BackgroundThe impact of B-type natriuretic peptide (BNP) level on the risk of left atrial appendage (LAA) thrombus in patients with nonvalvular atrial fibrillation (NVAF) has not been prospectively studied.MethodsIn two academic medical centers, we obtained BNP levels immediately prior to transesophageal echocardiogram performed to exclude LAA thrombus in patients with NVAF.ResultsAmong 261 subjects (mean age 65 ± 12 years; 30 % women) with NVAF, 17 (6.5 %) had LAA thrombus and 85 (32.6 %) had at least mild spontaneous echo contrast (SEC). Mean BNP level was significantly higher in patients with LAA thrombus [775 ± 678 vs. 384 ± 537, P = 0.001]. Receiver operator characteristics analysis demonstrated that BNP has a good discriminatory capacity for LAA thrombus (area under the curve, 0.74; 95 % confidence interval [CI], 0.63–0.85; P = 0.001); BNP ≥ 67 pg/mL was 100 % sensitive and 20 % specific for LAA thrombus. Multivariate logistic regression analysis demonstrated that BNP was not independently associated with LAA thrombus (odds-ratio, 1.05 per 100 pg/mL increment; CI, 0.99–1.12; P = 0.127) after adjusting for CHA2DS2-VASc score; while the latter was independently associated with LAA thrombus after adjusting for BNP level (odds-ratio, 1.46 per CHA2DS2-VASc point; CI, 1.09–1.96; P = 0.011). Nonetheless, BNP was associated with SEC in univariate and multivariate analysis, after adjusting for the CHA2DS2-VASc score, (odds-ratio, 1.08; CI, 1.02–1.14; P = 0.005).ConclusionsBNP is predictive of SEC. However, it does not provide significant incremental value in the prediction of LAA thrombus.
The relationship between cardiovascular risk factors and vascular remodeling is a relatively new area of investigation. We discuss the various mechanisms by which cardiovascular risk factors cause vascular remodeling. Endothelial dysfunction, lipoprotein alterations, inflammation, and platelet activation are the mechanisms by which remodeling occurs. Plaque composition also plays an important role in directing remodeling. Plaque with extensive calcification is more likely to undergo constrictive remodeling. Positive and negative remodeling is based on how these factors coordinate and determine the direction of remodeling. Matrix metalloproteinases perform a crucial role in vascular remodeling. Advanced glycation end-products are key substances involved in the negative remodeling associated with diabetes. Remodeling in hypertension can be either eutrophic or hypertrophic. Endothelial dysfunction and low-grade inflammation lead to negative remodeling in hypertension. Dyslipidemia can be associated with either positive or negative remodeling. High high-density lipoprotein is associated with positive remodeling and high low-density lipoprotein with negative remodeling. Smoking causes endothelial dysfunction, increased oxidative stress, and decreased nitric oxide synthesis leading to inward remodeling. Aging also causes endothelial dysfunction and predisposes to negative remodeling. Knowledge of these associations can elucidate various clinical presentations and guide therapeutic choices in the future.
We sought to determine and prospectively validate, with concomitantly performed transthoracic (TTE) and transesophageal echocardiograms (TEE), a TTE-assessed E/e' threshold that can be useful in predicting left atrial appendage (LAA) thrombus in patients with nonvalvular atrial fibrillation (NVAF). The retrospective derivation cohort was comprised of 297 patients with NVAF with TTE performed within 1 year of TEE. The validation cohort was comprised of 266 prospectively enrolled patients with TTE performed immediately prior to TEE. LAA thrombus was detected by TEE in 6.4 % of patients in both cohorts. Receiver operating characteristic (ROC) analyses demonstrated a good discriminatory capacity of lateral E/e' in predicting LAA thrombus in the derivation cohort (AUC 0.72; CI 0.63-0.82; P = 0.001) which was confirmed in the validation cohort (AUC 0.83; CI 0.75-0.91; P < 0.001). In the derivation cohort, ROC curve point-coordinates identified E/e' thresholds of both 9.0 and 8.0 to be associated with 100 % sensitivity, with specificities of 36 and 30 %, respectively. An E/e' threshold of ≥8 was selected a priori for prospective validation, and was associated with 100 % sensitivity and 41 % specificity for LAA thrombus, with positive and negative predictive values of 10 and 100 %, respectively, and positive and negative likelihood ratios of 1.69 and 0, respectively. We determined and validated an E/e' threshold of 8 as a highly sensitive and useful parameter that can aid in identifying patients at very low risk for LAA thrombus and potentially obviate the need for a TEE prior to electrophysiology procedures and restoration of sinus rhythm.
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