The Epidemiology of Valvular Heart Diseases: The Problem Is Growing

Borer²,

2013

Cardiology

Section: Changing Distribution Of Vhd Etiologies and Contributing Facmentioning

confidence: 99%

Section: Changing Distribution Of Vhd Etiologies and Contributing Facmentioning

confidence: 99%

Etiology of Valvular Heart Disease in the 21st Century

Borer²,

2013

Cardiology

Journal of Molecular and Cellular Cardiology

“…The formation of a bicuspid or bifoliate aortic valve (BAV) is the most common cardiovascular defect and occurs in 1% to 2% of the population [1-3]. A bicuspid valve is comprised of two rather than three semilunar cusps, which are also referred to as valvar leaflets.…”

Section: 1 Introductionmentioning

confidence: 99%

Insufficient versican cleavage and Smad2 phosphorylation results in bicuspid aortic and pulmonary valves

Dupuis

Osińska

Weinstein

et al. 2013

Bicuspid or bifoliate aortic valve (BAV) results in two rather than three cusps and occurs in 1-2% of the population placing them at higher risk of developing progressive aortic valve disease. Only NOTCH-1 has been linked to human BAV, and genetically modified mouse models of BAV are limited by low penetrance and additional malformations. Here we report that in the Adamts5−/− valves, collagen I, collagen III, and elastin were disrupted in the malformed hinge region that anchors the mature semilunar cusps and where versican, the ADAMTS5 proteoglycan substrate, accumulates. ADAMTS5 deficient prevalvular mesenchyme also exhibited a reduction of α-smooth muscle actin and filamin A suggesting versican cleavage may be involved in TGFβ signaling. Subsequent evaluation showed a significant decrease of pSmad2 in regions of prevalvular mesenchyme in Adamts5−/− valves. To test the hypothesis that ADAMTS5 versican cleavage is required, in part, to elicit Smad2 phosphorylation we further reduced Smad2 in Adamts5−/− mice through intergenetic cross. The Adamts5−/−;Smad2+/− mice had highly penetrant BAV and bicuspid pulmonary valve (BPV) malformations as well as increased cusp and hinge size compared to the Adamts5−/− and control littermates. These studies demonstrate that semilunar cusp malformations (BAV and BPV) can arise from a failure to remodel the proteoglycan-rich provisional ECM. Specifically, faulty versican clearance due to ADAMTS5 deficiency blocks the initiation of pSmad2 signaling, which is required for excavation of endocardial cushions during aortic and pulmonary valve development. Further studies using the Adamts5−/−;Smad2+/− mice with highly penetrant and isolated BAV, may lead to new pharmacological treatments for valve disease.

“…Primarily, calcified aortic stenosis is present in 2–7% of the population aged >65 years,1 and its prevalence increases with age and concomitant cardiovascular disease 2. According to current knowledge, the prognosis of patients who are diagnosed with symptomatic AVS is relatively good but worsens significantly after the onset of symptoms, with an average survival of only 2–3 years 3 4.…”

Section: Introductionmentioning

confidence: 99%

Prognosis of octogenarians with severe aortic valve stenosis at high risk for cardiovascular surgery

Schueler

Hammerstingl

Sinning

et al. 2010

Heart

BackgroundCalcified aortic valve stenosis (AVS) is a disease found in the elderly which is often complicated by severe co-morbidities.AimsTo assess the survival of conservatively treated patients >75 years with severe AVS compared to patients with non-severe AVS but who have a similar clinical risk profile; and to identify risk factors affecting prognosis.Methods and resultsFrom 2002 to 2006, 161 patients (mean age 86±7.7 years) were studied: 79 with aortic valve area (AVA) <1 cm2 (group A), 82 with AVA ≥1 cm2 (group B). Cumulative mortality rates were 77.5% in group A, and 44.4% in group B. Survival rates at 6, 12, 18 and 24 months in groups A and B were: 70.9% versus 98.8%, 65.8% versus 84.1%, 49.4% versus 69.5% and 41.8% versus 59.8%, respectively. Independent predictors for death in group A were pulmonary artery pressure (PAP), the STS-PROM score, serum creatinine and diabetes. PAP >30 mm Hg identified patients at high mortality risk. In group B the predictive variables were ejection fraction, PAP, serum creatinine, and treatment with β-blockers or ACE inhibitors.ConclusionSevere aortic valve stenosis is a medical condition with limited short-term survival in patients over the age of 75 years at high surgical risk. Clinical variables rather than symptomatic status were able to predict the patients' outcome. Patients with the highest surgical risk have the worst prognosis if AVS is not treated.