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.

The Impact of Sonothrombolysis on Left Ventricular Diastolic Function and Left Atrial Mechanics Preventing Left Atrial Remodeling in Patients With ST Elevation Acute Myocardial Infarction.

BACKGROUND: The diagnostic ultrasound-guided high mechanical index impulses during an intravenous microbubble infusion (sonothrombolysis) improve myocardial perfusion in acute ST segment elevation myocardial infarction, but its effect on left ventricular diastolic dysfunction (DD), left atrial (LA) mechanics and remodeling is unknown. We assessed the effect of sonothrombolysis on DD grade and LA mechanics. METHODS: One hundred patients (59 ± 10 years; 34% women) were randomized to receive either high mechanical index impulses plus percutaneous coronary intervention (PCI) (therapy group) or PCI only (control group) (n = 50 in each group). Diastolic dysfunction grade and LA mechanics were assessed immediately before and after PCI and at 48 to 72 hours, 1 month, and 6 months of follow-up. Diastolic dysfunction grades were classified as grades I, II, and III. The LA mechanics was obtained by two-dimensional speckle-tracking echocardiography-derived global longitudinal strain (GLS). RESULTS: As follow-up time progressed, increased DD grade was observed more frequently in the control group than in the therapy group at 1 month and 6 months of follow-up (all P < .05). The LA-GLS values were incrementally higher in the therapy group when compared with the control group at 48 to 72 hours, 24.0% ± 7.3% in the therapy group versus 19.6% ± 7.2% in the control group, P = .005; at 1 month, 25.3% ± 6.3% in the therapy group versus 21.5% ± 8.3% in the control group, P = .020; and at 6 months, 26.2% ± 8.7% in the therapy group versus 21.6% ± 8.5% in the control group, P = .015. The therapy group was less likely to experience LA remodeling (odds ratio, 2.91 [1.10-7.73]; P = .03). LA-GLS was the sole predictor of LA remodeling (odds ratio, 0.79 [0.67-0.94]; P = .006). CONCLUSION: Sonothrombolysis is associated with better DD grade and LA mechanics, reducing LA remodeling.

Comprehensive myocardial characterization using cardiac magnetic resonance associates with outcomes in low gradient severe aortic stenosis.

AIMS: This study sought to compare cardiac magnetic resonance (CMR) characteristics according to different flow/gradient patterns of aortic stenosis (AS) and to evaluate their prognostic value in patients with low-gradient AS. METHODS AND RESULTS: This international prospective multicentric study included 147 patients with low-gradient moderate to severe AS who underwent comprehensive CMR evaluation of left ventricular global longitudinal strain (LVGLS), extracellular volume fraction (ECV), and late gadolinium enhancement (LGE). All patients were classified as followings: classical low-flow low-gradient (LFLG) [mean gradient (MG) < 40 mmHg and left ventricular ejection fraction (LVEF) < 50%]; paradoxical LFLG [MG < 40 mmHg, LVEF ≥ 50%, and stroke volume index (SVi) < 35 ml/m2]; and normal-flow low-gradient (MG < 40 mmHg, LVEF ≥ 50%, and SVi ≥ 35 ml/m2). Patients with classical LFLG (n = 90) had more LV adverse remodelling including higher ECV, and higher LGE and volume, and worst LVGLS. Over a median follow-up of 2 years, 43 deaths and 48 composite outcomes of death or heart failure hospitalizations occurred. Risks of adverse events increased per tertile of LVGLS: hazard ratio (HR) = 1.50 [95% CI, 1.02-2.20]; P = 0.04 for mortality; HR = 1.45 [1.01-2.09]; P < 0.05 for composite outcome; per tertile of ECV, HR = 1.63 [1.07-2.49]; P = 0.02 for mortality; HR = 1.54 [1.02-2.33]; P = 0.04 for composite outcome. LGE presence also associated with higher mortality, HR = 2.27 [1.01-5.11]; P < 0.05 and composite outcome, HR = 3.00 [1.16-7.73]; P = 0.02. The risk of mortality and the composite outcome increased in proportion to the number of impaired components (i.e. LVGLS, ECV, and LGE) with multivariate adjustment. CONCLUSIONS: In this international prospective multicentric study of low-gradient AS, comprehensive CMR assessment provides independent prognostic value that is cumulative and incremental to clinical and echocardiographic characteristics.

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.

Improvement of renal function after transcatheter aortic valve replacement in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease is commonly found in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) and has marked impact in their prognosis. It has been shown however that TAVR may improve renal function by alleviating the hemodynamic barrier imposed by AS. Nevertheless, the predictors of and clinical consequences of renal function improvement are not well established. Our aim was to assess the predictors of improvement of renal function after TAVR. METHODS: The present work is an analysis of the Brazilian Registry of TAVR, a national non-randomized prospective study with 22 Brazilian centers. Patients with baseline renal dysfunction (estimated glomerular filtration rate [eGFR] < 60mL/min/1.73m2) were stratified according to renal function after TAVR: increase >10% in eGFR were classified as TAVR induced renal function improvement (TIRFI); decrease > 10% in eGFR were classified as acute kidney injury (AKI) and stable renal function (neither criteria). RESULTS: A total of 819 consecutive patients with symptomatic severe AS were included. Of these, baseline renal dysfunction (estimated glomerular filtration rate [eGFR] < 60mL/min/1.73m2) was present in 577 (70%) patients. Considering variance in renal function between baseline and at discharge after TAVR procedure, TIRFI was seen in 197 (34.1%) patients, AKI in 203 (35.2%), and stable renal function in 177 (30.7%). The independent predictors of TIRFI were: absence of coronary artery disease (OR: 0.69; 95% CI 0.48-0.98; P = 0.039) and lower baseline eGFR (OR: 0.98; 95% CI 0.97-1.00; P = 0.039). There was no significant difference in 30-day and 1-year all-cause mortality between patients with stable renal function or TIRFI. Nonetheless, individuals that had AKI after TAVR presented higher mortality compared with TIRFI and stable renal function groups (29.3% vs. 15.4% vs. 9.5%, respectively; p < 0.001). CONCLUSIONS: TIRFI was frequently found among baseline impaired renal function individuals but was not associated with improved 1-year outcomes.

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.

Myocardial Fibrosis in Classical Low-Flow, Low-Gradient Aortic Stenosis.

Background Few data exist on the degree of interstitial myocardial fibrosis in patients with classical low-flow, low-gradient aortic stenosis (LFLG-AS) and its association with left ventricular flow reserve (FR) on dobutamine stress echocardiography. This study sought to evaluate the diffuse interstitial fibrosis measured by T1 mapping cardiac magnetic resonance technique in LFLG-AS patients with and without FR. Methods Prospective study including 65 consecutive patients (41 LFLG-AS [mean age, 67.1±8.4 years; 83% men] and 24 high-gradient aortic stenosis used as controls) undergoing dobutamine stress echocardiography to assess FR and cardiac magnetic resonance to determine the extracellular volume (ECV) fraction of the myocardium, indexed ECV (iECV) to body surface area and late gadolinium enhancement. Results Interstitial myocardial fibrosis measured by iECV was higher in patients with LFLG-AS with and without FR as compared with high-gradient aortic stenosis (35.25±9.75 versus 32.93±11.00 versus 21.19±6.47 mL/m2, respectively; P<0.001). However, both ECV and iECV levels were similar between LFLG-AS patients with and without FR ( P=0.950 and P=0.701, respectively). Also, FR did not correlate significantly with ECV (r=-0.16, P=0.31) or iECV (r=0.11, P=0.51). Late gadolinium enhancement mass was also similar in patients with versus without FR but lower in high-gradient aortic stenosis (13.3±10.2 versus 10.5±7.5 versus 4.8±5.9 g, respectively; P=0.018). Conclusions Patients with LFLG-AS have higher ECV, iECV, and late gadolinium enhancement mass compared with high-gradient aortic stenosis. Moreover, among patients with LFLG-AS, the degree of myocardial fibrosis was similar in patients with versus those without FR. These findings suggest that diffuse myocardial fibrosis may not be the main factor responsible for the absence of FR in LFLG-AS patients.

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.

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.