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1.
Front Cardiovasc Med ; 10: 1202174, 2023.
Article in English | MEDLINE | ID: mdl-37840960

ABSTRACT

Objectives: It is uncertain whether concurrent mitral valve repair or replacement for moderate or greater secondary mitral regurgitation at the time of coronary artery bypass graft or aortic valve replacement surgery improves long-term survival. Methods: Patients undergoing coronary artery bypass graft and/or aortic valve replacement surgery with moderate or greater secondary mitral regurgitation were reviewed. The effect of concurrent mitral valve repair or replacement upon long-term mortality was assessed while accounting for patient and operative characteristics and mitral regurgitation severity. Results: Of 1,515 patients, 938 underwent coronary artery bypass graft or aortic valve replacement surgery alone and 577 underwent concurrent mitral valve repair or replacement. Concurrent mitral valve repair or replacement did not alter the risk of postoperative mortality for patients with moderate mitral regurgitation (hazard ratio = 0.93; 0.75-1.17) or more-than-moderate mitral regurgitation (hazard ratio = 1.09; 0.74-1.60) in multivariable regression. Patients with more-than-moderate mitral regurgitation undergoing coronary artery bypass graft-only surgery had a survival advantage from concurrent mitral valve repair or replacement in the first two postoperative years (P = 0.028) that did not persist beyond that time. Patients who underwent concurrent mitral valve repair or replacement had a higher rate of later mitral valve operation or reoperation over the five subsequent years (1.9% vs. 0.2%; P = 0.0014) than those who did not. Conclusions: These observations suggest that mitral valve repair or replacement for more-than-moderate mitral regurgitation at the time of coronary artery bypass grafting may be reasonable in a suitably selected coronary artery bypass graft population but not for aortic valve replacement, with or without coronary artery bypass grafting. Our findings are supportive of 2021 European guidelines that severe secondary mitral regurgitation "should" or be "reasonabl[y]" intervened upon at the time of coronary artery bypass grafting but do not support 2020 American guidelines for performing mitral valve repair or replacement concurrent with aortic valve replacement, with or without coronary artery bypass grafting.

2.
J Cardiothorac Vasc Anesth ; 37(10): 1904-1911, 2023 10.
Article in English | MEDLINE | ID: mdl-37394388

ABSTRACT

OBJECTIVES: To determine whether preoperative (preop) tricuspid regurgitation (TR) severity grade was associated with postoperative mortality, to examine the correlation between pre-op and intraoperative (intraop) TR grades, and to understand which TR grade had better prognostic predictability in cardiac surgery patients. DESIGN: Retrospective. SETTING: Single institution. PARTICIPANTS: Patients. INTERVENTIONS: Preop and intraop echocardiography TR grades of 4,232 patients who had undergone cardiac surgeries between 2004 and 2014 were examined. MEASUREMENTS AND MAIN RESULTS: Kaplan-Meier curves and Cox proportional hazard models were used to determine the association between TR grades and the primary endpoint of all-cause mortality. The Wilcoxon signed-rank test and Spearman's rank correlation were analyzed to assess the similarity and correlation between preop and intraop-grade pairs. Multivariate logistic regression models of the area under the curve characteristics were compared for prognostic implications. Kaplan-Meier curves demonstrated a strong relationship between preop grades and survival. Multivariate models showed significantly increased mortality starting at mild preop TR (mild TR: hazard ratio [HR] 1.24; 95% CI 1.05-1.46, p = 0.013; moderate TR: HR 1.60; 95% CI 1.05-1.97, p < 0.001; severe TR: HR 2.50; 95% CI 1.74-3.58, p < 0.001). Preop TR grades were mostly higher than intraop grades. Spearman's correlation was 0.55 (p < 0.001). The area under the curves of preop and intraop TR-based models were almost identical (0.704 v 0.702 1-year mortality and 0.704 v 0.700 2-year mortality). CONCLUSIONS: The authors found that echocardiographically-determined preop TR grade at the time of surgical planning was associated with long-term mortality, starting even at a mild grade. Preop grades were higher than intraop grades, with a moderate correlation. Preop and intraop grades exhibited similar prognostic implications.


Subject(s)
Cardiac Surgical Procedures , Tricuspid Valve Insufficiency , Humans , Tricuspid Valve Insufficiency/diagnostic imaging , Tricuspid Valve Insufficiency/surgery , Retrospective Studies , Proportional Hazards Models , Prognosis , Cardiac Surgical Procedures/adverse effects , Treatment Outcome , Severity of Illness Index
8.
Article in English | MEDLINE | ID: mdl-36084862

ABSTRACT

Acute postoperative pain (APOP) is often evaluated through granular parameters, though monitoring postoperative pain using trends may better describe pain state. We investigated acute postoperative pain trajectories in cardiac surgical patients to identify subpopulations of pain resolution and elucidate predictors of problematic pain courses. We examined retrospective data from 2810 cardiac surgical patients at a single center. The k-means algorithm for longitudinal data was used to generate clusters of pain trajectories over the first 5 postoperative days. Patient characteristics were examined for association with cluster membership using ordinal and multinomial logistic regression. We identified 3 subgroups of pain resolution after cardiac surgery: 37.7% with good resolution, 44.2% with moderate resolution, and 18.2% exhibiting poor resolution. Type I diabetes (2.04 [1.00-4.16], p = 0.05), preoperative opioid use (1.65 [1.23-2.22], p = 0.001), and illicit drug use (1.89 [1.26-2.83], p = 0.002) elevated risk of membership into worse pain trajectory clusters. Female gender (1.72 [1.30-2.27], p < 0.001), depression (1.60 [1.03-2.50], p = 0.04) and chronic pain (3.28 [1.79-5.99], p < 0.001) increased risk of membership in the worst pain resolution cluster. This study defined 3 APOP resolution subgroups based on pain score trend after cardiac surgery and identified factors that predisposed patients to worse resolution. Patients with moderate or poor pain trajectory consumed more opioids and received them for longer before discharge. Future studies are warranted to determine if altering postoperative pain monitoring and management improve postoperative course of patients at risk of moderate or poor pain resolution.

9.
Anesth Analg ; 133(1): 53-54, 2021 07 01.
Article in English | MEDLINE | ID: mdl-34127589
10.
J Cardiothorac Vasc Anesth ; 35(7): 1953-1963, 2021 07.
Article in English | MEDLINE | ID: mdl-33766471

ABSTRACT

The European Association of Cardiothoracic Anaesthesiology (EACTA) and the Society of Cardiovascular Anesthesiologists (SCA) aimed to create joint recommendations for the perioperative management of patients with suspected or proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection undergoing cardiac surgery or invasive cardiac procedures. To produce appropriate recommendations, the authors combined the evidence from the literature review, reevaluating the clinical experience of routine cardiac surgery in similar cases during the Middle East Respiratory Syndrome (MERS-CoV) outbreak and the current pandemic with suspected coronavirus disease 2019 (COVID-19) patients, and the expert opinions through broad discussions within the EACTA and SCA. The authors took into consideration the balance between established procedures and the feasibility during the present outbreak. The authors present an agreement between the European and US practices in managing patients during the COVID-19 pandemic. The recommendations take into consideration a broad spectrum of issues, with a focus on preoperative testing, safety concerns, overall approaches to general and specific aspects of preparation for anesthesia, airway management, transesophageal echocardiography, perioperative ventilation, coagulation, hemodynamic control, and postoperative care. As the COVID-19 pandemic is spreading, it will continue to present a challenge for the worldwide anesthesiology community. To allow these recommendations to be updated as long as possible, the authors provided weblinks to international public and academic sources providing timely updated data. This document should be the basis of future task forces to develop a more comprehensive consensus considering new evidence uncovered during the COVID-19 pandemic.


Subject(s)
Anesthesia, Cardiac Procedures , Anesthesiology , COVID-19 , Anesthesiologists , China , Consensus , Humans , Pandemics , SARS-CoV-2
11.
Interact Cardiovasc Thorac Surg ; 32(1): 9-19, 2021 01 01.
Article in English | MEDLINE | ID: mdl-33313764

ABSTRACT

OBJECTIVES: Functional mitral regurgitation (MR) is observed with ischaemic heart disease or aortic valve disease. Assessing the value of mitral valve repair or replacement (MVR/P) is complicated by frequent discordance between preoperative transthoracic echocardiographic (pTTE) and intraoperative transoesophageal echocardiographic (iTOE) assessment of MR severity. We examined the association of pTTE and iTOE with postoperative mortality in patients with or without MR, at the time of coronary artery bypass grafting (CABG) and/or aortic valve replacement without MVR/P. METHODS: Medical records of 6629 patients undergoing CABG and/or aortic valve replacement surgery with or without functional MR and who did not undergo MVR/P were reviewed. MR severity assessed by pTTE and iTOE were examined for association with postoperative mortality using proportional hazards regression while accounting for patient and operative characteristics. RESULTS: In 72% of 709 patients with clinically significant (moderate or greater) functional MR detected by pTTE, iTOE performed after induction of anaesthesia demonstrated a reduction in MR severity, while 2% of patients had increased severity of MR by iTOE. iTOE assessment of MR was better associated with long-term postoperative mortality than pTTE in patients with moderate MR [hazard ratio (HR) 1.31 (1.11-1.55) vs 1.02 (0.89-1.17), P-value for comparison of HR 0.025] but was not different for more than moderate MR [1.43 (0.96-2.14) vs 1.27 (0.80-2.02)]. CONCLUSIONS: In patients undergoing CABG and/or aortic valve replacement without MVR/P, these findings support intraoperative reassessment of MR severity by iTOE as an adjunct to pTTE in the prediction of mortality. Alone, these findings do not yet provide evidence for an operative strategy.


Subject(s)
Coronary Artery Bypass , Echocardiography, Transesophageal , Echocardiography , Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency/diagnostic imaging , Aged , Heart Valve Prosthesis , Humans , Male , Middle Aged , Mitral Valve Insufficiency/surgery , Myocardial Ischemia/surgery , Proportional Hazards Models , Retrospective Studies , Treatment Outcome
12.
Anesth Analg ; 130(2): 300-306, 2020 02.
Article in English | MEDLINE | ID: mdl-31453871

ABSTRACT

BACKGROUND: Currently available 2-dimensional (2D) echocardiographic methods for accurately assessing the mitral valve orifice area (MVA) after mitral valve repair (MVr) are limited due to its complex 3-dimensional (3D) geometry. We compared repaired MVAs obtained with commonly used 2D and 3D echocardiographic methods to a 3D orifice area (3DOA), which is a novel echocardiographic measurement and independent of geometric assumptions. METHODS: Intraoperative 2D and 3D transesophageal echocardiography (TEE) images from 20 adult cardiac surgery patients who underwent MVr for mitral regurgitation obtained immediately after repair were retrospectively reviewed. MVAs obtained by pressure half-time (PHT), 2D planimetry (2DP), and 3D planimetry (3DP) were compared to those derived by 3DOA. RESULTS: MVAs (mean value ± standard deviation [SD]) after MVr were obtained by PHT (3 ± 0.6 cm), 2DP (3.58 ± 0.75 cm), 3D planimetry (3DP; 2.78 ± 0.74 cm), and 3DOA (2.32 ± 0.76 cm). MVAs obtained by the 3DOA method were significantly smaller compared to those obtained by PHT (mean difference, 0.68 cm; P = .0003), 2DP (mean difference, 1.26 cm; P < .0001), and 3DP (mean difference, 0.46 cm; P = .003). In addition, MVA defined as an area ≤1.5 cm was identified by 3DOA in 2 patients and by 3DP in 1 patient. CONCLUSIONS: Post-MVr MVAs obtained using the novel 3DOA method were significantly smaller than those obtained by conventional echocardiographic methods and may be consistent with a higher incidence of MVA reduction when compared to 2D techniques. Further studies are still needed to establish the clinical significance of 3D echocardiographic techniques used to measure MVA after MVr.


Subject(s)
Echocardiography, Three-Dimensional/methods , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Echocardiography/methods , Echocardiography/standards , Echocardiography, Three-Dimensional/standards , Female , Humans , Male , Middle Aged , Retrospective Studies
14.
Anesth Analg ; 128(1): 25-32, 2019 01.
Article in English | MEDLINE | ID: mdl-29878942

ABSTRACT

BACKGROUND: Severe right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation increases morbidity and mortality. We investigated the association between intraoperative right heart hemodynamic data, echocardiographic parameters, and severe versus nonsevere RVF. METHODS: A review of LVAD patients between March 2013 and March 2016 was performed. Severe RVF was defined by the need for a right ventricular mechanical support device, inotropic, and/or inhaled pulmonary vasodilator requirements for >14 days. From a chart review, the right ventricular failure risk score was calculated and right heart hemodynamic data were collected. Pulmonary artery pulsatility index (PAPi) [(pulmonary artery systolic pressure - pulmonary artery diastolic pressure)/central venous pressure (CVP)] was calculated for 2 periods: (1) 30 minutes before cardiopulmonary bypass (CPB) and (2) after chest closure. Echocardiographic data were recorded pre-CPB and post-CPB by a blinded reviewer. Univariate logistic regression models were used to examine the performance of hemodynamic and echocardiographic metrics. RESULTS: A total of 110 LVAD patients were identified. Twenty-five did not meet criteria for RVF. Of the remaining 85 patients, 28 (33%) met criteria for severe RVF. Hemodynamic factors associated with severe RVF included: higher CVP values after chest closure (18 ± 9 vs 13 ± 5 mm Hg; P = .0008) in addition to lower PAPi pre-CPB (1.2 ± 0.6 vs 1.7 ± 1.0; P = .04) and after chest closure (0.9 ± 0.5 vs 1.5 ± 0.8; P = .0008). Post-CPB echocardiographic findings associated with severe RVF included: larger right atrial diameter major axis (5.4 ± 0.9 vs 4.9 ± 1.0 cm; P = .03), larger right ventricle end-systolic area (22.6 ± 8.4 vs 18.5 ± 7.9 cm; P = .03), lower fractional area of change (20.2 ± 10.8 vs 25.9 ± 12.6; P = .04), and lower tricuspid annular plane systolic excursion (0.9 ± 0.2 vs 1.1 ± 0.3 cm; P = .008). Right ventricular failure risk score was not a significant predictor of severe RVF. Post-chest closure CVP and post-chest closure PAPi discriminated severe from nonsevere RVF better than other variables measured, each with an area under the curve of 0.75 (95% CI, 0.64-0.86). CONCLUSIONS: Post-chest closure values of CVP and PAPi were significantly associated with severe RVF. Echocardiographic assessment of RV function post-CPB was weakly associated with severe RVF.


Subject(s)
Echocardiography, Doppler, Color , Heart Failure/therapy , Heart-Assist Devices , Hemodynamics , Monitoring, Intraoperative/methods , Prosthesis Implantation/instrumentation , Ventricular Dysfunction, Left/therapy , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Function, Left , Ventricular Function, Right , Adult , Aged , Cardiopulmonary Bypass/adverse effects , Central Venous Pressure , Diagnosis, Differential , Female , Heart Failure/diagnostic imaging , Heart Failure/mortality , Heart Failure/physiopathology , Humans , Male , Middle Aged , Predictive Value of Tests , Prosthesis Implantation/adverse effects , Prosthesis Implantation/mortality , Pulmonary Artery/physiopathology , Pulsatile Flow , Retrospective Studies , Risk Factors , Severity of Illness Index , Time Factors , Treatment Outcome , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/mortality , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/mortality , Ventricular Dysfunction, Right/physiopathology
16.
J Thorac Cardiovasc Surg ; 155(3): 1032-1038.e2, 2018 03.
Article in English | MEDLINE | ID: mdl-29246545

ABSTRACT

OBJECTIVES: To determine the association between intraoperative/presurgical grade of tricuspid regurgitation (TR) and mortality, and to determine whether surgical correction of TR correlated with an increased chance of survival compared with patients with uncorrected TR. METHODS: The grade of TR assessed by intraoperative transesophageal echocardiography (TEE) before surgical intervention was reviewed for 23,685 cardiac surgery patients between 1990 and 2014. Cox proportional hazard regression models were used to determine association between grade of TR and the primary endpoint of all-cause mortality. Association between tricuspid valve (TV) surgery and survival was determined with Cox proportional hazard regression models after matching for grade of TR. RESULTS: Kaplan-Meier survival curves demonstrated a relationship between all grades of TR. Multivariable analysis of the entire cohort demonstrated significantly increased mortality for moderate (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.1-1.4; P < .0001) and severe TR (HR, 2.02; 95% CI, 1.57-2.6; P < .0001). Mild TR displayed a trend for mortality (HR, 1.07; 95% CI, 0.99-1.16; P = .075). After matching for grade of TR and additional confounders, patients who underwent TV surgery had a statistically significant increased likelihood of survival (HR, 0.74; 95% CI, 0.61-0.91; P = .004). CONCLUSIONS: Our study of more than 20,000 patients demonstrates that grade of TR is associated with increased risk of mortality after cardiac surgery. In addition, all patients who underwent TV surgery had a statistically significantly increased likelihood of survival compared with those with the same degree of TR who did not undergo TV surgery.


Subject(s)
Cardiac Surgical Procedures/mortality , Tricuspid Valve Insufficiency/mortality , Tricuspid Valve Insufficiency/surgery , Aged , Aged, 80 and over , Cardiac Surgical Procedures/adverse effects , Cause of Death , Databases, Factual , Echocardiography, Transesophageal , Female , Humans , Male , Middle Aged , Postoperative Complications/mortality , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Time Factors , Treatment Outcome , Tricuspid Valve Insufficiency/diagnostic imaging
17.
Cardiovasc Diabetol ; 16(1): 87, 2017 07 07.
Article in English | MEDLINE | ID: mdl-28687077

ABSTRACT

BACKGROUND: Omentin-1, also known as Intelectin-1 (ITLN1), is an adipokine with plasma levels associated with diabetes, obesity, and coronary artery disease. Recent studies suggest that ITLN1 can mitigate myocardial ischemic injury but the expression of ITLN1 in the heart itself has not been well characterized. The purpose of this study is to discern the relationship between the expression pattern of ITLN1 RNA in the human heart and the level of circulating ITLN1 protein in plasma from the same patients following myocardial ischemia. METHODS: A large cohort of patients (n = 140) undergoing elective cardiac surgery for aortic valve replacement were enrolled in this study. Plasma and left ventricular biopsy samples were taken at the beginning of cardiopulmonary bypass and after an average of 82 min of ischemic cross clamp time. The localization of ITLN1 in epicardial adipose tissue (EAT) was also further characterized with immunoassays and cell fate transition studies. RESULTS: mRNA expression of ITLN1 decreases in left ventricular tissue after acute ischemia in human patients (mean difference 280.48, p = 0.001) whereas plasma protein levels of ITLN1 increase (mean difference 5.24, p < 0.001). Immunohistochemistry localized ITLN1 to the mesothelium or visceral pericardium of EAT. Epithelial to mesenchymal transition in mesothelial cells leads to a downregulation of ITLN1 expression. CONCLUSIONS: Myocardial injury leads to a decrease in ITLN1 expression in the heart and a corresponding increase in plasma levels. These changes may in part be due to an epithelial to mesenchymal transition of the cells that express ITLN1 following ischemia. Trial Registration Clinicaltrials.gov ID: NCT00985049.


Subject(s)
Coronary Artery Disease/metabolism , Cytokines/metabolism , Epithelial-Mesenchymal Transition/physiology , Lectins/metabolism , Myocardial Ischemia/metabolism , Pericardium/metabolism , Adipokines/metabolism , Adipose Tissue/metabolism , Aged , Aged, 80 and over , Aortic Valve/metabolism , Female , GPI-Linked Proteins/metabolism , Humans , Male , Middle Aged
18.
Anesth Analg ; 125(3): 774-780, 2017 09.
Article in English | MEDLINE | ID: mdl-28678069

ABSTRACT

BACKGROUND: A comprehensive evaluation of mitral stenosis (MS) severity commonly utilizes two-dimensional (2D) echocardiography techniques. However, the complex three-dimensional (3D) structure of the mitral valve (MV) poses challenges to accurate measurements of its orifice area by 2D imaging modalities. We aimed to assess MS severity by comparing measurements of the MV orifice area using conventional echocardiography methods to 3D orifice area (3DOA), a novel echocardiographic technique which minimizes geometric assumptions. METHODS: Routine 2D and 3D intraoperative transesophageal echocardiographic images from 26 adult cardiac surgery patients with at least moderate rheumatic MS were retrospectively reviewed. Measurements of the MV orifice area obtained by pressure half-time (PHT), proximal isovelocity surface area (PISA), continuity equation, and 3D planimetry were compared to those acquired using 3DOA. RESULTS: MV areas derived by PHT, PISA, continuity equation, 3D planimetry, and 3DOA (mean value ± standard deviation) were 1.12 ± 0.27, 1.03 ± 0.27, 1.16 ± 0.35, 0.97 ± 0.25, and 0.76 ± 0.21 cm, respectively. Areas obtained from the 3DOA method were significantly smaller than areas derived from PHT (mean difference 0.35 cm, P < .0001), PISA (mean difference: 0.28 cm, P = .0002), continuity equation (mean difference: 0.43 cm, P = .0015), and 3D planimetry (mean difference: 0.19 cm, P < .0001). MV 3DOAs also identified a significantly greater percentage of patients with severe MS (88%) compared to PHT (31%, P = .006), PISA (42%, P = .01), and continuity equation (39%, P = .017) but not in comparison to 3D planimetry (62%, P = .165). CONCLUSIONS: Novel measures of the stenotic MV 3DOA in patients with rheumatic heart disease are significantly smaller than calculated values obtained by conventional methods and may be consistent with a higher incidence of severe MS compared to 2D techniques. Further investigation is warranted to determine the clinical relevance of 3D echocardiographic techniques used to measure MV area.


Subject(s)
Echocardiography, Three-Dimensional/standards , Echocardiography, Transesophageal/standards , Image Interpretation, Computer-Assisted/standards , Mitral Valve Stenosis/diagnostic imaging , Adult , Echocardiography, Three-Dimensional/methods , Echocardiography, Transesophageal/methods , Female , Humans , Image Interpretation, Computer-Assisted/methods , Male
19.
Ann Thorac Surg ; 104(4): 1325-1331, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28577841

ABSTRACT

BACKGROUND: The association between long-term survival and aortic atheroma in cardiac surgical patients has not been comprehensively investigated. In this study we determine the relation between grade of atheroma and the risk of long-term mortality in a retrospective cohort of more than 20,000 patients undergoing cardiac operation during a 20-year period. METHODS: We included 22,304 consecutive intraoperative transesophageal and epiaortic ultrasound examinations performed at Brigham and Women's Hospital between 1995 and 2014, with long-term follow-up. The extent of atheromatous disease recorded in each examination was used for analysis. Mortality data were obtained from our institution's data registry. Mortality analyses were done using Cox proportional hazard regression models with follow-up as a time scale. We repeated the analysis in a subgroup of 14,728 patients with more detailed demographic characteristics, including postoperative stroke, queried from the institutional Society of Thoracic Surgeons database. RESULTS: A total of 7,722 mortality events and 872 stroke events occurred. Patients with atheromatous disease demonstrated a significant increase in mortality across all grades of severity, both for the ascending and descending aorta. This relation remained unchanged after adjusting for additional covariates. Adjustments for postoperative stroke resulted in only minimal attenuation in the risk of postoperative mortality related to aortic atheroma. CONCLUSIONS: Aortic atheromatous disease of any grade in the ascending and descending aorta is a significant long-term risk of long-term, all-cause mortality in cardiac operation patients. This association remains independent of other conventional risk factors and is not related to postoperative cerebrovascular accidents.


Subject(s)
Aortic Diseases/mortality , Cardiac Surgical Procedures , Plaque, Atherosclerotic/mortality , Aged , Analysis of Variance , Aorta/diagnostic imaging , Aortic Diseases/complications , Aortic Diseases/diagnostic imaging , Cardiac Surgical Procedures/adverse effects , Echocardiography , Female , Follow-Up Studies , Heart Diseases/complications , Heart Diseases/mortality , Heart Diseases/surgery , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Plaque, Atherosclerotic/complications , Plaque, Atherosclerotic/diagnostic imaging , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Stroke/etiology
20.
BMC Med Genomics ; 10(1): 25, 2017 05 02.
Article in English | MEDLINE | ID: mdl-28464817

ABSTRACT

BACKGROUND: Both ambulatory atrial fibrillation (AF) and post-operative AF (poAF) are associated with substantial morbidity and mortality. Analyzing the tissue-specific gene expression in the left atrium (LA) can identify novel genes associated with AF and further the understanding of the mechanism by which previously identified genetic variants associated with AF mediate their effects. METHODS: LA free wall samples were obtained intraoperatively immediately prior to mitral valve surgery in 62 Caucasian individuals. Gene expression was quantified on mRNA harvested from these samples using RNA sequencing. An expression quantitative trait loci (eQTL) analysis was performed, comparing gene expression between different genotypes of 1.0 million genetic markers, emphasizing genomic regions and genes associated with AF. RESULTS: Comparison of whole-genome expression between patients who later developed poAF and those who did not identified 23 differentially expressed genes. These included genes associated with the resting membrane potential modified by potassium currents, as well as genes within Wnt signaling and cyclic GMP metabolism. The eQTL analysis identified 16,139 cis eQTL relationships in the LA, including several involving genes and single nucleotide polymorphisms (SNPs) linked to AF. A previous relationship between rs3744029 and MYOZ1 expression was confirmed, and a novel relationship between rs6795970 and the expression of the SCN10A gene was identified. CONCLUSIONS: The current study is the first analysis of the human LA expression landscape using high-throughput RNA sequencing. Several novel genes and variants likely involved in AF pathogenesis were identified, thus furthering the understanding of how variants associated with AF mediate their effects via altered gene expression. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00833313 , registered 5. January 2009.


Subject(s)
Atrial Fibrillation/genetics , Gene Expression Regulation , Genetic Predisposition to Disease , Heart Atria/metabolism , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Aged , Atrial Fibrillation/metabolism , Atrial Fibrillation/physiopathology , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cyclic GMP/metabolism , Female , Genetic Association Studies , Heart Atria/physiopathology , High-Throughput Nucleotide Sequencing , Humans , Male , Membrane Potentials/genetics , Middle Aged , Muscle Proteins/genetics , Muscle Proteins/metabolism , NAV1.8 Voltage-Gated Sodium Channel/genetics , NAV1.8 Voltage-Gated Sodium Channel/metabolism , Postoperative Period , Sequence Analysis, RNA , Signal Transduction/genetics , White People/genetics
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