Martin R. Berk

Intravascular ultrasound assessment of lumen size and wall morphology in normal subjects and patients with coronary artery disease.

BackgroundNecropsy studies demonstrate that coronary artery disease (CAD) is frequently complex and eccentric. However, angiography provides only a silhouette of the vessel lumen. Intravascular ultrasound is a new tomographic imaging method for evaluation of coronary dimensions and wall morphology. Few data exist regarding intravascular ultrasound in patients with CAD, and no data exist for subjects with normal coronaries. Methods and ResultsWe used a multielement 5.5F, 20-MHz ultrasound catheter to examine eight normal subjects and 43 patients with CAD. We assessed the safety of coronary ultrasound and the effect of vessel eccentricity on comparison of minimum luminal diameter by angiography and ultrasound. Normal and atherosclerotic wall morphology and stenosis severity were also evaluated by intravascular ultrasound. The only untoward effect was transient coronary spasm in five patients. At 33 sites in normal subjects, the lumen was nearly circular, yielding a close correlation between angiographic and ultrasonic minimum diameter (r = 0.92). At 90 sites in patients with CAD, ultrasound demonstrated a concentric cross section; correlation was also close (r = 0.93). However, at 72 eccentric sites, correlation was not as close (r = 0.77). For 41 stenoses, correlation between angiography and ultrasound for area reduction was moderate (r = 0.63). In normal subjects, wall morphology revealed a thin (0.30 mm or less) intimal leading edge and subadjacent sonolucent zone (0.20 mm or less). Patients with CAD exhibited increased thickness and echogenicity of the leading edge, thickened sonolucent zones, and/or attenuation of ultrasound transmission. ConclusionsThese data establish that intravascular ultrasound is feasible and safe and yields luminal measurements that correlate generally with angiography. Differences between angiographic and ultrasonic measures of lumen size in eccentric vessels probably reflect the dissimilar perspectives of tomographic and silhouette imaging techniques. Intravascular ultrasound provides detailed images of normal and abnormal wall morphology not previously possible in vivo.

Prognostic value of Doppler transmitral flow patterns in patients with congestive heart failure

OBJECTIVES This study was designed to determine whether Doppler echocardiographic transmitral flow patterns can predict cardiac mortality in patients with congestive heart failure. BACKGROUND Previous studies have indicated that Doppler transmitral flow patterns are related to New York Heart Association functional class and exercise capacity in patients with congestive heart failure. However, the prognostic significance of these flow patterns is not known. METHODS We analyzed the relation of transmitral flow patterns and cardiac mortality in 100 consecutive patients (76 men, 24 women; mean [+/- SD] age 60 +/- 11 years) with congestive heart failure symptoms and left ventricular ejection fraction < 40%. At the time of entry into the study, functional class and ejection fraction by radionuclide angiography were determined, and Doppler echocardiography was performed in all patients. Transmitral flow was obtained from the apical four-chamber view at the mitral annulus level. Measurements included early (E) and atrial (A) filling velocities, E/A ratio and deceleration time of the E wave. The patients were assigned to two groups according to E/A ratio or deceleration time of transmitral flow patterns, or both: a non-restrictive group (42 patients) with E/A < or = 1 or E/A = 1 to 2 and deceleration time > 140 ms, and a restrictive group (58 patients) with E/A > or = 2 or E/A = 1 to 2 and deceleration time < or = 140 ms. RESULTS Of 100 patients, 26 died during a mean follow-up period of 16 +/- 8 months. The cumulative cardiac mortality rate determined by the Kaplan-Meier method was 14% at 1 year and 35% at 2 years. Cox proportional hazards model analysis revealed that transmitral flow (restrictive vs. nonrestrictive, chi-square 6.99, p = 0.008), patient gender (female vs. male, chi-square 4.59, p = 0.03) and New York Heart Association functional class (IV vs. II, chi-square 3.95, p = 0.05) were significantly related to cardiac mortality in patients with congestive heart failure. Mortality rate in the restrictive group was markedly higher than that in the nonrestrictive group at 1 year (19% vs. 5%, respectively, p < 0.05) and at 2 years (51% vs. 5%, respectively, p < 0.01) by log-rank test. Relative risk for cardiac death was estimated as 4.1 at 1 year and 8.6 at 2 years in the restrictive group compared with the nonrestrictive group. CONCLUSIONS In patients with congestive heart failure, a restrictive transmitral flow pattern, female gender and advanced functional class are predictive of higher cardiac mortality. The restrictive transmitral flow pattern by Doppler echocardiography is the single best clinical predictor for cardiac death in patients with congestive heart failure.

Efficacy and Safety of Oral Dofetilide in Converting to and Maintaining Sinus Rhythm in Patients With Chronic Atrial Fibrillation or Atrial Flutter The Symptomatic Atrial Fibrillation Investigative Research on Dofetilide (SAFIRE-D) Study

BackgroundThis double-blind, multicenter, placebo-controlled study determined the efficacy and safety of dofetilide in converting atrial fibrillation (AF) or atrial flutter (AFl) to sinus rhythm (SR) and maintaining SR for 1 year. Methods and ResultsPatients with AF or AFl (n=325) were randomized to 125, 250, or 500 &mgr;g dofetilide or placebo twice daily. Dosages were adjusted for QTc response and, after 105 patients were enrolled, for calculated creatinine clearance (ClCr). Pharmacological cardioversion rates for 125, 250, and 500 &mgr;g dofetilide were 6.1%, 9.8%, and 29.9%, respectively, versus 1.2% for placebo (250 and 500 &mgr;g versus placebo;P =0.015 and P <0.001, respectively). Seventy percent of pharmacological cardioversions with dofetilide were achieved in 24 hours and 91% in 36 hours. For the 250 patients who successfully cardioverted pharmacologically or electrically, the probability of remaining in SR at 1 year was 0.40, 0.37, 0.58 for 125, 250, and 500 &mgr;g dofetilide, respectively, and 0.25 for placebo (500 &mgr;g versus placebo, P =0.001). Two cases of torsade de pointes occurred, 1 on day 2 and the other on day 3 (0.8% of all patients given active drug); 1 sudden cardiac death, classified as proarrhythmic, occurred on day 8 (0.4% of all patients given active drug). ConclusionsDofetilide, a new class III antiarrhythmic agent, is moderately effective in cardioverting AF or AFl to SR and significantly effective in maintaining SR for 1 year. In-hospital initiation and dosage adjustment based on QTc and ClCr are necessary to minimize a small but nonnegligible proarrhythmic risk.

Reduction of left ventricular preload by lower body negative pressure alters Doppler transmitral filling patterns

The objective of this study was to evaluate the effect of alterations in preload induced by lower body negative pressure on Doppler transmitral filling patterns. Echocardiograms and Doppler recordings were performed in 18 normal young men (aged 23 to 32 years) during various levels of lower body negative pressure (0, -20 and -50 mm Hg). Lower body negative pressure induced a reduction in diastolic velocity integral (from 12.17 +/- 0.79 to 8.42 +/- 0.71 cm, p = 0.0067) and consequently left ventricular diastolic diameter (from 5.11 +/- 0.09 to 4.45 +/- 0.1 cm, p less than 0.0001). There was a significant reflex increase in heart rate from 59.9 +/- 1.9 to 77.1 +/- 2.4 beats/min (p less than 0.0001), but blood pressure was unchanged. This reduction in preload altered Doppler transmittral filling patterns as follows: 1) peak early velocity (E) decreased from 59.2 +/- 3.8 to 39.1 +/- 1.7 cm/s (p less than 0.0001); 2) atrial filing velocity (A) was unchanged (35.58 +/- 1.5 to 33.52 +/- 1.4 cm/s, p = 0.517); 3) E/A ratio decreased from 1.7 +/- 0.13 to 1.19 +/- 0.08 (p = 0.0087); 4) mean acceleration (from 482 +/- 37 to 390 +/- 27 cm/s2, p = 0.03) and mean deceleration (from 327 +/- 31 to 169 +/- 21 cm/s2, p less than 0.001) of the early filling wave were significantly reduced; and 5) peak acceleration (from 907 +/- 42 to 829 +/- 29 cm/s2) and peak deceleration (from 771 +/- 94 to 547 +/- 76 cm/s2) also decreased, but not significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of echocardiographic morphology of the mitral apparatus to mitral regurgitation in mitral valve prolapse: Assessment by Doppler color flow imaging

Few data exist regarding the relationship of valvular anatomy and coaptation to the presence of mitral regurgitation (MR) in patients with mitral valve prolapse (MVP). Therefore this study was undertaken to assess the ability of two-dimensional echocardiographic features of mitral valve morphology to predict the presence, direction, and magnitude of MR as assessed by color Doppler flow imaging. MR was present in 21 of 46 patients with MVP on two-dimensional echocardiography. Echocardiograms were specifically evaluated for leaflet apposition, leaflet morphology, and mitral anulus diameter. Color flow images were analyzed for presence of MR, direction of the regurgitant jet, and area encompassing the largest jet visible in any view. Abnormal mitral leaflet coaptation on two-dimensional echocardiography was strongly associated with the presence of MR (p = 0.003), being present in 15 of 21 patients with as compared with 5 of 25 patients without MR. Similarly, mitral leaflet thickness and MR were closely associated (p = 0.0035), with the latter being present in 9 of 30 patients with normal and 12 of 16 patients with excessive leaflet thickness. MR jet direction tended to be anterior to central with posterior leaflet prolapse and posterior or central with anterior leaflet prolapse (p = 0.02). Maximal jet area of MR tended to be larger in patients with compared with those without mitral annular dilatation (5.4 +/- 2.3 versus 2.1 +/- 1.9 cm2, p = 0.001), and in those with abnormal rather than normal leaflet thickness (4.5 +/- 2.7 versus 2.0 +/- 1.6 cm2, p = 0.009). Thus the presence, direction, and size of MR jets in MVP are related to structural abnormality of the mitral apparatus on echocardiography.

Effect of Blood Pressure and Afterload on Doppler Echocardiographic Measurements of Left Ventricular Systolic Function in Normal Subjects

Doppler echocardiographic measurements of blood flow velocity and acceleration in the ascending aorta have been shown to be useful descriptors of left ventricular (LV) systolic function. Few data exist, however, regarding the influence of loading conditions, particularly afterload, on these Doppler measurements in human subjects. Therefore, 14 normal volunteers (mean age 28 years) were studied using continuous wave Doppler echocardiography performed from the suprasternal notch both at baseline and during a controlled infusion of methoxamine. LV peak systolic (delta pk) and end-systolic (delta ES) wall stresses were calculated noninvasively using blood pressure and echocardiographic dimensions. Heart rate was kept constant by transesophageal atrial pacing. Methoxamine resulted in significant increases in mean systolic (163 +/- 8 vs 129 +/- 10 mm Hg) and diastolic (93 +/- 7 vs 71 +/- 12 mm Hg) blood pressure, as well as delta pk (277 +/- 25 vs 222 +/- 40 g/cm2 x 10(3] and delta ES (97 +/- 26 vs 77 +/- 19 g/cm2 x 10(3] (p less than or equal to 0.0004 for all). Conversely, peak velocity decreased from 0.91 +/- 0.18 m/s at baseline to 0.8 +/- 0.18 m/s (p less than or equal to 0.002) and peak acceleration decreased from 22 +/- 5 m/s2 at baseline to 19 +/- 5 m/s2 (p less than or equal to 0.006) during methoxamine infusion. Flow velocity integral and LV end-diastolic dimension remained unchanged. Thus, aortic flow velocity and peak acceleration are inversely related to afterload. This relation should be considered when using serial determinations of these Doppler parameters for patients in whom changing levels of afterload might occur.

A simplified method for determining regurgitant fraction by Doppler echocardiography in patients with aortic regurtitation

OBJECTIVES This study attempted to develop and validate a simple method for calculating aortic regurgitant fraction by use of pulsed wave Doppler echocardiography. BACKGROUND Although several investigators have been able to determine aortic regurgitant fraction by Doppler echocardiography, the methods used require accurate determination of the cross-sectional areas of intracardiac sites at which the volumetric flow is calculated. METHODS Our concept was based on a constant relation that exists between the cross-sectional area of the left ventricular outflow tract and the mitral valve annulus in normal subjects. To verify this, we used Doppler echocardiography to measure the flow velocity integral of the left ventricular outflow tract and the mitral annulus in the apical view in 50 normal subjects (32 men, 18 women, mean age 34 years). RESULTS Close correlation (r = 0.95) was observed between the flow velocity integral (FVI) of the outflow tract (OT) and that of the mitral annulus (MA): FVIMA/FVIOT = 0.77. Because mitral flow equals aortic flow in normal subjects, the ratio of the cross-sectional area of the mitral annulus to that of the outflow tract was 1/0.77. In patients with aortic regurgitation, the regurgitant fraction (RF) = (Aortic flow-Mitral flow)/Aortic flow = 1-Mitral flow/Aortic flow. Substituting 0.77 for the area component of flow, RF = 1-(1/0.77).(FVIMA/FVIOT). To evaluate the accuracy of this method, we compared the regurgitant fraction derived by Doppler echocardiography with that from catheterization findings in 20 patients with aortic regurgitation (an isolated lesion was found in 14). The regurgitant fraction by catheterization was the difference between total (angiographic) and forward (thermodilution) stroke volumes as a percent of total flow. Good correlation was observed between catheterization and Doppler regurgitant fraction (r = 0.88, SEE 9%, p < 0.01). CONCLUSIONS Thus, regurgitant fraction can be estimated from Doppler echocardiography in patients with aortic regurgitation by a method that requires only measurements of the flow velocity integral from the mitral annulus and left ventricular outflow tract.

Effect of mitral regurgitation and volume loading on pressure half-time before and after balloon valvotomy in mitral stenosis

Doppler pressure half-time (PHT) is frequently used to assess mitral valve area (MVA), but the reliability of PHT has recently been challenged, specifically in the setting of balloon mitral valvotomy when hemodynamics have been abruptly altered. The effect of volume loading both before and after balloon mitral valvotomy on computation of MVA by Gorlin and by PHT in 18 patients with high-fidelity micromanometer measurements of left atrial and left ventricular pressure was therefore examined. Echocardiographic MVA increased from 0.91 +/- 0.15 to 1.97 +/- 0.42 cm2 after valvotomy. Volume loading produced significant increases in left atrial pressure (16 to 23 before and 12 to 20 mm Hg after valvotomy), in cardiac output (3.7 to 4.1 before and 3.9 to 4.6 liters/min after valvotomy), and in mitral valve gradient (11 to 14 before and 5 to 7 mm Hg after valvotomy). These hemodynamic changes were associated with modest but significant decreases in PHT and increases in MVA estimated by 220/PHT (0.66 to 0.81 before and 1.64 to 1.96 cm2 after valvotomy), whereas the MVA by Gorlin was not affected in a consistent fashion by volume loading (0.85 to 0.89 before and 1.66 to 1.69 cm2 after valvotomy). The correlation between Gorlin MVA and 220/PHT was only fair (r = 0.73, p less than 0.001) and was significantly poorer among patients with greater than 1+ mitral regurgitation (r = 0.72) than among those with less or no regurgitation (r = 0.79) (p = 0.001 by analysis of covariance for mitral regurgitation effect).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of alterations in loading produced by lower body negative pressure on aortic blood flow acceleration.

The objectives of this study were to evaluate the effects of alterations in loading induced by lower body negative pressure on aortic blood flow velocity and acceleration. Twenty-seven normal men were studied during various levels of lower body negative pressure (0 to -60 mm Hg) during which echocardiographic, Doppler and hormonal measurements were obtained. Lower body negative pressure induced a decrease in left ventricular diastolic diameter from 5.18 +/- 0.08 to 4.41 +/- 0.1 cm (p less than 0.0001) and in left ventricular systolic diameter from 3.33 +/- 0.09 to 2.84 +/- 0.1 cm (p less than 0.0001). Shortening fraction remained unchanged. The decrease in diastolic diameter resulted in a reduction in flow velocity integral from 13.8 +/- 0.8 to 7.5 +/- 0.4 cm (p less than 0.0001) and, therefore, in stroke volume from 89.6 +/- 4.7 to 49.5 +/- 2.8 ml (p less than 0.0001). Heart rate reflexly increased from 62.5 +/- 1.9 to 82.2 +/- 2.3 beats/min (p less than 0.0001) as did systemic vascular resistance from 1,280.8 +/- 69.5 to 1,863.4 +/- 121.4 dyne.s.cm-5 (p less than 0.0001). The increase in heart rate was insufficient to maintain cardiac output, which decreased from 5.53 +/- 0.29 to 3.99 +/- 0.21 liters/min (p less than 0.0001). Systolic, diastolic and mean arterial blood pressure was maintained. The negative pressure resulted in a concomitant significant increase in norepinephrine levels from 1.46 +/- 0.09 to 2.056 +/- 0.2 nmol/liter (p = 0.0019) but no change in plasma epinephrine: 0.845 +/- 0.22 to 0.78 +/- 0.11 nmol/liter (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Left atrial function in congestive heart failure: assessment by transmitral and pulmonary vein Doppler

The relation of transmitral flow patterns and pulmonary venous velocities was analyzed from 50 heart failure patients (28 men, 22 women; mean [±SD] age 61 ± 9 years) with a left ventricular ejection fraction < 40%. Doppler echocardiography was performed in all patients. Transmitral flow measurements included early (E) and atrial (A) velocities and deceleration time of E wave (DT). Patients were assigned to two groups according to E/A ratio, DT, or both: 20 patients in the restrictive group, and 30 patients in the nonrestrictive group. Pulmonary venous flow was obtained by the transthoracic approach. Systolic (S), diastolic (D) and atrial reversal (Ar) velocities were measured. Of the study population, 13 patients had simultaneously determined pulmonary capillary wedge pressure (PCWP).The results showed a lower S (28 ± 11 vs. 51 ± 10 cm/sec, p < 0.01), a higher D (66 ± 13 vs. 44 ± 10 cm/sec, p < 0.01) and a smaller Ar (12 ± 10 vs. 24 ± 9 cm/sec, p < 0.01) in the restrictive group compared with those in nonrestrictive group. In the subgroup of patients undergoing invasive hemodynamic studies, there was no relationship between PCWP and atrial reversal velocity. However, a significant correlation was observed for pulmonary systolic (r = -0.70, p < 0.01) and diastolic (r = 0.76, p < 0.01) velocities to PCWP. These findings suggest a reduction in left atrial compliance and atrial systolic function and both play important roles in heart failure patients with the restrictive transmitral flow pattern.