Progression of Mitral Regurgitation in Rheumatic Valve Disease: Role of Left Atrial Remodeling.

Introduction: Mitral regurgitation (MR) is the most common valve abnormality in rheumatic heart disease (RHD) often associated with stenosis. Although the mechanism by which MR develops in RHD is primary, longstanding volume overload with left atrial (LA) remodeling may trigger the development of secondary MR, which can impact on the overall progression of MR. This study is aimed to assess the incidence and predictors of MR progression in patients with RHD. Methods: Consecutive RHD patients with non-severe MR associated with any degree of mitral stenosis were selected. The primary endpoint was a progression of MR, which was defined as an increase of one grade in MR severity from baseline to the last follow-up echocardiogram. The risk of MR progression was estimated accounting for competing risks. Results: The study included 539 patients, age of 46.2 ± 12 years and 83% were women. At a mean follow-up time of 4.2 years (interquartile range [IQR]: 1.2-6.9 years), 54 patients (10%) displayed MR progression with an overall incidence of 2.4 per 100 patient-years. Predictors of MR progression by the Cox model were age (adjusted hazard ratio [HR] 1.541, 95% CI 1.222-1.944), and LA volume (HR 1.137, 95% CI 1.054-1.226). By considering competing risk analysis, the direction of the association was similar for the rate (Cox model) and incidence (Fine-Gray model) of MR progression. In the model with LA volume, atrial fibrillation (AF) was no longer a predictor of MR progression. In the subgroup of patients in sinus rhythm, 59 had an onset of AF during follow-up, which was associated with progression of MR (HR 2.682; 95% CI 1.133-6.350). Conclusions: In RHD patients with a full spectrum of MR severity, progression of MR occurs over time is predicted by age and LA volume. LA enlargement may play a role in the link between primary MR and secondary MR in patients with RHD.

Proinflammatory Matrix Metalloproteinase-1 Associates With Mitral Valve Leaflet Disruption Following Percutaneous Mitral Valvuloplasty.

Mitral regurgitation (MR) is a major complication of the percutaneous mitral valvuloplasty (PMV). Despite high technical expertise and cumulative experience with the procedure, the incidence rate of severe MR has not decreased. Although some of MR can be anticipated by echocardiographic analysis; leaflet tearing, which leads to the most dreaded type of MR, remains unpredictable. Irregular valvular collagen remodeling is likely to compromise tissue architecture and increase the tearing risk during PMV balloon inflation. In this study, we evaluated histological and molecular characteristics of excised mitral valves from patients with rheumatic mitral stenosis (MS) who underwent emergency surgery after PMV due to severe MR caused by leaflet tear. Those findings were compared with patients who underwent elective mitral valve replacement surgery owing to severe MS, in whom PMV was not indicated. In vitro assay using peripheral blood mononuclear cells was performed to better understand the impact of the cellular and molecular alterations identified in leaflet tear mitral valve specimens. Our analysis showed that focal infiltration of inflammatory cells contributes to accumulation of MMP-1 and IFN-γ in valve leaflets. Moreover, we showed that IFN-γ increase the expression of MMP-1 in CD14+ cells (monocytes) in vitro. Thus, inflammatory cells contribute to unevenly remodel collagen resulting in variable thickening causing abnormalities in leaflet architecture making them more susceptible to laceration.

Mitral Regurgitation After Percutaneous Mitral Valvuloplasty: Insights Into Mechanisms and Impact on Clinical Outcomes.

OBJECTIVES: The aim of this study was to assess the incidence, mechanisms, and outcomes of mitral regurgitation (MR) after percutaneous mitral valvuloplasty (PMV). BACKGROUND: Significant MR continues to be a major complication of PMV, with a wide range in clinical presentation and prognosis. METHODS: Consecutive patients with mitral stenosis undergoing PMV were prospectively enrolled. MR severity was evaluated by using quantitative echocardiographic criteria, and its mechanism was characterized by 3-dimensional transesophageal echocardiography, divided broadly into 4 categories based on the features contributing to the valve damage. B-type natriuretic peptide levels were obtained before and 24 h after the procedure. Endpoints estimated cardiovascular death or mitral valve (MV) replacement due to predominant MR. RESULTS: A total of 344 patients, ages 45.1 ± 12.1 years, of whom 293 (85%) were women, were enrolled. Significant MR after PMV was found in 64 patients (18.6%). The most frequent mechanism of MR was commissural, which occurred in 22 (34.4%) patients, followed by commissural with posterior leaflet in 16 (25.0%), leaflets at central scallop or subvalvular damage in 15 (23.4%), and central MR in 11 (17.2%). During the mean follow-up period of 3 years (range 1 day to 10.6 years), 60 patients reached the endpoint. The event-free survival rates were similar among patients with mild or commissural MR, whereas patients with damaged central leaflet scallop or subvalvular apparatus had the worst outcome, with an event-free survival rate at 1 year of only 7%. Long-term outcome was predicted by net atrioventricular compliance (Cn) at baseline and post-procedural variables, including valve area, mean gradient, and magnitude of decrease in B-type natriuretic peptide levels, adjusted for the mechanism of MR. CONCLUSIONS: Significant MR following PMV is a frequent event, mainly related to commissural splitting, with favorable clinical outcome. Parameters that express the relief of valve obstruction and the mechanism by which MR develops were predictors of long-term outcomes.

The Importance of Conscious Sedation for Life-Saving Valve Procedures in Patients With Rheumatic Heart Disease From Low- to Middle-Income Countries.

BACKGROUND: Severe valve disease, which requires intervention, remains strongly associated with mortality in patients with rheumatic heart disease. Percutaneous mitral commissurotomy (PMC) is the procedure of choice for the treatment of patients with isolated or predominantly rheumatic mitral stenosis. This procedure has been performed under sedation to avoid the potential effects of general anesthesia on intracardiac pressure measurements. However, there are limited data on sedation during PMC, especially using easily available medications in low- and middle-income countries. OBJECTIVES: This study was designed to evaluate the efficacy and hemodynamic effects of conscious sedation during PMC in patients with significant mitral stenosis. METHODS: This study prospectively enrolled 23 patients who underwent PMC with the Inoue balloon technique for hemodynamically significant mitral stenosis. For conscious sedation, midazolam 25 µg/kg and fentanyl 1 µg/kg were administered, and 5 min after the infusion, the level of sedation was evaluated by Ramsay sedation scale. A range of invasive hemodynamic measurements, including cardiac output and pulmonary artery pressures, were recorded before and immediately after sedation. RESULTS: The mean age was 44.9 ± 10.8 years, and 19 patients (83%) were women. After sedation, the majority of patients were in categories 2 and 3 of the Ramsay sedation scale (cooperative, orientated, tranquil, and responding to commands). Oxygen saturation dropped from an average of 98.5% to 96.0% without supplementary oxygen. Left ventricular systolic pressure and central aortic pressures decreased after sedation. However, none of the other parameters changed significantly after sedation, including pulmonary artery pressures, pulmonary vascular resistance, and cardiac index. CONCLUSIONS: This simple model of conscious sedation was able to promote anxiolysis, analgesia, and comfort for the procedure without serious hemodynamic effects, which can be a reasonable choice in developing countries.

The impact of right ventricular stroke work on B-type natriuretic peptide levels in patients with mitral stenosis undergoing percutaneous mitral valvuloplasty.

OBJECTIVES: We aimed to explore the relationship between brain natriuretic peptide (BNP) levels and right ventricular (RV) function in patients with mitral stenosis (MS), and to investigate the hemodynamic parameters that predict reduction of BNP levels after percutaneous mitral valvuloplasty (PMV). BACKGROUND: Few studies have evaluated BNP in the context of MS, specifically the impact of the RV stroke work (RVSW) on serum BNP levels has not been defined. METHODS: Thirty patients with symptomatic rheumatic MS in sinus rhythm who were referred for a PMV were enrolled. Right and left heart pressures were obtained before and after valvuloplasty. RVSW index (RVSWI) was calculated by cardiac catheterization. RESULTS: Basal BNP levels were elevated in MS patients and correlated with several hemodynamic parameters including pulmonary pressure, pulmonary vascular resistance index, cardiac index (CI), and RVSWI. In multivariate analysis, CI and RVSWI were independent predictors of raised basal BNP levels. PMV resulted in a significant decrease in the RVSWI with a concurrent increase in CI (2.4 ± 0.43 to 2.9 ± 0.8 L/min/m(2), P = 0.010). Overall, plasma BNP levels significantly decreased from 124 (63/234) to 73 (48/148) pg/ml postvalvuloplasty. Multivariate analysis revealed that the reduction of left atrial (LA) pressure post-PMV was an independent predictor of change in BNP levels. CONCLUSIONS: Elevated baseline BNP level in MS patients was independently associated with CI and RVSWI. Plasma BNP levels were reduced after successful PMV, which was associated with the reduction of the LA pressure.

Dobutamine-stress echocardiography in asymptomatic patients with aortic regurgitation.

BACKGROUND: Decreased contractile reserve may already be present in asymptomatic patients with aortic regurgitation and normal ejection fraction (EF), thus indicating the need for frequent and accurate assessments of the left ventricular function for the early detection of systolic dysfunction. OBJECTIVE: To analyze if increments in EF with low dose dobutamine could predict surgery and/or death in patients with aortic regurgitation. METHODS: Dobutamine-stress echocardiography was performed in 24 patients with aortic regurgitation in order to analyze whether EF increments at low dobutamine doses could predict the need for surgery and/or death in this group of patients. RESULTS: Mean age was 37.8+/-16.8 years and 16 patients (66%) were male. EF increased from a mean baseline value of 62.3+/-7.9% to 71.5+/-10.5% at a dobutamine dose of 20 microg/kg/min (p<0.001). The patients were followed-up for 36.6+/-20.1 months; two patients died (one of cardiovascular death) and five underwent cardiac surgery. Baseline EF was correlated with surgery and death in the follow-up of patients. CONCLUSION: Baseline EF was correlated with surgery or death in the follow-up of young patients with aortic regurgitation. However, the percentage increase in EF at low dobutamine doses did not allow us to predict events in these patients.

Ecocardiograma sob estresse com dobutamina em pacientes assintomáticos com regurgitação aórtica / Ecocardiografía bajo estrés con dobutamina en pacientes asintomáticos con regurgitación aórtica / Dobutamine-stress echocardiography in asymptomatic patients with aortic regurgitation

FUNDAMENTO: A reserva contrátil diminuída pode já estar presente em pacientes portadores de regurgitação aórtica, assintomáticos com fração de ejeção (FE) normal, indicando a necessidade de avaliações frequentes e acuradas da função ventricular esquerda para detectar disfunção sistólica incipiente. OBJETIVO: Analisar se incrementos na FE em doses baixas de dobutamina podem predizer cirugia e/ou morte em pacientes com regurgitação aórtica. MÉTODOS: Eco de estresse com dobutamina foi realizado em 24 pacientes portadores de regurgitação aórtica para verificar se incrementos da FE em doses baixas de dobutamina seriam capazes de predizer a necessidade de cirurgia e/ou morte nesse grupo de pacientes. RESULTADOS: A idade média foi de 37,8±16,8 anos, e 16 (66 por cento) eram homens. A FE aumentou de um valor basal médio de 62,3±7,9 por cento para 71,5±10,5 por cento, na dose de 20 µg/kg/min de dobutamina (p < 0,001). Os pacientes foram acompanhados por 36,6±20,1 meses: dois pacientes morreram (um de morte cardiovascular) e cinco foram submetidos à cirurgia cardíaca. A FE basal se correlacionou com cirurgia e morte no seguimento de pacientes. CONCLUSÃO: A FE basal se correlacionou com cirurgia ou morte no seguimento de pacientes jovens com regurgitação aórtica. Porém, o incremento percentual na FE com dose baixa de dobutamina não foi capaz de predizer eventos nesses pacientes.

BACKGROUND: Decreased contractile reserve may already be present in asymptomatic patients with aortic regurgitation and normal ejection fraction (EF), thus indicating the need for frequent and accurate assessments of the left ventricular function for the early detection of systolic dysfunction. OBJECTIVE: To analyze if increments in EF with low dose dobutamine could predict surgery and/or death in patients with aortic regurgitation. METHDOS: Dobutamine-stress echocardiography was performed in 24 patients with aortic regurgitation in order to analyze whether EF increments at low dobutamine doses could predict the need for surgery and/or death in this group of patients. RESULTS: Mean age was 37.8±16.8 years and 16 patients (66 percent) were male. EF increased from a mean baseline value of 62.3±7.9 percent to 71.5±10.5 percent at a dobutamine dose of 20 µg/kg/min (p<0.001). The patients were followed-up for 36.6±20.1 months; two patients died (one of cardiovascular death) and five underwent cardiac surgery. Baseline EF was correlated with surgery and death in the follow-up of patients. CONCLUSION: Baseline EF was correlated with surgery or death in the follow-up of young patients with aortic regurgitation. However, the percentage increase in EF at low dobutamine doses did not allow us to predict events in these patients.

FUNDAMENTO: La reserva contráctil disminuida puede ya estar presente en pacientes portadores de regurgitación aórtica, asintomáticos con fracción de eyección (FE) normal, indicando la necesidad de evaluaciones frecuentes y cuidadosas de la función ventricular izquierda para detectar disfunción sistólica incipiente. OBJETIVO: Analizar se incrementos en la FE en dosis bajas de dobutamina pueden predecir cirugía y/o muerte en pacientes con regurgitación aórtica. MÉTODOS: Eco de estrés con dobutamina se realizó en 24 pacientes portadores de regurgitación aórtica para verificar se incrementos de la FE en dosis bajas de dobutamina serían capaces de predecir la necesidad de cirugía y/o muerte en ese grupo de pacientes. RESULTADOS: La edad promedio fue de 37,8±16,8, y 16 (66 por ciento) eran varones. La FE aumentó de un valor basal promedio de 62,3±7,9 por ciento para 71,5±10,5 por ciento, en la dosis de 20 µg/kg/min de dobutamina (p < 0,001). Los pacientes se siguieron por 36,6±20,1 meses: dos pacientes murieron (uno de muerte cardiovascular) y cinco se sometieron a cirugía cardiaca. La FE basal se correlacionó con cirugía y muerte en el seguimiento de pacientes. CONCLUSIÓN: La fe basal se correlacionó con cirugía o muerte en el seguimiento de pacientes jóvenes con regurgitación aórtica. Sin embargo, el incremento porcentual en la FE con dosis baja de dobutamina no fue capaz de predecir eventos en esos pacientes.

Diagnóstico pela ecocardiografia transesofágica e evoluçäo de 35 pacientes portadores de Flail Mitral Valve / Flail mitral valve leaflet diagnosis by transesophageal echocardiography. Repost and evolution of 35 cases

Objetivo - Descrever os achados ao ecocardiograma transesofágico e evolução clínica de portadores de flail mitral valve. Métodos - No período de janeiro/93 a março/97, 1675 pacientes foram submetidos, em nossa instituição, a ecocardiograma transesofágico, sendo que em 35 casos foi feito o diagnóstico de flail mitral valve e, posteriormente, obtida sua evolução clínica. Resultados - A idade dos pacientes variou 12 a 87 anos (média 65 + 15) e 27 (77 por cento) eram do sexo masculino. O folheto posterior foi o mais acometido (25 pacientes, 71 por cento). O mecanismo do flial foi ruptura de cordoalha tendínea em todos os casos, exceto um, que apresentava importante alongamento e redundância de cordoalha. A etiologia foi prolapso e/ou degeneração mixomatosa em 15 pacientes, degenerativa em 9, isquêmia em 5, reumática em 4 e endocardite em 3. Regurgitação mitral de grau importante ocorreu em 25 (71 por cento) pacientes e moderada em 10 (29 por cento). O tempo médio de acompanhamento foi de 375+395 dias (1 a 1380). Foram submetidos a tratamentoclínico 19 pacientes e a tratamento cirúrgico 16, sendo que em todos foi confirmado o diagnóstico transesofágico. O número total de óbitos (hospitalar e pós-hospitalar) foi alto (34 por cento), tanto em pacientes submetidos a tratamento clínico quanto cirúrgico. Entre os sobreviventes, 17 estão em classe funcional (CF) I e 6 em CF II da NYHA. Conclusão - O diagnóstico de flail mitral valve ao ecocardiograma transesofágico é acurado, permitindo a definição de sua etiologia e mecanismo. A alta mortalidade à época do diagnóstico, provavelmente, se relaciona à gravidade da doença subjacente. Embora os pacientes não operados estejam envoluindo bem, a baixa CF observada nestes pacientes pode ser atribuída ao curto período de seguimento.