The relationship between plasma proadrenomedullin level and severity of the disease in patients with isolated rheumatic mitral stenosis.

OBJECTIVE: In this study, we aimed to determine the plasma proadrenomedullin (ProADM) levels in patients with rheumatic mitral stenosis (MS), to evaluate the relationship between ProADM levels and the echocardiographic parameters that represent the severity of stenosis and symptoms, and to compare the ProADM and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, which is a well-known marker for rheumatic MS. METHODS: Our study included 53 consecutive patients with isolated rheumatic MS and 45 volunteers with similar age and gender features. Patients with MS were divided into two groups based on the presence of an indication for intervention. Detailed echocardiographic examinations were performed on all participants, and blood samples were collected to detect the NT-proBNP and ProADM levels. RESULTS: NT-proBNP and ProADM levels were significantly higher in the rheumatic MS group compared with the control group. In rheumatic MS groups, patients with an indication for intervention had higher levels of NT-proBNP and ProADM compared with patients without an indication for intervention. Moreover, NT-proBNP and ProADM levels were found to be significantly correlated with echocardiographic parameters, which revealed the severity of stenosis in various degrees. Both parameters increased as the New York Heart Association (NYHA) class increased, and this increase had a statistical significance. Additionally, the cut-off values of both parameters (NT-proBNP: 119.9 pg/mL, ProADM: 6.15 nmol/L) could detect patients with an indication for intervention with high sensitivity and specificity rates. NT-proBNP was found to be slightly more effective in this regard. CONCLUSION: The increased NT-proBNP and ProADM levels in patients with isolated rheumatic MS can help clinicians in distinguishing patients with an indication for intervention by providing additional information to echocardiography.

Implication of d-dimer in rheumatic severe mitral stenosis - A tertiary centre study.

BACKGROUND: In rheumatic mitral stenosis (MS), left atrial (LA) thrombus and LA spontaneous echo contrast (LA SEC) reflect hypercoagulability. The study focuses on whether D-dimer levels predict the existence of LA thrombus and SEC in patients with severe MS. METHODS: 95 consecutive patients with severe MS referred for transesophageal echocardiogram (TEE) between July 2011 and March 2012 to evaluate LA thrombus prior to balloon mitral valvotomy (BMV) were included in the study. D-Dimer levels in these patients were observed. RESULTS: Out of the 95 patients, 15 (15.8%) had LA thrombus and 52 patients had LA SEC (54.7%). Any correlation between D-Dimer levels and existence (or non-existence) of LA thrombus was not noticed from the receiver operating characteristics (ROC) curve with an area of .535. For patients with LA SEC, the D-Dimer levels were found to be considerably higher (776 ± 866 µg/L vs. 294 ± 331 µg/L, p = .001). An ideal cut-off level of 393 µg/L for diagnosing LA SEC was illustrated by the ROC curve with a sensitivity of 63.4%, specificity of 83.72%, positive predictive value of 82.5% and a negative predictive value of 65.45%. CONCLUSIONS: D-dimer levels were not representative of the presence or absence of LA thrombus in patients with severe MS. Nonetheless, this study demonstrated the substantial link between D-Dimer level and LA SEC. If a D-Dimer level of 400 µg/L or higher is taken as positive, it has high specificity and positive predictive value for diagnosing LA SEC.

Assessment of successful percutaneous mitral commissurotomy by MRproANP and sCD146.

BACKGROUND: We studied the course of plasma concentrations of 4 cardiovascular biomarkers: natriuretic peptides (BNP, NT-proBNP; mid-regional (MR) pro-atrial NP); and soluble endothelial CD146 (sCD146), in patients with severe mitral valve stenosis undergoing percutaneous mitral commissurotomy (PMC) to identify potential markers of procedural success. METHODS: Biomarkers were tested in 40 patients the day before and the day after PMC. Success was defined as mitral valve area ≥ 1.5 cm2; or an increase of ≥0.5 cm2 in mitral valve area associated with echocardiographic mitral regurgitation

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.

Relationship between presence of spontaneous echo contrast and platelet-to-lymphocyte ratio in patients with mitral stenosis.

BACKGROUND: Left atrial spontaneous echo contrast (SEC) is an existence of smoke-like echoes with a typical swirling motion of blood in left atrial cavity or appendage, and it is known to be a marker of prothrombotic state. Previous studies have revealed that there is an association between prothrombotic state and the platelet-to-lymphocyte ratio (PLR). Thus, we aimed to investigate the association between the presence of SEC and PLR in patients with mitral stenosis (MS). METHODS: A total of 306 consecutive patients with MS were enrolled in the study. Transoesophageal echocardiography was made to assess the SEC for all patients. Recruited patients were divided into two groups according to the formation of SEC in the left atrium. Complete blood counting parameters, biochemical tests and high-sensitive C-reactive protein (Hs-CRP) levels were measured. RESULTS: There were 182 patients (mean age 42.7 ± 11.9 and 78% female) in the SEC (-) group, and 124 patients (mean age 45.3 ± 10.5 and 68% female) in the SEC (+) group. Hs-CRP levels (3.9 ± 1.9 vs 5.1 ± 3.6, P < 0.001) were significantly different between the two groups. PLR (143.4 ± 77.7 vs 180.6 ± 108.7, P < 0.001) was significantly higher in the SEC (+) group. ROC curve analysis, PRL ≥123 had 71% sensitivity and 52% specificity in predicting SEC in patients with MS. CONCLUSION: Platelet-to-lymphocyte ratio is an inexpensive and easily calculated biomarker, which is useful to predict left atrial SEC in patients with mitral stenosis.

Effect of percutaneous transvenous mitral commissurotomy on brain natriuretic peptide in mitral stenosis in tertiary care hospitals of Peshawar.

The current study was planned to determine the effect of percutaneous transvenous mitral commissurotomy (PTMC) on brain natriuretic peptide (BNP) levels in mitral stenosis patients. It was conducted at the Postgraduate Medical Institute, Lady Reading Hospital, Peshawar, and Rehman Medical Institute Laboratory, Peshawar, Pakistan, from December 2013 to June 2014. Of the 100 patients, 63(63%) were females. The patients' age ranged from 14 to 58 years. Patients diagnosed with isolated mitral valve stenosis or with grade 1 or with grade 2 mitral regurgitation were randomly selected. BNP values before and after 24 hours of PTMC were calculated. The statistical analysis of the echocardiographic variables and BNP levels showed an increase in mitral valve area, drop in pulmonary artery systolic pressure, left atrium diameter and reduction in BNP levels (p<0,05 each) after PTMC that provides a concrete evidence for a successful PTMC procedure.

Evaluation of serum 25-hydroxyvitamin D levels in calcific rheumatic mitral stenosis- A cross sectional study.

BACKGROUND AND AIM OF THE STUDY: Rheumatic mitral stenosis (RMS) is an autoimmune, progressive destructive valve disease occurring as a sequele of streptococcal infection. Epidemiological studies support an association of vitamin D deficiency with initial susceptibility and severity of autoimmune diseases. The aim of the present study was to assess serum level of 25 hydroxyvitamin D in subjects of RMS and assess if any correlation exists with serum levels of vitamin D and severity of disease along with calcification assessed semi-quantitatively by echocardiography by applying Wilkins score. METHOD: Fifty five patients of RMS without any calcification of the valves (Group A) assessed by echocardiography along with fifty five patients of RMS with mild to moderately calcified valves (Group B, Wilkins calcium score 1 or 2) and 55 patients with severely calcified valves (Group C, Wilkins calcium score 3 or 4) were enrolled for the study. All subjects underwent clinical, echocardiographic, and biochemical evaluation. The total Wilkins score, Wilkins calcium score along with serum level of 25 hydroxyvitamin D was evaluated in all the patients. RESULTS: The median serum level of 25 hydroxyvitamin D was significantly lower in Group B (20.4ng/ml, p<0.001) and group C (11.4ng/ml, p<0.001) compared to Group A patients (27.9ng/ml). Similarly serum level of 25 hydroxyvitamin D in Group C patients were significantly less than Group B patients (p<0.001). A significant inverse correlation was identified between serum level of 25 hydroxyvitamin D and total Wilkins score (r=-0.65, p<0.001) as well as Wilkins calcium score (r=-0.69, p<0.001). But no correlation was identified between 25 hydroxyvitamin D levels and other echocardiographic parameters of RMS. CONCLUSION: Our study showed a significantly lower level of 25 hydroxyvitamin D in subjects of RMS with severely damaged and calcified valves as compared to those with less severely damaged non-calcified valves and it correlated with both Wilkins score and Wilkins calcification score. Thus a link may exist between vitamin D deficiency (an immunomodulator) and severity of autoimmune injury on the valves.

Sickening or Healing the Heart? The Association of Ficolin-1 and Rheumatic Fever.

Rheumatic fever (RF) and its subsequent progression to rheumatic heart disease (RHD) are chronic inflammatory disorders prevalent in children and adolescents in underdeveloped countries, and a contributing factor for high morbidity and mortality rates worldwide. Their primary cause is oropharynx infection by Streptococcus pyogenes, whose acetylated residues are recognized by ficolin-1. This is the only membrane-bound, as well as soluble activator molecule of the complement lectin pathway (LP). Although LP genetic polymorphisms are associated with RF, FCN1 gene's role remains unknown. To understand this role, we haplotyped five FCN1 promoter polymorphisms by sequence-specific amplification in 193 patients (138 with RHD and 55, RF only) and 193 controls, measuring ficolin-1 serum concentrations in 78 patients and 86 controls, using enzyme-linked immunosorbent assay (ELISA). Patients presented lower ficolin-1 serum levels (p < 0.0001), but did not differ according to cardiac commitment. Control's genotype distribution was in the Hardy-Weinberg equilibrium. Four alleles (rs2989727: c.-1981A, rs10120023: c.-542A, rs10117466: c.-144A, and rs10858293: c.33T), all associated with increased FCN1 gene expression in whole blood or adipose subcutaneous tissue (p = 0.000001), were also associated with increased protection against the disease. They occur within the *3C2 haplotype, associated with an increased protection against RF (OR = 0.41, p < 0.0001) and with higher ficolin-1 levels in patient serum (p = 0.03). In addition, major alleles of these same polymorphisms comprehend the most primitive *1 haplotype, associated with increased susceptibility to RF (OR = 1.76, p < 0.0001). Nevertheless, instead of having a clear-cut protective role, the minor c.-1981A and c.-144A alleles were also associated with additive susceptibility to valvar stenosis and mitral insufficiency (OR = 3.75, p = 0.009 and OR = 3.37, p = 0.027, respectively). All associations were independent of age, sex or ethnicity. Thus, minor FCN1 promoter variants may play a protective role against RF, by encouraging bacteria elimination as well as increasing gene expression and protein levels. On the other hand, they may also predispose the patients to RHD symptoms, by probably contributing to chronic inflammation and tissue injury, thus emphasizing the dual importance of ficolin-1 in both conditions.

High sensitive C-reactive protein and interleukin 6 in atrial fibrillation with rheumatic mitral stenosis from Indian cohort.

INTRODUCTION: Presence of chronic low grade inflammation has often been implicated in the etiology of atrial fibrillation (AF). Whether pre-existing inflammatory state promotes AF or initiation of AF activates inflammation is a dilemma among clinicians. This study investigates the role of high sensitive C reactive protein (hs-CRP) and interleukin 6 (IL-6) in AF with rheumatic mitral stenosis (Rh-MS) as markers of chronic inflammation. METHODS: This case control cohort included sixty five (n=65) Rh-MS patients having other valve lesions as trivial to mild. Out of them twenty nine (n=29; group C) had baseline AF and rest were normal sinus rhythm (NSR). A 24h holter recording was done in NSR patients to diagnose paroxysmal AF/tachyarrhythmia forming group B (n=12) and not having any tachyarrhythmia were designated as NSR; group A (n=24). RESULTS: hs-CRP and IL6 showed statistically significant increase in group C (permanent AF) compared to group A (95% CI: 4.2-0.9, p=0.007; 95% CI: 1.2-0.89; p=0.05 respectively), while it was non significant between group A and group B (p>0.05). A weak positive correlation was observed with hs-CRP and left atrial volume index (LAVi) (r=0.45, p=0.06) in AF group as compared to NSR group. 68.2% of patients in AF group (27/41) had moderate to severe spontaneous echo contrast (SEC) as compared to 37.5% (10/24) in NSR group. CONCLUSION: Increased hs-CRP and IL-6 levels in the paroxysmal and permanent AF group may favour the hypothesis that low grade chronic inflammation could be the cause of atrial fibrillation than a consequence.

Association of neutrophil/lymphocyte ratio and CHA2DS2-VASc score with left atrial thrombus in patients who are candidates for percutaneous mitral balloon valvuloplasty.

OBJECTIVE: Association between inflammation and pro-thrombotic state has been described previously. Aim of the present study was to investigate if presence of left atrial (LA) thrombus or spontaneous echocardiographic contrast (SEC) in rheumatic mitral stenosis (MS) was related to neutrophil/lymphocyte ratio (NLR), and to determine predictive utility of the CHA2DS2-VASc risk stratification score in patients with mitral stenosis complicated by LA thrombus. METHODS: NLR and CHA2DS2-VASc score of 188 patients with MS and 35 healthy controls were evaluated. All analyses were also conducted according to rhythm status, excluding control group. RESULTS: Among patients with MS, there were 31 patients in thrombus-positive group, 142 patients in SEC-positive group, and 15 patients in thrombus/SEC-negative group. Among patients with MS and sinus rhythm (SR) (n=105; 55.8%); 9.5% of them had LA thrombus, and 78% of them had SEC. In the SR group, median NLR was significantly higher in thrombus-positive group compared with thrombus/SEC-negative and control groups (p<0.001). Among patients with MS and atrial fibrillation (AF); there was no significant difference regarding NLR according to thrombus and SEC presence (p=0.214). In both SR and AF groups, there was no significant difference according to SEC/thrombus presence regarding median CHA2DS2-VASc score (p>0.05). CONCLUSION: Elevated NLR is related to presence of LA thrombus in patients with MS and SR. The utility of CHA2DS2-VASc score in patients with MS and SR complicated by LA thrombus is debatable, according to our results.

The impact of cardiac rhythm on the mitral valve area and gradient in patients with mitral stenosis.

OBJECTIVE: The aim of this study was to evaluate the effect of cardiac rhythm on the echocardiographic mitral valve area (MVA) and transmitral gradient calculation in relation to net atrioventricular compliance (Cn). METHODS: Patients (n=22) with mild or moderate pure rheumatic mitral stenosis (MS) (MVA <2 cm2 and MVA >1 cm2) and atrial fibrillation (AF) were evaluated. All patients underwent transthoracic electrical DC cardioversion under amiodarone treatment. Nineteen of the 22 patients were successfully converted to sinus rhythm (SR). The patients were evaluated with transthoracic echocardiography before and two to three days after DC cardioversion. In order to deal with variable R-R intervals, the measurements were averaged on five to eight consecutive beats in AF. Cn was calculated with a previously validated equation [Cn (mL/mm Hg)=1.270 x MVA/E-wave downslope]. The Cn difference between AF and SR was calculated as follows: [(AF Cn-SR Cn)/AF Cn] x 100. The percentage gradient (mean or maximal) difference between AF and SR was calculated as follows: [AF gradient (mean or maximal) - SR gradient (mean or maximal)]/[AF gradient (mean or maximal)] x 100. RESULTS: The MVA was lower (MVA planimetric; 1.62±0.29 vs. 1.54±0.27; p=.003, MVA PHT; 1.66±0.30 vs. 1.59±0.26; p=0.01) but transmitral gradient (mean gradient; 6.49±2.51 vs. 8.89±3.52; p=0.001, maximal gradient: 16.94±5.11 vs. 18.57±4.54; p=0.01) and Cn values (5.37±0.77 vs. 6.26±0.64; p<0.001) were higher in the AF than SR. There was a significant correlation between Cn difference and transmitral gradient difference (mean and maximal) (Cn difference-mean gradient difference; r=0.46; p=0.05; Cn difference-maximal gradient difference; r=0.72; p=0.001). CONCLUSION: Cardiac rhythm has a significant impact on echocardiographic evaluation of MVA, transmitral gradient, and Cn in patients with MS.

The change in NT-pro-BNP and post-PTMC echocardiography parameters in patients with mitral stenosis. A pilot study.

BACKGROUND: The change in the level of NT-pro-BNP (N-terminal-pro-Brain Natriuretic Peptide) is now considered as a reflection of the hemodynamic alterations and its circulatory reductions reported early after successful PTMC (percutaneous transvenous mitral commissurotomy). The present study aims to assess the change in the level of NT-pro BNP following PTMC in patients with mitral stenosis and also to determine the association between circulatory NT-pro-BNP reduction and post-PTMC echocardiography parameters. METHODS: Twenty five symptomatic consecutive patients with severe MS undergoing elective PTMC were prospectively enrolled. All patients underwent echocardiography before and also 24 to 48 hours after PTMC. Peripheral blood samples were taken for measurement of NT-pro-BNP before as well as 24 to 48 hours after PTMC. The patients were also classified in group with normal sinus rhythm or having atrial fibrillation (AF) based on their 12-lead electrocardiogram. RESULTS: It was shown a significant decrease in the parameters of PPG (Peak Pressure Gradient), MPG (Mean Pressure Gradient), PHT (Pressure Half Time), PAP (Pulmonary Arterial Pressure), LAV (Left Atrial Volume), and also a significant increase in MVA (Mitral Valve Area) RVS (Right Ventricular S velocity), and strains of lateral, septal, inferior and anterior walls of LA following PTMC. The mean LVEF remained unchanged after PTMC. The mean NT-pro-BNP before PTMC was 309.20 ± 17.97 pg/lit that significantly diminished after PTMC to 235.72 ± 22.46 pg/lit (p = 0.009). Among all echocardiography parameters, only MPG was positively associated with the change in NT-pro-BNP after PTMC. Comparing the change in echocardiography indices between the patients with normal rhythm and those with AF, lower change in PAP was shown in the group with AF. However, more change in the level of NT-pro-BNP after PTMC was shown in the patients with AF compared to those without this arrhythmia. CONCLUSION: PTMC procedure leads to reduce the level of NT-pro-BNP. The change in NT-pro-BNP is an indicator for change in MS severity indicated by decreasing MPG parameter. Lower change in PAP as well as higher change in NT-pro-BNP is predicted following PTMC in the group with AF compared to those with normal sinus rhythm.

The Presence of Left Atrial Thrombus is Associated with the Neutrophil-to-Lymphocyte Ratio in Patients with Rheumatic Mitral Valve Stenosis.

BACKGROUND: Rheumatic mitral valve stenosis (RMVS)-induced left atrial thrombus (LAT) and embolic complications may have clinically devastating consequences. Stasis in the left atrium induced by valvular obstruction is a major factor in the development of thrombus. However, the development of thrombus may not be solely associated with stasis, as it is known that the inflammatory process increases the tendency for thrombosis. The study aim was to examine the relationship between the neutrophil-to-lymphocyte ratio (NLR), an indicator of inflammation, and the existence of LAT. METHODS: A total of 313 consecutive patients with RMVS and mitral valve area (MVA) <2 cm2 was included in this cross-sectional study. Patients were allocated to two groups with or without LAT using transthoracic and transesophageal echocardiography. Routine biochemical analyses and electrocardiographic examinations were also carried out. The NLR was calculated utilizing blood count analysis. RESULTS: The presence of LAT was identified in 78 RMVS patients (24.9%). No significant differences in terms of age, gender, body mass index were found between the groups with and without LAT. On echocardiographic examination, a higher mean gradient and left atrial diameter, as well as a smaller MVA, were determined in patients with LAT (p<0.001). In those patients with LAT, higher C-reactive protein levels and higher leukocyte and neutrophil counts (p <0.001) and lower lymphocyte counts were noted (p = 0.001). The NLR was shown to be higher in patients with LAT (p <0.001). Multivariate regression analysis showed that the relationship between LAT and a high NLR continued independently (OR 5.3; 95% CI 2.9-9.4; p <0.001). CONCLUSIONS: The NLR is an easily obtained, low-cost and easily repeated parameter that seems effective for identifying RMVS patients who are at high risk of developing LAT.

Serum Levels of IL-17 and IL-23 in Patients With Rheumatic Mitral Stenosis.

Rheumatic mitral valve stenosis (RMS) is a complication of rheumatic heart disease (RHD) and leads to significant morbidity and mortality. RHD is a chronic inflammatory and autoimmune disease that is associated with cytokine activities. The etiology of RMS is not fully understood yet. Interleukin (IL)-17 and IL-23 have a key role in development of the autoimmunity. The expression of these cytokines in RMS remains unclear. In this study, we investigated the serum levels of IL-17 and IL-23 in RMS patients compared to healthy subjects.A total of 35 patients admitted to cardiology outpatient clinic between December 2014 and May 2015 who were diagnosed with RMS formed the study group. Age- and gender-matched 35 healthy subjects were included as the control group. Statistical analyses were performed using SPSS 18.0 and P value <0.05 was considered as statistically significant.The patients with RMS had higher WBC count, hsCRP, systolic pulmonary artery pressure (PAPs), left atrial diameter (LAD), IL-17, and IL-23 levels compared to the control subjects. The levels of IL-17 (P = 0.012) and IL-23 (P = 0.004) were significantly higher in the RMS group. Correlation analysis revealed that IL-17 and IL-23 levels had a significant correlation with each other and with hsCRP and LAD.We demonstrated that serum levels of IL-17 and IL-23 are significantly higher in patients with RMS compared to those of healthy subjects. IL-17 and IL-23 expression may have a possible role in inflammatory processes that result in RMS development.

Lipoprotein(a) is a risk factor for aortic and mitral valvular stenosis in peripheral arterial disease.

AIMS: Lipoprotein(a) (Lp(a)) levels have been associated with aortic valvular calcification and stenosis. The prevalence and risk factors, including Lp(a) level, for valvular heart disease (VHD) were investigated in patients with peripheral arterial disease (PAD). METHODS AND RESULTS: Echocardiography was performed in 861 patients with PAD to detect abnormal cardiac findings. Relationships between VHD and risk factors were analysed. The prevalence of VHD was 43.6%, and the prevalences of aortic valve regurgitation (AR), mitral valve regurgitation (MR), aortic valve stenosis (AS), mitral valve stenosis (MS), and tricuspid regurgitation (TR) were 26.8, 19.7, 5.9, 1.3, and 9.4%, respectively. In stepwise multiple regression analysis, severity of AR was related to age, albumin, and estimated glomerular filtration rate (eGFR); MR was related to eGFR and age; AS was related to eGFR, Lp(a), and age; MS was related to Lp(a) and female gender; and TR was related to age, body mass index, and total cholesterol (all P < 0.05). Lp(a) level was higher in patients with AS compared with those without AS [34.0 (16.7-50.0) vs. 20.0 (11.0-35.0) mg/dL, P = 0.002], in patients with MS compared with those without MS [37.0 (21.5-77.3) vs. 21.0 (11.0-35.0), P = 0.037], and in patients with AS and/or MS compared with those without AS and MS [34.0 (17.3-50.0) vs. 20.0 (11.0-35.0), P = 0.001]. Lp(a) levels were related to low-density lipoprotein cholesterol and high-sensitivity C-reactive protein levels (P = 0.004). CONCLUSIONS: The high prevalence of VHD is found, especially in AR and MR, and the Lp(a) level is associated with increased risks of AS and MS in patients with PAD.

Effect of heart rate control on coagulation status in patients of rheumatic mitral stenosis with atrial fibrillation--A pilot study.

BACKGROUND AND AIM OF STUDY: Systemic thromboembolism is a major complication in patients of mitral stenosis (MS) with atrial fibrillation (AF) due to induction of hypercoagulable state. The aim was to assess the relationship, if any, between control of ventricular rate and systemic coagulation factors. METHOD: 70 patients of moderate to severe MS in AF were studied. 35 patients with average heart rate > 100 beats/min over a 24 hour period assessed by Holter monitoring were considered as having a uncontrolled ventricular rate (Group A) and those with average heart rate ≤ 100 beats/min as controlled ventricular rate (Group B). 30 healthy volunteers acted as controls. RESULTS: Plasma concentration of prothrombin fragment 1+2 (PF1+2) 6600 pmol/ml [interquartile range (IQR) 5400.0-9500], thrombin antithrombin III 22.0 ng/ml [IQR 18.6-28.0], and plasminogen activator inhibitor 46.8 ng/ml [IQR 44.0-54.0] were elevated in Group A as compared to Group B (5400 pmol/ml [IQR 3600-7700] p = 0.009, 16.0 ng/ml [IQR 11.0-18.5] p<0.001, and 25.8 ng/ml [IQR 20.9-34.4] p < 0.001), respectively. A significant correlation was found between heart rate and all three coagulation markers. Multivariate multiple regression analysis showed only heart rate to be an independent predictor of systemic coagulation activation and risk of thrombus formation. CONCLUSION: Control of ventricular rate in subjects of MS with AF produces significant reduction in the activation of the coagulation system and may decrease risk of thrombosis.