Transcatheter or Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis and Small Aortic Annulus: A Randomized Clinical Trial.

BACKGROUND: The optimal treatment in patients with severe aortic stenosis and small aortic annulus (SAA) remains to be determined. This study aimed to compare the hemodynamic and clinical outcomes between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with a SAA. METHODS: This prospective multicenter international randomized trial was performed in 15 university hospitals. Participants were 151 patients with severe aortic stenosis and SAA (mean diameter <23 mm) randomized (1:1) to TAVR (n=77) versus SAVR (n=74). The primary outcome was impaired valve hemodynamics (ie, severe prosthesis patient mismatch or moderate-severe aortic regurgitation) at 60 days as evaluated by Doppler echocardiography and analyzed in a central echocardiography core laboratory. Clinical events were secondary outcomes. RESULTS: The mean age of the participants was 75.5±5.1 years, with 140 (93%) women, a median Society of Thoracic Surgeons predicted risk of mortality of 2.50% (interquartile range, 1.67%-3.28%), and a median annulus diameter of 21.1 mm (interquartile range, 20.4-22.0 mm). There were no differences between groups in the rate of severe prosthesis patient mismatch (TAVR, 4 [5.6%]; SAVR, 7 [10.3%]; P=0.30) and moderate-severe aortic regurgitation (none in both groups). No differences were found between groups in mortality rate (TAVR, 1 [1.3%]; SAVR, 1 [1.4%]; P=1.00) and stroke (TAVR, 0; SAVR, 2 [2.7%]; P=0.24) at 30 days. After a median follow-up of 2 (interquartile range, 1-4) years, there were no differences between groups in mortality rate (TAVR, 7 [9.1%]; SAVR, 6 [8.1%]; P=0.89), stroke (TAVR, 3 [3.9%]; SAVR, 3 [4.1%]; P=0.95), and cardiac hospitalization (TAVR, 15 [19.5%]; SAVR, 15 [20.3%]; P=0.80). CONCLUSIONS: In patients with severe aortic stenosis and SAA (women in the majority), there was no evidence of superiority of contemporary TAVR versus SAVR in valve hemodynamic results. After a median follow-up of 2 years, there were no differences in clinical outcomes between groups. These findings suggest that the 2 therapies represent a valid alternative for treating patients with severe aortic stenosis and SAA, and treatment selection should likely be individualized according to baseline characteristics, additional anatomical risk factors, and patient preference. However, the results of this study should be interpreted with caution because of the limited sample size leading to an underpowered study, and need to be confirmed in future larger studies. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03383445.

Cardiovascular findings in Williams-Beuren Syndrome: Experience of a single center with 127 cases.

Williams-Beuren syndrome (WBS) is a rare, microdeletion syndrome characterized by facial dysmorphisms, intellectual disability, a friendly personality, cardiovascular and other abnormalities. Cardiovascular defects (CVD) are among the most prevalent characteristics in WBS, being supravalvular aortic stenosis (SVAS) the most frequent, followed by peripheral pulmonary stenosis (PPS). A comprehensive retrospective review of medical records of 127 patients with molecular diagnosis of WBS, in a period of 20 years, was done to evaluate the incidence, the natural history of cardiovascular disease, and the need for surgical intervention, including heart transplantation (HT). A total of 94/127 patients presented with CVD. Of these 94 patients, 50% presented with SVAS and 22.3% needed heart surgery and/or cardiac catheterization including one that required HT due to severe SVAS-related heart failure at 19 years of age. The patient died in the postoperative period due to infectious complications. Cardiovascular problems are the major cause of sudden death in patients with WBS, who have a significantly higher mortality risk associated with surgical interventions. There is a higher risk for anesthesia-related adverse events and for major adverse cardiac events following surgery. End-stage heart failure due to myocardial ischemia has been described in WBS patients and it is important to consider that HT can become their only viable option. To our knowledge, the case mentioned here is the first HT reported in an adolescent with WBS. HT can be a viable therapeutic option in WBS patients with adequate evaluation, planning, and a multidisciplinary team to provide the required perioperative care and follow-up.

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.

Whole-Genome Cardiac DNA Methylation Fingerprint and Gene Expression Analysis Provide New Insights in the Pathogenesis of Chronic Chagas Disease Cardiomyopathy.

Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and affects 10 million people worldwide. Approximately 12000 deaths attributable to Chagas disease occur annually due to chronic Chagas disease cardiomyopathy (CCC), an inflammatory cardiomyopathy presenting with heart failure and arrythmia; 30% of infected subjects develop CCC years after infection. Genetic mechanisms play a role in differential progression to CCC, but little is known about the role of epigenetic modifications in pathological gene expression patterns in CCC patients' myocardium. DNA methylation is the most common modification in the mammalian genome. Methods: We investigated the impact of genome-wide cardiac DNA methylation on global gene expression in myocardial samples from end-stage CCC patients, compared to control samples from organ donors. Results: In total, 4720 genes were differentially methylated between CCC patients and controls, of which 399 were also differentially expressed. Several of them were related to heart function or to the immune response and had methylation sites in their promoter region. Reporter gene and in silico transcription factor binding analyses indicated promoter methylation modified expression of key genes. Among those, we found potassium channel genes KCNA4 and KCNIP4, involved in electrical conduction and arrythmia, SMOC2, involved in matrix remodeling, as well as enkephalin and RUNX3, potentially involved in the increased T-helper 1 cytokine-mediated inflammatory damage in heart. Conclusions: Results support that DNA methylation plays a role in the regulation of expression of pathogenically relevant genes in CCC myocardium, and identify novel potential disease pathways and therapeutic targets in CCC.

Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock after Cardiac Surgery: The VANCS Randomized Controlled Trial.

BACKGROUND: Vasoplegic syndrome is a common complication after cardiac surgery and impacts negatively on patient outcomes. The objective of this study was to evaluate whether vasopressin is superior to norepinephrine in reducing postoperative complications in patients with vasoplegic syndrome. METHODS: This prospective, randomized, double-blind trial was conducted at the Heart Institute, University of Sao Paulo, Sao Paulo, Brazil, between January 2012 and March 2014. Patients with vasoplegic shock (defined as mean arterial pressure less than 65 mmHg resistant to fluid challenge and cardiac index greater than 2.2 l · min · m) after cardiac surgery were randomized to receive vasopressin (0.01 to 0.06 U/min) or norepinephrine (10 to 60 µg/min) to maintain arterial pressure. The primary endpoint was a composite of mortality or severe complications (stroke, requirement for mechanical ventilation for longer than 48 h, deep sternal wound infection, reoperation, or acute renal failure) within 30 days. RESULTS: A total of 330 patients were randomized, and 300 were infused with one of the study drugs (vasopressin, 149; norepinephrine, 151). The primary outcome occurred in 32% of the vasopressin patients and in 49% of the norepinephrine patients (unadjusted hazard ratio, 0.55; 95% CI, 0.38 to 0.80; P = 0.0014). Regarding adverse events, the authors found a lower occurrence of atrial fibrillation in the vasopressin group (63.8% vs. 82.1%; P = 0.0004) and no difference between groups in the rates of digital ischemia, mesenteric ischemia, hyponatremia, and myocardial infarction. CONCLUSIONS: The authors' results suggest that vasopressin can be used as a first-line vasopressor agent in postcardiac surgery vasoplegic shock and improves clinical outcomes.

Infectious agents is a risk factor for myxomatous mitral valve degeneration: A case control study.

BACKGROUND: The etiology of myxomatous mitral valve degeneration (MVD) is not fully understood and may depend on time or environmental factors for which the interaction of infectious agents has not been documented. The purpose of the study is to analyze the effect of Mycoplasma pneumoniae (Mp), Chlamydophila pneumoniae (Cp) and Borrelia burgdorferi (Bb) on myxomatous mitral valve degeneration pathogenesis and establish whether increased in inflammation and collagen degradation in myxomatous mitral valve degeneration etiopathogenesis. METHODS: An immunohistochemical test was performed to detect the inflammatory cells (CD20, CD45, CD68) and Mp, Bb and MMP9 antigens in two groups. The in situ hybridization was performed to detect Chlamydophila pneumoniae and the bacteria study was performed using transmission electron microscopy. Group 1 (n = 20), surgical specimen composed by myxomatous mitral valve degeneration, and group 2 (n = 20), autopsy specimen composed by normal mitral valve. The data were analyzed using SigmaStat version 20 (SPSS Inc., Chicago, IL, USA). The groups were compared using Student's t test, Mann-Whitney test. A correlation analysis was performed using Spearman's correlation test. P values lower than 0.05 were considered statistically significant. RESULTS: By immunohistochemistry, there was a higher inflammatory cells/mm2 for CD20 and CD45 in group 1, and CD68 in group 2. Higher number of Mp and Cp antigens was observed in group 1 and more Bb antigens was detected in group 2. The group 1 exhibited a positive correlation between the Bb and MVD percentage, between CD45 and Mp, and between MMP9 with Mp. These correlations were not observed in the group 2. Electron microscopy revealed the presence of structures compatible with microorganisms that feature Borrelia and Mycoplasma characteristics. CONCLUSIONS: The presence of infectious agents, inflammatory cells and collagenases in mitral valves appear to contribute to the pathogenesis of MVD. Mycoplasma pneumoniae was strongly related with myxomatous mitral valve degeneration. Despite of low percentage of Borrelia burgdorferi in MD group, this agent was correlated with myxomatous degeneration and this may occour due synergistic actions between these infectious agents likely contribute to collagen degradation.

Myocardial Infarction-Associated Transcript, a Long Noncoding RNA, Is Overexpressed During Dilated Cardiomyopathy Due to Chronic Chagas Disease.

Long noncoding RNAs (lncRNAs) modulate gene expression at the epigenetic, transcriptional, and posttranscriptional levels. Dysregulation of the lncRNA known as myocardial infarction-associated transcript (MIAT) has been associated with myocardial infarction. Chagas disease causes a severe inflammatory dilated chronic cardiomyopathy (CCC). We investigated the role of MIAT in CCC. A whole-transcriptome analysis of heart biopsy specimens and formalin-fixed, paraffin-embedded samples revealed that MIAT was overexpressed in patients with CCC, compared with subjects with noninflammatory dilated cardiomyopathy and controls. These results were confirmed in a mouse model. Results suggest that MIAT is a specific biomarker of CCC.

Effect of Perioperative Goal-Directed Hemodynamic Resuscitation Therapy on Outcomes Following Cardiac Surgery: A Randomized Clinical Trial and Systematic Review.

OBJECTIVES: To evaluate the effects of goal-directed therapy on outcomes in high-risk patients undergoing cardiac surgery. DESIGN: A prospective randomized controlled trial and an updated metaanalysis of randomized trials published from inception up to May 1, 2015. SETTING: Surgical ICU within a tertiary referral university-affiliated teaching hospital. PATIENTS: One hundred twenty-six high-risk patients undergoing coronary artery bypass surgery or valve repair. INTERVENTIONS: Patients were randomized to a cardiac output-guided hemodynamic therapy algorithm (goal-directed therapy group, n = 62) or to usual care (n = 64). In the goal-directed therapy arm, a cardiac index of greater than 3 L/min/m was targeted with IV fluids, inotropes, and RBC transfusion starting from cardiopulmonary bypass and ending 8 hours after arrival to the ICU. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite endpoint of 30-day mortality and major postoperative complications. Patients from the goal-directed therapy group received a greater median (interquartile range) volume of IV fluids than the usual care group (1,000 [625-1,500] vs 500 [500-1,000] mL; p < 0.001], with no differences in the administration of either inotropes or RBC transfusions. The primary outcome was reduced in the goal-directed therapy group (27.4% vs 45.3%; p = 0.037). The goal-directed therapy group had a lower occurrence rate of infection (12.9% vs 29.7%; p = 0.002) and low cardiac output syndrome (6.5% vs 26.6%; p = 0.002). We also observed lower ICU cumulative dosage of dobutamine (12 vs 19 mg/kg; p = 0.003) and a shorter ICU (3 [3-4] vs 5 [4-7] d; p < 0.001) and hospital length of stay (9 [8-16] vs 12 [9-22] d; p = 0.049) in the goal-directed therapy compared with the usual care group. There were no differences in 30-day mortality rates (4.8% vs 9.4%, respectively; p = 0.492). The metaanalysis identified six trials and showed that, when compared with standard treatment, goal-directed therapy reduced the overall rate of complications (goal-directed therapy, 47/410 [11%] vs usual care, 92/415 [22%]; odds ratio, 0.40 [95% CI, 0.26-0.63]; p < 0.0001) and decreased the hospital length of stay (mean difference, -5.44 d; 95% CI, -9.28 to -1.60; p = 0.006) with no difference in postoperative mortality: 9 of 410 (2.2%) versus 15 of 415 (3.6%), odds ratio, 0.61 (95% CI, 0.26-1.47), and p = 0.27. CONCLUSIONS: Goal-directed therapy using fluids, inotropes, and blood transfusion reduced 30-day major complications in high-risk patients undergoing cardiac surgery.

The use of a high-power laser on swine mitral valve chordae tendineae.

Worldwide, rheumatic fever remains a significant cause of mitral valve insufficiency. It is responsible for approximately 90 % of early childhood valvular surgeries in Brazil. Elongated or flail chordae are frequently responsible and require surgical correction. The purpose of this study was to analyze and compare the histological tissues of the mitral valve chordae and the mechanical resistance generated by the chordae, both with and without the application of a high-power laser. Twenty normal porcine mitral valve chordae were measured and divided randomly into the following two groups: control group (not subjected to a high-power laser) and laser group (subjected to photonic irradiation). Laser surgery was performed under controlled conditions, using following parameters: λ = 980-nm wavelength, power = 3 W, and energy = 60 J. A mechanical test machine was used in combination with a subsequent histological study to measure chordae tensile properties. A histological analysis demonstrated a typical collagen bundle arrangement in the control group; however, under a particular reached temperature range (48), the collagen bundles assumed different arrangements in the laser group. Significant reductions in the chordae tendineae lengths and changes in their resistance in the laser group were observed, as these chordae exhibited less rigid fibers. The chordae tendineae of normal porcine valves subjected to a high-power laser exhibited its length reduction and less stiffness compared to the control group. A histological analysis of the laser treatment specimens demonstrated differences in collagen bundle spatial organization, following slight changes into tissue temperature.

Surgical Thrombectomy of Mechanical Valve Thrombosis.

BACKGROUND: The study aim was to review the authors' experience with the surgical thrombectomy of mechanical valve thrombosis at the Heart Institute of the Medical School of São Paulo University, Brazil. METHODS: Between January 1993 and March 2014, a total of 21 patients (16 females, five males; mean age 48.2 years) with mechanical valve thrombosis was treated surgically. Of these patients, 70% were in NYHA class IV, including two in cardiogenic shock; 71% of the patients had inadequate anticoagulation levels. The median period between the initial valve replacement and valve thrombosis was 105 months. Thrombosis occurred in the mitral position in 12 patients (57%) and in the aortic position in nine (43%). Clinical and surgical data were collected from hospital records. RESULTS: The major surgical finding was thrombus (57.1%), and pannus formation was found in 42.9% of patients. The mean cardiopulmonary bypass time was 90 min, and aortic cross-clamp time 63 min. Operative complications occurred in three patients (14%): two patients required revisions for bleeding and one patient needed ventricular assistance and hemodialysis. The operative mortality rate was 19% (n = 4). Two of these deaths occurred in patients who had been transferred to the operating room with cardiopulmonary resuscitation, one death was due to prolonged mechanical ventilator support and sepsis, and one was due to cardiac tamponade. The 11-year actuarial survival rate was 69.3 ± 12.9%, and the actuarial rate freedom from reintervention was 85.7 ± 13.2% during an 11-year follow up period. CONCLUSIONS: Early surgical intervention is a safe and effective treatment in patients with mechanical valve thrombosis.

Changing trends in clinical characteristics and in-hospital mortality of patients with infective endocarditis over four decades.

BACKGROUND: Infective endocarditis continues to be a significant concern and may be undergoing an epidemiological transition. METHODS: Were studied 1804 consecutive episodes of infective endocarditis between 1978 and 2022. The mean age was 48 ( ± 19), and 1162 (64%) patients were male. Temporal trends in demographic data, comorbidities, predisposing conditions, microorganisms, complications and in-hospital death have been studied over the decades (1978-1988, 1989-1999, 2000-2010 and 2011-2022). The outcomes and clinical characteristics were modeled using nonlinear cubic spline functions. FINDINGS: Valve surgery was performed in 50% of the patients and overall in-hospital mortality was 30%. From the first to the fourth decade studied, the average age of patients increased from 29 to 57 years (p < 0.001), with significant declines in the occurrence of rheumatic valvular heart disease (15% to 6%; p < 0.001) and streptococcal infections (46% to 33%; p < 0.001). Healthcare-associated infections have increased (9% to 21%; p < 0.001), as have prosthetic valve endocarditis (26% to 53%; p < 0.001), coagulase-negative staphylococcal infections (4% to 11%; p < 0.001), and related-complications (heart failure, embolic events, and perivalvular abscess; p < 0.001). These changes were associated with a decline in adjusted in-hospital mortality from 34% to 25% (p = 0.019). INTERPRETATION: In the 44 years studied, there was an increase in the mean age of patients, healthcare-related, prosthetic valve, coagulase-negative staphylococci/MRSA infections, and related complications. Notably, these epidemiological changes were associated with a decline in the adjusted in-hospital mortality.

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.

Safety, Effectiveness, and Hemodynamic Performance of the Bovine Pericardium Organic Valvular Bioprosthesis.

OBJECTIVE: To assess actual data on the safety, effectiveness, and hemodynamic performance of Bovine Pericardium Organic Valvular Bioprosthesis (BVP). METHODS: The BIOPRO Trial is an observational, retrospective, non-comparative, non-randomized, and multicenter study. We collected data from 903 patients with symptomatic, moderate, or severe valve disease who underwent BVP implants in the timeframe from 2013 to 2020 at three Brazilian institutions. Death, valve-related adverse events (AEs), functional recovery, and hemodynamic performance were evaluated at the hospital, at discharge, and six months and one year later. Primary analysis compared late (> 30 days after implant) linearized rates of valve-related AEs, such as thromboembolism, valve thrombosis, major hemorrhage, major paravalvular leak, and endocarditis, following objective performance criteria (OPC). Analysis was performed to include at least 400 valve-years for each valve position (aortic and mitral) for complete comparisons to OPC. Kaplan-Meier survival and major adverse cardiovascular and cerebrovascular event analyses were also performed. RESULTS: This retrospective study analyzed follow-up data collected from 903 patients (834.2 late patient-years) who have undergone surgery for 455 isolated aortic valve replacement (50.4%), 382 isolated mitral valve replacement (42.3%), and 66 combined valve replacement or other intervention (7.3%). The linearized rates of valve-related AEs were < 2 × OPC. One-year survival rates were 95.1% and 92.7% for aortic and mitral valve replacement, respectively. This study demonstrated an improvement in the New York Heart Association classification from baseline and hemodynamic performance within an expected range. CONCLUSION: According to this analysis, BVP meets world standards for safety and clinical efficacy.

Non-contrast transcatheter aortic valve implantation for patients with aortic stenosis and chronic kidney disease: a pilot study.

Background: Acute kidney injury (AKI) is frequently observed after transcatheter aortic valve implantation (TAVI). Of note, it is associated with a threefold increase in all-cause and cardiac death. We propose a new non-contrast strategy for evaluating and performing the TAVI procedure that can be especially valuable for patients with aortic stenosis (AS) and chronic kidney disease (CKD) to prevent AKI. Methods: Patients with severe symptomatic AS and CKD stage ≥3a were evaluated for TAVI using four non-contrast imaging modalities for procedural planning: transesophageal echocardiogram (TEE), cardiac magnetic resonance, multidetector computed tomography (MDCT), and aortoiliac CO2 angiography. Patients underwent transfemoral (TF) TAVI using the self-expandable Evolut R/Pro, and the procedures were guided by fluoroscopy and TEE. Contrast MDCT and contrast injection at certain checkpoints during the procedure were used in a blinded fashion to guarantee patient safety. Results: A total of 25 patients underwent TF-TAVI with the zero-contrast technique. The mean age was 79.9 ± 6.1 years, 72% in NYHA class III/IV, with a mean STS-PROM of 3.0% ± 1.5%, and creatinine clearance of 49 ± 7 ml/min. The self-expandable Evolut R and Pro were implanted in 80% and 20% of patients, respectively. In 36% of the cases, the transcatheter heart valve (THV) chosen was one size larger than the one by contrast MDCT, but none of these cases presented adverse events. Device success and the combined safety endpoint (at 30 days) both achieved 92%. Pacemaker implantation was needed in 17%. Conclusion: This pilot study demonstrated that the zero-contrast technique for procedural planning and THV implantation was feasible and safe and might become the preferable strategy for a significant population of CKD patients undergoing TAVR. Future studies with a larger number of patients are still needed to confirm such interesting findings.

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.

Redo aortic valve surgery in a case of dextrocardia with situs inversus totalis.

INTRODUCTION: Dextrocardia is a rare congenital cardiac anomaly where the base-apex axis of the heart is directed to the right side. It may be associated with situs solitus, situs inversus, or situs ambiguous. Such cases are technically challenging when heart surgery is needed. PRESENTATION OF CASE: We presented a case of a patient with dextrocardia and situs inversus totalis, who had severe aortic bioprosthetic valve degeneration needing a redo aortic valve replacement. Our operative strategy was to change the position of the main surgeon to the left side of the patient to perform most surgical steps. DISCUSSION: A meticulous pre-operative surgical plan involving the whole team was very important for a smooth intra-operative course and a favourable outcome. Regarding the position of the main surgeon standing on the left side of the patient, we believed this surgical team arrangement added much to the technical ease for the procedure, since the anatomy was opposite to what our minds are used to. Also, computed tomography scan played a crucial role for a proper preoperative anatomical evaluation and surgical planning. CONCLUSION: Our approach with the surgeon on the left side provided excellent exposure for redo aortic valve replacement in dextrocardia with situs inversus totalis. This surgical management played an important role for the good result in this technically challenging scenario.

Matrix Metalloproteinase 2 and 9 Enzymatic Activities are Selectively Increased in the Myocardium of Chronic Chagas Disease Cardiomyopathy Patients: Role of TIMPs.

Chronic Chagas disease (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis compared to other cardiomyopathies. We show the expression and activity of Matrix Metalloproteinases (MMP) and of their inhibitors TIMP (tissue inhibitor of metalloproteinases) in myocardial samples of end stage CCC, idiopathic dilated cardiomyopathy (DCM) patients, and from organ donors. Our results showed significantly increased mRNA expression of several MMPs, several TIMPs and EMMPRIN in CCC and DCM samples. MMP-2 and TIMP-2 protein levels were significantly elevated in both sample groups, while MMP-9 protein level was exclusively increased in CCC. MMPs 2 and 9 activities were also exclusively increased in CCC. Results suggest that the balance between proteins that inhibit the MMP-2 and 9 is shifted toward their activation. Inflammation-induced increases in MMP-2 and 9 activity and expression associated with imbalanced TIMP regulation could be related to a more extensive heart remodeling and poorer prognosis in CCC patients.

Quality improvement program in Latin America decreases mortality after cardiac surgery: a before-after intervention study.

BACKGROUND: The current challenge of cardiac surgery (CS) is to improve outcomes in adverse scenarios. The aim of this study was to assess the impact of a quality improvement program (QIP) on hospital mortality in the largest CS center in Latin America. METHODS: Patients were divided into two groups: before (Jan 2013-Dec 2015, n = 3534) and after establishment of the QIP (Jan 2017-Dec 2019, n = 3544). The QIP consisted of the implementation of 10 central initiatives during 2016. The procedures evaluated were isolated coronary artery bypass grafting surgery (CABG), mitral valve surgery, aortic valve surgery, combined mitral and aortic valve surgery, and CABG associated with heart valve surgery. Propensity Score Matching (PSM) was used to adjust for inequality in patients' preoperative characteristics before and after the implementation of QIP. A multivariate logistic regression model was built to predict hospital mortality and validated using discrimination and calibration metrics. RESULTS: The PMS paired two groups using 5 variables, obtaining 858 patients operated before (non-QIP) and 858 patients operated after the implementation of the QIP. When comparing the QIP versus Non-QIP group, there was a shorter length of stay in all phases of hospitalization. In addition, the patients evolved with less anemia (P = 0.001), use of intra-aortic balloon pump (P = 0.003), atrial fibrillation (P = 0.001), acute kidney injury (P < 0.001), cardiogenic shock (P = 0.011), sepsis (P = 0.046), and hospital mortality (P = 0.001). In the multiple model, among the predictors of hospital mortality, the lack of QIP increased the chances of mortality by 2.09 times. CONCLUSION: The implementation of a first CS QIP in Latin America was associated with a reduction in length of hospital stay, complications and mortality after the cardiac surgeries analyzed.

Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS's DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease.