Assessment of the American Society of Echocardiography-European Association of Echocardiography guidelines for diastolic function in patients with depressed ejection fraction: an echocardiographic and invasive haemodynamic study.

AIMS: There is controversy surrounding the accuracy of echo-Doppler variables, including early mitral inflow/mitral annular velocity (E/e'), for estimating left ventricular filling pressure (LVFP) in patients with depressed ejection fraction (EF < 50%). METHODS AND RESULTS: The American Society of Echocardiography-European Association of Echocardiography (ASE-EAE) algorithm for diastolic function in depressed LVEF was retrospectively applied to a database of patients who underwent echocardiography ≤20 min of cardiac catheterization. LV pre-atrial contraction pressure (pre-A) ≥15 mmHg was elevated. Of 62 patients studied, the mean age was 53.6 ± 10.6 years and the mean LVEF was 27.2 ± 11.8%. The correlations of E/e' (R = 0.43, P = 0.0005) and E (R = 0.39, P = 0.002) with LV pre-A were modest, compared with pulmonary artery pressure (PAP, R = 0.69, P = 0.0006), E/late mitral (A) velocity (R = 0.52, P < 0.0001), and mitral deceleration time (DT, R = -0.51, P < 0.0001). Using the ASE-ESE algorithm starting with E/A, E, and DT, 54 of 62 patients were accurately classified to predict LV pre-A >15 or <15 mmHg (sensitivity = 84%, specificity = 80%, area under the curve = 0.86, P < 0.001). The 6 of 6 patients with E/A < 1 and E < 50 and the 14 of 15 (93%) patients with E/A> 2 and DT < 150 were correctly classified as having normal and elevated LVFP, respectively, while 34 of 41 (83%) patients with E/A = 1-2 or E/A<1 and E>50 cm/s were correctly classified using the addition of E/e' and PAP. CONCLUSION: This retrospective study shows that in this population with depressed LVEF, no single echo-Doppler variable had high accuracy for predicting LV pre-A ≥15 mmHg. However, the ASE-EAE algorithm using multiple variables predicted LVFP with good accuracy, superior to any single echo-Doppler variable alone.

New, simple echocardiographic indexes for the estimation of filling pressure in patients with cardiac disease and preserved left ventricular ejection fraction.

BACKGROUND: There are few data on echocardiographic indexes incorporating peak mitral inflow velocity (E), left atrial volume index (LAVi), and pulmonary artery pressure (PAP) for estimation of left ventricular (LV) filling pressure in patients with preserved LV ejection fraction (EF ≥ 50%). METHODS: Patients underwent echocardiography ≤20 minutes of cardiac catheterization. Echocardiographic variables were compared to invasively measured LV end-diastolic pressure (LVEDP). RESULTS: Of the 122 patients, 67 (55%) were women, the mean age was 55 ± 9 years, the mean left ventricular ejection fraction (LVEF) was 61 ± 6%, 107 (88%) were hypertensive, and 79 (65%) had significant coronary artery disease at catheterization. E/Ea correlated with LVEDP (R = 0.68, P < 0.0001), compared to PAP (R = 0.53, P < 0.001), peak E velocity (R = 0.48, P < 0.001), and LAVi (R = 0.48, P < 0.001). E/Ea > 12 had 75% sensitivity and 78% specificity for LVEDP ≥ 20 mmHg (area under curve (AUC) = 0.79, P < 0.0001), compared with (PAP + LAVi)/2 > 30 (sensitivity = 72%, specificity = 80%, AUC = 0.84, P < 0.001) and (E + LAVi)/2 > 57 (sensitivity = 73% and specificity = 81%, AUC = 0.82, P < 0.001) (P = NS). E <60 cm/sec had 94% negative, and E>90 cm/sec had 96% positive, predictive value for LVEDP ≥ 20 mmHg. (E + LAVi)/2 added incrementally to E/Ea when E/Ea was in the gray zone. CONCLUSIONS: New, simple echocardiographic equations, (E + LAVi)/2 and (PAP + LAVi)/2, have comparable accuracy to E/Ea for LVEDP estimation in patients with cardiac disease and preserved LVEF, and (E + LAVi)/2 added incrementally to E/Ea alone when E/Ea was in the gray zone. Peak E velocity alone had high negative and positive predictive value for elevated LVEDP in this population. These simple echocardiographic variables could be used-in isolation or with E/Ea-in patients with cardiac disease and preserved LVEF for the diagnosis of diastolic heart failure.

Usefulness of new diastolic strain and strain rate indexes for the estimation of left ventricular filling pressure.

Tissue Doppler indexes of left ventricular (LV) filling pressure are prone to angulation errors and tethering and are less reliable in patients with preserved LV ejection fraction and indeterminate early peak transmitral diastolic flow (E)/mitral early diastolic velocity (Ea) (8 or =8 had higher sensitivity and specificity (95% and 94%, respectively; area under the curve = 0.96, p <0.0001) than E/Ea > or =15 (sensitivity 81%, specificity 75%; area under the curve = 0.85, p <0.0001) for the prediction of LV pre-A pressure > or =15 mm Hg (p = 0.01 for comparison). In patients with LV ejection fraction > or =50% and 8 or =50% or indeterminate E/Ea, both E/Ds and E/10DSr (a ratio based on global DSR) were better predictors of LV filling pressure than E/Ea.

Assessment of left ventricular systolic function using echocardiography in patients with preserved ejection fraction and elevated diastolic pressures.

There is controversy regarding the nature of systolic function in patients with elevated filling pressure and preserved left ventricular (LV) ejection fraction. In this study, tissue Doppler variables and 2-dimensional echocardiographic systolic strain (SS) and systolic strain rate (SSr) were measured in patients who underwent cardiac catheterization to determine correlations with invasively measured LV end-diastolic pressure (LVEDP), dP/dt, and LV mass. Forty patients were studied. Their mean age was 55.9+/-9.9 years, and their mean LV ejection fraction was 59.8+/-5.2%. Tissue Doppler systolic annular velocity (5.4+/-1.1 vs 6.4+/-1.0 cm/s, p=0.04), SS (13.4+/-3.7% vs 18.8+/-2.3%, p <0.001), and SSr (0.73+/-0.17 vs 0.98+/-0.14 s(-1), p <0.001) were significantly lower in patients with LVEDP >20 mm Hg compared with those with LVEDP <20 mm Hg. Tissue Doppler systolic velocity, SSr, and SS were correlated with LV mass (R=0.58, R=0.57, and R=0.52, respectively, all p values <0.001) and with LVEDP (R=0.49, p=0.002; R=0.79, p<0.001; and R=0.70, p<0.001, respectively). However, dP/dt was not significantly different between patients with LVEDP >20 mm Hg and those with LVEDP <20 mm Hg (1,387+/-520 vs 1,495+/-594 mm Hg/s, respectively, p=0.55) and was not correlated with LV mass (R=0.18, p=0.25). The optimum cut-off values for LVEDP >20 mm Hg were SSr <0.85 s(-1) (area under the curve 0.88, p<0.001, positive predictive value 89%, negative predictive value 86%) and SS<16% (area under the curve 0.84, p=0.002, positive predictive value 88%, negative predictive value 79%). In conclusion, as opposed to invasively measured dP/dt, tissue Doppler systolic velocity and 2-dimensional echocardiographic SS and SSr are significantly depressed in patients with preserved LV ejection fraction and LVEDP >20 mm Hg, suggesting that systolic abnormalities are present in at least some of these patients. These differences are likely because invasively measured dP/dt and these echocardiographic variables measure different systolic properties in patients with preserved LV ejection fraction.

Comparison of higher clopidogrel loading and maintenance dose to standard dose on platelet function and outcomes after percutaneous coronary intervention using drug-eluting stents.

Adequate antiplatelet therapy is paramount for good clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). The purpose of this study was to determine whether a high-dose regimen of clopidogrel in patients undergoing PCI is superior to standard dosing. A total of 119 patients undergoing PCI were blindly randomized in 2:1 fashion to receive clopidogrel loading 600 mg on the table immediately before PCI and 75 mg 2 times/day for 1 month (high-dose group) versus standard dosing (300 mg loading and 75 mg/day; low-dose group). Platelet aggregation was measured using light transmission aggregometry at baseline, 4 hours, and 30 days. The composite of cardiovascular death, myocardial infarction, and target vessel revascularization was studied at 30 days in addition to major and minor bleeding. Baseline characteristics and baseline platelet aggregation were similar in the 2 groups. Percent inhibitions of platelet activity were 41% and 27% in the high-dose group versus 19% and 10% in the low-dose group at 4 hours and 30 days (p = 0.046 and 0.047, respectively). Composite clinical end points were 10.3% in the high-dose group and 23.8% in the low-dose group (p = 0.04). No difference was noted in major or minor bleeding. In conclusion, a higher loading and maintenance dose of clopidogrel in patients undergoing PCI results in superior platelet inhibition and decreased cardiovascular events without increasing bleeding complications.

Segmental analysis of carotid arterial strain using speckle-tracking.

BACKGROUND: Increased arterial stiffness has been shown to be associated with aging and cardiovascular risk factors. Speckle-tracking algorithms are being used to measure myocardial strain. The aims of this study were to evaluate whether speckle-tracking could be used to measure carotid arterial strain (CAS) reproducibly in healthy volunteers and to determine if CAS was lesser in individuals with diabetes. METHODS: Bilateral electrocardiographically gated ultrasound scans of the distal common carotid arteries (three cardiac cycles; 14-MHz linear probe; mean frame rate, 78.7 ± 8.9 frames/sec) were performed twice (2-4 days apart) on 10 healthy volunteers to test repeatability. Differences in CAS between healthy subjects (n = 20) and patients with diabetes (n = 21) were examined. Peak CAS was measured in each of six equal segments, and averages of all segments (i.e., the global average), of the three segments nearest the probe, and of the three segments farthest from the probe (i.e., the far wall average) were obtained. RESULTS: Global CAS (intraclass correlation coefficient = 0.40) and far wall average (intraclass correlation coefficient = 0.63) had the greatest test-retest reliability. Global and far wall averaged CAS values were lower in patients with diabetes (4.29% [SE, 0.27%] and 4.30% [SE, 0.44%], respectively) than in controls (5.48% [SE, 0.29%], P = .001, and 5.58% [SE, 0.44%], P = .003, respectively). This difference persisted after adjustment for age, gender, race, and hemodynamic parameters. CONCLUSIONS: Speckle-tracking to measure CAS is feasible and modestly reliable. Patients with diabetes had lower CAS obtained with speckle-tracking compared with healthy controls.

Systolic and diastolic myocardial mechanics in patients with cardiac disease and preserved ejection fraction: impact of left ventricular filling pressure.

BACKGROUND: There are few data on the impact of left ventricular (LV) filling pressure on systolic and diastolic myocardial mechanics in patients with cardiac disease and preserved LV ejection fraction (LVEF) (≥ 50%). METHODS: Patients referred for cardiac catheterization underwent comprehensive echocardiography within 20 minutes of catheterization. Strain and strain rate in longitudinal, radial, and circumferential directions and torsion were measured in systole and diastole. LV preatrial contraction pressure (pre-A) was measured and averaged over 10 cardiac cycles. RESULTS: Sixty patients were studied (mean age, 55.3 ± 8.9 years). The 30 patients with LV pre-A ≥ 15 mm Hg had significantly lower longitudinal systolic strain and radial, circumferential, and torsional systolic strain rates than the 30 patients with LV pre-A < 15 mm Hg (P < .05 for all). Similar findings were seen for diastolic variables. There were significant correlations between several systolic and diastolic variables in multiple directions and LV pre-A. On multivariate analysis, the independent predictors of systolic and diastolic speckle-tracking parameters included LVEF and LV pre-A, depending on the specific parameter analyzed. CONCLUSIONS: In patients with preserved LVEF and cardiac disease, several systolic and diastolic myocardial mechanical parameters significantly correlate with LV filling pressure. These data highlight the notion that patients with preserved LVEF and elevated LV filling pressures have significant abnormalities in systolic function as detected by speckle imaging, findings that may challenge the concept of "isolated diastolic dysfunction." The extent of systolic and diastolic abnormalities in these patients may shed light on the mechanics of heart failure with preserved LVEF.

Do additional echocardiographic variables increase the accuracy of E/e' for predicting left ventricular filling pressure in normal ejection fraction? An echocardiographic and invasive hemodynamic study.

BACKGROUND: There are few data on adding left atrial volume index (LAVi) or pulmonary artery systolic pressure (PAP) to the ratio of early mitral inflow to mitral annular velocity (E/e') for the estimation of left ventricular (LV) filling pressure in patients with preserved LV ejection fractions (LVEFs) (>50%). METHODS: Patients underwent echocardiography within 20 minutes of cardiac catheterization. Echocardiographic variables were compared with invasively measured LV preatrial contraction pressure (pre-A). RESULTS: Of the 122 patients studied (mean age, 55 +/- 9 years; mean LVEF, 61 +/- 6%), 67 (55%) were women, 108 (88%) had hypertension, and 79 (65%) had significant coronary artery disease at catheterization. E/e' was significantly correlated with pre-A (R = 0.63, P < .0001) compared with LAVi (R = 0.49, P < .001) and PAP (R = 0.48, P < .001). E/e' > 13 had sensitivity of 70% and specificity of 93% (area under the curve [AUC], 0.82; P < .0001), LAVi > 31 mL/m2 had sensitivity of 78% and specificity of 76% (AUC, 0.80, P < .001), and PAP > 28 mm Hg had sensitivity of 80% and specificity of 64% for pre-A > 15 mm Hg (AUC, 0.77, P < .001). Adding LAVi >31 mL/m2 for E/e' = 8 to 13 significantly increased the accuracy of E/e' > 13 alone (sensitivity, 87%; specificity, 88%; AUC, 0.89; P = .01 for comparison). However, adding PAP > 28 mm Hg for E/e' = 8 to 13 did not significantly increase the accuracy of E/e' > 13 alone (AUC, 0.82; sensitivity, 82%; specificity, 72%; P = NS for comparison). CONCLUSIONS: In patients with preserved LVEFs, adding LAVi > 31 mL/m2 to E/e' (when E/e' was in the gray zone, but not when E/e' was >13) significantly increased the accuracy of E/e' alone for the estimation of LV filling pressure. These data support the notion of using several, rather than any single, Doppler echocardiographic parameter for the accurate assessment of LV diastolic function.

Sinus arrest during radiofrequency ablation of the atrioventricular-node slow pathway: implications and possible mechanisms.

Radiofrequency ablation has been associated with changes in autonomic function. In this case, a 52-year-old woman was referred for electrophysiologic study of recurrent supraventricular tachycardia. Typical slow/fast atrioventricular node re-entry tachycardia was induced and confirmed during the study. Radiofrequency ablation of the slow pathway of the atrioventricular node led to sinus arrest, which resolved once ablation was stopped. Given the distance of the ablation site from the sinus node, we inferred that mechanisms other than direct injury to the sinus node were involved. To our knowledge, this is only the 2nd reported finding of sinus arrest during slow-pathway ablation of the atrioventricular node. This case highlights the complex interaction between the autonomic nervous system and the cardiac conduction system. Possible mechanisms include a Bezold-Jarisch reflex and modification of the intrinsic autonomic nervous system.

In vitro inhibition of platelet aggregation in response to increasing concentrations of tirofiban in patients with significant renal insufficiency.

BACKGROUND: Patients with impaired renal function are a growing subset at higher risk for cardiovascular complications due to vasculopathic state, inducing accelerated atherosclerosis and arteriosclerosis. These patients are at increased risk for complications after coronary interventions, especially major bleeding events. As a result, this at-risk population of patients has not been well studied in most of the major clinical trials evaluating coronary interventions. Of particular interest is the optimal dosing of glycoprotein IIb-IIIa inhibitors in the setting of acute myocardial infarction. In this study, we attempted to find the in vitro concentration of tirofiban required to inhibit platelet aggregation to <10% in patients with moderate to severe renal insufficiency. METHODS: A total of 21 patients were divided into two groups based on estimated creatinine clearance (group 1 <46ml/min; group 2 >46ml/min). Platelet-rich plasma from each subject was then incubated in vitro with increasing concentrations of tirofiban (25, 37.5, and 50ng/ml), and light transmission aggregometry assay was used to assess the degree of platelet aggregation in response to adenosine diphosphate (ADP). RESULTS: Patients in group 1 had a baseline platelet aggregation of 45%, which decreased to 10% at a 25.0ng/ml concentration of tirofiban; the effect was enhanced to a platelet aggregation of <5% at higher doses. In contrast, subjects in group 2 with creatinine clearance >or=46ml/min had an average platelet aggregation inhibition of 12% with 50ng/ml of tirofiban.We found a significant decrease in platelet aggregation in group 2 at 25, 37.5, and 50ng/ml of tirofiban (p<0.05) in comparison with group 1. CONCLUSIONS: Our data indicate that patients with moderate to severe renal dysfunction suppress their platelet aggregation to <10% with 25ng/ml of tirofiban, one-third of the standard effective dose for patients with normal renal function.We suggest further clinical trials to define an objective means to calculate proper renal dosing of glycoprotein IIb-IIIa inhibitors in these patients to prevent potentially fatal complication of major hemorrhagic events.

Correlation of tissue Doppler and two-dimensional speckle myocardial velocities and comparison of derived ratios with invasively measured left ventricular filling pressures.

BACKGROUND: There are a paucity of data comparing spectral and color tissue Doppler (TD) with non-Doppler, speckle-based myocardial velocities, and it is unknown how early transmitral diastolic velocity/mitral annular velocity (E/Ea) calculated using speckle velocities compares with TD-derived E/Ea. METHODS: We measured systolic (Sa), Ea, and late diastolic (Aa) myocardial velocities using these 3 methods and compared calculated E/Ea with invasively measured left ventricular (LV) hemodynamics. Consecutive patients referred for cardiac catheterization were imaged, and LV pre-A contraction pressure was measured by retrograde aortic cardiac catheterization. RESULTS: Fifty patients (22 women, 44%) were studied with a mean age of 54 +/- 10 years and a mean LV ejection fraction of 48% +/- 19%. Speckle and color TD Sa, Ea, and Aa were significantly lower than spectral TD velocities, resulting in higher E/Ea values compared with spectral TD E/Ea. Spectral TD E/Ea (R = 0.65, P < .001), color TD E/Ea (R = 0.69, P < .001), and speckle E/Ea (R = 0.76, P < .001) all correlated with LV pre-A pressure. Different cutoff values were needed for spectral TD, color TD, and speckle E/Ea to predict LV pre-A pressure >or= 15 mm Hg; spectral E/Ea > 14 (area under the curve [AUC] = 0.87, P < .001, sensitivity = 83%, specificity = 77%), color E/Ea > 16 (AUC = 0.89, P < .0001, sensitivity = 79%, specificity = 81%), and speckle E/Ea > 18 (AUC = 0.87, P < .0001, sensitivity = 88%, specificity = 74%; P = not significant for comparisons between the groups). CONCLUSION: Spectral TD, color TD, and speckle imaging measure different velocities, and consequently different cutoff values are needed for E/Ea to predict invasively measured LV filling pressure.