Lipoprotein(a) and Calcific Aortic Valve Stenosis Progression: A Systematic Review and Meta-Analysis.

Importance: There are currently no pharmacological treatments available to slow hemodynamic progression of aortic stenosis. Plasma lipoprotein(a) concentrations predict incident aortic stenosis but its association with hemodynamic progression is controversial. Objective: To determine the association between plasma lipoprotein(a) concentrations and hemodynamic progression in patients with aortic stenosis. Design, Settings and Participants: The study included patients with aortic stenosis from 5 longitudinal clinical studies conducted from March 2001 to March 2023 in Canada and the UK. Of 757 total patients, data on plasma lipoprotein(a) concentrations and rates of hemodynamic progression assessed by echocardiography were available for 710, who were included in this analysis. Data were analyzed from March 2023 to April 2024. Exposure: Cohort-specific plasma lipoprotein(a) concentration tertiles. Main Outcomes and Measures: Hemodynamic aortic stenosis progression on echocardiography as assessed by annualized change in peak aortic jet velocity, mean transvalvular gradient, and aortic valve area. Results: Among the included patients, 497 (70%) were male and 213 (30%) were female. The mean (SD) age was 65.2 (13.1) years. Patients in the top lipoprotein(a) tertile demonstrated 41% (estimate, 1.41; 95% CI, 1.13-1.75) faster progression of peak aortic jet velocity and 57% (estimate, 1.57; 95% CI, 1.18-2.10) faster progression of mean transvalvular gradient than patients in the bottom tertile. There was no evidence of heterogeneity across the individual cohorts. Progression of aortic valve area was comparable between groups (estimate, 1.23; 95% CI, 0.71-2.12). Similar results were observed when plasma lipoprotein(a) concentrations were treated as a continuous variable. Conclusions and Relevance: In this study, higher plasma lipoprotein(a) concentrations were associated with faster rates of hemodynamic progression in patients with aortic stenosis. Lowering plasma lipoprotein(a) concentrations warrants further investigation in the prevention and treatment of aortic stenosis.

Impact of C-reactive protein levels on lipoprotein(a)-associated aortic stenosis incidence and progression.

Aims: Elevated lipoprotein(a) [Lp(a)] levels are associated with the risk of coronary artery disease (CAD) and calcific aortic valve stenosis (CAVS). Observational studies revealed that Lp(a) and C-reactive protein (CRP) levels, a biomarker of systemic inflammation, may jointly predict CAD risk. Whether Lp(a) and CRP levels also jointly predict CAVS incidence and progression is unknown. Methods and results: We investigated the association of Lp(a) with CAVS according to CRP levels in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study (n = 18 226, 406 incident cases) and the UK Biobank (n = 438 260, 4582 incident cases), as well as in the ASTRONOMER study (n = 220), which assessed the haemodynamic progression rate of pre-existing mild-to-moderate aortic stenosis. In EPIC-Norfolk, in comparison to individuals with low Lp(a) levels (<50 mg/dL) and low CRP levels (<2.0 mg/L), those with elevated Lp(a) (>50 mg/dL) and low CRP levels (<2.0 mg/L) and those with elevated Lp(a) (>50 mg/dL) and elevated CRP levels (>2.0 mg/L) had a higher CAVS risk [hazard ratio (HR) = 1.86 (95% confidence intervals, 1.30-2.67) and 2.08 (1.44-2.99), respectively]. A comparable predictive value of Lp(a) in patients with vs. without elevated CRP levels was also noted in the UK Biobank. In ASTRONOMER, CAVS progression was comparable in patients with elevated Lp(a) levels with or without elevated CRP levels. Conclusion: Lp(a) predicts the incidence and possibly progression of CAVS regardless of plasma CRP levels. Lowering Lp(a) levels may warrant further investigation in the prevention and treatment of CAVS, regardless of systemic inflammation.

Natural History of Mitral Annular Calcification and Calcific Mitral Valve Disease.

BACKGROUND: The natural history of mitral annular calcification (MAC) and risk for developing calcific mitral valve disease (CMVD) have been poorly defined. The aim of this study was to evaluate the progression rate of MAC and of the development of CMVD. METHODS: Patients with MAC and paired echocardiograms ≥1 year apart between 2005 and 2019 were included. Progression rates from mild or moderate to severe MAC and to CMVD (defined as severe MAC and significant mitral stenosis and/or regurgitation) were assessed, along with potential association with sex. RESULTS: A total of 11,605 patients (mean age, 73 ± 10 years; 51% men) with MAC (78% mild, 17% moderate, 5% severe) were included and underwent follow-up echocardiography at 4.2 ± 2.7 years. Among patients with mild or moderate MAC, 33% presented with severe MAC at 10 years. The rate of severe MAC was higher in women than in men (41% vs 24% [P < .001]; hazard ratio, 1.3; P < .001) and in patients with moderate versus mild MAC (71% vs 22% [P < .001]; hazard ratio, 6.1; P < .001). At 10 years, 10% presented with CMVD (4%, 23%, and 60% in patients with mild, moderate, and severe MAC, respectively), which was predicted by female sex (15% vs 5%; P < .0001), even after adjustment for MAC severity (hazard ratio, 1.9; P < .001). CONCLUSION: In this large cohort of patients with MAC, progression to severe MAC was common and frequently resulted in CMVD. Female sex was associated with higher progression rates. MAC and CMVD are expected to dramatically increase as the population ages, highlighting the importance of a better understanding of the pathophysiology of MAC to develop effective preventive medical therapies.

Evaluating the effectiveness of rosuvastatin in preventing the progression of diastolic dysfunction in aortic stenosis: A substudy of the aortic stenosis progression observation measuring effects of rosuvastatin (ASTRONOMER) study.

BACKGROUND: Tissue Doppler imaging (TDI) is a noninvasive echocardiographic method for the diagnosis of diastolic dysfunction in patients with varying degrees of aortic stenosis (AS). Little is known however, on the utility of TDI in the serial assessment of diastolic abnormalities in AS. OBJECTIVE: The aim of the current proposal was to examine whether treatment with rosuvastatin was successful in improving diastolic abnormalities in patients enrolled in the Aortic Stenosis Progression Observation Measuring Effects of Rosuvastatin (ASTRONOMER) study. METHODS: Conventional Doppler indices including peak early (E) and late (A) transmitral velocities, and E/A ratio were measured from spectral Doppler. Tissue Doppler measurements including early (E') and late (A') velocities of the lateral annulus were determined, and E/E' was calculated. RESULTS: The study population included 168 patients (56 ± 13 years), whose AS severity was categorized based on peak velocity at baseline (Group I: 2.5-3.0 m/s; Group II: 3.1-3.5 m/s; Group III: 3.6-4.0 m/s). Baseline and follow-up hemodynamics, LV dimensions and diastolic functional parameters were evaluated in all three groups. There was increased diastolic dysfunction from baseline to follow-up in each of the placebo and rosuvastatin groups. In patients with increasing severity of AS in Groups I and II, the lateral E' was lower and the E/E' (as an estimate of increased left ventricular end-diastolic pressure) was higher at baseline (p < 0.05). However, treatment with rosuvastatin did not affect the progression of diastolic dysfunction from baseline to 3.5 year follow-up between patients in any of the three predefined groups. CONCLUSION: In patients with mild to moderate asymptomatic AS, rosuvastatin did not attenuate the progression of diastolic dysfunction.

Clinical implications of left atrial size adjustment: Impact of obesity.

BACKGROUND: American and European societies recommend using left atrial (LA) volume adjusted to body surface area (BSA) as the means of indexing LA volume to the patient's body size irrespective of morphometric characteristics. AIM: To evaluate the impact of obesity on LA volume indexation to BSA on the presence and degree of LA enlargement. METHODS: From our echocardiography database, we extracted all consecutive adults referred for a transthoracic echocardiography in 2019 (n=28,725; 64±17 years; 55% male; 31% obese [body mass index≥30kg/m2]). LA volume indexed to BSA was calculated using measured weight (LAMeas) and ideal weight (LAIdeal) calculated using the Devine Formula. RESULTS: LAMeas and LAIdeal were 35±17mL/m2 and 40±19mL/m2, respectively (P<0.0001); 13% were classified as having a normal LAMeas but LAIdeal enlargement overall, 25% in obese patients and 7% in non-obese patients (P<0.0001). The percentages of patients with no, mild, moderate and severe LA dilatation were 57%, 19%, 9% and 16%, respectively, using LAMeas, and 45%, 20%, 11% and 24%, respectively, using LAIdeal (kappa=0.57). Degree of LA enlargement differed in 8194 patients (29%); 96% of the disagreement was related to underestimation of the degree of LA enlargement using LAMeas. Agreement for the degree of LA enlargement was poor in obese and good in non-obese patients (kappa=0.28 and 0.71, respectively). As illustrative clinical implications, diastolic function grade was modified in 8.3% of patients with preserved ejection fraction and 10.8% of patients with reduced left ventricular ejection fraction/myocardial disease, and timing for intervention was potentially different in 12.9% of patients with primary mitral regurgitation. CONCLUSIONS: Indexing LA volume to measured BSA versus ideal BSA markedly underestimates the presence and severity of LA enlargement, especially in obese patients, with potential important clinical implications.

Size-adjusted aortic valve area: refining the definition of severe aortic stenosis.

AIMS: Severe aortic valve stenosis (AS) is defined by an aortic valve area (AVA) <1 cm2 or an AVA indexed to body surface area (BSA) <0.6 cm/m2, despite little evidence supporting the latter approach and important intrinsic limitations of BSA indexation. We hypothesized that AVA indexed to height (H) might be more applicable to a wide range of populations and body morphologies and might provide a better predictive accuracy. METHODS AND RESULTS: In 1298 patients with degenerative AS and preserved ejection fraction from three different countries and continents (derivation cohort), we aimed to establish an AVA/H threshold that would be equivalent to 1.0 cm2 for defining severe AS. In a distinct prospective validation cohort of 395 patients, we compared the predictive accuracy of AVA/BSA and AVA/H. Correlations between AVA and AVA/BSA or AVA/H were excellent (all R2 > 0.79) but greater with AVA/H. Regressions lines were markedly different in obese and non-obese patients with AVA/BSA (P < 0.0001) but almost identical with AVA/H (P = 0.16). AVA/BSA values that corresponded to an AVA of 1.0 cm2 were markedly different in obese and non-obese patients (0.48 and 0.59 cm2/m2) but not with AVA/H (0.61 cm2/m for both). Agreement for the diagnosis of severe AS (AVA < 1 cm2) was significantly higher with AVA/H than with AVA/BSA (P < 0.05). Similar results were observed across the three countries. An AVA/H cut-off value of 0.6 cm2/m [HR = 8.2(5.6-12.1)] provided the best predictive value for the occurrence of AS-related events [absolute AVA of 1 cm2: HR = 7.3(5.0-10.7); AVA/BSA of 0.6 cm2/m2 HR = 6.7(4.4-10.0)]. CONCLUSION: In a large multinational/multiracial cohort, AVA/H was better correlated with AVA than AVA/BSA and a cut-off value of 0.6 cm2/m provided a better diagnostic and prognostic value than 0.6 cm2/m2. Our results suggest that severe AS should be defined as an AVA < 1 cm2 or an AVA/H < 0.6 cm2/m rather than a BSA-indexed value of 0.6 cm2/m2.

Mobile ventricular thrombus arising from the mitral annulus in patients with dense mitral annular calcification.

Mitral annular calcification (MAC) has been considered a risk factor for thrombo-embolic disease. Superimposed thrombus formation on MAC has not been well described as a possible underlying mechanism for this association. We report three patients with mobile left ventricular (LV) thrombus arising from the LV aspect of severe calcified mitral annulus in the setting of normal LV function, mitral valve function, and sinus rhythm.

Association of Bicuspid aortic valve morphology and aortic root dimensions: a substudy of the aortic stenosis progression observation measuring effects of rosuvastatin (ASTRONOMER) study.

BACKGROUND: Bicuspid aortic valve (BAV) is the leading cause of aortic stenosis in patients younger than the age of 50. A classification scheme of BAVs is based upon leaflet orientation: Type I (fusion of right and left coronary cusps) and Type II (fusion of right and noncoronary cusps). The correlation between BAV leaflet orientation and aortic root pathology however remains ill defined. OBJECTIVE: The objective was to describe a potential relationship between BAV leaflet morphology and aortic root measurements in the ASTRONOMER study, a multicenter study to assess the effect of rosuvastatin on the progression of AS. METHODS: BAV morphology was classified as Type I or Type II orientation based on the parasternal short-axis view. Echo measurements including left ventricular and aortic root dimensions were obtained. RESULTS: The study population included 89 patients (56 +/- 11 years; 44 males). There were 63 patients with Type I and 26 patients with Type II BAV. Baseline demographics, hemodynamics, and left heart dimensions were similar between both groups. Patients with Type I BAV had larger aortic annulus and ascending root dimensions compared to those patients with Type II BAV (P < 0.05). CONCLUSION: In patients with mild to moderate aortic stenosis due to a BAV, the presence of Type I valve orientation was associated with significantly greater aortic root parameters compared to Type II valve orientation.

Presentation and management of calcific mitral valve disease.

Little is known about the prevalence, presentation and management of calcific mitral valve disease (CMVD). We identified 167 patients (80 ± 10 years; 79% women) with significant CMVD undergoing transthoracic echocardiography at our institution in 2016. Patients presented with significant co-morbidities, 47% had moderate/severe mitral stenosis, 38% had 3+/4+ mitral regurgitation and 15% had a combination of both. Fifty-eight percent were symptomatic. Most symptomatic patients were managed conservatively and incurred higher mortality and mortality/heart failure admission rates than those managed surgically. These data highlight the importance of gaining mechanistic insights into CMVD to prevent its occurrence and avoid the need for high-risk surgery, which is seldom performed in contemporary practice.

Association of mitral annular calcification and aortic valve morphology: a substudy of the aortic stenosis progression observation measuring effects of rosuvastatin (ASTRONOMER) study.

AIMS: Mitral annular calcification (MAC) is characterized by calcium and lipid deposition in the annular fibrosa of the mitral valve. Although individuals with MAC are at increased risk of cardiovascular events, little is known about the significance of this finding in patients with concurrent aortic stenosis (AS). The aim of this study was to describe the association of baseline MAC and aortic valve morphology in asymptomatic patients enrolled in the ASTRONOMER study, a multicentre study to assess the effect of Rosuvastatin on the progression of AS. METHODS AND RESULTS: At baseline, transthoracic echocardiography was performed with two-dimensional and Doppler imaging following a standardized protocol. Echo measurements including left ventricular (LV) dimensions and aortic root dimensions were obtained according to the ASE recommendations. MAC was identified by bright echoes at the base of the mitral leaflets or annulus on 2D imaging, and aortic valve calcification by visualization of bright echoes on the aortic valve leaflets. The degree of calcification was semi-quantitated from absent to severe. The study population included 219 patients (57 +/- 14 years; 129 males), divided into two pre-specified categories; bicuspid (n = 133) and tricuspid (n = 86) aortic valves. Baseline LV dimensions, aortic valve haemodynamics, and cholesterol profiles were similar between the two groups at baseline. Individuals with tricuspid aortic valves were older, more hypertensive, with higher degrees of MAC and AV calcification (P < 0.001). The higher degree of MAC persisted in patients with tricuspid AV after adjustment for age and systolic blood pressure (P = 0.004). CONCLUSION: In patients with asymptomatic mild to moderate AS, MAC is more prevalent in those individuals with tricuspid AV, independent of age, and systolic blood pressure. Whether the degree of MAC may be a surrogate for atherosclerosis, and predict the subset of patients who will respond to statin therapy in preventing the progression of AS, remains to be determined.

Association of Mild to Moderate Aortic Valve Stenosis Progression With Higher Lipoprotein(a) and Oxidized Phospholipid Levels: Secondary Analysis of a Randomized Clinical Trial.

Importance: Several studies have reported an association of levels of lipoprotein(a) (Lp[a]) and the content of oxidized phospholipids on apolipoprotein B (OxPL-apoB) and apolipoprotein(a) (OxPL-apo[a]) with faster calcific aortic valve stenosis (CAVS) progression. However, whether this association is threshold or linear remains unclear. Objective: To determine whether the plasma levels of Lp(a), OxPL-apoB, and OxPL-apo(a) have a linear association with a faster rate of CAVS progression. Design, Setting, and Participants: This secondary analysis of a randomized clinical trial tested the association of baseline plasma levels of Lp(a), OxPL-apoB, and OxPL-apo(a) with the rate of CAVS progression. Participants were included from the ASTRONOMER (Effects of Rosuvastatin on Aortic Stenosis Progression) trial, a multicenter study conducted in 23 Canadian sites designed to test the effect of statin therapy (median follow-up, 3.5 years [interquartile range, 2.9-4.5 years]). Patients with mild to moderate CAVS defined by peak aortic jet velocity ranging from 2.5 to 4.0 m/s were recruited; those with peak aortic jet velocity of less than 2.5 m/s or with an indication for statin therapy were excluded. Data were collected from January 1, 2002, through December 31, 2005, and underwent ad hoc analysis from April 1 through September 1, 2018. Interventions: After the randomization process, patients were followed up by means of echocardiography for 3 to 5 years. Main Outcomes and Measures: Progression rate of CAVS as assessed by annualized progression of peak aortic jet velocity. Results: In this cohort of 220 patients (60.0% male; mean [SD] age, 58 [13] years), a linear association was found between plasma levels of Lp(a) (odds ratio [OR] per 10-mg/dL increase, 1.10; 95% CI, 1.03-1.19; P = .006), OxPL-apoB (OR per 1-nM increase, 1.06; 95% CI, 1.01-1.12; P = .02), and OxPL-apo(a) (OR per 10-nM increase, 1.16; 95% CI, 1.05-1.27; P = .002) and faster CAVS progression, which is marked in younger patients (OR for Lp[a] level per 10-mg/dL increase, 1.19 [95% CI, 1.07-1.33; P = .002]; OR for OxPL-apoB level per 1-nM increase, 1.06 [95% CI, 1.02-1.17; P = .01]; and OR for OxPL-apo[a] level per 10-nM increase, 1.26 [95% CI, 1.10-1.45; P = .001]) and remained statistically significant after comprehensive multivariable adjustment (ß coefficient, ≥ 0.25; SE, ≤ 0.004 [P ≤ .005]; OR, ≥1.10 [P ≤ .007]). Conclusions and Relevance: This study demonstrates that the association of Lp(a) levels and its content in OxPL with faster CAVS progression is linear, reinforcing the concept that Lp(a) levels should be measured in patients with mild to moderate CAVS to enhance management and risk stratification. Trial Registration: ClinicalTrials.gov Identifier: NCT00800800.

Autoantibodies and immune complexes to oxidation-specific epitopes and progression of aortic stenosis: Results from the ASTRONOMER trial.

BACKGROUND AND AIMS: Elevated levels of lipoprotein(a) [Lp(a)] and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) predict the progression of pre-existing mild-to-moderate calcific aortic valve stenosis (CAVS). Whether indirect markers of oxidation-specific epitopes (OSE) are also predictive is not known. The association between IgG and IgM autoantibodies and malondialdehyde-modified low density lipoprotein (MDA-LDL) and IgG and IgM apolipoprotein B immune complexes (apoB-IC), and the hemodynamic progression rate of CAVS was determined in the ASTRONOMER (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin, NCT00800800) trial. METHODS: Plasma levels of IgG and IgM MDA-LDL and apoB-IC were measured in 220 patients with mild-to-moderate CAVS from the ASTRONOMER trial. The endpoint of this study was the progression rate of CAVS, measured by the annualized increase in peak aortic jet velocity (Vpeak) over a median follow-up of 3.5 [2.9-4.5] years. RESULTS: There was no difference in the progression rate of CAVS across tertiles of IgG and IgM MDA-LDL and apoB-IC levels (all p > 0.05). After multivariable analysis, no marker reached significance level to predict faster CAVS progression or need for aortic valve replacement (all p > 0.05). There was no interaction between the OSE antibody titers and plasma levels of Lp(a) or OxPL-apoB, as well as age, with regards to the progression rate of CAVS. CONCLUSIONS: Autoantibody titers to MDA-LDL and apoB-IC, which are an indirect measurement of OSE, unlike direct measurements of OxPL-apoB or their major lipoprotein carrier Lp(a), do not predict the progression of CAVS or need for AVR.

Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis.

BACKGROUND: Elevated lipoprotein(a) (Lp[a]) is associated with aortic stenosis (AS). Oxidized phospholipids (OxPL) are key mediators of calcification in valvular cells and are carried by Lp(a). OBJECTIVES: This study sought to determine whether Lp(a) and OxPL are associated with hemodynamic progression of AS and AS-related events. METHODS: OxPL on apolipoprotein B-100 (OxPL-apoB), which reflects the biological activity of Lp(a), and Lp(a) levels were measured in 220 patients with mild-to-moderate AS. The primary endpoint was the progression rate of AS, measured by the annualized increase in peak aortic jet velocity in m/s/year by Doppler echocardiography; the secondary endpoint was need for aortic valve replacement and cardiac death during 3.5 ± 1.2 years of follow-up. RESULTS: AS progression was faster in patients in the top tertiles of Lp(a) (peak aortic jet velocity: +0.26 ± 0.26 vs. +0.17 ± 0.21 m/s/year; p = 0.005) and OxPL-apoB (+0.26 ± 0.26 m/s/year vs. +0.17 ± 0.21 m/s/year; p = 0.01). After multivariable adjustment, elevated Lp(a) or OxPL-apoB levels remained independent predictors of faster AS progression. After adjustment for age, sex, and baseline AS severity, patients in the top tertile of Lp(a) or OxPL-apoB had increased risk of aortic valve replacement and cardiac death. CONCLUSIONS: Elevated Lp(a) and OxPL-apoB levels are associated with faster AS progression and need for aortic valve replacement. These findings support the hypothesis that Lp(a) mediates AS progression through its associated OxPL and provide a rationale for randomized trials of Lp(a)-lowering and OxPL-apoB-lowering therapies in AS. (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin [ASTRONOMER]; NCT00800800).

Temporal variations in effective orifice area during ejection in patients with valvular aortic stenosis.

Effective orifice area (EOA) is the standard index for assessing aortic stenosis (AS) severity. However, EOA varies during ejection and a single measurement at 1 ejection time point may not fully describe the hemodynamic severity of a stenotic aortic valve. We investigated whether the dynamic change in EOA during ejection differs between patients with severe AS (EOA /=80% of maximum EOA for a shorter duration during ejection compared with control patients (49 +/- 25 vs 64 +/- 14%, P =.05). EOA opening rate, time to maximum V(LVOT), time to maximum V(AS), and time to 80% of maximum EOA correlated with mean pressure gradient (r = -0.80, 0.63, 0.42, and 0.54, respectively, n = 45). Indices of ejection dynamics and valve kinetics differ in patients with AS and may provide further insight into the hemodynamic or physiologic severity of a stenotic aortic valve.

Hemodynamic stability of valve area, valve resistance, and stroke work loss in aortic stenosis: a comparative analysis.

BACKGROUND: Although aortic valve area (AVA) has provided the standard index for assessing aortic stenosis severity, valve resistance and percent left ventricular stroke work (%LVSW) loss have been proposed as alternative flow independent indices of stenosis severity that may provide a more stable measure under diverse hemodynamic conditions. In 30 patients with moderate or severe aortic stenosis (AVA < or = 1.2 cm(2)), Doppler echocardiography indices of AVA, valve resistance, and %LVSW loss were measured at multiple transvalvular flow rates during dobutamine infusions (0-10 microg/kg/min) to compare their hemodynamic stability. RESULTS: From baseline to maximum dobutamine dose in the 30 patients, transvalvular flow rate increased 43% and resulted in a 42% increase in mean transvalvular pressure gradient, a 15% increase in Doppler AVA, and a 26% increase in %LVSW loss. Group mean valve resistance did not change for the total cohort. For individual patients, AVA and %LVSW loss demonstrated a linear relationship with transvalvular flow (median r = 0.74 and 0.84, respectively). In contrast, both flow-mediated increases and decreases in valve resistance were observed in individual patients, resulting in the apparent stability of the group mean valve resistance in the total cohort. For individual patients, Doppler AVA and valve resistance demonstrated comparable stability in response to changes in hemodynamic conditions and were significantly more stable than mean transvalvular pressure gradient and %LVSW loss. CONCLUSION: Doppler AVA and valve resistance provide stenotic indices of equivalent hemodynamic stability. However, transvalvular flow has a predictable directional effect on AVA and an unpredictable directional effect on valve resistance, potentially limiting valve resistance as a measure of hemodynamic severity.

Economic impact of contrast stress echocardiography on the diagnosis and initial treatment of patients with suspected coronary artery disease.

OBJECTIVE: To estimate the impact of contrast stress echocardiography on resource use in the treatment of patients with suspected coronary artery disease (CAD). METHODS: Fifty-nine patients with suspected CAD underwent nuclear perfusion imaging and contrast echocardiography examination. Further treatment was planned after each test and a final treatment was recommended after reviewing the results of both examinations. Medical resources and productivity losses were then collected for a 3-month follow-up period. RESULTS: Diagnosis was possible in 96.6% of patients with nuclear perfusion imaging and 93.2% with contrast echocardiography, resulting in a cost per successful diagnosis of $637 (Can) and $476 (Can), respectively. For the majority of patients (74%), both tests provided the same result, but for 12 patients nuclear imaging suggested abnormal perfusion, whereas contrast echocardiography indicated normal function and for 2 patients it was the opposite situation. Per-patient costs for the total patient population decreased from $316 (Can) after nuclear perfusion imaging to $250 (Can) when results from both tests were known. Three-month follow-up societal costs were $441 (Can) per patient, with hospitalization contributing 58% of this total cost. CONCLUSION: Contrast echocardiography has a similar success rate to nuclear perfusion imaging in diagnosing CAD, but has a 28% lower cost and has the potential of additional cost savings through the elimination of further diagnostic tests.

Nonbacterial thrombotic endocarditis presenting as aortic stenosis with suspected infective endocarditis: clinicopathological correlation.

Endocarditis has been traditionally classified as infective and non-bacterial thrombotic endocarditis (NBTE). NBTE has been associated with connective tissue diseases, chronic inflammatory processes and malignancy. During the pre-echocardiography era, the diagnosis of NBTE was most commonly determined at postmortem examination. A 63-year-old female patient with transient cerebral ischemic attacks and weight loss, who subsequently presented with aortic stenosis, is reported. She was treated for infective endocarditis, but developed a clinical picture of sepsis with disseminated intravascular coagulation. Despite aortic valve replacement, she died early postoperatively. Autopsy found valvular NBTE, multiple vascular thromboses and associated metastatic adenocarcinoma of unknown primary site. NBTE associated with malignancy April clinically mimic sepsis and infective endocarditis.