Non-toxigenic Corynebacterium diphtheriae infective endocarditis with embolic events: a case report.

BACKGROUND: Corynebacterium diphtheriae (C. diphtheriae) infections, usually related to upper airways involvement, could be highly invasive. Especially in developing countries, non-toxigenic C. diphtheriae strains are now emerging as cause of invasive disease like endocarditis. The present case stands out for reinforcing the high virulence of this pathogen, demonstrated by the multiple systemic embolism and severe valve deterioration. It also emphasizes the importance of a coordinated interdisciplinary work to address all these challenges related to infectious endocarditis. CASE PRESENTATION: A 21-year-old male cocaine drug abuser presented to the emergency department with a 1-week history of fever, asthenia and dyspnea. His physical examination revealed a mitral systolic murmur, signs of acute arterial occlusion of the left lower limb, severe arterial hypotension and acute respiratory failure, with need of vasoactive drugs, orotracheal intubation/mechanical ventilation, empiric antimicrobial therapy and emergent endovascular treatment. The clinical suspicion of acute infective endocarditis was confirmed by transesophageal echocardiography, demonstrating a large vegetation on the mitral valve associated with severe valvular regurgitation. Abdominal ultrasound was normal with no hepatic, renal, or spleen abscess. Serial blood cultures and thrombus culture, obtained in the vascular procedure, identified non-toxigenic C. diphtheriae, with antibiotic therapy adjustment to monotherapy with ampicillin. Since the patient had a severe septic shock with sustained fever, despite antimicrobial therapy, urgent cardiac surgical intervention was planned. Anatomical findings were compatible with an aggressive endocarditis, requiring mitral valve replacement for a biological prosthesis. During the postoperative period, despite an initial clinical recovery and successfully weaning from mechanical ventilation, the patient presented with a recrudescent daily fever. Computed tomography of the abdomen revealed a hypoattenuating and extensive splenic lesion suggestive of abscess. After sonographically guided bridging percutaneous catheter drainage, surgical splenectomy was performed. Despite left limb revascularization, a forefoot amputation was required due to gangrene. The patient had a good clinical recovery, fulfilling 4-weeks of antimicrobial treatment. CONCLUSION: Despite the effectiveness of toxoid-based vaccines, recent global outbreaks of invasive C. diphtheriae infectious related to non-toxigenic strains have been described. These infectious could be highly invasive as demonstrated in this case. Interdisciplinary work with an institutional "endocarditis team" is essential to achieve favorable clinical outcomes in such defiant scenarios.

Heart Transplant in Patients with Predominantly Rheumatic Valvular Heart Disease.

BACKGROUND AND AIM OF THE STUDY: International records indicate that only 2.6% of patients with heart transplants have valvular heart disease. The study aim was to evaluate the epidemiological and clinical profile of patients with valvular heart disease undergoing heart transplantation. METHODS: Between 1985 and 2013, a total of 569 heart transplants was performed at the authors' institution. Twenty patients (13 men, seven women; mean age 39.5 +/- 15.2 years) underwent heart transplant due to structural (primary) valvular disease. Analyses were made of the patients' clinical profile, laboratory data, echocardiographic and histopathological data, and mortality and rejection. RESULTS: Of the patients, 18 (90%) had a rheumatic etiology, with 85% having undergone previous valve surgery (45% had one or more operations), and 95% with a normal functioning valve prosthesis at the time of transplantation. Atrial fibrillation was present in seven patients (35%), while nine (45%) were in NYHA functional class IV and eight (40%) in class III. The indication for cardiac transplantation was refractory heart failure in seven patients (35%) and persistent NYHA class III/IV in ten (50%). The mean left ventricular ejection fraction (LVEF) was 26.6 +/- 7.9%. The one-year mortality was 20%. Histological examination of the recipients' hearts showed five (27.7%) to have reactivated rheumatic myocarditis without prior diagnosis at the time of transplantation. Univariate analysis showed that age, gender, LVEF, rheumatic activity and rejection were not associated with mortality at one year. CONCLUSION: Among the present patient cohort, rheumatic heart disease was the leading cause of heart transplantation, and a significant proportion of these patients had reactivated myocarditis diagnosed in the histological analyses. Thus, it appears valid to investigate the existence of rheumatic activity, especially in valvular cardiomyopathy with severe systolic dysfunction before transplantation.

Total surgical correction of Lutembacher syndrome associated with partial anomalous connection of the pulmonary veins and tricuspid regurgitation.

Lutembacher syndrome is characterized by the association of mitral stenosis and atrial septal defect (ASD), usually of the ostium secundum type. The association between superior vena cava-type ASD and partial anomalous pulmonary venous connection is unusual and there are few descriptions in the literature. We report this condition in a 24-year-old woman who was admitted to the hospital with a 1-year history of progressive dyspnea and describe the successful surgical repair following mitral commissurotomy and tunneling of the anomalous pulmonary veins to the left atrium, which determines the closure of the ASD and tricuspid repair.

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.

Rheumatic heart disease: 15 years of clinical and immunological follow-up.

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.

[Symptomatic severe chronic aortic valve disease: a comparative study of cardiac magnetic resonance imaging and echocardiography]. / Valvopatia aórtica crônica grave sintomática: estudo comparado da ressonância magnética cardíaca e ecocardiografia.

OBJECTIVE: To show the real value of cardiac magnetic resonance imaging (CMRI) in the evaluation of patients with symptomatic chronic aortic valve disease. METHODS: Seventy patients--35 with aortic stenosis (AoS) and 35 with aortic regurgitation (AoR) with surgical indication, who underwent preoperative echocardiogram (ECHO) and CMRI to assess ventricular function, volumes, and left ventricular mass index using cine magnetic resonance imaging, were studied. RESULTS: No statistically significant difference was observed between the AoS and AoR groups when ECHO and CMRI variables were compared. When compared with the type of symptom, ECHO and CMRI variables showed the same pattern. CONCLUSION: CMRI data were in agreement with ECHO data regarding the assessment of left ventricular volume and ejection fraction, and with the clinical presentation of patients with chronic 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.

Effect of enalapril on left ventricular diameters and exercise capacity in asymptomatic or mildly symptomatic patients with regurgitation secondary to mitral valve prolapse or rheumatic heart disease.

The effects of 12 months of therapy were evaluated in 47 mildly symptomatic patients with moderate to severe mitral valve regurgitation; 26 patients received enalapril and 21 received a placebo. Enalapril was associated with a significant reduction in left ventricular diameter and mitral regurgitation volume, with no evidence of change in systolic function indexes. However, enalapril did not hinder progressive aerobic impairment to effort.

Incidental histological diagnosis of acute rheumatic myocarditis: case report and review of the literature.

Rheumatic fever (RF) remains endemic in many countries and frequently causes heart failure due to severe chronic rheumatic valvular heart disease, which requires surgical treatment. Here, we report on a patient who underwent an elective surgical correction for mitral and aortic valvular heart disease and had a post-operative diagnosis of acute rheumatic carditis. The incidental finding of Aschoff bodies in myocardial biopsies is frequently reported in the nineteenth-century literature, with prevalences as high as 35%, but no clinical or prognostic data on the patients is included. The high frequency of this finding after cardiac surgery in classical reports suggests that these patients were not using secondary prophylaxis for RF. We discuss the clinical diagnosis of acute rheumatic myocarditis in asymptomatic patients and the laboratorial and imaging methods for the diagnosis of acute rheumatic carditis. We also discuss the prognostic implications of this finding and review the related literature.

Distinct mitral valve proteomic profiles in rheumatic heart disease and myxomatous degeneration.

Rheumatic heart disease (RHD) affects heart-valve tissue and is the most serious consequence of group A Streptococcus infection. Myxomatous degeneration (MXD) is the most frequent valvopathy in the western world. In the present work, key protein expression alterations in the heart-valve tissue of RHD and MXD patients were identified and characterized, with controls from cadaveric organ donors. Proteins were separated by two-dimensional (2D)-electrophoresis and identified by mass spectrometry. We found 17 differentially expressed protein spots, as compared to control samples. We observed an increased expression of ASAP-2 in the RHD patients' valves, while collagen-VI, haptoglobin-related protein, prolargin, and cartilage oligomeric protein showed reduced expression. Valve tissue of MXD patients, on the other hand, presented lower expression of annexin-A1 and A2, septin-2, SOD (Cu/Zn), and transgelin. Tissue samples from both valvopathies displayed higher expression of apolipoprotein-A1. Biglycan was downexpressed in both diseases. Vimentin and lumican showed higher expression in RHD and lower in MXD. These results suggest that key pathogenetic mechanisms are intrinsically distinct in RHD and MXD.

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.

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.

Prevalence of coronary artery disease and preoperative assessment in patients with valvopathy.

BACKGROUND: Coronary angiography has been indicated in the preoperative phase for patients with valvopathy over 35 years of age. However, the actual prevalence of obstructive coronary artery disease (CAD) in this population has been little studied. OBJECTIVE: To assess the prevalence of and the risk factors for CAD in candidates for valve surgery in Brazil. METHODS: Coronary angiography was performed in 3,736 patients who were candidates for valve surgery; prevalence of and risk factors for CAD associated with valvopathy were assessed. RESULTS: CAD was associated with valvopathy in 121 patients (prevalence of 3.42%). In 79 patients (68.1%), CAD was diagnosed by means of preoperative coronary angiography. Of these 79 patients, 50 (63.3%) had isolated aortic valvopathy or aortic valvopathy associated with mitral valvopathy. Smoking habit was observed in 54 patients (68.3%), hypertension in four (43%), family history in 24 (30.3%), diabetes mellitus in 15 (18.9%), and obesity in eight (10.1%). Of the 121 patients, 95.7% were over 50 years of age. Only five (4.3% of the patients with CAD) were below 50 years of age, and all of them had at least one risk factor for CAD. CONCLUSION: CAD prevalence was low in the patients studied. Aortic valvopathy was the most frequent valvopathy associated with CAD, and most patients were over 50 years of age. The ideal age for routine preoperative coronary angiography in patients with valvopathy should be reassessed.

Association of mannose-binding lectin gene polymorphism but not of mannose-binding serine protease 2 with chronic severe aortic regurgitation of rheumatic etiology.

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.