Diagnostic and prognostic value of serial dobutamine stress echocardiography for noninvasive assessment of cardiac allograft vasculopathy: a comparison with coronary angiography and intravascular ultrasound.

BACKGROUND: Routine methods for surveillance of cardiac allograft vasculopathy (CAV) are coronary angiography and intravascular ultrasound (IVUS). This study analyzed the diagnostic and prognostic value of dobutamine stress echocardiography (DSE) for noninvasive assessment of CAV. METHODS AND RESULTS: In 109 heart transplant recipients, 333 DSEs were compared with 285 coronary angiograms and 199 IVUS analyses. Studies were repeated after 1, 2, 3, 4, and >/=5 years in 88, 74, 37, 18, and 7 patients, respectively. Resting 2D echocardiography detected CAV defined by IVUS and angiography with a sensitivity of 57% (specificity 88%). DSE increased the sensitivity to 72% (P=0.002). M-mode analysis increased the sensitivity of 2D rest and stress analysis (P=0.001, 0.004). Cardiac events occurred after 1.9% of normal stress tests by 2D analysis (combined 2D and M-mode: 0%), compared with 6.3% (3.8%) of normal resting studies. Worsening of serial DSE indicated an increased risk of events compared with no deterioration (relative risk 7.26, P=0.0014). Serial deterioration detected by stress only was associated with a higher risk of events than changes evident from resting studies (relative risk 3.06, P=0.0374). CONCLUSIONS: DSE identifies patients at risk for events and facilitates monitoring of CAV. A normal DSE predicts an uneventful clinical course and justifies postponement of invasive studies. The prognostic value of DSE is comparable to that of IVUS and angiography.

Randomized comparison of coronary stent implantation under ultrasound or angiographic guidance to reduce stent restenosis (OPTICUS Study).

BACKGROUND: Observational studies in selected patients have shown remarkably low restenosis rates after ultrasound-guided stent implantation. However, it is unknown whether this implantation strategy improves long-term angiographic and clinical outcome in routine clinical practice. Methods and Results-- A total of 550 patients with a symptomatic coronary lesion or silent ischemia were randomly assigned to either ultrasound-guided or angiography-guided implantation of

Platelet activation in embolic and preembolic status of patients with nonrheumatic atrial fibrillation.

STUDY OBJECTIVE: Information on platelet activation possibly associated with a preembolic or embolic status in nonrheumatic atrial fibrillation (AF) with special regard to the role of platelet membrane activation markers (P-selectin and CD63). STUDY POPULATION: The study included 60 patients with nonrheumatic AF; 28 of them had a history of an embolic event. The age-matched control group consisted of 28 healthy subjects (13 men and 15 women). INTERVENTIONS: Patients underwent transesophageal echocardiography to detect eventual intracardiac thrombus or spontaneous echo contrast that would represent a preembolic status. Blood samples were taken from all persons to evaluate markers for platelet activation under these conditions. RESULTS: Measurements of hematologic variables did not differ significantly between normal subjects and patients presenting with AF but no preembolic or embolic status. Elevated concentrations of fibrinogen were significantly related to the presence of left atrial spontaneous echo contrast. The amount of circulating platelets expressing P-selectin and CD63 was significantly higher in the patients positive for both spontaneous echo contrast and left atrial thrombus or embolic events. Furthermore, in these groups, significantly more leukocyte-platelet conjugates were present. CONCLUSION: Platelet activation indicated by platelet membrane activation markers occurs in embolic and preembolic status of patients with nonrheumatic AF.

Assessment of cardiac adrenergic supply in mitral valve prolapse using m-[123I]iodobenzylguanidine scintigraphy.

Presynaptic as well as postsynaptic adrenergic regulation abnormalities are reported in symptomatic patients with mitral valve prolapse. This study was undertaken to evaluate presynaptic sympathetic supply by m-[123I]iodobenzylguanidine scintigraphy in 17 preselected patients with mitral valve prolapse and symptoms suggestive of hyperadrenergic dysautonomia as compared to normal scintigraphic findings. Mitral valve prolapse was echocardiographically proven within the left parasternal long axis view. Percentual activity of m-[123I]iodobenzylguanidine in 33 sectors of all oblique slices along the short axis was calculated relative to the maximal uptake, set at 100%. In general, no significant differences of mean values of sectoral quantitative uptake of m-[123I]iodobenzylguanidine were detectable between patients and the control group. Only in two sectors of the basal anterolateral region P values < 0.01 were present. Thus, using m-[123I]iodobenzylguanidine scintigraphy as marker of cardiac adrenergic supply, no evidence of altered presynaptic hyperadrenergic supply was present in patients with mitral valve prolapse. These findings suggest postsynaptic regulation abnormalities to be preponderant in this condition.

Assessment of spatial and temporal velocity profiles distal of normally functioning Björk-Shiley prosthesis by the Doppler method.

By Doppler echocardiography, the performance of heart valve prostheses is assessed with the aid of maximal transprosthetic velocities, which, however, may not be representative for the full spatial velocity profile in the vicinity of mechanical valve substitutes due to flow separation by the open occluder. The purpose of this study was to determine characteristics of velocity profiles downstream of a normally functioning Björk-Shiley prosthesis. In a pulsatile flow apparatus, different flow rates of 6.3 and 8.4 l/min were delivered. Using a spatially and temporally resolving ultrasonic Doppler method, velocity profiles 20 and 30 mm distal from the prosthesis were registered and displayed in a three-dimensional grid. The spatial velocity profile was found to deviate substantially from a flat profile at these transducer positions at the two flow conditions. Distal to the minor orifice, velocities measured only 70 and 80% of those downstream of the major orifice. In between, a region of relatively slow moving flow was present. The shape of the profiles remained essentially unchanged during acceleration and deceleration of flow. Thus, spatially resolved velocity profiles downstream of mechanical prostheses can be registered by an ultrasonic Doppler device. These findings may be useful for the detection of beginning malfunction both in the experimental and the clinical setting.

Limitations of Doppler echocardiography in the assessment of prosthetic valve hemodynamics.

The purpose of this study was to determine the relationship between effective orifice areas of mechanical valves in the aortic position assessed by Doppler echocardiography, and published data from in vitro studies. Eighty-six patients with a normally functioning Standard St. Jude Medical (n = 56) or Björk-Shiley (n = 30) prosthesis in the aortic position were studied. Valve sizes varied between 19 and 27 mm. Pressure gradient was calculated by the Bernoulli, and effective orifice area by the continuity equation. Published data on prosthetic orifice areas from in vitro pulsatile flow experiments using the Gorlin formula were used for comparison. A weak correlation was present between Doppler derived pressure gradient and in vitro estimated effective orifice area, which significantly decreased with increasing valve size (R = -0.61; p < 0.0001). There was only a moderate correlation between Doppler derived and in vitro estimated effective orifice areas whether sewing ring diameter or left ventricular outflow tract diameter was used in the Doppler studies (R = 0.75 and R = 0.71, p < 0.0001, respectively). The difference between in vitro measured and Doppler derived areas was greater with Standard St. Jude Medical than with Björk-Shiley valves, both using the sewing ring diameter (1.04 +/- 0.61 cm2 vs. 0.53 +/- 0.39 cm2, p < 0.0003) and the outflow tract diameter (1.20 +/- 0.68 vs. 0.68 +/- 0.46 cm2, p < 0.006). The presence of atrial fibrillation, concomitant mitral valve replacement, small prosthesis size (19 to 23 mm) or a postoperative interval of less than one year did not change the uniform underestimation of prosthetic orifice areas by Doppler echocardiography. These findings are attributable to pressure recovery and localized transprosthetic velocities, and should be taken into account in the case of a suspected prosthesis malfunction.

[Grading of the aortic valve regurgitation with the color Doppler echocardiography]. / Zur Schweregradbeurteilung von Aortenklappenregurgitationen mit Hilfe der Farb-Doppler-Echokardiographie.

This study was undertaken to assess whether various parameters of the extension of aortic regurgitation with color Doppler imaging are comparable with angiographic techniques for classification of severity. In 39 patients with aortic regurgitation, 14 women and 25 men, mean age 53 +/- 14 years, Doppler echocardiographic examinations were performed prospectively for determination of length, width and area of the maximal extension of regurgitant flow (Figure 1). Angiographic assessment of severity showed grade I regurgitation in nine, grade II in 14, grade III in twelve, and grade IV in four patients. The length of regurgitant flow in the color Doppler image showed an increasing tendency with increasing angiographic severity (r = 0.38, SEE = 13 mm), however, for various grades of severity, there was clear overlap. The area of regurgitation, similarly, due to substantial overlap, correlated only weakly with the angiographic data (r = 0.54, SEE = 196 mm2). To date, there is not theoretical basis for a correlation of the length and area of regurgitant flow with the severity and experimental studies have shown that there is no simple relationship. The best correlation was found for the width of the regurgitant flow (r = 0.63, SEE = 3 mm), however, here as well, there was clear overlap of data such that there was no statistically significant difference between grades II and III. Unequivocal differentiation of the values could only be achieved between grades I and IV. Based on a width of 7 mm, high-grade regurgitation could be detected with a sensitivity of 75% and a specificity of 74%.(ABSTRACT TRUNCATED AT 250 WORDS)

[Doppler echocardiography in the evaluation of the results of balloon catheter valvuloplasty in aortic valve stenosis]. / Doppler-Echokardiographie zur Beurteilung des Ergebnisses von Ballonkathetervalvuloplastien bei Aortenklappenstenose.

This study was undertaken to assess the diagnostic value of Doppler echocardiographic methods for determination of the mean pressure gradient and valve orifice area in the evaluation of the results of balloon valvuloplasty (PTVP) in aortic stenosis by comparison with invasively-determined measurements. In 16 patients with aortic valve stenosis, eight men and eight women, mean age 64 +/- 10 years, Doppler echocardiographic studies were performed one day before and after PTVP. The mean pressure gradient was calculated with the aid of the modified Bernoulli equation and the aortic valve orifice area with the continuity equation. After PTVP, on comparison of Doppler echocardiographic and invasively-determined pressure gradients, there was no significant correlation (n = 16, y = 0.3x + 18.7, r = 0.36, SEE = 9.3 mm Hg) (Figure 2). Prior to PTVP the two methods correlated reasonably well with each other (n = 16, y = 0.6x + 7.7, r = 0.54, SEE = 17.8 mm Hg) (Figure 2). On comparison of the Doppler echocardiographic and invasively-determined aortic valve orifice area, both after and before PTVP, there were significant linear correlations (n = 8, y = 0.41x + 0.41, r = 0.73, SEE = 0.12 cm2 and n = 14, y = 0.71x + 0.17, r = 0.86, SEE = 0.10 cm2, respectively) (Figure 4). Correspondingly, there was close agreement between the change in absolute aortic valve orifice areas determined invasively (0.18 +/- 0.15 cm2) and noninvasively (0.15 +/- 0.10 cm2, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler echocardiographic determination of geometric orifice areas in mechanical aortic valve prostheses.

In 63 St. Jude bileaflet and 34 Bjoerk-Shiley tilting disk aortic valve prostheses, Doppler continuity areas were compared to their corresponding geometric areas defined by the opening angle of the occluders. Continuity areas correlated significantly with geometric areas in Bjoerk-Shiley (p = 0.68) and St. Jude prostheses (p = 0.86). Differences between continuity and geometric areas were greater in St. Jude than in Bjoerk-Shiley valves (0.87 +/- 0.45 cm2 vs. 0.06 +/- 0.47 cm2, p < 0.0001). Exclusion of patients with atrial fibrillation, with a postoperative interval of less than 1 year or valve sizes of 19 and 21 mm did not change the results. Thus, underestimation of geometric areas is present in the St. Jude bileaflet aortic valves, while geometric and continuity areas are not significantly different in Bjoerk-Shiley prostheses. These results are attributable to the effect of valve-type-dependent velocity profiles.

[Ambulatory blood pressure monitoring: significance of blood pressure variability for progression of heart hypertrophy]. / Ambulantes Blutdruckmonitoring: Bedeutung der Blutdruckvariabilität für die Progression einer Herzhypertrophie.

It is known that ambulatory blood-pressure monitoring gives a better prediction of target organ damage and prognosis than clinical blood pressure. Many studies have found a closer correlation for ambulatory blood pressure with left ventricular hypertrophy than clinical blood pressure. One question that is discussed controversely is whether the variability of blood pressure is also a determinant of target organ damage independent of the average level. In 52 patients with elevated casual blood pressure a 24-h ambulatory blood-pressure measurement (Space Labs 90202) was performed and left ventricular hypertrophy was evaluated by M-mode echocardiography. The following parameters of blood pressure variability were calculated from the profiles: the standard deviation of the mean value, the variation coefficient and the parameter of variability as proposed by Schächinger et al. Furthermore a Fourier analysis of the blood pressure data was performed to quantify blood pressure variability. We found no statistically significant correlation between blood pressure variability and left ventricular mass. However, systolic and diastolic blood pressure level showed a significant correlation with left ventricular hypertrophy (r = 0.45 and r = 0.49, p < 0.05). Thus, blood pressure variability as calculated from the ambulatory, non-invasive blood pressure monitoring is a poor predictor for secondary damage of the heart.

Risk of endocarditis in transesophageal echocardiography.

The risk of endocarditis associated with transesophageal echocardiography was studied in 101 patients. To evaluate possible bacteremia, blood cultures were performed on samples from consecutive patients who did not have clinical or laboratory evidence of infection. The broth blood culture Signal system was used in all patients, and additionally, the lysis-centrifugation technique was performed in a subgroup of 40 patients to further ameliorate recovery of rapidly phagocytosed germs. Comprehensive criteria for differentiation between true bacteremia and possible contamination were provided by means of simultaneous blood sampling from two separate venipuncture sites and skin specimens from the venipuncture area. Oropharyngeal specimens were cultured for evaluation of possible association of oropharyngeal flora with positive blood culture findings. They revealed facultative pathogenic isolates, as well as physiologic residental flora, in 15 patients. All blood isolates that were recovered simultaneously 6 minutes after the procedure were found to be sterile. Correspondingly, clinical follow-up for 2 weeks was uneventful with regard to episodes of infection. These results indicate that the risk of bacteremia associated with transesophageal echocardiography is extremely low. Thus endocarditis prophylaxis is not required for this procedure.

[Applications and value of intravascular ultrasound imaging in coronary interventions]. / Anwendung und Bedeutung der intravaskulären Ultraschallbildgebung bei Koronarinterventionen.

Intravascular ultrasound (IVUS) is a twodimensional imaging technique that provides crossections of the coronary artery with a high spatial resolution and therefore became the new gold standard for quantifying complex lesions. The detailed information about vessel and lumen dimensions before and particularly after angioplasty is of high clinical value, because the acute luminal gain is an important predictor of restenosis. At the moment IVUS is the only way of analyzing the plaque composition in vivo. This allows plaque-specific interventional therapy of coronary lesions with balloon or modern alternative angioplasty techniques like directional atherectomy, rotational atherectomy, stenting or a combination of these. IVUS can also quantify the plaque burden in angiographically normal reference segments during balloon angioplasty and stenting. This often leads to the use of larger balloon diameters than those chosen by angiographic measurement of the reference segments. For stenting the prognostic significance of this additional luminal gain could be shown, for other interventional procedures this is currently being investigated in controlled studies.

Provocation of left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy. Comparison of orthostasis testing and nitrate application.

Several provocation maneuvers are described in hypertrophic cardiomyopathy to Doppler echocardiographically distinguish the obstructive from the non obstructive type. No data are available about the value of orthostasis testing in comparison with nitrate application in this disease. In this study, 16 consecutive patients with hypertrophic cardiomyopathy were examined. 11 patients with hypertrophic cardiomyopathy were classified as obstructive, 5 patients with hypertrophic cardiomyopathy as non obstructive. Normal left ventricular outflow tract velocities as detected by the Doppler method were defined as < 2.0 m/s. Doppler echocardiographic measurements were performed after 10 minutes in supine position, within 10 minutes after head-up tilt and again, within 10 minutes in supine position. If systolic blood pressure during this examination exceeded 100 mm Hg 2.5 mg isosorbiddinitrate were sprayed sublingually. Measurements were done after 20 minutes in supine position and within 10 minutes after head-up tilt. Only in 7 of the 11 patients with hypertrophic obstructive cardiomyopathy maximal left ventricular outflow tract velocity in supine position measured > 2.0 m/s (2.2 +/- 0.8). During head-up tilt, all patients showed increased values (3.8 +/- 1.2 m/s). No differences in maximal left ventricular outflow tract velocity between head-up tilt and nitrate application in supine position (3.5 +/- 1.4 m/s) were present. All patients with hypertrophic non obstructive cardiomyopathy showed maximal left ventricular outflow tract velocities < 2.0 m/s in every step of the examination. Consequently, orthostasis testing was able to identify all patients with hypertrophic obstructive cardiomyopathy and demonstrated a diagnostic value similar to nitrate application.

Coronary aneurysm after bailout stent implantation: diagnosis of a false lumen with intravascular ultrasound.

This case report describes the intravascular ultrasound (IVUS) evaluation of a coronary artery aneurysm, developed in a stented segment within 6 mo after bailout stenting. Analysis of the IVUS images provides in vivo insights in the vessel-remodeling process after mechanical injury. The proximal entrance of the false lumen could be clearly visualized as well as the relationship between the stent struts, neolumen, and vessel wall. The discussion is focused on the options for management of such patients.

Serial follow-up after optimized ultrasound-guided deployment of Palmaz-Schatz stents. In-stent neointimal proliferation without significant reference segment response.

BACKGROUND: The effects of ultrasound-guided high-pressure stenting on late stent and reference segment dimensions are unknown. In this study, we report about angiographic and ultrasound measurements to assess the amount and distribution of neointimal ingrowth within the stent and the changes of plaque burden and dimensions within the reference segments. METHODS AND RESULTS: Sixty-eight consecutive patients with 72 lesions received single or multiple Palmaz-Schatz coronary stents with a standardized protocol for stent optimization under ultrasound guidance. The residual angiographic diameter stenosis was 3 +/- 12% (reference diameter, 3.16 +/- 0.61 mm). At follow-up 4.8 +/- 2.5 months later, angiography revealed a diameter stenosis of 27 +/- 21% with a restenosis rate of 15.3% (confidence interval: 7.8% to 25.6%). Lumen renarrowing within the stent was exclusively due to neointimal ingrowth; no stent compression was observed. The neointima covered 20 +/- 20% of the stent area and was more pronounced in the midportion of the stent. Volumetric assessment performed in 26 patients resulted in 13 +/- 14% or 65 +/- 28% of the stent volume occupied by neointimal ingrowth in patients without or with restenosis, respectively. Vessel remodeling had an impact on lumen dimensions only at reference sites but not within the stent. Plaque burden of 46 +/- 11% and 48 +/- 11% at the proximal and distal reference sites, respectively, did not show a relevant progression during the follow-up. CONCLUSIONS: Serial ultrasound analyses did not show any evidence of stent compression or relevant vessel remodeling. Restenosis was solely due to neointimal ingrowth. Despite a considerable plaque burden within the reference segments, there was no relevant progression of the disease adjacent to the stent.

Nitrendipine vs. captopril in essential hypertension: effects on circadian blood pressure and left ventricular hypertrophy.

Both nitrendipine and captopril have been shown to reverse left ventricular hypertrophy in hypertensive patients. So far, no study allowed a true comparison of these drugs in this regard and with respect to their potential of reducing circadian blood pressure. Therefore, a total of 86 patients with newly diagnosed arterial hypertension and echocardiographic evidence of left ventricular hypertrophy underwent randomized treatment with captopril (n = 43) or nitrendipine (n = 43). Eighteen patients had to be put on a combination therapy of nitrendipine and captopril during the course of the study to control blood pressure effectively. Before and after the 6th and 38th weeks of treatment all patients underwent ambulatory 24-hour blood pressure monitoring, M-mode echo assessment of left ventricular mass and Doppler evaluation of left ventricular filling. The 24-hour blood pressure data were smoothed with a Fourier series and then compared with a normotensive reference profile with respect to blood pressure load and variability. The daytime and nighttime mean and the office blood pressure were also analyzed. Substance-specific profiles of action were obtained by subtracting the smoothed profiles after therapy from the profiles before therapy. After 38 weeks ambulatory blood pressure had decreased from 152 +/- 11/101 +/- 7 to 137 +/- 13/87 +/- 10 mm Hg on nitrendipine and from 147 +/- 11/99 +/- 6 to 134 +/- 13/89 +/- 9 mm Hg on captopril. The substance-specific profiles calculated for captopril and nitrendipine showed a balanced antihypertensive effect throughout the day and the night. The mean percentage decreases in left ventricular muscle mass under nitrendipine was 15% and did not differ significantly from the decrease of 21% under treatment with captopril (p < 0.001). There is no significant association between the reduction in blood pressure and the regression of left ventricular hypertrophy. In patients with disturbances of left ventricular diastolic function the early-to-late diastolic left ventricular flow ratio and the isovolumetric relaxation time were improved independent of the drug used. It is concluded that a long-term therapy with captopril and nitrendipine leads to a comparable degree of circadian blood pressure reduction and regression of hypertensive left ventricular hypertrophy.

One balloon approach for optimized Palmaz-Schatz stent implantation: the MUSCAT trial.

BACKGROUND: After stent deployment, larger balloons are frequently needed to optimize stent expansion according to angiographic and intravascular ultrasound (IVUS) criteria. The objective of this trial was to assess the feasibility and safety of a single-balloon approach for predilation, stent implantation, and optimization with a differential-compliant balloon allowing for focal overexpansion. We also evaluated the achieved degree of stent expansion according to IVUS criteria. METHODS AND RESULTS: Forty-seven consecutive patients with 50 lesions received single or multiple Palmaz-Schatz coronary stents. The final angiographic diameter stenosis was -2.6 +/- 12.6% (reference diameter, 2.89 +/- 0.44 mm), and the residual lumen area stenosis (IVUS) was 13.0 +/- 12.3% (reference area 10.8 +/- 3.0 mm2). This result was achieved in two steps (first angiographic, then IVUS-guided stent optimization). The balloon inflation pressure increased from 13.1 +/- 3.0 bar at step 1 to 16.1 +/- 3.0 bar at step 2, which resulted in a balloon to artery ratio of 0.97 +/- 0.12 and 1.10 +/- 0.15, respectively, at the low-compliant peripheral balloon segments. The more compliant central balloon segments showed a balloon to artery ratio of 1.09 +/- 0.17 and 1.28 +/- 0.17, respectively. The primary success rate for stent deployment was 94%. Acute complications included two type A and one type B dissection without clinical sequelae. CONCLUSIONS: The single-balloon approach for stenting is feasible and safe. The acute result is comparable to that of other studies with IVUS-guided stent optimization, the primary success rate, however, is slightly lower with the presently available catheter.

Quantitative changes in reference segments during IVUS-guided stent implantation: impact on the criteria for optimal stent expansion.

Intravascular ultrasound is an established method to optimize stent implantation. Stent expansion is estimated from the relation between minimal in-stent cross-sectional area and reference lumen area. We analyzed the periprocedural lumen increment in the reference segments and its impact on intravascular ultrasound (IVUS) criteria for optimized stenting. Seventy-five consecutive patients were studied with a 2.9 Fr, 30-MHz system and motorized pullback (0.5 mm/sec). Lumen area was measured by planimetry; absolute and relative differences in area (delta area) were calculated. Lumen area increment for reference segments proximal and distal to the stent was 6.4% +/- 10.3% and 6.1% +/- 10.8%; 49/75 patients fulfilled all IVUS criteria for optimal stent expansion at the final IVUS assessment, and 10/75 patients met all the IVUS criteria in relation to the first measurement of reference lumen area, but not in relation to the final measurement of reference lumen area. During high-pressure dilatation within the stent, reference lumen increment is visible. If reference lumen planimetry is not repeated after additional high-pressure balloon inflation, the final relative stent expansion may be overestimated.