Flávio Tarasoutchi

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.

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.

Influence of the maze procedure on the treatment of rheumatic atrial fibrillation – evaluation of rhythm control and clinical outcome in a comparative study

OBJECTIVE The aim of this study was to evaluate the influence of the maze procedure on the treatment of rheumatic atrial fibrillation in patients with mitral valve disease. METHODS Fifty-five patients (mean age 51 years; 47 females) with rheumatic mitral valve disease and associated atrial fibrillation in New York Heart Association functional class III or IV, preoperatively, were operated upon. Thirty-five had double dysfunction, 19 had stenosis, and one had mitral regurgitation. None had other associated heart diseases or previous operations. The patients were divided into two groups: GI, 20 patients were treated for mitral valve disease with associated maze procedure; GII, 35 patients were treated for mitral valve disease without the maze procedure. The preoperative echocardiogram showed a left atrial diameter in GI of 5.35 mm and in GII of 5.57 mm (P=0.779). The groups were considered clinically similar (P=0.759). Cardiopulmonary bypass was used in all patients. The mitral valve was replaced with a biological prosthesis in 24 patients and repaired in 31 patients. RESULTS Three hospital deaths occurred, one in GI, two in GII. After cardiopulmonary bypass, 37.1% of patients in GII remained in atrial fibrillation. All patients in GI recovered regular rhythm (P<0.0001). In the ICU, atrial fibrillation was detected in 80% of patients in GII and maintained in 76.4% in a mean follow-up period of 38.5 months. In GI, atrial fibrillation occurred in 20% of patients in the ICU and maintained in 5.3% in 41 months of mean follow-up (P=0.0001). None of the patients in GI and 20.6% of patients in GII had a thromboembolic episode 1-63 months after the operation (P=0.041). Four late deaths occurred (two in each group), two being due to progression of valvular disease, one after an episode of pulmonary infection and one with no cardiac cause. CONCLUSION The maze procedure is effective in treating atrial fibrillation in patients with rheumatic mitral valve disease. The results are sustained in the mid-term follow-up period, preventing postoperative thromboembolic episodes, and with acceptable morbidity and mortality.

Multivariate analysis of risk factors for hospital mortality in valvular reoperations for prosthetic valve dysfunction

OBJECTIVES The purpose of the study was to analyze risk factors for hospital mortality in patients undergoing valvular reoperations for prosthetic valve dysfunction. METHODS We performed a prospective analysis of 146 patients who underwent valvular reoperations for prosthetic valve dysfunction between July 1995 and June 1999 at the Heart Institute of the University of São Paulo Medical School. Multivariate statistical analysis with logistic regression was used to analyze preoperative and intraoperative variables to determine risk factors for hospital mortality. RESULTS The overall hospital mortality was 10.9% (16 patients). Univariate analysis showed that the following variables were associated with higher mortality rates: advanced New York Heart Association (NYHA) functional class, increased creatinine level, prolonged extracorporeal circulation time and treatment of annular abscess. Logistic multivariate analysis identified advanced NYHA functional class and a creatinine level higher than 1.5 mg/dl as independent predictors of hospital mortality. CONCLUSIONS Advanced NYHA functional class and higher creatinine levels were independent predictors of hospital mortality in patients submitted for valvular reoperations for prosthetic valve dysfunction.

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.

Symptoms, left ventricular function, and timing of valve replacement surgery in patients with aortic regurgitation

BACKGROUND Because cardiac decompensation is subtle, the best time to perform aortic valve replacement surgery may be difficult to determine. We investigated the relation of symptoms to left ventricular (LV) function and the timing of valve replacement in patients with aortic regurgitation (AR) of largely rheumatic origin. METHODS Sixty-eight initially asymptomatic patients (mean age 29 years) with severe chronic AR were monitored for 36 months. Assessments included baseline and yearly echocardiograms and radioisotope ventriculography (resting and exercise) and clinical examinations every 6 months. RESULTS Forty-seven patients (69%) remained asymptomatic and 21 (31%) had symptoms develop after 24 to 36 months. Compared with symptomatic patients, asymptomatic patients had significantly (P <.05) lower baseline LV end-diastolic diameter, end-systolic diameter, end-systolic stress, and volume/mass ratio but greater shortening fraction and ejection fraction (EF) at rest. These variables remained stable without statistically significant change until surgical correction in symptomatic patients. Percent variation of EF from rest to exercise increased in patients who remained asymptomatic (EF 2.8% +/- 10.6%) but decreased in those who became symptomatic (EF -4.2% +/- 13%; P <.05). Twenty symptomatic patients (New York Heart Association class III/IV, angina and/or syncope) had valve replacement surgery, after which all were in New York Heart Association class I/II and had significant decreases of LV end-diastolic and end-systolic diameters and an increase on percent variation of EF from rest to exercise (P <.0001). CONCLUSIONS Development of symptoms did not correlate with change in any ventricular function indexes. Surgery on appearance of symptoms restored LV function to near normal.

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.

Comparison between Percutaneous Balloon Valvuloplasty and Open Commissurotomy for Mitral Stenosis

Eighty patients with tight and pliable mitral stenosis were randomized in a prospective trial comparing percutaneous balloon valvuloplasty and open commissurotomy. Mitral valve area increased significantly in both groups immediately after the procedures. However, a decrease in mitral valve area occurred in both groups at 6, 12 and 24 months during the follow-up. There was no death in either group. Two patients had significant mitral regurgitation after percutaneous balloon valvuloplasty. After 24 months, all patients in the commissurotomy group and 97.4% of the patients in the balloon valvuloplasty group were in New York Heart Association functional class I or II.