The predictive value of clinical, radiographic, echocardiographic variables and cardiac biomarkers for assessing risk of the onset of heart failure or cardiac death in dogs with preclinical myxomatous mitral valve disease enrolled in the DELAY study.

OBJECTIVES: To identify the predictive value on time to onset of heart failure (HF) or cardiac death of clinical, radiographic, and echocardiographic variables, as well as cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I in dogs with preclinical myxomatous mitral valve disease (MMVD). ANIMALS: One hundred sixty-eight dogs with preclinical MMVD and left atrium to aortic root ratio ≥1.6 (LA:Ao) and normalized left ventricular end-diastolic diameter ≥1.7 were included. METHODS: Prospective, randomized, multicenter, single-blinded, placebo-controlled study. Clinical, radiographic, echocardiographic variables and plasma cardiac biomarkers concentrations were compared at different time points. Using receiving operating curves analysis, best cutoff for selected variables was identified and the risk to develop the study endpoint at six-month intervals was calculated. RESULTS: Left atrial to aortic root ratio >2.1 (hazard ratio [HR] 3.2, 95% confidence interval [95% CI] 1.9-5.6), normalized left ventricular end-diastolic diameter > 1.9 (HR: 6.3; 95% CI: 3.3-11.8), early transmitral peak velocity (E peak) > 1 m/sec (HR: 3.9; 95% CI: 2.3-6.7), and NT-proBNP > 1500 ρmol/L (HR: 5.7; 95% CI: 3.3-9.5) were associated with increased risk of HF or cardiac death. The best fit model to predict the risk to reach the endpoint was represented by the plasma NT-proBNP concentrations adjusted for LA:Ao and E peak. CONCLUSIONS: Logistic and survival models including echocardiographic variables and NT-proBNP can be used to identify dogs with preclinical MMVD at higher risk to develop HF or cardiac death.

DELay of Appearance of sYmptoms of Canine Degenerative Mitral Valve Disease Treated with Spironolactone and Benazepril: the DELAY Study.

INTRODUCTION: Efficacy of renin-angiotensin-aldosterone system (RAAS) blockade using angiotensin-converting enzyme inhibitors (ACEi) in dogs with preclinical myxomatous mitral valve disease (MMVD) is controversial. HYPOTHESIS: Administration of spironolactone (2-4 mg q 24 h) and benazepril (0.25-0.5 mg q 24 h) in dogs with preclinical MMVD, not receiving any other cardiac medications, delays the onset of heart failure (HF) and cardiac-related death. Moreover, it reduces the progression of the disease as indicated by echocardiographic parameters and level of cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). ANIMALS: 184 dogs with pre-clinical MMVD and left atrium-to-aortic root ratio (LA:Ao) ≥1.6 and normalized left ventricular end-diastolic diameter (LVEDDn) ≥1.7. METHODS: This is a prospective, randomized, multicenter, single-blinded, placebo-controlled study. Primary outcome variable was time-to-onset of first occurrence of HF or cardiac death. Secondary end points included effect of treatment on progression of the disease based on echocardiographic and radiographic parameters, as well as variations of NT-proBNP and cTnI concentrations. RESULTS: The median time to primary end point was 902 days (95% confidence interval (CI) 682-not available) for the treatment group and 1139 days (95% CI 732-NA) for the control group (p = 0.45). Vertebral heart score (p = 0.05), LA:Ao (p < 0.001), LVEDDn (p < 0.001), trans-mitral E peak velocity (p = 0.011), and NT-proBNP (p = 0.037) were lower at the end of study in the treatment group. CONCLUSIONS: This study failed in demonstrating that combined administration of spironolactone and benazepril delays onset of HF in dogs with preclinical MMVD. However, such treatment induces beneficial effects on cardiac remodeling and these results could be of clinical relevance.

Assessment of mitral regurgitation severity by Doppler color flow mapping of the vena contracta in dogs.

BACKGROUND: Quantitative and semiquantitative methods have been proposed for the assessment of MR severity, and though all are associated with limitations. Measurement of vena contracta width (VCW) has been used in clinical practice. OBJECTIVE: To measure the VCW in dogs with different levels of MR severity. ANIMALS: Two hundred and seventy-nine dogs were classified according to 5 levels of MR severity. METHODS: This was a retrospective study. EROA and regurgitant volume calculated by the PISA method, were measured and indexed to BSA. Descriptive statistics were calculated for VCW and VCW index for all categories of MR severity. Spearman's rank correlation coefficients (ρs ) were calculated to compare the results of the different methods (VCW and VCW index vs RV PISA, RV PISA index, EROA, EROA index), and between VCW and VCW index versus MR severity. RESULTS: All Spearman's rank correlation coefficients were significant (P < .001). The median values of VCW resulted of 2.9 mm (IQR 3.4-2.5) and of 4.6 mm (IQR 5.4-4.1) in the groups previously classified as mild-to-moderate and moderate-to-severe, respectively. The median values of VCW index resulted of 4.4 mm/m(2) (IQR = 5.5-4.2) in mild-to-moderate MR and of 10.8 mm/m(2) (IQR = 12.8-9.4) in moderate-to-severe MR. CONCLUSION AND CLINICAL IMPORTANCE: This is not a validation study against any previously validated invasive gold standard, the VCW method has proved easy to employ and it might be an additional tool in quantifying disease severity that supports, rather than replace, data coming from other techniques in daily clinical practice and research.

Detection of benzo(a)pyrene photodegradation products using DNA electrochemical sensors.

The reactivity of photodegradation products of benzo(a)pyrene vs. DNA has been assessed using both genomic and oligonucleotide based DNA electrochemical sensors. The kinetic of a photooxidation reaction of benzo(a)pyrene (BaP) carried out in controlled conditions using a 6 W UV lamp peaked at 365 nm has been studied using LC with fluorimetric detection. Degradation of benzo(a)pyrene by both UV and UV/H(2)O(2) exhibited pseudo-first-order reaction kinetics with half-lives ranging from 3.0 to 9.8h depending on the pH and on the amount of H(2)O(2). The oxidation products of benzo(a)pyrene obtained in different conditions were tested on genomic ssDNA electrochemical sensors obtained via immobilisation of salmon testis ss-DNA on graphite screen-printed electrodes. Guanines oxidation signals obtained using chronopotentiometry were used to detect the interaction of the products with DNA. The dose-response curve obtained with benzo(a)pyrene incubated 24 h at pH 4.7 was different from that of the parent compound indicating a different type of interaction with DNA. A DNA hybridisation sensor was also assembled using a thiolated/biotynilated 24-mer oligonucleotide immobilised on a gold screen-printed electrode and avidin-alkaline phosphatase conjugate. A voltammetric detection of naphtol was used to detect the hybridisation reaction. A net inhibition of the hybridisation reaction was observed after incubation with benzo(a)pyrene oxidation products that was attributed to the formation of stable adducts with the guanines of the biotinylated strand. LC-MS-MS studies of the oxidation products confirmed the presence of chemical species potentially forming adducts with DNA. The data reported demonstrate that DNA electrochemical sensors have the potential to be used to monitor remediation processes and to assess the potential toxicity vs. DNA of chemicals forming stable DNA adducts.