High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis

Aims: High-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis. We sought to investigate the mechanism for troponin release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome. Methods and results: Plasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay. First, in the Mechanism Cohort, 122 patients with aortic stenosis (median age 71, 67% male, aortic valve area 1.0 ± 0.4 cm2) underwent cardiovascular magnetic resonance and echocardiography to assess left ventricular (LV) myocardial mass, function, and fibrosis. The indexed LV mass and measures of replacement fibrosis (late gadolinium enhancement) were associated with cTnI concentrations independent of age, sex, coronary artery disease, aortic stenosis severity, and diastolic function. In the separate Outcome Cohort, 131 patients originally recruited into the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact of REgression (SALTIRE) study, had long-term follow-up for the occurrence of aortic valve replacement (AVR) and cardiovascular deaths. Over a median follow-up of 10.6 years (1178 patient-years), 24 patients died from a cardiovascular cause and 60 patients had an AVR. Plasma cTnI concentrations were associated with AVR or cardiovascular death HR 1.77 (95% CI, 1.22 to 2.55) independent of age, sex, systolic ejection fraction, and aortic stenosis severity. Conclusions: In patients with aortic stenosis, plasma cTnI concentration is associated with advanced hypertrophy and replacement myocardial fibrosis as well as AVR or cardiovascular death

Children's daily travel to school in Johannesburg-Soweto, South Africa: geography and school choice in the Birth to Twenty cohort study

This paper has two aims: to explore approaches to the measurement of children’s daily travel to school in a context of limited geospatial data availability, and to provide data regarding school choice and distance travelled to school in Soweto-Johannesburg, South Africa. The paper makes use of data from the Birth to Twenty cohort study (n=1428) to explore three different approaches to estimating school choice and travel to school. Firstly, straight-line distance between home and school is calculated. Secondly, census geography is used to determine whether a child's home and school fall in the same area. Thirdly, distance data are used to determine whether a child attends the nearest school. Each of these approaches highlights a different aspect of mobility, and all provide valuable data. Overall, primary school aged children in Soweto-Johannesburg are shown to be travelling substantial distances to school on a daily basis. Over a third travel more than 3km, one-way, to school, 60% attend schools outside of the suburb in which they live, and only 18% attend their nearest school. These data provide evidence for high levels of school choice in Johannesburg-Soweto, and that families and children are making substantial investments in pursuit of high quality educational opportunities. Additionally, these data suggest that two patterns of school choice are evident: one pattern involving travel of substantial distances and requiring a higher level of financial investment, and a second pattern, involving choice between more local schools, requiring less travel and a more limited financial investment

Influence of mitral valve repair versus replacement on the development of late functional tricuspid regurgitation

ObjectivesTo study the determinants of functional tricuspid regurgitation (TR) progression after surgical correction of mitral regurgitation, including the influence of mitral valve (MV) repair (MVr) versus replacement (MVR) for degenerative mitral regurgitation.MethodsFrom January 1995 to January 2006, 747 adults with MV prolapse underwent isolated MVr (n = 683) or MVR (n = 64; mechanical in 32). The mean age was 60.8 years, and 491 were men (66.0%). Moderate preoperative functional TR was present in 115 (15.4%). The MVR group had a greater likelihood of New York Heart Association class III or IV (75.0% vs 34.4%, P < .001), atrial fibrillation (20.3% vs 8.3%, P = .002), a lower left ventricular ejection fraction (61.0% vs 65.2%, P < .003), and a higher pulmonary artery pressure (50.1 vs 41.2 mm Hg, P = .001). The patients were monitored for a mean of 6.9 years (MVr) or 7.7 years (MVR; P = .075).ResultsDuring late follow-up, no difference was found between the groups in the development of moderately severe or severe TR: 1 to 5 years (3.0% vs 3.3%, P = .91) and >5 years (6.1% vs 6.5%; P = .93). The univariate predictors of severe TR after 5 years were older age (hazard ratio [HR], 1.1; P = .011), female gender (HR, 6.86; P = .005), higher pulmonary artery pressure (HR, 1.05; P = .022), and larger left atrial size (HR, 2.11; P = .035). Two patients (0.26%) who had undergone initial MVr required reoperation for late functional TR. Another 2 patients had had the tricuspid valve addressed concurrent with reoperation for MVr failure. No tricuspid reoperations were required in the MVR group.ConclusionsThe risk of TR progression was low after MVr or MVR for MV prolapse. Timely MV surgery before the development of left atrial dilatation or pulmonary hypertension could further decrease the risk of TR progression during follow-up

Regular Exercise or Changing Diet Does Not Influence Aortic Valve Disease Progression in LDLR Deficient Mice

BACKGROUND: The development and progression of calcific aortic valve disease (CAVD) shares a number of similarities with atherosclerosis. Recently we could demonstrate that regular exercise training (ET) as primary prevention prevents aortic valve disease in LDL-receptor deficient (LDLR(-/-)) mice. We aimed to investigate the impact of exercise training on the progression of CAVD in LDLR(-/-) mice in the setting of secondary prevention METHODS AND RESULTS: Sixty-four LDLR(-/-) mice were fed with high cholesterol diet to induce aortic valve sclerosis. Thereafter the animals were divided into 3 groups: group 1 continuing on high cholesterol diet, group 2 continuing with cholesterol diet plus 1 h ET per day, group 3 continuing with normal mouse chow. After another 16 weeks the animal were sacrificed. Histological analysis of the aortic valve thickness demonstrated no significant difference between the three groups (control 98.3±4.5 µm, ET 88.2±6.6 µm, change in diet 87.5±4.0). Immunohistochemical staining for endothelial cells revealed a disrupted endothelial cell layer to the same extend in all groups. Furthermore no difference between the groups was evident with respect to the expression of inflammatory, fibroblastic and osteoblastic markers. CONCLUSION: Based on the present study we have to conclude that once the development of a CAVD is initiated, exercise training or a change in diet does not have the potential to attenuate the progress of the CAVD

Baseline mitral regurgitation predicts outcome in patients referred for dobutamine stress echocardiography

Purpose: A number of parameters recorded during dobutamine stress echocardiography (DSE) are associated with worse outcome. However, the relative importance of baseline mitral regurgitation (MR) is unknown. The aim of this study was to assess the prevalence and associated implications of functional MR with long-term mortality in a large cohort of patients referred for DSE. Methods: 6745 patients (mean age 64.9±12.2 years) were studied. Demographic, baseline and peak DSE data were collected. All-cause mortality was retrospectively analyzed. DSE was successfully completed in all patients with no adverse outcomes. Results: MR was present in 1019 (15.1%) patients. During a mean follow up of 5.1±1.8 years, 1642 (24.3%) patients died and MR was significantly associated with increased all-cause mortality (p<0.001). With Kaplan-Meier analysis, survival was significantly worse for patients with moderate and severe MR (p<0.001). With multivariate Cox regression analysis, moderate and severe MR (HR 2.78; 95% CI 2.17 - 3.57; and HR 3.62; 95% CI 2.89 - 4.53, respectively) were independently associated with all-cause mortality. The addition of MR to C statistic models significantly improved discrimination. Conclusions: MR is associated with all-cause mortality and adds incremental prognostic information among patients referred for DSE. The presence of MR should be taken into account when evaluating the prognostic significance of DSE results

Cost-effectiveness analysis of stand-alone or combined non-invasive imaging tests for the diagnosis of stable coronary artery disease: results from the EVINCI study

Aim: This study aimed at evaluating the cost-effectiveness of different non-invasive imaging-guided strategies for the diagnosis of obstructive coronary artery disease (CAD) in a European population of patients from the Evaluation of Integrated Cardiac Imaging in Ischemic Heart Disease (EVINCI) study. Methods and results: Cost-effectiveness analysis was performed in 350 patients (209 males, mean age 59 ± 9&nbsp;years) with symptoms of suspected stable CAD undergoing computed tomography coronary angiography (CTCA) and at least one cardiac imaging stress-test prior to invasive coronary angiography (ICA) and in whom imaging exams were analysed at dedicated core laboratories. Stand-alone stress-tests or combined non-invasive strategies, when the first exam was uncertain, were compared. The diagnostic end-point was obstructive CAD defined as &gt; 50% stenosis at quantitative ICA in the left main or at least one major coronary vessel. Effectiveness was defined as the percentage of correct diagnosis (cd) and costs were calculated using country-specific reimbursements. Incremental cost-effectiveness ratios (ICERs) were obtained using per-patient data and considering “no-imaging” as reference. The overall prevalence of obstructive CAD was 28%. Strategies combining CTCA followed by stress ECHO, SPECT, PET, or stress CMR followed by CTCA, were all cost-effective. ICERs values indicated cost saving from − 969€/cd for CMR-CTCA to − 1490€/cd for CTCA-PET, − 3092€/cd for CTCA-SPECT and − 3776€/cd for CTCA-ECHO. Similarly when considering early revascularization as effectiveness measure. Conclusion: In patients with suspected stable CAD and low prevalence of disease, combined non-invasive strategies with CTCA and stress-imaging are cost-effective as gatekeepers to ICA and to select candidates for early revascularization

Long-Term Implications of Atrial Fibrillation in Patients With Degenerative Mitral Regurgitation

Background: Scientific guidelines consider atrial fibrillation (AF) complicating degenerative mitral regurgitation (DMR) a debated indication for surgery. Objectives: This study analyzed the prognostic/therapeutic implications of AF at DMR diagnosis and long-term. Methods: Patients were enrolled in the MIDA (Mitral Regurgitation International Database) registry, which reported the consecutive, multicenter, international experience with DMR due to flail leaflets echocardiographically diagnosed. Results: Among 2,425 patients (age 67 \ub1 13 years; 71% male, 67% asymptomatic, ejection fraction 64 \ub1 10%), 1,646 presented at diagnosis with sinus rhythm (SR), 317 with paroxysmal AD, and 462 with persistent AF. Underlying clinical/instrumental characteristics progressively worsened from SR to paroxysmal to persistent AF. During follow-up, paroxysmal and persistent AF were associated with excess mortality (10-year survival in SR and in paroxysmal and persistent AF was 74 \ub1 1%, 59 \ub1 3%, and 46 \ub1 2%, respectively; p &lt; 0.0001), that persisted 20 years post-diagnosis and independently of all baseline characteristics (p values &lt;0.0001). Surgery (n = 1,889, repair 88%) was associated with better survival versus medical management, regardless of all baseline characteristics and rhythm (adjusted hazard ratio: 0.26; 95% confidence interval: 0.23 to 0.30; p &lt; 0.0001) but post-surgical outcome remained affected by AF (10-year post-surgical survival in SR and in paroxysmal and persistent AF was 82 \ub1 1%, 70 \ub1 4%, and 57 \ub1 3%, respectively; p &lt; 0.0001). Conclusions: AF is a frequent occurrence at DMR diagnosis. Although AF is associated with older age and more severe presentation of DMR, it is independently associated with excess mortality long-term after diagnosis. Surgery is followed by improved survival in each cardiac rhythm subset, but persistence of excess risk is observed for each type of AF. Our study indicates that detection of AF, even paroxysmal, should trigger prompt consideration for surgery

Post-stenotic aortic dilatation

Aortic stenosis is the most common valvular heart disease affecting up to 4% of the elderly population. It can be associated with dilatation of the ascending aorta and subsequent dissection. Post-stenotic dilatation is seen in patients with AS and/or aortic regurgitation, patients with a haemodynamically normal bicuspid aortic valve and following aortic valve replacement. Controversy exists as to whether to replace the aortic root and ascending aorta at the time of aortic valve replacement, an operation that potentially carries a higher morbidity and mortality. The aetiology of post-stenotic aortic dilatation remains controversial. It may be due to haemodynamic factors caused by a stenotic valve, involving high velocity and turbulent flow downstream of the stenosis, or due to intrinsic pathology of the aortic wall. This may involve an abnormality in the process of extracellular matrix remodelling in the aortic wall including inadequate synthesis, degradation and transport of extracellular matrix proteins. This article reviews the aetiology, pathology and management of patients with post-stenotic aortic dilatation