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.

Updating the Dermal Sensitisation Thresholds using an expanded dataset and an in silico expert system.

The Dermal Sensitisation Thresholds (DST) are Thresholds of Toxicological Concern, which can be used to justify exposure-based waiving when conducting a skin sensitisation risk assessment. This study aimed to update the published DST values by expanding the size of the Local Lymph Node Assay dataset upon which they are based, whilst assigning chemical reactivity using an in silico expert system (Derek Nexus). The potency values within the expanded dataset fitted a similar gamma distribution to that observed for the original dataset. Derek Nexus was used to classify the sensitisation activity of the 1152 chemicals in the expanded dataset and to predict which chemicals belonged to a High Potency Category (HPC). This two-step classification led to three updated thresholds: a non-reactive DST of 710 µg/cm2 (based on 79 sensitisers), a reactive (non-HPC) DST of 73 µg/cm2 (based on 331 sensitisers) and an HPC DST of 1.0 µg/cm2 (based on 146 sensitisers). Despite the dataset containing twice as many sensitisers, these values are similar to the previously published thresholds, highlighting their robustness and increasing confidence in their use. By classifying reactivity in silico the updated DSTs can be applied within a skin sensitisation risk assessment in a reproducible, scalable and accessible manner.

Application of the dermal sensitization threshold concept to chemicals classified as high potency category for skin sensitization assessment of ingredients for consumer products.

Skin sensitization evaluation is a key part of the safety assessment of ingredients in consumer products, which may have skin sensitizing potential. The dermal sensitization threshold (DST) concept, which is based on the concept of the thresholds of toxicological concern, has been proposed for the risk assessment of chemicals to which skin exposure is very low level. There is negligible risk of skin sensitization if a skin exposure level for the substance of interest was below the reactive DST which would protect against 95% of protein-reactive chemicals. For the remaining 5%, the substance with the defined knowledge of chemical structure (i.e., High Potency Category (HPC) rules) needs to be excluded from the application. However, the DST value for HPC chemicals has not yet been proposed. In this study, we calculated the 95th percentile probabilities estimate from distributions of skin sensitization potency data and derived a novel DST for HPC chemicals (HPC DST) of 1.5 µg/cm2. This value presents a useful default approach for unidentified substances in ingredients considering, as a worst-case scenario, that the unidentified compound may be a potent skin sensitizer. Finally, we developed a novel risk assessment workflow incorporating the HPC DST along with the previously published DSTs.

Pulmonary arterial stiffness assessed by cardiovascular magnetic resonance imaging is a predictor of mild pulmonary arterial hypertension.

Early detection of mild pulmonary arterial hypertension (PAH) based on clinical evaluation and echocardiography remains quite challenging. In addition to enhanced right ventricular (RV) assessment, cardiac magnetic resonance (CMR) imaging may accurately reflect deleterious remodeling and increased stiffness of the central pulmonary arteries based on pulsatility, or percent change of the PA during the cardiac cycle. The purpose of this study is to assess the utility of measuring PA pulsatility by CMR as a potential early maker in PAH. We hypothesize that pulsatility may help discriminate mild PAH from normal control subjects. Consecutive patients with PAH (n = 51) were prospectively enrolled to receive same day CMR and right heart catheterization (RHC). PA stiffness indices including pulsatility, distensibility, compliance, and capacitance were calculated. Comparisons were made between patients with varying severities of PAH and normal controls (n = 18). Of the 51 subjects, 20 had mild PAH, and 31 moderate-severe based on hemodynamic criteria. PA pulsatility demonstrated a progressive decline from normal controls (53%), mild PAH (22%), to moderate-severe PAH (17%; p < 0.001). There was no difference in RV size, function or mass between mild PAH and normal controls. PA pulsatility below 40% had an excellent ability to discriminate between mild PAH and normal controls with a sensitivity of 95% and specificity of 94%. CMR assessment of PA stiffness may noninvasively detect adverse pulmonary vascular remodeling and mild PAH, and thus be a valuable tool for early detection of PAH. Trial Registration: ClinicalTrials.gov Identifier: NCT01451255; https://clinicaltrials.gov/ct2/show/NCT01451255 .

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.

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.

High-risk echocardiographic features predict mortality in pulmonary arterial hypertension.

AIMS: Echocardiography is the most common imaging modality for assessment of the right ventricle in patients with pulmonary arterial hypertension (PAH). Echocardiographic parameters were identified as independent risk factors for mortality in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) and other PAH cohorts. We sought to identify readily obtained echocardiographic features associated with PAH survival. METHODS AND RESULTS: Retrospective analysis of 175 patients with Group 1 was performed. Baseline clinical and laboratory assessment including REVEAL risk criteria were obtained and standard 2-Dimensional and Doppler echocardiography performed at baseline was reviewed. Univariate and multivariate analyses of echocardiographic parameters were performed. Estimated right atrial pressure> 15 mmHg (HR 2.39, P = .02), tricuspid regurgitation ≥ moderate (HR 2.16, P = .04), and presence of pericardial effusion (HR 1.8, P = .05) were identified as independent, high-risk echocardiographic features in PAH. A validation cohort of 677 patients was identified and Kaplan-Meier survival analysis was performed in both cohorts. High-risk echocardiographic features stratified survival curves of both cohorts (P < .01 for all). The presence of 3 high-risk echocardiographic features greatly increased risk of 1-year (RR 4.86) and 3-year (RR 3.35) mortality (P < .05 for both). CONCLUSION: Estimated right atrial pressure> 15, tricuspid regurgitation ≥ moderate, and presence of pericardial effusion are high-risk echocardiographic features in PAH. When seen in combination, these features greatly increase risk of mortality in PAH and may lead to more timely enhanced therapy for patients identified as having an increased risk for death.

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.

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.

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.

Extension of the Dermal Sensitisation Threshold (DST) approach to incorporate chemicals classified as reactive.

The evaluation of chemicals for their skin sensitising potential is an essential step in ensuring the safety of ingredients in consumer products. Similar to the Threshold of Toxicological Concern, the Dermal Sensitisation Threshold (DST) has been demonstrated to provide effective risk assessments for skin sensitisation in cases where human exposure is low. The DST was originally developed based on a Local Lymph Node Assay (LLNA) dataset and applied to chemicals that were not considered to be directly reactive to skin proteins, and unlikely to initiate the first mechanistic steps leading to the induction of sensitisation. Here we have extended the DST concept to protein reactive chemicals. A probabilistic assessment of the original DST dataset was conducted and a threshold of 64 µg/cm(2) was derived. In our accompanying publication, a set of structural chemistry based rules was developed to proactively identify highly reactive and potentially highly potent materials which should be excluded from the DST approach. The DST and rule set were benchmarked against a test set of chemicals with LLNA/human data. It is concluded that by combining the reactive DST with knowledge of chemistry a threshold can be established below which there is no appreciable risk of sensitisation for protein-reactive chemicals.

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.

Principles for identification of High Potency Category Chemicals for which the Dermal Sensitisation Threshold (DST) approach should not be applied.

An essential step in ensuring the toxicological safety of chemicals used in consumer products is the evaluation of their skin sensitising potential. The sensitising potency, coupled with information on exposure levels, can be used in a Quantitative Risk Assessment (QRA) to determine an acceptable level of a given chemical in a given product. Where consumer skin exposure is low, a risk assessment can be conducted using the Dermal Sensitisation Threshold (DST) approach, avoiding the need to determine potency experimentally. Since skin sensitisation involves chemical reaction with skin proteins, the first step in the DST approach is to assess, on the basis of the chemical structure, whether the chemical is expected to be reactive or not. Our accompanying publication describes the probabilistic derivation of a DST of 64 µg/cm(2) for chemicals assessed as reactive. This would protect against 95% of chemicals assessed as reactive, but the remaining 5% would include chemicals with very high potency. Here we discuss the chemical properties and structural features of high potency sensitisers, and derive an approach whereby they can be identified and consequently excluded from application of the DST.

Echocardiographic assessment of estimated right atrial pressure and size predicts mortality in pulmonary arterial hypertension.

BACKGROUND: Elevated mean right atrial pressure (RAP) measured by cardiac catheterization is an independent risk factor for mortality. Prior studies have demonstrated a modest correlation with invasive and noninvasive echocardiographic RAP, but the prognostic impact of estimated right atrial pressure (eRAP) has not been previously evaluated in patients with pulmonary arterial hypertension (PAH). METHODS: A retrospective analysis of 121 consecutive patients with PAH based on right-sided heart catheterization and echocardiography was performed. The eRAP was calculated by inferior vena cava diameter and collapse using 2005 and 2010 American Society of Echocardiography (ASE) definitions. Accuracy and correlation of eRAP to RAP was assessed. Kaplan-Meier survival analysis by eRAP, right atrial area, and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) risk criteria as well as univariate and multivariate analysis of echocardiographic findings was performed. RESULTS: Elevation of eRAP was associated with decreased survival time compared with lower eRAP (P < .001, relative risk = 7.94 for eRAP > 15 mm Hg vs eRAP ≤ 5 mm Hg). Univariate analysis of echocardiographic parameters including eRAP > 15 mm Hg, right atrial area > 18 cm², presence of pericardial effusion, right ventricular fractional area change < 35%, and at least moderate tricuspid regurgitation was predictive of poor survival. However, multivariate analysis revealed that eRAP > 15 mm Hg was the only echocardiographic risk factor that was predictive of mortality (hazard ratio = 2.28, P = .037). CONCLUSIONS: Elevation of eRAP by echocardiography at baseline assessment was strongly associated with increased risk of death or transplant in patients with PAH. This measurement may represent an important prognostic component in the comprehensive echocardiographic evaluation of PAH.

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.

Effects of exercise training on outcomes in women with heart failure: analysis of HF-ACTION (Heart Failure-A Controlled Trial Investigating Outcomes of Exercise TraiNing) by sex.

OBJECTIVES: The authors hypothesized that the women enrolled in the HF-ACTION (Heart Failure-A Controlled Trial Investigating Outcomes of Exercise TraiNing) trial and randomly assigned to exercise training (ET) would improve functional capacity as measured by peak oxygen uptake (VO2) compared with those in the usual care group. Furthermore, they hypothesized that the improvement in peak VO2 would correlate with prognosis. They explored whether exercise had a differential effect on outcomes in women versus men. BACKGROUND: There is less evidence for the benefit of ET in women with heart failure (HF) compared with men because of the small numbers of women studied. METHODS: HF-ACTION was a randomized trial of ET versus usual care in 2,331 patients with class II-IV HF and a left ventricular ejection fraction of ≤35%. Sex differences in the effects of randomized treatment on clinical outcomes were assessed through the use of a series of Cox proportional hazards models, controlling for covariates known to affect prognosis in HF-ACTION. RESULTS: Women had lower baseline peak VO2 and 6-min walk distance than did men (median, 13.4 vs. 14.9 ml/min/kg and 353 vs. 378 m, respectively). An increase in peak VO2 at 3 months was present in women and men in the ET group (mean ± SD; median, 0.88 ± 2.2, 0.80 and 0.77 ± 2.7, 0.60, respectively, women vs. men; p = 0.42). Women randomly assigned to ET had a significant reduction in the primary endpoint, (hazard ratio: 0.74) compared with men (hazard ratio: 0.99) randomly assigned to ET, with a significant treatment-by-sex interaction (p = 0.027). CONCLUSIONS: Although there is no significant difference between men and women in the effect of ET on peak VO2 change at 3 months, ET in women with HF is associated with a larger reduction in rate of the combined endpoint of all-cause mortality and hospital stay than in men.

Cardiac MRI as a diagnostic tool in pulmonary hypertension.

Pulmonary hypertension is characterized by alterations in the viscoelastic properties of the pulmonary arteries, leading to increased pulmonary arterial stiffness and elevated pressures. Early detection and accurate quantification of pulmonary hypertension are limitations to conventional noninvasive imaging and may have therapeutic implications. Cardiac MRI provides important information that can aid the clinician, particularly relating to morphologic right ventricular alterations and quantification of stiffness, as well as providing a novel prognostic framework.

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.

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.