Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve.

BACKGROUND: The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain. METHODS: In this randomized trial, we compared rivaroxaban (20 mg once daily) with dose-adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months. RESULTS: A total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval [CI], -1.4 to 16.3; P<0.001 for noninferiority). Death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). Major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The frequency of other serious adverse events was similar in the two groups. CONCLUSIONS: In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months. (Funded by PROADI-SUS and Bayer; RIVER ClinicalTrials.gov number, NCT02303795.).

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

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.

Relation of mitral valve morphology to surgical repair results in patients with mitral valve prolapse: A three-dimensional transesophageal echocardiography study.

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.

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.

Myocardial Injury After Transcatheter Mitral Valve Replacement Versus Surgical Reoperation.

This study aimed to evaluate the incidence and clinical implications of myocardial injury, as determined by cardiac biomarker increase, in patients who underwent mitral bioprosthesis dysfunction treatment with transcatheter mitral valve replacement (TMVR) versus surgical mitral valve replacement reoperation (SMVR-REDO). Between 2014 and 2023, 310 patients with mitral bioprosthesis failure were included (90 and 220 patients for TMVR and SMVR-REDO, respectively). Multivariable analysis and propensity score matching were performed to adjust for the intergroup differences in baseline characteristics. Creatinine kinase-MB (CK-MB) and cardiac troponin I (cTn) were collected at baseline and 6 to 12, 24, 48, and 72 hours after intervention. The cardiac biomarkers values were evaluated in relation to their reference values. The outcomes were determined according to the Mitral Valve Academic Research Consortium criteria. CK-MB and cTn increased above the reference level in almost all patients after SMVR-REDO and TMVR (100% vs 94%, respectively), with the peak occurring within 6 to 12 hours. SMVR-REDO was associated with a two- to threefold higher increase in cardiac biomarkers. After 30 days, the mortality rates were 13.3% in the TMVR and 16.8% in the SMVR-REDO groups. At a median follow-up of 19 months, the mortality rates were 21.1% in the TMVR and 17.7% in the SMVR-REDO groups. Left ventricular ejection fraction, estimated glomerular filtration rate, CK-MB, and cTn were predictors of mortality. In conclusion, some degree of myocardial injury occurred systematically after the treatment of mitral bioprosthetic degeneration, especially after SMVR, and higher CK-MB and cTn levels were associated with increased cumulative late mortality, regardless of the approach.

B-type natriuretic peptide and N-terminal Pro-B-type natriuretic peptide in severe aortic stenosis: a comprehensive literature review.

B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro BNP) are cardiac biomarkers that are released in response to increased ventricular and atrial wall stress. Aortic stenosis (AS) leads to hemodynamic changes and left ventricular hypertrophy and may be associated with natriuretic peptide levels. Several studies have shown that increased natriuretic peptide levels are correlated with AS severity and can predict the need for intervention. It can be useful in risk stratification, monitoring follow-up, and predicting cardiovascular outcomes of patients with severe AS. This paper aims to summarize the evidence of the role of BNP and NT-pro BNP in AS, before and after intervention.

Incidental Diagnosis of Rheumatic Myocarditis during Cardiac Surgery-Impact on Late Prognosis.

Rheumatic fever (RF) and rheumatic heart disease (RHD) are still highly prevalent, particularly in low- and middle-income countries. RHD is a neglected and underdiagnosed disease for which no specific laboratory diagnostic test is completely reliable. This is a retrospective observational study, which included 118 patients with RHD who underwent cardiac surgery from 1985 to 2018. The aim of this investigation was to evaluate the clinical, epidemiological, echocardiographic and pathological characteristics in two cohorts of RHD patients: one cohort with Aschoff bodies present in their pathological results and the other without such histopathological characteristics. No conventional clinical and laboratory tests for RHD myocarditis were able to identify active carditis during the preoperative phase of valve repair or replacement. Patients who had Aschoff bodies in their pathological results were younger (median age of 13 years (11-24 years) vs. 27 years (17-37 years), p = 0.001) and had higher rate of late mortality (22.9% vs. 5.4%, p = 0.043). In conclusion, the presence of Aschoff bodies in pathological findings may predict increased long-term mortality, emphasizing the importance of comprehensive pathology analysis for suspected myocarditis during heart surgery.

Postoperative myocardial fibrosis assessment in aortic valvular heart diseases-a cardiovascular magnetic resonance study.

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.

Risk prediction in patients with classical low-flow, low-gradient aortic stenosis undergoing surgical intervention.

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 ≤1.0 cm2, mean transaortic gradient <40 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 >25 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 >25 mmHg [2.0 (0.0-8.9) g vs. 8.5 (2.3-15.0) 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) 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 ≤25 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 ≤25 mmHg. The absence of left ventricular FR had no prognostic impact on long-term outcomes.

Multimodality imaging methods and systemic biomarkers in classical low-flow low-gradient aortic stenosis: Key findings for risk stratification.

Objectives: The aim of the present study is to assess multimodality imaging findings according to systemic biomarkers, high-sensitivity troponin I (hsTnI) and B-type natriuretic peptide (BNP) levels, in low-flow, low-gradient aortic stenosis (LFLG-AS). Background: Elevated levels of BNP and hsTnI have been related with poor prognosis in patients with LFLG-AS. Methods: Prospective study with LFLG-AS patients that underwent hsTnI, BNP, coronary angiography, cardiac magnetic resonance (CMR) with T1 mapping, echocardiogram and dobutamine stress echocardiogram. Patients were divided into 3 groups according to BNP and hsTnI levels: Group 1 (n = 17) when BNP and hsTnI levels were below median [BNP < 1.98 fold upper reference limit (URL) and hsTnI < 1.8 fold URL]; Group 2 (n = 14) when BNP or hsTnI were higher than median; and Group 3 (n = 18) when both hsTnI and BNP were higher than median. Results: 49 patients included in 3 groups. Clinical characteristics (including risk scores) were similar among groups. Group 3 patients had lower valvuloarterial impedance (P = 0.03) and lower left ventricular ejection fraction (P = 0.02) by echocardiogram. CMR identified a progressive increase of right and left ventricular chamber from Group 1 to Group 3, and worsening of left ventricular ejection fraction (EF) (40 [31-47] vs. 32 [29-41] vs. 26 [19-33]%; p < 0.01) and right ventricular EF (62 [53-69] vs. 51 [35-63] vs. 30 [24-46]%; p < 0.01). Besides, there was a marked increase in myocardial fibrosis assessed by extracellular volume fraction (ECV) (28.4 [24.8-30.7] vs. 28.2 [26.9-34.5] vs. 31.8 [28.9-35.5]%; p = 0.03) and indexed ECV (iECV) (28.7 [21.2-39.1] vs. 28.8 [25.4-39.9] vs. 44.2 [36.4-51.2] ml/m2, respectively; p < 0.01) from Group 1 to Group 3. Conclusions: Higher levels of BNP and hsTnI in LFLG-AS patients are associated with worse multi-modality evidence of cardiac remodeling and fibrosis.

Clinical Profile and 30-Day Outcomes of Patients with Bicuspid Aortic Valve Undergoing Aortic Valve and/or Aorta Surgery. / Perfil Clínico e Desfechos em 30 Dias de Pacientes Portadores de Valva Aórtica Bicúspide Submetidos à Cirurgia em Valva Aórtica e/ou Aorta.

BACKGROUND: The bicuspid aortic valve (BAV) affects 0.5 to 2% of the population and is associated with valve and aortic alterations. There is a lack of studies on the profile of these patients in the Brazilian population. OBJECTIVE: To describe the profile of patients with BAV undergoing valve and/or aortic surgery in a tertiary cardiology center, in addition to the outcomes related to the intervention. METHODS: Retrospective cohort including 195 patients (mean age 54±14 years, 73.8% male) diagnosed with BAV who underwent surgical approach (valvular and/or aorta) from 2014 to 2019. Clinical data, echocardiographic and tomographic studies were evaluated, as well as characteristics of the intervention and events in 30 days. A value of p<0.05 was considered statistically significant. RESULTS: We found a high prevalence of aortic aneurysm (56.5%), with a mean diameter of 46.9±10.2 mm. Major aortic regurgitation was found in 25.1% and major aortic stenosis in 54.9%. Isolated aortic valve surgery was performed in 48.2%, isolated aortic surgery in 6.7% and combined surgery in 45.1%. The 30-day mortality was 8.2%. In the multivariate analysis, the predictors of the combined outcome at 30 days (death, atrial fibrillation and reoperation) were age (OR 1.044, 95% CI 1.009-1.081, p=0.014) and left ventricular mass index (OR 1.009, 95% CI 1.000-1.018, p=0.044). CONCLUSION: Patients with BAV approached in our service have a higher incidence of aortopathy, with the additional need to evaluate the aorta with computed tomography or magnetic resonance imaging.

FUNDAMENTO: A válvula aórtica bicúspide (VAB) atinge de 0,5 a 2% da população e está associada a alterações valvares e de aorta. Há carência de estudos sobre o perfil desses pacientes na população brasileira. OBJETIVO: Descrever o perfil de pacientes com VAB submetidos à cirurgia valvar e/ou de aorta em um centro cardiológico terciário, assim como os desfechos relacionados à intervenção. MÉTODOS: Coorte retrospectiva incluindo 195 pacientes (idade média 54±14 anos, 73,8% do sexo masculino) com diagnóstico de VAB submetidos à abordagem cirúrgica (valvar e/ou de aorta) no período de 2014 a 2019. Foram avaliados dados clínicos, ecocardiográficos e tomográficos, além das características da intervenção e eventos em 30 dias. O valor de p<0,05 foi considerado estatisticamente significante. RESULTADOS: Encontramos alta prevalência de aneurisma de aorta (56,5%), com diâmetro médio de 46,9±10,2 mm. Insuficiência aórtica importante foi encontrada em 25,1% e estenose aórtica importante em 54,9%. Cirurgia isolada em valva aórtica foi realizada em 48,2%, cirurgia isolada de aorta em 6,7% e cirurgia combinada em 45,1%. A mortalidade em 30 dias foi de 8,2%. Na análise multivariada, os fatores preditores de desfecho combinado em 30 dias (morte, fibrilação atrial e reoperação) foram idade (OR 1,044, IC 95% 1,009-1,081, p=0,014) e o índice de massa do ventrículo esquerdo (OR 1,009, IC 95% 1,000-1,018, p=0,044). CONCLUSÃO: Pacientes com VAB abordados no nosso serviço apresentam uma maior incidência de aortopatia, com a necessidade adicional de avaliação da aorta com tomografia computadorizada ou ressonância magnética.

Delayed left main coronary obstruction following transfemoral inovare transcatheter aortic valve replacement: A challenging case.

Coronary obstruction is an uncommon and severe complication after a transcatheter aortic valve replacement (TAVR), that occurs during the procedure in the vast majority of patients. In the present case even in the absence of classic risk factors, an acute coronary syndrome occurred one day after TAVR. Selective angiography revealed a severe left main ostium obstruction by the bulky native leaflet calcification. This is the first case of delayed presentation of coronary obstruction with a transfemoral balloon-expandable valve using the Inovare bioprosthesis (Braile Biomedica, Brazil). In addition, after drug-eluting stent placement in the left main coronary, intravascular ultrasound revealed severe stent underexpansion, so that a second layer of a bare-metal stent and high-pressure balloon post-dilatation was necessary to improve the final result. The patient was discharged after 7 days, and at the 6-month follow-up remained asymptomatic. .

Performance of Prediction Models for Contrast-Induced Acute Kidney Injury after Transcutaneous Aortic Valve Replacement.

BACKGROUND: Acute kidney injury (AKI) has shown to adversely affect outcomes in patients undergoing transcutaneous aortic valve replacement (TAVR), and its correct risk estimation may interfere in procedural planning and strategies. The aim of the study was to test and compare 6 scores in predicting AKI after TAVR. METHODS: We tested 6 scores (the contrast material limit score, volume-to-creatinine clearance ratio, ACEF, CR4EATME3AD3, Mehran model A, and Mehran model B) in a total of 559 consecutive patients included in the Brazilian TAVR registry. RESULTS: All scores had a poor accuracy and calibration to predict the occurrence of AKI grade 1 or 2. All scores improved the accuracy of AKI risk prediction when stratified for AKI grade 2/3 and AKI grade 3 for all scores. The CR4EATME3AD3 was the best predictor of AKI stage 2/3 (AUC: 0.62; OR: 1.12; 95% CI 1.01-1.26; p = 0.04) and AKI stage 3 (AUC: 0.64; OR: 1.16; 95% CI 1.02-1.32; p = 0.02). Mehran models A and B were both good models for AKI stage 3 (AUC: 0.63; OR: 1.10; 95% CI 1.01-1.22; p = 0.05; and AUC: 0.62; OR: 1.10; 95% CI 1.00-1.21; p = 0.05, respectively). CONCLUSIONS: None of the current models demonstrated validity in detecting AKI when its lower grades were evaluated. CR4EATME3AD3 was the best score in predicting moderate to severe AKI after TAVR. These findings suggest that contrast-induced AKI may not be the only factor related to kidney injury after TAVR.

StreptInCor, a Group A Streptococcal Adsorbed Vaccine: Evaluation of Repeated Intramuscular Dose Toxicity Testing in Rats.

Streptococcus pyogenes infections continue to be a worldwide public health problem, causing various diseases in humans, with rheumatic fever and rheumatic heart disease being the most harmful manifestations. Impetigo and post-streptococcal glomerulonephritis are also important sequelae of skin infections. We have developed a candidate vaccine epitope (StreptInCor) that presents promising results in diverse animal models. To assess whether the StreptInCor alum-adsorbed vaccine could induce undesirable effects, a certified independent company conducted a repeated intramuscular dose toxicity evaluation in Wistar rats, a choice model for toxicity studies. We did not observe significant alterations in clinical, hematological, biochemical, anatomical, or histopathological parameters due to vaccine administration, even when the animals received the highest dose. In conclusion, repeated intramuscular doses did not show signs of macroscopic or other significant changes in the clinical or histopathological parameters, indicating that StreptInCor can be considered a safe candidate vaccine.

Demographic, cardiological, microbiologic, and dental profiles of Brazilian patients who developed oral bacteria-related endocarditis.

OBJECTIVE: Infective endocarditis (IE) may cause devastating complications with high morbidity and mortality rates. The aim of the present study was to study the demographic, cardiological, microbiologic, and dental profiles of patients with oral bacteria-related IE. STUDY DESIGN: We present a retrospective study of patients with oral bacteria-related IE treated at Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de Sao Paulo, Brazil, between January 2009 and December 2019. RESULTS: Of the 100 patients included, 70% were male with a mean age of 45.4 years at diagnosis. The most affected sites were aortic and mitral valves, 60% in prosthetic heart valves, 34% in native valves, and 3% in pacemakers. The most common cause of valvular disease was rheumatic cardiopathy (51.9%), and the most frequent complications were valvular and perivalvular damage (26%). Streptococcus viridans was the most common species (96%), dental caries were present in 57% of the patients, 78% had tooth loss, 45% had apical periodontitis, and 77% were at high/moderate risk for periodontal disease. CONCLUSION: Oral bacteria-related IE among Brazilians was predominant in the prosthetic heart valves of young male adults previously affected by rheumatic cardiopathy. Streptococcus viridans was the main cause of IE, which was linked to patients with a poor oral health status.

Heyde's Syndrome: Therapeutic Strategies and Long-Term Follow-Up. / Síndrome de Heyde: Estratégias Terapêuticas e Seguimento de Longo Prazo.

BACKGROUND: Heyde's syndrome is the association of severe aortic stenosis with episodes of gastrointestinal bleeding due to angiodysplastic lesion. Little is known about the factors associated with new episodes of bleeding and long-term outcomes. Furthermore, most data are restricted to case reports and small case series. OBJECTIVE: To assess the clinical, laboratory and echocardiography profile of patients with Heyde's syndrome who underwent valve intervention or drug therapy. METHODS: Prospective cohort of 24 consecutive patients from 2005 to 2018. Clinical, laboratory and echocardiography data were assessed, as well as those related to valve intervention and outcomes after diagnosis. A P <0.05 was used to indicate statistical significance. RESULTS: Half of the 24 patients presented with bleeding requiring blood transfusion on admission. Angiodysplasias were more frequently found in the ascending colon (62%). Valve intervention (surgical or transcatheter) was performed in 70.8% of the patients, and 29.2% remained on drug therapy. News episodes of bleeding occurred in 25% of the cases, and there was no difference between clinical and intervention groups (28.6 vs 23.5%, p = 1.00; respectively). Mortality at 2-year and 5-year was 16% and 25%, with no difference between the groups (log-rank p = 0.185 and 0.737, respectively). CONCLUSIONS: Patients with Heyde's syndrome had a high rate of bleeding requiring blood transfusion on admission, suggesting that it is a severe disease with high mortality risk. No difference was found between clinical and intervention group regarding the rate of rebleeding and late mortality.

FUNDAMENTOS: A síndrome de Heyde é a associação de estenose aórtica importante com episódio de sangramento gastrointestinal por lesões angiodisplásicas. Pouco é conhecido sobre os fatores associados a novos sangramentos e desfechos em longo prazo. Além disso, a maioria dos dados é restrita a relatos de casos e pequenas séries. OBJETIVO: Avaliar o perfil clínico, laboratorial e ecocardiográfico de pacientes com síndrome de Heyde submetidos a intervenção valvar ou tratamento medicamentoso. MÉTODOS: Coorte prospectiva de 24 pacientes consecutivos entre 2005 e 2018. Foram avaliados dados clínicos, laboratoriais, ecocardiográficos e relacionados à intervenção valvar e a desfechos após o diagnóstico. Valor de p<0,05 foi considerado estatisticamente significante. RESULTADOS: Metade dos 24 pacientes apresentou sangramento com necessidade de transfusão sanguínea na admissão. Angiodisplasias foram encontradas mais frequentemente no cólon ascendente (62%). Intervenção valvar (cirúrgica ou transcateter) foi realizada em 70,8% dos pacientes, e 29,2% foram mantidos em tratamento clínico. Novos episódios de sangramento ocorreram em 25% dos casos, e não houve diferença entre os grupos clínico e intervenção (28,6 vs. 23,5%, p=1,00; respectivamente). A mortalidade no seguimento de 2 e 5 anos foi de 16% e 25%, sem diferença entre os grupos (log-rank p = 0,185 e 0,737, respectivamente). CONCLUSÕES: Pacientes com síndrome de Heyde tiveram alta taxa de sangramento com necessidade de transfusão sanguínea na admissão, sugerindo ser uma doença grave e com risco elevado de mortalidade. Não encontramos diferenças entre os grupos submetidos ao tratamento clínico e à intervenção valvar em relação a taxas de ressangramento e mortalidade tardia.

Rheumatic Myocarditis: A Poorly Recognized Etiology of Left Ventricular Dysfunction in Valvular Heart Disease Patients.

Background: Heart failure occurs in ~10% of patients with acute rheumatic fever (RF), and several studies have shown that cardiac decompensation in RF results primarily from valvular disease and is not due to primary myocarditis. However, the literature on this topic is scarce, and a recent case series has shown that recurrent RF can cause ventricular dysfunction even in the absence of valvular heart disease. Methods: The present study evaluated the clinical, laboratory and imaging characteristics of 25 consecutive patients with a clinical diagnosis of myocarditis confirmed by 18F-FDG PET/CT or gallium-67 cardiac scintigraphy and RF reactivation according to the revised Jones Criteria. Patients underwent three sequential echocardiograms at (1) baseline, (2) during myocarditis and (3) post corticosteroid treatment. Patients were divided according to the presence (Group 1) or absence (Group 2) of reduced left ventricular ejection fraction (LVEF) during myocarditis episodes. Results: The median age was 42 (17-51) years, 64% of patients were older than 40 years, and 64% were women. Between Group 1 (n = 16) and in Group 2 (n = 9), there were no demographic, echocardiographic or laboratory differences except for NYHA III/IV heart failure (Group 1: 100.0% vs. Group 2: 50.0%; p = 0.012) and LVEF (30 [25-37] vs. 56 [49-62]%, respectively; p < 0.001), as expected. Group 1 patients showed a significant reduction in LVEF during carditis with further improvement after treatment. There was no correlation between LVEF and valvular dysfunction during myocarditis. Among all patients, 19 (76%) underwent 18F-FDG PET/CT, with a positive scan in 68.4%, and 21 (84%) underwent gallium-67 cardiac scintigraphy, with positive uptake in 95.2%, there was no difference between these groups. Conclusion: Myocarditis due to rheumatic fever reactivation can cause left ventricular dysfunction despite valvular disease, and it is reversible after corticosteroid treatment.

3D Echocardiography for Rheumatic Heart Disease Analysis: Ready for Prime Time.

Rheumatic heart disease (RHD) remains to be a very important health issue worldwide, mainly in underdeveloped countries. It continues to be a leading cause of morbidity and mortality throughout developing countries. RHD is a delayed non-suppurative immunologically mediated inflammatory response to the throat infection caused by a hemolytic streptococcus from the A group (Streptococcus pyogenes). RHD keeps position 1 as the most common cardiovascular disease in young people aged <25 years considering all the continents. The disease can lead to valvular cardiac lesions as well as to carditis. Rheumatic fever valvular injuries lead most commonly to the fusion and thickening of the edges of the cusps and to the fusion, thickening, and shortening of the chordae and ultimately to calcification of the valves. Valvular commissures can also be deeply compromised, leading to severe stenosis. Atrial and ventricular remodeling is also common following rheumatic infection. Mixed valvular lesions are more common than isolated valvular disorders. Echocardiography is the most relevant imaging technique not only to provide diagnostic information but also to enable prognostic data. Further, it presents a very important role for the correction of complications after surgical repair of rheumatic heart valvulopathies. Three-dimensional (3D) echocardiography provides additional anatomical and morphofunctional information of utmost importance for patients presenting rheumatic valvopathies. Accordingly, three-dimensional echocardiography is ready for routine use in patients with RHD presenting with valvular abnormalities.

Transcatheter Valve-in-Valve Procedures for Bioprosthetic Valve Dysfunction in Patients With Rheumatic vs. Non-Rheumatic Valvular Heart Disease.

Background: Bioprosthetic heart valve has limited durability and lower long-term performance especially in rheumatic heart disease (RHD) patients that are often subject to multiple redo operations. Minimally invasive procedures, such as transcatheter valve-in-valve (ViV) implantation, may offer an attractive alternative, although data is lacking. The aim of this study was to evaluate the baseline characteristics and clinical outcomes in rheumatic vs. non-rheumatic patients undergoing ViV procedures for severe bioprosthetic valve dysfunction. Methods: Single center, prospective study, including consecutive patients undergoing transcatheter ViV implantation in aortic, mitral and tricuspid position, from May 2015 to September 2020. RHD was defined according to clinical history, previous echocardiographic and surgical findings. Results: Among 106 patients included, 69 had rheumatic etiology and 37 were non-rheumatic. Rheumatic patients had higher incidence of female sex (73.9 vs. 43.2%, respectively; p = 0.004), atrial fibrillation (82.6 vs. 45.9%, respectively; p < 0.001), and 2 or more prior surgeries (68.1 vs. 32.4%, respectively; p = 0.001). Although, device success was similar between groups (75.4 vs. 89.2% in rheumatic vs. non-rheumatic, respectively; p = 0.148), there was a trend toward higher 30-day mortality rates in the rheumatic patients (21.7 vs. 5.4%, respectively; p = 0.057). Still, at median follow-up of 20.7 [5.1-30.4] months, cumulative mortality was similar between both groups (p = 0.779). Conclusion: Transcatheter ViV implantation is an acceptable alternative to redo operations in the treatment of patients with RHD and severe bioprosthetic valve dysfunction. Despite similar device success rates, rheumatic patients present higher 30-day mortality rates with good mid-term clinical outcomes. Future studies with a larger number of patients and follow-up are still warranted, to firmly conclude on the role transcatheter ViV procedures in the RHD population.