Aortic Stenosis: Diagnosis and Treatment.

Aortic stenosis affects 3% of persons older than 65 years. Although survival in asymptomatic patients is comparable to that in age- and sex-matched control patients, it decreases rapidly after symptoms appear. During the asymptomatic latent period, left ventricular hypertrophy and atrial augmentation of preload compensate for the increase in afterload caused by aortic stenosis. As the disease worsens, these compensatory mechanisms become inadequate, leading to symptoms of heart failure, angina, or syncope. Aortic valve replacement is recommended for most symptomatic patients with evidence of significant aortic stenosis on echocardiography. Watchful waiting is recommended for most asymptomatic patients. However, select patients may also benefit from aortic valve replacement before the onset of symptoms. Surgical valve replacement is the standard of care for patients at low to moderate surgical risk. Transcatheter aortic valve replacement may be considered in patients at high or prohibitive surgical risk. Patients should be educated about the importance of promptly reporting symptoms to their physicians. In asymptomatic patients, serial Doppler echocardiography is recommended every six to 12 months for severe aortic stenosis, every one to two years for moderate disease, and every three to five years for mild disease. Cardiology referral is recommended for all patients with symptomatic moderate and severe aortic stenosis, those with severe aortic stenosis without apparent symptoms, and those with left ventricular systolic dysfunction. Medical management of concurrent hypertension, atrial fibrillation, and coronary artery disease will lead to optimal outcomes.

Atrial Fibrillation: One Size Fits All?

Patients with atrial fibrillation not associated with other cardiac conditions require different individualized treatment strategies. However, in all patients it is critical to address modifiable risk factors, assess stroke risk, minimize atrial fibrillation burden, and identify the patient's individual goals of care.

Noninvasive assessment of right heart function and hemodynamics during exercise in patients with pulmonary arterial hypertension.

OBJECTIVES: Noninvasive assessment of right heart function and hemodynamics in patients with pulmonary arterial hypertension (PAH) is most often performed at rest, whereas the symptoms, in general, present with exertion. Assessment during exertion is limited to symptom assessment and the 6-minute walk distance. We investigated the feasibility of obtaining echocardiographic data that could accurately reflect pulmonary artery pressures (PAP), particularly mean PAP and right ventricular function during exercise in patients with PAH. METHODS: We investigated right ventricular function and hemodynamics using echocardiography during symptom-limited exercise in 10 consecutive patients undergoing right heart catheterization (RHC) as part of their clinical evaluation for PAH. We further assessed these measurements for correlation with known predictors of outcome in PAH in an exploratory analysis. RESULTS: We were able to successfully obtain complete right heart measurements by echocardiography, including mean PAP, in the majority (9 of 10) of the subjects. One patient had an incomplete tricuspid regurgitation jet at rest and with exercise. Echocardiographic pulmonary vascular resistance correlated with RHC cardiac output and brain natriuretic peptide level, whereas tricuspid annular plane systolic excursion during exercise correlated with right atrial pressure on RHC, brain natriuretic peptide, and 6-minute walk distance. Tricuspid regurgitation velocity and mean PAP with exercise correlated moderately with mean PAP and cardiac output by RHC. CONCLUSIONS: Exercise echocardiography can provide meaningful data in patients with PAH, including measuring mean PAP. The presence of correlations in this small number of patients indicates promising targets for future investigation.

Platelet Function Analyzer 100 and Brain Natriuretic Peptide as Biomarkers in Obstructive Hypertrophic Cardiomyopathy.

To test dual blood biomarkers compared with electrocardiogram (ECG) for hypertrophic cardiomyopathy (HC) screening, we performed 3 analyses and cut-point assessments. First, we measured platelet function analyzer (PFA)-100 (n = 99) and normalized B-type natriuretic peptide (BNP) or NT-proBNP (BNP/upper limit of normal [ULN], n = 92) in 64 patients with HC and 29 normal controls (NCs). Second, from the regression equation between PFA and gradient (r = 0.77), we derived estimated PFA in a population of 189 patients with functional class I HC in whom measured BNP/ULN and ECG were available, and calculated single and dual biomarker sensitivity and specificity compared with ECG. Finally, we compared BNP/ULN in class I patients based on mutation and familial history status. In 42 patients with obstructive HC versus NCs, there was a slight overlap of PFA and BNP/ULN, but for the product of PFA × BNP/ULN, there was near-complete separation of values. Among patients with class I obstructive HC, estimated PFA × BNP/ULN had a sensitivity of 93% and a specificity of 100%; in latent and nonobstructive HC, sensitivity dropped to 61% and 72%; for ECG in obstructive, latent, and nonobstructive HC, sensitivity was 71%, 34%, and 67%. Functional class I patients with positive (n = 28) and negative (n = 36) sarcomere mutations and a positive (n = 71) or a negative (n = 109) family history had significant elevations of BNP/ULN versus NC, with no between-group differences. In conclusion, PFA and BNP were highly associated with obstructive HC and could potentially be used for screening; BNP was not uniquely elevated in patients with familial versus nonfamilial or mutation-positive versus mutation-negative HC.

Von Willebrand factor multimer quantitation for assessment of cardiac lesion severity and bleeding risk.

BACKGROUND: von Willebrand factor (VWF) multimer quantitation has been utilized in the assessment of valvular heart disease, however, there is no standardized method for quantitation. We compared three methods of assessment which utilized a normal plasma control. METHODS: We analyzed 476 samples and their control plasma from 368 patients with valvular heart disease, hypertrophic cardiomyopathy, or LVAD therapy, and 27 normal subjects. VWF multimers were assessed as normalized VWF multimer ratios (NMR) of gel bands >15/2-15 (NMR15) or gel bands >10/2-10 (NMR10). Associations of VWF laboratory and multimeric assessments with cardiac lesion severity and acquired bleeding were investigated. RESULTS: Abnormal multimers were present in 78% of patients with moderate to severe hemodynamic abnormalities compared to 19% of patients with normal or mildly abnormal hemodynamics. NMR showed strong association with severe cardiac lesions (NMR15: OR 15.29, CI 9.04-27.18; NMR10: OR 14.18, CI 8.88-23.21). PFA-CADP was strongly associated with moderate to severe cardiac lesions (OR 14.91, CI 9.08-24.50). PFA-CADP and NMR15 showed excellent ability to discriminate ≥moderate (AUC 0.86, CI 0.83-0.89 and 0.83, CI 0.79-0.87 respectively) and severe cardiac lesions (AUC 0.84, CI 0.81-0.88 and 0.85, CI 0.81-0.88 respectively). NMR was less strongly associated with bleeding (OR 4.01 for NMR10, CI 2.49-6.58). CONCLUSION: Quantification of VWF multimers may provide clinical utility in circumstances where clinical estimation of cardiac lesion severity is challenging, such as with dysfunctional prosthetic valves. The presence of abnormal VWF multimers is associated with bleeding, however further quantitation provided only modest improvement in risk stratification.

Pulmonary hypertension and thyroid disease.

BACKGROUND: The association between thyroid dysfunction and pulmonary hypertension (PH) has not been well characterized. METHODS: This retrospective study comprised 356 consecutive PH patients seen at Mayo Clinic Jacksonville Pulmonary Hypertension Center from 1992 to 2006 and 698 sex-matched control subjects without PH. Thyroid disease was defined as an abnormal thyroid-stimulating hormone level, with or without an abnormal free or total thyroxine level, a history of thyroid disease on replacement, or an elevated thyroperoxidase antibody level. The main outcome measure was prevalence of thyroid disease in each group. RESULTS: Median age of the 356 PH patients was 65 years; 230 patients (65%) were female. The control group of 698 patients had the same sex ratio and median age of 68 years. Most PH patients had severe PH, as categorized by World Health Organization (WHO) class (74% class 3-4) and pulmonary artery systolic pressure. Among those with PH, 85 patients (24%) had thyroid disease vs 107 control patients (15%). After adjusting for age and sex, the prevalence of thyroid disease was increased in PH patients compared with control patients. Increased prevalence was most prominent in WHO group 1, pulmonary artery hypertension confirmed by right-heart catheterization (odds ratio, 2.53; 95% confidence interval, 1.55 to 4.08; p < 0.001). Most patients had mild thyroid disease and were hypothyroid. Only 14 of 85 patients (16%) had previously undiagnosed thyroid disease. CONCLUSIONS: Patients with PH have a higher prevalence of thyroid disease than other pulmonary patients. Evaluation of thyroid function in PH patients may be warranted to detect and assess coexisting thyroid disease.

Computed tomographic angiography of the coronary arteries: techniques and applications.

Computed tomographic coronary angiography (CT-CA) is a direct but minimally invasive method of visualizing coronary arteries. Multidetector-row computed tomography (MDCT) is currently the CT modality most commonly used for coronary artery imaging. MDCT has been successfully used to detect stenoses in coronary arteries and coronary artery bypass grafts and to assess congenital coronary anomalies. Patients should not undergo CT-CA with MDCT if they have an irregular heart rhythm, a heart rate greater than 70 beats/min, and contraindications to pharmacologic agents for heart rate control, or if they have severe coronary artery disease or are likely to require revascularization.

von Willebrand Factor Abnormalities and Heyde Syndrome in Dysfunctional Heart Valve Prostheses.

IMPORTANCE: Limited data suggest that von Willebrand factor (VWF) abnormalities may accompany the high-shear state associated with prosthetic valve dysfunction. If true, laboratory testing could add value in quantifying prosthesis dysfunction and could suggest a pathophysiological explanation for acquired bleeding in some patients. OBJECTIVES: To determine whether dysfunctional valve prostheses are associated with VWF abnormalities compared with normally functioning valve prostheses, to identify the severity of the VWF abnormality relative to other conditions, and to describe associated bleeding and the occurrence of gastrointestinal angiodysplasia. DESIGN, SETTING, AND PARTICIPANTS: Cohort study in a multispecialty practice setting from August 2010 through November 2015. To assess the severity of VWF dysfunction, data were compared with those from previously reported healthy controls and patients with aortic stenosis, mitral regurgitation, and left ventricular assist devices. Patients underwent assessment of multiple VWF laboratory tests and echocardiography. MAIN OUTCOMES AND MEASURES: Loss of high-molecular-weight multimers of VWF. RESULTS: A total of 136 patients were included in this study. During the study period, we assessed 26 patients with normally functioning surgical or transcatheter aortic valve replacement, 24 patients with dysfunctional aortic valve replacement, 36 patients with normally functioning mitral valve replacement or repair, 19 patients with dysfunctional mitral valve replacement or repair, and 31 patients with native aortic regurgitation without coexisting aortic stenosis. von Willebrand factor multimers were abnormal in 1 of 26 normal aortic valve replacements and in 2 of 36 normal mitral valve replacements or repairs but were abnormal in 20 of 24 dysfunctional aortic valve replacements and in 14 of 19 dysfunctional mitral valve replacements or repairs (P < .001 for both). Normal aortic valve replacement also had a higher VWF activity to antigen ratio, mean (range) 0.94 (0.84-0.99) compared to dysfunctional aortic valve replacement, 0.78 (0.73-0.87), P < .001, as did normal mitral valve replacement or repair, 0.90 (0.86-0.93) compared to dysfunctional mitral valve replacement or repair, 0.78 (0.70-0.90), P = .005. Platelet function analyzer closure times were lower with normal aortic valve replacement, mean (range) 92 (82-112) seconds compared to dysfunctional aortic valve replacement, 139 (122-177) seconds, P < .001, and also in normally functioning mitral valve replacement or repair, 85 (74-96) seconds compared to dysfunctional mitral valve replacement or repair, 143 (128-192) seconds, P < .001. Gastrointestinal bleeding was noted in 6 of 24 patients with aortic prosthesis dysfunction and in 5 of 19 patients with mitral prosthesis/repair dysfunction and was associated with a lower normalized VWF multimer ratio than in patients without bleeding. Gastrointestinal angiodysplasia was noted in 5 of 6 bleeding patients with dysfunctional aortic prostheses and in 3 of 5 bleeding patients with dysfunctional mitral prostheses/repair. CONCLUSIONS AND RELEVANCE: Acquired abnormalities of VWF multimers are associated with aortic and mitral prosthesis dysfunction, with occasional gastrointestinal bleeding and gastrointestinal angiodysplasia. Quantitative VWF tests may provide adjunctive value in the difficult assessment of prosthetic valve dysfunction.

Usefulness of Von Willebrand Factor Activity Indexes to Predict Therapeutic Response in Hypertrophic Cardiomyopathy.

Degraded by shear stress, loss of high-molecular-weight multimers of von Willebrand factor (VWF) correlates strongly with pressure gradient in aortic stenosis (AS) and obstructive hypertrophic cardiomyopathy (HC). We assessed VWF tests before and after interventions in HC and contrasted the severity of abnormalities in HC to patients with AS, mitral regurgitation, and left ventricular assist devices. Ninety patients with median (interquartile range) age 66 (53 to 72) years, 51% men, with HC had assessments of 3 VWF parameters and B-type natriuretic peptide before and after 26 discreet medical/pacing interventions, 22 alcohol septal ablations, and 28 ventricular septal myectomies. VWF multimers were abnormal in 87% of patients with obstructive HC versus 48% of patients with latent obstruction (p = 0.0001). VWF measurements correlated with peak instantaneous left ventricular outflow tract gradient, Spearman ρ 0.51 to 0.61, p <0.0001. For B-type natriuretic peptide, correlation with left ventricular outflow tract gradient was weaker, ρ = 0.37, p = 0.0005, but stronger with septal thickness or mitral E/e'. In pre-/post-medical treatment of HC, VWF multimers were abnormal in 73%/68% of patients, p = 0.74; pre-/post-septal ablation 74%/26%, p = 0.0035; and pre-/post-septal myectomy 75%/0%, p <0.0001. In obstructive HC, the degree VWF multimer loss was greater than in severe AS or severe mitral regurgitation and overlapped that seen in left ventricular assist devices. In conclusion, VWF activity indexes were predictably abnormal in patients with HC with resting obstruction to a degree where bleeding could be anticipated, accurately reflected gradient changes after intervention, and demonstrated complete normalization after septal myectomy.

Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

BACKGROUND: Stroke and systemic thromboembolism are serious problems for patients with atrial fibrillation (AF), but their incidence can be substantially reduced by appropriate anticoagulation. Bleeding is the major complication of anticoagulant treatment, and the relative risks for bleeding vs stroke must be considered when starting anticoagulation. METHODS: The AFFIRM trial included patients with AF and at least one risk factor for stroke, randomly assigning them to either a rate-control or rhythm-control strategy. All patients were initially treated with warfarin. The incidence of protocol-defined major and minor bleeding was documented during follow-up. Variables associated with bleeding were determined using a Cox proportional hazards model, using baseline and time-dependent covariates. RESULTS: The 4060 patients in the AFFIRM trial were followed for an average of 3.5 years. Major bleeding occurred in 260 patients, an annual incidence of approximately 2% per year, with no significant difference between the rate-control and rhythm-control groups. Increased age, heart failure, hepatic or renal disease, diabetes, first AF episode, warfarin use, and aspirin use were significantly associated with major bleeding. Minor bleeding was common in both treatment arms, with 738 patients reporting this problem in one or more visits. CONCLUSIONS: Bleeding is a significant problem that complicates management of patients with AF. Risk factors for bleeding can be identified, and knowledge of these risk factors can be used to plan therapy.

Clinical factors associated with abandonment of a rate-control or a rhythm-control strategy for the management of atrial fibrillation in the AFFIRM study.

OBJECTIVE: The objective of the current study was to determine the clinical factors that were associated with abandonment of a rate-control or a rhythm-control strategy in patients with atrial fibrillation (AF). BACKGROUND: Although the AFFIRM Study demonstrated that outcomes are similar with a primary strategy of rate-control or rhythm-control for AF, there may be clinical or demographic factors associated with abandonment of the initial treatment strategy. Knowledge of these risk factors would be useful so that patients may be given appropriate initial therapy and, as appropriate, switched to alternative treatments earlier. METHODS: Patients in the AFFIRM Study were subdivided into those who were maintained on their initial treatment strategy versus those who abandoned initial treatment strategy for alternative therapies. We determined the clinical and demographic factors associated with change in initial treatment strategy. RESULTS: At 5 years the original treatment strategy was maintained in 85% of the patients in the rate-control arm versus 62% of those in the rhythm-control arm (P <.0001). Length of the qualifying episode of AF was associated with abandonment of both rhythm-control and rate-control strategies. Antiarrhythmic drug failure before randomization and a history of thyroid disease also were associated with abandonment of rhythm-control. Patients were more likely to maintain rate-control if they already had an implanted pacemaker or if they were older than 75 years, while an ejection fraction <30% was associated with abandonment of the rate-control strategy. CONCLUSIONS: In patients with AF, rhythm-control strategies are abandoned significantly more often than rate-control strategies. Patients with long durations of AF on presentation or previous antiarrhythmic drug failure might be considered for rate-control as initial treatment.

Impact of exercise stress testing on diagnostic gene expression in patients with obstructive and nonobstructive coronary artery disease.

A blood-based gene expression test can diagnose obstructive coronary artery disease (CAD). The test is sensitive to inflammatory and immune processes associated with atherosclerosis. Acute exercise engages short-term inflammatory pathways, and exercise stress testing may affect results of gene expression testing during the same diagnostic workup. The objective of this study was to evaluate the effect of exercise on diagnostic gene expression testing. Ten patients with obstructive CAD (≥50% stenosis) and 10 with no/minimal CAD (≤20% stenosis) were identified by angiography. Blood samples for gene expression were obtained at baseline, peak exercise, 30 to 60 minutes after testing, and 24 to 36 hours after testing. Core-lab gene expression analysis yielded raw gene expression scores (GES) for each time point. Linear models were used to estimate changes in GES, adjusting for CAD status and other covariates. GES increased during peak exercise across both genders, with no significant differences as a function of CAD status. The overall adjusted mean GES increase at peak exercise was 0.29 (95% confidence interval 0.22 to 0.36; p <0.001). GES after exercise were not significantly different from baseline. The change in gene expression levels during peak exercise may reflect a transient inflammatory response to acute exercise that may be independent of patient gender or CAD status. In conclusion, CAD GES increase at peak exercise testing and rapidly return to baseline. Such may reflect a transient inflammatory response to acute exercise independent of gender or extent of CAD.

Imaging of congenital coronary anomalies with multislice computed tomography.

OBJECTIVE: To describe a single-center experience of using retrospectively gated multislice computed tomographic (MSCT) coronary angiography for imaging congenital coronary anomalies. PATIENTS AND METHODS: We retrospectively reviewed the clinical information and imaging studies for 9 patients diagnosed as having congenital coronary anomalies on invasive, selective coronary angiography between February 2001 and October 2003 at the Mayo Clinic in Jacksonville, Fla. Two experienced observers classified by consensus the origin and proximal course of the abnormal coronary arteries as seen on MSCT. RESULTS: In 1 patient, MSCT showed a normal but extremely anterior origin of the right coronary artery from the right aortic sinus of Valsalva. In the other 8 patients, the origin and course of 4 anomalous right coronary arteries, 2 anomalous left circumflex coronary arteries, and 2 single coronary arteries were recognized easily on MSCT. CONCLUSION: Similar to electron beam computed tomography and magnetic resonance imaging, widely available MSCT can characterize the proximal course of congenitally abnormal coronary arteries and thus aid in clinical decision making for patients with such anomalies.

Current results and new developments of coronary angiography with use of contrast-enhanced computed tomography of the heart.

Electron beam computed tomography (EBCT) is the reference standard for x-ray-based tomographic imaging of the heart because of its high temporal resolution, but it is available in only a few centers. Quantification of coronary calcium is the most widely recognized use of EBCT for cardiac imaging. This technique requires no contrast media and provides an accurate assessment of overall plaque burden in the coronary tree; however, it does not directly identify or localize coronary stenoses. Multislice spiral (helical) CT (MSCT) is a new technology that provides images of the beating heart in diagnostic quality under many circumstances and may facilitate the broader application of cardiac and coronary CT. Currently, for imaging of the heart, much more experience exists with EBCT than with MSCT. Contrast-enhanced CT coronary angiography (CTCA) can be done with EBCT or MSCT to obtain images of the major branches of the coronary tree and to define luminal narrowing. Studies at experienced centers performed with small numbers of patients show that sensitivity, specificity, and negative predictive value are good with CTCA in the assessment of obstructive coronary artery disease, but CTCA remains an investigational technique for these applications. Computed tomographic coronary angiography can be clinically useful for assessing coronary artery bypass graft patency and congenital coronary abnormalities.

Simulation and new learning technologies.

Changes in medical practice that limit patient availability and instructors' time have resulted in poor physical diagnosis skills by learners at all levels. Advanced simulation technology, including the use of sophisticated multimedia computer systems, helps to address this problem. For many years 'Harvey', the Cardiology Patient Simulator, and the UMedic Multimedia Computer system have proven to be effective tools to teach and assess bedside cardiovascular skills when they are integrated into the required curriculum of medical school and postgraduate training. In the future, virtual reality technology, based initially on data from the Visible Human Data set, will provide the majority of simulation-based training. Models that provide a high level of visual fidelity and use sophisticated haptic devices that simulate the 'touch' and 'feel' of a procedure or examination are now being used in selected medical centers. The presence of these tools is not enough. Evidence-based outcomes must show these systems to be effective instruments for teaching and assessment, and medical educators must be willing to effect change in medical education to ensure the appropriate use of these systems in the next millennium.

Characterization of first-time hospitalizations in patients with newly diagnosed pulmonary arterial hypertension in the REVEAL registry.

BACKGROUND: Hospitalization is an important outcome in pulmonary arterial hypertension (PAH), shown previously to correlate with survival. Using the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry), we sought to characterize first-time hospitalizations and their effect on subsequent hospitalization and survival in patients with newly diagnosed disease. METHODS: Patients with newly diagnosed PAH (n = 862, World Health Organization group 1) were evaluated for first-time hospitalization. The hospitalizations were categorized as PAH related or PAH unrelated based on the case report form. Categories for PAH-related and PAH-unrelated hospitalization were defined before independent review. Patient demographics and disease characteristics are described as well as freedom from hospitalization and survival. RESULTS: Of 862 patients, 490 (56.8%) had one or more hospitalizations postenrollment: 257 (52.4%) PAH related, 214 (43.7%) PAH unrelated, and 19 (3.9%) of undetermined causes. The most common causes of PAH-related hospitalization were congestive heart failure and placement/removal of a central venous catheter. Patients with PAH-related hospitalizations were more likely to receive parenteral therapy, be in functional class III/IV, and have higher risk scores before hospitalization at enrollment. Following discharge, 25.4% ± 3.2% and 31.0% ± 4.0% of patients with PAH-related and PAH-unrelated first hospitalization, respectively, remained hospitalization-free for 3 years (P = .11). Survival estimates at 3 years postdischarge were 56.8% ± 3.5% and 67.8% ± 3.6% (P = .037) for patients with PAH-related and PAH-unrelated hospitalization, respectively. CONCLUSIONS: In the REVEAL Registry, PAH-related hospitalization was associated with relatively more rehospitalizations and worse survival at 3 years. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.

Indexes of von Willebrand factor as biomarkers of aortic stenosis severity (from the Biomarkers of Aortic Stenosis Severity [BASS] study).

We correlated von Willebrand factor (VWF) activity indexes and brain natriuretic peptide (BNP) with measures of aortic stenosis (AS) severity, bleeding, symptoms, and freedom from death or aortic valve replacement. Patients with AS (n = 66 [16 mild, 20 moderate, and 30 severe]) and aortic valve replacement (n = 21) were assessed with VWF antigen, VWF latex agglutination immunoturbidic activity, platelet function analyzer collagen plus adenosine diphosphate (PFA-CADP), VWF multimer ratio, and BNP level after echocardiography. In patients with AS, the mean gradient correlated with BNP (Spearman r = 0.29, p = 0.02), VWF latex agglutination immunoturbidic activity/VWF antigen ratio (r = -0.41, p <0.001), PFA-CADP (r = 0.49, p <0.001), and VWF multimer ratio (r = -0.76, p <0.001). The area under the curve for detection of severe AS was 0.62 (95% confidence interval [CI] 0.48 to 0.77) by elevated BNP, 0.81 (95% CI 0.69 to 0.92) by PFA-CADP closure time, 0.69 (95% CI 0.55 to 0.82) by VWF latex agglutination immunoturbidic activity/VWF antigen ratio, and 0.86 (95% CI 0.76 to 0.95) by VWF multimer ratio. For the VWF multimer ratio, a threshold of 0.15 yielded a sensitivity and specificity for severe AS of 77% and positive predictive value of 74%. Bleeding (in 14%) was associated with a prolonged PFA-CADP time and reduced VWF latex agglutination immunoturbidic activity/VWF antigen ratio. Symptoms were associated with elevated BNP and low Duke Activity Status Index score. In 66 patients with AS, freedom from death (n = 4) or aortic valve replacement (n = 22) was associated with PFA-CADP (p = 0.003), VWF high-molecular-weight multimers (p = 0.009), and VWF latex agglutination immunoturbidic activity/VWF antigen ratio (p <0.001) but not BNP (p = 0.32). In severe AS versus aortic valve replacement, the PFA-CADP and VWF multimer ratio differed (p <0.001), but BNP and the VWF latex agglutination immunoturbidic activity/VWF antigen ratio did not. In conclusion, the VWF activity indexes were associated with AS severity and bleeding and were predictive of cardiovascular outcomes.

Usefulness of Doppler echocardiographic left ventricular diastolic function and peak exercise oxygen consumption to predict cardiovascular outcomes in patients with systolic heart failure (from HF-ACTION).

Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) was a multicenter, randomized controlled trial designed to examine the safety and efficacy of aerobic exercise training versus usual care in 2,331 patients with systolic heart failure (HF). In HF-ACTION patients with rest transthoracic echocardiographic measurements, the predictive value of 8 Doppler echocardiographic measurements-left ventricular (LV) diastolic dimension, mass, systolic (ejection fraction) and diastolic (mitral valve peak early diastolic/peak late diastolic [E/A] ratio, peak mitral valve early diastolic velocity/tissue Doppler peak early diastolic myocardial velocity [E/E'] ratio, and deceleration time) function, left atrial dimension, and mitral regurgitation severity-was examined for a primary end point of all-cause death or hospitalization and a secondary end point of cardiovascular disease death or HF hospitalization. Also compared was the prognostic value of echocardiographic variables versus peak oxygen consumption (Vo(2)). Mitral valve E/A and E/E' ratios were more powerful independent predictors of clinical end points than the LV ejection fraction but less powerful than peak Vo(2). In multivariate analyses for predicting the primary end point, adding E/A ratio to a basic demographic and clinical model increased the C-index from 0.61 to 0.62, compared with 0.64 after adding peak Vo(2). For the secondary end point, 6 echocardiographic variables, but not the LV ejection fraction or left atrial dimension, provided independent predictive power over the basic model. The addition of E/E' or E/A to the basic model increased the C-index from 0.70 to 0.72 and 0.73, respectively (all p values <0.0001). Simultaneously adding E/A ratio and peak Vo(2) to the basic model increased the C-index to 0.75 (p <0.0005). No echocardiographic variable was significantly related to the change from baseline to 3 months in exercise peak Vo(2). In conclusion, the addition of echocardiographic LV diastolic function variables improves the prognostic value of a basic demographic and clinical model for cardiovascular disease outcomes.

Comparison of body habitus in patients with pulmonary arterial hypertension enrolled in the Registry to Evaluate Early and Long-term PAH Disease Management with normative values from the National Health and Nutrition Examination Survey.

OBJECTIVE: To investigate the correlation between body mass index (BMI) and pulmonary artery systolic pressure in a large population of patients with pulmonary arterial hypertension (PAH). PATIENTS AND METHODS: The BMI of patients with group 1 PAH enrolled in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) was compared with that of age- and sex-matched controls in the National Health and Nutrition Examination Survey (NHANES) to clarify whether obesity is linked with PAH. The diagnosis of PAH was defined in REVEAL by right-sided heart catheterization. Differences in BMI and the percentage of patients considered obese (BMI ≥30) and underweight (BMI <18.5) in various subgroups of patients enrolled in REVEAL from March 30, 2006, through September 11, 2007, were determined. RESULTS: Mean BMI was no different for patients with PAH (n=2141) than for the NHANES normal comparison group; however, the proportion of obese and underweight patients was increased in patients with PAH. Subgroup analysis demonstrated that subgroups with idiopathic PAH and those with PAH associated with drugs and toxins had both higher BMI and percentage of obese patients, whereas 3 other subgroups (those with PAH associated with congenital heart disease, connective tissue disease, and human immunodeficiency virus) had lower mean BMI. CONCLUSION: Mean BMI of the REVEAL patients was the same as that of the NHANES normal comparison group; however, there were higher percentages of obese and underweight patients in REVEAL. This discrepancy can be explained by the balancing effect of more overweight and underweight patients in different PAH subgroups. The reason for the increased frequency of obesity in idiopathic PAH is unknown, and additional study is needed.