Impact of B-type natriuretic peptide level on the risk of left atrial appendage thrombus in patients with nonvalvular atrial fibrillation: a prospective study.

BACKGROUND: The 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. METHODS: In two academic medical centers, we obtained BNP levels immediately prior to transesophageal echocardiogram performed to exclude LAA thrombus in patients with NVAF. RESULTS: Among 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). CONCLUSIONS: BNP is predictive of SEC. However, it does not provide significant incremental value in the prediction of LAA thrombus.

Derivation and validation of E/e' ratio as a parameter in the evaluation of left atrial appendage thrombus formation in patients with nonvalvular atrial fibrillation.

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.

Impact of Diastolic Function Parameters on the Risk for Left Atrial Appendage Thrombus in Patients with Nonvalvular Atrial Fibrillation: A Prospective Study.

BACKGROUND: In patients with nonvalvular atrial fibrillation (NVAF), the impact of left ventricular diastolic function on the risk for left atrial appendage (LAA) thrombus has not been prospectively studied. METHODS: At two academic medical centers, patients with NVAF were prospectively enrolled to undergo investigational transthoracic echocardiography immediately before clinically indicated transesophageal echocardiography. Mitral inflow E velocity and tissue Doppler septal and lateral mitral annulus velocities (e') were measured, and E/e' ratios were calculated. RESULTS: Among 266 subjects (mean age, 65 years; 32% women), 17 (6.4%) had LAA thrombus. Patients with LAA thrombus had a higher mean CHA2DS2-VASc score (4.6 ± 1.7 vs 3.0 ± 1.8, P < .001), a higher mean lateral E/e' ratio (19.4 ± 10.1 vs 10.2 ± 5.6, P < .001), and a lower mean lateral e' velocity (7.0 ± 3.2 vs 10.4 ± 3.7 cm/sec, P = .001). There was a good discriminative capacity for E/e' (area under the curve, 0.83; P < .001) and e' velocity (area under the curve, 0.76; P = .001). None of the patients with normal E/e' ratios or normal e' velocities had LAA thrombus. Both E/e' (odds ratio, 1.13 per point; 95% CI, 1.06-1.20; P < .001) and e' velocity (odds ratio, 0.76 per 1 cm/sec; 95% CI, 0.63-0.92; P = .005) provided independent and incremental predictive value beyond the CHA2DS2-VASc score; however, E/e' provided greater incremental value than e' velocity (P = .036). Analyses using septal and averaged E/e' and septal e' velocity yielded similar results. Diastolic function parameters were also associated with the presence and intensity of left atrial spontaneous echo contrast, a precursor of LAA thrombus. CONCLUSIONS: This prospective and concomitant evaluation of diastolic function and LAA thrombus in patients with NVAF demonstrates that E/e' ratio and e' velocity are associated with LAA thrombus, independent of CHA2DS2-VASc score, and may play a role in identifying patients at low risk for LAA thrombus. These data suggest that diastolic function assessment may improve stroke prediction in patients with NVAF.

Pathophysiology of coronary vascular remodeling: relationship with traditional risk factors for coronary artery disease.

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.

Incidence and management of gastrointestinal bleeding with continuous flow assist devices.

BACKGROUND: Continuous flow left ventricular assist devices (CF-LVADs) have emerged as the standard of care for patients in advanced heart failure (HF) requiring long-term mechanical circulatory support. Gastrointestinal (GI) bleeding has been frequently reported within this population. METHODS: A retrospective analysis of 101 patients implanted with the Heart Mate II from January 2005 to August 2011 was performed to identify incidence, etiology, and management of GI bleeding. Univariate and multivariate regression analysis was conducted to identify related risk factors. RESULTS: A significant incidence of GI bleeding (22.8%) occurred in our predominantly destination therapy (DT) (93%) population. Fifty-seven percent of the patients with bleeding episodes bled from the upper GI (UGI) tract (with 54% bleeding from gastric erosions and 37% from ulcers/angiodysplasias), whereas 35% of patients bled from the lower GI (LGI) tract. Previous history of GI bleeding (odds ratio [OR], 22.7; 95% CI, 2.2-228.6; p=0.008), elevated international normalized ratio (INR) (OR, 3.9; CI, 1.2-12.9; p=0.02), and low platelet count (OR, -0.98; CI, 0.98 -0.99; p=0.001) were independent predictors of GI hemorrhage. Recurrent bleeding was more common in older patients (mean, 70 years; p=0.01). The majority of bleeders (60%) rebled from the same site. Management strategies included temporarily withholding anticoagulation, decreasing the speed of LVADs, and using octreotide. Octreotide did not impact the amount of packed red blood cells used, rebleeding rates, length of hospital stay, or all-cause mortality. Only 1 patient died as a direct consequence of GI bleeding. CONCLUSIONS: Multiple factors account for GI bleeding in patients on CF-VADs. A previous history of bleeding increases risk significantly and warrants careful monitoring.