Guilherme Sobreira Spina

Prognostic Significance of Myocardial Fibrosis Quantification by Histopathology and Magnetic Resonance Imaging in Patients With Severe Aortic Valve Disease

OBJECTIVES We sought to determine whether the quantitative assessment of myocardial fibrosis (MF), either by histopathology or by contrast-enhanced magnetic resonance imaging (ce-MRI), could help predict long-term survival after aortic valve replacement. BACKGROUND Severe aortic valve disease is characterized by progressive accumulation of interstitial MF. METHODS Fifty-four patients scheduled to undergo aortic valve replacement were examined by ce-MRI. Delayed-enhanced images were used for the quantitative assessment of MF. In addition, interstitial MF was quantified by histological analysis of myocardial samples obtained during open-heart surgery and stained with picrosirius red. The ce-MRI study was repeated 27+/-22 months after surgery to assess left ventricular functional improvement, and all patients were followed for 52+/-17 months to evaluate long-term survival. RESULTS There was a good correlation between the amount of MF measured by histopathology and by ce-MRI (r=0.69, p<0.001). In addition, the amount of MF demonstrated a significant inverse correlation with the degree of left ventricular functional improvement after surgery (r=-0.42, p=0.04 for histopathology; r=-0.47, p=0.02 for ce-MRI). Kaplan-Meier analyses revealed that higher degrees of MF accumulation were associated with worse long-term survival (chi-square=6.32, p=0.01 for histopathology; chi-square=5.85, p=0.02 for ce-MRI). On multivariate Cox regression analyses, patient age and the amount of MF were found to be independent predictors of all-cause mortality. CONCLUSIONS The amount of MF, either by histopathology or by ce-MRI, is associated with the degree of left ventricular functional improvement and all-cause mortality late after aortic valve replacement in patients with severe aortic valve disease.

Effectiveness of the Maze Procedure Using Cooled-Tip Radiofrequency Ablation in Patients With Permanent Atrial Fibrillation and Rheumatic Mitral Valve Disease

Background—Although the Cox-Maze III procedure is effective for treating permanent atrial fibrillation (AF), its high complexity limits its use. The Saline-Irrigated Cooled-tip Radiofrequency Ablation (SICTRA) System is an alternative source of energy used to ablate AF. The aim of this study was to evaluate the effectiveness of the SICTRA for the treatment of permanent AF in patients with rheumatic mitral valve (MV) disease. Methods and Results—Between February 2002 and April 2003, 70 patients with permanent AF and rheumatic MV disease were randomly assigned to undergo a modified Maze III procedure using SICTRA associated with MV surgery (group A) or MV surgery alone (group B). Groups A and B were similar in terms of baseline characteristics. The in-hospital mortality rate was 2.3% (1 death) in group A versus 0% (no deaths) in group B (P>0.99). The additional time required for the left-sided radiofrequency ablation in group A was 14.2±5.1 minutes and for right-sided ablation was 12.3±4.2 minutes. The mean postoperative follow-up periods were 13.8±3.4 and 11.5±7.3 months, respectively, in groups A and B. The overall mid-term survival rate was 95.1% in group A and 92.8% in group B (P>0.99). The cumulative rates of sinus rhythm were 79.4% in group A and 26.9% in group B (P=0.001). Doppler echocardiography documented biatrial transport function in 90.3% of group A patients in sinus rhythm. Conclusions—The SICTRA is effective for treating permanent AF associated with rheumatic MV disease.

Ten-year clinical laboratory follow-up after application of a symptom-based therapeutic strategy to patients with severe chronic aortic regurgitation of predominant rheumatic etiology.

OBJECTIVES This study was designed to assess the feasibility and the long-term results of a symptom-based strategy of aortic valve replacement in a Brazilian population with predominant rheumatic etiology. BACKGROUND Optimal criteria for valve replacement in aortic regurgitation (AR) are still not entirely clear. The appearance of symptoms is an indication for surgery, but may be associated with myocardial damage. Although cardiac imaging data have provided a safer guide for such decisions, the use of symptom-based surgical indication has not been validated and might conceivably be better in populations with predominant rheumatic etiology and younger age. METHODS Echocardiography and rest-exercise radionuclide ventriculography were performed in 75 patients with severe AR, age 28 +/- 9 years, over a period of 10 +/- 0.69 years. Thirty-seven patients developed symptoms and underwent aortic valve replacement surgery within six months. Thirty-eight patients remained asymptomatic and were managed medically. RESULTS Survival was 100% in asymptomatic patients and 82% in symptomatic. Surgical treatment caused marked ventricular remodeling, with ventricular diameter involution and an improvement of rest-exercise ejection fraction percent variation. Multivariate analysis showed that the probability of developing symptoms within 10 years was 58% for a patient with a left ventricular end-diastolic diameter > or =70 mm and 76% for a patient with left ventricular end-systolic (LVESD) > or =50 mm. Logistic regression identified LVESD and age as the most predictive and specific, but not sensitive, indicators of symptom development. CONCLUSIONS Application of a standardized therapeutic strategy to patients with severe AR and predominant rheumatic etiology resulted in 90.6% survival after 10 years of follow-up.

Association of Mannose-Binding Lectin Gene Polymorphism but Not of Mannose-Binding Serine Protease 2 with Chronic Severe Aortic Regurgitation of Rheumatic Etiology

ABSTRACT N-Acetylglucosamine (GlcNAc) is the major immunoepitope of group A streptococcal cell wall carbohydrates. Antistreptococcal antibodies cross-reactive with anti-GlcNAc and laminin are present in sera of patients with rheumatic fever. The cross-reactivity of these antibodies with human heart valvular endothelium and the underlying basement membrane has been suggested to be a possible cause of immune-mediated valve lesion. Mannose-binding lectin (MBL) encoded by the MBL2 gene, a soluble pathogen recognition receptor, has high affinity for GlcNAc. We postulated that mutations in exon 1 of the MBL2 gene associated with a deficient serum level of MBL may contribute to chronic severe aortic regurgitation (AR) of rheumatic etiology. We studied 90 patients with severe chronic AR of rheumatic etiology and 281 healthy controls (HC) for the variants of the MBL2 gene at codons 52, 54, and 57 by using a PCR-restriction fragment length polymorphism-based method. We observed a significant difference in the prevalence of defective MBL2 alleles between patients with chronic severe AR and HC. Sixteen percent of patients with chronic severe AR were homozygotes or compound heterozygotes for defective MBL alleles in contrast to 5% for HC (P = 0.0022; odds ratio, 3.5 [95% confidence interval, 1.6 to 7.7]). No association was detected with the variant of the MASP2 gene. Our study suggests that MBL deficiency may contribute to the development of chronic severe AR of rheumatic etiology.

Contrast-enhanced magnetic resonance imaging identifies focal regions of intramyocardial fibrosis in patients with severe aortic valve disease: Correlation with quantitative histopathology.

BACKGROUND Chronic aortic valve disease (AVD) is characterized by progressive accumulation of interstitial myocardial fibrosis (MF). However, assessment of MF accumulation has only been possible through histologic analyses of endomyocardial biopsies. We sought to evaluate contrast-enhanced magnetic resonance imaging (ce-MRI) as a noninvasive method to identify the presence of increased MF in patients with severe AVD. METHODS Seventy patients scheduled to undergo aortic valve replacement surgery were examined by cine and ce-MRI in a 1.5-T scanner. Cine images were used for the assessment of left ventricular (LV) volumes, mass, and function. Delayed-enhancement images were used to characterize the regions of MF. In addition, histologic analyses of myocardial samples obtained during aortic valve replacement surgery were used for direct quantification of interstitial MF. Ten additional subjects who died of noncardiac causes served as controls for the quantitative histologic analyses. RESULTS Interstitial MF determined by histopathologic analysis was higher in patients with AVD than in controls (2.7% +/- 2.0% vs 0.6% +/- 0.2%, P = .001). When compared with histopathologic results, ce-MRI demonstrated a sensitivity of 74%, a specificity of 81%, and an accuracy of 76% to identify AVD patients with increased interstitial MF. There was a significant inverse correlation between interstitial MF and LV ejection fraction (r = -0.67, P < .0001). Accordingly, patients with identifiable focal regions of MF by ce-MRI exhibited worse LV systolic function than those without MF (45% +/- 14% vs 65% +/- 14%, P < .0001). CONCLUSIONS Contrast-enhanced MRI allows for the noninvasive detection of focal regions of MF in patients with severe AVD. Moreover, patients with identifiable MF by ce-MRI exhibited worse LV functional parameters.

Perfil neuro-hormonal de pacientes reumáticos com insuficiência aórtica crônica importante

BACKGROUND Neurohormones are involved in the physiopathology of heart failure, but little is known about its behavior in significant chronic aortic regurgitation (AR). We aimed at analyzing the behavior of these mediators in AF. OBJECTIVE We aimed at analyzing the behavior of these mediators in AF. METHODS We analyzed 89 patients with AF, whose mean age was 33.6+/-11.5 years and of whom 84.6% were males, 60% asymptomatic, all with rheumatic etiology. After the clinical and echocardiographic assessment, plasma measurements of tumor necrosis factor (TNF), soluble TNF receptor types I and II (sTNFRI e sTNFRII), interleukin-6 (IL-6), its soluble receptor (sIL6R), endothelin-1 and B-type natriuretic peptide (BNP) were carried out; 12 healthy individuals were used as controls. RESULTS The mean values of the left ventricle diastolic diameter (LVDD) were 71.9+/-8.3mm, whereas the mean values of the LV systolic diameter (LVSD) were 50.4+/-9.3mm. The neurohormonal levels were elevated in patients with AF (TNF 92.65+/-110.24 pg/mL vs. 1.67+/-1.21 pg/ml in controls, p<0.001), (IL-6 7.17+/-7.78 pg/ml vs. 0.81+/-0.38 pg/mL in controls, p=0.0001) and TNFRI (894.75+/-348.87 pg/mL vs. 521.42+/-395.13 pg/ml, p=0.007). Except for the BNP levels, symptomatic and asymptomatic patients presented a similar neurohormonal profile. There was a correlation between TNFRII and LVDD (r=-0.329, p=0.038) and LVSD (r=-0.352, p=0.027). BNP levels were significantly higher in symptomatic patients and only in the latter it was possible to establish a correlation between BNP and ventricular diameters. CONCLUSION Patients with significant chronic AF present high neurohormonal levels, with no correlation with the symptomatic status. The TNFRII and BNP levels could be correlated with ventricular diameters, but only the latter could be correlated with symptoms.FUNDAMENTO: Os neuro-hormonios estao envolvidos na fisiopatologia da insuficiencia cardiaca, mas pouco se sabe sobre seu comportamento na insuficiencia aortica cronica importante (IAo). OBJETIVO: Analisar o comportamento desses mediadores na IAo. METODOS: Analisamos 89 pacientes com IAo, com media etaria de 33,6±11,5 anos, 84,6% do sexo masculino, 60% assintomaticos, todos de etiologia reumatica. Apos avaliacao clinica e ecocardiografica, realizaram-se dosagens plasmaticas de fator de necrose tumoral (TNF), seus antagonistas receptores soluveis tipos I e II (sTNFRI e sTNFRII), interleucina-6 (IL-6), seu receptor soluvel, endotelina-1 e peptideo natriuretico tipo B (BNP). Doze individuos saudaveis serviram como controle. RESULTADOS: O valor medio de diâmetro diastolico (DD) do ventriculo esquerdo (VE) foi de 71,9±8,3 mm, e o do diâmetro sistolico (DS) do VE, de 50,4±9,3 mm. Os niveis de neuro-hormonios estavam elevados nos pacientes com IAo: TNF 92,65±110,24 pg/ml vs. 1,67±1,21 pg/ml nos controles, p<0,001; IL-6 7,17±7,78 pg/ml vs. 0,81±0,38 pg/ml nos controles, p = 0,0001; e TNFRI 894,75±348,87 pg/ml vs. 521,42±395,13 pg/ml, p = 0,007. Com excecao dos niveis de BNP, os pacientes sintomaticos e assintomaticos apresentaram perfil neuro-hormonal semelhante. Houve correlacao entre TNFRII e diâmetro diastolico do ventriculo esquerdo (DDVE) (r = -0,329, p = 0,038) e diâmetro sistolico do ventriculo esquerdo (DSVE) (r = -0,352, p = 0,027). Os niveis de BNP estavam significativamente mais altos em pacientes sintomaticos, e apenas nestes foi possivel correlacao entre BNP e diâmetros ventriculares. CONCLUSAO: Pacientes com insuficiencia aortica cronica importante apresentam altos niveis neuro-hormonios, sem correlacao com o status sintomatico. Os niveis de TNFRII e BNP puderam ser correlacionados com diâmetros ventriculares, mas apenas este ultimo com sintomas.

Comparison of Inhaled Nitric Oxide Versus Oxygen on Hemodynamics in Patients With Mitral Stenosis and Severe Pulmonary Hypertension After Mitral Valve Surgery

Pulmonary hypertension represents an important cause of morbidity and mortality in patients with mitral stenosis who undergo cardiac surgery, especially in the postoperative period. The aim of this study was to test the hypothesis that inhaled nitric oxide (iNO) would improve the hemodynamic effects and short-term clinical outcomes of patients with mitral stenosis and severe pulmonary hypertension who undergo cardiac surgery in a randomized, controlled study. Twenty-nine patients (4 men, 25 women; mean age 46 ± 2 years) were randomly allocated to receive iNO (n = 14) or oxygen (n = 15) for 48 hours immediately after surgery. Hemodynamic data, the use of vasoactive drugs, duration of stay, and short-term complications were assessed. No differences in baseline characteristics were observed between the groups. After 24 and 48 hours, patients receiving iNO had a significantly greater increase in cardiac index compared to patients receiving oxygen (p <0.0001). Pulmonary vascular resistance was also more significantly reduced in patients receiving iNO versus oxygen (-117 dyne/s/cm(5), 95% confidence interval -34 to -200, vs 40 dyne/s/cm(5), 95% confidence interval -34 to 100, p = 0.005) at 48 hours. Patients in the iNO group used fewer systemic vasoactive drugs (mean 2.1 ± 0.14 vs 2.6 ± 0.16, p = 0.046) and had a shorter intensive care unit stay (median 2 days, interquartile range 0.25, vs median 3 days, interquartile range 7, p = 0.02). In conclusion, iNO immediately after surgery in patients with mitral stenosis and severe pulmonary hypertension improves hemodynamics and may have short-term clinical benefits.

Sangramento durante a anticoagulação oral: alerta sobre um mal maior

BACKGROUND Bleeding is one of the main concerns in patients undergoing oral anticoagulation therapy. OBJECTIVE To investigate the determinant causes of bleeding in patients undergoing oral anticoagulant therapy. METHODS A total of 360 patients with atrial fibrillation (AF) undergoing oral anticoagulant (ACo) therapy, with a target INR of 2.0-3.5, were followed prospectively for a period of 48 +/- 7.2 months. The patients were evaluated on average every 30 days and were investigated regarding the presence of associated pathology that could lead to bleeding. RESULTS A total of 338 patients participated in the present study. Of these, 210 (62.13%) were females. Mitral stenosis was present in 218 patients (64.4%), a mitral biological prosthesis in 64 (18.9%) and mitral valve failure in 56 (16.5%) patients. Bleeding occurred in 65 patients (19.2%), being severe in 7 (10%) patients. In 38/65 patients, a new associated disease was identified, which facilitated bleeding. An associated disease was identified in 100% of the patients with bleeding within the therapeutic range, against 49.05% of associated disease diagnosis in those with an INR > 3.5 (p=0.001). CONCLUSION The diagnosis of a local disease associated to the bleeding was frequent among those patients undergoing oral anticoagulant therapy (58.5%). There was an association between bleeding with an INR within the therapeutic range (INR=2.0-3.5) and the diagnosis of a pathology predisposing to bleeding (p<0.001). It is mandatory to investigate the cause of bleeding in patients undergoing oral anticoagulant therapy, especially if the INR is within the therapeutic range.FUNDAMENTO: Sangramento e uma das grandes preocupacoes em pacientes sob anticoagulacao oral. OBJETIVO: Investigar causas determinantes do sangramento em usuarios de anticoagulante oral. METODOS: Foram acompanhados prospectivamente, por 48 ± 7,2 meses, 360 pacientes com fibrilacao atrial (FA), todos em uso de anticoagulante oral (ACo) com INR-alvo de 2,0-3,5, avaliados em media a cada 30 dias. Os pacientes foram investigados quanto a presenca de patologia associada que levasse a sangramento. RESULTADOS: Participaram deste estudo 338 pacientes. Desses, 210 (62,13%) eram do sexo feminino. A estenose mitral estava presente em 218 pacientes (64,4%), a protese biologica mitral em 64 (18,9%) e a insuficiencia da valva mitral em 56 (16,5%). O sangramento ocorreu em 65 pacientes (19,2%) e de forma grave em 7 (10%). Em 38/65 pacientes (58,5%), identificou-se nova doenca associada, facilitadora do sangramento. Em 100% dos pacientes com sangramento na faixa terapeutica, foi encontrada doenca associada, contra 49,05% de diagnostico de doencas associadas naqueles com INR > 3,5 (p = 0,001). CONCLUSAO: O diagnostico de doenca local associada ao sangramento foi frequente entre os medicados com anticoagulante oral (58,5%). Houve associacao entre sangramento com INR na faixa terapeutica (INR 2,0-3,5) e diagnostico de patologia predisponente a sangramento (p < 0,001). Em pacientes em uso de anticoagulante oral que apresentam sangramento, e mandatoria a investigacao da causa, sobretudo se a INR estiver na faixa terapeutica.

Troca valvar com preservação de cordas e plástica na cirurgia da insuficiência mitral crônica

OBJECTIVE To compare, from the clinical and laboratory points of view, 3 groups of patients undergoing surgical treatment for isolated chronic mitral insufficiency. One group underwent valvuloplasty, and the other 2 groups underwent mitral valve replacement with different techniques for chordal preservation. METHODS Twenty-eight patients with a mean age of 54.1 years, no coronary or multivalvular disease, and no reoperation, underwent surgery as follows: 9 underwent valvuloplasty; 10 underwent mitral valve replacement with chordal preservation in both leaflets; and 9 underwent mitral valve replacement with chordal preservation only in the posterior leaflet. Clinical, Doppler echocardiographic, and radionuclide ventriculographic assessments were performed until the 6th month of follow-up. RESULTS At the end, 88.8% of the patients were in functional class I. One died due to intracranial hemorrhage during anticoagulant treatment. The left ventricular diastolic diameter (P<0.0001) and end-diastolic volume (P<0.0001) decreased in the 3 groups. Only the patients undergoing valvuloplasty had a decrease in systolic diameter (P=0.0003) and in end-systolic volume (P=0.0040), with no change in the ejection fraction (P=0.5586). The patients undergoing mitral valve replacement had a similar drop in ejection fraction (P=0.0001 and P=0.0296). CONCLUSION The 3 surgical techniques used provided clinical improvement. Patients undergoing valvuloplasty had better preservation of ventricular function. No significant difference was observed in cardiac performance between the 2 groups undergoing mitral valve replacement with chordal preservation within a 6-month follow-up.

Varfarina ou Aspirina na prevenção de fenômenos embólicos na valvopatia mitral com fibrilação atrial

BACKGROUND: Atrial fibrillation (AF) associated to rheumatic mitral valve disease (RMVD) increases the incidence of thromboembolism (TE), with warfarin being the standard therapy, in spite of difficulties in treatment adherence and therapeutic control. OBJECTIVE: To compare the effectiveness of Aspirin vs Warfarin in TE prevention in patients with AF and RMVD. METHODS: A total of 229 patients (pts) with AF and RMVD were followed in a prospective and randomized study. The first group consisted of 110 pts receiving Aspirin - 200 mg/day (Group Aspirin - GA) and the second group consisted of 119 pts receiving Warfarin at individually-adjusted doses (Group Warfarin - GW). RESULTS: There were 15 embolic events in GA and 24 in GW (p = 0.187), of which 21 presented INR < 2.0. Thus, after excluding patients with inadequate INR, there was a higher number of embolic events in GA than in GW (15 vs 3) (p < 0.0061). The GW showed lower treatment adherence (p = 0.001). Neither group presented episodes of major bleeding. Small bleeding episodes were more frequent in the GW (p < 0.01). Increased serum levels of cholesterol and triglycerides constituted a risk factor for a higher number of thromboembolic events in the studied population, with no difference between the groups. CONCLUSION: In patients presenting RMVD with AF for less than a year and no previous embolism, Aspirin is little effective in preventing TE. Patients with lower-risk mitral valvulopathy (mitral regurgitation and mitral biological prosthesis), especially in cases presenting contraindication to or low adherence to Warfarin, Aspirin use can present some benefit in TE prevention.BACKGROUND Atrial fibrillation (AF) associated to rheumatic mitral valve disease (RMVD) increases the incidence of thromboembolism (TE), with warfarin being the standard therapy, in spite of difficulties in treatment adherence and therapeutic control. OBJECTIVE To compare the effectiveness of Aspirin vs Warfarin in TE prevention in patients with AF and RMVD. METHODS A total of 229 patients (pts) with AF and RMVD were followed in a prospective and randomized study. The first group consisted of 110 pts receiving Aspirin - 200 mg/day (Group Aspirin - GA) and the second group consisted of 119 pts receiving Warfarin at individually-adjusted doses (Group Warfarin - GW). RESULTS There were 15 embolic events in GA and 24 in GW (p = 0.187), of which 21 presented INR < 2.0. Thus, after excluding patients with inadequate INR, there was a higher number of embolic events in GA than in GW (15 vs 3) (p < 0.0061). The GW showed lower treatment adherence (p = 0.001). Neither group presented episodes of major bleeding. Small bleeding episodes were more frequent in the GW (p < 0.01). Increased serum levels of cholesterol and triglycerides constituted a risk factor for a higher number of thromboembolic events in the studied population, with no difference between the groups. CONCLUSION In patients presenting RMVD with AF for less than a year and no previous embolism, Aspirin is little effective in preventing TE. Patients with lower-risk mitral valvulopathy (mitral regurgitation and mitral biological prosthesis), especially in cases presenting contraindication to or low adherence to Warfarin, Aspirin use can present some benefit in TE prevention.