Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

First Experience of Sutureless Redo on Mitral Valve Using Valve-in-Valve Technique: Two-Stage Implantation on a Large Animal.

Sutureless implantation of the mitral valve bioprosthesis using the valve-in-valve method was performed on a large animal (sheep). According to the results of a two-stage implantation (primary implantation of a xenopericardial 26-mm framed bioprosthesis and reimplantation of the developed 23-mm bioprosthesis), minor changes in quantitative indicators were revealed: an increase in the transprosthetic gradient by 1.3 mm Hg and a decrease in the area of the mitral orifice by 21.6%. Considerable reduction in the intervention time by 18 min was achieved (by 40% in comparison with the primary prosthesis). The absence of adverse events in the animal and complications in the post-operative period, as well as physiological hemodynamic indicators indicate the safety of the developed medical device.

Rheumatic Mitral Stenosis: Long-Term Follow-Up of Adult Patients with Nonsevere Initial Disease.

INTRODUCTION: There is no consensus regarding the natural history of rheumatic mitral stenosis (MS) among adults presenting with nonsevere disease. This study aims to describe the progression of stenosis among adult rheumatic MS patients, to identify predictive factors for progression, and to assess the incidence of complications. METHODS: A retrospective cohort analysis was performed among patients with rheumatic MS treated at a single center. Eighty-five patients were included with mild to moderate MS, ≥30 years old on initial echocardiography. Demographics, medical history, echocardiographic reports over at least 10 years, and related complications were obtained from a computerized database. RESULTS: Over a period of 13.1 ± 2.38 years, 75 patients (88%) had no significant progression in stenosis severity. The final echocardiographic assessment demonstrated 2 groups with a significant difference between them regarding the mitral valve area (1.58 ± 0.44 vs. 1.1 ± 0.26 cm2, p = 0.001) and mean valvular pressure gradient (6.27 ± 2.52 vs. 8.5 ± 2.69 mm Hg, p = 0.01). Patients with indolent MS (group A) were compared to patients with progressive disease (group B), and a higher percent of Bedouin patients were found in group B (OR 8.036, p = 0.015). No significant differences were found in other parameters. Complications including atrial fibrillation, cerebral ischemic events, and impaired right ventricle function, although frequent, were not statistically different between the groups. CONCLUSIONS: An indolent natural progression of rheumatic MS was observed in our study. Despite this finding, it still has potentially deleterious effects. Bedouin patients have a higher risk for progressive disease.

CD4+ T cells and TGFß1/MAPK signal pathway involved in the valvular hyperblastosis and fibrosis in patients with rheumatic heart disease.

The aim of this study was to investigate the roles of CD4+ T cells and transforming growth factor beta (TGFß1) in the pathological process of valvular hyperblastosis and fibrosis of patients with rheumatic heart disease (RHD). A total of 151 patients were enrolled, among whom, 78 patients were with RHD, and 73 were age and gender matched RHD negative patients. Blood samples and valve specimens were collected for analysis. Pathological changes and collagen fibers contents of valves were analyzed using HE and Masson staining. Percentage of peripheral blood CD4+ T cells was tested through flow cytometry. TGFß1 level in serum were identified by ELISA. CD4+ T cells infiltration and expression of TGFß1, p-p38, p-JNK, p-ERK in valves were detected by immunohistochemistry. The mRNA and protein levels of p38, JNK, ERK, TGFß1, I-collagen and α-SMA were detected by qRT-PCR and western blotting, respectively. The heart valve tissues of RHD patients showed higher degrees of fibrosis, calcification and lymphocytes infiltration, which were mainly CD4+ T cells. In addition, compared with control group, RHD patients had more total CD4+ T cells in peripheral blood and valve tissues. Expression of TGFß1, phosphorylation of JNK and p38, and synthesis of I-collagen in valve tissues of RHD patients were also significantly increased. Furthermore, we found a strong positive correlation between TGFß1 expression and phosphorylation of JNK and p38. CD4+ T cells, and fibrogenic cytokine TGFß1, which activate the intracellular MAPK signaling pathway may participate in the fibrosis of heart valve in RHD patients.

Coronary Arterial Abnormalities in Hypoplastic Left Heart Syndrome: Pathologic Characteristics of Archived Specimens.

Palliation of patients with hypoplastic left heart syndrome remains challenging. Although coronary ischemia can be catastrophic, the prevalence and pathologies of anomalies of the coronary arteries remains unknown. We reviewed 119 specimens with the features of hypoplastic left heart syndrome, focusing our attention on the aortic root and the coronary arteries. We found 36 (30%) specimens with the combination of mitral and aortic atresia, 26 (22%) with mitral and aortic stenosis, and 57 (48%) with mitral stenosis combined with aortic atresia. In 29 specimens (24%), the coronary arteries were not located in the center of any sinuses, while in 24 specimens (21%) at least 1 coronary artery was located very proximal to a raphe or commissure, with potential for obstruction. The specimens with combined stenosis were more likely to have eccentric positions of the coronary arteries (11 specimens, 42%), compared to the 3 specimens with combined atresia (9%, P = 0.009). The specimens with combined stenosis were also more likely to have positioning at risk for obstruction (9 specimens, 35%), compared to those with combined atresia (3 specimens, 9%, P = 0.05). Coronary arterial fistulous communications were found in 11 specimens (9%), significantly more frequently in specimens with mitral stenosis and aortic atresia (9 specimens, 16%, P = 0.041). The origins of the coronary arteries in patients with hypoplastic left heart syndrome place them at potential risk for ischemia, with fistulous communications being a particular risk in those with mitral stenosis combined with aortic atresia.

Morphological and functional characteristics of mitral annular calcification and their relationship to stroke.

BACKGROUND: Mitral annular calcification (MAC) is associated with risk of stroke. This study aimed to define the morphological and functional characteristics of MAC that are related to stroke. METHODS: A total of 460 subjects with MAC from transthoracic echocardiography in a single center from 2012 to 2016 was retrospectively reviewed. Subjects were classified into two groups according to history of stroke [Group 1 (n = 366): without stroke; Group 2 (n = 94): with stroke]. Morphological and functional features of MAC on echocardiogram were scored from 0 to 3 according to MAC mobility, presence of echodense mass with central echolucencies in the periannular region suggesting caseous necrosis, and functional stenosis. RESULTS: Significantly more patients in group 2 were men and had history of diabetes mellitus, dyslipidemia, atrial fibrillation, or infective endocarditis. Although MAC thickness and extent did not differ between the two groups, group 2 showed a considerably higher MAC score than group 1 (0.50 ± 0.77 vs. 0.23 ±0.52 p<0.001) as a result of the higher prevalence of each component in group 2 [mobility (22 vs. 11%, p = 0.003), echodense mass with central areas of echolucencies suggesting caseous necrosis (23 vs. 7%, p<0.001), and functional mitral stenosis (12 vs. 7%, p = 0.042)]. On logistic regression analysis, MAC score was independently associated with stroke and showed significant incremental value to demographic factors and comorbidities in association with stroke in a consecutive manner. CONCLUSIONS: In conclusion, morphological and functional characteristics of MAC had incremental value in association with stroke over traditional risk factors. MAC score consisting of MAC mobility, typical echodense mass with central echolucencies suggesting caseous necrosis, and functional mitral stenosis was independently associated with stroke. MAC with high-risk features may act as a source of stroke or more potent composite surrogate markers for stroke-related risk factors.

[Transcatheter aortic valve implantation and conduction disturbances]. / Implantation percutanée de valve aortique et troubles conductifs.

Transcatheter aortic valve implantation (TAVI) is currently becoming the treatment of choice for patients with calcific aortic stenosis. Despite several technical improvements, the incidence of conduction disturbances has not diminished and remains TAVI's major complication. These disturbances include the occurrence of left bundle branch block and/or high-grade atrioventricular block often requiring pacemaker implantation. The proximity of the aortic valve to the conduction system (conduction pathways) accounts for the occurrence of these complications. Several factors have been identified as carrying a high risk of conduction disturbances like the presence of pre-existing right bundle branch block, the type of valve implanted, the volume of aortic and mitral calcifications, the size of the annulus and the depth of valve implantation. Left bundle branch block is the most frequent post TAVI conduction disturbance. Whereas the therapeutic strategy for persistent complete atrioventricular block is simple, it becomes complex in the presence of fluctuating changes in PR interval and left bundle branch block duration. The QRS width threshold value (150-160 ms) indicative of the need for pacemaker implantation is still being debated. Although there are currently no recommendations regarding the management of these conduction disturbances, the extension of TAVI indications to patient at low surgical risk calls for a standardization of our practice. However, a decision algorithm was recently proposed by a group of experts composed of interventional cardiologists, electrophysiologists and cardiac surgeons. There are still uncertainties about the appropriate timing of pacemaker implantation and the management of new onset left bundle branch block.

Minimally Invasive Thoracoscopic Mitral Valve Replacement in Rheumatic Disease With Continuous Suture Technique.

Minimally invasive mitral valve surgery has become routine in many institutions. Disadvantages of this approach include prolonged aortic cross-clamp and cardiopulmonary bypass times. Mitral valve replacement with a continuous suture technique may reduce operative times. We present a case of a 51-year-old man suffering from severe rheumatic mitral disease to highlight our continuous suture technique for minimally invasive mitral valve replacement. We also report preliminary results from our series of 15 patients suffering various rheumatic mitral pathology treated with this technique.

Unrecognized Cardiac Amyloidosis at the Time of Mitral Valve Surgery: Incidence and Outcomes.

OBJECTIVE: It is increasingly recognized that cardiac amyloidosis can occur in patients with severe aortic stenosis undergoing both surgical and transcatheter valve replacements. We aimed to investigate whether unrecognized cardiac amyloidosis may also occur in patients with severe mitral valve disease undergoing surgery. METHODS: The pathology department database at our center was retrospectively analyzed over a 10-year period for cases in which the mitral valve or another type of cardiac tissue removed at the time of mitral surgery demonstrated incidental amyloidosis. Clinical and echocardiographic variables were collected from the electronic medical record and the echocardiographic database. RESULTS: Between 2007 and 2016, a total of 7,733 mitral valve surgical specimens were received. Of these, there were 15 cases in which the mitral valve, or another type of cardiac tissue removed at surgery, demonstrated incidentally detected amyloidosis. The most frequent comorbidities were hypertension (87%) and atrial fibrillation (80%); 13 patients (87%) underwent bioprosthetic mitral valve replacement, and 2 patients (13%) underwent mitral valve repair. Sites of amyloid deposition were the mitral valve (80%), left atrial appendage (33%), and subaortic tissue (7%); 14 patients (93%) had wild-type transthyretin amyloid. The mean duration of follow-up was 1,023 days (range: 29-2,811 days). There were no surgical complications in the follow-up period. CONCLUSIONS: Over a 10-year period, incidentally detected cardiac amyloidosis occurred in 0.2% of the mitral valve surgical cases. The outcomes for these patients undergoing mitral valve surgery were excellent, with no complications or deaths attributable to surgery at a mean follow-up of 1,023 days.

The association between severe mitral stenosis and the size of the aortic root and the ascending thoracic aorta.

OBJECTIVE: The aim of this study was to examine the role of isolated rheumatic mitral stenosis (MS) in remodeling of the aorta at various locations. METHODS: In this prospective study, patients who were to undergo transesophageal echocardiography for various indications were screened. The study participants were classified into 2 groups according to the presence of MS with a valve area ≤1.5 cm2. Factors associated with the index dimensions of the aorta at the levels of the annulus, root, sinotubular junction (STJ), and the proximal ascending portion (5 cm from the annulus) were evaluated. Multivariate linear models were constructed including factors that affect the size of the aorta at any of the aforementioned levels. Pearson's correlation coefficient was used to investigate the association between mitral valve area, mitral valve gradient, and dimensions of the aorta. RESULTS: A total of 179 men and 354 women were enrolled. Eighty-four patients had MS (15.8%). The patients with MS were younger and less likely to have hypertension. In univariate analysis, patients with MS had a smaller annulus and STJ (p=0.003 and p=0.043, respectively). Multivariate analysis indicated that MS was correlated with a smaller indexed size of the aortic annulus, yielding a regression coefficient value of 0.541 (p=0.005). CONCLUSION: The presence of significant stenosis at the level of the mitral valve is associated with a smaller diameter in the aortic annulus. It is yet to be clarified whether this phenomenon occurs due to chronic, long-standing, low stroke volume or involvement of the aortic annulus in the fibrotic process of mitral disease.

Modeling mitral valve stenosis: A parametric study on the stenosis severity level.

New computational techniques providing more accurate representation of human heart pathologies could help uncovering relevant physical phenomena and improve the outcome of medical therapies. In this framework, the present work describes an efficient computational model for the evaluation of the ventricular flow alteration in presence of mitral valve stenosis. The model is based on the direct numerical simulation of the Navier-Stokes equations two-way coupled with a structural solver for the left ventricle and mitral valve dynamics. The presence of mitral valve stenosis is mimicked by a single-parameter constraint acting on the kinematics of the mitral leaflets. Four different degrees of mitral valve stenosis are considered focusing on the hemodynamic alterations occurring in pathologic conditions. The mitral jet, generated during diastole, is seen to shrink and strengthen when the stenosis gets more severe. As a consequence, the kinetic energy of the flow, the tissues shear stresses, the transvalvular pressure drop and mitral regurgitation increase. It results that, as the stenosis severity level increases, the geometric and effective orifice areas decrease up to 50% with respect the normal case due to the reduced leaflets mobility and stronger blood acceleration during the diastolic phase. The modified intraventricular hemodynamics is also related to a stronger pressure gradient that, for severe stenosis, can be more than ten times larger than the healthy valve case. These computational results are fully consistent with the available clinical literature and open the way to the virtual assessment of surgical procedures and to the evaluation of prosthetic devices.

Surgical Myectomy: Subaortic, Midventricular, and Apical.

Surgical septal myectomy is the preferred method of septal reduction for most patients with obstructive hypertrophic cardiomyopathy whose symptoms do not respond to medical management. Transaortic extended septal myectomy has low operative mortality and provides durable relief of symptoms. Surgical treatment is possible for patients with less common phenotypes, such as complex long-segment septal hypertrophy, midventricular obstruction, or apical hypertrophic cardiomyopathy. For these anatomic subtypes, transapical myectomy can be used alone or combined with transaortic myectomy. This article describes both of these surgical techniques and discusses preoperative considerations and postoperative management for patients with hypertrophic cardiomyopathy.

Involvement of Apelin/APJ Axis in Thrombogenesis in Valve Heart Disease Patients with Atrial Fibrillation.

The mechanism underlying thrombosis in atrial fibrillation (AF) is not yet clearly understood. The apelin/APJ axis parallel and counter-regulate with the angiotensin system. The present study hypothesizes that apelin/APJ axis exert its anti-thrombus effect in normal left atrial tissue and is disrupted by up-regulated renin-angiotensin-aldosterone system (RAAS) signaling during AF. The specimens of left atrial appendages collected from patients with rheumatic mitral stenosis who underwent valve replacement were divided into 3 groups: sinus rhythm, AF+/thrombus-, and AF+/thrombus+. The amounts of angiotensin II receptor subtype 1 (AT1), apelin/APJ and its downstream plasminogen activator inhibitor-1 (PAI-1) were detected by western blot. The expression of apelin/APJ was significantly decreased in the AF+/thrombus+ group compared with the sinus rhythm and AF+/thrombus- groups. Meanwhile the expressions of AT1 and PAI-1 were highest in the AF+/thrombus+ group compared to the other two groups. Taken together, the present study reveals apelin/APJ axis might be correlated with thrombosis in patients with AF mediated by PAI-1.

Association between late gadolinium enhancement and global longitudinal strain in patients with rheumatic mitral stenosis.

The correlation between the extent of myocardial fibrosis and subclinical left ventricle (LV) systolic dysfunction in rheumatic mitral stenosis (MS) has not been widely studied. We sought to evaluate the correlation between the extent of LV myocardial fibrosis quantified by late gadolinium enhancement (LGE) using cardiac magnetic resonance (CMR) and global longitudinal strain (GLS) by speckle tracking echocardiography (STE) in patients with rheumatic MS. We prospectively evaluated 36 consecutive rheumatic MS patients who were planning to undergo mitral valve surgery. Then we evaluate the correlation between the extent of LV myocardial fibrosis quantified by LGE CMR and the systolic LV function by GLS using STE. Thirty-six patients with mean age of 45.7 ± 9.9 years old, showed mean LGE was 4.9 ± 2.7%. The mean LV ejection fraction (EF) measured by CMR was 50 ± 10.8%, and the mean LV GLS was 13.5 ± 3.9%. There was a moderate correlation between GLS and LGE (r - 0.432, p = 0.009). There were no correlations between GLS with mitral valve area (MVA) with r 0.149, p = 0.385, mean mitral valve gradient (MVG) with r -0.078, p = 0.653, and LVEF (r 0.299, p = 0.076). There was a moderate correlation between LGE and GLS in patients with rheumatic MS.

Quantification of rheumatic mitral stenosis severity with three-dimensional vena contracta area.

INTRODUCTION: Rheumatic mitral stenosis (MS) is an important health issue in developing countries. Assessment of the correct mitral valve area (MVA) is essential for the timing of intervention. Most of the parameters for the assessment of rheumatic MS are derived from Two-dimensional (2D) echocardiography. Three-dimensional (3D) echocardiography is commonly used in our daily practice at the present time. The aim of this study was to assess the value of 3D echocardiography mitral valve vena contracta area (VCA) in predicting the severity of Rheumatic MS by comparing 3D planimetry. METHODS: The patients, who had been diagnosed as mild, moderate, and severe rheumatic MS with conventional methods (pressure half time, planimetry) by 2D transesophageal echocardiography (TEE)/ transthoracic echocardiography (TTE), underwent 3D TEE evaluation. Also, the patients who had an atrial fibrillation and more than moderate aortic regurgitation were included in the study. 3D TEE full volume mitral valve VCA was measured in end-diastole during its largest dimensions. 3D TEE full volume and 3D zoom MVA planimetry were measured at the end-diastole during the mitral valve`s largest opening. RESULTS: We studied 40 patients (the mean age: 51.1 ± 11.6 years, 31 females) with rheumatic MS. 3D TEE VCA was found to be highly correlated with the 3D TEE MVA (r = 0.82, P < 0.001). CONCLUSION: Our study findings provide evidence that 3D TEE mitral valve VCA can be additionally used in detecting the severity of rheumatic MS.

[Assessment of Contraindications to Percutaneous Mitral Commissurotomy (PMC) in Abidjan Heart Institute, Côte d'Ivoire]. / Evaluation des contre-indications à la commissurotomie mitrale percutanée (CMP) à l'Institut de cardiologie d'Abidjan en Côte d'Ivoire.

Rheumatic mitral stenosis is still common in sub-Saharan Africa. The aim of this study was to evaluate the clinical and echocardiographic contraindications to the realization of percutaneous mitral commissurotomy (PMC) in Abidjan Heart Institute. We conducted a prospective, transversal and analytical study in the Exploration Unit from March 30, 2017 to March 30, 2018. Mitral stenosis was severe with an average anatomical surface area of 0.87cm2, an average gradient of 13.7 mmHg and an upstream repercussion (dilatation of the left atrium (78 ml/m2); moderate dilatation of the right atrium (22.3 cm2) and average pulmonary arterial hypertension (PAH) of 55 mmHg). The main clinical contraindications were a history of rest dyspnoea at 66.7%, permanent atrial fibrillation at 53.3 % and clinical manifestations of severe PAH in 40 %. Unfavourable anatomy (95.7 %) evaluated by scores of Wilkins, Cormier and especially Echoscore revisited; bicommissural fusion (95.7 %) and severe aortic valvulopathy (31.1%) were the main barriers in transthoracic echocardiography. In multivariate analysis after linear regression, valvular anatomy, as assessed by the various scores, was significantly related to low socioeconomic status (p=0.018), level of education (p=0.04), severity of mitral stenosis evaluated by the mean gradient (p=0.033) and the impact on the left atrium (p=0.015). Mitral stenosis presents several clinical and echocardiographic contraindications. Adverse anatomy is the main obstacle and is related to low socio-economic status, educational level and severity of stenosis.

La sténose rhumatismale mitrale est courante en Afrique subsaharienne. Le but de cette étude était d'évaluer les contre-indications cliniques et échocardiographiques de la commissurotomie mitrale percutanée (CMP) à l'Institut de cardiologie d'Abidjan. Nous avons mené une étude prospective, transversale et analytique dans l'unité d'exploration du 30 mars 2017 au 30 mars 2018. La sténose mitrale était sévère, avec une surface anatomique moyenne de 0,87 cm2, un gradient moyen de 13,7 mmHg et une répercussion en amont (dilatation) de l'oreillette gauche (78 ml/m2) ; dilatation modérée de l'oreillette droite (22,3 cm2) et hypertension artérielle pulmonaire moyenne (HAP) de 55 mmHg). Les principales contre-indications cliniques étaient des antécédents de dyspnée de repos à 66,7 %, de fibrillation auriculaire permanente à 53,3 % et de manifestations cliniques de HAP sévère à 40 %. L'anatomie défavorable évaluée par les scores de Wilkins, Cormier et surtout l'échoscore revisité ; la fusion bicommissurale (95,7 %) et la valvulopathie aortique sévère (31,1 %) étaient les principaux obstacles à l'échocardiographie transthoracique. Dans l'analyse multivariée après régression linéaire, l'anatomie valvulaire, évaluée par les différents scores, était significativement liée au faible statut socio-économique (p = 0,018), au niveau d'éducation (p = 0,04), à la gravité de la sténose mitrale évaluée par le gradient moyen (p = 0,033) et l'impact sur l'oreillette gauche (p = 0,015). La sténose mitrale présente plusieurs contre-indications cliniques et échocardiographiques. L'anatomie défavorable est le principal obstacle et est liée au faible statut socio-économique, au niveau d'éducation et à la gravité de la sténose.