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To compare conventional and three-dimensional (3D) echocardiographic indices of right ventricular (RV) systolic function in dogs with various stages of myxomatous mitral valve disease (MMVD), classified according to the 2009 guidelines of the American College of Veterinary Internal Medicine (ACVIM), with those from normal dogs. Seventy-eight unsedated dogs (22 healthy controls, 23 ACVIM stage B1 MMVD, 20 ACVIM stage B2 MMVD, and 13 ACVIM stage C MMVD) were included in the study. All dogs underwent conventional and 3D echocardiography. Three-dimensional RV end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) were recorded. Right ventricular EDV, ESV, and SV were indexed to bodyweight. Echocardiographic variables were compared across groups using a Kruskal–Wallis test with subsequent post hoc analysis using Dunn's method for multiple comparisons between groups. A P-value of <0.05 was considered significant. Right ventricular EDV was smaller in stage B1 (P=0.012), stage B2 (P=0.035), and stage C (P=0.004) dogs than in controls. Stage B2 (P=0.003) and stage C (P<0.001) dogs had smaller RV ESV than controls. Stage B1 dogs had smaller RV SV than controls (P=0.012). Right ventricular EF was greater in stage C dogs than in controls (P=0.003) and in stage B1 (P=0.017) dogs. Several 3D echocardiographic indices of RV systolic function differ between dogs with advanced MMVD when compared with normal dogs. Further investigation is required to determine if these differences have clinical implications. [ABSTRACT FROM AUTHOR]

Background: Reliability of echocardiographic calculations for stroke volume and mitral regurgitant fraction (RFMR) are affected by observer variability and lack of a gold standard. Variability is used to calculate critical change values (CCVs) that are thresholds representing real change in a measure not associated with observer variability. Hypothesis: Observed intra‐ and interobserver accuracy and variability in healthy dogs help model CCV for RFMR. Animals: Reliability cohort of 34 healthy dogs; allometric scaling cohort of 99 dogs with heart disease and 25 healthy dogs. Methods: Accuracy, variability, and CCV of 2 observers using geometric and flow‐based echocardiography were prospectively compared against a standard of RFMR = 0% and extrapolated across a range of expected RFMR values in the reliability cohort partly derived from cardiac dimensions predicted by the allometric cohort. Results: Accuracy of methods to determine RFMR in descending order was 4‐chamber bullet (Bullet4CH), mitral inflow, cube formula, and Simpson's method of disks. Intraobserver variability was relatively high. The CCV for RFMR ranged from 28% to 88% and was inversely related to RFMR when extrapolated for use in affected dogs. For both observers, the Bullet4CH method had the lowest intraobserver CCV (Operator 1:28%, Operator 2:41%). Interobserver strength of agreement was low with intraclass correlation coefficients ranging from 0.210 to 0.413. Conclusions and Clinical Importance: Echocardiographic volumetric methods used to calculate stroke volume and RFMR have low accuracy and high variability in healthy dogs. Extrapolation of observed CCV to a range of expected RFMR suggests observers and methods are not interchangeable and variability might hinder routine clinical usage. Individual observers should be aware of their own variability and CCV. [ABSTRACT FROM AUTHOR]

Background: Re-evaluation of reconstructive possibilities in the correction of degenerative mitral valve disease is of great clinical necessity nowadays. Material and methods: Analyzing the nature of the pathologies that determined the development mechanism of valve insufficiency, 136 cases of anterior cusp prolapse and 152 cases of posterior cusp prolapse were determined. Results: Cord rupture was established in 79 (58.9%) patients, cusp defects (”Cleft”) were appreciated in positions A1, A2, A3 – 15 cases (5.9%) and in P1, P2, P3 – in 92 (86.6%) cases. The surgical techniques performed were separated into: (1) resection – for the anterior and posterior cusps – 45 cases and accompanied by the slide – in 30 cases; (2) with Gore-Tex neo-chordal implantation – 115 cases, with cord transfer – 30; (3) Cusp enlargement with autologous pericardium – 5 cases, Alfieri procedure – 8. Implantation of a support ring required 130 (97.0%) patients. The correction of the associated valve disease required 125 patients (De Vega – 89.1%, ring – 8). Coronary bypass was required – 16 patients. There were no postoperative fatal cases. Conclusions: Based on the data obtained, reconstructive repair surgery can be can recommend for valves of degenerative, post-traumatic, ischemic, post-endocardial etiology as effective and sustainable techniques over time, being a superior alternative to replacement with prosthetic valves.

High-throughput metabolomics techniques are a useful tool to understand many disease conditions including cardiovascular disease such as valvular heart disease(s) (VHD). VHD involves damage to heart valves, mostly presenting as stenosis, regurgitation or prolapse and can be classified into degenerative, rheumatic, congenital, or prosthetic valve disease. Gaps remain in our understanding of the pathogenesis of the common VHD. It is now fitting to place into perspective the contribution of metabolomics in the mechanism of development, diagnosis, and prognosis of VHD. A structured search for metabolomics studies centred on human VHD was undertaken. Biomarkers associated with the pathogenesis of bicuspid aortic valve disease, mitral valve disease, rheumatic heart disease, and degenerative aortic valve stenosis are reviewed and discussed. In addition, metabolic biomarkers reported to prognosticate patient outcomes of post-valve repair or replacement are highlighted. Finally, we also review the pitfalls and limitations to consider when designing metabolomics studies, especially from a clinician's viewpoint. In the future, reliable and simple metabolic biomarker(s) may supplement the existing diagnostic tools in the early diagnosis of VHD. [ABSTRACT FROM AUTHOR]

High-throughput metabolomics techniques are a useful tool to understand many disease conditions including cardiovascular disease such as valvular heart disease(s) (VHD). VHD involves damage to heart valves, mostly presenting as stenosis, regurgitation or prolapse and can be classified into degenerative, rheumatic, congenital, or prosthetic valve disease. Gaps remain in our understanding of the pathogenesis of the common VHD. It is now fitting to place into perspective the contribution of metabolomics in the mechanism of development, diagnosis, and prognosis of VHD. A structured search for metabolomics studies centred on human VHD was undertaken. Biomarkers associated with the pathogenesis of bicuspid aortic valve disease, mitral valve disease, rheumatic heart disease, and degenerative aortic valve stenosis are reviewed and discussed. In addition, metabolic biomarkers reported to prognosticate patient outcomes of post-valve repair or replacement are highlighted. Finally, we also review the pitfalls and limitations to consider when designing metabolomics studies, especially from a clinician’s viewpoint. In the future, reliable and simple metabolic biomarker(s) may supplement the existing diagnostic tools in the early diagnosis of VHD.

Objectives: To determine the frequency of obstructive coronary artery disease in patients undergoing valvular heart disease surgery. Study Design: Cross-sectional study. Setting: Department of Cardiology, Faisalabad Institute of Cardiology, Faisalabad. Period: Ten months, from 02 February, 2017 to 02 November, 2017. Material & Methods: After taking approval from hospital ethical committee, patients coming through outpatient department who fulfilled the inclusion criteria were enrolled and informed consent was taken from them. History of smoking, diabetes mellitus, renal dysfunction, dyslipidemia, hypertension and family history of coronary artery disease was assessed. Coronary angiography was performed by senior consultant interventional cardiologist for assessing obstructive coronary artery disease as per operational definition. All the information was collected on prespecified Performa. Results: In this study, out of 140 cases of valvular heart disease (VHD), 47.14%(n=66) were between 3050 years of age whereas 52.86%(n=74) were between 51-70 years of age, mean ±sd was calculated as 51.71± 9.09 years, 57.14%(n=80) were male while 42.86%(n=60) were female, frequency of obstructive coronary artery disease in patients undergoing valvular heart surgery was recorded as 29.3% (n=41) whereas 70.7% (n=99) had no such finding. Conclusion: The frequency of obstructive coronary artery disease was (29.3%) in patients undergoing valvular heart disease surgery. However, coronary artery disease was less frequent in rheumatic as compared to degenerative heart valve disease. [ABSTRACT FROM AUTHOR]

Abstract: Myxomatous mitral valve disease (MMVD) is the most commonly diagnosed cardiovascular disease in the dog accounting for more than 70% of all cardiovascular disease in dogs. As are most canine diseases with genetic underpinnings, risk of MMVD is greatly increased in a subset of breeds. What is uncommon is that the vast majority of the breeds at elevated risk for MMVD are small or toy breeds with average adult weights under 9 kg. These breeds appear to have little in common other than their diminutive size. In the following review we propose a number of mechanisms by which relatively unrelated small breeds may have developed a predisposition for chronic valvular disorders. Although factors such as age are key in the expression of MMVD, taking a comprehensive look at the commonalities, as well as the differences, between the susceptible breeds may assist in finding the causal variants responsible for MMVD and translating them to improved treatments for both dogs and humans. [Copyright &y& Elsevier]

ortic stenosis (AS) is the most frequent valvular heart disease. Severe AS results in concentric left ventricular hypertrophy, and ultimately, the heart dilates and fails. During a long period of time patients remain asymptomatic. In this period a pathology progression should be monitored and effectively thwarted by targeted measures. A cascade of cellular and molecular events leads to chronic degeneration of aortic valves. There are some molecular attributes characteristic for the process of valvular degeneration with clear functional link between shifted cell-cycle control, calcification and tissue remodelling of aortic valves. Bioactivity of implanted bioprosthesis is assumed to result in its dysfunction. Age, gender (females), smoking, Diabetes mellitus, and high cholesterol level dramatically shorten the re-operation time. Therefore, predictive and preventive measures would be highly beneficial, in particular for young female diabetes-predisposed patients. Molecular signature of valvular degeneration is reviewed here with emphases on clinical meaning, risk-assessment, predictive diagnosis, individualised treatments. [ABSTRACT FROM AUTHOR]

Age-related, degenerative aortic valve disease is of great concern for the current aging population, and the only current treatment option is replacement, necessitating open-chest surgery. While the initial disease mechanism may involve the endothelial cells that sheath the valve leaflets, there is strong evidence supporting the notion that it is in fact a malfunction of the robust interstitial cells within the leaflet tissue that perpetuate the disease through a presently unclear sequence of events. In this article, recent data are discussed regarding mechanobiology of the interstitial cell, with particular focus on modulation of the phenotype and subsequent biosynthetic function. Moreover, speculation of potential mechanisms that may ultimately lead to degenerative aortic valve disease are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Background: Phenotypically, aortic valve interstitial cells are dynamic myofibroblasts, appearing contractile and activated in times of development, disease, and remodeling. The precise mechanism of phenotypic modulation is unclear, but it is speculated that both biomechanical and biochemical factors are influential. Therefore, we hypothesized that isolated and combined treatments of cyclic tension and transforming growth factor-β1 would alter the phenotype and subsequent collagen biosynthesis of aortic valve interstitial cells in situ. Methods and results: Porcine aortic valve leaflets received 7- and 14-day treatments of 15% cyclic stretch (Tension); 0.5 ng/ml transforming growth factor-β1 (TGF); 15% cyclic stretch and 0.5 ng/ml transforming growth factor-β1 (Tension+TGF); or neither mechanical nor cytokine stimuli (Null). Tissues were homogenized and assayed for aortic valve interstitial cell phenotype (smooth muscle α-actin) and collagen biosynthesis (via heat shock protein 47, which was further verified with type I collagen C-terminal propeptide). At both 7 and 14 days, smooth muscle α-actin, heat shock protein 47, and type I collagen C-terminal propeptide quantities were significantly greater (P<.001) in the Tension+TGF group than in all other groups. Additionally, Tension alone appeared to maintain smooth muscle α-actin and heat shock protein 47 levels that were measured on Day 0, while TGF alone elicited an increase in smooth muscle α-actin and heat shock protein 47 compared to Day 0 levels. Null treatment revealed diminished proteins at both time points. Conclusions: Elevated transforming growth factor-β1 levels, in the presence of cyclic mechanical tension, resulted in synergistic increases in contractile and biosynthetic proteins in aortic valve interstitial cells. Since cyclic mechanical stimuli can never be relieved in vivo, the presence of transforming growth factor-β1 (possibly from infiltrating macrophages) may result in overly biosynthetic aortic valve interstitial cells, leading to altered extracellular matrix architecture, compromised valve function, and, ultimately, degenerative valvular disease. [Copyright &y& Elsevier]

Objectives We aimed to assess the influence of type of operation on outcome in degenerative mitral regurgitation. Methods We compared outcomes in 278 consecutive patients who underwent mitral valve repair (167 patients), replacement with subvalvular preservation (22 patients) and without subvalvular preservation (89 patients) for degenerative mitral regurgitation. Results There was a trend towards lower mortality with repair and replacement with subvalvular preservation compared to replacement without subvalvular preservation. Thirty-day mortality was 1·2% vs 0·0% vs 4·7% (ns) respectively. Six-year survival was, respectively, 67·8±7·4% (P=0·088) vs 80·8±11·0% (P=0·25 vs 63·3±5·9% for all-cause death, 78·5±6·8% (P=0·063) vs 95·5±4·4% (P=0·092) vs 67·6±5·9% for all complication-related death and 80·5±6·9% (P=0·076) vs 100·0±0·0% (P=0·045) vs 72· ± 5·8% for complication-related death due to myocardial failure. Multivariate analysis confirmed independent beneficial effects from repair compared to replacement without subvalvular preservation on complication-related death (hazard ratio 0·42, P=0·010) and death from myocardial failure (hazard ratio 0·40 P=0·014), and from repair compared to mechanical replacement on thromboembolism (hazard ratio 0·45, P=0·029) and anticoagulation-related haemorrhage (hazard ratio 0·19, P=0·026). Conclusions Mitral valve repair is superior to replacement. The greatest survival advantage is in reduced mortality from myocardial failure. Repair should be the operation of choice for degenerative mitral regurgitation. [ABSTRACT FROM PUBLISHER]

Objectives: Little is known about contemporary characteristics and management of valvular heart disease (VHD) in China. This study aimed to examine the clinical characteristics, aetiology and type of VHD, interventions and in-hospital outcomes of patients with VHD hospitalised in China., Methods: We used a two-stage random sampling design to create a nationally representative sample of patients with VHD hospitalised in 2015 in China and included adult patients with mild, moderate or severe VHD. We abstracted data from medical records, including echocardiogram reports, on patient characteristics, aetiology, type and severity of VHD, interventions and in-hospital outcomes. We weighted our findings to estimate nationally representative hospitalisations. We performed multivariable logistic regression analysis to identify factors associated with valve intervention., Results: In 2015, 38 841 patients with VHD were hospitalised in 188 randomly sampled hospitals, representing 662 384 inpatients with VHD in China. We sampled 9363 patients, mean age 68.7 years (95% CI 42.2 to 95.2) and 46.8% (95% CI 45.8% to 47.8%) male, with an echocardiogram. Degenerative origin was the predominant aetiology overall (33.3%, 95% CI 32.3% to 34.3%), while rheumatic origin was the most frequent aetiology among patients with VHD as the primary diagnosis (37.4%, 95% CI 35.9% to 38.8%). Rheumatic origin was also the most common aetiology among patients with moderate or severe VHD (27.3%, 95% CI 25.6% to 29.0% and 33.6%, 95% CI 31.9% to 35.2%, respectively). The most common VHD was mitral regurgitation (79.1%, 95% CI 78.2% to 79.9%), followed by tricuspid regurgitation (77.4%, 95% CI 76.5% to 78.2%). Among patients with a primary diagnosis of severe VHD who were admitted to facilities capable of valve intervention, 35.6% (95% CI 33.1% to 38.1%) underwent valve intervention during the hospitalisation. The likelihood of intervention decreased significantly among patients with higher operative risk., Conclusions: Among patients with VHD hospitalised in China, the predominant aetiology was degenerative in origin; among patients with moderate or severe VHD, rheumatic origin was the most common aetiology. Targeted strategies and policies should be promoted to address degenerative VHD. Patients with severe VHD may be undertreated, particularly those with high operative risk., Competing Interests: Competing interests: JL reported receiving research grants, through Fuwai Hospital, from the People's Republic of China for work to improve the management of hypertension and blood lipids and to improve care quality and patient outcomes of cardiovascular disease; receiving research agreements, through the National Center Centre for Cardiovascular Diseases and Fuwai Hospital, from Amgen for a multicenter clinical trial assessing the efficacy and safety of omecamtiv mecarbil and for dyslipidemic patient registration; receiving a research agreement, through Fuwai Hospital, from Sanofi for a multicentre clinical trial on the effects of sotagliflozin; receiving a research agreement, through Fuwai Hospital, with the University of Oxford for a multicenter clinical trial of empagliflozin; receiving a research agreement, through the National Centre for Cardiovascular Diseases, from AstraZeneca for clinical research methods training outside the submitted work; and receiving a research agreement, through the National Centre for Cardiovascular Diseases, from Lilly for physician training outside the submitted work. SSD reported receiving research funding from the US Food and Drug Administration (FDA), the National Evaluation System for Health Technology Coordinating Center (NESTcc), the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) (K12HL138046), the National Institute for Healthcare Management, Arnold Ventures, and the Greenwall Foundation., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Degenerative myxomatous disease is common and is associated with aging. Poor prognostic indicators for equine aortic regurgitation specifically include ventricular ectopy, increased pulse pressure, and hyperkinetic pulses. Valvular prolapse is a functional abnormality diagnosed echocardiographically, about which knowledge is limited. A better understanding of its role in valvular regurgitation is needed. Infective endocarditis presents with fever and other systemic signs accompanying valvular regurgitation. The prognosis is poor, warranting aggressive therapy. Other forms of valvular disease occur rarely, but often presenting with severe regurgitation. Management of horses with valvular disease is focused on assessment of severity and regular clinical, echocardiographic, and electrocardiographic monitoring., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective To evaluate outcomes after mitral valve repair. Methods Between May 1999 and June 2015, 446 patients underwent mitral valve repair. Isolated mitral valve annuloplasty was excluded. A total of 398 (89%) had degenerative valve disease. Mean follow-up was 5.5 ± 3.8 years. Postoperative echocardiograms were obtained in 334 patients (75%) at a mean of 24.3 ± 13.7 months. Results Survival was 97%, 96%, 95%, and 94% at 1, 3, 5, and 10 years. Risk factor analysis showed age >60 years and nondegenerative etiology predict death (hazard ratio, 2.91; 95% confidence interval, 1.06-8.02, P = .038; and hazard ratio, 1.87; 95% confidence interval, 1.16-3.02, P = .010, respectively). Considering competing risks due to mortality, the cumulative incidence of reoperation was 2.8%, 4.2%, 5.1%, and 9.6% at 1, 3, 5, and 10 years. Competing risk proportional hazard survival regression identified nondegenerative etiology and previous cardiac surgery as predictors of reoperation, and posterior repair was protective (all P < .05). Cumulative incidence of progression of mitral regurgitation (2 or more grades) with mortality as a competing risk was 4.7%, 10.5%, 21.0%, and 35.8% at 1, 3, 5, and 10 years. Patients with previous sternotomy, repair or coronary artery bypass grafting, and concurrent tricuspid valve procedure or isolated anterior leaflet repair were more likely to develop progression of mitral regurgitation (all P < .05), and posterior leaflet repair was protective ( P = .038). On multivariate analysis diabetes, previous coronary artery bypass grafting and concurrent tricuspid valve intervention predicted MR progression. Conclusions Mitral valve repair has excellent outcomes. Our results demonstrate failures appear to occur less in those who undergo posterior leaflet repair. [ABSTRACT FROM AUTHOR]

Aim: To investigate the accuracy of a rotational C-arm CT-based 3D heart model to predict an optimal C-arm configuration during transcatheter aortic valve replacement (TAVR)., Methods: Rotational C-arm CT (RCT) under rapid ventricular pacing was performed in 57 consecutive patients with severe aortic stenosis as part of the pre-procedural cardiac catheterization. With prototype software each RCT data set was segmented using a 3D heart model. From that the line of perpendicularity curve was obtained that generates a perpendicular view of the aortic annulus according to the right-cusp rule. To evaluate the accuracy of a model-based overlay we compared model- and expert-derived aortic root diameters., Results: For all 57 patients in the RCT cohort diameter measurements were obtained from two independent operators and were compared to the model-based measurements. The inter-observer variability was measured to be in the range of 0°-12.96° of angular C-arm displacement for two independent operators. The model-to-operator agreement was 0°-13.82°. The model-based and expert measurements of aortic root diameters evaluated at the aortic annulus ( r = 0.79, P < 0.01), the aortic sinus ( r = 0.93, P < 0.01) and the sino-tubular junction ( r = 0.92, P < 0.01) correlated on a high level and the Bland-Altman analysis showed good agreement. The interobserver measurements did not show a significant bias., Conclusion: Automatic segmentation of the aortic root using an anatomical model can accurately predict an optimal C-arm configuration, potentially simplifying current clinical workflows before and during TAVR., Competing Interests: Conflict-of-interest statement: Tobias Z and Verena V receive honoraria from St. Jude Medical for lectures. Philips Healthcare and the University Hospital Duesseldorf have a master research agreement. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.