Prospective registry of symptomatic severe aortic stenosis in octogenarians: a need for intervention.

OBJECTIVE To study the factors associated with choice of therapy and prognosis in octogenarians with severe symptomatic aortic stenosis (AS). STUDY DESIGN Prospective, observational, multicenter registry. Centralized follow-up included survival status and, if possible, mode of death and Katz index. SETTING Transnational registry in Spain. SUBJECTS We included 928 patients aged ≥80 years with severe symptomatic AS. INTERVENTIONS Aortic-valve replacement (AVR), transcatheter aortic-valve implantation (TAVI) or conservative therapy. MAIN OUTCOME MEASURES All-cause death. RESULTS Mean age was 84.2 ± 3.5 years, and only 49.0% were independent (Katz index A). The most frequent planned management was conservative therapy in 423 (46%) patients, followed by TAVI in 261 (28%) and AVR in 244 (26%). The main reason against recommending AVR in 684 patients was high surgical risk [322 (47.1%)], other medical motives [193 (28.2%)], patient refusal [134 (19.6%)] and family refusal in the case of incompetent patients [35 (5.1%)]. The mean time from treatment decision to AVR was 4.8 ± 4.6 months and to TAVI 2.1 ± 3.2 months, P < 0.001. During follow-up (11.2-38.9 months), 357 patients (38.5%) died. Survival rates at 6, 12, 18 and 24 months were 81.8%, 72.6%, 64.1% and 57.3%, respectively. Planned intervention, adjusted for multiple propensity score, was associated with lower mortality when compared with planned conservative treatment: TAVI Hazard ratio (HR) 0.68 (95% confidence interval [CI] 0.49-0.93; P = 0.016) and AVR HR 0.56 (95% CI 0.39-0.8; P = 0.002). CONCLUSION Octogenarians with symptomatic severe AS are frequently managed conservatively. Planned conservative management is associated with a poor prognosis.

Prospective registry of symptomatic severe aortic stenosis in octogenarians: a need for intervention.

OBJECTIVE To study the factors associated with choice of therapy and prognosis in octogenarians with severe symptomatic aortic stenosis (AS). STUDY DESIGN Prospective, observational, multicenter registry. Centralized follow-up included survival status and, if possible, mode of death and Katz index. SETTING Transnational registry in Spain. SUBJECTS We included 928 patients aged ≥80 years with severe symptomatic AS. INTERVENTIONS Aortic-valve replacement (AVR), transcatheter aortic-valve implantation (TAVI) or conservative therapy. MAIN OUTCOME MEASURES All-cause death. RESULTS Mean age was 84.2 ± 3.5 years, and only 49.0% were independent (Katz index A). The most frequent planned management was conservative therapy in 423 (46%) patients, followed by TAVI in 261 (28%) and AVR in 244 (26%). The main reason against recommending AVR in 684 patients was high surgical risk [322 (47.1%)], other medical motives [193 (28.2%)], patient refusal [134 (19.6%)] and family refusal in the case of incompetent patients [35 (5.1%)]. The mean time from treatment decision to AVR was 4.8 ± 4.6 months and to TAVI 2.1 ± 3.2 months, P < 0.001. During follow-up (11.2-38.9 months), 357 patients (38.5%) died. Survival rates at 6, 12, 18 and 24 months were 81.8%, 72.6%, 64.1% and 57.3%, respectively. Planned intervention, adjusted for multiple propensity score, was associated with lower mortality when compared with planned conservative treatment: TAVI Hazard ratio (HR) 0.68 (95% confidence interval [CI] 0.49-0.93; P = 0.016) and AVR HR 0.56 (95% CI 0.39-0.8; P = 0.002). CONCLUSION Octogenarians with symptomatic severe AS are frequently managed conservatively. Planned conservative management is associated with a poor prognosis.

Natural history of very severe aortic stenosis

We sought to assess the outcome of asymptomatic patients with very severe aortic stenosis.

Outcome of adults with asymptomatic severe aortic stenosis

Objectives: To evaluate clinical and echocardiographic variables that could be used to predict outcomes in patients with asymptomatic severe aortic valve stenosis. Management of asymptomatic severe aortic stenosis is controversial. Because prophylactic surgery may be protective, independent predictors of events that could justify early surgery have been sought. Methods: Outpatients (n= 133; mean [+/- SD] age, 66.2 +/- 13.6 years) with isolated severe asymptomatic aortic stenosis but normal left ventricular function and no previous myocardial infarction were followed up prospectively at a tertiary care hospital. Interventions: We use a ""wait-for-events"" strategy. Clinical and echocardiographic variables were analyzed. Results: Nineteen patients developed angina; 40, dyspnea; 5, syncope; and 7, sudden death during a mean follow-up period of 3.30 +/- 1.87 years. Event-free survival was 90.2 +/- 2.6% at 1 year, 73.4 +/-.9% at 2 years, 70.7 +/- 4.3% at 3 years, 57.8 +/- 4.7% at 4 years, 40.3 +/- 5.0% at 5 years, and 33.3 +/- 5.2% at 6 years. The mean follow-up period until sudden death (1.32 +/- 1.11 years) was shorter than that for dyspnea (2.44 +/- 1.84 years), syncope (2.87 +/- 1.26 years) and angina (3.03 +/- 1.68 years). Cox regression analysis disclosed only reduced but within normal limits ejection fraction as independent predictor of total events. Conclusions: Management on ""wait-for-events"" strategy is generally safe. Progressive left ventricular ejection fraction reduction even within normal limits identified patients at high risk for events in whom valve replacement surgery should be considered. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Aortic valve dysfunction and aortic dilation in adults with coarctation of the aorta.

OBJECTIVES: To determine the prevalence of aortic valve dysfunction, aortic dilation, and aortic valve and ascending aortic intervention in adults with coarctation of the aorta (CoA). BACKGROUND: Aortic valve dysfunction and aortic dilation are rare among children and adolescents with CoA. With longer follow-up, adults may be more likely to have progressive disease. METHODS: We retrospectively reviewed all adults with CoA, repaired or unrepaired, seen at our center between 2004 and 2010. RESULTS: Two hundred sixteen adults (56.0% male) with CoA were identified. Median age at last evaluation was 28.3 (range 18.0 to 75.3) years. Bicuspid aortic valve (BAV) was present in 65.7%. At last follow-up, 3.2% had moderate or severe aortic stenosis, and 3.7% had moderate or severe aortic regurgitation. Dilation of the aortic root or ascending aorta was present in 28.0% and 41.6% of patients, respectively. Moderate or severe aortic root or ascending aortic dilation (z-score > 4) was present in 8.2% and 13.7%, respectively. Patients with BAV were more likely to have moderate or severe ascending aortic dilation compared with those without BAV (19.5% vs. 0%; P < 0.001). Age was associated with ascending aortic dilation (P = 0.04). At most recent follow-up, 5.6% had undergone aortic valve intervention, and 3.2% had aortic root or ascending aortic replacement. CONCLUSION: In adults with CoA, significant aortic valve dysfunction and interventions during early adulthood were uncommon. However, aortic dilation was prevalent, especially of the ascending aorta, in patients with BAV.

Aortic valve dysfunction and aortic dilatation in adults with coarctation of the aorta

Objectif: Déterminer la prévalence de la dysfonction de la valve aortique, de la dilatation de l'aorte proximale et des interventions au niveau de la valve aortique et de l'aorte ascendante chez les adultes avec une coarctation de l'aorte. Contexte: La dysfonction de la valve aortique et la dilatation de l'aorte proximale sont rares chez les enfants et les adolescents avec une coarctation de l'aorte. A long terme, les adultes pourraient être plus à risque de développer ce type de pathologie. Méthode: Nous avons rétrospectivement passé en revue tous les adultes avec une coarctation de l'aorte corrigée ou pas suivis au « Boston Children's Hospital » entre 2004 et 2010. Résultats: 216 adultes (56 % d'hommes) avec une coarctation ont été identifiés. L'âge médian à la dernière évaluation était de 28 (de 18 à 75) ans. Une bicuspidie aortique était présente dans 66% des cas. Au dernier contrôle, 3% avaient une sténose aortique modérée ou sévère et 4% avaient une insuffisance aortique modérée à sévère. Une dilatation de la racine de l'aorte ou de l'aorte ascendante était présente dans 28%, respectivement 42% des patients. Une dilatation au moins modérée de la racine de l'aorte ou de l'aorte ascendante (score Z > 4) était présente dans 8%, respectivement 14%. Les patients avec une bicuspidie aortique étaient plus sujets à avoir une dilatation au moins modérée de la racine de l'aorte ou de l'aorte ascendante comparés à ceux sans bicuspidie (20% contre 0%; p<0.001). L'âge était associé à une dilatation de l'aorte ascendante (p=0.04). Au dernier suivi, 6% avait nécessité une intervention au niveau de la valve aortique et 3% un remplacement de la racine de l'aorte ou de l'aorte ascendante.

Abnormal extracellular matrix protein transport associated with increased apoptosis of vascular smooth muscle cells in Marfan syndrome and bicuspid aortic valve thoracic aortic aneurysm

Background - Marfan syndrome (MS) is a genetic disorder caused by a mutation in the fibrillin gene FBN1. Bicuspid aortic valve (BAV) is a congenital heart malformation of unknown cause. Both conditions are associated with ascending aortic aneurysm and premature death. This study examined the relationship among the secretion of extracellular matrix proteins fibrillin, fibronectin, tenascin, and vascular smooth muscle cell (VSMC) apoptosis. The role of matrix metalloproteinase (MMP)- 2 in VSMC apoptosis was studied in MS aneurysm. Methods and Results - Aneurysm tissue was obtained from patients undergoing surgery ( MS: 4 M, 1 F, age 27 - 45 years; BAV: 3 M, 2 F, age 28 - 65 years). Normal aorta from subjects with nonaneurysm disease was also collected ( 4 M, 1 F, age 23 - 93 years). MS and BAV aneurysm histology showed areas of cystic medial necrosis (CMN) without inflammatory infiltrate. Immunohistochemical study of cultured MS and BAV VSMC showed intracellular accumulation and reduction of extracellular distribution of fibrillin, fibronectin, and tenascin. Western blot showed no increase in expression of fibrillin, fibronectin, or tenascin in MS or BAV VSMC and increased expression of MMP-2 in MS VSMCs. There was 4-fold increase in loss of cultured VSMC incubated in serum-free medium for 24 hours in both MS ( 27 +/- 8%) and BAV ( 32 +/- 14%) compared with control ( 7 +/- 5%). Conclusions - In MS and BAV there is alteration in both the amount and quality of secreted proteins and an increased degree of VSMC apoptosis. Up-regulation of MMP-2 might play a role in VSMC apoptosis in MS VSMC. The findings suggest the presence of a fundamental cellular abnormality in BAV thoracic aorta, possibly of genetic origin.

Follow-up study of morphology and cardiac function in rats undergoing induction of supravalvular aortic stenosis

OBJECTIVE: To characterize the follow-up of an experimental model of left ventricular hypertrophy (LVH) induced by supravalvular ascending aortic stenosis in young rats. METHODS: Wistar rats were submitted to thoracotomy and aortic stenosis was created by placing a clip on the ascending aorta (AoS group, n=12). Age-matched control animals underwent a sham operation (C group, n=12). Cardiac function was analysed by echocardiograms performed 6, 12, and 21 weeks after aortic banding. Myocardial morphological features and myocardial hydroxyproline concentration (HOP) were evaluated 2, 6, 12, and 21 weeks after surgery in additional animals. RESULTS: Aortic banding promoted early concentric LVH and a progressive increase in HOP. Under light microscopy, we observed myocyte hypertrophy and wall thickening of the intramural branches of the coronary arteries due to medial hypertrophy. Cardiac function was supranormal after 6 weeks (percentage of fractional shortening - EAo6: 70.3±10.8; C6: 61.3±5.4; p<0.05), and depressed in the last period. Diastolic dysfunction was detected after 12 weeks (ratio of early-to-late filling velocity - EAo12: 4.20±3.25; C12: 1.61±0.16; p<0.05). CONCLUSION: Ascending aortic stenosis promotes concentric LVH with myocardial fibrosis and minimal histological changes. According to the period of evaluation, cardiac function may be improved, normal, or depressed. The model is suitable and useful for studies on pathophysiology and treatment of the different phases of cardiac hypertrophy.

Quantification of aortic flow by phase-contrast magnetic resonance in patients with bicuspid aortic valve.

AIMS: Bicuspid aortic valve (BAV) causes complex flow patterns in the ascending aorta (AAo), which may compromise the accuracy of flow measurement by phase-contrast magnetic resonance (PC-MR). Therefore, we aimed to assess and compare the accuracy of forward flow measurement in the AAo, where complex flow is more dominant in BAV patients, with flow quantification in the left ventricular outflow tract (LVOT) and the aortic valve orifice (AV), where complex flow is less important, in BAV patients and controls. METHODS AND RESULTS: Flow was measured by PC-MR in 22 BAV patients and 20 controls at the following positions: (i) LVOT, (ii) AV, and (iii) AAo, and compared with the left ventricular stroke volume (LVSV). The correlation between the LVSV and the forward flow in the LVOT, the AV, and the AAo was good in BAV patients (r = 0.97/0.96/0.93; P < 0.01) and controls (r = 0.96/0.93/0.93; P < 0.01). However, in relation with the LVSV, the forward flow in the AAo was mildly underestimated in controls and much more in BAV patients [median (inter-quartile range): 9% (4%/15%) vs. 22% (8%/30%); P < 0.01]. This was not the case in the LVOT and the AV. The severity of flow underestimation in the AAo was associated with flow eccentricity. CONCLUSION: Flow measurement in the AAo leads to an underestimation of the forward flow in BAV patients. Measurement in the LVOT or the AV, where complex flow is less prominent, is an alternative means for quantifying the systolic forward flow in BAV patients.

Carotid-subclavian arteries Index (CSI), a new echocardiographic index to recognize coarctation of the aorta in neonates and infants

Introduction: Coarctation of the aorta is a common congenital heart malformation. Mode of diagnosis changed from clinically to almost exclusively by echocardiogram and MRI. We claim to find a new echocardiographic index, based on simple and reliable morphologic measurements, to facilitate the diagnosis of aortic coarctation in the newborn.We reproduce the same procedure for older child to validate this new index. Material and Methods: We reviewed echocardiographic studies of 47 neonates with diagnosis of coarctation who underwent cardiac surgery between January 1997 and February 2003 and compared them with a matched control group. We measured 12 different sites of the aorta, aortic arch and the great vessels on the echocardiographic bands. In a second time we reviewed 23 infants for the same measurements and compare them with a matched control group. Results: 47 neonates with coarctation were analysed, age 11.8 _ 10 days,weight 3.0 _ 0.6 kg, body surface 0.20 _ 0.02m2. The control group was of 16 newborns aged 15.8 _ 10 days,weight 3.2 _ 0.9 kg and body surface 0.20 _ 0.04m2. A significant difference was noted in many morphologic measurement between the both groups, the most significant being the distance between the left carotid artery and the left subclavian artery (coarctation vs control: 7.3 _ 3mm vs 2.4 _ 0.8mm, p _ 0.0001). We then defined a new index, the carotid-subclavian arteries index (CSI) as the diameter of the distal tranverse aortic arch divided to the distance left carotid artery to left subclavian artery being also significaly different (coarctation vs control: 0.76 _ 0.86 vs 2.95 _ 1.24, p _ 0.0001). With the cutoff value of this index of 1.5 the sensitivity for aortic coarctation was 98% and the specificity of 92%. In an older group of infant with coarctation (16 patients) we apply the same principle and find for a cut-off value of 1.5 a sensitivity of 95% and a specificity of 100%. Conclusions: The CSI allows to evaluate newborns and infants for aortic coarctation with simple morphologic measurement that are not depending of the left ventricular function, presence of a patent ductus arteriosus or not. Further aggressive evaluation of these patient with a CSI _ 1.5 is indicated.

Follow-up study of morphology and cardiac function in rats undergoing induction of supravalvular aortic stenosis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)