Search

Objectives: With concomitant Doppler echocardiography and multidetector computed tomography (MDCT) measuring aortic valve calcification (AVC) load, this study aimed at defining: 1) independent physiologic/structural determinants of aortic valve area (AVA)/mean gradient (MG) relationship; 2) AVC thresholds best associated with severe aortic stenosis (AS); and 3) whether, in AS with discordant MG, severe calcified aortic valve disease is generally detected., Background: Aortic stenosis with discordant markers of severity, AVA in severe range but low MG, is a conundrum, unresolved by outcome studies., Methods: Patients (n = 646) with normal left ventricular ejection fraction AS underwent Doppler echocardiography and AVC measurement by MDCT. On the basis of AVA-indexed-to-body surface area (AVAi) and MG, patients were categorized as concordant severity grading (CG) with moderate AS (AVAi >0.6 cm²/m², MG <40 mm Hg), severe AS (AVAi ≤0.6 cm²/m², MG ≥ 40 mm Hg), discordant-severity-grading (DG) with low-MG (AVAi ≤0.6 cm(2)/m(2), MG <40 mm Hg), or high-MG (AVAi >0.6 cm(2)/m(2), MG ≥40 mm Hg)., Results: The MG (discordant in 29%) was strongly determined by AVA and flow but also independently and strongly influenced by AVC-load (p < 0.0001) and systemic arterial compliance (p < 0.0001). The AVC-load (median [interquartile range]) was similar within patients with DG (low-MG: 1,619 [965 to 2,528] arbitrary units [AU]; high-MG: 1,736 [1,209 to 2,894] AU; p = 0.49), higher than CG-moderate-AS (861 [427 to 1,519] AU; p < 0.0001) but lower than CG-severe-AS (2,931 [1,924 to 4,292] AU; p < 0.0001). The AVC-load thresholds separating severe/moderate AS were defined in CG-AS with normal flow (stroke-volume-index >35 ml/m(2)). The AVC-load, absolute or indexed, identified severe AS accurately (area under the curve ≥0.89, sensitivity ≥86%, specificity ≥79%) in men and women. Upon application of these criteria to DG-low MG, at least one-half of the patients were identified as severe calcified aortic valve disease, irrespective of flow., Conclusions: Among patients with AS, MG is often discordant from AVA and is determined by multiple factors, valvular (AVC) and non-valvular (arterial compliance) independently of flow. The AVC-load by MDCT, strongly associated with AS severity, allows diagnosis of severe calcified aortic valve disease. At least one-half of the patients with discordant low gradient present with heavy AVC-load reflective of severe calcified aortic valve disease, emphasizing the clinical yield of AVC quantification by MDCT to diagnose and manage these complex patients., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study evaluated the predictive factors and prognostic value of new-onset persistent left bundle branch block (LBBB) in patients undergoing transcatheter aortic valve implantation (TAVI) with a balloon-expandable valve., Background: The predictors of persistent (vs. transient or absent) LBBB after TAVI with a balloon-expandable valve and its clinical consequences are unknown., Methods: A total of 202 consecutive patients with no baseline ventricular conduction disturbances or previous permanent pacemaker implantation (PPI) who underwent TAVI with a balloon-expandable valve were included. Patients were on continuous electrocardiographic (ECG) monitoring during hospitalization and 12-lead ECG was performed daily until hospital discharge. No patient was lost at a median follow-up of 12 (range: 6 to 24) months, and ECG tracing was available in 97% of patients. The criteria for PPI were limited to the occurrence of high-degree atrioventricular block (AVB) or severe symptomatic bradycardia., Results: New-onset LBBB was observed in 61 patients (30.2%) after TAVI, and had resolved in 37.7% and 57.3% at hospital discharge and 6- to 12-month follow-up, respectively. Baseline QRS duration (p = 0.037) and ventricular depth of the prosthesis (p = 0.017) were independent predictors of persistent LBBB. Persistent LBBB at hospital discharge was associated with a decrease in left ventricular ejection fraction (p = 0.001) and poorer functional status (p = 0.034) at 1-year follow-up. Patients with persistent LBBB and no PPI at hospital discharge had a higher incidence of syncope (16.0% vs. 0.7%; p = 0.001) and complete AVB requiring PPI (20.0% vs. 0.7%; p < 0.001), but not of global mortality or cardiac mortality during the follow-up period (all, p > 0.20). New-onset LBBB was the only factor associated with PPI following TAVI (p < 0.001)., Conclusions: Up to 30% of patients with no prior conduction disturbances developed new LBBB following TAVI with a balloon-expandable valve, although it was transient in more than one third. Longer baseline QRS duration and a more ventricular positioning of the prosthesis were associated with a higher rate of persistent LBBB, which in turn determined higher risks for complete AVB and PPI, but not mortality, at 1-year follow-up., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Valve hemodynamics and clinical outcomes among patients with a small aortic annulus who underwent transcatheter aortic valve implantation (TAVI) were examined., Background: The presence of a small aortic annulus may complicate the surgical management of patients with severe aortic stenosis (AS). TAVI is an alternative to aortic valve replacement (AVR) in high-risk patients, but few data exist on the results of TAVI in patients with a small aortic annulus., Methods: Between 2007 and 2010, 35 patients (mean age 79.2 ± 9.4 years) with severe AS and an aortic annulus diameter <20 mm (mean 18.5 ± 0.9 mm) underwent TAVI with a 23-mm Edwards SAPIEN bioprosthesis (Edwards Lifesciences, Inc., Irvine, California). Echocardiographic parameters and clinical outcomes were assessed prior to discharge and at 6, 12, and 24 months., Results: Procedural success was achieved in 34 patients (97.1%). There was 1 in-hospital death. Peak and mean transaortic gradients decreased from 76.3 ± 33.0 mm Hg and 45.2 ± 20.6 mm Hg at baseline to 21.8 ± 8.4 mm Hg and 11.7 ± 4.8 mm Hg post-procedure, respectively, both p < 0.0001. Mean indexed effective orifice area (IEOA) increased from 0.35 ± 0.10 cm(2)/m(2) at baseline to 0.90 ± 0.18 cm(2)/m(2) post-procedure, p < 0.0001. Severe prosthesis-patient mismatch (IEOA <0.65 cm(2)/m(2)) occurred in 2 patients (5.9%). At a mean follow-up of 14 ± 11 months, gradients remained low and 30 of the 31 remaining survivors were in New York Heart Association functional class I or II., Conclusions: In high-risk patients with severe AS and a small aortic annulus, TAVI is associated with good post-procedural valve hemodynamics and clinical outcomes. TAVI may provide a reasonable alternative to conventional AVR in elderly patients with a small aortic annulus., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to determine the prevalence of valvular aortic stenosis requiring surgery in patients with a pre-existing diagnosis of subaortic stenosis., Background: Classic teachings emphasize aortic regurgitation as the most common complication associated with discrete subaortic stenosis. We hypothesized that significant aortic stenosis may also be an important valve lesion associated with this condition., Methods: Clinical outcomes in patients with subaortic stenosis were examined. The primary outcome of interest was the prevalence of valvular aortic stenosis requiring surgery (surgical valvotomy or valve replacement). Logistic regression was used to identify variables associated with the need for surgery for aortic stenosis., Results: One hundred twenty-one adults with subaortic stenosis (median age 32 years) were evaluated in our clinic. Associated lesions were common: 23% had bicuspid valves and 21% had coarctation of the aorta. Seventy-nine percent of the patients had at least 1 surgical resection of subaortic tissue (median age 12 years). Moderate to severe aortic regurgitation was present in 16% of patients (19 of 121), 3 of whom required surgical intervention in adulthood. Twenty-six percent of patients (32 of 121) required surgery for valvular aortic stenosis. Valve surgery for aortic stenosis was more common in patients with concomitant bicuspid aortic valve disease (p = 0.008), coarctation of the aorta (p = 0.03), and supravalvular stenosis (p = 0.02)., Conclusions: Valvular aortic stenosis is a surprisingly common finding in patients with discrete subaortic stenosis. Careful clinical follow-up of this population to monitor aortic valve status continues to be warranted even after a successful surgical resection., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This prospective cohort study in patients with aortic stenosis (AS) aimed to identify surrogates of myocardial fibrosis that are easy to derive in clinical practice, allow the differentiation of low-gradient severe AS from moderate AS, and have an impact on clinical outcome., Background: In patients with symptomatic aortic AS, a characteristic subgroup (i.e., up to one-third) exhibits severe AS with a concomitant low mean valve gradient either with preserved or reduced ejection fraction (EF). It is hypothesized that these patients tend to have an advanced stage of myocardial fibrosis and poor clinical outcome., Methods: Eighty-six patients with moderate or severe AS were examined by echocardiography including conventional aortic valve assessment, mitral ring displacement, and strain-rate imaging. Replacement fibrosis was quantified by late-enhancement magnetic resonance imaging. Biopsy samples were taken from patients with severe AS (n = 69) at aortic valve replacement. All patients were followed for 9 months., Results: Patients were divided into 4 groups according to aortic valve area (<1.0 cm(2)), mean valve gradient ≥40 mm Hg, and EF (<50%): group 1, moderate AS (n = 17); group 2, severe AS/high gradient (n = 49); group 3, severe AS/low gradient/preserved EF (n = 11); and group 4, severe AS/low gradient/decreased EF (n = 9). At baseline, a significant decrease in mitral ring displacement and systolic strain rate was detected in patients with low-gradient AS. In low-gradient groups, a higher degree of interstitial fibrosis in biopsy samples and more late-enhancement magnetic resonance imaging segments were observed. A close inverse correlation was found between interstitial fibrosis and mitral ring displacement (r = -0.79, p < 0.0001). Clinical outcome was best for patients in group 1, whereas mortality risk increased substantially in groups 2 through 4., Conclusions: In severe AS, a low gradient is associated with a higher degree of fibrosis, decreased longitudinal function, and poorer clinical outcome despite preserved EF. Mitral ring displacement differentiates between moderate AS and low-gradient/severe AS with preserved EF., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The objective of this study was to investigate the associations of mitral annular calcification, aortic annular calcification, and aortic valve sclerosis with covert magnetic resonance imaging (MRI)-defined brain infarcts., Background: Clinically silent brain infarcts defined by MRI are associated with increased risk for cognitive decline, dementia, and future overt stroke. Left-sided cardiac valvular and annular calcifications are suspected as risk factors for clinical ischemic stroke., Methods: A total of 2,680 CHS (Cardiovascular Health Study) participants without clinical histories of stroke or transient ischemic attack underwent brain MRI in 1992 and 1993, 1 to 2 years before echocardiographic exams (1994 to 1995)., Results: The mean age of the participants was 74.5 ± 4.8 years, and 39.3% were men. The presence of any annular or valvular calcification (mitral annular calcification, aortic annular calcification, or aortic valve sclerosis), mitral annular calcification alone, or aortic annular calcification alone was significantly associated with a higher prevalence of covert brain infarcts in unadjusted analyses (p < 0.01 for all). In models adjusted for age, sex, race, body mass index, physical activity, creatinine, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, diabetes, coronary heart disease, and congestive heart failure, the presence of any annular or valve calcification remained associated with covert brain infarcts (risk ratio: 1.24; 95% confidence interval: 1.05 to 1.47). The degree of annular or valvular calcification severity showed a direct relation with the presence of covert MRI findings., Conclusions: Left-sided cardiac annular and valvular calcifications are associated with covert MRI-defined brain infarcts. Further study is warranted to identify mechanisms and determine whether intervening in the progression of annular and valvular calcification could reduce the incidence of covert brain infarcts as well as the associated risk for cognitive impairment and future stroke., (2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We sought to determine whether the quantitative assessment of myocardial fibrosis (MF), either by histopathology or by contrast-enhanced magnetic resonance imaging (ce-MRI), could help predict long-term survival after aortic valve replacement., Background: Severe aortic valve disease is characterized by progressive accumulation of interstitial MF., Methods: Fifty-four patients scheduled to undergo aortic valve replacement were examined by ce-MRI. Delayed-enhanced images were used for the quantitative assessment of MF. In addition, interstitial MF was quantified by histological analysis of myocardial samples obtained during open-heart surgery and stained with picrosirius red. The ce-MRI study was repeated 27+/-22 months after surgery to assess left ventricular functional improvement, and all patients were followed for 52+/-17 months to evaluate long-term survival., Results: There was a good correlation between the amount of MF measured by histopathology and by ce-MRI (r=0.69, p<0.001). In addition, the amount of MF demonstrated a significant inverse correlation with the degree of left ventricular functional improvement after surgery (r=-0.42, p=0.04 for histopathology; r=-0.47, p=0.02 for ce-MRI). Kaplan-Meier analyses revealed that higher degrees of MF accumulation were associated with worse long-term survival (chi-square=6.32, p=0.01 for histopathology; chi-square=5.85, p=0.02 for ce-MRI). On multivariate Cox regression analyses, patient age and the amount of MF were found to be independent predictors of all-cause mortality., Conclusions: The amount of MF, either by histopathology or by ce-MRI, is associated with the degree of left ventricular functional improvement and all-cause mortality late after aortic valve replacement in patients with severe aortic valve disease., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to determine the prevalence of dilation and abnormal elastic properties of aortic root in first-degree relatives (FDRs) of bicuspid aortic valve (BAV) patients., Background: Evidence indicates that BAV is a genetic disorder. Although FDRs of affected individuals have an increased prevalence of BAV, their risk of aortic root abnormalities is unknown., Methods: We studied dimensions as well as the elastic properties of the ascending aorta in 48 FDRs with morphologically normal tricuspid aortic valves, 54 BAV patients, and 45 control subjects using 2-dimensional echocardiography., Results: The prevalence of aortic root dilation was 32% in FDRs and 53% in BAV patients, whereas all control subjects showed normal aortic dimensions (p < 0.001). The FDRs and BAVs had significantly lower aortic distensibility (1.7 +/- 1.4 x 10(-3) mm Hg and 1.4 +/- 2.0 x 10(-3) mm Hg vs. 2.5 +/- 1.6 x 10(-3) mm Hg, p < 0.001) and greater aortic stiffness index (26.7 +/- 25.8 and 55.9 +/- 76.8 vs. 18.7 +/- 40.1, p = 0.001) compared with control subjects. This difference remained significant in subjects without aortic root dilation or hypertension (p = 0.002 and p = 0.004, respectively)., Conclusions: The aortic root is functionally abnormal and dilation is common (32%) in first-degree relatives of patients with BAV. Screening of FDRs by transthoracic 2-dimensional echocardiography should be considered for detection of aortic valve malformation and dilated ascending aorta.

Objectives: We investigated in vivo in aortic valve stenosis (AVS) whether there is: 1) thermal heterogeneity within the valve leaflets; 2) temperature difference between the leaflets and the ascending aortic wall; and 3) a possible correlation between heat production, inflammation, and neoangiogenesis., Background: Histological studies have demonstrated a potential role of inflammation and neoangiogenesis in AVS., Methods: We examined 96 leaflets scheduled for aortic valve replacement. Twenty-five patients had AVS, and 7 had aortic valve insufficiency (AVI). Temperature measurements were performed right before hypothermic cardioplegia. Temperature difference (DeltaT) was assigned as the mean temperature of each leaflet minus the temperature of the aortic wall. Histological, immunohistological analysis, and vascular endothelial growth factor (VEGF) immunoreactivity was performed., Results: Significant thermal heterogeneity was recorded within the leaflets of AVS, compared with AVI (1.52 +/- 1.35 degrees C vs. 0.13 +/- 0.11 degrees C, p < 0.01). In AVS DeltaT was greater in all leaflets compared with the AVI group (p < 0.01). Leaflets of AVS had increased inflammatory cell infiltration, calcium deposit, and anti-VEGF expression compared with AVI (p < 0.01)., Conclusions: Thermal heterogeneity is increased in AVS and correlates with inflammatory mononuclear cell infiltration, expression of pro-inflammatory cytokines and neoangiogenic factors.

Objectives: We evaluated a large multicenter series of patients operated on for low-flow/low-gradient aortic stenosis (LF/LGAS) to stratify the operative risk, assess whether perioperative mortality has decreased over recent years, and analyze the post-operative outcome., Background: Although LF/LGAS is classically associated with a high operative risk, few data are available concerning the results of surgery in this setting., Methods: A total of 217 consecutive patients (168 men, 77%) with severe aortic stenosis (area <1 cm(2)), low ejection fraction (EF) (

With the current shift toward an older population, calcific aortic valve stenosis (AVS) is likely to become a major societal and economic burden. For many years, AVS was regarded as a degenerative and nonmodifiable process. However, molecular studies unanimously demonstrated that AVS is an actively regulated disorder with several potential therapeutic targets. Many factors are predicted to cause AVS, and an important genetic predisposition is anticipated. In this review, we describe candidate genes and signaling pathways identified by genetic research and incorporate this new knowledge into a more comprehensive picture of factors involved in the pathogenesis of AVS. We also emphasize the need for additional studies to elucidate its complete genetic architecture. Recent advances in genomic research offer a remarkable opportunity to investigate AVS at the most fundamental level. The benefits of these new approaches can be observed in many complex diseases, but the field of AVS is trailing behind. We discuss the future utility of these new genomic approaches to improve our understanding of AVS and to refine the management of patients in terms of diagnosis, prevention, and treatment.

Objectives: This study was designed to study the behavior of a stent deployed inside human stenotic aortic valves., Background: Endovascular valved stent (VS) implantation is a promising new therapy for patients with severe calcific aortic stenosis (AS). The precise characteristics of stent deployment in humans have been poorly studied so far., Methods: Thirty-five patients with severe AS were included in the study. Sixteen patients (46%) had bicuspid aortic valves. A self-expandable stent specifically designed for VS implantation was deployed intraoperatively inside the aortic valve before surgical aortic valve replacement., Results: In tricuspid aortic valves, the shape of stent deployment was circular, triangular, or elliptic in 68%, 21%, or 11%, respectively. Noncircular stent deployment was frequent in bicuspid aortic valves (the elliptic deployment being the rule [79%]), and stent underdeployment was constant. The incidence of gaps between the stent external surface and the aortic valve did not differ between tricuspid and bicuspid valves (58% vs. 43%; p = 0.49). Sharp calcific excrescences protruding inside the stent lumen were present in 3 cases (9%). Ex vivo study of a homemade VS confirmed that the regularity of the coaptation line of the leaflets was critically dependent on the presence or the absence of stent misdeployment., Conclusions: Stent misdeployment was constant in bicuspid valves and occurred in one-third of cases of tricuspid valves. Premature failure of implanted VS (secondary to valve distortion or traumatic injury to the leaflets by calcific excrescences) might be an important concern in the future.

Objectives: The purpose of this study was to examine the relationship between C-reactive protein (CRP) and calcific aortic valve disease in a large, randomly selected, population-based cohort., Background: The pathobiology of calcific aortic stenosis involves an active inflammatory, atheromatous, osteogenic process. Elevations in CRP, a measure of systemic inflammation, have been associated with aortic stenosis., Methods: Two-dimensional and Doppler echocardiography and CRP measurement were performed at baseline in 5,621 participants in the Cardiovascular Health Study. Multivariable analysis was used to identify CRP as a predictor of baseline and incident aortic stenosis., Results: At a mean echocardiographic follow-up of 5 years, 9% of subjects with aortic sclerosis progressed to some degree of aortic stenosis. Increasing age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.09 to 1.16; p < 0.001) and male gender (OR 3.05, 95% CI 1.76 to 5.27; p < 0.001) were related to risk of incident aortic stenosis, whereas increasing height (OR 0.96, 95% CI 0.94 to 0.99; p = 0.013) and African-American ethnicity conveyed a lower risk (OR 0.49, 95% CI 0.25 to 0.95; p = 0.035). C-reactive protein, treated as a continuous variable, was not associated with baseline aortic stenosis, progression to aortic sclerosis (adjusted OR 0.93, 95% CI 0.85 to 1.02; p = 0.107), or progression to aortic stenosis (adjusted OR 0.85, 95% CI 0.70 to 1.03; p = 0.092)., Conclusions: In this large population-based cohort, approximately 9% of subjects with aortic sclerosis progressed to aortic stenosis over a 5-year follow-up period. There was no association between CRP levels and the presence of calcific aortic-valve disease or incident aortic stenosis. C-reactive protein appears to be a poor predictor of subclinical calcific aortic-valve disease.

Objectives: The purpose of this study was to describe the relationship between neo-aortic root size, neo-aortic insufficiency (AI), and reintervention at mid-term follow-up., Background: Data on neo-aortic valve function and growth after the Ross procedure in children are limited., Methods: A total of 74 of 119 Ross patients from January 1995 to December 2003 had > or =2 follow-up echocardiograms at our institution and were included. Neo-aortic dimensions were converted to z-scores and modeled over time. Kaplan-Meier analysis was used to assess freedom from neo-aortic outcomes, and predictors were identified through multivariate analysis., Results: Median age at Ross was 9 years (range 3 days to 34 years). Over 4.7 years (range 3 months to 9.3 years) follow-up, there was disproportionate enlargement of the neo-aortic root (z-score increase of 0.75/year [p < 0.0001]). Neo-AI progressed > or =1 grade in 36% of patients and > or =2 grades in 15%. Nine patients (12%) had neo-aortic reintervention at 2.0 years (range 1.1 to 9.5 years) after the Ross procedure owing to severe neo-AI (n = 7), neo-aortic root dilation (n = 1), and neo-aortic pseudoaneurysm (n = 1). At 6 years after the Ross procedure, freedom from neo-aortic reintervention was 88%. Freedom from neo-aortic root z-score >4 was only 3% and from moderate or greater neo-AI was 60%. Longer follow-up time was associated with neo-aortic root dilation (p < 0.0001). Prior ventricular septal defect (VSD) repair predicted neo-AI (p = 0.02) and reintervention (p = 0.03). Prior aortic valve replacement (p = 0.002) also predicted neo-AI. Neo-aortic root dilation was not associated with neo-AI or reintervention., Conclusions: At mid-term follow-up after the Ross procedure, neo-aortic root size increases significantly out of proportion to somatic growth, and neo-AI is progressive. Prior VSD repair and aortic valve replacement were associated with neo-AI and reintervention.

Objectives: This study was designed to investigate the association between hypertension and aortic valve stenosis (AVS) in a rabbit model., Background: Degenerative AVS is a prevalent disease in elderly persons. Its molecular mechanisms remain unclear, in part because of the absence of experimental models. Epidemiologic data suggest a link between hypertension and AVS. However, there has been no evidence of a cause-effect relationship., Methods: New Zealand White rabbits were divided into two groups: 1) animals (n = 20) instrumented according to one-kidney/one-clip hypertensive model; and 2) control animals (n = 10) sham operated. Echocardiography (S12 MHz) was used to assess aortic valve (AV) morphology and function as well as left ventricular mass at baseline and after two and four months of hypertension., Results: Blood pressure and left ventricular mass increase were highly significant in the animal model but not in controls at two months, without noticeable AV function abnormalities. After 4 months, however, 14 hypertensive survived animals showed a 14.6% reduction of AV area (0.240 +/- 0.063 cm2 vs. 0.205 +/- 0.060 cm2, p < 0.05), a 19.6% increase of AV thickness (0.056 +/- 0.011 cm vs. 0.067 +/- 0.010 cm, p < 0.001), a 40.4% increase of transvalvular mean gradient (5.35 +/- 2.26 mm Hg vs. 7.51 +/- 3.73 mm Hg, p < 0.05) and a 63.6% increase of transvalvular maximal gradient (10.56 +/- 3.68 mm Hg vs. 17.28 +/- 10.95 mm Hg, p < 0.05). Control animals did not show significant changes., Conclusions: We report a novel experimental model of AVS in rabbits that may prove useful in studying the progression of the disease and the efficacy of new treatments. The present findings support the hypothesis of a causal link between hypertension and AVS.

Objectives: The purpose of this study was to validate and re-evaluate our previously reported scoring systems for predicting optimal management in neonates with aortic stenosis (AS)., Background: In 1991, we reported a multivariate discriminant equation and an ordinal scoring system for predicting which neonates with AS are suitable for biventricular repair and which are better served by single ventricle management., Methods: Retrospective analysis was performed to: 1) validate our scoring systems in 89 additional neonates with AS and normal mitral valve area, 2) assess the effects of 5% measurement variation on predictive scores, 3) evaluate our cohort with the Congenital Heart Surgeons' Society scoring system, and 4) repeat the discriminant analysis on the basis of all 126 patients., Results: The original scores each predicted outcome accurately in 68 patients (77%). Minor (5%) measurement variation changed the outcome predicted by the discriminant equation in 8 patients (9%) and by the threshold system in 13 patients (15%). The most accurate model for predicting survival with a biventricular circulation among the full cohort is: 10.98 (body surface area) + 0.56 (aortic annulus z-score) + 5.89 (left ventricular to heart long-axis ratio) - 0.79 (grade 2 or 3 endocardial fibroelastosis) - 6.78. With a cutoff of -0.65, outcome was predicted accurately in 90% of patients., Conclusions: Both of our original scoring systems are less accurate at predicting outcome than in our original analysis. Revised discriminant analysis yielded a model similar to our original equation that was 90% accurate at predicting survival with a biventricular circulation among neonates with AS and a mitral valve area z-score >-2.

Objectives: We aimed to test the diagnostic accuracy of cardiovascular magnetic resonance (CMR) imaging in distinguishing pathological left ventricular non-compaction (LVNC) from lesser degrees of trabecular layering seen in healthy volunteers and, in those with cardiomyopathies and concentric left ventricular hypertrophy, potential differential diagnoses. We hypothesized that pathological trabeculation could be distinguished by determining the ratio of non-compacted to compacted myocardium (NC/C ratio)., Background: Left ventricular non-compaction is characterized by a non-compacted myocardial layer in the left ventricle. Cardiovascular magnetic resonance images this layer with unprecedented quality, particularly in the ventricular apex, where echocardiography has inherent difficulties., Methods: We analyzed magnetic resonance cine images, using the 17-segment model in 45 healthy volunteers, 25 athletes, 39 patients with hypertrophic cardiomyopathy and 14 with dilated cardiomyopathy, 17 with hypertensive heart disease, and 30 with aortic stenosis, as well as images from 7 patients previously diagnosed with LVNC whose diagnoses were supported by additional features., Results: Areas of non-compaction were common and occurred more frequently in all groups studied in apical and lateral, rather than in basal or septal, segments. A NC/C ratio of >2.3 in diastole distinguished pathological non-compaction, with values for sensitivity, specificity, and positive and negative predictions of 86%, 99%, 75%, and 99%, respectively., Conclusions: Left ventricular non-compaction is diagnosed accurately with CMR using the NC/C ratio in diastole.

Objectives: The purpose of this study was to correlate the weights of operatively excised stenotic aortic valves to preoperative transvalvular peak systolic gradients and to calculated aortic valve areas., Background: No previous publication has correlated the weights of stenotic aortic valves to the transvalvular gradients or to the calculated aortic valve areas., Methods: We weighed operatively excised stenotic aortic valves in 324 adults who had undergone preoperative left-sided cardiac catheterization., Results: As the weights of the operatively excised stenotic aortic valves increased (from <1 g to >6 g), the average transvalvular peak systolic pressure gradients progressively increased. For any valve weight, in general, the women had higher average transvalvular gradients (p

Objectives: The aim of this study was to determine the relationship between aortic valve morphology and valve dysfunction., Background: The morphology of the bicuspid or bicommissural aortic valve (BAV) may predict the severity of valve dysfunction. Therefore, we assessed the relationship between BAV, aortic coarctation, and the degree of valve pathology in children., Methods: A retrospective review of 1,135 patients with BAV who were identified between 1986 and 1999 was performed. Patients younger than 18 years of age with BAV that was identifiable via echocardiography were included. The most recent or last study of each patient before intervention or endocarditis was reviewed. Mild stenosis was defined as a valve gradient > or =2 m/s, moderate or greater aortic stenosis as > or =3.5 m/s. Aortic regurgitation was quantified using standard criteria., Results: Median age was 3 years (range, 1 day to 17.9 years), and 67% of the patients were male. Right-coronary and left-coronary leaflet fusion were the most common types of BAV (70%). Aortic stenosis that was moderate or greater was observed most often in patients with right-coronary and non-coronary leaflet fusion (odds ratio 2.4, 95% confidence interval 1.6 to 3.6; p < or = 0.001). Similarly, right-coronary and non-coronary leaflet fusion was more often associated with moderate aortic regurgitation or greater (odds ratio 2.4, 95% confidence interval 1.2 to 4.7; p = 0.01). The majority of patients with aortic coarctation had fusion of the right-coronary and left-coronary leaflets (89%), and aortic coarctation was associated with lesser degrees of valve stenosis or regurgitation., Conclusions: Analysis of BAV morphology is of clinical and prognostic relevance. Fusion of the right-coronary and non-coronary leaflets was associated with more significant valve pathology, whereas fusion of the right-coronary and left-coronary leaflets was associated overwhelmingly with aortic coarctation and less aortic valve pathology.

Objectives: We studied the role of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in fibrosis formation in the transition from hypertrophy to heart failure (HF) as well as the cellular source of MMPs and TIMPs., Background: Human pressure-overloaded hearts are characterized by a significant increase in cardiac fibrosis. However, the contribution of the proteolytic/antiproteolytic system in aortic stenosis (AS) during hypertrophy progression has not yet been elucidated., Methods: Three groups of AS patients (I: EF >50%, n = 12; II: EF 50% to 30%, n = 10; III: EF <30%, n = 12) undergoing aortic valve replacement and seven controls were studied. Tissue samples were investigated by immunoconfocal microscopy, Western blotting, and zymography., Results: Quantitative analysis by immunoconfocal microscopy and Western blotting showed an upregulation of MMP-1, -2, -3, -9, -13, and -14 in group I and further increases in later stages. Tissue inhibitors of metalloproteinase-1 and -2 were enhanced and TIMP-4 was decreased in comparison to control. Gelatinolytic activity of MMP-2 significantly (p < 0.05) increased 1.2-fold (group I), 1.5-fold (group II), and 1.6-fold (group III) over control. The level of collagen I was significantly upregulated in all AS groups. Immunoconfocal microscopy showed that MMPs and TIMPs are produced predominantly by fibroblasts. The number of proliferating fibroblasts was significantly elevated during the transition to HF (0.67 n/mm(2)-control, 5.03-group III, p < 0.05)., Conclusions: In human hearts a continuous turnover of the extracellular matrix occurs during the progression from compensated hypertrophy to HF that is characterized by the upregulation of MMPs and inadequate inhibition by TIMPs. The altered balance between proteolysis/antiproteolysis with accompanying proliferation of fibroblasts results in fibrosis progression.

Aortic stenosis (AS) is the most common valvular disease requiring valve replacement. Its prevalence increases with age. When the severity of AS is only mild to moderate, it is well tolerated. When it becomes severe, AS confers significant morbidity and mortality. Adverse events can be avoided if it is possible to prevent or retard the progression from mild or moderate AS to severe AS. Progression of AS parallels the progression of sclerotic changes involving the aortic valve, which share histological and immunochemical similarities with the process of atherosclerosis. Far from being just a degenerative process, the development of AS is a complex and highly regulated process with a number of modifiable factors. One of the key factors appears to be lipoproteins, which are intimately involved in several pathways crucial to the development of AS. The importance of lipoproteins is further supported by epidemiological and clinical studies showing a strong association between lipoproteins and AS. The time has come to initiate prospective studies to assess the effect of cholesterol lowering on the progression of AS.

Objectives: We sought to determine whether the cardiac renin-angiotensin system (RAS) is activated in human aortic valve disease depending on left ventricular function, and we analyzed the concomitant regulation of the extracellular matrix components., Background: In animal models with pressure or volume load, activation of the cardiac RAS increases fibrosis. In human aortic valve disease, the ventricular collagen protein content is increased, but only scarce data on the activation state of the cardiac RAS and its effects on collagen and fibronectin messenger ribonucleic acid (mRNA) are available., Methods: In left ventricular biopsies from patients with aortic valve stenosis (AS) and aortic valve regurgitation and from control subjects, we quantitated mRNAs for angiotensin-converting enzyme (ACE), chymase, transforming growth factor-beta1 (TGF-beta1), collagen I, collagen III and fibronectin by reverse-transcription polymerase chain reaction. Proteins were localized by immunohistochemistry; ACE activity was determined by high performance liquid chromatography; and TGF-beta protein by quantitative enzyme immunoassay., Results: Protein, ACE and TGF-beta1 mRNA were significantly increased in patients with AS and AR (1.5- to 2.1-fold) and correlated with each other. The increase occurred also in patients with normal systolic function. Collagen I and III and fibronectin mRNAs were both upregulated about twofold in patients with AS and AR. In AS, collagen and fibronectin mRNA expression levels were positively correlated with left ventricular end-diastolic pressure and inversely with left ventricular ejection fraction (LVEF)., Conclusions: In human hearts, pressure and volume overload increases cardiac ACE and TGF-beta1 in the early stages. This activation of the cardiac RAS may contribute to the observed increase in collagen I and III and fibronectin mRNA expression. The increase in extracellular matrix already exists in patients with a normal LVEF, and it increases with functional impairment.

Objectives: We sought to develop an index of flow dependence of valve area in aortic valve (AoV) stenosis and to determine whether this index is related to structural characteristics of the diseased valve., Background: Many studies of AoV stenosis using Gorlin or continuity equation methods have demonstrated flow dependence (an increase in valve area with increased flow). Variation in flow dependence between patients despite similar flow rates remains unexplained., Methods: Dobutamine Doppler echocardiography was used to calculate flow rate and valve area by the continuity equation in 27 patients with aortic stenosis. For each patient the slope of the regression line of valve area to flow rate was determined (slope of flow dependence). Transesophageal echocardiography was used to evaluate features of valve morphology potentially related to the etiology of AoV stenosis and the mechanism of flow dependence., Results: Mean slope of flow dependence was 0.28 cm2/100 ml per s (range -0.06 to 0.53); flow dependence was significantly >0 in 21 patients and was lower for bicuspid valves (slope 0.21 cm2/100 ml per s) than for tricuspid valves with <10% commissural fusion (slope 0.35, p < 0.01). Off-center/ovoid orifices demonstrated the least flow dependence (slope 0.19), whereas star-shaped orifices showed the most (slope 0.36, p < 0.01). Greater flow dependence was related to a lower percentage of commissural fusion (r = -0.46, p = 0.02) as well as diffuse sclerosis, primarily involving the cusp bodies, rather than localized sclerosis, with involvement of cusp margins., Conclusions: The slope of flow dependence of valve area in AoV stenosis differs markedly between patients. More flow dependence was associated with tricuspid valves and the morphologic features characteristic of calcific AoV stenosis, whereas less flow dependence was associated with bicuspid valves and the features of rheumatic disease.

Objectives: The aim of this study was to evaluate the reliability of transthoracic two-dimensional echocardiography in measuring aortic valve area (AVA) by planimetry., Background: Planimetry of AVA using two-dimensional transesophageal echocardiographic images has been reported to be a reliable method for measuring AVA in patients with aortic stenosis. Recent advances in resolution of two-dimensional echocardiography permit direct visualization of an aortic valve orifice from the transthoracic approach more easily than before., Methods: Forty-two adult patients with valvular aortic stenosis were examined. A parasternal short-axis view of the aortic valve was obtained with transthoracic two-dimensional echocardiography. AVA was measured directly by planimetry of the inner leaflet edges at the time of maximal opening in early systole. AVA was also measured by planimetry using transesophageal echocardiography, by the continuity equation and by cardiac catheterization (Gorlin formula)., Results: In 32 (76%) of the 42 study patients, AVA could be detected by using the transthoracic planimetry method. There were good correlations between results of transthoracic two-dimensional echocardiographic planimetry and the continuity equation (y = 0.90x + 0.09, r = 0.90, p < 0.001, SEE = 0.09 cm2), transesophageal echocardiographic planimetry (y = 1.05x - 0.02, r = 0.98, p < 0.001, SEE = 0.04 cm2) and the Gorlin formula (y = 1.02x + 0.05, r = 0.89, p < 0.001, SEE = 0.10 cm2)., Conclusions: Transthoracic two-dimensional echocardiography provides a feasible and reliable method in measuring AVA in patients with aortic stenosis.

Objectives: The purpose of this study was to examine the echocardiographic abnormalities of the left ventricular outflow tract associated with subaortic stenosis in children., Background: Considerable evidence suggests that subaortic stenosis is an acquired and progressive lesion, but the etiology remains unknown. We have proposed a four-stage etiologic process for the development of subaortic stenosis. This report addresses the first stage by defining the morphologic abnormalities of the left ventricular outflow tract present in patients who develop subaortic stenosis., Methods: Two study groups were evaluated-33 patients with isolated subaortic stenosis and 12 patients with perimembranous ventricular septal defect and subaortic stenosis-and were compared with a size- and lesion-matched control group. Subjects ranged in age from 0.05 to 23 years, and body surface area ranged from 0.17 to 2.3 m2. Two independent observers measured aortoseptal angle, aortic annulus diameter and mitral-aortic separation from previously recorded echocardiographic studies., Results: The aortoseptal angle was steeper in patients with isolated subaortic stenosis than in control subjects (p < 0.001). This pattern was also true for patients with ventricular septal defect and subaortic stenosis compared with control subjects (p < 0.001). Neither age nor body surface area was correlated with aortoseptal angle. A trend toward smaller aortic annulus diameter indexed to patient size was seen between patients and control subjects but failed to achieve statistical significance (p = 0.08). There was an excellent interrater correlation in aortoseptal angle and aortic annulus measurement. The mitral-aortic separation measurement was unreliable. Our results, specifically relating steep aortoseptal angle to subaortic stenosis, confirm the results of other investigators., Conclusions: This study demonstrates that subaortic stenosis is associated with a steepened aortoseptal angle, as defined by two-dimensional echocardiography, and this association holds in patients with and without a ventricular septal defect. A steepened aortoseptal angle may be a risk factor for the development of subaortic stenosis.

Objectives: The objective of this study was to show elevations in septal shear stress in response to morphologic abnormalities that have been associated with discrete subaortic stenosis (SAS) in children. Combined with the published data, this critical connection supports a four-stage etiology of SAS that is advanced in this report., Background: Subaortic stenosis constitutes up to 20% of left ventricular outflow obstruction in children and frequently requires surgical removal, and the lesions may reappear unpredictably after the operation. The etiology of SAS is unknown. This study proposes a four-stage etiology for SAS that I) combines morphologic abnormalities, II) elevation of septal shear stress, III) genetic predisposition and IV) cellular proliferation in response to shear stress., Methods: Morphologic structures of a left ventricular outflow tract were modeled based on measurements in patients with and without SAS. Septal shear stress was studied in response to changes in aortoseptal angle (AoSA) (120 degrees to 150 degrees), outflow tract convergence angle (45 degrees, 22.5 degrees and 0 degree), presence/location of a ventricular septal defect (VSD) (3-mm VSD; 2 and 6 mm from annulus) and shunt velocity (3 and 5 m/s)., Results: Variations in AoSA produced marked elevations in septal shear stress (from 103 dynes/cm2 for 150 degrees angle to 150 dynes/cm2 for 120 degrees angle for baseline conditions). This effect was not dependent on the convergence angle in the outflow tract (150 to 132 dynes/cm2 over full range of angles including extreme case of 0 degree). A VSD enhanced this effect (150 to 220 dynes/cm2 at steep angle of 120 degrees and 3 m/s shunt velocity), consistent with the high incidence of VSDs in patients with SAS. The position of the VSD was also important, with a reduction of the distance between the VSD and the aortic annulus causing further increases in septal shear stress (220 and 266 dynes/cm2 for distances of 6 and 2 mm from the annulus, respectively)., Conclusions: Small changes in AoSA produce important changes in septal shear stress. The levels of stress increase are consistent with cellular flow studies showing stimulation of growth factors and cellular proliferation. Steepened AoSA may be a risk factor for the development of SAS. Evidence exists for all four stages of the proposed etiology of SAS.

Objectives: We sought to study the possible presence of Chlamydia pneumoniae in aortic valve stenosis (AVS)., Background: Inflammation and immune mechanisms are considered important for the pathogenesis of nonrheumatic AVS. All chlamydial species are able to cause heart infections, and seroepidemiologic studies have indicated an association between chronic C. pneumoniae infection and coronary artery disease. Furthermore, the organism has been demonstrated in atherosclerotic lesions., Methods: Aortic valve specimens with varying degrees of macroscopic disease were obtained from 35 subjects--17 consecutive patients undergoing aortic valve replacement for treatment of nonrheumatic AVS and 18 age-matched subjects at autopsy. The possible presence of C. pneumoniae in aortic valves was studied by immunohistochemical analysis, polymerase chain reaction or transmission electron microscopy, or a combination of these., Results: Positive immunohistochemical staining with C. pneumoniae specific antibody was found in 9 (53%) of 17 patients with advanced aortic valve disease requiring surgical treatment (group A), 8 (80%) of 10 cadavers with clearly macroscopic aortic valve pathology (group B) and 1 (12%) of 8 grossly normal cadaver control subjects (group C). Statistical significance with regard to the presence of C. pneumoniae was found when combined diseased subjects (groups A and B: total 17 of 27 subjects) were compared with group C (p = 0.018). However, when group A was compared with group C, there was only marginal statistical significance (p = 0.088). Finally, there was a strong statistical significance (p = 0.015) when groups B and C were compared. Chlamydia pneumoniae DNA was also found in three stenotic valves, and in two of the three tested valve specimens chlamydia-like particles were seen by electron microscopy., Conclusions: Chlamydia pneumoniae is frequently present in nonrheumatic AVS. Similarly, the high number of C. pneumoniae infections detected in the early lesions of "degenerative" AVS suggest that this pathogen may play an etiologic role in the development of this disease. The validity of this relation requires additional study.

Objectives: This study was designed to analyze the functional characteristics of fibroblasts present in aortic valves with degenerative stenosis., Background: Morphologic analysis of degenerative stenosis of tricuspid aortic valves has revealed an extensive interstitial fibrosis., Methods: Stenotic aortic valves collected during aortic valve replacement and control valves collected at autopsy were fixed in formaldehyde, cryosectioned and stained with antibodies against leukocyte markers, HLA-DR and intracellular filaments. Fibroblasts isolated from stenotic valve and skin explants were grown in cell culture, and their proliferative activity was analyzed by cell counting and uptake of tritiated thymidine., Results: In the stenotic valves nearly all interstitial cells expressed vimentin, and approximately 60% of the cells also expressed alpha-actin and desmin. HLA-DR was present on inflammatory cells as well as on one-third of the fibroblast-like cells in the interstitium. Macrophages were found in the interstitium and T lymphocytes close to calcium deposits and in subendothelial areas. In control valves, fibroblasts expressed vimentin but not alpha-actin or desmin. Few inflammatory cells were present in these valves, and HLA-DR expression was restricted to the endothelial surface. In culture, stenotic valve fibroblasts had a reduced ability to proliferate in serum and to activate DNA synthesis in response to growth factors compared with skin fibroblasts from the same patient., Conclusions: The observation that fibroblasts present in aortic valves with degenerative stenosis express smooth muscle cell characteristics and HLA-DR antigen and show signs of cellular senescence in vitro suggests that they are in a state of chronic activation similar to that observed in fibromatosis and scleroderma lesions.

Objectives: Cell-specific antibodies were used to identify immunocompetent cells in a comparison of valves from patients who had symptomatic tricuspid aortic stenosis with subjects who had no evidence of valvular heart disease., Background: Nonrheumatic valvular aortic stenosis is the most common valvular heart disease among adults. The biologic processes involved in the development of this disease are poorly understood., Methods: Tricuspid stenotic aortic valves were obtained from 19 patients undergoing surgery for nonrheumatic valvular aortic stenosis, and 10 control valves were collected at autopsy. The valves were fixed in formaldehyde, cryosectioned and stained with antibodies against fibroblasts, endothelial cells, macrophages, T lymphocytes and interleukin-2 receptors. A subset of valves were also analyzed with antibodies against T-helper cells and cytotoxic T cells., Results: Stenotic valves were characterized by a basal accumulation of calcium deposits and a cell-rich subendothelial thickening. The immunohistologic analysis indicated that the cells in the subendothelial connective tissue were fibroblasts. T lymphocytes appeared to be the most common cell type in the vicinity of the calcium deposits and were also found close to the endothelial lining of the valves. T-helper cells were more frequent than cytotoxic T cells. Expression of interleukin-2 receptors occurred at the same location as T lymphocytes. Control valves lacked subendothelial thickening and contained only few cells reacting with antibodies against lymphocytes and macrophages., Conclusions: The presence of activated T lymphocytes in tricuspid stenotic valves suggests that immunologic mechanisms may be involved in the etiology of nonrheumatic aortic stenosis.

Objectives: We investigated the relation between the extent and pattern of left ventricular hypertrophy and surgical outcome in 54 patients undergoing aortic valve replacement for severe aortic stenosis., Background: Previous work from our laboratory has demonstrated that a subgroup of patients, mostly elderly women with Doppler evidence of abnormal intracavitary flow acceleration, had an unexpectedly high in-hospital mortality rate after aortic valve replacement for aortic stenosis. We hypothesized that marked concentric hypertrophy, rather than the Doppler signal itself, was related to the poor outcome., Methods: A retrospective analysis of the clinical, hemodynamic and echocardiographic data in patients who survived aortic valve replacement versus those who died in the hospital was performed., Results: There were no differences between the 42 survivors and 12 nonsurvivors with regard to the clinical or hemodynamic variables. Of the echocardiographic variables analyzed, diastolic relative wall thickness was found to be significantly different between the two groups. Patients who died had significantly greater relative wall thickness (mean +/- SD) than those who survived (0.72 +/- 0.38 vs. 0.56 +/- 0.15, p = 0.04). Analysis by gender demonstrated that the relation between ventricular geometry and mortality held true only for women., Conclusions: We conclude that excessive ventricular hypertrophy, manifested as a markedly increased relative wall thickness, is associated with a significantly increased risk of postoperative mortality after aortic valve replacement for aortic stenosis.

Objectives: The purpose of this study was to evaluate left ventricular structure-function interplay in aortic valve disease., Background: An increase in myocardial fibrosis has been demonstrated in aortic valve disease, but changes in the collagen network and their effect on ventricular function have not been defined., Methods: Left ventricular structure was assessed from left ventricular endomyocardial biopsy specimens obtained in 32 patients with aortic valve disease (aortic stenosis in 25, aortic regurgitation in 7). Total collagen volume fraction, orthogonal collagen fiber meshwork (cross-hatching), endocardial fibrosis, muscle fiber diameter and volume fraction of myofibrils were determined by morphologic-morphometric evaluation. Control biopsy data were obtained from six donor hearts before transplantation. Eleven other patients with normal left ventricular function served as hemodynamic status control subjects. Left ventricular biplane cineangiography and high fidelity pressure measurements were carried out in all patients. Systolic function was assessed from ejection fraction. Diastolic function was evaluated by the time constant of relaxation, early and late peak filling rates and the constant of passive myocardial stiffness. Patients were assigned to three groups according to increasing severity of nonmyocyte tissue alterations. Group 1 comprised 10 patients with elevated total collagen volume fraction. Group 2 comprised 6 patients with normal total collagen volume fraction and the presence of increased cross-hatching or endocardial fibrosis, or both. Group 3 comprised 16 patients with elevated total collagen volume fraction and the presence of cross-hatching or endocardial fibrosis, or both., Results: Muscle fiber diameter was increased in the three groups with aortic valve disease, whereas the volume fraction of myofibrils was comparable in all four study groups. Ejection fraction was depressed in groups 2 and 3 compared with the control group. The time constant of relaxation was prolonged in the three groups with aortic valve disease. No differences in early and late peak filling rate were observed in the four study groups, but the constant of myocardial stiffness increased in groups 2 and 3., Conclusions: In aortic valve disease, changes in collagen architecture are associated with altered systolic function and passive diastolic properties. The sole increase in total collagen volume fraction without a change in architecture leaves systolic and passive diastolic function unaltered.

Objectives: This study was conducted to determine the utility of aortic valve resistance in assessing the severity of aortic stenosis., Background: Assessment of the severity of aortic stenosis has traditionally employed hemodynamic data and the Gorlin formula to calculate the area of the aortic valve. Recently, flow dependence of the Gorlin formula has been identified and the accuracy of the formula challenged. Aortic valve resistance, the quotient of gradient and cardiac output, has been advanced as potentially useful in assessing the severity of valve stenosis., Methods: We studied 48 symptomatic patients with an initial diagnosis of severe aortic stenosis based on a calculated aortic valve area of less than or equal to 0.8 cm2 by the Gorlin formula. Forty of these patients (Group I) were confirmed to have severe aortic stenosis, whereas 8 (Group II) were subsequently proved not to have severe aortic stenosis. The 18 patients in Group I with a valve area of 0.6 to 0.8 cm2 (Group IA) were directly compared with Group II patients who had a similar valve area., Results: Aortic valve area was nearly identical in Group IA and Group II patients (0.69 +/- 0.05 and 0.71 +/- 0.06 cm2, respectively, p = NS). However, aortic valve resistance was much less in Group II patients (212 +/- 6 vs. 316 +/- 11 dynes.s.cm-5, p less than 0.0001). In this small cohort, aortic valve resistance achieved nearly complete separation of patients in Groups IA and II., Conclusions: In some patients with relatively mild aortic stenosis, the calculated valve area may indicate that the stenosis is severe. The use of aortic valve resistance in conjunction with the Gorlin formula helps separate patients with truly severe aortic stenosis from those with milder disease.

Objectives: This study was designed to study pressure recovery in various models of aortic valve stenosis by performing hemodynamic measurements under physiologic conditions in a pulsatile aortic flow circuit. The results were used to validate calculations of pressure recovery based on theoretic considerations derived from fluid dynamics., Background: Pressure recovery in aortic stenosis has not been systematically analyzed., Methods: Stenoses varying in size, shape (circular, Y-shaped, slitlike) and inlet configuration (sharp-edged, nozzle-shaped inlet, artificially stenosed bioprostheses) were used. Aortic pressures were measured at multiple sites distal to the stenotic orifice to determine pressure gradients and recovery., Results: With decreasing orifice area (2, 1.5, 1 and 0.5 cm2) pressure recovery increased (5, 7, 10 and 16 mm Hg, respectively) and the index pressure recovery to maximal peak to peak gradient decreased (56%, 37%, 24% and 14%, respectively). For a given orifice size of 0.5 cm2, this index ranged between 12% for a Y-shaped orifice and 15% for a circular orifice with a nozzle (cardiac output 4 liters/min). Increasing the cardiac output increased pressure recovery, whereas the ratio of pressure recovery to maximal pressure gradient remained constant., Conclusions: The index pressure recovery to transvalvular pressure gradient, which expresses the hemodynamic relevance of pressure recovery, decreases with increasing severity of aortic stenosis but is independent of transvalvular flow. Thus, pressure recovery is of minor importance in severe aortic stenosis but may account for discrepancies between Doppler and manometric gradients observed in patients with mild to moderate aortic stenosis or a prosthetic valve in the aortic position.

Preliminary findings from clinical trials of percutaneous balloon aortic valvuloplasty and intraoperative debridement of calcific deposits in patients with aortic stenosis have suggested that calcified, congenitally bicuspid aortic valves may be less amenable to these techniques than are calcified tricuspid aortic valves. Accordingly, we evaluated the histoarchitecture of calcific deposits in 30 operatively excised aortic valves. Light microscopic sections taken through the calcified aortic valve leaflets disclosed two principal types of histoarchitecture. In 11 aortic valves nodular calcific deposits were superimposed on an underlying fibrotic aortic valve leaflet (type A); in 17 valves calcific deposits were diffusely distributed throughout the body (spongiosa) of the aortic valve leaflets (type B). Two aortic valves could not be classified histologically. These histologic subtypes were not randomly distributed with regard to gross valvular morphology. All 14 bicuspid valves (100%) were type B; in contrast, 11 (69%) of 16 tricuspid aortic valves were type A, and only 3 (19%) of 16 tricuspid valves were type B (p less than 0.01). Both valves with nonclassifiable histologic features were tricuspid on the basis of gross examination. Thus, the histoarchitectural distribution of calcific deposits is different for bicuspid than for tricuspid stenotic aortic valves. The more diffuse distribution of calcium throughout the body of calcified bicuspid aortic valve leaflets may render these valves less amenable to operative and percutaneous valvuloplasty than are calcified tricuspid aortic valve leaflets on which calcific deposits are typically superimposed in nodular form.

Fourteen patients, aged 1 month to 13 years, with congenital semilunar valve stenosis (11 pulmonary and 3 aortic) were studied for orifice area quantification calculated from a Doppler echocardiographic equation: Area = SV/0.88 X V2 X VET, where SV = stroke volume, V2 = maximal velocity and VET = ventricular ejection time. Results from individual measurements used in this formula and derived area were compared with individual results from cardiac catheterization and valve area derived from the Gorlin formula. Ventricular ejection time by cardiac catheterization ranged from 0.17 to 0.44 second (mean +/- standard deviation [SD] 0.27 +/- 0.09), and by Doppler study from 0.20 to 0.41 second (mean +/- SD 0.29 +/- 0.06) (r = 0.65, standard error of the estimate [SEE] = 0.03, y = 0.149 + 0.528x). Pressure gradient by catheterization ranged from 30 to 125 mm Hg (mean +/- SD 56.6 +/- 33.1), and by Doppler study from 17.6 to 100 mm Hg (mean +/- SD 46.8 +/- 27.9) (r = 0.91, SEE = 8.8, y = 1.23 + 0.904x). Stroke volume was measured by Doppler study simultaneously with cardiac catheterization in nine patients; results at cardiac catheterization with thermodilution measurements (cardiac output/heart rate) ranged from 5.5 to 53.4 cc (mean +/- SD 24.7 +/- 20), and by Doppler study from 5.8 to 46.9 cc (mean +/- SD 23 +/- 18) (r = 0.96, SEE = 3.5). Area quantification was performed in two ways. In Group 1, heart rate-matched stroke volumes from cardiac catheterization were used in the derived equation for Doppler study (all patients). In Group 2, the stroke volume used was that obtained by Doppler study, which was performed simultaneously with cardiac catheterization (nine patients).(ABSTRACT TRUNCATED AT 250 WORDS)

The role of two-dimensional echocardiography in the management of any congenital cardiovascular anomaly depends on the lesion's natural history and surgical alternatives. Diagnostic assessment of subaortic stenosis and postoperative follow-up of Fontan and Mustard/Senning procedures and tetralogy of Fallot reconstruction illustrate the application of two-dimensional echocardiography to the management of these problems in the older child. Two-dimensional echocardiography displays the static anatomic as well as dynamic functional sequels of left ventricular outflow obstruction. Detailed anatomic display of Fontan reconstruction is compromised by its somewhat unpredictable spatial organization. Combining two-dimensional imaging with gated pulsed Doppler techniques, however, supplements limited anatomic definition with flow profile data specific to the varied surgical interpretations of the Fontan principle. In a similar manner, combined imaging after Senning/Mustard procedures permits detailed anatomic and hemodynamic interrogation of pulmonary and systemic venous return to the neo-left and neo-right atria. The limitations of cardiac ultrasound imaging of the older child after tetralogy of Fallot reconstruction offer some insight into the future directions that are necessary in the application of this imaging technique. Imaging of these patients is compromised by the prosthetic material, which compromises the assessment of right ventricular outflow pulmonary artery reconstruction and ventricular septal closure. Although gated pulsed Doppler echocardiography overcomes some of these limitations, better tissue characterization in the presence of bioprosthetic material is necessary.

Thirty adult patients with aortic stenosis had Doppler echocardiography within 1 day of cardiac catheterization. Noninvasive measurement of the mean transaortic pressure gradient was calculated by applying the simplified Bernoulli equation to the continuous wave Doppler transaortic velocity recording. Stroke volume was measured noninvasively by multiplying the systolic velocity integral of flow in the left ventricular outflow tract (obtained by pulsed Doppler ultrasonography) by the cross-sectional area of the left ventricular outflow tract (measured by two-dimensional echocardiography). Non-invasive measurement of aortic valve area was calculated by two methods. In method 1, the Gorlin equation was applied using Doppler-derived mean pressure gradient, cardiac output and systolic ejection period. Method 2 used the continuity equation. These noninvasive measurements were compared with invasive measurements using linear regression analysis, and mean pressure gradients correlated well (r = 0.92). Aortic valve area by either noninvasive method also correlated well with cardiac catheterization values (method 1, r = 0.87; method 2, r = 0.88). The sensitivity of Doppler detection of critical aortic stenosis was 0.86, with a specificity of 0.88 and a positive predictive value of 0.86. Cardiac output measured nonsimultaneously showed poor correlation (r = 0.51). Doppler echocardiography can distinguish critical from noncritical aortic stenosis with a high degree of accuracy. Measurement of aortic valve area aids interpretation of Doppler-derived mean pressure gradient data when the gradients are in an intermediate range (30 to 50 mm Hg).