Project description:Evaluation of global expression patterns provides a molecular portrait of mitral valve disease, yields insight into the pathophysiologic aspects of DMVD, and identifies intriguing genes and pathways for further study. (Am J Vet Res 2006;67:1307–1318) Keywords: control vs diseased 4 controls( beagle crosses) and 4 affected (1 Daschund, 1 Lhasa apso, 2 miniature poodles)
Project description:ObjectiveIntraoperative predictors of functional mitral valve (MV) stenosis after surgical repair of mitral regurgitation (MR) caused by prolapse remain poorly characterised. This study evaluated the effect of annuloplasty size on postoperative MV haemodynamics during exercise and evaluated predictors of MV hemodynamics.Methods104 patients were randomly assigned to leaflet resection or preservation for surgical repair of MR in the Canadian Mitral Research Alliance CardioLink-2 study. In this post hoc analysis, we compared MV haemodynamics between the two surgical groups and examined the relationship between annuloplasty size and MV haemodynamics 1 year after repair in the combined groups. Echocardiograms were performed at baseline and intraoperatively. Exercise transthoracic echocardiography was performed 1 year postoperatively. Multivariable linear regression analysis was used to identify predictors of exercise MV gradients at follow-up.ResultsMean age of participants was 65±10 years, and 83% were male. Median annuloplasty size was 34 (IQR 32-36). Dividing by the median, 48 (46%) had annuloplasty size of <34 mm and 56 (54%) had ≥34 mm. Mean and peak exercise gradients at 1 year were 11±5 mm Hg and 22±9 mm Hg in <34, and 6±3 mm Hg and 14±5 mm Hg in ≥34 (p<0.001). Rate of residual MR was similar in both groups. In multivariable analyses, annuloplasty size of ≥34 mm was associated with lower mean and peak exercise gradients at 12 months, after adjustment for repair type, age, sex, heart rate and body surface area (β -4.1, 95% CI -6 to -3, p<0.001, and β -7 95% CI -10 to -4, p<0.001, respectively). Intraoperative mean and peak MV gradients by transesophageal echocardiography independently predicted mean and peak resting and exercise gradients at follow-up (p<0.001). Similar results were obtained in both leaflet resection and preservation.ConclusionAnnuloplasty size of ≥34 mm is associated with a 4 and 7 mm Hg reduction in mean and peak exercise MV gradients, respectively, 1 year post MV repair regardless of the repair strategy used. Intraoperative TEE MV gradients predict exercise MV gradients 1 year post repair.Trial registration numberNCT02552771.
Project description:Evaluation of global expression patterns provides a molecular portrait of mitral valve disease, yields insight into the pathophysiologic aspects of DMVD, and identifies intriguing genes and pathways for further study. (Am J Vet Res 2006;67:1307–1318) Keywords: control vs diseased
Project description:Degenerative mitral valve disease (DMVD) is the most common cardiac disease in dogs. Some signaling pathways have been implicated in DMVD, including the serotonin and TGF-beta pathways. We sought to identify additional molecular and metabolic pathways that contribute to DMVD using transcriptomic and metabolomic studies. RNA-seq gene expression evaluated on total RNA isolated from left ventricle (LV) and mitral valve (MV) identified 812 differentially expressed transcripts (DETs) in LV and 263 DETs in MV. Out of 15 transcripts selected for RT-qPCR validation, we confirmed 13. In addition, serum samples were collected for metabolomic evaluation. Endothelial nitric oxide synthase (eNOS) was significantly up-regulated in both LV and MV while the level of circulating asymmetrical dimethyl arginine (ADMA), an endogenous NOS inhibitor, was lower in DMVD. Expressions of matrix metalloproteinases (MMP) and their endogenous inhibitor tissue inhibitor of matrix metallopeptidases (TIMP) were altered. This study demonstrates transcript and metabolite differences consistent with increased nitric oxide (NO) and reactive oxygen species (ROS) production, impaired fatty acid transport and oxidation, and increased glucose uptake and glycolysis in DMVD. Our findings are consistent with metabolic conversion in the DMVD heart from oxidative metabolism to glycolysis along with an increased concentration of NO and ROS activity suggesting an alternative signaling effect. Alterations of redox-sensitive NO signaling may play a role in ECM (ECM) homeostasis via modulating MMP and TIMP expression.
Project description:ObjectivesThe risk factors and clinical effect of elevated mitral valve (MV) gradients after valve repair for degenerative valve disease remain insufficiently understood.MethodsBetween January 2004 and December 2015, a total of 484 patients underwent valve repair for degenerative disease. A true-sized full annuloplasty ring was implanted in all cases. We analysed the effect of preoperative and intraoperative factors on the postrepair gradient. Additionally, we explored the effect of postrepair gradients on long-term outcomes.ResultsOn linear regression analysis, postrepair MV gradients were associated with patient age (coefficient?=?-0.110, standard error?=?0.005, P?=?0.034), body surface area (coefficient?=?0.905, standard error?=?0.340, P?=?0.008), implanted annuloplasty ring size (coefficient?=?-0.181, standard error?=?0.018, P?<?0.001) and the use of Physio I ring (coefficient?=?0.414, standard error?=?0.122, P?=?0.001). On multivariable analysis, postrepair MV gradient was not associated with overall survival [hazard ratio (HR) 1.034, 95% confidence interval (CI) 0.889-1.203; P?=?0.66] or freedom from atrial fibrillation (HR 0.849, 95% CI 0.682-1.057; P?=?0.14), but did emerge as a risk factor for MV reintervention (HR 1.378, 95% CI 1.033-1.838; P?=?0.029). Two out of 11 reinterventions were performed due to MV stenosis and in both patients, high postrepair gradients were seen readily on predischarge echocardiography.ConclusionsFollowing valve repair for degenerative MV disease, elevated gradients occur even when true-sized annuloplasty is performed. The late clinical results of valve repair with elevated postrepair gradient are impaired and further studies are needed to explore preventive measures aimed at resolving the issue.
Project description:PurposeThis study explored the sex differences in the outcomes of degenerative mitral valve repair (MVr).MethodsFrom 2010 to 2019, 1069 patients who underwent MVr due to degenerative mitral disease at Beijing Anzhen Hospital were analyzed. The average patient follow-up was 5.1 years (interquartile range: 5-7 years). The primary endpoint was overall survival. Secondary endpoints were freedom from reoperation and recurrent mitral regurgitation. A propensity-matched analysis was used to compare the outcomes of males and females.ResultsFemales were older, had a higher prevalence of atrial fibrillation and moderate-to-severe tricuspid regurgitation, and had smaller left atrial, left ventricular end-diastolic, and left ventricular end-systolic diameters. Males were more likely to undergo concomitant coronary artery bypass grafting and had longer cardiopulmonary bypass and aortic cross-clamp times. The in-hospital mortality was <1% (10/1,069). After propensity score matching of 331 pairs of patients, most variables were well balanced. Before and after propensity score matching, the long-term survival and freedom from reoperation rates were similar. Males had higher durability after surgery compared with females.ConclusionsFemales were referred to surgery later and had more complications than males. Long-term survival and freedom from reoperation rates were not significantly different between the sexes.
Project description:We aimed to compare the outcomes of mitral valve repair with flexible band (FB) versus complete semirigid ring (SR) in degenerative mitral valve disease patients.From September 2011 to 2014, 171 patients were randomized and underwent successful mitral valve repair using a SR (n?=?85) or FB (n?=?86). There were no significant between-group differences at baseline.There were no early mortalities. The mean follow up was 24.7 months. The 2-year survival was 96.0?±?2.3% (95% confidence interval [CI], 88.6-98.7%) and 94.3?±?2.8% (95% CI, 85.5-97.9%) in the SR and FB groups, respectively (p?=?0.899). The left ventricle remodeling was similar between the groups. Higher transmitral peak (8.5 [3.9-17] vs. 6 [2.1-18] mmHg, p?<?0.001), mean pressure gradients (3.7 [1.3-8] vs. 2.8 [0.6-6.8] mmHg, p?=?0.001), and systolic pulmonary artery pressure (34.5 [20-68] vs. 29.5 [8-48] mmHg, p?<?0.001) was observed in the SR group. The 2-year freedom from recurrence of significant mitral regurgitation was significantly higher in the FB group than the SR group (p?=?0.002). Residual mitral regurgitation was an independent prognostic factor of recurrence of mitral regurgitation. The 3-year freedom from reoperation was significantly higher in the FB group than the SR group (p?=?0.044).Patients with degenerative mitral valve disease may benefit from valve repair with FBs. Residual mitral regurgitation before discharge is an independent risk factor of late insufficiency recurrence.ClinicalTrials.gov NCT03278574 , retrospectively registered on 06.09.2017.
Project description:ObjectiveThe relationship of mitral annular (MA) kinetics to left ventricular (LV) and left atrial (LA) function before and after mitral valve (MV) repair has not been well studied. Here we sought to provide comprehensive analysis that relates to MA motions, and LA and LV diastolic function post MV repair.MethodsThree-dimensional analyses of mitral annular motion, LA function, and LV volumetric and diastolic strain rates were performed on 35 degenerative mitral regurgitation (MR) patients at baseline and 1-year post MV repair, and 51 normal controls, utilizing cardiac magnetic resonance imaging with tissue tagging.ResultsAll had normal LV ejection fraction (EF) at baseline. LV and LA EFs decreased 1-year post-surgery vs. controls. LV early diastolic myocardial strain rates decreased post-surgery along with decreases in normalized early diastolic filling rate, E/A ratio, and early diastolic MA relaxation rates. Post-surgical LA late active kick remained higher in MR patients vs. control. LV and LA EFs were significantly associated with peak MA centroid to apex shortening. Furthermore, during LV systolic phase, peak LV ejection and LA filling rates were significantly correlated with peak MA centroid to apex shortening rate, respectively. While during LV diastolic phase, both peak early diastolic MA centroid to apex relaxation rate and LA ejection rate were positively significantly associated with LV peak early diastolic filling rate.ConclusionMA motion is significantly associated with LA and LV function. Mitral annular motion, left atrial function, and LV diastolic strain rates are still impaired 1 year post MV repair. Long-term effects of these impairments should be prospectively evaluated.
Project description:Objective:The aim of this study is to evaluate mitral valve hemodynamics after mitral valve repair for degenerative disease, and seek the impact of type/size of annuloplasty prosthesis on resting cardiac hemodynamics. Methods:Between October 2012 and June 2019, 301 patients underwent isolated mitral valve repair for degenerative disease were enrolled. Correlation between postoperative mitral hemodynamics and type/size of annuloplasty prosthesis was evaluated. Results:There were significant correlations between annuloplasty size and peak velocity (r = -0.41, p < 0.001), peak transmitral pressure gradient (TMPG) (r = -0.40, p < 0.001), mean TMPG (r = -0.41, p < 0.001), effective orifice area (EOA) (r = 0.26, p < 0.001), and pulmonary artery systolic pressure (r = -0.15, p = 0.010). In patients with larger annuloplasty prostheses (?30 mm), the type of annuloplasty prosthesis (band or ring) did not influence the mitral hemodynamics, however, mean TMPG was significantly greater in patients with a full ring (2.9 mmHg [2.1-3.7] vs. 4.0 mmHg [2.8-5.0], p < 0.001) in patients with smaller annuloplasty (<30 mm). Left ventricular ejection fraction and stroke volume were significantly associated with an increase of TMPG (r = 0.14, p = 0.016 and r = 0.24, p < 0.001). Conclusions:A larger partial band had the potential to improve mitral hemodynamics after mitral repair for degenerative disease. However, echocardiographic mitral hemodynamics was influenced by LV function. Therefore, a more accurate method is required to elucidate the true impact of mitral repair on hemodynamics.
Project description:BackgroundSeveral risk factors already have been determined for dogs with degenerative mitral valve disease (DMVD). Risk factors often have been considered in isolation and have not always taken into account additional information provided by the history and physical examination (PE).Hypothesis/objectivesData obtained from history and PE of dogs with DMVD provide prognostic information and can be used for risk stratification.AnimalsClient-owned dogs (n = 244) with DMVD recruited from first opinion practice.MethodsProspective longitudinal follow-up of dogs with DMVD. History and PE data were obtained at 6-month intervals and analyzed with time-dependent Cox models to derive relative risk of cardiac death. Independent hazard ratios were used to derive a clinical severity score (CSS), the prognostic value of which was evaluated by analyzing the median survival times for different risk groups and ROC analysis. Analysis of the progression of CSS over time also was undertaken.ResultsHistory of cough, exercise intolerance, decreased appetite, breathlessness (difficulty breathing) and syncope with PE findings of heart murmur intensity louder than III/VI and absence of respiratory sinus arrhythmia were independently associated with outcome and allowed development of the CSS. Clinical severity score distinguished groups of dogs with significantly different outcomes.Conclusions and clinical importanceRoutinely obtained clinical findings allow risk stratification of dogs with DMVD. Results of ancillary diagnostic tests may be complementary to history and PE findings and always should be interpreted in conjunction with these findings.