Gregory L. Pearce

Impact of electrical cardioversion for atrial fibrillation on left atrial appendage function and spontaneous echo contrast: Characterization by simultaneous transesophageal echocardiography

OBJECTIVES This study assessed the function of the left atrial appendage in the pericardioversion period to gain insights into mechanisms involved in thromboembolism after cardioversion of atrial fibrillation. BACKGROUND Systemic embolization associated with electrical cardioversion of atrial fibrillation is thought to originate from the left atrium or left atrial appendage, or both. However, the mechanism involved is poorly understood. METHODS We studied left atrial appendage function with transesophageal echocardiography in 20 patients with atrial fibrillation before and after successful electrical cardioversion. We measured left atrial appendage emptying and filling velocities by pulsed wave Doppler echocardiography, characterized Doppler emptying patterns, measured atrial appendage areas and assessed the presence or absence of spontaneous echo contrast or thrombus. RESULTS Organized left atrial appendage function returned in 16 (80%) of 20 patients immediately after cardioversion. Atrial appendage emptying velocities before cardioversion were greater in patients without (0.39 +/- 0.02 m/s) than in those with (0.25 +/- 0.12 m/s) spontaneous echo contrast (p = 0.045). Furthermore, emptying velocities before cardioversion were significantly greater than late diastolic emptying velocities after cardioversion (0.31 +/- 0.15 vs. 0.14 +/- 0.12 m/s, p = 0.0001), as well as in both the group with (0.25 +/- 0.12 vs. 0.13 +/- 0.13 m/s, p = 0.001) and the group without (0.39 +/- 0.02 vs. 0.15 +/- 0.12 m/s, p = 0.01) spontaneous echo contrast. In addition, left atrial and atrial appendage spontaneous echo contrast developed in 4 of 20 patients and increased in intensity in 3 of 20 patients in the immediate postcardioversion period. CONCLUSIONS Organized left atrial appendage function returns in most patients immediately after cardioversion of atrial fibrillation. However, its function is impaired compared with that before cardioversion. Furthermore, spontaneous echo contrast increased in 7 (35%) of 20 patients after cardioversion. These observations suggest that stunned left atrial appendage function after cardioversion may predispose the chamber to thrombus formation, which may play a role in the mechanism involved in the occurrence of embolization after cardioversion.

Statins do not meet expectations for lowering low-density lipoprotein cholesterol levels when used in clinical practice

BACKGROUND Statins have become a mainstay in the treatment of hyperlipidemia, based on their potency and favorable side-effect profile. Drug choice is presumed to be guided by the estimated degree of low-density lipoprotein (LDL) cholesterol lowering required in a particular patient and the projected efficacy of any drug-dose combination, as contained in the package inserts for each medication. We investigated whether these expectations were met in a clinical practice. METHODS Data were analyzed for 367 hyperlipidemic patients in a preventive cardiology practice who were not taking statins at entry, who were given a standard statin dose at their first visit, and who had at least one follow-up visit on the same drug/dose. Expected LDL cholesterol reductions were calculated for each patient based on guidelines in the package inserts for each drug. RESULTS The mean (+/-SD) observed LDL cholesterol reduction of 26% +/- 20% was significantly less than expected (34% +/- 7%, P < 0.001). The ratio of observed to expected reduction was not different for the three statins used (atorvastatin, 0.79 +/- 0.48; simvastatin, 0.88 +/- 0.61; pravastatin, 0.75 +/- 0.69; P = 0.39). CONCLUSIONS The use of statins in a clinical practice led to observed reductions in LDL cholesterol level that were significantly less than those projected by package insert guidelines. We believe this gap reflects the reduced patient compliance frequently observed in clinical practice settings, rather than any inherent difference in statin responsiveness of a practice versus a trial population. Physicians should be aware of this disparity when using statins in the clinical setting.

Association Between Apolipoprotein E Alleles and Calcific Valvular Heart Disease

Background—Studies on apolipoprotein E (apoE) alleles have reported an increased risk of coronary heart disease in patients with the apoE4 allele. Given the risk factor and histological similarities between coronary and calcific valvular heart disease (aortic stenosis [AS] and mitral annular calcification [MAC]), we postulated that apoE alleles might be associated with the development of these valvular lesions. Methods and Results—We evaluated the association between apoE alleles and calcific valvular lesions in 802 patients undergoing transthoracic echocardiography using logistic regression analyses. No difference was noted in genotype distribution (P =0.59) or prevalence of apoE4 between those with or without MAC (30% versus 27%, respectively; P =0.57). Compared with patients without AS, the genotype distribution of patients with AS differed significantly (P =0.03), with increasing prevalences of the apoE 4 allele (27% in those without versus 40% in those with AS; P =0.01). In multivariate analyses adjusting for age, gender, low-density lipoprotein cholesterol levels, and coronary artery disease, increasing age and the apoE4 allele were significant independent predictors of AS (odds ratio, 1.94; 95% confidence interval, 1.01 to 3.71; P =0.046), whereas the apoE4 allele was not predictive of MAC. Conclusions—These findings support extension of the importance of the apoE4 allele beyond atherosclerosis and Alzheimer’s disease to calcific AS.

Effects of mitral regurgitation on pulmonary venous flow and left atrial pressure: An intraoperative transesophageal echocardiographic study

OBJECTIVES AND BACKGROUND Pulmonary venous flows recorded by pulsed wave Doppler transesophageal echocardiography examination can be used to assess the severity of mitral regurgitation. Pulmonary venous flows are also related to left atrial pressures; however, the determinants of these flows have yet to be characterized in the presence of mitral regurgitation. METHODS We simultaneously recorded intraoperative pulmonary venous flows by transesophageal echocardiography and left atrial pressures by direct left atrial puncture in 16 patients with different grades of mitral regurgitation: 2+ (n = 5), 3+ (n = 4) and 4+ (n = 7). Pulmonary venous peak systolic and diastolic flow velocities and peak reversed systolic flow velocities were compared with left atrial pressure a and v waves, a-x and v-y descent values and left atrial volumes. RESULTS Pulmonary venous systolic to diastolic flow ratios correlated with decreases in left atrial pressure a/v ratios and with increases in the v waves of patients with higher grades of mitral regurgitation. Univariate analysis revealed that the best determinants of the pulmonary venous systolic to diastolic flow ratio were the left atrial pressure v wave (r = -0.76), the v-y descent value (r = -0.73) and the a/v ratio (r = 0.71). Lower correlations were found for left atrial end-systolic (r = -0.48) and end-diastolic (r = -0.42) volumes. Reversed systolic flow was present in patients with 4+ mitral regurgitation, despite left atrial enlargement. CONCLUSIONS Pulmonary venous flow can be used to assess the severity of mitral regurgitation and reflects the effects of mitral regurgitation severity on the left atrial pressure a and v waves.

Features and predictors of ascending aortic dilatation in association with a congenital bicuspid aortic valve.

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Differentiation of constrictive pericarditis from restrictive cardiomyopathy by Doppler transesophageal echocardiographic measurements of respiratory variations in pulmonary venous flow

OBJECTIVES The purpose of this study was to test the utility of measuring respiratory variation in pulmonary venous flow by transesophageal echocardiography. BACKGROUND Respiratory variation of atrioventricular and central venous flow velocities by Doppler echocardiography has been used to differentiate constrictive pericarditis from restrictive cardiomyopathy. METHODS We performed pulsed wave Doppler transesophageal echocardiography of the left or right pulmonary veins in 31 patients with diastolic dysfunction. Fourteen patients had constrictive pericarditis, and 17 had restrictive cardiomyopathy. We measured the pulmonary venous peak systolic and diastolic flow velocities and the systolic/diastolic flow ratio with transesophageal echocardiography during expiration and inspiration. The percent change in Doppler flow velocity from expiration to inspiration (%E) was calculated. RESULTS Pulmonary venous peak systolic flow in both inspiration and expiration was greater in constrictive pericarditis than in restrictive cardiomyopathy. The %E for peak systolic flow tended to be higher in constrictive pericarditis (19% vs. 10%, p = 0.09). In contrast, pulmonary venous peak diastolic flow during inspiration was lower in constrictive pericarditis than in restrictive cardiomyopathy. The %E for peak diastolic flow was larger in constrictive pericarditis (29% vs. 16%, p = 0.008). The pulmonary venous systolic/diastolic flow ratio was greater in constrictive pericarditis in both inspiration and expiration. The combination of pulmonary venous systolic/diastolic flow ratio > or = 0.65 in inspiration and a %E for peak diastolic flow > or = 40% correctly classified 86% of patients with constrictive pericarditis. CONCLUSIONS The relatively larger pulmonary venous systolic/diastolic flow ratio and greater respiratory variation in pulmonary venous systolic, and especially diastolic, flow velocities by transesophageal echocardiography can be useful signs in distinguishing constrictive pericarditis from restrictive cardiomyopathy.

Lipid Effects of Peroxisome Proliferator-Activated Receptor-Δ Agonist GW501516 in Subjects With Low High-Density Lipoprotein Cholesterol: Characteristics of Metabolic Syndrome

Objective—Peroxisome proliferator-activated receptor-&dgr;–induced upregulation in skeletal muscle fatty acid oxidation would predict the modulation of lipid/lipoproteins. Methods and Results—GW501516 (2.5, 5.0, or 10.0 mg) or placebo was given for 12 weeks to patients (n=268) with high-density lipoprotein (HDL) cholesterol <1.16 mmol/L. Fasting lipids/apolipoproteins (apos), insulin, glucose, and free fatty acid were measured; changes from baseline were calculated and assessed. A second smaller exploratory study (n=37) in a similar population was conducted using a sequence of 5 and 10 mg dosing for the assessment of lipoprotein particle concentration. GW501516 demonstrated HDL cholesterol increases up to 16.9% (10 mg) and apoA-I increases up to 6.6%. Reductions were observed in low-density lipoprotein (LDL) cholesterol (−7.3%), triglycerides (−16.9%), apoB (−14.9%), and free fatty acids (−19.4%). The exploratory study showed significant reductions in the concentration of very LDL (−19%), intermediate-density lipoprotein (−52%), and LDL (−14%, predominantly a reduction in small particles), whereas the number of HDL particles increased (+10%; predominantly medium and large HDL). Conclusion—GW501516 produced significant changes in HDL cholesterol, LDL cholesterol, apoA1, and apoB. Fewer very LDL and larger LDL support a transition toward less atherogenic lipoprotein profiles. These data are consistent with peroxisome proliferator-activated receptor-&dgr; being a potentially important target for providing cardiovascular protection in metabolic syndrome-like patients.

Elevated Fibrinogen and Homocysteine Levels Enhance the Risk of Mortality in Patients From a High-Risk Preventive Cardiology Clinic

Fibrinogen (Fib) plays an important role in platelet aggregation and thrombus formation, and homocysteine (tHcy) causes endothelial dysfunction and injury. Therefore, an interaction toward an enhanced risk of thrombotic events and consequent mortality might be expected in patients with both factors elevated. To determine whether patients exposed jointly to high Fib and high tHcy were at increased risk of mortality, we compared them with those with only one or neither risk factors elevated. Prevalence of coronary artery disease (cross-section) and short-term mortality (30±14 months) were assessed in 2084 patients with available baseline tHcy and Fib. Upper quartiles were used to define high tHcy (>14.2 &mgr;mol/L) and high Fib (>382 mg/dL). Cox models adjusting for Framingham risk score, creatinine, and coronary artery disease status were used to estimate the risk of high tHcy and high Fib and their combinations. Mean age of the patients was 56±12 years (35% women) with 71 (3.4%) recorded deaths. Risk-adjusted longitudinal models showed a hazard ratio of 2.14 (P =0.03) for isolated high tHcy, 2.28 (P =0.02) for isolated high Fib, and 3.29 (P <0.001) for both high tHcy and high Fib in comparison with neither risk factor high. Independence of each parameter and lack of synergism was found on longitudinal as well as cross-sectional analyses. Conjoint elevation of Fib and tHcy increased the risk of death by approximately 3-fold in three years. Although no significant interaction between Fib and tHcy was demonstrated, both provided independent information after adjustment for traditional risk factors.

Importance of Sampling Both Pulmonary Veins in Grading Mitral Regurgitation by Transesophageal Echocardiography

Pulmonary venous flow patterns have been used to assess severity of mitral regurgitation; however, the issue of which pulmonary veins to sample has not been determined. We performed pulsed wave Doppler transesophageal echocardiography of both the left and right upper pulmonary veins in 80 patients who had mitral regurgitation determined by independent transesophageal echocardiography color flow mapping. Pulmonary venous flow patterns, peak systolic and diastolic flow, and the presence of reversed systolic flow were compared between the left and right pulmonary veins for each grade of mitral regurgitation. Flow patterns were discordant in 20 (25%) of the 80 patients. Of the 43 patients with 4+ mitral regurgitation, there was discordant flow in 16 (37%) of the patients with mainly reversed systolic flow in the right upper vein, while there was blunted or normal systolic flow in the left upper vein. Of the 16 patients with discordant flows, 14 had eccentric jets, mainly anteromedial jets. We conclude that if discordant flow can occur in 25% of patients with mitral regurgitation and in 37% of patients with 4+ mitral regurgitation, then both pulmonary veins must be evaluated when assessing the severity of mitral regurgitation with pulsed wave Doppler transesophageal echocardiography.

Effects of mitral stenosis on pulmonary venous flow as measured by Doppler transesophageal echocardiography

Pulmonary venous flow as assessed by transesophageal echocardiography (TEE) is influenced by changes in left atrial pressure and function. In mitral stenosis (MS), normal left atrial hemodynamics are altered because there is a prolonged decay in diastolic pressure from the left atrium to the left ventricle and atrial function may be altered because of atrial fibrillation. To assess the effect of the prolonged atrial diastolic pressure decay caused by MS on pulmonary venous flow, we studied 27 patients with MS (mitral valve range 0.7 to 2.4 cm2) by pulsed-wave Doppler TEE of the left or right upper pulmonary vein, and compared results with those of 13 normal subjects. Of the 27 subjects with MS, 61% showed a blunted systolic flow pattern and 39% showed a normal flow pattern with greater systolic to diastolic flow ratio. Patients with atrial fibrillation had a predominantly blunted pattern, whereas patients with normal sinus rhythm exhibited both blunted and normal flow patterns. Patients with MS had a lower pulmonary venous peak systolic flow velocity and a longer diastolic pressure halftime than control subjects. Pulmonary venous peak systolic flow velocity was significantly decreased in the presence of atrial fibrillation (p = 0.004). The mitral valve pressure halftime significantly correlated with pulmonary venous diastolic pressure halftime (r = 0.54; p = 0.004) mitral valve area (r = -0.46; p = 0.02). In conclusion, it was found that MS alters pulmonary venous flow patterns, showing a decreased pulmonary venous systolic flow and a prolonged diastolic flow, which may be useful in assessing the hemodynamics of MS.