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BACKGROUND: The identification of predictors of mitral valve (MV) repair results is important for quality improvement in cardiac surgery. The aim of this study was to evaluate the relationship between MV morphological quantification by three-dimensional (3D) transesophageal echocardiography and mitral repair results. METHODS: Fifty-four patients with MV prolapse who were submitted to surgical repair were divided into 2 groups according to their postoperative mitral regurgitation (MR) degree (group 1, grade 0-I MR; group 2, ≥grade II MR). Morphological parameters related to the mitral ring, dimension of leaflets and prolapse, coaptation line, distance from papillary muscles to the leaflet border and valve angles were analyzed by 3D MV quantification. Cardiac remodeling and MR quantitative parameters were also evaluated. RESULTS: There was no correlation between 3D MV quantification and surgical results; a multivariate analysis did not show an association between morphological parameters and surgical outcome. The distance from the posteromedial papillary muscle to the leaflet border was higher (P = .038) in patients with ≥grade II postoperative MR. The left atrial diameter, left ventricular end-systolic diameter, left ventricular end-diastolic and end-systolic volumes were larger in patients with a significant residual MR (P < .05). CONCLUSION: Three-dimensional MV quantification did not predict the postoperative MR grade; however, the distance from the posteromedial papillary muscles to the leaflet border may be related to suboptimal repair results. Furthermore, excessive cardiac remodeling was related to postoperative MR ≥ grade II, what could suggest a potential benefit of early surgical treatment.
Subject(s)
Echocardiography, Three-Dimensional/methods , Echocardiography, Transesophageal/methods , Mitral Valve Prolapse/surgery , Female , Humans , Male , Middle Aged , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Treatment OutcomeABSTRACT
OBJECTIVES: To evaluate the effects of goal-directed therapy on outcomes in high-risk patients undergoing cardiac surgery. DESIGN: A prospective randomized controlled trial and an updated metaanalysis of randomized trials published from inception up to May 1, 2015. SETTING: Surgical ICU within a tertiary referral university-affiliated teaching hospital. PATIENTS: One hundred twenty-six high-risk patients undergoing coronary artery bypass surgery or valve repair. INTERVENTIONS: Patients were randomized to a cardiac output-guided hemodynamic therapy algorithm (goal-directed therapy group, n = 62) or to usual care (n = 64). In the goal-directed therapy arm, a cardiac index of greater than 3 L/min/m was targeted with IV fluids, inotropes, and RBC transfusion starting from cardiopulmonary bypass and ending 8 hours after arrival to the ICU. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite endpoint of 30-day mortality and major postoperative complications. Patients from the goal-directed therapy group received a greater median (interquartile range) volume of IV fluids than the usual care group (1,000 [625-1,500] vs 500 [500-1,000] mL; p < 0.001], with no differences in the administration of either inotropes or RBC transfusions. The primary outcome was reduced in the goal-directed therapy group (27.4% vs 45.3%; p = 0.037). The goal-directed therapy group had a lower occurrence rate of infection (12.9% vs 29.7%; p = 0.002) and low cardiac output syndrome (6.5% vs 26.6%; p = 0.002). We also observed lower ICU cumulative dosage of dobutamine (12 vs 19 mg/kg; p = 0.003) and a shorter ICU (3 [3-4] vs 5 [4-7] d; p < 0.001) and hospital length of stay (9 [8-16] vs 12 [9-22] d; p = 0.049) in the goal-directed therapy compared with the usual care group. There were no differences in 30-day mortality rates (4.8% vs 9.4%, respectively; p = 0.492). The metaanalysis identified six trials and showed that, when compared with standard treatment, goal-directed therapy reduced the overall rate of complications (goal-directed therapy, 47/410 [11%] vs usual care, 92/415 [22%]; odds ratio, 0.40 [95% CI, 0.26-0.63]; p < 0.0001) and decreased the hospital length of stay (mean difference, -5.44 d; 95% CI, -9.28 to -1.60; p = 0.006) with no difference in postoperative mortality: 9 of 410 (2.2%) versus 15 of 415 (3.6%), odds ratio, 0.61 (95% CI, 0.26-1.47), and p = 0.27. CONCLUSIONS: Goal-directed therapy using fluids, inotropes, and blood transfusion reduced 30-day major complications in high-risk patients undergoing cardiac surgery.
Subject(s)
Cardiac Surgical Procedures , Hemodynamics , Postoperative Complications , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Adrenergic beta-1 Receptor Agonists/therapeutic use , Cardiac Output , Cardiac Surgical Procedures/methods , Cardiac Surgical Procedures/mortality , Dobutamine/therapeutic use , Fluid Therapy/methods , Hemodynamics/physiology , Intensive Care Units , Length of Stay , Meta-Analysis as Topic , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Treatment OutcomeABSTRACT
Worldwide, rheumatic fever remains a significant cause of mitral valve insufficiency. It is responsible for approximately 90 % of early childhood valvular surgeries in Brazil. Elongated or flail chordae are frequently responsible and require surgical correction. The purpose of this study was to analyze and compare the histological tissues of the mitral valve chordae and the mechanical resistance generated by the chordae, both with and without the application of a high-power laser. Twenty normal porcine mitral valve chordae were measured and divided randomly into the following two groups: control group (not subjected to a high-power laser) and laser group (subjected to photonic irradiation). Laser surgery was performed under controlled conditions, using following parameters: λ = 980-nm wavelength, power = 3 W, and energy = 60 J. A mechanical test machine was used in combination with a subsequent histological study to measure chordae tensile properties. A histological analysis demonstrated a typical collagen bundle arrangement in the control group; however, under a particular reached temperature range (48), the collagen bundles assumed different arrangements in the laser group. Significant reductions in the chordae tendineae lengths and changes in their resistance in the laser group were observed, as these chordae exhibited less rigid fibers. The chordae tendineae of normal porcine valves subjected to a high-power laser exhibited its length reduction and less stiffness compared to the control group. A histological analysis of the laser treatment specimens demonstrated differences in collagen bundle spatial organization, following slight changes into tissue temperature.
Subject(s)
Chordae Tendineae/surgery , Heart Valve Diseases/surgery , Laser Therapy/methods , Mitral Valve , Animals , Collagen , Light , Swine , TemperatureABSTRACT
AIMS: Left ventricular remodelling occurs during the chronic course of aortic regurgitation (AR) and aortic stenosis (AS), leading to myocardial hypertrophy and fibrosis. Several studies have shown that extracellular volume fraction (ECV) and indexed extracellular volume (iECV) are important surrogate markers of diffuse myocardial fibrosis (MF). Postoperative data on these cardiovascular magnetic resonance (CMR) extracellular expansion parameters for either AS or AR are scarce. This study aimed to demonstrate the postoperative changes that occur in diffuse MF, and the influence of preoperative MF on the reversal of LV remodelling, in patients with AR or AS. METHODS AND RESULTS: Patients with severe AR or AS and indications for surgery were prospectively enrolled. Patients underwent pre- and postoperative CMR, and ECV and iECV were quantified. Data from 99 patients were analysed (32 with AR and 67 with AS). After surgery, the left ventricle mass index decreased in both groups (AR: 110 vs. 91 g/m2; AS: 86 vs. 68 g/m2, both P < 0.001). The late gadolinium enhancement fraction (AR: preoperative 1.9% vs. postoperative 1.7%, P = 0.575; AS: preoperative 2.4% vs. postoperative 2.4%, P = 0.615) and late gadolinium enhancement mass (AR: preoperative 3.8 g vs. postoperative 2.5 g, P = 0.635; AS: preoperative 3.4 g vs. postoperative 3.5 g, P = 0.575) remained stable in both groups. Preoperative iECV and ECV were greater in the AR group (iECV: 30 mL/m2 vs. 22 mL/m2, P = 0.001; ECV: 28.4% vs. 27.2%, P = 0.048). Indexed extracellular volume decreased after surgery in both groups (AR: 30-26.5 mL/m2, AS: 22-18.2 mL/m2, both P < 0.001); it was still greater in the AR group (AR: 26.5 mL/m2 vs. AS: 18.2 mL/m2, P < 0.001). Postoperative ECV remained stable in the AR group (preoperative 28.4% vs. postoperative 29.9%; P = 0.617) and increased in the AS group (preoperative 27.2% vs. postoperative 28.6%; P = 0.033). CONCLUSION: Patients with both AR or AS presented reduction in iECV after surgery, unfolding the reversible nature of diffuse MF. In contrast to patients with AS, those with AR developed postoperative iECV regression with stable ECV, suggesting a balanced reduction in both intracellular and extracellular myocardial components.
Subject(s)
Aortic Valve Insufficiency , Aortic Valve Stenosis , Cardiomyopathies , Humans , Contrast Media , Gadolinium , Prospective Studies , Myocardium/pathology , Cardiomyopathies/pathology , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/pathology , Fibrosis , Aortic Valve Insufficiency/diagnostic imaging , Aortic Valve Insufficiency/surgery , Aortic Valve Insufficiency/pathology , Magnetic Resonance Spectroscopy , Magnetic Resonance Imaging, Cine , Ventricular RemodelingABSTRACT
Introduction: Classical low-flow, low-gradient aortic stenosis (LFLG-AS) is an advanced stage of aortic stenosis, which has a poor prognosis with medical treatment and a high operative mortality after surgical aortic valve replacement (SAVR). There is currently a paucity of information regarding the current prognosis of classical LFLG-AS patients undergoing SAVR and the lack of a reliable risk assessment tool for this particular subset of AS patients. The present study aims to assess mortality predictors in a population of classical LFLG-AS patients undergoing SAVR. Methods: This is a prospective study including 41 consecutive classical LFLG-AS patients (aortic valve area ≤1.0â cm2, mean transaortic gradient <40â mmHg, left ventricular ejection fraction <50%). All patients underwent dobutamine stress echocardiography (DSE), 3D echocardiography, and T1 mapping cardiac magnetic resonance (CMR). Patients with pseudo-severe aortic stenosis were excluded. Patients were divided into groups according to the median value of the mean transaortic gradient (≤25 and >25â mmHg). All-cause, intraprocedural, 30-day, and 1-year mortality rates were evaluated. Results: All of the patients had degenerative aortic stenosis, with a median age of 66 (60-73) years; most of the patients were men (83%). The median EuroSCORE II was 2.19% (1.5%-4.78%), and the median STS was 2.19% (1.6%-3.99%). On DSE, 73.2% had flow reserve (FR), i.e., an increase in stroke volume ≥20% during DSE, with no significant differences between groups. On CMR, late gadolinium enhancement mass was lower in the group with mean transaortic gradient >25â mmHg [2.0 (0.0-8.9)â g vs. 8.5 (2.3-15.0)â g; p = 0.034), and myocardium extracellular volume (ECV) and indexed ECV were similar between groups. The 30-day and 1-year mortality rates were 14.6% and 43.8%, respectively. The median follow-up was 4.1 (0.3-5.1)â years. By multivariate analysis adjusted for FR, only the mean transaortic gradient was an independent predictor of mortality (hazard ratio: 0.923, 95% confidence interval: 0.864-0.986, p = 0.019). A mean transaortic gradient ≤25â mmHg was associated with higher all-cause mortality rates (log-rank p = 0.038), while there was no difference in mortality regarding FR status (log-rank p = 0.114). Conclusions: In patients with classical LFLG-AS undergoing SAVR, the mean transaortic gradient was the only independent mortality predictor in patients with LFLG-AS, especially if ≤25â mmHg. The absence of left ventricular FR had no prognostic impact on long-term outcomes.
ABSTRACT
CONTEXT: Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. OBJECTIVE: To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. DESIGN, SETTING, AND PATIENTS: The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n = 502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. INTERVENTION: Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit ≥30%) or to a restrictive strategy (hematocrit ≥24%). MAIN OUTCOME MEASURE: Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at -8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). RESULTS: Hemoglobin concentrations were maintained at a mean of 10.5 g/dL (95% confidence interval [CI], 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.0-9.2) in the restrictive-strategy group (P < .001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P < .001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% [95% CI, -6% to 4%]; P = .85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 [95% CI, 1.1-1.4]; P = .002). CONCLUSION: Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01021631.
Subject(s)
Anemia/therapy , Cardiac Surgical Procedures , Erythrocyte Transfusion/methods , Aged , Anemia/prevention & control , Brazil , Cardiac Surgical Procedures/mortality , Elective Surgical Procedures , Erythrocyte Transfusion/adverse effects , Erythrocyte Transfusion/standards , Female , Hematocrit , Hospitals, University , Humans , Intensive Care Units , Male , Middle Aged , Morbidity , Perioperative Care , Prospective StudiesABSTRACT
OBJECTIVES: The aim of this study was to analyze mitral annulus (MA) dynamics using cardiac magnetic resonance (CMR) in patients with degenerative mitral insufficiency who underwent mitral valve repair (MVR). METHODS: Mitral valve imaging was performed by CMR in twenty-nine patients with degenerative mitral insufficiency who underwent MVR between July 2014 and August 2016, with quadrangular resection of the posterior leaflet without ring annuloplasty. They were prospectively followed up from the preoperative period up to 2 years postoperatively. RESULTS: We observed a significant reduction in all measurements of the MA after surgery. The mean systolic circumference of the MA was reduced from 13.28±1.95 cm to 11.50±1.59 cm, and the diastolic circumference was reduced from 12.51±2.01 cm to 10.66±2.09 cm in the immediate postoperative period, measures that remained stable 2 years after MVR (p<0.001). The mean maximum area of the MA was significantly reduced from 14.34±4.03 to 10.45±3.17 cm2 when comparing the immediate postoperative period and the 2 year follow-up (p<0.001). The same occurred with the mean minimum area of the MA, which was reduced from 12.53±3.68 cm2 to 9.23±2.84 cm2 in the same period, and this reduction was greater in the antero-posterior diameter than in the mid-lateral diameter. The mobility of the MA was preserved after surgery, ranging between 19.6% and 25.7% at 2-year follow-up. CONCLUSION: We observed a significant reduction in the MA size after MVR, with preservation of the MA mobility at the 2-year follow-up.
Subject(s)
Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency , Diastole , Follow-Up Studies , Humans , Magnetic Resonance Spectroscopy , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Treatment OutcomeABSTRACT
OBJECTIVE: We hypothesized that reactive oxygen species (ROS) contribute to progression of aortic valve (AV) calcification/stenosis. METHODS AND RESULTS: We investigated ROS production and effects of antioxidants tempol and lipoic acid (LA) in calcification progression in rabbits given 0.5% cholesterol diet +10(4) IU/d Vit.D2 for 12 weeks. Superoxide and H2O2 microfluorotopography and 3-nitrotyrosine immunoreactivity showed increased signals not only in macrophages but preferentially around calcifying foci, in cells expressing osteoblast/osteoclast, but not macrophage markers. Such cells also showed increased expression of NAD(P)H oxidase subunits Nox2, p22phox, and protein disulfide isomerase. Nox4, but not Nox1 mRNA, was increased. Tempol augmented whereas LA decreased H2O2 signals. Importantly, AV calcification, assessed by echocardiography and histomorphometry, decreased 43% to 70% with LA, but increased with tempol (P < or = 0.05). Tempol further enhanced apoptosis and Nox4 expression. In human sclerotic or stenotic AV, we found analogous increases in ROS production and NAD(P)H oxidase expression around calcifying foci. An in vitro vascular smooth muscle cell (VSMC) calcification model also exhibited increased, catalase-inhibitable, calcium deposit with tempol, but not with LA. CONCLUSIONS: Our data provide evidence that ROS, particularly hydrogen peroxide, potentiate AV calcification progression. However, tempol exhibited a paradoxical effect, exacerbating AV/vascular calcification, likely because of its induced increase in peroxide generation.
Subject(s)
Antioxidants/pharmacology , Aortic Valve Stenosis/pathology , Calcinosis/pathology , Hydrogen Peroxide/metabolism , Reactive Oxygen Species/metabolism , Animals , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/enzymology , Cholesterol, Dietary/administration & dosage , Disease Models, Animal , Disease Progression , Echocardiography , Fluorescence , Humans , Hydrogen Peroxide/adverse effects , Immunohistochemistry , NADPH Oxidases/metabolism , Oxidation-Reduction , Oxidative Stress , Probability , Rabbits , Random Allocation , Reactive Oxygen Species/adverse effects , Reference Values , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Tissue Culture TechniquesABSTRACT
Background Few data exist on the degree of interstitial myocardial fibrosis in patients with classical low-flow, low-gradient aortic stenosis (LFLG-AS) and its association with left ventricular flow reserve (FR) on dobutamine stress echocardiography. This study sought to evaluate the diffuse interstitial fibrosis measured by T1 mapping cardiac magnetic resonance technique in LFLG-AS patients with and without FR. Methods Prospective study including 65 consecutive patients (41 LFLG-AS [mean age, 67.1±8.4 years; 83% men] and 24 high-gradient aortic stenosis used as controls) undergoing dobutamine stress echocardiography to assess FR and cardiac magnetic resonance to determine the extracellular volume (ECV) fraction of the myocardium, indexed ECV (iECV) to body surface area and late gadolinium enhancement. Results Interstitial myocardial fibrosis measured by iECV was higher in patients with LFLG-AS with and without FR as compared with high-gradient aortic stenosis (35.25±9.75 versus 32.93±11.00 versus 21.19±6.47 mL/m2, respectively; P<0.001). However, both ECV and iECV levels were similar between LFLG-AS patients with and without FR ( P=0.950 and P=0.701, respectively). Also, FR did not correlate significantly with ECV (r=-0.16, P=0.31) or iECV (r=0.11, P=0.51). Late gadolinium enhancement mass was also similar in patients with versus without FR but lower in high-gradient aortic stenosis (13.3±10.2 versus 10.5±7.5 versus 4.8±5.9 g, respectively; P=0.018). Conclusions Patients with LFLG-AS have higher ECV, iECV, and late gadolinium enhancement mass compared with high-gradient aortic stenosis. Moreover, among patients with LFLG-AS, the degree of myocardial fibrosis was similar in patients with versus those without FR. These findings suggest that diffuse myocardial fibrosis may not be the main factor responsible for the absence of FR in LFLG-AS patients.
Subject(s)
Aortic Valve Stenosis/pathology , Aortic Valve/physiopathology , Hemodynamics , Myocardium/pathology , Aged , Aortic Valve/diagnostic imaging , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/physiopathology , Case-Control Studies , Echocardiography, Stress , Female , Fibrosis , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Prospective StudiesABSTRACT
OBJECTIVE: To analyze the behavior of platelets after transcatheter valve-in-valve implantation for the treatment of degenerated bioprosthesis and how they correlate with adverse events upon follow-up. METHODS: Retrospective analysis of 28 patients who received a valve-in-valve implant, 5 in aortic, 18 in mitral and 5 in tricuspid positions. Data were compared with 74 patients submitted to conventional redo valvular replacements during the same period, and both groups' platelet curves were analyzed. Statistical analysis was conducted using the IBM SPSS Statistics(r) 20 for Windows. RESULTS: All patients in the valve-in-valve group developed thrombocytopenia, 25% presenting mild (<150.000/µL), 54% moderate (<100.000/µL) and 21% severe (<50.000/µL) thrombocytopenia. The platelet nadir was on the 4th postoperative day for aortic ViV, 2nd for mitral and 3rd for tricuspid patients, with the majority of patients recovering regular platelet count. However, the aortic subgroup comparison between valve-in-valve and conventional surgery showed a statistically significant difference from the 7th day onwards, where valve-in-valve patients had more severe and longer lasting thrombocytopenia. This, however, did not translate into a higher postoperative risk. In our study population, postoperative thrombocytopenia did not correlate with greater occurrence of adverse outcomes and only normal preoperative platelet count could significantly predict a postoperative drop >50%. CONCLUSION: Although thrombocytopenia is an extremely common finding after valve-in-valve procedures, the degree of platelet count drop did not correlate with greater incidence of postoperative adverse outcomes in our study population.
Subject(s)
Heart Valve Prosthesis Implantation/adverse effects , Postoperative Complications/blood , Postoperative Complications/etiology , Thrombocytopenia/blood , Thrombocytopenia/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Bioprosthesis/adverse effects , Female , Heart Valve Prosthesis/adverse effects , Heart Valve Prosthesis Implantation/methods , Humans , Male , Middle Aged , Mitral Valve/surgery , Platelet Count/methods , Predictive Value of Tests , Reference Values , Reoperation , Retrospective Studies , Risk Assessment , Risk Factors , Statistics, Nonparametric , Time Factors , Transcatheter Aortic Valve Replacement/adverse effects , Treatment Outcome , Tricuspid Valve/surgery , Young AdultABSTRACT
BACKGROUND: Mortality prediction after cardiac procedures is an essential tool in clinical decision making. Although rheumatic cardiac disease remains a major cause of heart surgery in the world no previous study validated risk scores in a sample exclusively with this condition. OBJECTIVES: Develop a novel predictive model focused on mortality prediction among patients undergoing cardiac surgery secondary to rheumatic valve conditions. METHODS: We conducted prospective consecutive all-comers patients with rheumatic heart disease (RHD) referred for surgical treatment of valve disease between May 2010 and July of 2015. Risk scores for hospital mortality were calculated using the 2000 Bernstein-Parsonnet, EuroSCORE II, InsCor, AmblerSCORE, GuaragnaSCORE, and the New York SCORE. In addition, we developed the rheumatic heart valve surgery score (RheSCORE). RESULTS: A total of 2,919 RHD patients underwent heart valve surgery. After evaluating 13 different models, the top performing areas under the curve were achieved using Random Forest (0.982) and Neural Network (0.952). Most influential predictors across all models included left atrium size, high creatinine values, a tricuspid procedure, reoperation and pulmonary hypertension. Areas under the curve for previously developed scores were all below the performance for the RheSCORE model: 2000 Bernstein-Parsonnet (0.876), EuroSCORE II (0.857), InsCor (0.835), Ambler (0.831), Guaragna (0.816) and the New York score (0.834). A web application is presented where researchers and providers can calculate predicted mortality based on the RheSCORE. CONCLUSIONS: The RheSCORE model outperformed pre-existing scores in a sample of patients with rheumatic cardiac disease.
Subject(s)
Cardiac Surgical Procedures/adverse effects , Heart Valve Diseases/mortality , Rheumatic Fever/mortality , Rheumatic Heart Disease/mortality , Aged , Female , Heart Valve Diseases/physiopathology , Heart Valve Diseases/surgery , Hospital Mortality , Humans , Male , Middle Aged , Rheumatic Fever/physiopathology , Rheumatic Fever/surgery , Rheumatic Heart Disease/physiopathology , Rheumatic Heart Disease/surgery , Risk Assessment , Risk FactorsABSTRACT
Molecular mimicry between streptococcal and human proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic fever (RF) and rheumatic heart disease (RHD). In this review we focus on the studies on genetic susceptibility markers involved in the development of RF/RHD and molecular mimicry mediated by T cell responses of RHD patients against streptococcal antigens and human tissue proteins. We identified several M protein epitopes recognized by peripheral T cells of RF/RHD patients and by heart tissue infiltrating T cell clones of severe RHD patients. The regions of the M protein preferentially recognized by human T cells were also recognized by murine T cells. By analyzing the T cell receptor (TCR) we observed that some Vbeta families detected on the periphery were oligoclonal expanded in the heart lesions. These results allowed us to confirm the major role of T cells in the development of RHD lesions.
Subject(s)
Antigens, Bacterial/immunology , Bacterial Outer Membrane Proteins/immunology , Carrier Proteins/immunology , Myocardium/immunology , Rheumatic Fever/immunology , T-Lymphocytes/immunology , Amino Acid Sequence , Animals , Antibodies, Bacterial/biosynthesis , Antigens, Bacterial/genetics , Autoantibodies/biosynthesis , Bacterial Outer Membrane Proteins/genetics , Carrier Proteins/genetics , Cross Reactions , Genetic Predisposition to Disease , Humans , Immunity, Cellular , Mice , Molecular Mimicry , Molecular Sequence Data , Receptors, Antigen, T-Cell, alpha-beta/genetics , Receptors, Antigen, T-Cell, alpha-beta/metabolism , Rheumatic Fever/genetics , Rheumatic Fever/microbiology , Streptococcus pyogenes/genetics , Streptococcus pyogenes/immunology , Streptococcus pyogenes/pathogenicityABSTRACT
Rheumatic fever (RF) is a sequel of group A streptococcal throat infection and occurs in untreated susceptible children. Rheumatic heart disease (RHD), the major sequel of RF, occurs in 30%-45% of RF patients. RF is still considered endemic in some regions of Brazil and is responsible for approximately 90% of early childhood valvular surgery in the country. In this study, we present a 15-year clinical follow-up of 25 children who underwent surgical valvular repair. Histopathological and immunological features of heart tissue lesions of RHD patients were also evaluated. The patients presented severe forms of RHD with congestive symptoms at a very young age. Many of them had surgery at the acute phase of RF. Histological analysis showed the presence of dense valvular inflammatory infiltrates and Aschoff nodules in the myocardium of 21% of acute RHD patients. Infiltrating T-cells were mainly CD4+ in heart tissue biopsies of patients with rheumatic activity. In addition, CD4+ and CD8+ infiltrating T-cell clones recognized streptococcal M peptides and cardiac tissue proteins. These findings may open the possibilities of new ways of immunotherapy. In addition, we demonstrated that the surgical procedure during acute phase of the disease improved the quality of life of young RHD patients.
Subject(s)
Rheumatic Heart Disease/immunology , Rheumatic Heart Disease/pathology , Adolescent , Antigens, Bacterial/immunology , Bacterial Outer Membrane Proteins/immunology , Biopsy , CD4-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , Carrier Proteins/immunology , Child , Clone Cells/immunology , Female , Follow-Up Studies , Heart Valve Diseases/pathology , Heart Valve Diseases/surgery , Humans , Immunohistochemistry , Male , Myocardium/pathology , Quality of LifeABSTRACT
OBJECTIVE: The human heart expresses the type 2 deiodinase (D2) that activates thyroxine (T4) to triiodothyronine (T3). At the same time, the inactivating type 3 deiodinase (D3) has been found in a rat model of right ventricular hypertrophy. It is not known whether the human myocardium metabolizes thyroid hormone. This study examined myocardial thyroid hormone metabolism in patients with aortic valve stenosis (AS) undergoing aortic valve replacement and in patients with coronary artery disease (CAD) undergoing coronary artery bypass grafting surgery. METHODS: Myocardial thyroid hormone metabolism was assessed by analyzing the difference in serum thyroid hormone levels between the aortic root (incoming blood) and the coronary sinus (outgoing blood) of patients undergoing cardiac surgery. A total of 23 patients with AS and 35 patients with CAD were included. Patients received a pre-surgical echocardiogram, and pre-, during and post-surgical thyroid hormone serum levels were collected in the myocardial and peripheral circulations. RESULTS: Patients with AS exhibited the expected left ventricle (LV) hypertrophy (i.e., 20-30% increase in LV posterior wall and interventricular septum thickness and â¼10% increase in AS in LV diastolic diameter). Immediately before cardiopulmonary bypass, blood flowing through the AS myocardium exhibited a 4.6% reduction in T3 and 6.9% increase in rT3 levels, decreasing the serum T3/rT3 ratio by 9.6%. T4 and thyrotropin serum levels remained similar between the aortic root and coronary sinus. In contrast, no myocardial thyroid hormone metabolism was observed in CAD patients. Notably, the AS myocardium lost the ability to inactivate thyroid hormone after cardiopulmonary bypass, possibly due to myocardial stunning. CONCLUSIONS: There is accelerated thyroid hormone inactivation in the AS myocardium, which is likely the result of D3 expression. No evidence to suggest thyroid hormone activation in the myocardium was obtained in the present study.
Subject(s)
Aortic Valve Stenosis/metabolism , Myocardium/metabolism , Triiodothyronine/blood , Aged , Aortic Valve Stenosis/pathology , Female , Humans , Male , Middle Aged , Myocardium/pathologyABSTRACT
BACKGROUND: Renal dysfunction is an independent predictor of morbidity and mortality in cardiac surgery. For a better assessment of renal function, calculation of creatinine clearance (CC) may be necessary. OBJECTIVE: To objectively evaluate whether CC is a better risk predictor than serum creatinine (SC) in patients undergoing cardiac surgery. METHODS: Analysis of 3,285 patients registered in a prospective, consecutive and mandatory manner in the Sao Paulo Registry of Cardiovascular Surgery (REPLICCAR) between November 2013 and January 2015. Values of SC, CC (Cockcroft-Gault) and EuroSCORE II were obtained. Association analysis of SC and CC with morbidity and mortality was performed by calibration and discrimination tests. Independent multivariate models with SC and CC were generated by multiple logistic regression to predict morbidity and mortality following cardiac surgery. RESULTS: Despite the association between SC and mortality, it did not calibrate properly the risk groups. There was an association between CC and mortality with good calibration of risk groups. In mortality risk prediction, SC was uncalibrated with values > 1.35 mg /dL (p < 0.001). The ROC curve showed that CC is better than SC in predicting both morbidity and mortality risk. In the multivariate model without CC, SC was the only predictor of morbidity, whereas in the model without SC, CC was not only a mortality predictor, but also the only morbidity predictor. CONCLUSION: Compared with SC, CC is a better parameter of renal function in risk stratification of patients undergoing cardiac surgery.
Subject(s)
Cardiac Surgical Procedures/mortality , Creatinine/blood , Glomerular Filtration Rate/physiology , Renal Insufficiency/blood , Renal Insufficiency/mortality , Risk Assessment/methods , Aged , Calibration , Cross-Sectional Studies , Female , Humans , Logistic Models , Male , Middle Aged , Morbidity , Prospective Studies , Reference Standards , Reference Values , Reproducibility of Results , Risk Factors , Sensitivity and SpecificityABSTRACT
BACKGROUND: Few studies evaluated systemic arterial embolism after beginning of symptoms of infective endocarditis in a large series of patients. METHODS: We studied 629 patients with left-sided infective endocarditis, aged 37.9+/-17.3 years, 396(63%) men and 233(37%) women. Endocarditis occurred on native valves in 405(64.4%) patients and on prosthetic heart valves in 224(35.6%). Infecting microorganisms were streptococci in 297(47.3%) patients, Staphylococcus aureus in 77(12.3%), Staphylococcus epidermidis in 56(8.9%), enterococci in 51(8.1%), Gram-negative bacteria in 33(5.2%), fungi in 9(1.4%) and other microorganisms in 27(4.2%). In 79(12.6%) patients blood cultures were negative. RESULTS: 146 embolic events occurred in 133(21.1%) out of 629 patients; in 63(47.4%) of them emboli affected the central nervous system, in 57(42.9%) affected peripheral organs and in 13(9.7%) affected both the central nervous system and peripheral organs. Embolism occurred between beginning of symptoms of endocarditis and antimicrobial therapy in 56(42.1%) patients and on the day therapy started in 18(13.5%); 109(81.9%) embolic events occurred up to the 15th day of antimicrobial therapy. Embolic risk was higher in S. aureus endocarditis (relative risk 2.97); in patients with a mitral (relative risk 2.4) or aortic (relative risk 3.3) prosthetic valve and vegetations on echocardiography. Embolic risk was lower in patients with a longer duration of symptoms. The death risk doubled in patients with embolism (relative risk 2.01). CONCLUSIONS: Embolic events were more frequently early events after beginning of symptoms of infective endocarditis. Embolic risk was higher in S. aureus endocarditis and in patients with prosthetic heart valves and vegetations on echocardiography.
Subject(s)
Embolism/complications , Embolism/diagnosis , Endocarditis/complications , Endocarditis/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Embolism/microbiology , Endocarditis/microbiology , Female , Humans , Infant , Male , Middle Aged , Probability , Prognosis , Risk Factors , Survival Rate , Time FactorsABSTRACT
BACKGROUND AND AIM OF THE STUDY: The study aim was to review the long-term results of mitral valve replacement (MVR) with the Biocor porcine bioprosthesis, in order to investigate patient survival and valve-related complications. METHODS: Data were presented for 546 patients (320 females, 226 males; mean age 49.2 +/- 17.1 years) who underwent MVR with the Biocor porcine bioprosthesis between March 1983 and December 2000. Preoperatively, rheumatic fever was present in 42.3% of patients. Associated procedures were performed in 179 patients (32.7%), and myocardial revascularization in 54 (9.9%). Preoperatively, 41.9% of patients were in NYHA class IV. Postoperative follow up was conducted by telephone interviews, questionnaires, or examination of hospital records. RESULTS: The hospital mortality was 9.5% (n=52); of these patients, 30 died after their first MVR and 22 after mitral reoperation. Mortality after isolated MVR was 7.6%. The total follow up was 2,148.9 patient-years, and actuarial survival was 45.0 +/- 15.8% at 15 years. Freedom from structural valve deterioration (SVD) was 51.8 +/- 13.8% for patients aged <50 years, 88.7 +/- 5.1% for those aged 51-60 years, and 84.0 +/- 9.8% for those aged 61-80 years. The incidence of prosthetic valve endocarditis was low, with 88.8 +/- 6.1% non-recurrence in 15 years. Freedom from reoperation was 33.9 +/- 10.4%, and from thromboembolism was 82.3 +/- 15.0%. Freedom from valve-related mortality was 80.7 +/- 12.5% during a 15-year period. CONCLUSION: The 15-year clinical results with the Biocor porcine bioprosthesis in the mitral position were excellent in a young, predominantly rheumatic, patient population which, preoperatively, was in a grave clinical condition. The incidence of valve-related complications was low, as was that of SVD in patients aged >50 years.
Subject(s)
Heart Valve Prosthesis/statistics & numerical data , Mitral Valve Insufficiency/mortality , Mitral Valve Insufficiency/surgery , Prosthesis-Related Infections/mortality , Risk Assessment/methods , Adolescent , Adult , Bioprosthesis/statistics & numerical data , Brazil/epidemiology , Child , Child, Preschool , Comorbidity , Disease-Free Survival , Equipment Failure Analysis , Female , Hospital Mortality , Humans , Incidence , Longitudinal Studies , Male , Prosthesis Failure , Risk Factors , Survival Analysis , Survival Rate , Treatment OutcomeABSTRACT
Commercial bioprosthetic heart valves are commonly preserved in glutaraldehyde and are cytotoxic to host cells, preventing spontaneous endothelialization. The aim of this study was to demonstrate the potential for in vivo endothelialization of bioprostheses treated by the L-Hydro process which consists of mild extraction of antigenic substances and incorporation of antiinflammatory and antithrombotic agents. Seven stented porcine heart valves treated by the L-Hydro process and 3 glutaraldehyde-fixed porcine heart valves were implanted in the mitral position in juvenile sheep. The valves were evaluated by echocardiography, angiography, histology, and histochemistry. No hemodynamic differences were observed, but scanning and transmission electron microscopy showed nearly complete coverage by endothelial cells of all leaflets in the L-Hydro-treated valves after 5 months of implantation. The endothelial cells were in direct contact with the underlying collagen and expressed von Willebrand-related antigens. The surfaces of the glutaraldehyde-treated valves were covered by fibrin, macrophages, calcium, and thrombotic material; only sparse endothelial cells were observed and contact with the underlying tissue was incomplete. These data indicate that L-Hydro-treated porcine valves are capable of inducing spontaneous endothelialization.
Subject(s)
Bioprosthesis , Fixatives , Glutaral , Heart Valve Prosthesis , Tissue Preservation/methods , Animals , Anti-Infective Agents, Local , Anti-Inflammatory Agents, Non-Steroidal , Calcinosis/pathology , Cell Differentiation , Collagen/metabolism , Endothelial Cells/cytology , Endothelium, Vascular/metabolism , Factor VIII/metabolism , Fibrinolytic Agents , Hydrogen Peroxide , Microscopy , Mitral Valve , Polyethylene Glycols , Sheep , SolventsABSTRACT
OBJECTIVES: Epidemiological differences can be found between Brazilian and European valvular heart disease patients. The prevalence of heart valve diseases due to rheumatic disease is significantly higher in the Brazilian compared with the European population. Therefore, they could have different risks during and after cardiac surgery. The aim of this study was to evaluate the applicability of the additive and logistic EuroSCORE and EuroSCORE II in a cohort of high-risk patients with valvular heart disease of predominantly rheumatic aetiology submitted to surgery. METHODS: Between 1 February and 30 December 2009, 540 consecutive patients scheduled for valvular heart surgery were included in this study. In this set of patients, we examined the performance of the additive, logistic, and EuroSCORE II models for predicting in-hospital mortality. Calibration of each model was assessed by comparing predicted and observed in-hospital mortality and by the goodness of fit of the Hosmer-Lemeshow chi-square test. Discrimination performance of the model was evaluated with the receiver operating characteristic (ROC) curve analysis. RESULTS: The mean age was 56 ± 16 years, 50.6% were female, and the mortality rate was 16.0% (6.0% in elective surgery and 34.0% in emergency/urgency surgery). Mortality rates were estimated according to the additive and logistic EuroSCORE and EuroSCORE II at 6.1%, 8.7%, and 4.3%, respectively. The AUC was 0.76 (95% confidence interval [95% CI] 0.70-0.81) for the additive EuroSCORE, 0.76 (95% CI 0.70-0.81) for the logistic EuroSCORE and 0.81 (95% CI 0.76-0.86) for EuroSCORE II. Hosmer-Lemeshow goodness-of-fit statistics were P = 0.52, P = 0.07, and P = 0.12 for additive, logistic EuroSCORE, and EuroSCORE II. CONCLUSIONS: In this cohort of Brazilian patients with valvular heart disease submitted to surgical procedure, the EuroSCORE models had a good discriminatory capacity; however, the calibration was compromised because of an underestimation of the mortality rate.