to compare the intermodality differences between transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) derived LA strain, as well as reproducibility of strain measurements. We evaluated 70 subjects (mean age 42.1 ± 17 years, 44% males) with no significant cardiovascular disease who underwent both CMR and TTE within 6 months of each other. LA strain measurements i.e. reservoir strain (ƐR), conduit strain (ƐCD), and contractile strain (ƐCT), were compared using speckle-tracking echocardiography (STE) and CMR feature tracking (CMR-FT). Correlation and systematic bias between modalities was evaluated using intraclass correlation coefficient (ICC) and proportional bias. TTE was performed before CMR with a median duration of 33 days (IQR 14-69 days). ICC for ƐR, ƐCT, ƐCD was 0.66 (95% CI 0.44-0.79), 0.63 (95% CI 0.4-0.77) and 0.56 (95% CI 0.3-0.73) respectively. There was evidence of systematic bias between modalities, on average LA volume was found to be 19% higher on CMR than TTE. Strain values were also higher by CMR-FT compared to STE with mean difference of 9.9 ± 12 (26.1%), 3.1 ± 5.5 (21.9%), 4.0 ± 9.9 (16.6%) for ƐR, ƐCT and ƐCD respectively. Regression showed proportional bias for both ƐR, and ƐCT (beta 0.76, 0.54 respectively; P < 0.0001). There were modest differences in intraobserver reproducibility between both modalities with better reproducibility for STE compared to CMR-FT. There was a modest intermodality correlation between STE and CMR-FT derived LA strain components. There were systematic differences and proportional bias in measurements between modalities. These differences should be considered when interpreting LA strain using either modality.

Biomarkers of Thrombo-Inflammatory Responses in Pulmonary Embolism Patients With Pre-Existing Versus New-Onset Atrial Fibrillation.

Pulmonary embolism (PE) patients have an increased prevalence and incidence of atrial fibrillation (AF). Because comorbid AF increases risk of morbidity and mortality, we sought to investigate the role of thrombo-inflammatory biomarkers in risk stratifying patients who experience an acute PE episode. Study participants were enrolled from a Pulmonary Embolism Response Team (PERT) registry between March 2016 and March 2019 at Loyola University Medical Center and Gottlieb Memorial Hospital. This cohort was divided into 3 groups: PE patients with a prior diagnosis of AF (n = 8), PE patients with a subsequent diagnosis of AF (n = 11), and PE patients who do not develop AF (n = 71). D-dimer, CRP, PAI-1, TAFIa, FXIIIa, A2A, MP, and TFPI were profiled using the ELISA method. All biomarkers were significantly different between controls and PE patients (P < 0.05). Furthermore, TFPI was significantly elevated in PE patients who subsequently developed AF compared to PE patients who did not develop AF (157.7 ± 19.0 ng/mL vs. 129.0 ± 9.3 ng/mL, P = 0.0386). This study suggests that thrombo-inflammatory biomarkers may be helpful in indicating an acute PE episode. Also, elevated TFPI levels may be associated with an increased risk of developing AF after a PE.

Clinical characteristics and outcomes of patients with severe left ventricular dysfunction undergoing cardiac MRI viability assessment prior to revascularization.

Coronary artery bypass grafting improves survival in patients with ischemic cardiomyopathy, however, these patients are at high risk for morbidity and mortality. The role of viability testing to guide revascularization in these patients is unclear. Cardiac magnetic resonance imaging (CMR) has not been studied adequately in this population despite being considered a reference standard for infarct imaging. We performed a multicenter retrospective analysis of patients (n = 154) with severe left ventricular systolic dysfunction [ejection fraction (EF) < 35%] on CMR who underwent CMR viability assessment prior to consideration for revascularization. Using the AHA16-segment model, percent total myocardial viability was determined depending on the degree of transmural scar thickness. Patients with or without revascularization had similar clinical characteristics and were prescribed similar medical therapy. Overall, 43% of patients (n = 66) experienced an adverse event during the median 3 years follow up. For the composite outcome (death, myocardial infarction, heart failure hospitalization, stroke, ventricular tachycardia) patients receiving revascularization were less likely to experience an adverse event compared to those without revascularization (HR 0.53, 95% CI 0.33-0.86, p = 0.01). Patients with > 50% viability on CMR had a 47% reduction in composite events when undergoing revascularization opposed to medical therapy alone (HR 0.53, p = 0.02) whereas patients with a viability < 50% were 2.7 times more likely to experience an adverse event (p = 0.01). CMR viability assessment may be an important tool in the shared decision-making process when considering revascularization options in patients with severe ischemic cardiomyopathy.

ACR Appropriateness Criteria® Blunt Chest Trauma-Suspected Cardiac Injury.

Blunt cardiac injuries range from myocardial concussion (commotio cordis) leading to fatal ventricular arrhythmias to myocardial contusion, cardiac chamber rupture, septal rupture, pericardial rupture, and valvular injuries. Blunt injuries account for one-fourth of the traumatic deaths in the United States. Chest radiography, transthoracic echocardiography, CT chest with and without contrast, and CT angiography are usually appropriate as the initial examination in patients with suspected blunt cardiac injury who are both hemodynamically stable and unstable. Transesophageal echocardiography and CT heart may be appropriate as examination in patients with suspected blunt cardiac injuries. This publication of blunt chest trauma-suspected cardiac injuries summarizes the literature and makes recommendations for imaging based on the available data and expert opinion. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Procalcitonin as a Marker of Comorbid Atrial Fibrillation in Chronic Kidney Disease and History of Sepsis.

Cardiovascular disease and infection are the leading causes of mortality in patients with stage 5 chronic kidney disease on hemodialysis (CKD5-HD). Inflammation is a large component in the pathogenesis of both atrial fibrillation (AF) and sepsis and may link these conditions in CKD5-HD. Procalcitonin (PCT) is an inflammatory biomarker elevated in systemic infection and CKD5-HD, yet its value with regard to comorbid AF has not been thoroughly investigated. The aim of this study sought to evaluate circulating inflammatory markers, including PCT, Angiopoietin-1, Angiopoetin-2, CD40-L, C-reactive protein, d-dimer, and von Willebrand factor in relation to these conditions. Plasma levels of inflammatory markers were measured by enzyme linked immunosorbent assay method in CKD5-HD (n = 97) patients and controls (n = 50). Procalcitonin levels were significantly elevated (P = .0270) in CKD5-HD with comorbid AF compared to those without AF. Further analysis of patients with a history of sepsis demonstrated significantly elevated levels of PCT (P = .0405) in those with comorbid AF (160.7 ± 39.5 pg/mL) compared to those without AF (117.4 ± 25.3 pg/mL). This study demonstrates that the inflammatory biomarker PCT is further elevated in the presence of both AF and a history of sepsis in hemodialysis patients and suggests that underlying chronic inflammation following sepsis resolution may place these patients at greater risk of developing AF.

Relationship Between 25-Hydroxyvitamin D, Renin, and Collagen Remodeling Biomarkers in Atrial Fibrillation.

The interplay between vitamin D, the renin-angiotensin system (RAS), and collagen remodeling has been implicated in the pathogenesis of various cardiovascular diseases. This study sought to explore this relationship in atrial fibrillation (AF) by profiling plasma levels of 25-hydroxyvitamin D, RAS biomarkers, and collagen remodeling biomarkers using the enzyme-linked immunosorbent assay method. We hypothesized that 25-hydroxyvitamin D levels would inversely correlate with RAS biomarkers and that levels of RAS and collagen remodeling biomarkers would positively correlate with each other. Although our AF cohort (n = 37) did not exhibit decreased 25-hydroxyvitamin D levels compared to normal controls (n = 26), these levels inversely correlated with renin (Spearman r = -0.57, P = 0.005). Renin levels were elevated in patients with AF compared to normal controls (1233 ± 238 ng/mL vs 401 ± 27 ng/mL, P = 0.0002) and positively correlated with levels of matrix metalloproteinase 1 (MMP-1; Spearman r = 0.89, P = 0.01) and MMP-2 (Spearman r = 0.82, P = 0.03). These data suggest that 25-hydroxyvitamin D may influence RAS activation, and renin may help mediate the collagen remodeling process in AF. Understanding mediators of RAS dysregulation in AF may elucidate targets for therapeutic intervention to prevent collagen remodeling.

Biomarker Profiling in Stage 5 Chronic Kidney Disease Identifies the Relationship between Angiopoietin-2 and Atrial Fibrillation.

Atrial fibrillation (AF) is prevalent in nearly 27% of patients with stage 5 chronic kidney disease on hemodialysis (CKD5-HD), suggesting a strong association between these 2 pathologies. It is hypothesized that the relationship between these 2 diseases may be mediated by inflammation. Angiopoietin-2 (Ang-2), a pro-inflammatory biomarker of endothelial instability, inflammation, and vascular remodeling, is elevated in CKD5-HD and AF, yet has not been evaluated in patients with concomitant AF and CKD5-HD. The aim of this study is to analyze circulating levels of inflammatory and thrombotic biomarkers in patients with concomitant AF and CKD5-HD. Plasma levels of Ang-2 were measured via sandwich enzyme-linked immunosorbent assay method in CKD5-HD patients (n = 96), patients with AF (n = 38), and controls (n = 50). Angiopoietin-2 was markedly elevated in CKD5-HD with comorbid AF as compared to CKD5-HD alone, and AF alone, respectively (13.05 ± 1.56 vs 9.57 ± 0.71 ng/mL; P = .00169; vs 2.48 ± 0.57 ng/mL; P < .0001). The results of this study suggest an additive effect of Ang-2 with coexistence of AF and CKD5-HD, which may be useful in the detection of AF within this patient population.

Biomarkers of Inflammation, Thrombogenesis, and Collagen Turnover in Patients With Atrial Fibrillation.

The purpose of this study was to determine whether there are any differences in the levels of inflammatory, thrombotic, and collagen turnover biomarkers between individuals with atrial fibrillation (AF) and healthy volunteers. Circulating plasma levels of plasminogen activator inhibitor 1 (PAI-1), CD40-ligand (CD40-L), nucleosomes (which are indicators of cell death), C-reactive protein (CRP), procollagen III N-terminal propeptide (PIIINP), procollagen III C-terminal propeptide (PIIICP), procollagen I N-terminal propeptide, tissue plasminogen activator, and von Willebrand factor were analyzed as potential biomarkers of AF. Baseline plasma was collected from patients with AF prior to ablation surgery at Loyola University Medical Center. Individuals with AF had statistically significantly increased levels of PAI-1, CD40-L, and nucleosomes, when compared to the normal population ( P < .0001). Additionally, there was a statistically significant increase in the CRP ( P = .01), PIIINP ( P = .04), and PIIICP ( P = .0008) when compared to normal individuals. From this study, it is concluded that the prothrombotic, inflammatory, and collagen turnover biomarkers PAI-1, CD40-L, nucleosomes, CRP, PIIICP, and PIIINP are elevated in AF.