Assessment of myocardial fibrosis by late gadolinium enhancement imaging and biomarkers of collagen metabolism in chronic rheumatic mitral regurgitation.

BACKGROUND: In chronic rheumatic mitral regurgitation (CRMR), involvement of the myocardium in the rheumatic process has been controversial. Therefore, we sought to study the presence of fibrosis using late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) and biomarkers of collagen turnover in CRMR. METHODS: Twenty-two patients with CRMR underwent CMR and echocardiography. Serum concentrations of matrix metalloproteinase- 1 (MMP-1), tissue inhibitor of MMP-1 (TIMP- 1), MMP-1-to-TIMP-1 ratio, procollagen III N-terminal pro-peptide (PIIINP) and procollagen type IC peptide (PIP) were measured. RESULTS: Four patients had fibrosis on LGE-CMR. PICP and PIIINP concentrations were similar to those of the controls, however MMP-1 concentration was increased compared to that of the controls (log MMP-1 3.5 ± 0.7 vs 2.7 ± 0.9, p = 0.02). There was increased MMP-1 activity as the MMP-1-to- TIMP-1 ratio was higher in CRMR patients compared to the controls ( -1.2 ± 0.6 vs -2.1 ± 0.89, p = 0.002). CONCLUSIONS: Myocardial fibrosis was rare in CRMR patients. CRMR is likely a disease characterised by the predominance of collagen degradation rather than increased synthesis and myocardial fibrosis.

Serum paraoxonase 1 activity and lipid metabolism parameter changes in Dachshunds with chronic mitral valve disease. Assessment of its diagnostic usefulness.

Chronic mitral valve disease, which is frequently diagnosed in Dachshunds, leads to structural, hemodynamic and redox state changes in dogs. The aim of this study was to investigate serum paraoxonase 1 (PON1) activity and lipid metabolism in different disease stages. Standardized PON1 activity (PON1/HDL ratio) was lower in asymptomatic dogs, B1 and B2 Stages when compared to healthy ones and symptomatic Dachshunds in Stage C (ACVIM classfication). PON1 paraoxonase activity was elevated in Stage C dogs, with no changes found in PON1 activity towards phenyl acetate. Dachshunds in Stage B2 and C showed increased triglyceride levels, with no changes in cholesterol and lipoprotein concentration in comparison to healthy ones. Our data suggest that standardized PON1 activity changes could be used in laboratory diagnostics to differentiate the CMVD of affected asymptomatic (Stage B1 and B2) dogs from healthy (Stage A) and clinically affected (Stage C) dogs. Also, a standardized PON1 activity increase might be a prognostic progression signal of the disease to Stage C.

Usefulness of NT-proBNP in the assessment of patients with aortic or mitral regurgitation.

BACKGROUND: Recent application of brain natriuretic peptide and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in cardiac valvular disease is very promising. AIMS: To test the usefulness of NT-proBNP in the assessment of patients with aortic or mitral regurgitation. PATIENTS AND METHODS: Sixty-seven patients - 23 with aortic and 12 with mitral regurgitation vs. 32 controls - were examined by color Doppler echocardiography, cardiopulmonary exercise testing, Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and plasma NT-proBNP assay at rest (T0) and after maximal physical exercise (T1). RESULTS: NT-proBNP was significantly higher in patients than in controls, both at T0 (298 +/- 85 vs. 46 +/- 11 pg/ml; P < 0.01) and at T1 (366 +/- 106 vs. 50 +/- 12 pg/ml; P < 0.01). MLWHFQ score was significantly higher in patients (19 +/- 3 vs. 1 +/- 0.6; P < 0.001) with a significant inverse correlation with VO2max (r = -0.538, P < 0.001) and a direct correlation with NT-proBNP (T0: r = 0.415, P < 0.01; T1: r = 0.458, P < 0.01). NT-proBNP was inversely correlated with VO2max (T0: r = -0.444, P < 0.001; T1:r = -0.428, P < 0.001) and directly correlated with left atrial diameter (T0: r = 0.370, P < 0.01; T1: r = 0.409, P = 0.001), and left ventricular mass index (r = 0.279, P < 0.01, and r = 0.272, P < 0.01). No correlations were found between echocardiographic parameters of valvular disease severity and VO2max, NT-proBNP and MLWHFQ. CONCLUSIONS: NT-proBNP is useful in the assessment of the cardiac functional damage secondary to mitral and aortic regurgitation.

Plasma N-terminal protype-B natriuretic peptide levels in risk assessment of patients with mitral regurgitation secondary to ischemic and nonischemic dilated cardiomyopathy.

BACKGROUND: Functional mitral regurgitation (MR) is a factor affecting prognosis of patients with chronic left ventricular (LV) dysfunction. The aim of the study was to investigate whether the evaluation of plasma N-terminal protype-B natriuretic peptide (NT-proBNP) concentrations is useful for prognostic assessment of patients with functional MR due to either ischemic or nonischemic chronic LV dysfunction. METHODS: Echocardiograms were obtained in 207 patients with chronic LV dysfunction (ejection fraction or=0.7 cm raised MR grade to severe. Median follow-up duration was 29 months. RESULTS: The NT-proBNP levels increased significantly with MR severity. At multivariate analysis, NT-proBNP was an independent predictor of cardiac death (hazard ratio 2.17, CI 1.10-4.30, P = .026) and the most powerful predictor of cardiac death or heart failure-related hospitalization (hazard ratio 3.19, CI 1.89-5.37, P < .0001). A progressively worse outcome was apparent when patients were stratified by a graded increase in MR severity and by quartiles of NT-proBNP levels. Increased NT-proBNP concentrations and more-than-mild MR identified patients with the highest risk of cardiac mortality. CONCLUSION: Assessment of plasma NT-proBNP allows for stratifying patients with functional MR regardless of their degree of valvular incompetence. Even in case of only mild or moderate MR, but increased NT-proBNP, patients have to face poor outcome.

Assessment of changes in hemostatic markers in Cavalier King Charles Spaniels with myxomatous mitral valve disease.

OBJECTIVE: To evaluate markers of hemostasis and their relationship to the degree of mitral regurgitation (MR) and platelet function in Cavalier King Charles Spaniels (CKCSs) with myxomatous mitral valve disease. ANIMALS: 76 clinically healthy CKCSs and 24 control dogs. PROCEDURE: All dogs underwent echocardiographic examination; various hemostatic, hematologic, and biochemical variables were evaluated in blood. The CKCSs were allocated to 1 of 3 groups on the basis of MR severity. In 8 control dogs and 8 CKCSs, plasma von Willebrand factor (vWF) multimer analysis was performed. RESULTS: Compared with control dogs, plasma fibrinogen concentration was higher in all CKCSs and related to left ventricular end diastolic diameter and left atrial-to-aortic root ratio among all CKCSs. The activated partial thromboplastin times and plasma D-dimer concentration were similar among the 4 groups. Plasma vWF concentration was lower in CKCSs with moderate to severe MR, compared with that of CKCSs with no MR and control dogs. There was a relationship between plasma vWF concentration and platelet function in CKCSs but not in control dogs. In 4 CKCSs with moderate to severe MR and low plasma vWF concentration, amounts of vWF high-molecular-weight multimers (HMWMs) were low. CONCLUSIONS AND CLINICAL RELEVANCE: In CKCSs, MR appeared to be associated with a low plasma vWF concentration and likely a loss of vWF HMWMs (possibly through their destruction via shear stress to the blood). The importance of the changes in plasma fibrinogen concentration and the thromboembolic risk in dogs with MR remain to be investigated.