Increased plasma levels of soluble P-selectin in rheumatic mitral stenosis

BACKGROUND: Previous studies have demonstrated that platelet activation occurs in peripheral blood of patients with rheumatic mitral stenosis (MS). However, in patients with MS, the plasma level of soluble P-selectin (a marker of platelet activation) remains unsettled. METHODS AND RESULTS: A total of 20 patients with symptomatic MS undergoing percutaneous transluminal mitral valvuloplasty (PTMV) were studied (group 1; 16 patients in permanent atrial fibrillation, and 4 patients in sinus rhythm). The plasma levels of soluble P-selectin in the femoral vein and artery, and right and left atria before PTMV and those in the peripheral venous blood at the 1-week and 4-week follow-ups after PTMV were determined by solid-phase, sandwich, enzyme-linked immunosorbent assay. The mitral valve area was calculated by means of the Doppler pressure half-time method. In addition, we measured plasma concentrations of soluble P-selectin in the peripheral venous blood samples obtained from 22 control patients (including 14 healthy volunteers in sinus rhythm [group 2] and 8 patients in permanent lone atrial fibrillation [group 3]). The plasma levels of soluble P-selectin were significantly elevated in group 1 patients (49.78 +/- 37.72 ng/mL) [mean +/- SD] compared with group 2 (25.52 +/- 15.38 ng/mL) and group 3 patients (32.17 +/- 14.18 ng/mL) [p < 0.005]. In group 1 patients, the plasma levels of soluble P-selectin in the left atrium did not significantly differ from those in the right atrium, femoral vein, or femoral artery (p = 0.05). The area of mitral valve increased significantly after PTMV (1.06 +/- 0.17 cm(2) vs 1.48 +/- 0.32 cm(2), p < 0.0001). The mean left atrial pressure fell significantly and immediately after PTMV (23.0 +/- 5.1 mm Hg vs 17.6 +/- 5.9 mm Hg, p < 0.0001). The peripheral venous plasma levels of soluble P-selectin obtained before PTMV did not significantly fall after PTMV (before, 49.8 +/- 37.7 ng/mL; 10 min after, 39.8 +/- 19.1 ng/mL; 1 week after, 46.1 +/- 20.8 ng/mL; and 4 weeks after, 41.2 +/- 15.9 ng/mL; p = 0.145). CONCLUSIONS: The venous plasma levels of soluble P-selectin in patients with moderate-to-severe MS were significantly higher than those in healthy volunteers or patients with lone atrial fibrillation. In addition, in patients with MS, there was no difference in the plasma levels of soluble P-selectin between the left and right atrial blood and between peripheral and atrial blood. Moreover, there was no change in soluble P-selectin levels as a result of PTMV.     

Percutaneous transluminal mitral valvuloplasty reduces circulating vascular cell adhesion molecule-1 in rheumatic mitral stenosis

BACKGROUND: The circulating levels of adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), have been demonstrated to be elevated in patients with rheumatic mitral stenosis (MS). However, the impact of percutaneous transluminal mitral valvuloplasty (PTMV) on the elevated circulating levels of VCAM-1 and ICAM-1 in patients with MS has never been investigated. METHODS: and results: A total of 19 patients with symptomatic MS undergoing PTMV were studied (group 1) [15 patients in chronic atrial fibrillation, and 4 patients in sinus rhythm]. The plasma levels of soluble VCAM-1 and ICAM-1 in the femoral vein and artery, and right and left atria before PTMV, and those in the peripheral venous blood at the 1-week and 4-week follow-ups after PTMV were determined by solid-phase sandwich enzyme-linked immunosorbent assay. The mitral valve area was calculated by means of the Doppler pressure half-time method. In addition, we measured plasma concentrations of soluble VCAM-1 and ICAM-1 in the peripheral venous blood samples obtained from 22 control patients (including 14 healthy volunteers in sinus rhythm [group 2] and 8 patients in chronic lone atrial fibrillation [group 3]). The plasma level of soluble VCAM-1 was significantly elevated in group 1 patients (1,205.4 +/- 462.4 ng/mL [mean +/- SD]) compared with group 2 (580.9 +/- 208.0 ng/mL) and group 3 patients (716.4 +/- 221.6 ng/mL) [p < 0.0001]. In group 1 patients, the plasma levels of soluble VCAM-1 and ICAM-1 in the left atrium did not differ from those in the right atrium, femoral vein, or femoral artery (p = 0.668 for VCAM-1, and p = 0.232 for ICAM-1). The area of mitral valve increased significantly after PTMV (1.08 +/- 0.14 cm(2) vs 1.48 +/- 0.33 cm(2), p < 0.0001). The mean left atrial pressure fell significantly after PTMV (22.9 +/- 5.2 mm Hg vs 17.7 +/- 6.0 mm Hg, p < 0.0001). The peripheral venous plasma level of soluble VCAM-1 obtained before PTMV fell significantly after PTMV (before, 1,205.4 +/- 462.4 ng/mL; 1 week after PTMV, 915.7 +/- 280.2 ng/mL; 4 weeks after PTMV, 859.0 +/- 298.7 ng/mL; p < 0.0001). CONCLUSIONS: In patients with moderate-to-severe MS, the venous plasma level of soluble VCAM-1 fell significantly after PTMV, and the elevated plasma soluble VCAM-1 concentration was associated with hemodynamic abnormality rather than with rheumatic activity.     

Increased circulating endothelin-1 in rheumatic mitral stenosis: irrelevance to left atrial and pulmonary artery pressures

BACKGROUND: Increased plasma endothelin (ET)-1 concentrations have been observed in patients with rheumatic mitral stenosis (MS). However, the mechanisms of increased circulating ET-1 in patients with MS remain unclear. METHODS: We measured plasma concentrations of ET-1 in blood samples from the femoral vein and artery, and right and left atria obtained from 20 patients with moderate-to-severe rheumatic MS before and after percutaneous transluminal mitral valvuloplasty (PTMV) [group 1; 16 patients in chronic atrial fibrillation and 4 patients in sinus rhythm]. In addition, we measured plasma concentrations of ET-1 in the peripheral venous blood samples obtained from 22 control patients (including 14 healthy volunteers in sinus rhythm [group 2] and 8 patients in chronic lone atrial fibrillation [group 3]). Plasma ET-1 concentrations were measured by solid-phase, sandwich enzyme-linked immunosorbent assay. RESULTS: The peripheral venous plasma concentrations of ET-1 were significantly higher in group 1 patients (2.46 +/- 0.90 pg/mL) than in group 2 and group 3 patients (0.74 +/- 0.42 pg/mL and 0.99 +/- 0.41 pg/mL, respectively [mean +/- SD]; p < 0.0001). However, there was no significant difference in the peripheral venous concentrations of ET-1 between group 2 and group 3 patients. In group 1 patients, the plasma ET-1 concentration in the femoral vein (2.46 +/- 0.90 pg/mL) was significantly higher than that in the right atrium (2.02 +/- 0.69 pg/mL), left atrium (2.11 +/- 0.99 pg/mL), and femoral artery (2.05 +/- 0.75 pg/mL) [p = 0.0001]. The plasma ET-1 concentration in the femoral vein was not correlated with the mean left atrial pressure (r = 0.05; p = 0.838) and mean pulmonary artery pressure (r = 0.07; p = 0.757). The plasma ET-1 concentration in the left atrium was also not correlated with the mean left atrial pressure (r = 0.11; p = 0.656), mean pulmonary artery pressure (r = 0.06; p = 0.788), or mitral valve area (r = 0.02; p = 0.936). Although the area of mitral valve increased significantly (1.06 +/- 0.17 cm(2) vs 1.48 +/- 0.32 cm(2); p < 0.0001), and the mean left atrial pressure (23.0 +/- 5.1 mm Hg vs 17.6 +/- 5.9 mm Hg; p < 0.0001) and mean pulmonary arterial pressure (31.0 +/- 7.9 mm Hg vs 25.5 +/- 7.0 mm Hg; p < 0.001) fell significantly and immediately after PTMV, there were no significant changes in the plasma ET-1 concentrations in the femoral vein, right atrium, left atrium, and femoral artery immediately after PTMV. CONCLUSION: Increased production of ET-1 in the pulmonary circulation in response to increased pulmonary artery pressure was not the mechanism of increased circulating ET-1 concentration in patients with MS. We proposed that one of the mechanisms of increased ET-1 concentration in the femoral vein was increased peripheral ET-1 release due to increased systemic venous pressure and mechanical damage of the endothelium.     

Mechanism of reducing platelet activity by percutaneous transluminal mitral valvuloplasty in patients with rheumatic mitral stenosis

BACKGROUND: Previous studies have demonstrated that platelet activity significantly decreased after optimal percutaneous transluminal mitral valvuloplasty (PTMV) in patients with rheumatic mitral stenosis (MS). However, the mechanism of reducing platelet activity by valvuloplasty remains unclear. METHODS AND RESULTS: We studied 19 patients with symptomatic MS who were undergoing PTMV. The fractions of unstimulated platelets expressing P-selectin in the venous blood obtained before, and at the 1-week and 4-week follow-ups after PTMV were determined by flow cytometry. The mitral valve areas, measured before and at the 1-week follow-up after PTMV, were calculated by means of the Doppler pressure half-time method. The mean (+/- SD) area of the mitral valve increased significantly after PTMV (1.05 +/- 0.17 vs 1.44 +/- 0.27 cm2, respectively; p < 0.0001). The mean left atrial area was reduced in size significantly after PTMV (36.6 +/- 11.4 vs 33.9 +/- 13.4 cm2, respectively; p < 0.05). The mean left atrial pressure (23.3 +/- 5.1 vs 18.0 +/- 5.8 mm Hg, respectively; p < 0.0001) and the mean pulmonary arterial pressure (31.4 +/- 7.8 vs 26.1 +/- 7.7 mm Hg, respectively; p < 0.0001) fell significantly after PTMV. The fraction of platelets expressing P-selectin in the venous blood fell significantly after PTMV (before PTMV, 4.7 +/- 2.4%; 1 week after PTMV, 2.2 +/- 2.1%; 4 weeks after PTMV, 2.0 +/- 1.7%; p < 0.0001). Correlation analysis demonstrated that there was a significantly direct relationship between the magnitude of increase in mitral valve area and the magnitude of decrease in the fraction of platelets expressing P-selectin in the venous blood 4 weeks after PTMV (p = 0.0013; r = 0.682). However, there was no significant correlation between the magnitude of decrease in the fraction of platelets expressing P-selectin in the venous blood and the magnitude of decrease in the left atrial area, the decrease in left atrial pressure, or the decrease in the pulmonary artery pressure after PTMV. CONCLUSIONS: In patients with moderate-to-severe MS, increased platelet activation fell significantly after PTMV. It was the increase in mitral valve area by PTMV, instead of hemodynamic and echocardiographic factors, that accounted for the decrease in the fraction of venous platelets expressing P-selectin after PTMV.     

Balance between plasma levels of tumor necrosis factor-alpha and interleukin-10 in rheumatic mitral stenosis

The study population consisted of 16 patients with rheumatic mitral stenosis undergoing percutaneous transluminal mitral valvuloplasty (group 1). The plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in the femoral vein and the right and left atria before valvuloplasty were determined by ELISA. Additionally, we measured plasma concentrations of TNF-alpha and IL-10 in the venous blood obtained from 19 control patients, including 12 healthy volunteers in sinus rhythm (group 2) and 7 patients in permanent lone atrial fibrillation (group 3). The venous plasma levels of TNF-alpha were significantly elevated in group 1 patients compared with group 2 patients (p < 0.002). Correlation analysis demonstrated that there was a significantly direct relationship between the plasma TNF-alpha and IL-10 concentrations in the left atrial, right atrial and peripheral venous blood (p < 0.008, r = 0.640; p < 0.04, r = 0.538; p< 0.03, r = 0.571, respectively). In conclusion, the plasma concentrations of TNF-alpha of patients with rheumatic mitral stenosis were significantly higher than those of healthy volunteers. In addition, there was a significantly direct relationship between the soluble TNF-alpha and IL-10 concentrations in the atrial and peripheral venous blood, indicating a balance between circulating TNF-alpha and IL-10 levels in patients with rheumatic mitral stenosis.     

The effect of percutaneous balloon mitral valvuloplasty on N-terminal- pro B- type natriuretic peptide plasma levels in mitral stenosis

The objectives of this study were to assess the effect of percutaneous mitral balloon valvuloplasty (PBMV) on the plasma levels of N-terminal-pro B-type natriuretic peptide (NT-proBNP) in patients with mitral stenosis (MS) and to investigate the relationship between the changes in hemodynamic variables and NT-proBNP levels after PBMV. Plasma NT-proBNP concentrations were obtained from 60 symptomatic patients with rheumatic MS who underwent PBMV, and in 35 age- and gender-matched healthy volunteers. Patients with MS were found to have significantly higher levels of plasma NT-proBNP compared to the control group (293 [77-1093] pg/mL versus 24 [12-67] pg/mL, respectively; [P < 0.001]). The mean preprocedural NT-proBNP level fell significantly from 293 (77-1093) pg/mL to 214 (69-1028) pg/mL (P < 0.001) following PBMV. The percentage decrease in plasma NT- proBNP levels was correlated only with the percentage decrease in systolic pulmonary artery pressure (r = 0.687, P < 0.001) and this correlation persisted in linear regression analysis (beta = -0.013; 95% CI [-0.018- -0.008] and P < 0.001). However, NT-proBNP levels did not correlate with the percentage of improvement in NYHA functional class, mitral valve gradients, or left atrial pressure (all P > 0.05). These findings indicate that NT-proBNP measurement following PBMV may be valuable for evaluating changes in pulmonary artery pressure and that elevated NT- proBNP levels in patients with MS may reflect the increased wall stress in the left atrium and right side of the heart.     

Atrial natriuretic peptide and vasopressin during percutaneous transvenous mitral valvuloplasty and relation to renin-angiotensin-aldosterone system and renal function

To study the relation between plasma atrial natriuretic peptide (ANP) and cardiac pressure, and to assess the pathophysiologic significance of ANP in water and electrolyte metabolism, the changes in plasma levels of ANP and arginine vasopressin (AVP) were examined in 11 patients with mitral stenosis who underwent percutaneous transvenous mitral valvuloplasty, and compared with the changes in the renin-angiotensin-aldosterone system and renal function. Immediately after valvuloplasty, plasma ANP levels decreased significantly with a concomitant decrease in mean pressures in the left atrium, the pulmonary artery and the right atrium. Plasma ANP levels decreased to the normal range in 4 of the 6 patients with normal sinus rhythm, while all 5 patients with atrial fibrillation had higher levels despite a similar degree of decrease in atrial pressure. There were significant positive correlations between plasma ANP levels and the mean left atrial pressure (r = 0.61, p less than 0.01), the mean pulmonary arterial pressure (r = 0.49, p less than 0.01) and the mean right atrial pressure (r = 0.54, p less than 0.01). The mean plasma AVP levels, on the other hand, showed a transient increase after valvuloplasty from 0.5 +/- 0.1 to 1.2 +/- 0.4 pg/ml (p less than 0.05). The mean plasma renin activity (1.3 +/- 0.3 vs 2.7 +/- 0.8 ng/ml/hr, p less than 0.05) and plasma aldosterone concentration (8.6 +/- 2.3 vs 17.2 +/- 5.2 ng/dl, p less than 0.05) also increased significantly 30 minutes after valvuloplasty.(ABSTRACT TRUNCATED AT 250 WORDS)     

Responsiveness of plasma atrial natriuretic factor to short-term changes in left atrial hemodynamics after percutaneous balloon mitral valvuloplasty

To assess the effect of short-term alteration of left atrial pressure and volume on the circulating plasma level of atrial natriuretic factor, 11 patients with left atrial hypertension due to mitral stenosis were studied at the time of percutaneous balloon mitral valvuloplasty. Hemodynamic measurements and plasma atrial natriuretic factor levels were obtained before, immediately (5 to 10 min) after and 24 h after valvuloplasty, and echocardiographic left atrial size was determined before and 24 h after valvuloplasty. Immediately after valvuloplasty, left atrial pressure decreased from 28 +/- 2 to 10 +/- 1 mm Hg (p less than 0.0005), mitral pressure gradient decreased from 20 +/- 2 to 7 +/- 1 mm Hg (p less than 0.0005), mitral valve area increased from 0.8 +/- 0.1 to 1.9 +/- 0.2 cm2 (p less than 0.0005) and plasma atrial natriuretic factor level rose from 249 +/- 42 to 348 +/- 50 pg/ml (p less than 0.01). This short-term rise in atrial natriuretic factor level may reflect a transient increase in left atrial pressure associated with balloon occlusion of the mitral valve.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left atrial platelet activity with rheumatic mitral stenosis: correlation study of severity and platelet P-selectin expression by flow cytometry

BACKGROUND: Previous studies have demonstrated that platelet activation, evaluated by measuring the secretory substances of platelets (ie, platelet factor 4 and beta-thromboglobulin), occurs in the peripheral blood of patients with rheumatic mitral stenosis (MS). However, the differences in platelet activation between peripheral and atrial blood, and the relationship between regional left atrial platelet P-selectin expression and the severity of MS have never been investigated. METHODS AND RESULTS: A total of 16 patients with symptomatic MS undergoing percutaneous transluminal mitral valvuloplasty were studied (group 1). The fractions of platelets expressing P selectin in the prevalvuloplasty left atrial, right atrial, peripheral venous, and arterial blood were determined by flow cytometry. The mitral valve area was calculated by means of the Doppler pressure half-time method. Peripheral venous platelet activity also was evaluated in 23 control patients (including 15 healthy volunteers who were in sinus rhythm [group 2] and 8 patients who had chronic lone atrial fibrillation [group 3]). The fraction of peripheral venous platelets expressing P selectin among group 1 patients was significantly higher than that of group 2 or 3 patients (p = 0.008). In group 1 patients, the fraction of platelets expressing P selectin in the left atrium was significantly higher than that in the right atrium, the femoral vein, or the femoral artery (p < 0.01). Correlation analysis demonstrated that there was a significantly direct relationship between the severity of MS and the fraction of left atrial platelets expressing P selectin (p = 0.01; r = -0.620). The fraction of peripheral venous platelets expressing P selectin among group 2 patients did not differ from that of group 3 patients CONCLUSIONS: In patients with rheumatic MS, increased regional left atrial platelet P-selectin expression had a significantly direct relationship with the severity of MS. The increased regional left atrial platelet P-selectin expression was not reflected in peripheral venous blood samples.     

Increased platelet activation and endothelial dysfunction in patients with atrial fibrillation immediately following percutaneous balloon mitral valvuloplasty

BACKGROUND: Immediately following percutaneous balloon mitral valvuloplasty (PBMVP), patients have a 3% risk of systemic thromboembolism. HYPOTHESIS: We hypothesized that this may in part be due to an increase in hypercoagulability (as indicated by abnormal coagulation, platelet activation, and endothelial dysfunction) in such patients. METHODS: We measured indices of platelet activation [soluble P-selectin (sPsel), ELISA], endothelial dysfunction [von Willebrand factor (vWf), ELISA], and coagulation (fibrinogen, modified Clauss) in 16 patients (15 women, mean age 59 +/- 10 years) with chronic atrial fibrillation admitted for PBMVP, and 16 healthy age- and gender-matched controls. Blood samples were obtained as follows: (1) peripheral venous samples prior to PBMVP, immediately following PBMVP, and 24 h after PBMVP; and (2) arterial samples prior to and immediately following PBMVP. RESULTS: Patients with mitral stenosis and chronic atrial fibrillation demonstrated significantly higher mean levels of vWf [148 (SD 24) vs. 102 (SD 37); t-test, p < 0.001] and plasma fibrinogen [4.2 (SD 0.8) vs. 3.3 (SD 0.8); p = 0.003] at baseline than matched healthy controls. There was a nonsignificant trend toward lower median sP-sel levels in patients with mitral stenosis [64 (inter quartile range 47-91) vs. 109 (46-128); Mann-Whitney test, p = 0.08]. Following PBMVP, there was a significant increase in venous sP-sel levels immediately post procedure (paired Wilcoxon test, p = 0.03) and at 24 h afterward (p = 0.01). Arterial s-Psel levels correspondingly increased immediately post procedure (p = 0.008). There was a significant increase in mean venous (at 24 h) but not arterial vWf levels post PBMVP. There were no significant changes in mean venous or arterial plasma fibrinogen levels following PBMVP. CONCLUSION: Patients with mitral stenosis and chronic atrial fibrillation have increased plasma levels of vWf and fibrinogen levels compared with healthy controls, suggesting increased endothelial dysfunction and coagulation at baseline in these patients. The increased levels of sP-sel immediately post procedure and at 24 h, in association with increased vWf levels at 24 h after PBMVP, are in keeping with an increase in platelet activation and endothelial dysfunction following PBMVP. These changes may contribute to the increased risk of thromboembolism following PBMVP and suggest the need for adequate antithrombotic therapy following PBMVP.     

Decreased platelet activation and endothelial dysfunction after percutaneous mitral balloon valvuloplasty

OBJECTIVE: This study was conducted to assess the changes in platelet activation and endothelial dysfunction in patients with mitral stenosis (MS) and sinus rhythm (SR) following percutaneous mitral balloon valvuloplasty (PMBV). BACKGROUND: Systemic thromboembolism is a serious complication in patients with valvular heart disease, and its incidence is highest in those with mitral stenosis. A hypercoagulable state has also been reported in patients with mitral stenosis and sinus rhythm. A recent study has shown that patients with previous PMBV had a lower incidence of thromboembolism. METHODS AND RESULTS: The study was conducted in 21 patients (two men, 19 women, mean age=34+/-6 years) with mitral stenosis and sinus rhythm (SR) who underwent percutaneous mitral balloon valvuloplasty and 17 healthy control subjects (two men, 15 women, mean age=33+/-6 years). Biochemical markers of platelet activity (beta thromboglobulin, BTG, and soluble P-selectin, sPsel) and endothelial dysfunction (von Willebrand Factor, vWF) were measured in both control subjects' and patients' serum samples taken immediately before PMBV and 24 h after PMBV procedure. All patients underwent successful PMBV. Significant improvement of mitral valve area, pulmonary artery pressure, mean mitral gradients, and left atrial diameter were achieved in all patients after PMBV. Compared with control subjects, patients with MS had higher plasma levels of BTG (66+/-26 ng/ml vs. 14+/-6 ng/ml, P<0.001), vWF (177+/-67 units/dl vs. 99+/-37 units/dl, P<0.0001), sPsel (226+/-74 ng/ml vs. 155+/-66 ng/ml, P<0.001). There was a significant reduction of plasma levels of BTG (66+/-26 ng/ml vs. 48+/-20 ng/ml, P=0.002), vWF (177+/-67 units/dl vs. 134+/-60 units/dl, P=0.001) and P-selectin (226+/-74 ng/ml vs. 173+/-71 ng/ml, P=0.008,) 24 h after PMBV. CONCLUSION: We have shown that patients with severe MS and SR have increased platelet activation and endothelial dysfunction compared with control subjects and PMBV results in decreased platelet activity and improvement of endothelial injury.     

Regional left atrial coagulation and fibrinolytic activities in patients with mitral stenosis

Systemic thromboembolism is a major complication of mitral stenosis (MS), especially in those patients having atrial fibrillation (AF). Recent evidence has suggested that regional left atrial coagulation activity may be increased in MS and may contribute to the pathophysiology of left atrial thrombus. However, the relation of left atrial coagulation activity to factors that predispose to left atrial thrombus formation is unknown. Also, the relations between left atrial and systemic coagulation activity, fibrinolysis, and platelet activation remain unresolved. Left atrial and peripheral venous levels of fibrinogen, antithrombin III, factor VII and factor VIII for coagulation, D-dimer, tPA and PAI-I, plasmin and antiplasmin for fibrinolysis, and platelet factor 4 and vWF for platelet activation, and endothelial dysfunction were measured in 46 patients with MS and normal clotting times who were undergoing percutaneous mitral valvuloplasty. Left atrial tPA, plasmin, PAI-I, antiplasmin, PF4, and vWF levels exceeded the corresponding peripheral venous levels (P < 0.05) in patients with MS, being more significant in the AF subgroup. There were no significant differences between left atrial and peripheral venous levels of fibrinogen, D-dimer, factor VII, and factor VIII within the patient group (P > 0.05). The results suggest that there are significant variations in the indices of coagulation, fibrinolytic system and platelet activation, and endothelial dysfunction between left atrial and peripheral venous blood samples of patients with MS that may be due to limited spillover from the left atrium to the systemic circulation.     

Plasma atrial natriuretic factor and cyclic GMP in mitral stenosis treated by balloon valvulotomy. Effect of atrial fibrillation

To study the relation between plasma atrial natriuretic factor (ANF) and cardiac pressures, we measured plasma ANF in 24 patients with mitral stenosis 30 minutes before and 20 minutes after balloon mitral valvulotomy. All patients were without physical signs of congestive heart failure. Normal sinus rhythm was present in 15 (group 1), whereas the other nine (group 2) had permanent atrial fibrillation. There were no significant differences between groups for basal mean pressures in right atrium (RA), left atrium (LA), and pulmonary artery (PA). Valvulotomy resulted in a fall in both groups (p less than 0.001) in LA and PA mean pressures, whereas heart rate, cardiac index, and RA and aorta (AO) pressures did not change significantly. Basal ANF was not different in either group in RA (240 +/- 43 vs. 266 +/- 35 pg/ml) or AO (441 +/- 92 vs. 643 +/- 70 pg/ml) but tended to be higher in group 2 in LA (428 +/- 88 vs. 682 +/- 84 pg/ml; p = 0.059) and PA (488 +/- 93 vs. 759 +/- 92 pg/ml; p = 0.057). Plasma ANF was the highest in PA, and about 50% ANF was extracted in the systemic circulation. After valvulotomy, plasma ANF was greater (p less than 0.05) in group 2 (372 +/- 90, 755 +/- 152, 805 +/- 134, and 707 +/- 144 pg/ml) than in group 1 (206 +/- 36, 386 +/- 47, 429 +/- 66, and 421 +/- 49 pg/ml), regardless of the site of blood collection (RA, LA, PA, and AO, respectively). PA ANF was correlated with LA pressure (p less than 0.05) in group 1 before as well as after valvulotomy, whereas there was no such correlation in group 2. Cyclic GMP (cGMP) in LA was correlated (p less than 0.01) with PA ANF in group 1, and LA cGMP (10.0 +/- 1.2 and 9.1 +/- 1.8 pmol/ml in groups 1 and 2, respectively) was higher (p less than 0.05) than PA cGMP (9.1 +/- 1.0 and 8.0 +/- 1.5 pmol/ml in groups 1 and 2, respectively) before valvulotomy, which suggests the presence of ANF receptors in the pulmonary circulation. Taken together, these results indicate that in patients in sinus rhythm with mitral stenosis, there is an increase in ANF secretion depending on LA pressure. ANF secretion is also high in patients with mitral stenosis and atrial fibrillation but does not respond appropriately to changes in LA pressure.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pulmonary venous flow dynamics before and after balloon mitral valvuloplasty as determined by transesophageal Doppler echocardiography.

The pattern of left atrial filling was studied in 14 patients with severe mitral stenosis in sinus rhythm before and immediately after successful balloon mitral valvuloplasty by transesophageal pulsed Doppler echocardiography of the left superior pulmonary vein. Mean mitral valve orifice area increased from 0.8 +/- 0.1 to 2.2 +/- 0.3 cm2 (p less than 0.0001), and left atrial mean pressure decreased from 30 +/- 5 to 12 +/- 4 mm Hg (p less than 0.0001) after the procedure. After balloon mitral valvuloplasty, significant increases in peak systolic pulmonary velocity (35 +/- 16 to 44 +/- 10 cm/s; p less than 0.01), systolic flow velocity time integral (3.3 +/- 1.5 to 5.9 +/- 2.0 cm; p less than 0.001) and the ratio of systolic/diastolic pulmonary venous flow velocity time integrals (0.8 +/- 0.4 to 1.4 +/- 0.5; p less than 0.001) were observed. An acute increase in mitral valve orifice area caused no significant changes in peak diastolic forward flow velocity (40 +/- 7 to 41 +/- 9 cm/s; p = not significant [NS]), diastolic forward flow velocity time integral (4.3 +/- 1.7 to 4.6 +/- 1.8 cm; p = NS) and atrial flow reversal velocity (30 +/- 3 to 35 +/- 3 cm/s; p = NS) compared with at baseline. The results suggest that in patients with severe mitral stenosis and sinus rhythm, left atrial filling is biphasic with a diastolic preponderance, and successful mitral valvuloplasty is associated with an immediate increase in pulmonary venous systolic forward flow.     

Favorable effect of balloon mitral valvuloplasty on the incidence of atrial fibrillation in patients with severe mitral stenosis.

BACKGROUND: The long-term effect of balloon mitral valvuloplasty (BMV) on the incidence of atrial fibrillation (AF) in patients with severe mitral stenosis (MS) remains undetermined. AIMS: To assess the effect of successful BMV on the incidence of chronic AF in patients with severe MS, compare the results with historical controls, and identify factors associated with AF in such patients. METHODS: Retrospective analysis of 382 consecutive patients with severe MS and in sinus rhythm (SR) who underwent successful BMV (post procedure mitral valve area (MVA) > or =1.5 cm(2), mitral regurgitation (MR) < or =2/4) at our hospital and followed-up for 1-15.6 (mean 5.6 +/- 3.9) years with clinical and echocardiographic examination. RESULTS: Thirty-four (8.9%) patients developed AF at follow-up (group A) and 348 patients (group B) remained in SR. At baseline, and in comparison with group B, patients who developed AF (group A) were older, had higher mitral echo score but equal MVA and left atrial (LA) size. The postprocedure MVA was smaller in group A (1.7 +/- 0.3 cm(2)) than in group B (2.0 +/- 0.2 cm(2;) P = 0.002). At follow-up, and in comparison to group B, group A had smaller MVA (1.5 +/- 0.4 cm(2) vs 1.8 +/- 0.4 cm(2) P <0.0001), larger LA dimension (49.4 +/- 6.5 vs 42 +/- 6.5 mm; P <0.0001) and higher restenosis rate (35% vs 14%; P = 0.001). Multivariate logistic regression analysis identified age at follow-up (P < 0.0001), LA size at follow-up (P = 0.004), and MVA at follow-up (P = 0.006) as predictors of AF. CONCLUSIONS: This study demonstrated favorable effect of BMV on the incidence of AF (8.9%) in patients with severe MS in comparison with reported series (29%) of patients with severe MS with similar baseline characteristics who were not submitted to any intervention. The predictors of AF were age, larger LA, and smaller MVA, at follow-up.     

Echocardiographic and hemodynamic findings in patients with mitral stenosis undergoing percutaneous mitral commissurotomy comparing those with chronic atrial fibrillation versus those with normal sinus rhythm

Chronic atrial fibrillation (AF) is common in patients with mitral stenosis (MS). Because AF induces electrical and mechanical remodeling of the left atrium, left atrial (LA) compliance is likely to be changed in its presence. This study was performed to investigate the influence of AF on LA compliance in patients with moderate to severe MS. Data were analyzed for 356 patients (282 women; mean age 40 +/- 11 years; range 17 to approximately 71) who were registered in the percutaneous mitral commissurotomy database. Mean LA pressure was lower (21 +/- 7 vs 26 +/- 8 mm Hg; p <0.001), but LA volume was higher in the AF than sinus-rhythm group (126 +/- 62 vs 74 +/- 27 ml; p <0.001), indicating higher LA compliance, which was further confirmed by lower LA v wave at catheterization in the AF group (27 +/- 9 for AF vs 32 +/- 10 mm Hg for sinus rhythm; p <0.001). In conclusion, the presence of AF has a significant influence on LA compliance in patients with moderate to severe MS.     

Effects of percutaneous balloon mitral valvuloplasty on plasma B-type natriuretic peptide in rheumatic mitral stenosis with and without atrial fibrillation

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the effect of percutaneous balloon mitral valvuloplasty (PBMV) on plasma B-type natriuretic peptide (BNP) levels in patients in sinus rhythm (SR) and with atrial fibrillation (AF). METHODS: Thirty patients with rheumatic mitral stenosis who underwent successful PBMV were included in the study. Of these patents, 21 were in SR (SR group) and nine had AF (AF group). Plasma BNP levels were measured using the Triage BNP Test in all patients before, and at 20 min and 24 h after, PBMV. Control levels were measured in eight healthy volunteers. RESULTS: Basal plasma BNP levels in patients were significantly higher than those in controls (123.5 +/- 69.5 versus 16.4 +/- 7.6 pg/ml, p < 0.01), and correlated with mean left atrial pressure (mLAP; r = 0.441, p < 0.05) and pulmonary artery pressure (PAP; r = 0.488, p < 0.01). No significant difference was observed in BNP levels between the SR and AF groups. In the SR group, BNP levels decreased after PBMV (pre-PBMV 128.7 +/- 75.9 pg/ml; at 20 min, 88.6 +/- 62.0 pg/ml; at 24 h, 43.4 +/- 26.7 pg/ml; respectively, p < 0.05). Changes in plasma BNP (deltaBNP) correlated positively with those in mLAP (deltamLAP) (r = 0.696, p < 0.01) and PAP (deltaPAP) (r = 0.456, p < 0.05). Left ventricular end-diastolic volume (LVEDV) (96.1 +/- 21.6 versus 111.5 +/- 25.2 ml, p < 0.01) and stroke volume (SV) (59.2 +/- 15.8 versus 69.0 +/- 17.9 ml, p < 0.05) augmented accordingly without any changes in left ventricular end-diastolic pressure (LVEDP) (p = NS). In contrast, in group AF, BNP levels remained unchanged (pre-PBMV 111.6 +/- 53.4 pg/ml; at 20 min, 122.0 +/- 68.7 pg/ml; at 24 h, 106.1 +/- 56.2 pg/ml; respectively, p = NS), while LVEDP increased (6.4 +/- 3.6 versus 8.6 +/- 3.2 mmHg, p < 0.01), without any changes in LVEDV and SV (p = NS). CONCLUSION: The study results indicate that, in mitral stenosis patients, a high BNP level is associated with high mLAP and PAP. Cardiac rhythm may play an important role in changes of BNP level after PBMV. BNP may be a valid marker to reflect changes in mLAP and PAP after PBMV in patients with SR, but not in those with AF.     

分级次二尖瓣球囊扩张术治疗重度二尖瓣狭窄伴心房颤动的临床研究

为评价分级扩张法行经皮穿刺二尖球囊扩张术（PBMV）的临床疗效。采用分级次扩张法对52例风湿性二尖瓣狭窄（MS）患者进行,分重度MS伴心房颤动（AF）组和中，重度MS无AF组。根据身高2确定首次扩张直径，每次递量0.5-1mm，直至疗效满意。术前，术后进行二维超声和多普勒，血流动力学检查。结果显示，52例PBMV均获成功，术后血流动力学明显改善，心功能明显提高，无重要并发症发生，两组间比较无明显差异。提示分级次扩张法可有效预防二尖瓣反流，低心排，急性左心衰，栓塞等并发症，并获得良好效果，尤其对重度MS伴AE者，不失为一种理想的治疗方法。     

Immediate effect of balloon valvuloplasty on hemostatic changes in mitral stenosis

This study was conducted to assess right and left atrial hemostatic function in patients with mitral stenosis (MS) and to investigate the immediate effect of balloon mitral valvuloplasty (BMV) on hemostatic function. BMV was performed in 28 patients with MS (age 29 +/- 8 years) who had sinus rhythm and no left atrial (LA) thrombus. Right and left atrial biochemical markers of platelet activity (platelet factor 4 [PF4] and B thromboglobulin [BTG]), coagulation (thrombin-antithrombin III complex [TAT]), and fibrinolytic activity (D-dimer) were measured before and 30 minutes after BMV. Right atrial levels of these markers were also measured in 20 control subjects. Compared with control subjects, patients with MS had higher right atrial levels of PF4 (30 +/- 15 vs 5 +/- 2 IU/ml), BTG (231 +/- 53 vs 30 +/- 8 IU/ml), TAT (7 +/- 4 vs 2 +/- 0.3 microg/L), and D-dimer (380 +/- 145 vs 160 +/- 35 ng/ml, p < 0.0001 in all). TAT levels were higher in the left atrium than in the right atrium of patients before BMV (8 +/- 4 vs 7 +/- 4 microg/L, p < 0.0001). BMV was successful (final mitral valve area > or = 1.5 cm2 and > or = 50% increase of the initial valve area) in all patients. There was a significant reduction of LA levels of PF4 (35 +/- 8 to 26 +/- 9 IU/ml, p < 0.0001), BTG (225 +/- 41 to 196 +/- 28 IU/ml, p < 0.001), and TAT (10 +/- 5 to 7 +/- 1 microg/L, p < 0.05) in the 16 patients with LA pressure < 10 mm Hg after BMV, whereas these markers were not reduced in the 12 patients with left atrial pressure > or = 10 mm Hg after BMV. These data indicate that platelet function, coagulation status, and fibrinolytic activity are increased regionally in the left atrium and in the systemic circulation in patients with MS and sinus rhythm in the absence of LA thrombus. Successful BMV induces a significant reduction of prethrombotic status in patients with low LA pressure after the procedure. Patients with high LA pressure after BMV maintain a high prethrombotic state and may be considered at an increased risk of thromboembolism after the procedure.     

Effect of percutaneous transvenous mitral commissurotomy for the preservation of sinus rhythm in patients with mitral stenosis

OBJECTIVES: Atrial fibrillation is frequently associated with mitral stenosis and is considered to be an unfavorable factor for the long-term prognosis. The efficacy of percutaneous transvenous mitral commissurotomy(PTMC) was examined for the preservation of sinus rhythm in patients with mitral stenosis after PTMC. METHODS: Long-term clinical data after PTMC were obtained from 71 patients who had undergone PTMC from March 1989 to September 1999. Eighteen patients in sinus rhythm before PTMC were divided into two groups: the SR group(n = 5) who remained in sinus rhythm, and the Af group(n = 13) who showed change from sinus rhythm to persistent or paroxysmal atrial fibrillation after PTMC. RESULTS: Age, sex, mitral valve area(1.4 +/- 0.3 vs 1.2 +/- 0.3 cm2), mean mitral pressure gradient(14.3 +/- 5.5 vs 12.6 +/- 5.9 mmHg), mean left atrial pressure(15.9 +/- 7.6 vs 19.0 +/- 7.7 mmHg), left ventricular end-diastolic pressure(7.5 +/- 2.8 vs 9.3 +/- 3.9 mmHg), left ventricular end-diastolic volume index(77 +/- 13 vs 82 +/- 14 ml/m2), left ventricular ejection fraction(60 +/- 6% vs 55 +/- 4%) and cardiac output(5.1 +/- 0.4 vs 4.9 +/- 0.8 l/m2) before PTMC were not different between the two groups. Changes in mean mitral pressure gradient, mean left atrial pressure and cardiac output immediately after PTMC were not different statistically. Mitral valve area immediately after PTMC was significantly greater in the SR group compared to the Af group(2.3 +/- 0.3 vs 1.8 +/- 0.3 cm2, p < 0.05). The change in mitral valve area was also greater in the SR group(1.0 +/- 0.2 vs 0.6 +/- 0.4 cm2, p < 0.05), but there was no statistical difference in the percentage change of mitral valve area between before and immediately after PTMC(SR group 78 +/- 35% vs Af group 50 +/- 35%). End-diastolic pressure, end-diastolic volume index and ejection fraction immediately after PTMC were not statistically different. CONCLUSIONS: The final mitral valve area immediately after PTMC in the patients with mitral stenosis in sinus rhythm, but not the changes of mean mitral pressure gradient, mean left atrial pressure or cardiac output, is important for the maintenance of sinus rhythm.